{'fraction_non_alphanumeric': 0.026237254414324795, 'fraction_numerical': 0.0145071706872254, 'mean_word_length': 5.097295931261057, 'pattern_counts': {'":': 0, '<': 2, '<?xml version=': 0, '>': 3, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Myocardial bridging analysis by coronary computed tomographic angiography in a Saudi population World Journal of Cardiology

AIM: To assess the incidence, location, morphology and clinical association of myocardial bridging in a Saudi population using coronary computed tomographic angiography (CCTA). METHODS: A total of 350 CCTA of Saudi patients were included in this study (236 men, 114 women) with a mean age of 56.3 years. All patients were examined for appropriateness criteria of CCTA indications (typical chest pain, recent onset cardiomyopathy, left bundle branch block, etc.). The scans were retrospectively re-viewed for the presence of myocardial bridging and any other pathological association. RESULTS: Myocardial bridging was found in 89 of 350 (22.5%) patients. Most of the intramuscular segments were of the superficial type and found in the mid left anterior descending (LAD) (24.6%), followed by distal LAD (3.7%), diagonal branches (2%), ramus intermedius artery (1.4%) and obtuse marginal artery (0.8%). No myocardial bridging was detected in the right coronary or circumflex arteries. No significant differences were found between males and females (P = 0.14). Coronary artery atherosclerosis was found in 51 of 89 (57.3%) patients with MB. Atherosclerotic plaques were not detected in the intramuscular or distal segment of bridging arteries. Dynamic compression was observed in 35 (94.5%) patients with full encasement. No evidence of myocardial hypoperfusion was found in the territories supplied by the bridging arteries. CONCLUSION: CCTA is excellent in analyzing myocardial bridging in a Saudi population and the results are comparable to other populations. However, finding the real incidence may need a large multicenter study. segment of a or its major branch travels through instead of on surface of the myo- cardium . Coronary computed tomographic angiography (CCTA) is able to visualize myocardial bridging in a more sensitive and comprehensive way than conventional coronary angiography. The prevalence of myocardial bridging var-ies widely between different studies.


INTRODUCTION
Myocardial bridging (MB) is an inborn abnormality. It occurs when a segment of a coronary artery or its major branch travels through the myocardium instead of on the surface of the myocardium, resulting in a tunneled arterial segment [1] . In an autopsy study, Ferreira et al [2] distinguished two types of MB: superficial bridges crossing the artery perpendicularly or at an acute angle towards the apex and deep bridges characterized by muscle bundles arising from the right ventricular apical trabeculae that cross the affected artery transversely, obliquely or helically before terminating in the interventricular septum [2] . The clinical outcome of patients with MBs has been considered benign when it is not associated with hemodynamic changes [3] . However, the relationship of MB and ischemia remains controversial. Myocardial bridging is considered clinically significant when it is associated with regional hemodynamic compression.
Atherosclerotic changes usually affect the segment immediately proximal to the myocardial bridge, whereas its occurrence in the tunneled coronary segment is still controversial [3][4][5] .
Coronary angiography was considered the gold standard for the diagnosis of myocardial bridging [6,7] . However, it is an invasive procedure and requires a great deal of experience for its interpretation. Also, a superficial type of myocardial bridges may be missed on angiography.
Recently, coronary computed tomographic angiography (CCTA) has been introduced as a noninvasive imaging of the coronary arteries. CCTA is able to visualize the lumens of coronary arteries as well as their walls and the neighboring myocardium in any plane. The depiction rate of MB is greater with 64-section multi-detector computed tomography (MDCT) than with conventional coronary angiography; the higher prevalence of MB on MDCT is considered to be due to the inclusion of partial and full encasement on CCTA, the use of short-axis images obtained perpendicular to the long axis of the left anterior descending (LAD) for all analysis and measurement, and the consistently high image quality of MDCT. Coronary CT Angiography is able to visualize myocardial bridging in a more sensitive and comprehensive way than conventional coronary angiography, in which the diagnosis is not made by the direct visualization of the intramuscular course but the indirect finding of systolic compression of the coronary artery indicated by the milking effect [8,9] . Based on CCTA, Kim et al [9] classified myocardial bridging of LAD into three types. Type I is myocardial bridging with partial encasement with the artery within the interventricular gorge and in direct contact with left ventricular myocardium. Type Ⅱ is myocardial bridging with full encasement of LAD by myocardium but without measurable overlying myocardium. Type Ⅲ is myocardial bridging with full encasement of LAD by myocardium but with measurable overlying myocardium (> 0.7 mm) [9] .
The objective of the present study is to assess the incidence of myocardial bridging, as well as their location and morphology, in Saudi patients by using CCTA and comparing the national results to the international worldwide published studies. The clinical association and pathological changes in relationship to myocardial bridging will be also assessed.

