How to Assess Functional Significance of Myocardial Bridges in Athletes: A Personalized Medicine Approach

Myocardial bridging is a congenital coronary anomaly involving a segment of coronary artery coursing through myocardial wall, in a different depth and length, potentially affected by systolic compression. In athletes, such coronary anomaly is most often an incidental finding, due to increased use of high sensitivity noninvasive diagnostic tests. However, since myocardial bridge might potentially precipitate ischemia and even be responsible for sudden cardiac death, athletes need to be cleared for competition by an appropriate diagnostic test. Which is the ideal diagnostic test in such peculiar condition, in which the pathophysiological mechanism of ischemia is unknown and potentially different in different subjects, remains to be investigated. We focused on different diagnostic tests proposed and classified according to the most likely pathophysiological mechanism of ischemia in myocardial bridge. Accordingly, we analysed and discussed on ideal test in athletes with such condition.


Introduction
Myocardial bridge (MB), first mentioned by Reyman in 1737 [1], is the term that refers to muscle overlying the intramyocardial segment of an epicardial coronary artery. It is characterized by systolic compression of the tunneled segment and remains clinically silent in the majority of cases. The incidence of MB in pathologic series has been reported ranging between 15% and 85% [2,3]; they are currently increasingly recognized in vivo due to the expansion of advanced non-invasive cardiovascular imaging techniques including computer tomography imaging and cardiovascular magnetic resonance [4], while in angiographic series such incidence ranges from 0.5% to 2.5% [5][6][7]. This large discordance suggests that only a minority of patients with MB are, in fact, at increased risk for clinical symptoms and cardiac events.
Myocardial bridges are most commonly localized in the middle segment of the left anterior descending coronary artery. Diagonal and marginal branches may be involved in 18% and 40% of cases, respectively [8].
Clinical interest and systematic research have been triggered by an observed association of myocardial bridges with myocardial ischemia [8,9]. However, functional and anatomical characteristics of bridges able to precipitate ischemia as well as pathophysiological mechanisms of ischemia are still unclear. In fact, since myocardial blood flow is diastolic, while possible compression of muscle overlaying bridged coronary segment would occur in systole, in theory, myocardial bridges should not be responsible for myocardial ischemia. However, there are patients in whom myocardial bridges can be identified as the only source of ischemia [8] (Figure 1). It has been shown that diastolic myocardial compression may occur in 34-41% of bridged coronary vessel and that increased early diastolic flow velocity with changes in flow profile may be present DOI: 10.26717/BJSTR.2020. 26.004313 in myocardial bridges [8]. Preliminary and anecdotal data suggest that coronary flow reserve may be reduced, being between 2 and 2.6 distally to myocardial bridges, as measured by diastolic fractional flow reserve [10], while microvascular flow reserve may be impaired in patients with myocardial bridges [11][12][13], with possible, but not constant, normalization after invasive or surgical treatment of the bridge [14][15][16]. Furthermore, vascular compression in myocardial bridges is not only systolic, but it persists in the early phase of diastole and it is associated with reduced coronary flow reserve [12].  [10,17]. Since the precise mechanism of myocardial ischemia in subjects with myocardial bridges is unknown and it may even be different according to the anatomy of the bridge and the characteristics of myocardial muscle, it derives that which is the best method to assess ischemia in such cases remains to be investigated and clarified. Anomalous coronary arteries have been documented in athletes [18] in whom the determination of the presence of such anomalies is crucial, since sudden death is associated with exercise [19,20]. Moreover, during exercise, diastole shortens due to increased heart rate with increased systolic/diastolic flow ratio and increased inotropic response produces not only systolic, but also diastolic compression, thus reducing flow. Lastly, de novo formation of myocardial bridges might occur in patients with hypertrophic cardiomyopathies [21] and in transplanted hearts [22], thus it is conceivable that they might develop also in athlete's heart.
The interest in diagnosing the presence and functional significance of bridges in athletes resides in the finding of MB as the only pathological findings in autopsies of subjects died for sudden cardiac arrest during sports [19,20]. Functional significance of myocardial bridges in athletes subjected to intense athletic training, reaching very high heart rates, undergoing adrenergic stimulation and possible myocardial hypertrophy, is even more complex to be assessed. An increase in sympathetic drive during stress or exercise likely facilitates ischemia, since tachycardia leads to an increase of systolic-diastolic time ratio at the expense of diastolic flow.
Increased contractility during stress further aggravates systolic (and diastolic) compression. Endothelial dysfunction and coronary artery spasm may also contribute to constriction of the tunneled segment [23]. Furthermore, in athletes, functional implications of anomalous coronary arteries need to be clearly defined during the pre-participation screening in order to establish eligibility/ disqualification decisions in competitions [24].
The purpose of this point of view article is to focus and discuss on which is the ideal and most effective diagnostic method to reveal ischemia in athletes with myocardial bridges. Since modern medicine needs to be personalized, it is conceivable that, even in this field, appropriate diagnostic approach might reside on the identification of the mechanism of ischemia in each specific subject.
Therefore, diagnostic potential in the detection of ischemia of different tests is discussed along the mechanism of ischemia that each of them is able to explore.

Conclusion
Based on the anatomical and functional characteristics of the bridges and on the clinical presentation of patients, ischemic potential of MB con be evaluated by personalized test approach.
However, in athletes, particularly if clearance for competition needs to be released, exercise stress test with an associated imaging modality seems to be the ideal and most appropriate test.