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Cardiac Syndrome X (CSX)

Angina with Normal Coronary Arteries

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Updated November 12, 2011

Cardiac Syndrome X (CSX) causes angina, even with "normal" coronary arteries. As such, CSX often causes confusion and frustration on the part of both patients and doctors. It is far more common in women than men.

Typically, a patient with CSX will have angina with exertion, and a stress test will show changes on the electrocardiogram (ECG) that are strongly suggestive of ischemia (i.e, poor blood flow in the heart muscle). But when the cardiac catheterization is done, the coronary arteries will appear normal. So the the chief characteristics of CSX are:

  • Angina during exertion
  • ECG changes during stress testing indicative of ischemia
  • Normal coronary arteries on cardiac catheterization, with no evidence of coronary artery spasm

Who Gets CSX?

While CSX can affect anyone, it is usually seen in women, and most often begins around the age of menopause. All too often, women with CSX are written off as having anxiety or hysteria because they complain of significant symptoms but have diagnostic results that fail to show any clear problems.

What Causes CSX?

Nobody knows for sure what causes CSX, but it now appears likely that most cases are caused by a disorder of the small arteries in the heart muscle (arteries that are too small to be seen during catheterization). Evidence now suggests that these small arteries do not dilate normally (for instance, during exercise) in patients with CSX, thus reducing the amount of blood that can be supplied to the heart muscle.

Another "explanation" for CSX invoked by some doctors is so-called "enhanced pain sensitivity," which appears to mean that women with CSX experience pain (and complain about it) more than doctors think they should. This explanation is not particularly helpful for treatment.

In some women with CSX, there is evidence of abnormalities of the autonomic nervous system (i.e., of dysautonomia) - specifically in the case of CSX, an increase in sympathetic tone (i.e., adrenaline levels) has sometimes been seen. Furthermore, CSX has been associated with other dysautonomia syndromes, such as fibromyalgia and inappropriate sinus tachycardia.

Finally, recent evidence suggests that some women who are labeled as having CSX actually may have "female-pattern" coronary artery disease, that is, true coronary artery disease due to atherosclerosis, but which develops in a pattern that makes the coronary arteries appear normal on cardiac catheterization.

What Are the Consequences of CSX?

The majority of women with CSX have a very good prognosis, and while they may continue to have symptoms with exertion, they do not develop life-threatening heart disease. However, there are two possible exceptions to this general rule.

First, there is suggestive evidence that women who develop stress cardiomyopathy (also known as broken-heart syndrome) may have underlying CSX. So patients with CSX may be more prone to this condition.

And second, women with CSX have been known to develop acute coronary syndrome (ACS), which is a very serious medical condition. At present, however, it appears likely that those who develop ACS may not have CSX at all, but may actually have "female-pattern" coronary artery disease.

How Is CSX diagnosed?

There is no test that definitively "proves" that you have CSX. Indeed, the diagnosis is made primarily by excluding all other causes of chest pain. However, several tests can be helpful in making the diagnosis. These include:
  • Stress testing, which usually reproduces the pain and shows characteristic changes on the ECG.
  • Cardiac catheterization, which shows normal coronary arteries and no inducible spasm.
  • MRI scanning has been used in research centers to demonstrate abnormal blood flow in the heart muscle of patients with CSX. MRI scanning is not a routine test in patients suspected of CSX, but has offered the strongest evidence to date that patients with CSX have a true physiological (and not merely psychological) abnormality.

How Is CSX Treated?

If you have CSX, the chief goal of therapy will be to control your chest pain to allow you to lead a normal life.

Good pain control can usually be achieved with medical therapy, but complete success often requires a trial-and-error approach (and thus will require patience on your part as well as your doctor's). Anti-anginal drugs that have been shown to be effective in treating CSX include the beta blockers and nitrates. (For reasons unknown, calcium blockers often do not do much good in CSX, though they may be worth a try if other drugs are insufficiently effective.)

Recently, studies have strongly suggested that treatment with ACE inhibitors and statins can greatly reduce the symptoms of CSX. Finally, imipramine can be beneficial in the treatment of CSX, as it is for various types of chronic pain.

Summary

Like several other disorders that produce angina with "normal" coronary arteries, CSX is a real medical condition that can be treated once it is diagnosed. If you are a woman who has had angina-like chest pain but your cardiac catheterization study has shown "normal" coronary arteries, you and your doctor should be aware that your work is not yet finished. In this setting, a "normal" angiography study does not rule out a cardiac problem. Instead, it means that further investigation is needed to find the cause of your symptoms.

Sources:

Kaski, JC. Pathophysiology and management of patients with chest pain and normal coronary arteriograms (cardiac syndrome X). Circulation 2004; 109:568.

Pizzi, C, Manfrini, O, Fontana, F, Bugiardini, R. Angiotensin-converting enzyme inhibitors and 3-hydroxy-3-methylglutaryl coenzyme A reductase in cardiac Syndrome X: role of superoxide dismutase activity. Circulation 2004; 109:53.

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