MATERIALS AND METHODS
The study was designed to be a retrospective observational study. A total of 350 Saudi Caucasian subjects were included in this study. Patients of other ethnic groups were excluded from the study. The patients included 236 men and 114 women, with an average age of 56.3 ± 11 years. The patients were examined for different clinical cardiac conditions (Table 1). All CCTA studies were done between January 2010 and February 2013. Written informed consent was taken from all patients included in the study. The ethics committee in the hospital approved the use of the clinical and imaging data.
Machines used for CCTA are dual-source 128-slice scanners (Siemens Definition Flash, Forchheim, Germany) and 64-slice CT scanners (Light Speed VCT, GE Healthcare, Waukesha, Wisconsin, United States). Briefly, the technique used for CCTA is as follows. Volumetric data set for the coronary arteries is acquired; the data set covers the entire heart from the proximal ascending aorta (approximately 1-2 cm below the carina) to the diaphragmatic surface of the heart. The scan is acquired in a single breath-hold during inspiration and starts with the injection of a nonionic contrast agent with a concentration of 300-400 mg I/mL at a flow rate of 4-6 mL/s. The total volume of contrast agent depends on the scan length, but typically 60-80 mL is injected, followed by a saline bolus (40-70 mL at 4-6 mL/s). Scanning delay was determined according to the test bolus technique and the region of interest was placed on the ascending aorta. The subjects were instructed to maintain an inspiratory breath-hold during which the CT data and ECG trace were acquired. Retrospective ECG-gated reconstructions were generated at best systolic and diastolic phases  or any other phase of the R-R interval according to the situation. All patients included in this study were in sinus rhythm and were always pre-medicated with nitroglycerin (5 mg sublingually 1 min before the examination) to dilate the coronary arteries. The heart rate ranged between 50 and 78 BPM with a mean of 65 BPM. Most patients received beta-blockers to control their heart rate within this range, as metoprolol tartarate (5 mg/mL Ⅳ bolus) can be repeated according to HR (Beloc ampule, AstraZeneca).

Image reconstruction and interpretation
Two experienced readers certified with level Ⅲ CCTA blindly interpreted the CCTA images for all patients. Interpretation started with the axial resource images, then other multiplanar reconstructions. If myocardial bridging was detected, the depth and length of the tunneled segment were measured. Myocardial bridge was defined as a segment of a coronary artery that courses through the myocardium. Coronary artery disease (CAD) was defined as coronary wall atheromatous change (calcified and noncalcified plaque) with or without luminal reduction. Hemodynamically significant stenosis was defined as equal or greater than 50% reduction of the lumen diameter [10] . Each involved coronary artery was assessed for the presence of atherosclerotic changes and the location of those changes in relationship to the tunneled segment. The exact anatomy of a normal coronary artery or a tunneled segment was identified in both axial and reformatted images in all planes. The tunneled segment is considered superficial or deep if the depth of the covering myocardium is ≤ 1 or > 1 mm respectively [11] .
Superficial MB was further subdivided into complete and incomplete based on the full or partial encasement of the LAD within the left ventricular myocardium [9] .
The relationship between length, thickness of the bridge, and severity of the stenosis in the coronary artery proximal to the bridge was studied. The coronary CTA findings were classified as the following: no atheromatous changes or luminal narrowing as normal; atheromatous changes without luminal narrowing as mild disease; atheromatous changes with insignificant stenosis as moderate disease; and atheromatous changes with significant stenosis as severe disease. Because the LAD is the most common artery involved with MB, we compared coro-nary CTA findings in subjects with myocardial bridge with other patients without bridging.

