Prinzmetal Angina

Etiology

Diffuse or segmental spasm in the coronary arteries causes Printzmetal angina. There is a decrease in blood supply to the myocardium generating symptoms like chest pain. The coronary arteries may develop spasm as a result of exposure to cold weather, exercise, or a substance that promotes vasoconstriction as alpha-agonists (pseudoephedrine and oxymetazoline). Recreational drug use, for example, cocaine use, is associated with the development of vasospastic angina, especially when used concurrently with cigarette smoking.[3]

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 difference between the Japanese population and the Caucasian population is that the former has a three times higher risk. The average age of presentation of vasospastic angina is around the fifth decade of life. Females are more likely within the Japanese population to experience vasospastic angina.[4][5]

Pathophysiology

The underlying mechanism in the development of coronary artery spasm is multifactorial. One mechanism that might 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 low coronary flow 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 might 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.[6][7]

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. A metabolic disorder such as 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 coronaries.

History and Physical

Patients with vasospastic angina present with the following:

• A chronic pattern of episodes of chest pain at rest that last 5 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, like Raynaud phenomenon or a migraine, can be associated with this subset of patients. Patients may complain of recent or past episodes with some symptom-free periods.

Evaluation

Clinical history and an electrocardiographic recording during a spontaneous episode are major elements in the clinical diagnosis of vasospastic angina.[8][9][10]

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, further studies might 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 or 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 warranted 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 remember that when a patient has acute chest pain or angina, the 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. This is one of the critical interventions in reducing the frequency of episodes. Avoiding medications or drugs that can trigger coronary vasospasm, for example, cocaine, marijuana, and ephedrine-based products) is also important.[11][10](A1)

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 at midnight and early in the 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.

Differential Diagnosis

• Acute pericarditis

• Angina pectoris

• Anxiety disorders

• Aortic dissection

• Cocaine toxicity

• Esophageal spasms

• Gastroesophageal reflux disease 

• Myocardial infarction

• Panic disorder

• Unstable angina

Complications

• Arrhythmia
• Sudden death
• Myocardial infarction