How important is microcirculation in clinical practice?

Abstract

Patient with chronic angina have an increased risk of adverse cardiovascular events. These patients also have an increased risk of complications with consequent higher healthcare expenditure. Furthermore, angina symptoms can considerably limit daily activities, quality of life, and often cause early retirement. Angina pectoris is caused by myocardial ischaemia, and for more than two centuries epicardial atherosclerotic coronary artery disease (CAD) has been recognized as its main cause. The clinical manifestations of chronic CAD are secondary to the progressive decrease in tissue perfusion due to the growth of plaques inside the vessel lumen and the consequent reduction of the coronary flow reserve (CFR), that is, the ratio between blood flow duringmaximal coronary vasodilation and resting flow. The clinical demonstration of the CFR reduction is ischaemia from increased oxygen demand and effort angina. The non-invasive tests for inducible ischaemia, such as nuclear perfusion imaging or stress echocardiography, could demonstrate reversible regional perfusion abnormalities or impairedmyocardial contractility usually confirmed by ST-segment depression on the electrocardiogram (ECG). Coronary angiogram usually demonstrates one or more stenoses in the epicardial coronary arteries with more than 70% lumen reduction. Some patients, however, do not manifest the classical angina symptoms. Angina can occur at rest, rather than with effort, during night-time, in bouts, and the stress test could be normal. The ECG during the angina episode could reveal an elevation of the ST-segment when the focal spasm is >90%, determining trans-mural ischaemia. When the spasm is not focal, but still >90%, and affects one or more segments of the vessel, it determines subendocardial ischaemia, and the ST-segment on the ECG is depressed. In a good number of these patients, CAD could coexist (Prinzmetal variant angina). Ong et al. studied a large cohort of consecutive patients (921) undergoing coronary angiogram for suspected myocardial ischaemia, but without evidence of obstructive CAD. All patients underwent acetylcholine provocative test, and the documented overall frequency of epicardial coronary arteries spasm was 33.4%. Furthermore, 24.2% of the patients had evidence of microvascular spasm (angina and ECG ischaemic changes without epicardial coronary arteries spasm after acetylcholine infusion). A significant fraction of patients undergoing coronary angiogram for angina has normal coronary arteries or nonobstructive CAD (stenosis <50%). A study by Cannon and Epstein, demonstrated that patients with chest pain and normal coronary arteries at angiogram, as compared to a group of asymptomatic controls, had an enhanced sensibility to coronary microcirculation vasoconstrictive stimuli, and a limitedmicrocirculatory vasodilation response during pacing-induced atrial tachycardia; the condition was definedmicrovascular angina. In its entirety, the coronary arterial system comprises three functional components, albeit not clearly distinct anatomically. The proximal component includes the large epicardial coronary arteries with a diameter between 2–5mm and 500lm; they function as capacitance vessels and offer little resistance to the blood flow. During systole, the epicardial coronary arteries increase their blood volume up to 25%, storing in this way elastic energy which is converted in kinetic energy at the beginning of diastole, thus contributing to the re-opening of the intra-myocardial vessels, compressed during systole. The intermediate component is represented by the pre-arterioles, with a diameter between 500lmand 100lm, and is characterized by pressure loss throughout its course. These vessels are not subject to the vasomotor control by the myocardial metabolites due to their extra-myocardial localization and the thickness of their wall. Their specific function is the maintenance of pressure at the origin of the arterioles within a narrow range when the pressure or the coronary flow change. The proximal pre-arterioles react more readily to changes in flow, whether the distal pre-arterioles are