Although CACr has not been associated with specific clinical repercussions, knowledge of this anomaly is significant not only for practical purposes when performing coronary artery angiograms, but also for therapeutic purposes, because it may affect the accuracy of identifying the culprit lesion in cases of acute coronary syndrome and the choice and execution of revascularization procedures. The case of crossing LAD and LCx arteries arising independently from the left aortic sinus reported by Sen et al. [5] highlights the challenge of depicting this anomaly using conventional angiography. The authors were only able to demonstrate the LAD artery selectively; therefore, the authors obtained a non-selective view of the left coronary artery system in a left anterior oblique caudal projection, which showed that the LAD and LCx arteries had switched positions with the LCx artery depicted to the “left” of the LAD artery. The LCx artery was subsequently selectively engaged with a counterclockwise rotation, hence an anteriorly directed catheter. The anatomy was clarified through CTCA, which showed the crossing proximal courses of the LAD and LCx arteries, with the LAD artery arising posterior to the LCx artery. In cases of an absent left main coronary artery without crossing between the LAD and LCx arteries, the ostium of the LAD artery generally has a more anterior origin than the ostium of the LCx artery. Failure to selectively engage these vessels using the usual technique and catheters should alert the physician to the possibility of proximal crossing between them. Accordingly, suspicion of this specific anomaly should arise in case the ostium of the LAD artery is selectively engaged with a clockwise rotation, hence a posteriorly directed catheter, perhaps with a shorter secondary curve; thus, an upward pointing tip, such as a Judkins Left 3.5 catheter. Finally, the ostium of the LCx artery is selectively engaged with a counterclockwise rotation, hence an anteriorly directed catheter, perhaps with a longer secondary curve; thus, a more horizontal tip, such as a Judkins Left 4.5. Of course, a full depiction of the anomaly would require catheter engagement of the ostia of the LAD and LCx arteries and simultaneous visualization of these vessels.

Furthermore, in the case of acute coronary syndrome owing to an occlusion of a DgA leaving an avascular area at the anterolateral aspect of the left ventricle, the difficulty in identifying a stump-like thrombotic occlusion of a normally arising DgA across the LAD artery should alert the physician to the possibility of occlusion in a DgA arising proximal and contralateral to the origin of other diagonal branches and a crossing of the LAD artery. Therefore, knowledge of this specific anomaly facilitates the correct diagnosis and revascularization procedure. In patients with CACr who are potential candidates for surgical revascularization, the possibility of intramural coursing of significantly stenosed crossing branches needing revascularization should be investigated before surgery because intramural coronary branches, which may not be readily identifiable on conventional CA, are not amenable to bypass grafting. Adjunctive imaging modalities possess a higher sensitivity than invasive CA in detecting intramyocardial coronary arteries, such as CTCA, and may be employed for such a purpose. If a severely narrowed crossing coronary artery/branch cannot be bypassed because of its intramural course, the surgeon may create an arterio-arterial shunt at the point of the crossing, provided the other branch does not contain a flow-limiting stenosis. If this is not possible, stent angioplasty may be selected as a more suitable revascularization option, should leaving such intramyocardial branches unrevascularized be judged unacceptable. Of course, it is currently unknown whether any specific circumstances, currently unknown but potentially present in the area of vessel crossover, pose particular risks if stent angioplasty is performed in that specific area.

Although CACr has not been linked to specific clinical repercussions, it may be associated with clinically relevant, functional coronary artery abnormalities. However, to our knowledge, this potential association has yet to be investigated in any prior study. For example, in the clinical context of myocardial ischemia with non-obstructive (50%) coronary artery disease (CAD), demonstration of CACr should alert the physician to the possibility of spasm, to which crossing coronary arteries with an intramyocardial course are susceptible [20, 27]. Vascular tone testing with intracoronary acetylcholine would be required in such cases for diagnosis, management, and risk stratification purposes. Furthermore, whether the segments of the arteries at the crossover area are subject to mechanical stimulation from each other, inducing endothelial dysfunction and an enhanced local vascular reactivity to systemic vasoconstrictor stimuli, is currently unknown. An additional issue worthy of investigation is whether the abnormal anatomy of crossing LAD and LCx arteries is associated with unique patterns of coronary blood flow and wall shear stress, potentially increasing the risk of atherosclerosis development [28]. A long-term follow-up is necessary for such an investigation, which should be based on computational fluid dynamics. Yet, the patient with crossed LAD and LCx arteries reported by Sen et al. [5] and the patient with a single coronary ostium and crossed LAD artery and ramus medianus reported by Njeim et al. [23] did not experience any clinical events during a 2-year follow-up.

Traditional knowledge teaches that proximal coronary artery stems develop following fusion of the multiple endothelial strands emerging from the aortic peritruncal plexus and penetrating the aortic wall of the facing sinuses [29]. Since it would be difficult to hypothesize an altered fusion process of the multiple endothelial strands that would result in the formation of crossing channels, the anomaly of crossing LAD and LCx arteries challenges this “ingrowth” model of proximal coronary artery stem development. Given newer evidence documenting that the coronary ostia and most proximal part of the coronary artery stems are formed by limited outgrowth of the aortic endothelium through endocardial sprouting, it may be considered more plausible that independent origin of the LAD and LCx arteries from the left aortic sinus with crossing between their more proximal segments results from a defective outgrowth mechanism [30].

Overall, knowledge of the anomaly and being an astute observer are necessary to diagnose CACr accurately. However, diagnosing crossed LAD and LCx arteries arising from separate ostia remains challenging. Depicting the LCx artery to the “left” of the LAD artery in non-selective conventional angiography in a left anterior oblique caudal projection helps the physician suspect the anomaly [5]. Yet, catheter engagement of the ostia and simultaneous visualization of these vessels would be necessary to depict crossed proximal courses. Alternatively, the anomaly can be reliably defined through CTCA. Patients who present with myocardial ischemia and are diagnosed with CACr should have their angiogram scrutinized for signs of crossed coronary arteries with an intramyocardial course. Such a course is typically diagnosed via the angiographic “milking effect” and a “step down–step up” phenomenon induced by systolic compression of the tunneled segment. An intracoronary bolus dose of vasodilators, such as nitroglycerin or isosorbide dinitrate, can significantly improve diagnostic sensitivity. Yet, the presence of the “step down–step up” phenomenon without angiographic “milking” or a corkscrew appearance of either or both crossed coronary arteries should prompt investigation using CTCA to visualize an intramyocardial coronary artery course more sensitively and comprehensively than conventional angiography. In the case of non-obstructive (50%) CAD, irrespective of an intramyocardial course of the crossed coronary arteries, the patient could undergo spasm provocation testing. The occurrence of a spasm in a “bridged” segment of the crossed coronary arteries may entail a high risk of myocardial infarction and a worse long-term prognosis in general [27]. Such a diagnosis may inform treatment decisions, such as treating the patient with a calcium channel blocker and avoiding prescribing a beta-blocker, which may exacerbate coronary spasm, or nitrates. Indeed, nitrates will likely worsen the symptoms experienced by the patient owing to exacerbated myocardial bridge behavior secondary to decreased intrinsic coronary wall tension and increased reflex sympathetic stimulation of contractility. Conversely, suppose surgical revascularization is contemplated in a patient with obstructive ($\ge$50%) CAD also affecting the crossed coronary arteries. In that case, the surgeon should fully know the relevant anatomy to plan the procedure properly. In the event that a crossed coronary artery requires percutaneous revascularization for a stenosis at the area of vessel crossover, where specific circumstances may pose risks in the case of stent angioplasty, one may choose to proceed with angioplasty using drug-coated balloons.