Coronary Vasospasm
Definition
Coronary vasospasm (epicardial coronary vasospasm) is intense vasoconstriction of an epicardial coronary artery resulting in >90% reduction of luminal diameter and compromised myocardial blood flow. It may occur spontaneously or in response to drugs/toxins. Prolonged episodes can cause myocardial infarction (MINOCA) and life-threatening arrhythmias. Vasospastic angina is the clinical disorder defined by rest angina and dynamic ST-elevation on ECG attributable to coronary spasm.
Key Concepts
Pathophysiology
- Vascular smooth muscle hyperreactivity is the central mechanism; endothelial and adventitial inflammatory pathways are increasingly recognized sources/minoca-aha-2019 (high)
- Triggers: cocaine, 5-fluorouracil, ergotamine (migraine medications), sympathomimetics, ergonovine; spontaneous dysregulation of coronary vasomotor tone
- First described by Prinzmetal et al. in patients with obstructive CAD but more commonly encountered in nonobstructive disease
Prevalence and Demographics
- Diagnosed in 46% of MINOCA patients undergoing provocative testing (Montone et al., n=80, within 48h of admission) sources/minoca-aha-2019 (high)
- Strong Asian predilection: post-discharge vasospasm positivity: Japanese 81%, Korean 61%, vs whites 15%
- More common cause of MINOCA than previously recognized in Western populations when systematic provocative testing is performed
Diagnosis
- Spontaneous episodes occasionally captured on ambulatory ECG (dynamic ST-elevation during angina at rest)
- Gold standard: intracoronary acetylcholine provocation testing (20–100 µg bolus over 20 s); positive result = ≥90% epicardial vasoconstriction + symptoms or ischemic ECG changes sources/minoca-aha-2019 (high)
- COVADIS diagnostic criteria (2025 EHRA consensus): Epicardial CAS requires all three: (1) reproduction of chest pain, (2) ischaemic ECG changes, AND (3) ≥90% vasoconstriction leading to flow limitation (sources/pharmacological-provocation-europace-2025 — high)
- Acetylcholine protocol (2025 EHRA): Escalating intracoronary doses — 2 → 20 → 50 µg (manual); automated pump: 0.182 → 1.82 → 18.2 µg/mL over 2-min steps. Max 50 µg for right coronary artery/dominant left; up to 100 µg for non-dominant left. Intracoronary GTN (200–400 µg) or ISDN promptly reverses spasm (sources/pharmacological-provocation-europace-2025 — high)
- Safety (2025 data): 0% mortality; <4% AF, <2% VT/VF, 0.1% SCA; events more common during right coronary testing (sources/pharmacological-provocation-europace-2025 — high)
- CAS as cause of out-of-hospital cardiac arrest: 2% of OHCA survivors causally attributed to vasospasm; 30–75% of OHCA survivors may have positive coronary reactivity test — but causal attribution requires clinical context (sources/pharmacological-provocation-europace-2025 — high)
- Contraindications to acetylcholine testing: Haemodynamic instability, early AMI, AV block, NYHA III/IV HF, left main >50%, three-vessel obstructive CAD; ergonovine also contraindicated in pregnancy, severe hypertension, severe LV dysfunction (sources/pharmacological-provocation-europace-2025 — high)
- Testing advised only when CAS is suspected to have a causal role and all other tests are normal; test only by operators with established experience in specialist centres
- Contemporary catheterization laboratory–based testing: acceptable safety profile — no reported procedure-related deaths; arrhythmias in 5% (comparable to spontaneous episodes) sources/minoca-aha-2019 (high)
- Ergonovine bedside testing (historical): associated with deaths in 1970s — no longer recommended for routine non-catheter use
- Combined testing for epicardial spasm + microvascular dysfunction using acetylcholine is practical; see concepts/Coronary-Microvascular-Dysfunction
- Blood toxicology and medication review (cocaine, ergotamine, fluorouracil) should accompany provocation testing
Management
| Agent | Evidence | Notes |
|---|---|---|
| Calcium channel blockers (dihydropyridine/non-DHP) | Cornerstone therapy | Suppress angina; absence is independent CV event predictor |
| Dual CCBs (different receptor subtypes) | Refractory cases | Shown to alleviate symptoms in refractory vasospastic angina |
| Sublingual/intracoronary nitrates | Acute spasm relief | Short-acting; intracoronary nitrates rapidly abort acute episodes |
| Long-acting nitrates | Uncertain | Nitrate tolerance limits chronic utility |
| Nicorandil | Alternative | Potassium channel opener with nitrate properties |
| Cilostazol | Alternative | Phosphodiesterase-3 inhibitor |
| β-blockers | Contraindicated | Unopposed alpha-adrenergic stimulation worsens spasm |
sources/minoca-aha-2019 (high)
Relationship to MINOCA
- Vasospasm is the most common single identified cause of MINOCA when provocative testing is performed in specialized centres
- Prolonged spasm → transmural ischemia → troponin elevation → fulfils MINOCA definition
- Treat with calcium channel blockers (first-line); avoid β-blockers (can precipitate or worsen spasm)
- Early provocative testing (within 48h) is safe in MINOCA patients and changes management
Contradictions / Open Questions
- Routine provocative testing in Western centres remains uncommon despite acceptable safety data; practice patterns differ substantially from Asian centres sources/minoca-aha-2019 (high)
- Long-acting nitrates are standard practice in some centres despite limited evidence for chronic symptom benefit sources/minoca-aha-2019 (high)
Connections
- Related to concepts/MINOCA — vasospasm is leading identified cause; management diverges from standard AMI-CAD secondary prevention
- Related to concepts/Coronary-Microvascular-Dysfunction — microvascular spasm is a distinct entity (ECG changes + symptoms on acetylcholine without epicardial spasm); both assessed with acetylcholine testing
- Related to concepts/Drug-Induced-Arrhythmia — cocaine and fluorouracil are recognized drug triggers for coronary vasospasm-mediated MINOCA
- Related to concepts/Pharmacological-Provocation-Testing — acetylcholine/ergonovine protocol, COVADIS criteria, safety data