Statistical analysis
The SPSS software package was used for the statistical data analysis. In the descriptive statistical analysis, quantitative variables were expressed as mean ± SDs, whereas categorical variables were expressed as a percentage. Statistical significance was set at P value < 0.05.

RESULTS
All CCTA scans interpreted in this study were of a good image quality and all involved tunneled segments were assessable. Myocardial bridging was found in 89 of 350 (22.5%) patients. No significant differences were found between males and females (P = 0.14). The total intramuscular segment was 96; thus, in 7 patients, more than 1 intramuscular segment was found. Most of the intramuscular segments were in the LAD artery. No myocardial bridging was detected in the right coronary artery or proximal LAD. The coronary arteries involved are presented in Table 2.
The length of the intramuscular segments ranged from 6 to 24 mm (average 15 ± 7 mm). The mean diameter of the intramuscular segments was 3 ± 3 mm and 1.6 ± 0.5 mm for LAD and the remaining arteries, respectively. The diameter of the proximal segments was significantly larger than that of the intramuscular segment, 2.8 ± 0.5 mm for the LAD and 1.8 ± 0.6 mm for the remaining arteries (P > 0.001). The depth of the intramuscular segments ranged from 1 to 6.2 mm and the mean thickness was 2.3 ± 3.9 mm.
Two anatomical patterns of intramuscular segments were identified according to the depth and the course of the intramuscular segment of LAD: the superficial type [46 segments (61.3%)] in which the intramuscular artery had a superficial course along the interventricular septum (Figure 1) and was covered by a thin layer of tissue (< 1 mm thick) and the deep type [29 segments (38.6%)] in which the intramuscular segment penetrated the interventricular septum at a depth between 1 and 6.2 mm (Figure 2).
Imaging evidence of coronary artery atherosclerosis was found in 51 of 89 (57.3%) patients and in 41 of 261 (15.7%) patients without bridging. Atherosclerotic plaques were not detected in the tunneled or distal segment to myocardial bridging in any case. No evidence of myocardial hypoperfusion was found in the myocardial territories subtended by the tunneled coronary arteries.
In 81 patients with a LAD-myocardial bridge, atherosclerotic changes were found in 37 subjects (45.7%) and were consistently localized in the coronary segment proximal to the bridge. Dynamic compression was observed in two patients with partial encasement (5.5%) and 35   anomaly but in exceptional cases, it is associated with clinical manifestations. Coronary angiography was considered the gold standard for the diagnosis of myocardial bridging [6,7] . With the introduction of MDCT into clinical practice, a great revolution has happened in the imaging of coronary arteries and their diseases. By reviewing the current literature, there is no research studying the prevalence of MB in a Saudi population. This study is considered the first to investigate the prevalence of MB in a Saudi population and its clinical significance in a relatively big sample size (350 patients). There is a wide discrepancy in the reported prevalence of myocardial bridging between autopsy findings (average 33%, range 15% to 85%) [12,13] and those of conventional angiography (average 5%, range 0.5% to 16%) [14][15][16][17][18][19][20][21][22][23] . This discordance occurs because most patients with MB have unrelated overt symptoms that are rarely referred for CCA. Also, CCA is not sensitive enough to detect a milking effect (temporary occlusion of artery during systole) with superficial MB [16] .
Recently with an apparent increase in the detection rates of MB, a prevalence as high as 44% has been found [23] . Multiple studies have reported myocardial bridging by coronary CTA, showing a wide range of frequencies.
The exact course of the coronary arteries was easily recognized on reformatted MDCT in all our cases together with the consequences of myocardial bridging making it possible for the clinician to see the problem and start the management plan. The length and depth of myocardial bridging in the current study are in agreement changes were detected in three with diagonal artery MB, in two patients with ramus intermediate artery MB, and in one patient with obtuse marginal artery MB. with the results of many studies [7,42] . In the vast majority of cases, angiographic localization of myocardial bridges is in the LAD [43] . Localization other than the LAD is extremely rare [14] . This study shows that the intramuscular course of coronary arteries most commonly involves the middle segment of LAD, followed by its distal segment, and no cases were reported to have MB of the proximal LAD, circumflex or right coronary arteries. These results are in contrast with Loukas et al [44] who demonstrated that the presence of myocardial bridges appeared to be related to coronary dominance and it goes with their results in detecting MB in LAD, diagonals, OM and RCA in descending order. On the other hand, Arjomand et al [45] reported the first case of myocardial bridging of the circumflex artery (mid-portion) association with acute myocardial infarction.

