Myocardial ischaemia is usually caused by abnormalities of the epicardial coronary arteries. In the past 30 years, however, several studies have shown that abnormalities in the coronary microcirculation may also cause or contribute to myocardial ischaemia in several conditions. In a number of patients who present with anginal attacks in the absence of any apparent cardiac or systemic disease, coronary microvascular dysfunction (CMD) has been suggested to be the unique cause of symptoms.^w1 Myocardial blood flow (MBF) abnormalities and the consequent myocardial alterations related to CMD may differ substantially from those caused by flow limiting stenoses in epicardial coronary arteries. In the latter case, the impairment of MBF is generally regional and distributed within the territories subtended by the stenosed artery, resulting in detectable segmental impairment of contractile function. In contrast, in the case of CMD, the abnormality may not necessarily involve the territory subtended by a major coronary branch, but it may affect the whole left ventricle diffusely or be distributed in a scattered manner.1 ^w1

CMD may be sustained by several pathogenetic mechanisms including structural, functional, and extravascular alterations that can contribute to the condition in different ways. On the basis of the clinical settings in which it occurs, CMD can be classified into four types: (1) dysfunction occurring in the absence of coronary artery disease (CAD) and myocardial diseases; (2) dysfunction occurring in the absence of CAD, but in the presence of myocardial diseases; (3) dysfunction occurring concomitantly with CAD; (4) iatrogenic dysfunction.1

CMD in the presence of myocardial diseases is sustained in most instances by adverse remodelling of intramural coronary arterioles, and can be identified by invasive or non-invasive assessment of coronary flow reserve (CFR). CFR—the ratio of MBF during near maximal coronary vasodilatation to basal MBF—is an integrated measure of flow through both …