Myocardial Ischemia Is Not Always Due to Epicardial Atheromatous Disease

Abstract

Symptoms related to myocardial ischemia, for the most part, are due to high‐grade epicardial coronary artery stenoses. However, in some instances at coronary angiography, no such lesions are seen to account for symptoms due to an imbalance between myocardial oxygen supply and myocardial oxygen demand. Thus, the finding of normal or nonobstructive epicardial coronary arteries at coronary angiography does not exclude the presence of myocardial ischemia in some patients. Copyright © 2011 Wiley Periodicals, Inc.

The author has no funding, financial relationships, or conflicts of interest to disclose.

Nonobstructive Epicardial Coronary Artery Disease and Myocardial Ischemia

When catheter‐based coronary angiography or other imaging techniques are done to assess symptoms thought to be related to myocardial ischemia, and a “normal” coronary angiogram is found, the physician and the patient may be confused as to the reason for the symptom. When investigated diligently in the cardiac catheterization laboratory, other causes of decreased myocardial oxygen supply or increased oxygen demand may be found.

For example, the Women's Ischemia Syndrome Evaluation investigators have reported significant associations between decreased coronary flow reserve and adverse outcomes.1 This National Heart, Lung, and Blood Institute‐sponsored study was aimed at improving diagnostic evaluation and understanding pathologic mechanisms of ischemic heart disease in women. Coronary reactivity to adenosine was assessed in a stenosis‐free area of the left anterior descending or left circumflex coronary artery using a Doppler‐tipped guide wire. Coronary flow reserve of >2.32 was determined to be a discriminating threshold for adverse outcomes at a mean of 5.4 years in 152 women without obstructive coronary artery disease. These findings are highly suggestive of coronary microvessel disease.

Galiuto and colleagues2 reported reversible coronary microvascular dysfunction in 15 women patients with classical apical ballooning and no evidence of obstructive coronary disease. Myocardial contrast echocardiography during adenosine infusion at 140 μg/kg/min was assessed with multiple indices of myocardial perfusion and ventricular function at baseline and at 1‐month follow‐up. At baseline, the indices were abnormal, but at 1 month these indices of perfusion and myocardial dysfunction returned to normal. Their data strongly suggest acute and reversible coronary microvascular constriction in these patients with apical ballooning.

Other Disease States With Normal Coronary Angiograms and Myocardial Ischemia

Microcirculatory disease can occur in patients with polyarteritis, diabetes mellitus, and myocardial diseases such as amyloid aortic stenosis and ventricular hypertrophy secondary to severe hypertension. In patients with severe left ventricular hypertrophy, the probable mechanism for myocardial ischemic pain is related to decreased coronary flow reserve in the subendocardium.3

Hypertrophic cardiomyopathy with or without pressure differences in the ventricle can be responsible for ischemic cardiac symptoms based on the markedly hypertrophied cardiac muscle, which increases myocardial oxygen demand despite the usually large epicardial coronary arteries. The source of the ischemic symptoms may be related to the microcirculation, as it might be in a restrictive cardiomyopathy.

“Microvascular angina” is a term used frequently in the cardiac literature. The term in English actually means “microvascular pain,” which does not make much sense to me. The term implies that symptoms of myocardial ischemia are related to microcirculatory problems. I think it might be more appropriate to use the term “myocardial ischemia secondary to problems in the microcirculatory vessels.”

Another term that implies microvascular coronary dysfunction is “syndrome X.”4 This term tells the reader nothing about mechanism. Once again, rather than using this term to describe the clinical situation, I think it is more appropriate to describe the clinical observations of these patients. For example, in patients who have documented myocardial ischemia but normal coronary angiograms, and are considered as cardiac syndrome X, they have for the most part effort‐induced angina and some ST segment depression or nuclear studies suggestive of myocardial ischemia either spontaneous or provoked. They have no evidence of spontaneous or provoked epicardial coronary artery spasm or other possible causes for myocardial ischemia, such as cardiomyopathies, systemic hypertension, or diabetes. Unfortunately many patients who have chest discomfort but none of the above characteristic changes are categorized as syndrome X, thus contributing to the confusion relating to the etiology of the chest discomfort.

Without evidence for myocardial ischemia, I think it is inappropriate to use the term “cardiac syndrome X” to characterize these patients. For example, if there is no transient ST segment depression during chest discomfort or reversible perfusion defects on nuclear imaging, then this is probably a different group of patients (ie, chest pain of uncertain etiology).

Myocardial Ischemia Due to Epicardial Obstruction Without Atheromatous Causes5

Coronary Embolism

Mitral Stenosis and Prosthetic Valve Devices:

Although this is a relatively rare cause of ischemic cardiac pain, conditions such as mitral stenosis, particularly in patients with atrial fibrillation and clots in the atrial appendage, can embolize the artery resulting in chest pain and/or acute myocardial infarction. Mitral or aortic valve prosthetic devices can be responsible for thrombus embolization into the coronary circulation even in patients properly anticoagulated.

Cardiac Tumors

Myxoma is a relatively benign tumor, but when attached to the left atrial septum with prolapse across the mitral valve, particles can break off and flow across the mitral valve to the systemic circulation and embolize the coronary arteries as well as other organs.

Aortic Valve Disease

Patients with infective endocarditis, particularly of the aortic valve, are at risk for embolization of infective debris into the coronary circulation. Myocardial ischemia can also occur in patients with aortic stenosis due to increased oxygen demand or involvement of the left main or right coronary ostia as well as embolization of calcific material into the coronary circulation.

Ostial Stenosis of the Left Main Coronary Artery

Left main coronary ostial stenosis as an isolated finding usually occurs as a result of disease of the ascending aorta. Aortitis of any etiology, valve replacement therapy, or dissection of the ascending aorta can occlude or partially occlude either right or left coronary ostia.

Coronary Artery Thrombosis

Rupture of a coronary artery plaque is the most common cause of coronary artery thrombosis, but coronary artery thrombosis has been associated with coronary artery spasm in a few instances. Rarely, coronary artery thrombosis can occur in young women taking contraceptive agents who are cigarette smokers. Patients with coagulopathies also may thrombose a coronary artery.

Spontaneous Coronary Artery Dissection

Coronary artery dissection occurring spontaneously can occur in patients with Marfan syndrome, coarctation of the aorta, Ehlers‐Danlos syndrome, and in women during pregnancy.

Iatrogenic Coronary Artery Dissection

In the past, coronary angiography rarely was associated with iatrogenic dissection of the coronary arteries; however, dissection resulting in compromise of the coronary circulation is much more frequent in the modern era of percutaneous coronary interventions and stent placement.

Congenital Coronary Artery Disease as a Cause of Ischemic Symptoms

The most common congenital abnormality of the coronary circulation is anomalous origin of a coronary artery, and the most common anomalous origin is a circumflex originating from the right coronary artery. Most coronary anomalies are benign, but pathologists have consistently observed a fibrous ridge at the ostium of tangentially oriented ectopic coronary arteries.6 Such ridges may have potentially catastrophic consequences, but atheromatous plaques that rupture are seldom seen.

Summary

Patients presenting with symptoms of myocardial ischemia may not have demonstrable high‐grade epicardial coronary artery stenoses secondary to atherosclerosis. Other sources must be searched for in patients undergoing modern imaging studies, particularly in patients whose symptoms and physiologic studies suggest myocardial ischemia despite a normal coronary angiogram. The finding of normal or nonobstructive epicardial coronary arteries at coronary angiography does not exclude the presence of myocardial ischemia in some patients.