What is Prinzmetal's angina?

Prinzmetal's Angina: Definition and Management

Prinzmetal's angina (variant angina) is a form of unstable angina characterized by transient coronary artery spasm causing temporary ST-segment elevation that resolves spontaneously or with nitroglycerin, typically occurring at rest without progression to myocardial infarction. 1

Clinical Characteristics

• Timing and Presentation:

  • Occurs predominantly at rest, often in the early morning hours
  • Episodes frequently occur in clusters with asymptomatic periods lasting weeks to months
  • Chest pain is not typically precipitated by increased myocardial oxygen demand
  • May simulate unstable angina/NSTEMI secondary to coronary atherosclerosis 1

• Triggers:

  • Emotional stress
  • Hyperventilation
  • Exercise (less commonly)
  • Exposure to cold 1

• Patient Demographics:

  • Patients are typically younger than those with chronic stable angina
  • Often have fewer coronary risk factors except for smoking
  • More common in women 2
  • Associated with other vasospastic disorders like migraine headache and Raynaud's phenomenon 1, 2

Pathophysiology

The underlying mechanism involves:

• Endothelial dysfunction exposing medial smooth muscle to vasoconstrictors:

  • Catecholamines
  • Thromboxane A2
  • Serotonin
  • Histamine
  • Endothelin 1

• Imbalance between vasodilator factors (prostacyclin, nitric oxide) and vasoconstrictor factors (endothelin, angiotensin II) 1

• Autonomic nervous system involvement with:

  • Reduced parasympathetic tone
  • Enhanced reactivity of alpha-adrenergic vascular receptors 1

• Coronary anatomy:

  • Spasm is typically focal but can occur at multiple sites simultaneously
  • Can occur in angiographically normal or diseased vessels
  • Even "normal" coronary segments often have evidence of mural atherosclerosis on intravascular ultrasound 1, 2

Diagnosis

The key diagnostic finding is documentation of ST-segment elevation during transient chest discomfort that resolves when pain abates 1.

Diagnostic Approach:

1. ECG monitoring during episodes of chest pain

   • Continuous 12-lead ECG monitoring improves diagnostic sensitivity

2. Exercise testing

   • One-third show ST-segment elevation
   • One-third show ST-segment depression
   • One-third show no ST-segment changes
   • Results may not be reproducible and are more often positive in early morning 1

3. Coronary angiography

   • Recommended in patients with episodic chest pain accompanied by transient ST-segment elevation (Class I recommendation) 1
   • Spasm may develop spontaneously during angiography, aiding diagnosis
   • Reveals that many patients have underlying coronary artery disease:
     • 39% have single-vessel disease
     • 19% have multi-vessel disease 1

4. Provocative testing

   • May be considered in patients with no significant angiographic CAD and no documentation of transient ST-segment elevation (Class IIb recommendation)
   • Not recommended in patients with high-grade obstructive stenosis (Class III recommendation)
   • Tests include cold pressor test, hyperventilation, or pharmacological agents 1

Treatment

First-Line Therapy:

Treatment with nitrates and calcium channel blockers is recommended (Class I recommendation) 1.

1. Nitrates:

   • Nitroglycerin is exquisitely effective in relieving acute spasm
   • Long-acting nitrates for prevention

2. Calcium Channel Blockers:

   • First-line agents for long-term management
   • Verapamil dilates coronary arteries and is a potent inhibitor of coronary artery spasm 3
   • Typical dosing:
     • Verapamil: 240-480 mg per day
     • Diltiazem: 180-360 mg per day
     • Nifedipine: 60-120 mg per day 1
   • Combination of different classes may be needed for refractory cases

3. Risk Factor Modification:

   • Smoking cessation is essential
   • Patients with atherosclerotic lesions are considered higher risk 1

Special Considerations:

• Beta-blockers have theoretical adverse potential and are generally contraindicated in Prinzmetal's angina 2
• Alpha-receptor blockers may benefit patients not responding to calcium channel blockers and nitrates 1
• Percutaneous coronary intervention may be considered in patients with chest pain, transient ST-segment elevation, and significant coronary artery stenosis (Class IIb recommendation) 1

Prognosis and Complications

• Prognosis is generally good when there is no significant coronary artery stenosis

• When associated with coronary atherosclerosis, prognosis is determined by the severity of underlying disease 2

• Potential complications:

  • Myocardial infarction
  • High-degree AV block
  • Life-threatening ventricular tachycardia
  • Sudden death 1

Prompt recognition and appropriate management with calcium channel blockers and nitrates are essential to prevent these potentially serious complications.