Mechanisms of Coronary Artery Spasm

The term coronary artery spasm (CAS) refers to a sudden,\udintense vasoconstriction of an epicardial coronary artery\udthat causes vessel occlusion or near occlusion. Although CAS\udmay be involved in other coronary syndromes, it represents\udthe usual cause of variant angina.\udThe variant form of angina was first described in 1959 by\udPrinzmetal et al,1 who used this term to indicate that angina\udattacks, unlike the most common form of effort angina,\udoccurred at rest and were associated with ST-segment elevation,\udrather than ST-segment depression, on the ECG (Figure\ud1). Because myocardial ischemia occurred in the absence of\udany change in myocardial oxygen demand, the authors\udhypothesized that it was caused by an increased tonus of\udvessels at the level of coronary stenoses.1\udSome years later, in fact, coronary angiography, performed\udduring spontaneous angina attacks, demonstrated that CAS is\udthe usual cause of variant angina.2 4 Coronary angiography\udalso showed that CAS could occur at the site of a stenosis\ud(either minor or severe) or in angiographically normal coronary\udarteries,5 usually at a localized segment of an epicardial\udartery (focal spasm) (Figure 2).6 However, sometimes CAS\udinvolves 2 or more segments of the same (multifocal spasm)\udor of different (multivessel spasm) epicardial coronary arteries,\udor may also involve diffusely one or multiple coronary\udbranches.7\udCareful assessment of clinical history and 24- to 72-hour\udambulatory ECG monitoring are usually sufficient to achieve\udthe diagnosis of variant angina, whereas the use of provocative\udtests of CAS (eg, intravenous ergonovine, intracoronary\udergonovine, or acetylcholine administration) is required in\udabout 10% of patients.7\udTransmural myocardial ischemia caused by occlusive CAS\udcan be complicated by malignant ventricular arrhythmias,8,9\udwhich can result in sudden death, or, if prolonged, by acute\udmyocardial infarction.10 Accordingly, a prompt diagnosis\udwould be essential to prevent these serious complications,\udeven though calcium antagonists are very effective in preventing\udCAS.11,12 However, the diagnosis of variant angina is\udoften overlooked for several months after its manifestation.7\udSixty years after the first description of variant angina, the\udcauses and the mechanisms of CAS are still poorly defined.\udThe research in this field has indeed been refrained by several\udfactors, including the low incidence of the disease and the\udconsiderable efficacy of nonspecific vasodilator therapy.12\udHowever, in 10% to 20% of patients, CAS is refractory to\udstandard treatment, or high doses of calcium antagonists are\udneeded to effectively prevent its recurrence. Thus, elucidating\udthe mechanisms responsible for CAS could make treatment of\uddifficult or refractory cases easier.13\udIn this article, we review the state of knowledge regarding\udthe etiopathogenesis of CAS in patients with the clinical\udsyndrome of Prinzmetal variant angina