Coronary Microvascular Dysfunction
Definition
Coronary microvascular dysfunction (MVD) is impaired function of coronary microcirculation (vessels <0.5 mm diameter), which accounts for ~70% of coronary resistance in the absence of obstructive CAD. MVD may be endothelium-dependent or -independent and manifests as impaired coronary flow reserve, microvascular spasm, or the coronary slow-flow phenomenon. In the context of acute ischemia without obstructive CAD, it is one of the six recognized causes of MINOCA; in stable patients it underlies ischemia with nonobstructive coronary artery disease (INOCA) without MI.
Key Concepts
Diagnostic Criteria
Three criteria for impaired coronary flow sources/minoca-aha-2019 (high):
- Coronary flow reserve (CFR) <2.0 in response to adenosine or other vasodilators (invasive or non-invasive)
- Microvascular spasm: chest discomfort + ischemic ECG changes induced by intracoronary acetylcholine in the absence of epicardial vasospasm
- Coronary slow-flow phenomenon: delayed angiographic contrast passage requiring ≥3 beats to fill a vessel at rest (increased basal microvascular resistance on haemodynamic studies)
Epidemiology and Demographics
- Detected in 30–50% of patients with chest discomfort and nonobstructive CAD on invasive coronary angiography sources/minoca-aha-2019 (high)
- More common in women and patients with CV risk factors (increasing age, diabetes, hypertension, smoking, dyslipidemia)
- Prior evidence of infarction (myocardial scar on CMR) uncommon in stable INOCA patients: only 8% (26/340 women with stable microvascular disease in WISE study) had CMR evidence of myocardial scar
MINOCA vs INOCA Distinction
- INOCA: stable ischemic symptoms + nonobstructive CAD + no AMI — MVD is the underlying mechanism sources/minoca-aha-2019 (high)
- MINOCA: AMI + nonobstructive CAD — MVD may be the cause of infarction, or may be a consequence of myocardial injury (from any cause, including myocarditis)
- Limited overlap: most INOCA patients do not have evidence of prior MI; most MINOCA patients have identifiable alternative causes
Pathophysiological Challenge in MINOCA
- 2/3 of female MINOCA patients showed inducible perfusion abnormalities on stress CMR → implying microvascular dysfunction sources/minoca-aha-2019 (high)
- However, perfusion defects occur with any cause of myocardial oedema (including myocarditis) — directionality between MVD and MINOCA is unresolved
- Invasive microvascular assessment in MINOCA may not definitively establish MVD as the AMI cause
- Combined acetylcholine testing (epicardial spasm + microvascular spasm) is the most practical invasive approach
Management
| Category | Agent | Mechanism |
|---|---|---|
| Conventional antianginal | Calcium channel blockers | Symptom relief (most evidence) |
| Conventional antianginal | β-blockers | Symptom relief |
| Conventional antianginal | Nitrates | Less effective than in epicardial disease |
| Endothelial function | l-arginine | Small RCT evidence |
| Endothelial function | Statins | Small RCT evidence |
| Endothelial function | Enalapril | Small RCT evidence |
| Microvascular vasodilation | Dipyridamole | Small RCT evidence |
| Microvascular vasodilation | Ranolazine | Small RCT evidence |
| Visceral analgesia | Imipramine | Small RCT evidence |
| Visceral analgesia | Aminophylline | Small RCT evidence |
sources/minoca-aha-2019 (high)
- No revascularization option — all management is pharmacological
- Conventional antianginal drugs less effective on the microvasculature than on epicardial vessels
- Most trials excluded AMI patients — evidence base derived from stable INOCA/microvascular angina populations
Contradictions / Open Questions
- MVD as cause vs consequence of MINOCA: currently unresolvable without prospective mechanistic data sources/minoca-aha-2019 (high)
- Heterogeneous mechanisms within MVD (endothelial vs smooth muscle vs structural) likely explain discordant clinical trial results — patient selection for trials remains a major challenge sources/minoca-aha-2019 (high)
Connections
- Related to concepts/MINOCA — MVD is one of six mechanistic causes; distinguished from INOCA by presence of infarction biomarkers
- Related to concepts/Coronary-Vasospasm — microvascular spasm (subtype of MVD) vs epicardial spasm: differentiated by acetylcholine provocation response; microvascular spasm = symptoms + ECG changes but no >90% epicardial constriction
- Related to concepts/Late-Gadolinium-Enhancement — CMR LGE/stress perfusion used to identify myocardial scarring and inducible ischemia in microvascular disease workup