The term coronary artery spasm (CAS) refers to a sudden, intense vasoconstriction of an epicardial coronary artery that causes vessel occlusion or near occlusion. Although CAS may be involved in other coronary syndromes, it represents the usual cause of variant angina. The variant form of angina was first described in 1959 by Prinzmetal et al,1 who used this term to indicate that angina attacks, unlike the most common form of effort angina, occurred at rest and were associated with ST-segment elevation, rather than ST-segment depression, on the ECG (Figure 1). Because myocardial ischemia occurred in the absence of any change in myocardial oxygen demand, the authors hypothesized that it was caused by an increased tonus of vessels at the level of coronary stenoses.1 Some years later, in fact, coronary angiography, performed during spontaneous angina attacks, demonstrated that CAS is the usual cause of variant angina.2 4 Coronary angiography also showed that CAS could occur at the site of a stenosis (either minor or severe) or in angiographically normal coronary arteries,5 usually at a localized segment of an epicardial artery (focal spasm) (Figure 2).6 However, sometimes CAS involves 2 or more segments of the same (multifocal spasm) or of different (multivessel spasm) epicardial coronary arteries, or may also involve diffusely one or multiple coronary branches.7 Careful assessment of clinical history and 24- to 72-hour ambulatory ECG monitoring are usually sufficient to achieve the diagnosis of variant angina, whereas the use of provocative tests of CAS (eg, intravenous ergonovine, intracoronary ergonovine, or acetylcholine administration) is required in about 10% of patients.7 Transmural myocardial ischemia caused by occlusive CAS can be complicated by malignant ventricular arrhythmias,8,9 which can result in sudden death, or, if prolonged, by acute myocardial infarction.10 Accordingly, a prompt diagnosis would be essential to prevent these serious complications, even though calcium antagonists are very effective in preventing CAS.11,12 However, the diagnosis of variant angina is often overlooked for several months after its manifestation.7 Sixty years after the first description of variant angina, the causes and the mechanisms of CAS are still poorly defined. The research in this field has indeed been refrained by several factors, including the low incidence of the disease and the considerable efficacy of nonspecific vasodilator therapy.12 However, in 10% to 20% of patients, CAS is refractory to standard treatment, or high doses of calcium antagonists are needed to effectively prevent its recurrence. Thus, elucidating the mechanisms responsible for CAS could make treatment of difficult or refractory cases easier.13 In this article, we review the state of knowledge regarding the etiopathogenesis of CAS in patients with the clinical syndrome of Prinzmetal variant angina.
- coronary spasm