Prinzmetal Angina

Synonym: variant angina; coronary artery vasospasm

First described by Prinzmetal et al in 1959, this syndrome is due to focal coronary artery vasospasm and may be associated with acute myocardial infarction, serious ventricular arrhythmias and sudden death.¹ Most patients have underlying coronary artery disease, but some have normal arteries.

• Estimates are that 2-3% of all patients undergoing diagnostic cardiac catheterisation for chest pain have variant angina.
• Risk factors include smoking, hyperinsulinaemia and insulin resistance.²
• There is an increased prevalence in Japan.³

• Variant angina occurs at rest and exhibits a circadian pattern, with most episodes occurring in the early hours of the morning.
• The pain is often severe and may be associated with palpitations or syncope secondary to arrhythmia.
• A minority of patients with variant angina may have an abnormality of vasomotor tone, and also present with symptoms of migraine headache and Raynaud's phenomenon.
• Examination findings in patients with variant angina are usually normal, but a fourth heart sound or mitral regurgitation may be heard during episodes of pain.
• Finding other evidence of diffuse atherosclerotic disease does not differentiate patients with variant angina from those with unstable angina, and physical examination does not reliably differentiate between variant angina and occlusive coronary artery disease.

• Other causes of chest pain.
• Distinguishing unstable angina pectoris related to coronary atherosclerosis from variant angina may be difficult and requires special investigations, including coronary angiography.
• Many patients with variant angina have obstructive coronary artery disease.
• The absence of risk factors for atherosclerotic coronary artery disease suggests variant angina, although cigarette smoking is a common risk factor for both clinical syndromes and is reported in most patients with variant angina.

• Full blood count, renal function, electrolytes and lipid profiles to exclude anaemia, infection, primary platelet disorder, renal failure, hyperglycaemia, electrolyte abnormality, and dyslipidaemia. Cardiac enzymes and troponins if myocardial infarction is suspected.
• ECG: transient ST-segment elevation during attacks is the characteristic finding in patients with variant angina.
• Ambulatory ECG: Many episodes of coronary artery vasospasm are brief and may be asymptomatic. ST-segment changes may be detected by ambulatory electrocardiography.
• Coronary angiography is the standard for the diagnosis of variant angina when coupled with the clinical syndrome of angina pectoris at rest with transient ST-segment elevation. In some patients, it may be necessary to perform provocative testing (e.g. with ergonovine maleate, methylergonovine maleate, acetylcholine, or hyperventilation) to induce coronary artery spasm.
• Holter monitoring: Variant angina, which is associated with ventricular dysrhythmia and sudden cardiac death, may be detected during ambulatory Holter monitoring.

• Patients with angina at rest should be admitted to a hospital for observation, evaluation, and initial management.
• Co-existing atherosclerosis is common so advice includes smoking cessation, exercise, healthy diet, weight reduction if necessary, and evaluation of other cardiovascular risk factors such as hyperlipidaemia, diabetes and hypertension.
• Nitrates and calcium channel blockers are the mainstay of medical therapy.⁴
• Nitroglycerin effectively treats episodes of angina and myocardial ischaemia within minutes of administration, and the long-acting nitrate preparations reduce the frequency of recurrent events.
• Nifedipine, amlodipine, verapamil, and diltiazem effectively prevent coronary vasospasm and variant angina.
• Selective beta-blockers can be beneficial in patients with fixed coronary artery stenoses and exertional angina pectoris and are sometimes necessary in combination with the nitrates and calcium channel blockers to achieve control of symptoms, especially in patients with significant fixed stenoses. Non-selective beta blockers should not be used.
• Spontaneous remission following an early period of acute activity may occur.⁵ Therefore, it may be possible to reduce the dose of medications after a 3-month symptom-free period.
• Coronary stenting may be required for refractory spasm.⁶
• Coronary artery bypass surgery may be helpful in patients with a mixed presentation.

• Myocardial infarction:
  • Incidence depends on the relevant diagnostic criteria, but it is as high as 30% in some series.
  • The incidence and prognosis of MI in patients with variant angina appears to be associated with the extent and severity of any underlying fixed atherosclerotic coronary stenoses.
• Arrhythmias:
  • Syncope and pre-syncope are recognised symptoms that are associated with variant angina and are likely due to significant arrhythmias, which cause haemodynamic deterioration.
  • An increased incidence of sudden cardiac death, ventricular tachycardia, ventricular fibrillation, and complete atrioventricular block have been observed during episodes of variant angina and myocardial ischaemia.
  • The risk of sudden death is approximately 2% and is most common in patients with multivessel spasm and prior serious arrhythmia during anginal attacks.⁷

• Overall, the prognosis of patients with variant angina is good. Three-year survival rates vary between 84-98%, and MI-free survival at 3 years varies between 63-98%, depending on application of the relevant diagnostic criteria and the study population.⁸
• A prolonged attack may lead to ventricular arrhythmia, myocardial infarction, heart block, and sudden death.
• Early and late mortality and morbidity are related to the degree of underlying atherosclerotic coronary artery disease. Patients without a stenosis of 70% or more have a 93% 1-year MI-free survival rate, while patients with multivessel atherosclerotic coronary artery disease and variant angina only have a 65% 1-year MI-free survival rate.⁹
• Patients who develop serious arrhythmias during episodes of pain and/or who have evidence of diminished left ventricular ejection fraction are at increased risk of early mortality.