Contemporary Reviews in Cardiovascular Medicine Primary Coronary Microvascular Dysfunction Clinical Presentation, Pathophysiology, and Management

Myocardial ischemia is usually caused by abnormalities of epicardial coronary arteries. In the past 30 years, however, several studies have shown that abnormalities in coronary microcirculation may also cause or contribute to myocardial ischemia in several conditions. Accordingly, Camici and Crea1 have recently proposed a classification of coronary microvascular dysfunction (CMVD) based on the clinical setting in which it occurs (eg, obstructive coronary artery disease [CAD], cardiomyopathy, and systemic diseases) (Table 1). In these various conditions, CMVD can be caused by specific mechanisms related to the underlying disease. In a number of patients who present with angina attacks in the absence of any apparent cardiac or systemic disease, CMVD has been suggested to be the unique cause of symptoms. This condition is known as microvascular angina (MVA)2 and can be better defined as primary MVA to distinguish it from MVA occurring in the setting of specific diseases, which can be defined as secondary MVA. In clinical practice, primary MVA is usually suspected, by exclusion, in patients with sufficiently typical chest pain in whom, despite abnormalities of the ECG and/or stress test results indicative of myocardial ischemia, arteriography surprisingly fails to show fixed or dynamic obstructions in epicardial coronary arteries.3 Primary MVA, however, includes heterogeneous groups of patients, with different pathogenetic and pathophysiological mechanisms of CMVD, who might have different clinical implications and need different diagnostic and therapeutic approaches. In several previous studies, however, patients with different characteristics of chest pain, possibly related to different mechanisms of CMVD or even to nonischemic or noncardiac causes, have often been considered together, usually under the general descriptive term of chest pain with normal coronary arteries, which may have contributed to generate contrasting results and some confusion about the clinical manifestations and implications of CMVD and MVA.4 In this article, we suggest a classification of primary MVA in 2 main forms, a stable (chronic) and an unstable (acute) form (Figure 1), which can be distinguished on the basis of clinical presentation, and we review their possible pathogenetic mechanisms and clinical approach and implications. Furthermore, we also discuss the evidence for a primary role of CMVD in 2 specific clinical syndromes characterized by ST-segment elevation: microvascular spasm angina and stress-related cardiomyopathy.