Microvascular Angina or Cardiac Syndrome X

Cardiac Syndrome X, or microvascular angina, is diagnosed when a person has angina, with evidence of cardiac ischemia on stress testing, but with normal-looking coronary arteries on cardiac catheterization. In most cases, microvascular angina is caused by a disorder of the small branches of the coronary arteries in which these tiny vessels fail to dilate normally, thus producing a lack of blood flow to the heart muscle. Since the problem is now thought to be localized to the small arteries, the older name of cardiac syndrome X has largely been supplanted by the more descriptive term, microvascular angina. Notably, however, some experts believe that people with this condition may instead have an abnormal sensitivity to cardiac muscle pain.

Woman speaking with her doctor

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Microvascular angina is much more common in women (typically, postmenopausal women) than in men. There are several possible causes of the small artery dysfunction that is thought to be present in microvascular angina, including insulin resistance, inflammation, increased adrenalin activity, estrogen deficiency, and dysautonomia. It is likely that different patients with microvascular angina may have different underlying causes.

While most people with microvascular angina have a favorable prognosis—in that the risk of acute coronary syndrome caused by microvascular angina is quite low—it is not uncommon for the chest pain produced by this condition to be a significant, and sometimes disabling, problem.


Whenever you see a long list of possible treatments for some medical condition, it’s a sign that treating that condition may be difficult. (Likely, that’s why so many treatments have been tried in the first place.) Such is the case with microvascular angina.

Many medications have been found helpful in at least some patients with microvascular angina. However, in finding the “best” treatment for any given individual, a trial-and-error approach is often required. This means that both the patient and doctor may need to be patient and persistent in order to find the optimal therapy.

Here is a list of treatments often used in treating microvascular angina:

Traditional Angina Drugs

Non-Traditional Angina Drugs

  • Ranolazine: quite effective in small clinical trials
  • ACE inhibitors: especially in patients with hypertension
  • Ivabradine: also effective in small clinical trials
  • Statins: especially in patients with high cholesterol levels
  • Estrogens: in post-menopausal women
  • Imipramine: not an angina drug, but can be effective with pain control
  • L-arginine: may help to restore normal dilation of small blood vessels
  • Viagra (sildenafil): not well studied for microvascular angina, but may be quite effective in some people
  • Metformin: support for this drug in treating microvascular angina is purely anecdotal, and is not confirmed by clinical data.

Non-Drug Therapy

  • EECP: shown in one small study to be effective for microvascular angina
  • Spinal cord stimulation: shown to be helpful in some patients in whom drug treatment has failed.
  • Exercise training has been quite helpful, especially in patients who are out of shape.

General Approach to Treatment

Given all these possibilities, most cardiologists will attempt to optimize the treatment of microvascular angina using a step-wise approach. If adequate control of symptoms is not obtained with any given step, the doctor and patient will move on to the next step.

  • Step 1 is usually to use sublingual nitroglycerin to relieve symptoms whenever they occur. A program of physical training is often strongly recommended as part of a first step as well. If this does not provide sufficient relief the next step is tried.
  • Step 2 is usually to add a beta blocker. 
  • Step 3 is usually to stop the beta blocker and substitute a calcium channel blocker.
  • Step 4 is usually to try ranolazine, either alone or with a beta blocker or calcium blocker.
  • Step 5 is to consider other drugs or to add non-drug therapy, with spinal cord stimulation or EECP.

In addition to taking steps like these, an ACE inhibitor also should be strongly considered if hypertension is present, and a statin should be seriously considered if risk factors for typical coronary artery disease are also present. In women who are recently menopausal, estrogen therapy might be worth considering as well. 

With patience—perhaps a good deal of patience—adequate control of symptoms can eventually be achieved in the large majority of people who have microvascular angina. And while progressing through these steps, people with microvascular angina should keep in mind that their long-term prognosis is generally very good.

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By Richard N. Fogoros, MD
Richard N. Fogoros, MD, is a retired professor of medicine and board-certified in internal medicine, clinical cardiology, and clinical electrophysiology.