Pathophysiological Mechanisms of Myocardial Bridging-Related Angina and Ischemia with Implications for Therapeutic Strategies

Myocardial bridging (MB) is a congenital coronary anomaly characterized by systolic compression of the intramyocardial arterial segment and delayed early diastolic artery relaxation, resulting in reduced vessel luminal diameter in diastole. Current evidence suggests that MB, particularly in the left anterior descending artery, may cause anginal symptoms and/or myocardial ischemia through several different pathophysiological and cellular mechanisms acting independently or synergistically: (1) delayed early diastolic relaxation of intramyocardial arterial segment; (2) impaired endothelial-dependent vasodilation with vessel smooth muscle cell hyperactivity in the coronary artery with MB, especially within the bridged segment; (3) focal (septal) ischemia due to "septal steal" phenomenon; and (4) development and progression of an atherosclerotic lesion in the coronary artery segment proximal to MB. Patients with isolated-MB may also experience anginal pain and/or myocardial ischemia due to concomitant structural and/or functional abnormalities of the coronary microcirculation. Both MB and coronary microvascular dysfunction refer to a subgroup of patients with angina and/or ischemia with non-obstructive coronary arteries (ANOCA/INOCA). Therefore, it may be challenging to determine whether MB is causing anginal pain and/or ischemia, particularly since both phenomena have also been reported without MB's existence. Therefore, comprehensive coronary physiology testing should be encouraged in patients with this coronary anomaly to identify the underlying cause of anginal pain and/or myocardial ischemia, enabling optimal therapeutic strategies in these patients. This review is focused on different pathophysiological and cellular mechanisms of MB-related angina and/or ischemia and future perspectives in the functional assessment of MB severity, bearing in mind the complexity of coronary physiology in the presence of this anomaly.