Angina, Prinzmetal

Article Author:
Mary Rodriguez Ziccardi
Article Editor:
Jason Hatcher
Updated:
10/26/2018 1:31:56 PM
PubMed Link:
Angina, Prinzmetal

Introduction

Vasospastic angina, variant angina, or Prinzmetal angina is a known clinical entity characterized by chest pain at rest with transient ischemic electrocardiographic changes in the ST segment, with a prompt response to nitrates. These symptoms are attributed to coronary arteries spasm.

Etiology

The cause of Prinzmetal Angina is a diffuse or segmental spasm in the coronary arteries which generate a decrease in blood supply to the myocardium generating chest pain. The coronary arteries may spasm as a result of exposure to cold weather, exercise, or a substance that promotes vasoconstriction such as alpha-agonists (pseudoephedrine and oxymetazoline). The use of recreation drugs such as cocaine has also been associated with the development of vasospastic angina, especially when associated the use of cigarettes.

Epidemiology

Incidence or prevalence of Prinzmetal angina is still unknown. The reason for this is the possible misdiagnosis or confusion with other conditions that might present with the same symptoms, and further evaluation is not sought. Some studies show that the Japanese population has an increased risk of developing vasospastic angina when compared with Caucasian populations. The incidence in the Japanese population compared to the Caucasian population is up to three times higher. The average age of presentation of vasospastic angina is around the fifth decade of life. Within the Japanese population, females are more likely to experience vasospastic angina. 

Pathophysiology

The underlying mechanism in the development of coronary artery spasm is multifactorial. One of the mechanisms that may generate the spasm is an increased reactivity of the vessels to vasoconstrictive stimuli and subsequent high-grade stenosis in a segment of the coronary or diffusely, creating decreased coronary artery perfusion and with this myocardial injury due to ischemia. The etiology of the hyperreactivity of the coronary vessels is unclear but could be related to endothelial dysfunction and primary smooth muscle cells of the coronary vessels that may have impaired regulatory mechanism for vasoconstriction and vasodilation. Balances within the sympathetic and parasympathetic tone is also an important factor that regulates flow in the coronaries. Imbalance in this system can predispose exaggerated vasoconstriction under normal circumstance and during exposure of acetylcholine and methacholine.

Risk Factors

Typical cardiovascular risk factors have not directly been associated with the presence of vasospastic angina, except for cigarette smoking and inflammatory states determined by high hs-CRP levels. Insulin resistance has also been associated with vasospastic angina.

Precipitating Factors

Multiple triggers have been associated with the development of vasospastic angina.

Several drugs such as ephedrine and sumatriptan can cause typical chest pain due to coronary spasm. Recreational drugs like cocaine, amphetamines, alcohol, and marijuana are also possible precipitating factors.

Environmental factors such as cold water can cause spasms in the coronaries. Valsalva maneuver, hyperventilation, and coronary manipulation through cardiac catheterization also can produce hyperreactivity of the coronary arteries.

History and Physical

Patients with vasospastic angina typically present with:

  • A chronic pattern of episodes of chest pain at rest that last five to 15 minutes, from midnight to early morning.
  • Pain decreases with the use of short-acting nitrates.
  • Typically, these patients have ischemic ST-segment changes on an electrocardiogram during an episode of chest discomfort, which returns to baseline on symptom resolution.
  • Typically, the chest pain is not triggered by exertion or alleviated with rest as is typical angina.
  • Often, the patient is younger with few or no classical cardiovascular risk factors.

Other vasospastic disorders, such as Raynaud phenomenon or a migraine, can be associated in this subset of patients. Patients complain of recent or episodes past with some symptom-free periods.

Evaluation

A clinical history and an electrocardiographic recording during a spontaneous episode are major elements in the clinical diagnosis of vasospastic angina.

The international study group of coronary vasomotion disorders known as COVADIS, created a diagnostic criterion to determine the presence of Prinzmetal angina. These include:

1. Clinical response to nitrates during a spontaneous anginal episode. 

2. Transient electrocardiographic changes with concern for ischemia during a spontaneous anginal episode. These include ST segment elevation or depression = 0.1 mV or new U waves.

