Article Contents
2. Introduction
The 2019 ESC (European Society of Cardiology) Guidelines for the diagnosis and management of chronic coronary syndromes introduced the term chronic coronary syndromes (CCS)1 to describe the clinical presentations of coronary artery disease (CAD) during stable periods, particularly those preceding or following an acute coronary syndrome (ACS). CAD was defined as the pathological process characterized by atherosclerotic plaque accumulation in the epicardial arteries, whether obstructive or non-obstructive. Based on expanded pathophysiological concepts, a new, more comprehensive definition of CCS is introduced:
‘CCS are a range of clinical presentations or syndromes that arise due to structural and/or functional alterations related to chronic diseases of the coronary arteries and/or microcirculation. These alterations can lead to transient, reversible, myocardial demand vs. blood supply mismatch resulting in hypoperfusion (ischaemia), usually (but not always) provoked by exertion, emotion or other stress, and may manifest as angina, other chest discomfort, or dyspnoea, or be asymptomatic. Although stable for long periods, chronic coronary diseases are frequently progressive and may destabilize at any moment with the development of an ACS.’
Of note, ‘disease’ refers to the underlying coronary pathology, and ‘syndrome’ refers to the clinical presentation.
2.1. Evolving pathophysiological concepts of chronic coronary syndromes
Our understanding of the pathophysiology of CCS is transitioning from a simple to a more complex and dynamic model. Older concepts considered a fixed, focal, flow-limiting atherosclerotic stenosis of a large or medium coronary artery as a sine qua non for inducible myocardial ischaemia and ischaemic chest pain (angina pectoris). Current concepts have broadened to embrace structural and functional abnormalities in both the macro- and microvascular compartments of the coronary tree that may lead to transient myocardial ischaemia. At the macrovascular level, not only fixed, flow-limiting stenoses but also diffuse atherosclerotic lesions without identifiable luminal narrowing may cause ischaemia under stress;2,3 structural abnormalities such as myocardial bridging4 and congenital arterial anomalies5 or dynamic epicardial vasospasm may be responsible for transient ischaemia. At the microvascular level, coronary microvascular dysfunction (CMD) is increasingly acknowledged as a prevalent factor characterizing the entire spectrum of CCS;6 functional and structural microcirculatory abnormalities may cause angina and ischaemia even in patients with non-obstructive disease of the large or medium coronary arteries [angina with non-obstructive coronary arteries (ANOCA); ischaemia with non-obstructive coronary arteries (INOCA)].6 Finally, systemic or extracoronary conditions, such as anaemia, tachycardia, blood pressure (BP) changes, myocardial hypertrophy, and fibrosis, may contribute to the complex pathophysiology of non-acute myocardial ischaemia.7
The risk factors that predispose to the development of epicardial coronary atherosclerosis also promote endothelial dysfunction and abnormal vasomotion in the entire coronary tree, including the arterioles that regulate coronary flow and resistance,8–10 and adversely affect myocardial capillaries,6,11–14 leading to their rarefaction. Potential consequences include a lack of flow-mediated vasodilation in the epicardial conductive arteries9 and macro- and microcirculatory vasoconstriction.15 Of note, different mechanisms of ischaemia may act concomitantly.