Figure 1 Coronary computed tomographic angiography in transverse axis (A) and long axis (B) show a thin layer of myocardium covering midleft anterior descending (superficial myocardial bridging).
Also, Tuncer et al [46] reported a 63-year-old man with myocardial bridging of the left circumflex coronary artery with significant systolic narrowing at the mid segment after the first obtuse marginal branch.
The length of the intramuscular segments and their mean diameters were clearly determined by CCTA in the current study. The diameter of the proximal segments and the depth of the intramuscular segments were also evaluated. The results revealed a significant decrease in the diameter of the intramuscular segment compared with the adjacent proximal segment. Similar observations were reported in other literature [26,47] . These structural differences between intramuscular and epicardial segments and the reduced diameter of the intramuscular segments have been associated with the detection of atherosclerotic changes detected in our cases.
Depth criteria is not clear cut for the classification of MB into superficial or deep types depicted on CT. However, some research classified MB as superficial or deep depending on the thickness of the covering muscular layer, either ≤ 1 mm or ≥ 1 mm respectively [11] . In addition, superficial MB can be classified as complete or incomplete in accordance with the extent of the vessel encasement by the myocardium [9] . This subdivision of superficial MB into complete and incomplete types based on the full or partial encasement is in our study. The incidence of superficial MB (61.3%) was higher than that of the deep type (38.6%). Nearly the same results were illustrated by Hwang et al [7] as they found that the prevalence of superficial MB (66%) was higher than that of deep MB (34%). This study illustrated that dynamic compression was detected in two patients with partial encasement (5.5%) and 35 patients with full encasement (94.5%). The results indicated that dynamic compression occurred almost exclusively in myocardial bridging with full encasement, which is in concordance with Kim et al [9] who reported that dynamic compression occurred almost exclusively (97.5%) in patients with full encasement of the LAD coronary artery regardless of the presence of overlying muscle [9] .
Atherosclerotic changes detected in our series are limited exclusively to the arteries proximal to the deeptunneled segments. No atherosclerotic changes were found in the superficial type of bridging, which can be explained by the lower shear stress that may contribute to atherosclerosis at proximal segment of MB, whereas higher shear stress may protect it from atherosclerosis at the tunneled segment of MB [48] . Another explanation is that due to the high-pressure gradient at the proximal segment, the local wall tension and subsequent endothelial dysfunction will enhance atherosclerotic changes in that segment [49] . This observation was in agreement with other investigators who reported that the tunneled segments are free of atheroma [50] . Duygu et al [51] found a significant positive correlation between hs-CRP and the percentage of atherosclerotic stenosis on the IVUS study of patients with stable angina pectoris and detected MB in LAD. They concluded that their results indicate the presence of low-grade inflammation in patients with an atherosclerotic lesion in bridged segments.
On the other hand, Duygu et al [52] studied 71 patients with MB diagnosed by coronary angiography and they concluded that a myocardial bridge may initiate the development of an atherosclerotic lesion or may facilitate progression of atherosclerosis in the proximal segment of the vessel. The risk of acute coronary syndrome rises when atherosclerosis is superimposed on MB.
Zoghi et al [53] studied 50 patients with MB in LAD on coronary angiography. All coronary artery segments were evaluated by IVUS and endothelial function was assessed with measurement of flow mediated dilatation in the brachial artery. They concluded that endothelial function is impaired in patients with MB and there is an increased tendency for atherosclerosis proximal to the bridge in MB patients.
However, our results do not agree with other studies showing that the atherosclerotic process occurs in the tunneled coronary segment with the same severity and frequency as the epicardial coronary segments [54] .
Some studies showed that such instances of myocardial bridging are linked to clinical complications that include ischemia, acute coronary syndrome, coronary spasm, arrhythmia and sudden death, although in the vast majority of cases, myocardial bridging remains clinically silent [3,4,15,16] . Because dynamic compression occurs almost exclusively in myocardial bridging with full encasement, the incidence of myocardial bridging with full encasement is considered to be more meaningful in the clinical setting [55] .
Finally, our results support the classic belief that myocardial bridging is a normal variant and has no clinical consequences as none of our patients required specific medical or invasive treatment for MB. These findings are supported by Kramer et al [56] and Nakanishi et al [23] who demonstrated that MB is an incidental finding associated with an excellent survival rate of 97% at 5 years. They postulated that the clinical significance of a MB appears to be related to the anatomic properties of a tunneled segment of coronary artery, the presence of associated myocardial ischemia, and the presence of proximal and distal atherosclerotic disease. They concluded that medical treatment is the choice for symptomatic patients. Coronary stenting and surgery should be kept for resistant cases that have not responded well to medical therapy. Preoperative mapping of MB allows the surgeon to be ready to deal with myocardial bridging and this will shorten the surgery time and operative risks significantly.

