What is a normal index of microcirculatory resistance (IMR) after testing with acetylcholine in an adult patient with a history of cardiovascular disease?

Normal Index of Microcirculatory Resistance After Acetylcholine Testing

A normal IMR after acetylcholine testing is less than 25 units, with values of 25 units or greater indicating microvascular dysfunction. 1, 2

Diagnostic Threshold and Clinical Context

The threshold of IMR <25 units applies regardless of whether the measurement is obtained during adenosine-induced hyperemia (the standard approach) or acetylcholine provocation testing. 2 This cutoff is consistently endorsed across major international guidelines:

• The 2019 ESC Guidelines explicitly state that IMR ≥25 units defines abnormal microcirculatory resistance and triggers specific treatment algorithms 1
• The 2023 AHA/ACC Guidelines similarly use IMR >25 as a diagnostic criterion for microvascular angina 1

Understanding IMR in the Context of Acetylcholine Testing

When acetylcholine is administered during coronary function testing, you are simultaneously assessing two distinct pathophysiologic mechanisms:

Epicardial vasomotor response: Acetylcholine can provoke epicardial coronary spasm if vasospastic angina is present 1

Microvascular function: IMR measured during acetylcholine-induced hyperemia quantifies structural microvascular resistance, independent of epicardial spasm 2

Critical Clinical Algorithm

The interpretation of acetylcholine testing with IMR measurement follows this decision tree:

1. If IMR <25 units with negative acetylcholine test (no angina, no ECG changes, no epicardial spasm): Normal coronary vasomotor function 1

2. If IMR ≥25 units with negative acetylcholine test: Structural microvascular dysfunction without vasospastic component—treat with beta-blockers, ACE inhibitors, statins, and lifestyle modifications 1

3. If angina and ECG changes occur during acetylcholine without severe epicardial vasoconstriction: Microvascular spasm—treat as vasospastic angina with calcium channel blockers and long-acting nitrates 1

4. If all three components present (angina, ECG changes, severe epicardial vasoconstriction): Epicardial vasospastic angina 1

Measurement Technique and Reproducibility

IMR is calculated during maximal hyperemia using the formula: IMR = Pd × Tmn, where Pd is distal coronary pressure and Tmn is mean transit time of a 3 mL room temperature saline bolus measured by thermodilution. 2 This measurement is independent of hemodynamic variations because it is obtained during hyperemia, making it more reproducible than coronary flow reserve (CFR). 2

Important Nuances and Pitfalls

IMR vs. CFR discordance: A patient can have normal IMR (<25) but abnormal CFR (<2.0), suggesting functional microvascular dysfunction or diffuse epicardial disease rather than structural microvascular disease. 2, 3 Conversely, abnormal IMR (≥25) with abnormal CFR (<2.0) indicates structural microvascular disease. 2, 3

Elevated resting flow states: Recent evidence demonstrates that some patients with low CFR/low IMR present with elevated resting coronary blood flow rather than impaired hyperemic flow—these patients tend to be younger women with fewer cardiovascular risk factors. 4 This represents a distinct endotype that may require different therapeutic approaches, though guidelines have not yet incorporated this nuance.

Angiography-derived IMR limitations: While non-invasive angiography-based IMR calculations are emerging, they require a higher cutoff value (>46.5 units) to achieve acceptable specificity for detecting CMD, and correlation with invasive IMR remains modest. 5 Wire-based thermodilution remains the gold standard.

Treatment Targets

When IMR ≥25 units is documented with abnormal CFR <2.0 and negative acetylcholine provocation testing, target IMR reduction to <25 units as an objective treatment endpoint when optimizing medical therapy. 2, 3 Repeat invasive coronary function testing at 3-6 months after medication optimization to objectively measure improvement. 3

Critical contraindication: Beta-blockers should never be initiated if there is any vasospastic component on acetylcholine testing, as they can precipitate coronary spasm by leaving α-mediated vasoconstriction unopposed. 6 Acetylcholine provocation testing must be performed before starting beta-blocker therapy in patients with suspected microvascular disease. 3