What type of microvascular dysfunction is indicated by an Index of Microvascular Resistance (IMR) of 17 with adenosine and 29 with Acetylcholine (ACh)?

Microvascular Vasospasm (Endothelium-Dependent Microvascular Dysfunction)

This patient has microvascular vasospasm, characterized by normal structural microvascular resistance at baseline (adenosine IMR <25) but abnormal endothelium-dependent vasoconstriction (acetylcholine IMR ≥25). 1

Interpretation of the Test Results

Normal Endothelium-Independent Microvascular Function

• The adenosine IMR of 17 is below the diagnostic threshold of ≥25, indicating normal structural microvascular resistance and preserved endothelium-independent vasodilation 1
• This rules out fixed structural microvascular disease, which would manifest as elevated IMR with adenosine 1

Abnormal Endothelium-Dependent Microvascular Function

• The acetylcholine IMR of 29 exceeds the diagnostic threshold of ≥25, indicating microvascular dysfunction specifically related to endothelial dysfunction 1
• The increase in IMR from 17 (adenosine) to 29 (acetylcholine) demonstrates paradoxical vasoconstriction in response to the endothelium-dependent vasodilator 1
• This pattern is diagnostic of microvascular vasospasm rather than structural microvascular disease 1

Mechanistic Understanding

Why This Pattern Indicates Vasospasm

• Adenosine is an endothelium-independent vasodilator that directly relaxes vascular smooth muscle, bypassing endothelial function 1, 2
• Acetylcholine is an endothelium-dependent vasodilator that requires intact endothelial function to release nitric oxide and cause vasodilation 1, 2
• When endothelial dysfunction is present, acetylcholine paradoxically causes vasoconstriction through direct smooth muscle effects unopposed by endothelial nitric oxide release 1
• The elevated resistance with acetylcholine (IMR 29) compared to adenosine (IMR 17) indicates functional rather than structural microvascular disease 3

Clinical Significance and Diagnostic Criteria

ESC Guideline Diagnostic Framework

• The 2024 ESC Guidelines classify microvascular dysfunction into two categories based on vasoreactivity testing 1:
  • Abnormal vasodilation (structural): IMR >25 with adenosine
  • Abnormal vasoconstriction (functional): Positive response to high-dose acetylcholine (100-200 μg)
• Your patient has isolated abnormal vasoconstriction without structural disease 1

Distinguishing Microvascular from Epicardial Vasospasm

• Microvascular spasm is diagnosed when acetylcholine provokes symptoms and ischemic ECG changes with <90% epicardial lumen reduction on angiography 1
• If lumen reduction is ≥90%, this would indicate macrovascular (epicardial) vasospasm instead 1
• The IMR measurement specifically isolates microvascular resistance, making it superior to angiography alone for diagnosing microvascular vasospasm 4

Important Clinical Caveats

Elevated Resting Flow Phenotype

• Patients with low CFR but normal/low IMR (like your patient with adenosine IMR 17) often have elevated resting coronary blood flow rather than impaired hyperemic flow 3
• This phenotype is more common in younger women with fewer cardiovascular risk factors 3
• These patients may have distinct pathophysiology requiring different therapeutic approaches 3

Protocol Considerations

• The ESC protocol specifies that acetylcholine testing should be performed first, followed by adenosine testing at the end of the procedure 1, 2
• Intracoronary nitroglycerin should be administered between acetylcholine and adenosine to reverse any vasospastic effects 1, 2
• If this protocol was not followed, the acetylcholine IMR measurement may be less reliable 2

Therapeutic Implications

Contraindicated Medications

• Beta-blockers are absolutely contraindicated in vasospastic angina because they leave alpha-mediated vasoconstriction unopposed, potentially precipitating severe spasm 5, 6

Recommended First-Line Therapy

• Calcium channel blockers (particularly non-dihydropyridines like diltiazem or verapamil) are first-line therapy for microvascular vasospasm 5
• Ranolazine is specifically beneficial for microvascular spasm and can be added for refractory symptoms 5, 6
• ACE inhibitors and statins should be initiated to improve endothelial function regardless of blood pressure or lipid levels 5, 6