Coronary vasospasm

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Coronary vasospasm
Other names: Prinzmetal angina, variant angina, coronary artery spasm, vasospastic angina[1]
a) Preoperative angiogram b) postoperative angiogram with focal spasm at the arrow c) resolution after intracoronary nitroglycerin
SymptomsChest pain not related to exercise; may be variable[2]
ComplicationsArrhythmias, sudden cardiac death[1]
Usual onsetEarly hours of the morning[1]
CausesSmoking, genetics[1]
Risk factorsStimulants, psychological stress, alcohol, anaphylaxis, certain types of chemotherapy[1][2]
Diagnostic methodNormal coronary arteries on cardiac catheterization, coronary reactivity testing[1]
TreatmentCalcium channel blockers, nitrates, statin, ACE inhibitors, implantable cardioverter defibrillator[1]
Frequency2.5% to 15% of heart related chest pain[1]

Coronary vasospasm, also known as Prinzmetal angina, is a temporary partial or complete blockage of a coronary artery due to vasoconstriction.[1][2] Symptoms often include chest pain not related to exercise.[2] Onset is typically in the early hours of the morning and may wake a person from sleep.[1] Though symptoms may be variable.[2] Complications may include arrhythmias and sudden cardiac death.[1]

Risk factors include smoking.[1] Triggers may include stimulants such as cocaine, psychological stress, a few hours following alcohol, anaphylaxis, and certain types of chemotherapy.[1][2] An ECG often shows ST elevation during the attack, which resolves with nitroglycerin.[2] Diagnosis is supported by normal coronary arteries on cardiac catheterization and confirmed by coronary reactivity testing.[1]

Treatment may involve the use of calcium channel blockers, such as diltiazem, and nitrates, such as nitroglycerin.[1] Statin and ACE inhibitors may also be used.[1] An implantable cardioverter defibrillator (ICD) may be used in those with certain arrhythmias.[1] Beta blockers and aspirin are generally not used.[1]

Coronary vasospasm is estimated to represent 2.5% to 15% of presumed heart related chest pain.[1] It affects women more often than men.[1] Those of East Asian decent are more commonly affected.[1] It was first described in 1959 by Myron Prinzmetal who referred to it as variant angina.[1][3]

Signs and symptoms

Coronary vasospasm classically produces chest pain at rest, also known as vasospastic angina.[4] Chest pain is more common at certain times of the day, usually from late night to early morning.[5] These episodes can be accompanied by nausea, vomiting, cold sweating, and even syncope.[6][7] Coronary vasospasm is also associated with symptoms of fatigue and tiredness, dyspnea, and palpitations.[4] These can sometimes be the primary presenting symptoms, but they can also occur in conjunction with chest pain.[4]

There are cases of coronary vasospasm that occur without any symptoms at all, leading to episodes of silent or asymptomatic myocardial ischemia.[6][7]


Depending on how long the occlusion lasts, a spectrum of different myocardial ischemic syndromes can occur. Shorter episodes of occlusion can lead to what is referred to as silent myocardial ischemia due to its asymptomatic nature.[8] These episodes can also be accompanied by arrhythmias.[8] Longer episodes of occlusion can lead to stable or unstable angina, myocardial infarction, and sudden cardiac death.[8]

Risk factors

Unlike classical angina pectoris, traditional cardiovascular risk factors are not thought to be significantly associated with coronary vasospasm.[9] The exception to this is with smoking, which is known to be a modifiable risk factor for vasospastic angina.[9][10]

There are several risk factors that are thought to precipitate, or trigger, episodes of coronary vasospasm. Many of these factors work by exerting effects on the autonomic nervous system. One of the mechanisms through which this occurs is via increasing sympathetic nervous system activity. The resulting increased sympathetic outflow leads to vasoconstrictive effects on blood vessels.[9] For example, cocaine use can trigger vasospasm in coronary arteries through its actions on adrenergic receptors causing vasoconstriction.[11] Exercise, cold weather, physical activity or exertion, mental stress, hyperventilation are additional precipitating factors.[9][6]


