Coronary Artery Spasm as a Cause of Angina
Coronary vasoconstriction has moved in and out of fashion for more than a century. The initial descriptions of angina considered vasomotor instability as a key mechanism,1 but pathologic studies2 and the invention of coronary angiography in the middle of the last century focused attention on structural stenoses and occlusions attributed to atheromatous plaques. When Prinzmetal et al3 described a variant form of angina, which was later confirmed as a coronary spasm,4 vasomotor instability returned to the limelight. Variant angina is characterized by symptoms at rest (not exertion) with ST elevation on ECG (not depression). It usually occurs in the early hours of the morning during depressed vagal tone and is associated with occlusion or near occlusion (>90% stenosis) of a focal proximal coronary segment on angiography.
Provocative Tests for Coronary Spasm in Variant Angina
In the late 1970s and early 1980s, several groups used intravenous or intracoronary ergonovine to provoke coronary vasospasm in patients with variant angina.5–9 Ergonovine causes vasoconstriction of the vascular smooth muscle, which is usually mild in patients without variant angina. In variant angina, ergonovine causes severe focal epicardial spasm with ST elevation and typical angina symptoms.10 Ergonovine causes this response in ≈4% of patients referred for angiography for a variety of indications but in >80% of patients with variant angina. Spasm most often occurs at sites of mild-to-moderate atheromatous stenoses,5,6 but even sites that are angiographically normal have atheroma by intravascular ultrasound.11
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Ergonovine has a relatively long half-life, and, given intravenously, often causes headaches, nausea, and hypertension. Intracoronary and intravenous administration have small risks of ventricular fibrillation, myocardial infarction, or spasm refractory to systemic nitroglycerin requiring intracoronary nitroglycerin.5–7,12,13 Acetylcholine has a much shorter half-life and is considered safer than ergonovine, although …