Vasospastic Angina

Vasospastic angina, also known as Prinzmetal or variant angina, is an uncommon cause of chest pain due to transient coronary artery spasms. The pathophysiology is distinguished from stable or unstable angina secondary to atherosclerotic coronary artery disease (CAD). Clinical presentation is characterized by spontaneous episodes of chest pain from a transient decrease in blood flow to the epicardial arteries. Diagnosis is made by clinical history, normal exam, and ECG findings of ST-segment changes during an episode. Cardiac enzymes and angiography are usually normal. Management includes the prevention of vasospasm with calcium channel blockers and the relief of angina with nitrates.

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Overview

Definition

Vasospastic angina refers to episodes of chest pain (angina), which occur spontaneously while at rest secondary to coronary artery vasospasm, usually in the absence of atherosclerotic coronary artery disease (CAD).

Epidemiology

  • Uncommon cause of angina (< 5% of cases)
  • Average onset is usually < 50 years of age (younger than CAD onset)
  • 3x more common in the Japanese population

Etiology

Possible triggers include:

  • Smoking
  • Stimulants and vasoconstrictive drugs:
    • Cocaine
    • Amphetamine
    • Pseudoephedrine
    • Oxymetazoline
    • Selective serotonin 5-HT1 receptor agonists 
  • Magnesium deficiency
  • Hyperventilation
  • Cold weather
  • Exercise
  • Foodborne botulism

Pathophysiology

  • Sudden coronary artery vasospasm → transient obstruction of blood flow → chest pain
  • The vasospasm may be superimposed upon underlying CAD with atherosclerotic narrowing.
  • The cause of vasospasm is not well agreed on, but may include:
    • Impaired regulation of myofibril contraction in the smooth muscle cells of coronary vessels
    • Endothelial dysfunction
    • Nitric oxide deficiency (a natural vasodilator)
    • Imbalance of sympathetic and parasympathetic tone

Clinical Presentation

Clinical presentation

  • Recurrent, substernal chest pain occurring with no inciting factors:
    • Gradual onset and resolution
    • Duration: approximately 5–15 minutes
    • May radiate to the arm and jaw
    • Occurs in an atypical pattern:
      • Frequently at rest
      • Clustered from midnight to early morning
  • Possible associated symptoms:
    • Nausea
    • Diaphoresis
    • Dizziness
    • Dyspnea
    • Palpitations

Complications and sequelae

  • Syncope may occur due to arrhythmias.
  • MI may result from prolonged, ↓ coronary blood flow.

Diagnosis and Management

Diagnosis

  • Laboratory evaluation: negative cardiac enzymes:
    • Troponin I
    • MB isoenzyme of creatine kinase (CKMB)
  • ECG: 
    • ST elevation or depression > 1 mm can be seen during an episode of vasospastic angina.
    • New, negative U waves
    • ECG changes resolve when spasms and pain subside.
  • Stress testing:
    • Usually normal
    • Can be abnormal in patients with exercise-induced spasm
  • Cardiac catheterization:
    • Characteristically reveals normal coronary arteries without atherosclerotic burden
    • A definitive diagnosis is made through ergonovine or acetylcholine injection to induce vasospasm.

Management

  • Smoking cessation 
  • Avoid inciting medications or drugs.
  • Medical therapy: avoid nonselective beta-blockers (can exacerbate vasospasm):
    • Calcium channel blockers:
      • 1st line to prevent vasospasm
      • Options: diltiazem, amlodipine, nifedipine, verapamil
    • Nitrates:
      • Short-acting nitrates in the acute setting to relieve chest pain
      • Long-acting nitrates to prevent vasospasm 
    • Statins:
      • May suppress vasospasm and prevent complications by improving endothelial function
      • May be used in the absence of atherosclerotic disease

Differential Diagnosis

  • Acute coronary syndrome (ACS): caused by occlusive CAD and reduced blood flow to the heart, which leads to unstable angina or MI. Patients present with chest pain, dyspnea, diaphoresis, and nausea. Diagnosis involves an abnormal ECG, elevated cardiac enzymes, and sometimes coronary angiography to rule-out vasospastic angina. Management includes revascularization with medical therapy, percutaneous stenting, or coronary bypass surgery.
  • Pulmonary embolism: venous thromboembolism in the lungs presenting with pleuritic pain (unlike vasospastic angina), dyspnea, tachycardia, and occasionally chest pain. Diagnosis is made with visualization of the embolism on CT angiography. Management includes anticoagulation to prevent further propagation of the blood clot.
  • Pericarditis: inflammation of the pericardium due to infection, medications, or malignancy. Patients develop chest pain which worsens laying down (unlike vasospastic angina). Electrocardiogram may show diffuse elevation of the ST segment; echocardiogram may show fluid accumulation in the pericardium. Management is supportive and includes analgesics and anti-inflammatory medications.
  • Costochondritis: occurs due to inflammation of cartilage in the rib cage and presents with chest pain reproducible by palpation. Costochondritis can occur due to trauma, strain, or viral infection. Diagnosis is made clinically and includes the exclusion of coronary disease with appropriate testing. Treatment is with local measures and NSAIDs.
  • Esophageal spasm: painful contraction of the esophagus presenting with severe, intermittent chest pain. Diagnosis is made by exclusion of cardiac causes of chest pain, esophageal manometry, and barium swallow study. Management may include antispasmodic medications and possibly surgery.
  • Anxiety or panic disorder: characterized by sudden attacks of fear or anxiety (with or without an appropriate stimulus). Patients may report chest pain, palpitations, dyspnea, and other associated symptoms. Diagnosis is made by excluding cardiac causes of chest pain. Management is with psychotherapy, benzodiazepines, and/or antidepressants.

References

  1. Ishii, M., Kaikita, K., et al. (2016). Impact of Statin Therapy on Clinical Outcome in Patients With Coronary Spasm. Journal of the American Heart Association, 5(5). https://doi.org/10.1161/jaha.116.003426
  2. Pinto, D.S., et al. (2019). Vasospastic angina. UpToDate. Retrieved May 20, 2021, from https://www.uptodate.com/contents/vasospastic-angina
  3. Sweis, R.N., and Jivan, A. (2020). Variant angina (Prinzmetal angina). [online] MSD Manual Professional Version. Retrieved June 3, 2021, from https://www.msdmanuals.com/professional/cardiovascular-disorders/coronary-artery-disease/variant-angina
  4. Rodriquez Ziccardi, M., and Hatcher, J.D. (2020). Prinzmetal angina. [online] StatPearls. Retrieved June 3, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK430776/
  5. Wang, S.S. (2018). Coronary artery vasospasm. Medscape. Retrieved June 3, 2021, from https://emedicine.medscape.com/article/153943-overview

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