Coronary microvascular dysfunction in the clinical setting: from mystery to reality

Abstract

Far more extensive than the epicardial coronary vasculature that can be visualized angiographically is the coronary microcirculation, which foregoes routine imaging. Probably due to the lack of techniques able to provide tangible evidence of its crucial role, the clinical importance of coronary microvascular dysfunction is not fully appreciated. However, evidence gathered over the last several decades indicates that both functional and structural abnormalities of the coronary microvasculature can lead to myocardial ischaemia, often comparable with that caused by obstructive coronary artery disease. Indeed, a marked increase in coronary microvascular resistance can impair coronary blood flow and trigger angina pectoris, ischaemic ECG shifts, and myocardial perfusion defects, and lead to left ventricular dysfunction in patients who otherwise have patent epicardial coronary arteries. This condition--often referred to as 'chest pain with normal coronary arteries' or 'cardiac syndrome X'--encompasses several pathogenic mechanisms involving the coronary microcirculation. Of importance, coronary microvascular dysfunction can occur in conjunction with several other cardiac disease processes. In this article, we review the pathogenic mechanisms leading to coronary microvascular dysfunction and its diagnostic assessment, as well as the different clinical presentations and prognostic implications of microvascular angina. As such, this review aims to remove at least some of the mystery surrounding the notion of coronary microvascular dysfunction and to show why it represents a true clinical entity.

Figure 1

Angiogram of the right coronary artery (left panel) and a dominant left coronary artery system (middle panel), which do not reveal the rich microvascular network noted on an ex vivo arteriogram.

Figure 2

Coronary blood flow is driven by the pressure difference between the aorta and the capillary bed and modulated further by various physical and neural factors, which affect the microcirculation. Moreover, the different compartments of the microcirculation are influenced by one main physiological mechanism to control their vascular tone with cardiac metabolism as the final determining factor.

Figure 3

Illustration of two cases of anterior myocardial infarction with the restoration of blood flow in the left anterior descending artery (A–C, upper and lower panel). In the presence of microvascular integrity, the following can be seen: myocardial blush grade 3 (D, upper panel) a lack of oedema, homogeneous myocardial perfusion, subendocardial anteroseptal enhancement of 25–50% wall thickness on magnetic resonance imaging (MRI, E–G, upper panel) and normal perfusion on myocardial contrast echocardiography (MCE, H, upper panel). On the contrary, in the setting of coronary microvascular impairment, myocardial blush is poor (D, lower panel) along with a large area of oedema, an anteroseptal perfusion defect and extensive delayed enhancement with microvascular obstruction on MRI (E–G, lower panel), and a large perfusion defect on MCE (H, lower panel). Modified from Porto et al. Used with the permission of Elsevier.

Figure 4

Illustration of the prognostic indicator function of the coronary microcirculation in acute myocardial infarction. Whether assessed by TIMI flow, myocardial blush grade or ST-segment resolution, myocardial contrast echocardiography, or magnetic resonance imaging, prognosis is significantly worse if myocardial perfusion is not restored despite an open epicardial artery. Images used with the permission of the American Heart Association.

Figure 5

Although the discussion of management strategies is beyond the scope of the present manuscript, this figure shows a flow chart outlining a suggested algorithm for the management of patients with chest pain despite angiographically normal coronary arteries, in whom the underlying mechanism is coronary microvascular dysfunction. ACS, acute coronary syndrome; CAD, coronary artery disease; CFR, coronary flow reserve; CV, cardiovascular; ETA, endothelin-type A receptor; IMR, index of microvascular resistance; IVUS, intravascular ultrasound; MBF, myocardial blood flow.