Acute Coronary Syndrome: Coronary Vasospasm

Basics

Description

  • Spontaneous episodes of chest pain due to coronary artery vasospasm in the absence of increase in myocardial oxygen demand in either normal or diseased coronary vessels
  • Also known as Prinzmetal angina or variant angina, originally described in 1959
  • Most common in younger patients and men
  • Usually occurs in patients without cardiac risk factors or coronary artery disease but may occur concurrently with obstructive coronary artery disease
  • 12-mo major cardiac events in patients with myocardial infarction (MI) secondary to vasospasm is comparable to AMI with single- or double-vessel disease
  • Risk factors:
    • Smoking (up to 75% of cases)
    • Hypertension
    • Hypercholesterolemia
    • Diabetes mellitus
    • Cocaine use
    • Less commonly marijuana, alcohol, and amphetamine use

Etiology

  • High prevalence of microvascular and epicardial vessel involvement
  • Defined by 3 types:
    • Focal: Localized, often at or near a site of stenosis of a single artery
    • Multifocal: 2 or more segments of the same artery
    • Multivessel: Involving different coronary arteries
  • Can occur in the absence of preceding increased oxygen demand
  • Unopposed α-sympathetic stimulation
  • Sympathetic stimulation by endogenous hormones with hyperreactivity can cause vasoconstriction
  • Conversely, also associated with increased vagal tone or withdrawal from vagal tone leading to microvascular dysfunction, as proven with acetylcholine provocative testing
  • Endothelial dysfunction possibly from genetic mutations in nitric oxide synthase
  • Newer research suggests potential increase in ρ-kinase and phospholipase C leading to increased calcium sensitivity and smooth muscle hyperreactivity

Diagnosis

Signs And Symptoms

  • Chest pain or discomfort:
    • Retrosternal
    • Radiates to neck, jaw, left shoulder, or arm
    • Occurs at rest
    • Occurs more frequently at night or in the morning
    • Not associated with position
    • May be associated with diaphoresis, nausea, vomiting, dizziness
  • Palpitations
  • Presyncope or syncope
  • Associated with migraine headaches and Raynaud disease in a minority of patients
  • May occur during cold weather or stress
  • May be prolonged in duration compared with typical angina
  • May be elicited by hyperventilation
  • May be elicited by exercise
  • Additional triggers include sympathomimetic illicit or prescribed medications, allergic reactions, and magnesium deficiency
  • Circadian pattern, typically at night or early morning when vagal tone is higher
  • Coronary Vasomotor Disorders International Study Group (COVADIS) diagnostic criteria:
    • Nitrate-responsive angina
    • Transient ischemic ECG changes
    • Angiographic evidence of high-grade transient coronary artery spasm

History

May mimic angina; occurrences in the early morning should raise suspicion for vasospasm, but also ask about relationship to stress, exercise, and cold weather

Physical Exam

Physical exam is typically nondiagnostic

Essential Workup

  • Must include an ECG
  • Use of other tests depends on history

Diagnostic Tests And Interpretation

  • ECG:
    • Transient ST-segment elevation is characteristic, is typically quite pronounced
    • Often with reciprocal changes
    • May be followed by ST depression or T-wave inversion
    • May have associated dysrhythmia during coronary spasm
    • Heart block with right coronary artery spasm
    • Ventricular tachycardia with LAD spasm
    • In rare cases can present with sudden death during prolonged spasm period

Lab

  • Troponin frequently negative
  • High-sensitivity troponin may be elevated in prolonged duration episodes
  • Toxicology screen:
    • Helpful if cocaine or other illicit substances are suspected as etiology of chest pain

Imaging

  • CXR:
    • May be helpful to rule out other etiologies such as pneumonia, pneumothorax, or aortic dissection
  • Noninvasive coronary imaging (nuclear perfusion, coronary CTA, coronary MR):
    • Typically only helpful when combined with provocative testing

Diagnostic Procedures/Surgery

  • Exercise stress testing:
    • Usually not helpful, but can help define those with true ischemic disease
  • Noninvasive provocative hyperventilation:
    • Highly specific, moderately sensitive, tends to favor those with increased disease activity
    • Paired with either ECG or ECG plus perfusion imaging
  • Holter monitor:
    • Can be helpful in silent cases or dysrhythmia
  • Cardiac magnetic resonance imaging:
    • May identify the underlying cause in as many as 87% of patients
  • Coronary angiography:
    • Mild atherosclerosis is often the norm
    • Provocative test with acetylcholine is the gold standard

Differential Diagnosis

  • Angina pectoris
  • Anxiety and panic disorders
  • Aortic dissection
  • Cocaine chest pain
  • Esophageal rupture
  • Esophageal spasm
  • Esophagitis
  • GERD
  • Microvascular angina
  • Mitral valve prolapse
  • Musculoskeletal chest pain
  • MI
  • Myocarditis/pericarditis
  • Peptic ulcer disease
  • Pericarditis
  • Pneumothorax
  • Pulmonary embolism
  • Spontaneous coronary artery dissection
  • Takotsubo cardiomyopathy

