Microvascular Dysfunction

Figure source

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• ⚠️ Can also be present in patients with obstructive CAD
  • ∴ unrecognized CMD may explain the 20-40% of patients who continue to experience angina following “technically successfully” revascularization
• CMD is the underlying cause of INOCA in one-half of cases²
• Mechanisms of CMD
  • impaired dilation (vasodilator abnormalities) and/or an ↑ constriction of coronary microvessels (microvascular spasm)
  • Impaired vasodilation may be endothelium-dependent and/or endothelium-independent
    • endothelium-mediated: ↓ production and/or ↑ degradation of NO
      • tested using intracoronary infusion of Acetylcholine
    • endothelium-independent is suggested by attenuated vasodilator responses to papaverine, adenosine, or dipyridamole
      • likely involves an impaired relaxation of VSMCs
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    • Figure Source: Box 1 of ³
• CMD includes either
  • CFR <2.0 and/or
  • IMR ≥25 and/or
  • evidence of coronary endothelial dysfunction, typically demonstrated with intracoronary ACh → angina w/ ST-depression and epicardial artery constriction

Drug administered	Results	Diagnosis
Adenosine	Coronary flow reserve < 2.5	Nonendothelial-dependent microvascular dysfunction
Acetylcholine	< 50% increase in coronary blood flow	Endothelial-dependent microvascular dysfunction
	< 5% increase in coronary artery diameter	Endothelial-dependent macrovascular dysfunction
	> 90% decrease in coronary artery diameter Chest pain and ischemic ST-segment changes on electrocardiography	Epicardial coronary spasm
	Chest pain and ischemic ST-segment changes on electrocardiography in the absence of significant epicardial coronary vasoconstriction	Microvascular coronary spasm
Nitroglycerin	< 20% increase in coronary artery diameter	Nonendothelial-dependent macrovascular dysfunction

Adenosine testing

CFR	IMR	Interpretation
✅ (≥ 2)	✅ (< 25)	Normal
❌ (< 2)	✅ (< 25)	Functional CMD
✅ (≥ 2)	❌ (≥ 25)	Structural CMD (early in course?)
❌ (< 2)	❌ (≥ 25)	Structural CMD

• Acetylcholine testing

Treatments

Source: ²

Endothelial dysfunction	Nonendothelial dysfunction	Vasospasm	Nociceptive abnormality
Angiotensin-converting enzyme inhibitor	Angiotensin-converting enzyme inhibitor	Calcium channel blocker	Tricyclic antidepressant
Angiotensin receptor blocker	Beta-blocker	Nitrate	Spinal cord stimulation
Statin	Alpha-/beta-blocker		Cognitive behavior therapy
L-arginine	Ranolazine
Cardiac rehabilitation	Ivabradine
Enhanced external counterpulsation	Phosphodiesterase-5 inhibitor

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Footnotes

1. Schindler TH, Dilsizian V. Coronary microvascular dysfunction: clinical considerations and noninvasive diagnosis. JACC Cardiovasc Imaging 2020;13:140-55. ↩

2. Tjoe B, Barsky L, Wei J, Samuels B, Azarbal B, Merz CNB, Shufelt C. Coronary microvascular dysfunction: Considerations for diagnosis and treatment. Cleve Clin J Med. 2021 Oct 1;88(10):561-571. doi: 10.3949/ccjm.88a.20140. PMID: 34598921; PMCID: PMC8813544. ↩ ↩²

3. Camici, P. G., d’Amati, G., & Rimoldi, O. (2014). Coronary microvascular dysfunction: mechanisms and functional assessment. Nature Reviews Cardiology, 12(1), 48–62. https://doi.org/10.1038/nrcardio.2014.160 ↩

4. Bairey Merz CN, Pepine CJ, Shimokawa H, Berry C. Treatment of coronary microvascular dysfunction. Cardiovasc Res 2020;116:856-70. ↩