How can epicardial vasospasm be distinguished from microvascular no‑reflow on coronary angiography?

Distinguishing Epicardial Vasospasm from Microvascular No-Reflow

The key distinction is angiographic: epicardial vasospasm shows ≥90% reduction in epicardial coronary artery lumen diameter on angiography with symptoms and ischemic ECG changes, while microvascular no-reflow demonstrates inadequate myocardial perfusion despite patent epicardial vessels (TIMI flow <3 or TIMI 3 with myocardial blush grade 0-1) without visible epicardial obstruction. 1, 2

Angiographic Differentiation

Epicardial Vasospasm Characteristics

• Visible epicardial vessel narrowing ≥90% on coronary angiography during acetylcholine provocation testing 1
• The spasm is focal or diffuse and affects the epicardial coronary arteries that are visible on angiography 3
• Rapidly reversible with intracoronary nitroglycerin (200 μg), confirming the vasospastic nature 1
• Accompanied by reproduction of symptoms and ischemic ST-segment changes on ECG 1

Microvascular No-Reflow Characteristics

• No visible epicardial obstruction, dissection, or distal vessel cutoff on angiography 2, 4, 5
• Reduced TIMI flow grade (<3) or TIMI 3 flow with poor myocardial blush grade (0 or 1) despite patent epicardial vessels 2
• Increased TIMI frame count (>25 frames) indicating slow flow at the microvascular level 1
• ST-segment resolution <70% within 4 hours post-procedure 2
• The epicardial vessel appears adequately dilated but distal myocardial perfusion is impaired 4, 5

Diagnostic Algorithm During Angiography

When Reduced Flow is Observed:

1. First, assess epicardial vessel appearance:

   • If ≥90% epicardial narrowing visible → suspect epicardial vasospasm 1
   • If epicardial vessel appears patent without mechanical obstruction → suspect microvascular no-reflow 2, 4

2. Administer intracoronary nitroglycerin (200 μg):

   • Epicardial vasospasm: Prompt reversal with improved flow and resolution of vessel narrowing 1
   • Microvascular no-reflow: Minimal or no improvement in distal perfusion despite patent epicardial vessels 6

3. Assess response to intracoronary verapamil:

   • Microvascular no-reflow: 89% show improved TIMI flow grade with verapamil (50-1000 μg), with marked reduction in frames to distal opacification 6
   • Mechanical epicardial obstruction: Only 19% improve with verapamil, minimal frame count reduction 6

Provocative Testing for Vasospasm

For suspected epicardial vasospasm without spontaneous occurrence, acetylcholine provocation testing is the gold standard 1, 3:

• Protocol: Incremental intracoronary acetylcholine doses (2 μg → 20 μg → 100 μg → 200 μg) over 60 seconds 1
• Positive for epicardial vasospasm: ≥90% angiographic lumen reduction with symptoms and ischemic ECG changes 1
• Positive for microvascular spasm: <90% lumen reduction with symptoms and ischemic ECG changes 1

Microvascular Dysfunction Assessment

If epicardial vessels appear normal but ischemia is suspected, measure microvascular indices 1:

• Coronary flow reserve (CFR) <2.5 suggests microvascular dysfunction 1
• Index of microcirculatory resistance (IMR) >25 confirms microvascular impairment 1
• Hyperaemic myocardial velocity resistance (HMR) >2.5 indicates microvascular disease 1

Clinical Context Clues

Epicardial Vasospasm Presentation:

• Rest angina, particularly between night and early morning hours 1
• Marked diurnal variation in exercise tolerance, reduced in morning 1
• Hyperventilation can precipitate episodes 1
• Calcium channel blockers suppress episodes (not beta-blockers) 1
• Exquisitely responsive to nitroglycerin 1

Microvascular No-Reflow Context:

• Occurs during PCI for acute MI (10-40% of STEMI cases) or saphenous vein graft interventions 2, 4
• Post-procedural phenomenon following successful epicardial vessel dilation 2, 4
• Associated with downstream microembolization of thrombotic or atheromatous debris 2, 7

Critical Pitfall to Avoid

Do not confuse microvascular spasm (induced by acetylcholine with <90% epicardial narrowing) with microvascular no-reflow (post-PCI phenomenon). Both are microvascular disorders but have different etiologies and contexts 1, 2. Microvascular spasm is a functional vasomotor disorder diagnosed during provocative testing, while no-reflow is a structural/embolic microvascular obstruction occurring after reperfusion therapy 2, 4, 7.

Overlap Syndrome

Epicardial vasospasm frequently coexists with coronary microvascular dysfunction, creating a mixed phenotype with worse prognosis than isolated epicardial spasm 3. In these cases, both ≥90% epicardial narrowing AND abnormal microvascular indices (CFR <2.5, IMR >25) may be present 1, 3.