The exact pathophysiology behind coronary vasospasm has not been elucidated. Instead, a combination of different factors has been proposed to contribute to coronary vasospasm.[12] In general, it is thought that an abnormality within a coronary artery causes it to become hyperreactive to vasoconstrictor stimuli. This abnormality can be located in one segment of the coronary artery, or it may be diffuse and present throughout the entire artery. If and when vasoconstrictor stimuli act upon the hyperreactive segment of the artery, then vasospasm can result.[9] Ultimately, when large coronary arteries undergo vasospasm, this can lead to either complete or transient occlusion of blood flow within the artery. As a result, ischemia to the tissues served by the artery can occur. Symptoms due to ischemia can follow.[13]

Some of the factors that have been proposed to contribute to coronary vasospasm include the following:[8][12]

  • Endothelial dysfunction
    • Certain vasodilatory agents exert their effects by working via the endothelium, the cells that make up the lining of blood vessels. Specifically, these agents work by enhancing the production of nitric oxide from endothelial nitric oxide synthase. Normally, nitric oxide then works to promote vasodilation in a blood vessel through its own mechanisms such as inhibiting the release of agents that cause vasoconstriction.[12]
    • Endothelial dysfunction wherein there is a deficiency in the production of nitric oxide has been found to be associated with coronary vasospasm in some but not all cases.[12] Vasodilatory agents with mechanisms dependent on a functional endothelial nitric oxide synthase can cause vasoconstriction instead in the setting of endothelial dysfunction, leading to coronary vasospasm.[12]
  • Chronic inflammation
    • Various markers of low-grade chronic inflammation have been found in cases of coronary vasospasm.[14][15]
    • In addition to this, one of the risk factors for coronary vasospasm is smoking.[9][10] Chronic inflammation due to smoking has been shown to be damaging to endothelial cell function.[16]
  • Oxidative Stress
    • Oxygen free radicals contribute to the pathogenesis of coronary vasospasm through their damaging effects on vascular endothelial cells and degrading nitric oxide, an important vasodilatory agent.[8][12][17]
  • Smooth Muscle Hypercontractility
    • At a cellular level, pathways that lead to enhanced myosin light chain phosphorylation promote vasoconstriction. Increased activity of Rho-kinase leading to enhanced myosin light chain phosphorylation has been implicated in the pathogenesis of coronary vasospasm.[8][18]


There are no set criteria to diagnose coronary vasospasm. Thorough history taking by a clinician can assist in the diagnosis of coronary vasospasm. In cases where symptoms of chest pain are present, identifying features that distinguish episodes of vasospastic angina from traditional angina can aid in the diagnosis.[5] Features such as chest pain at rest, a diurnal variation in tolerance for exercise with a reduction in tolerance for exercise in the morning, and responsiveness of chest pain to calcium channel blockers as opposed to beta blockers can be important clues.[5]

EKG can occasionally be used to diagnose episodes of coronary vasospasm. However, relying on EKG is not always possible due to the transient nature of coronary vasospasm episodes.[5][19] Due to the challenge of capturing episodes of coronary vasospasm spontaneously, provocative testing to induce coronary vasospasm during coronary catheterization can be used to make the diagnosis.[19] Provocative testing relies upon the use of pharmacological agents that promote or trigger episodes of vasospasm. Agents commonly administered include ergonovine and acetylcholine. Both pharmacological agents have vasoconstrictive effects on coronary arteries.[19] However, in the clinical setting, provocative testing is not routinely performed.[20] The reason for this is due to the adverse effects of these pharmacological agents.[20]


Prinzmetal angina showing significant ST elevation

When coronary vasospasm causes an artery to undergo complete occlusion, an EKG might show evidence of ST-segment elevation in the leads indicative of that artery's territory. Transient ST-segment depression can also occur, usually in the setting of sub-total occlusion of an artery.[6]

Additional EKG findings in coronary vasospasm include evidence of arrhythmias that might be induced by ischemia: ventricular premature contractions, ventricular tachycardia, ventricular fibrillation, and more.[6]


Chest pain due to coronary vasospasm was described in the medical literature by Prinzmetal et al. in 1959.[3] This discovery led to this type of angina being referred to in the literature as Prinzmetal angina.[21][20] A following study further distinguished this angina from classical angina pectoris due to the fact that the results showed that the patients with chest pain due to coronary vasospasm lacked evidence of atherosclerosis on cardiac catheterization.[21][20] Angina due to coronary vasospasm is also known as variant angina.[20]


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