Mechanisms of coronary artery spasm

The term coronary artery spasm (CAS) refers to a sudden,\r\nintense vasoconstriction of an epicardial coronary artery\r\nthat causes vessel occlusion or near occlusion. Although CAS\r\nmay be involved in other coronary syndromes, it represents\r\nthe usual cause of variant angina.\r\nThe variant form of angina was first described in 1959 by\r\nPrinzmetal et al,1 who used this term to indicate that angina\r\nattacks, unlike the most common form of effort angina,\r\noccurred at rest and were associated with ST-segment elevation,\r\nrather than ST-segment depression, on the ECG (Figure\r\n1). Because myocardial ischemia occurred in the absence of\r\nany change in myocardial oxygen demand, the authors\r\nhypothesized that it was caused by an increased tonus of\r\nvessels at the level of coronary stenoses.1\r\nSome years later, in fact, coronary angiography, performed\r\nduring spontaneous angina attacks, demonstrated that CAS is\r\nthe usual cause of variant angina.2 4 Coronary angiography\r\nalso showed that CAS could occur at the site of a stenosis\r\n(either minor or severe) or in angiographically normal coronary\r\narteries,5 usually at a localized segment of an epicardial\r\nartery (focal spasm) (Figure 2).6 However, sometimes CAS\r\ninvolves 2 or more segments of the same (multifocal spasm)\r\nor of different (multivessel spasm) epicardial coronary arteries,\r\nor may also involve diffusely one or multiple coronary\r\nbranches.7\r\nCareful assessment of clinical history and 24- to 72-hour\r\nambulatory ECG monitoring are usually sufficient to achieve\r\nthe diagnosis of variant angina, whereas the use of provocative\r\ntests of CAS (eg, intravenous ergonovine, intracoronary\r\nergonovine, or acetylcholine administration) is required in\r\nabout 10% of patients.7\r\nTransmural myocardial ischemia caused by occlusive CAS\r\ncan be complicated by malignant ventricular arrhythmias,8,9\r\nwhich can result in sudden death, or, if prolonged, by acute\r\nmyocardial infarction.10 Accordingly, a prompt diagnosis\r\nwould be essential to prevent these serious complications,\r\neven though calcium antagonists are very effective in preventing\r\nCAS.11,12 However, the diagnosis of variant angina is\r\noften overlooked for several months after its manifestation.7\r\nSixty years after the first description of variant angina, the\r\ncauses and the mechanisms of CAS are still poorly defined.\r\nThe research in this field has indeed been refrained by several\r\nfactors, including the low incidence of the disease and the\r\nconsiderable efficacy of nonspecific vasodilator therapy.12\r\nHowever, in 10% to 20% of patients, CAS is refractory to\r\nstandard treatment, or high doses of calcium antagonists are\r\nneeded to effectively prevent its recurrence. Thus, elucidating\r\nthe mechanisms responsible for CAS could make treatment of\r\ndifficult or refractory cases easier.13\r\nIn this article, we review the state of knowledge regarding\r\nthe etiopathogenesis of CAS in patients with the clinical\r\nsyndrome of Prinzmetal variant angina.