Vasospastic angina (VSA), variant angina or Prinzmetal angina is a clinical entity that refers to a hyper-reactive response of the epicardial coronary arteries to vasoconstrictor stimuli.

Epidemiology

Incidence and prevalence seem not entirely explored and are highly variable between certain populations. It seems to be higher in Asia than in western countries ¹. The condition is most often diagnosed in patients between the age of 40 to 70 years ².

Risk factors

Risk factors for vasospastic angina include the following conditions ^1-3:

• smoking
• migraine

Associations

Vasospastic angina can be associated with the following clinical conditions ^1,2:

• acute coronary syndrome
• chronic coronary syndrome
• arrhythmias
• syncope
• non-ischaemic cardiomyopathy

Diagnosis

The diagnosis of vasospastic angina is based on clinical criteria and typical findings on coronary angiography either spontaneous or in response to provocative stimuli.

Diagnostic criteria

Diagnostic criteria proposed by Coronary Vasomotion Disorders International Study Group (COVADIS) ^2,3:

• spontaneous event of angina responsive to nitrates associated with one of the following:
  • angina under resting conditions – often at night and early morning
  • diurnal variance in exercise tolerance
  • can be triggered by hyperventilation
  • prompt response to calcium channel blockers (but not beta-blockers)
• transient ischaemic ECG changes during a spontaneous event in at least two adjacent lead with one of the following: 
  • ST-segment elevation >0.1 mV
  • ST-segment depression >0.1 mV
  • new negative U waves
• spontaneous or stimulated coronary vasospasm on coronary angiogram defined by constriction >90% of the vessel lumen associated with angina and typical ischaemic changes on ECG

Diagnostic clues

Clinical and imaging-related information that might point towards the diagnosis without the information of coronary angiogram with spasm provocation:

• multiple admissions to the emergency department with angina unrelated to exercise and improving with nitrates
• obstructive coronary artery disease ruled out by coronary angiography or cardiac CT
• transient ST-segment changes on an electrocardiogram during the chest discomfort

Clinical presentation

The typical clinical presentation is angina associated with cold sweats and/or under resting conditions instantaneously improving on the administration of short-acting nitrates. Symptoms are not usually caused by physical activity but might be triggered by hyperventilation and can be suppressed by calcium channel blockers ^1-3.

It can be precipitated by many factors, including emotional stress, alcohol consumption, stimulating drugs, sympathomimetic, parasympathomimetic and vasoconstricting medications ^1,2. 

An electrocardiogram might reveal peaked symmetrical T waves during vasospasm in about 50% of cases. Other changes included ST-segment elevation or depression, negative U-wave, negative T wave and changes in the R wave ¹.

Complications

Complications of vasospastic angina include the following conditions ^1,2:

• syncope
• arrhythmias or atrioventricular block
• myocardial infarction with non-obstructive coronary arteries
• sudden cardiac death

Pathology

Vasospastic angina is characterised by an abnormal vasomotor response of the epicardial coronary arteries in response to vasoconstrictive stimuli. The following mechanisms are considered to have a role in the pathogenesis ^1-4:

• vascular smooth muscle hyperactivity
• endothelial dysfunction
• magnesium deficiency
• low-grade inflammation
• autonomic dysfunction
• oxidative stress
• genetic factors

Radiographic features

Coronary vasospasm is a transient luminal constriction > 90% with concomitant resting angina and ischaemic changes on electrocardiogram ⁴.

If the coronary vasospasm is confined to one coronary segment, it is called ‘focal’. If two or more adjacent coronary segments are affected, it is called ‘diffuse’.

Echocardiography

Echocardiography can identify regional wall-motion abnormalities in the acute setting ².

CT

Coronary CTA can rule out coronary artery disease or significant coronary stenosis ². Coronary CTA has also been described as showing relevant stenosis, which has been confirmed as coronary vasospasm on invasive coronary angiography (ICA) at a later stage ^4,5.

Coronary angiography

Invasive coronary artery spasm provocation is typically done by intracoronary injection of acetylcholine or administration of ergonovine (intracoronary or intravenously).

The test is only considered positive if all of the following can be shown in response to the applied stimulus ^1-4:

• usual chest pain
• ischaemic ECG changes
• transient luminal obstruction >90% in one isolated coronary segment (focal vasospasm) or more adjacent coronary segments (diffuse vasospasm)

If not all three criteria are met, the test is considered equivocal ³.

Spontaneous focal coronary vasospasms are challenging to diagnose, and intracoronary nitroglycerine might be useful to differentiate them from plaque-related coronary artery stenosis ¹.

Optical coherence tomography (OCT) or intravascular ultrasound (IVUS) might give further insights into structural alterations of the vascular wall caused by coronary vasospasms and can show intimal thickening without calcium or lipid content ⁴.

MRI

Cardiac MRI might identify regional wall-motion abnormalities, myocardial oedema, myocardial fibrosis and myocardial scar tissue ². Subendocardial late gadolinium enhancement in a coronary territory indicates myocardial scar tissue due to myocardial ischaemia and aids in narrowing down the differential diagnosis, especially in the absence of non-obstructive coronary artery disease.

Radiology report

The radiological report should include a description of the following features based on the AHA coronary artery segments or the cardiac segmentation model:

• cardiac CT
  • suspected coronary vasospasm
  • absence of coronary artery disease or significant coronary stenosis (if applicable)
• cardiac MRI
  • regional wall motion abnormalities
  • signs of myocardial ischaemia
  • myocardial scar

Treatment and prognosis

Vasospastic angina is associated with major adverse cardiovascular events and arrhythmias ¹. Long-term prognosis is considered reasonable with survival rates of 97% and 93% for 5 and 10 years in patients without coronary artery disease or 83% and 81% in patients with concomitant coronary artery disease but without myocardial infarction ¹.

Main treatment steps include lifestyle modifications and pharmacotherapy ^1-3:

• lifestyle modification
  • smoking cessation
  • weight loss
  • avoidance of aggravating factors as mental stress, alcohol, cocaine-like products and vasospastic agents 
• pharmacological therapy
  • calcium channel blockers
  • nitrates
  • lipid-lowering agents (statins)
  • α₁-receptor antagonists
  • rho-kinase inhibitors
  • nicorandil
  • antiplatelet therapy (high-dose aspirin should be avoided)

In patients with life-threatening arrhythmias, an implantable cardioverter-defibrillator can be considered for secondary prevention ¹. 

History and etymology

Vasospastic angina was first described as ‘variant angina’ by M. Prinzmetal and colleagues in 1959 ^4,6.

Differential diagnosis

Conditions that can mimic the clinical presentation or appearance of variant angina include ¹:

• coronary artery disease (acute and chronic coronary syndromes)
• coronary microvascular dysfunction
• coronary artery dissection
• gastrooesophageal reflux disease