Coronary spastic angina; Variant angina; Vasospastic angina; Prinzmetal angina
Definition and Characteristics
No overall value for the prevalence of coronary spasm can be given. However, there seems to be a racial heterogeneity in coronary spasm  with coronary spasm observed more frequently in Eastern populations.
Because endothelial dysfunction is one of the causes of coronary spasm, endothelial nitric oxide synthase (eNOS) gene variants (T-786→C mutation and a missense Glu298 Asp variant) have been associated with coronary spasm.
Molecular and Systemic Pathophysiology
The precise mechanisms underlying coronary spasm remain to be elucidated, but several factors have been implicated in the pathogenesis of coronary spasm. First, the provocation of coronary spasm by acetylcholine (ACh) and its prevention by atropine and alpha-adrenergic receptor blockers may suggest an important role for the parasympathetic nervous system and for the activation of alpha-adrenergic receptors. Second, endothelial dysfunction, due to eNOS gene mutation, an increased concentration of reactive oxygen species induced by cigarette smoking, vitamin C deficiency, insulin resistance, and vascular inflammation, may be responsible for the pathogenesis of coronary spasm. Third, hyperreactivity of coronary smooth muscle cells due to an increase in the calcium-sensitivity of the vascular myosin chain has been proposed as one of the mechanisms of coronary spasm.
With respect to spasm-provocative medications, there are mainly two agents: ergonovine maleate (EM) and ACh. Intravenous administration of EM was used previously but has not been widely adopted because there is a risk of causing multivessel coronary spasm including right and left coronary arteries, simultaneously. Therefore, instead of intravenous administration, intracoronary infusion of EM has often been used. ACh also is infused intracoronarily as a spasm-provocative drug. The spasm-provocation tests using intracoronary infusion of these drugs are effective in producing coronary spasm with fewer major complications . However, the duration of coronary spasm seems to be shorter using ACh than using EM and thus ACh may be safer in performing spasm-provocation tests on both the left and right coronary arteries. On the other hand, ACh itself causes sinus bradycardia and atrioventricular block and thus a temporary pacemaker is needed to prevent such arrhythmias induced during ACh infusion. A positive provocative test is defined as the presence of subtotal or total occlusion of a coronary artery due to coronary spasm on the angiogram accompanied by chest pain and/or ST segment changes on the ECG. Nitroglycerin is infused intracoronarily to relieve coronary spasm when the diagnosis of coronary spasm is made.
Prohibiting cigarette smoking is important and may reduce the activity of coronary spasm. Long-acting calcium channel blockers are the first line therapy, and additional long-acting nitrates and/or nicorandil also are effective. However, these medications do not always prevent coronary spasm and patients should be advised to use sublingual nitrates without hesitation when they experience symptoms. Furthermore, it has been shown that the potential for causing coronary spasm does not disappear and patients should be advised not to stop taking vasodilators by themselves even if they have symptoms for a long time. It is known that abrupt cessation of vasodilators therapy sometimes causes severe rebound anginal attacks. Monotherapy with beta blockers should be avoided because it can worsen coronary spasm due to a relative increase in alpha-adrenergic activity. When coronary spasm is refractory to conventional therapy, medications such as vitamin C, anti-depressive drugs, and denopamine are occasionally effective. Treatment with coronary stenting has been shown to be effective in such patients while the long-term prognosis, including restenosis, remains unclear.