Treatment

Prehospital

Treat as any other acute coronary syndrome

Initial Stabilization/Therapy

  • IV access
  • Oxygen
  • Cardiac monitoring
  • Vital signs and oxygen saturation

Ed Treatment/Procedures

  • All patients with chest pain in which cardiac ischemia is a consideration should receive an aspirin upon arrival to the ED:
    • Paradoxically may increase severity of Prinzmetal angina due to inhibition of biosynthesis of naturally occurring coronary vasodilator—prostacyclin
  • Nitroglycerin should still be administered and usually will help relieve both ischemic and vasospastic chest pain
  • A trial of calcium channel blockers is indicated if clinical history is consistent with coronary vasospasm
  • Heparin and β-blockers are not helpful in true coronary vasospasm:
    • β-Blockers may be detrimental due to unopposed α-mediated vasoconstriction and should be avoided in suspected cocaine chest pain

Medication

  • Aspirin: 325 mg PO
  • Diltiazem: 240–360 mg PO daily
  • Amlodipine 5–10 mg PO daily
  • Nitroglycerin, either:
    • 0.4 mg sublingual
    • 10–20 mcg/min IV; USE NON-PVC tubing, titrating to effect
    • 1–2 in of nitro paste
  • Verapamil: 40–80 mg PO (immediate release)

First Line

  • Calcium channel blockers (diltiazem, amlodipine)
  • Short acting nitroglycerin: Sublingual (spray or tablet) or transdermal paste
  • Long-acting nitrates (isosorbide mononitrate)

Second Line

  • α-Blocking agents (clonidine, cilostazol)
  • Statin therapy
  • Percutaneous intervention with stenting of fixed lesions in area of vasospasm controversial; can lead to spasm in other areas of coronary tree
  • Pacemaker placement for patients with recurrent syncope or AV nodal block from vasospastic angina

Follow-Up

Disposition

Admission Criteria

  • New-onset chest pain
  • Rule-in with positive biochemical markers or provocative testing
  • Rule-in with positive biochemical markers or stress testing
  • Many patients previously admitted to the hospital can now be effectively evaluated in a chest pain observation unit or clinical decision unit

Discharge Criteria

  • Stable (chronic chest pain)
  • Negative ischemic workup

Follow-Up Recommendations

  • Cardiology follow-up within 7 d of ED evaluation
  • ASCVD risk factor modification
  • Smoking cessation education

Pearls And Pitfalls

  • 95% survival at 5 yr
  • Typical patient will have no traditional coronary risk factors other than smoking
  • Calcium channel blockers are 1st-line therapy
  • 30–40% of patients are refractory to treatment and will have repeat episodes
  • May present as ST-elevation MI (STEMI), however true infarction is almost always relegated to patient with preexisting coronary atherosclerotic disease
  • β-Blockers can lead to worsening of vasospasm due to unopposed α-vasoconstriction
  • In patients with vasospastic angina and migraines, avoid the use of triptans for acute treatment of migraine
  • Patients with prolonged vasospasm can present with STEMI, ventricular arrhythmias, and sudden death

Additional Readings

  1. Hokimoto S, Kaikita K, Yasuda S, et al. JCS/CVIT/JCC 2023 guideline focused update on diagnosis and treatment of vasospastic angina (coronary spastic angina) and coronary artery microvascular dysfunction. Circ J. 2023;87:879–936.  [PMID:36908169]
  2. JCS Joint Working Group. Guidelines for diagnosis and treatment of patients with vasospastic angina (coronary spastic angina). Circ J. 2014;78:2779–2801.  [PMID:25273915]
  3. Lindahl B, Baron T, Erlinge D, et al. Medical therapy for secondary prevention and long-term outcome in patients with myocardial infarction with nonobstructive coronary artery disease. Circulation. 2017;135:1481–1489.  [PMID:28179398]
  4. Nguyen TH, Ong GJ, Girolamo OC, et al. Angina due to coronary artery spasm (variant angina): Diagnosis and intervention strategies. Expert Rev Cardiovasc Ther. 2021;19:917–927.  [PMID:34633245]
  5. Ong P, Aziz A, Hansen HS, Prescott E, Athanasiadis A, Sechtem U. Structural and functional coronary artery abnormalities in patients with vasospastic angina pectoris. Circ J. 2015;79:1431–1438.  [PMID:26084380]
  6. Ong P, Camici PG, Beltrame JF, et al. International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018;250:16–20.  [PMID:29031990]
  7. Pasupathy S, Tavella R, Beltrame JF. Myocardial infarction with nonobstructive coronary arteries (MINOCA): The past, present, and future management. Circulation. 2017;135:1490–1493.  [PMID:28416521]

See Also (Topic, Algorithm, Electronic Media Element)

  • ACS Unstable Angina
  • ACS Myocardial Infarction

Authors

Jamie L. Adler

Shamai A. Grossman