Abnormal shear stress and residence time are associated with proximal coronary atheroma in the presence of myocardial bridging

Highlights

• A myocardial bridge (MB) is associated with low wall shear stress (WSS) proximally.

• Areas of low WSS correlate with sites of atheroma on intravascular ultrasound.

• Patients with an MB and pathogenic WSS perturbations may benefit from lipid lowering.

Abstract

Background

Atheromatous plaques tend to form in the coronary segments proximal to a myocardial bridge (MB), but the mechanism of this occurrence remains unclear. This study evaluates the relationship between blood flow perturbations and plaque formation in patients with an MB.

Methods and results

A total of 92 patients with an MB in the mid left anterior descending artery (LAD) and 20 patients without an MB were included. Coronary angiography, intravascular ultrasound, and coronary physiology measurements were performed. A moving-boundary computational fluid dynamics algorithm was used to derive wall shear stress (WSS) and peak residence time (PRT). Patients with an MB had lower WSS (0.46 ± 0.21 vs. 0.96 ± 0.33 Pa, p < 0.001) and higher maximal plaque burden (33.6 ± 15.0 vs. 14.2 ± 5.8%, p < 0.001) within the proximal LAD compared to those without. Plaque burden in the proximal LAD correlated significantly with proximal WSS (r = −0.51, p < 0.001) and PRT (r = 0.60, p < 0.001). In patients with an MB, the site of maximal plaque burden occurred 23.4 ± 13.3 mm proximal to the entrance of the MB, corresponding to the site of PRT.

Conclusions

Regions of low WSS and high PRT occur in arterial segments proximal to an MB, and this is associated with the degree and location of coronary atheroma formation.

Introduction

While generally incidental, myocardial bridging has been associated with angina, myocardial infarction, ventricular arrhythmia, and sudden cardiac death [[1], [2], [3], [4], [5], [6], [7]]. A myocardial bridge (MB) is an anatomical variant in which the coronary artery, most frequently the left anterior descending artery (LAD), is covered by myocardium for a varying degree of length, depth, and location [5]. The reported prevalence of an MB varies greatly, depending on the cohort studied and the type of imaging test performed [8]. Studies utilizing cardiac computed tomography angiography have reported a prevalence of ~30% in the general population [9], while we have found the prevalence to be nearly double that in patients with angina in the absence of obstructive coronary artery disease [1,10,11].

Histopathology and intravascular ultrasound (IVUS) studies have demonstrated that MB segments are generally spared of coronary atheroma, while atheromatous plaques tend to develop proximal to the MB [1,10,[12], [13], [14], [15]]. The presence of an MB is also associated with unstable plaque features and occurrence of myocardial infarction at an earlier age than would be expected [2]. The underlying mechanistic link between the physiological disturbances caused by an MB and the development of atheromatous plaques remains poorly understood [4].

Wall shear stress (WSS) refers to the tangential force applied to the vessel wall due to blood flow. Abnormalities in WSS within coronary arteries have been shown to be associated with endothelial dysfunction and the development of atherosclerosis [[16], [17], [18]]. Specifically, low WSS is associated with flat, polygonal, and polymorphic endothelial cells, and the development of atherosclerotic plaques [17]. In addition to WSS, there are other hemodynamic factors, such as flow recirculation and blood peak residence time (PRT) that may influence arterial plaque initiation and progression [19,20]. Previous studies have suggested that an MB can induce abnormal WSS within, as well as proximal to the MB, and this may explain the predisposition to atheroma formation in these arteries. However, these studies have been largely theoretical [5,21,22].

In the current study, we systematically investigated the association between an MB, wall shear stress, and atheroma development by studying a cohort of patients with an MB vs. a cohort without an MB. We developed and used a novel, pulsatile flow fluid-structure interaction simulation that incorporated dynamic vessel compression to account for the MB and characterized shear stress and other flow parameters within the coronary arteries. IVUS and three-dimensional (3D) quantitative coronary angiography (QCA) were used to reconstruct geometries of the coronary arteries. Pressure and flow velocities were also measured within these arteries to determine the boundary conditions.