Reference Work Entry

Encyclopedia of Molecular Mechanisms of Disease

pp 451-453

Coronary Spasm

  • Hiroki TeragawaAffiliated withDepartment of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University
  • , Kazuaki ChayamaAffiliated withDepartment of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University


Coronary spastic angina; Variant angina; Vasospastic angina; Prinzmetal angina

Definition and Characteristics

Coronary spasm is defined as a dynamic and transient reduction in the luminal diameter of epicardial coronary arteries due to increased vasomotor tone, leading to myocardial ischemia. It was first reported as variant angina by Prinzmetal et al. [1], who demonstrated reversible myocardial ischemia accompanied by ST segment elevation on the electrocardiogram (ECG). At present, it is believed that coronary spasm plays an important role in the pathogenesis of not only variant angina but ischemic heart disease as well, including other forms of angina, acute myocardial infarction, and ischemic sudden death. In general, patients with coronary spasm are younger than those with organic coronary stenosis and cigarette smoking is considered to be a major risk factor for coronary spasm. Typically, there is a circadian variation with an increased prevalence of anginal attacks from midnight to the early morning. During coronary spasm, ST segment elevation on the ECG is frequently observed (Fig. 1) although ST segment depression is sometimes seen when the coronary artery is not completely occluded due to coronary spasm. Therefore, clinical syndromes caused by coronary spasm, including variant angina, are collectively known as coronary spastic angina (CSA). In addition, life-threatening arrhythmias such as atrioventricular block, ventricular tachycardia, and ventricular fibrillation, are also frequently observed during coronary spasm.
Coronary Spasm. Figure 1

Ambulatory monitoring in a patient with coronary spasm. (a) In the asymptomatic state, there were no significant ST changes on the ECG. (b) When the patient had chest pain at 4:40 in the early morning, the ECG demonstrated marked ST elevation in the precordial leads, accompanied by premature ventricular contractions.


No overall value for the prevalence of coronary spasm can be given. However, there seems to be a racial heterogeneity in coronary spasm [2] 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.

Diagnostic Principles

There have been no established criteria for diagnosing coronary spasm. In fact, treatment with vasodilators may sometimes be initiated when ST segment elevation is documented during an ambulatory monitoring in patients who have chest symptoms at rest, especially from midnight to the early morning. In addition, treatment with vasodilators may be continued when such drugs, prescribed as a test drug, are effective in relieving anginal attacks in such patients. Hyperventilation testing may cause coronary spasm, especially in the early morning although this test is thought to be less sensitive but highly specific in diagnosing coronary spasm. Coronary angiography is useful in patients with suspected coronary spasm, not only to establish a final diagnosis of coronary spasm using spasm-provocative medications but also to exclude the presence of organic coronary stenosis (Fig. 2).
Coronary Spasm. Figure 2

Coronary angiography and spasm-provocative testing in a patient with coronary spasm. (a) There was no organic coronary stenosis on the angiogram. (b) After intracoronary infusion of ergonovine maleate (EM, 30 μg), coronary angiography demonstrated a total occlusion in the proximal segment of the left circumflex coronary artery. (c) After intracoronary administration of nitroglycerin, coronary spasm completely resolved and the coronary artery dilated.

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 [3]. 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.

Therapeutic Principles

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.

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© Springer-Verlag GmbH Berlin Heidelberg 2009
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