Prinzmetal Angina


Article Author:
Mary Rodriguez Ziccardi


Article Editor:
Jason Hatcher


Editors In Chief:
William Gossman


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
12/19/2018 12:06:34 PM

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.[1][2]

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]

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.

Complications

  • Arrhythmia
  • Sudden death
  • Myocardial infarction

Enhancing Healthcare Team Outcomes

An interprofessional approach to Prinzmetal angina is recommended.

Prinzmetal angina is not an easy diagnosis to make and may require tests including cardiac catheterization with provocation. An interprofessional team of healthcare workers best manages the disorder.

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 5 years. The factor that might independently determine the free infarct 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. Half of the patients with angina will have persistent symptoms.

Half of the patients with vasospastic angina will have recurring symptoms, even during treatment, within the first 3 years after onset. The development of arrhythmias with the episodes of vasospastic angina has been associated with a poor prognosis, with the main association with ventricular fibrillation and sudden cardiac death.[12][13]


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Prinzmetal Angina - Questions

Take a quiz of the questions on this article.

Take Quiz
Which is the drug of choice to relieve variant angina?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the chief cause of Prinzmetal angina?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the primary therapy for Prinzmetal angina?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following may be a pathophysiologic mechanism of Prinzmetal angina?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient with Prinzmetal angina is started on nitroglycerin. At what time should the nitrate-free period occur?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is most effective in a patient with ischemic Prinzmetal angina?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is not an accurate statement concerning myocardial ischemia?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Primary treatment of Prinzmetal angina should not include which of the following?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 40-year-old female presents with severe chest pain. The pain occurs at night and only while at rest. She has a history of migraine headaches and her body mass index is 30. She smokes about a pack of cigarettes daily and drinks alcohol occasionally. She is not taking any medication. Coronary angiography reveals focal spasm but no obstruction. What treatment most likely will reduce the risk of recurrence of her symptoms?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What type of angina is associated with coronary artery spasm?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A patient with angina has cardiac catheterization showing 55 percent right coronary artery stenosis. The working diagnosis is Prinzmetal angina. The next day the patient has chest pain. Select the finding that would be consistent with this diagnosis.



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Select the medication that is not the primary treatment for Prinzmetal angina.



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which is true regarding coronary artery vasospasm or Prinzmetal angina?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the drug of choice for long-term treatment of Prinzmetal angina?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 27-year-old male, smoker, with no other significant past medical history was admitted in the early morning hours to the emergency department after experiencing excruciating chest pain. The patient woke up at midnight with substernal chest pain, pressure like. He mentioned previous episodes of chest pain but less intense episodes of pain during the past year; most of them also during the early morning hours. On admission, ECG showed a 2 mm ST elevation which returned to baseline after his pain subsiding. Cardiac biomarkers were normal. A treadmill stress test was done, showing good exercise capacity and no ST changes even at target heart rate. Which is the most likely diagnosis in this patient?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 31 year old Japanese female complains of substernal chest every morning when she goes outside for a run. She said that the pain started several months ago but has been more frequent during the winter season. She denies any medical condition. She is a current smoker. No family history of cardiac disease. She has a previous visit to the emergency department for chest pain that improved after sublingual nitroglycerin and had an electrocardiogram without evidence of ST segment elevation or depression. She had normal cardiac biomarkers. She had a exercise stress test that showed no electrocardiographic changes for ischemia and no angina during appropriated test. Because of her age and few risk factor for fixed obstructive coronary artery disease vasospastic angina is considered as the possible diagnosis. Which of the following tests is the next most appropriated to determine the etiology of this patient symptoms?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Prinzmetal Angina - References

References

Picard F,Sayah N,Spagnoli V,Adjedj J,Varenne O, Vasospastic angina: A literature review of current evidence. Archives of cardiovascular diseases. 2018 Sep 6     [PubMed]
Cenko E,Bergami M,Varotti E,Bugiardini R, Vasospastic Angina and its Relationship with the Coronary Microcirculation. Current pharmaceutical design. 2018     [PubMed]
Swarup S,Grossman SA, Coronary Artery Vasospasm . 2018 Jan     [PubMed]
    [PubMed]
    [PubMed]
    [PubMed]
    [PubMed]
    [PubMed]
    [PubMed]
    [PubMed]
    [PubMed]
    [PubMed]
    [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Adult Ambulatory-Medical Student. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Adult Ambulatory-Medical Student, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Adult Ambulatory-Medical Student, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Adult Ambulatory-Medical Student. When it is time for the Adult Ambulatory-Medical Student board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Adult Ambulatory-Medical Student.