Perspective:

The following are 10 points to remember about coronary microvascular dysfunction (CMD):

1. In 1985, Cannon and Epstein introduced the term ‘microvascular angina’ (MVA) to describe the many patients (approximately 40%) who undergo coronary arteriography because of chest pain thought to be due to coronary artery disease (CAD). They proposed it was due to heightened sensitivity of the coronary microcirculation to vasoconstrictor stimuli associated with a limited microvascular vasodilator capacity.

2. Classic mechanisms for myocardial ischemia include atherosclerotic obstructive disease, vasospastic disease of the epicardial vessels, and CMD, each of which may be seen in association with one or more of the others.

3. Microvascular obstruction can contribute to clinical presentation with several mechanisms: distal embolization from plaque and thrombi either spontaneous or associated with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), ischemic injury, and reperfusion injury.

4. MVA in the absence of CAD shows no or minimal response to nitrates, which may worsen the ST response to exercise. Reduction in coronary flow reserve using pharmacologic positron emission tomography (PET) (inverse perfusion/metabolism mismatch) can be used to identify MVA and CMD in persons with angina and no obstructive CAD.

5. The term ‘coronary microvascular dysfunction’ now refers to four types based on clinical setting: (i) in the absence of myocardial diseases and obstructive CAD (risk factors and MVA), (ii) in myocardial diseases (e.g., hypertrophic cardiomyopathy, dilated cardiomyopathy, myocarditis, aortic stenosis), (iii) in obstructive CAD (stable angina, acute coronary syndrome), and (iv) iatrogenic (PCI, CABG).

6. Pathogenesis includes endothelial dysfunction, smooth muscle cell dysfunction, vascular remodeling, extrinsic compression, luminal obstruction, and autonomic dysfunction.

7. CMD and reduced endothelial-dependent vasodilation is increased in diabetes, chronic inflammation/pro-inflammatory cytokines, and associated with classic risk factors and use of estrogens.

8. Estimates are that at least 3–4 million patients in the United States alone have signs and symptoms of ischemia despite no evidence of obstructive atherosclerosis, with associated poor quality of life, psychological distress, and health care costs that approximate those of patients with obstructive CAD. Terms ‘coronary microvascular dysfunction’ and ‘microvascular angina’ should be used for these patients, rather than ‘angina with normal coronary arteries.’ Sympathetic activation with CMD is thought to be the mechanism of stress cardiomyopathy or Takotsubo syndrome.

9. First-line therapy for MVA should include lifestyle improvement with smoking cessation, weight loss, and exercise, which may reduce adrenergic response of the small vessels. Additionally, statins and angiotensin-converting enzyme (ACE) inhibitors in hypertensive patients may induce arteriole reverse remodeling.

10. Strategies for reducing symptoms and ischemia in MVA include beta-blockers and calcium channel blockers; ranolazine, xanthines, ACE inhibitors, ivabradine (not in US), nicorandil (not in US); tricyclics; and if necessary, enhanced external counterpulsation and spinal cord stimulation.