Limitations of the study
This study is the first to investigate such a relatively large patient group in Saudi Arabia. However, this study has a few limitations, including that it is just a descriptive study; we do not compare CCTA with other techniques like coronary angiography for a radiation dose. Also, we did not correlate our results with the clinical outcome after treatment. These limitations can be avoided by including a wide spectrum of patients from different provinces of the country. Also, multicenter clinical studies of larger groups are required to determine the degree to which myocardial bridging is responsible for symptoms such as angina, myocardial infarction and life-threatening arrhythmias. Prospective multicenter studies of larger groups are definitely still required to determine the true national prevalence and whether myocardial bridging is responsible for cardiac symptoms or not.
In conclusion, the study shows clearly that CCTA offers an excellent non-invasive way to detect and characterize myocardial bridging. The national prevalence of MB in Saudi Arabia is comparable to worldwide prevalence. Also the anatomical and associated pathological findings of the tunneled arteries are similar to many other studies. However, multicenter clinical studies of larger groups are required to determine the real national incidence of MB, as well as the true clinical and physiological significance of myocardial bridging. However, it is still remains unclear which patients require further testing after the detection of myocardial bridging.

Background
Myocardial bridging occurs when a segment of a coronary artery or its major branch travels through the myocardium instead of on the surface of the myocardium. Coronary computed tomographic angiography (CCTA) is able to visualize myocardial bridging in a more sensitive and comprehensive way than conventional coronary angiography. The prevalence of myocardial bridging varies widely between different studies.

Research frontiers
The current study assessed the incidence, location and morphology of myocardial bridging in Saudi patients by using CCTA and comparing the results to other international studies. The clinical association and pathological changes in relationship to myocardial bridging was also assessed.

Innovations and breakthroughs
This study highlighted the usefulness of CCTA as a non-invasive method to detect and characterize myocardial bridging. The incidence, location and clinical significance of myocardial bridging (MB) in Saudi patients do not differ from most of other populations.

Applications
CCTA is an excellent imaging modality to assess the real incidence and clinical significance of myocardial bridging in Saudi patients.

Terminology
MB is an inborn abnormality. It occurs when a segment of a coronary artery or its major branch travels through the myocardium. CCTA is the use of CT imaging to visualize the courses, lumens and relationships of the coronary arteries.

Peer review
In this study, the authors retrospectively examined the incidence of myocardial bridges in Saudi people, as well as their location and morphology from 350 individuals with coronary CT angiography. This paper is the first to describe the prevalence and clinical significance of MB in Saudi patients.