3. Evidence of coronary vasospasm during angiography. 

Because of the lack of electrocardiographic evidence upon resolution of symptoms, further studies may be considered. The initial workup should be to evaluate the possibility of fixed obstructive coronary artery disease.

If appropriated, a noninvasive stress test can be performed. Most of these patients will have a normal stress test whis is negative for ischemia. However, a subgroup of patients (10% to 30%) can have exercise-induced spasms with electrocardiographic changes for ischemia that are not specific for vasospastic angina versus fixed coronary obstruction. This group of patients should undergo coronary catheterization to determine obstructive coronary disease. Also, a negative stress test with suspicion for coronary obstruction should be evaluated with cardiac catheterization.

During cardiac catheterization, coronary spasms can be visualized spontaneously or under drug induction.

Ergonovine, acetylcholine, and hyperventilation, can be used in the catheterization laboratory in an attempt to confirm the diagnosis of coronary vasospasm. These tests are done only when the diagnosis of vasospastic angina is suspected, but not firmly established. At present, provocative pharmacologic testing is not frequently performed.

An ambulatory electrocardiogram also can be used to record transient electrocardiographic changes during acute spontaneous events.

It is important to clarify that, in the setting of acute chest pain or angina, the main focus is to evaluate for possible fixed coronary obstruction.

Treatment / Management

Treatment is focused on decreasing episodes of angina and preventing complications like myocardial injury and arrhythmia. Lifestyle modifications should be encouraged, especially smoking cessation. Smoking cessation is one of the critical interventions in reducing the frequency of episodes. Avoiding medications or drugs that can trigger coronary vasospasm (e.g., cocaine, marijuana, and ephedrine-based products) is also important.

Pharmacological therapy:

  • Calcium antagonist plays an important role in the management of vasospastic angina. It is a first-line treatment due to a vasodilation effect in the coronary vasculature. Calcium antagonist is effective in alleviating symptoms in 90% of patients. Moreover, one study demonstrated that the use of calcium channel blocker therapy was an independent predictor of myocardial infarct-free survival in vasospastic angina patients.
  • The use of a long-acting calcium antagonist is recommended to be given at night as the episodes of vasospasm are more frequent from midnight to early morning. A high dose of long-acting calcium antagonists like diltiazem, amlodipine, nifedipine, or verapamil are recommended, and titration should be done on an individual basis with an adequate response and minimal side effects. In some cases, the use of a two-calcium antagonist (dihydropyridine and non-dihydropyridine) can be effective in patients with poor response to one agent.
  • The use of long-acting nitrates are also effective in preventing vasospastic events, but chronic use is associated with tolerance. In patients on calcium antagonist without an adequate response to treatment, long-acting nitrates can be added.
  • Nicorandil, a nitrate, and K-channel activator also suppress vasospastic attacks.
  • The use of beta-blockers, especially those with nonselective adrenoceptor blocking effects, should be avoided because these drugs can aggravate the symptoms.
  • Treatment with guanethidine, clonidine, or cilostazol has been reported to be beneficial in patients taking calcium channel antagonists. However, these drugs are not well-studied in this setting.
  • The use of fluvastatin has been shown to be effective in preventing coronary spasm and may exert benefits via endothelial nitric oxide or direct effects on the vascular smooth muscle.

Pearls and Other Issues

In general, the long-term prognosis for vasospastic angina is good if patients get adequate treatment. Overall, 75% of patients can be free of myocardial infarct at five years. Half of the patients with vasospastic angina will have a persistence of symptoms. Studies have reported that half of the patients continue to experience angina at three years.

Factors that may independently determine the infarct free survival includes; the presence and severity of pre-existing coronary stenosis, the number of vessels with hyperreactivity or spams, and the use of calcium channel blockers.  Another determinant of poor prognosis is arrhythmia during vasospastic episodes. Arrhythmia during episodes can cause ventricular fibrillation and sudden cardiac arrest. The development of arrhythmias during episodes of vasospastic angina has been associated with a poor prognosis as the main arrhythmias associated are ventricular fibrillation and sudden cardiac death.