Is Index of Microvascular Resistance (IMR) a primary diagnostic test for vasospastic angina?

Is IMR a Test for Vasospastic Angina?

No, IMR (Index of Microvascular Resistance) is not a primary diagnostic test for vasospastic angina—it measures microvascular dysfunction, not epicardial coronary spasm. The gold standard for diagnosing vasospastic angina remains intracoronary provocation testing with acetylcholine or ergonovine during coronary angiography, which directly visualizes epicardial coronary artery spasm 1.

Understanding the Distinction

What IMR Actually Measures

• IMR specifically assesses structural microvascular resistance and is used to diagnose coronary microvascular dysfunction, not epicardial vasospasm 1.
• An IMR ≥25 units indicates structural microvascular disease, which is a completely different pathophysiological entity from epicardial vasospastic angina 1.
• IMR is measured using thermodilution-based intracoronary pressure and flow data during maximal hyperemia 1.

The Correct Diagnostic Pathway for Vasospastic Angina

Primary diagnostic approach requires three components:

1. Clinical documentation: Capture transient ST-segment elevation or depression on 12-lead ECG during spontaneous rest angina episodes that resolve with nitrates 1, 2.
2. Anatomic assessment: Perform invasive coronary angiography or coronary CTA to exclude obstructive coronary disease 1, 2.
3. Definitive confirmation: Conduct intracoronary provocation testing with acetylcholine or ergonovine (Class IIa, Level B recommendation) 1, 2.

The Gold Standard: Provocation Testing

A positive provocation test for vasospastic angina requires all three criteria:

• Anginal symptoms during testing 1, 2
• Ischemic ECG changes (ST-segment elevation ≥0.1 mV or depression ≥0.1 mV) 1, 2
• Severe epicardial vasoconstriction (>90% transient coronary artery narrowing) 1, 2

If all three components are not present, the test is equivocal 1, 2.

When IMR Becomes Relevant: The Overlap Scenario

Microvascular Spasm vs. Epicardial Spasm

Here's the critical nuance: While IMR doesn't diagnose epicardial vasospastic angina, it plays a role in the comprehensive evaluation when patients have persistent symptoms but negative epicardial spasm testing 1.

• Patients who develop angina and ECG changes with acetylcholine but WITHOUT severe epicardial vasoconstriction may have microvascular spasm 1.
• These patients should be treated similarly to vasospastic angina patients with calcium channel blockers and nitrates 1.
• Guidewire-based CFR and/or IMR measurements should be considered (Class IIa, Level B) in patients with persistent symptoms and angiographically normal or non-obstructive coronary arteries 1.

The CorMicA Trial Evidence

The CorMicA trial demonstrated that stratified therapy based on invasive coronary physiology testing (including IMR, CFR, and acetylcholine testing) significantly improved outcomes 1:

• Patients were randomized to stratified medical treatment based on CFR, IMR, and acetylcholine testing versus standard care 1.
• The intervention improved Seattle Angina Questionnaire scores by 11.7 units at 6 months 1.
• Quality of life improvements were sustained at 1-year follow-up 1.

Clinical Algorithm for Suspected Vasospastic Angina

Step 1: Initial Documentation

• Attempt to capture 12-lead ECG during spontaneous rest angina episodes 2.
• Deploy extended Holter monitoring (potentially >1 week) if symptoms are infrequent 1, 2.
• Look for ST-segment shifts occurring at normal heart rate (not during tachycardia) 1, 2.

Step 2: Anatomic Evaluation

• Perform invasive coronary angiography or coronary CTA to exclude fixed obstructive disease (Class I, Level C recommendation) 1, 2.

Step 3: Provocation Testing

• If coronary arteries are normal or show non-obstructive lesions with preserved FFR/iFR, proceed to intracoronary acetylcholine or ergonovine provocation testing 1, 2.
• Safety note: Ventricular arrhythmias occur in 3.2% and bradyarrhythmias in 2.7% during testing, similar to spontaneous spasm rates 1.
• Have intracoronary nitrates immediately available to reverse triggered spasm 1.

Step 4: If Epicardial Spasm Testing is Negative

• Consider microvascular assessment with CFR and IMR measurements if symptoms persist 1.
• Perform acetylcholine testing specifically to assess for microvascular spasm (Class IIb, Level B) 1.

Critical Pitfalls to Avoid

Don't Confuse the Two Entities

Epicardial vasospastic angina and microvascular dysfunction are distinct pathophysiological processes:

• Epicardial vasospastic angina involves transient total or subtotal occlusion (>90% constriction) of epicardial coronary arteries 1.
• Microvascular dysfunction involves structural or functional changes in the coronary microvasculature without epicardial spasm 1.
• Both can coexist, which is associated with worse prognosis 1.

IMR Has Different Diagnostic Thresholds

• IMR ≥25 units indicates structural microvascular disease 1.
• CFR <2.0-2.5 indicates microvascular dysfunction 1.
• These thresholds do NOT diagnose epicardial vasospasm 1.

Geographic and Population Variations

• Japanese and Taiwanese populations have markedly higher prevalence of coronary vasospasm (24.3% and 19.3% with multiple vessel involvement) compared to Caucasians (7.5%) 1.
• This may influence pre-test probability and testing strategies 1.

The Bottom Line

IMR is a test for microvascular dysfunction, not vasospastic angina. The definitive diagnosis of epicardial vasospastic angina requires intracoronary provocation testing with acetylcholine or ergonovine that demonstrates all three criteria: symptoms, ECG changes, and severe epicardial vasoconstriction 1, 2. However, IMR plays an important complementary role in the comprehensive evaluation of patients with persistent angina and non-obstructive coronary arteries, particularly when epicardial spasm testing is negative but microvascular spasm is suspected 1.