Myocardial Infarction in Patients With a Normal Cardiac Catheterization

Robert D. Glatter, MD


December 28, 2009


What are possible explanations for acute myocardial infarction in patients presenting to the emergency department with recently "negative" cardiac catheterization results?

Response from Robert D. Glatter, MD
Attending Physician, Department of Emergency Medicine, Lenox Hill Hospital, New York, NY

When patients present to the emergency department with symptoms of an acute coronary syndrome (ACS) or myocardial infarction (MI), but they have recently had a "negative" cardiac catheterization, physicians must still proceed with caution in their evaluation.

First, it is important to be aware of the patient's impression of their catheterization results. One should verify that the results truly were negative for coronary lesions; when patients say that their results were "negative," it may be that coronary artery disease (CAD) was found but no intervention or stenting was performed. In other words, the patient may interpret "negative" as meaning that no coronary artery disease was found, but to the physician, it may mean that no intervention was required for the patient's 40% proximal right circumflex artery lesion. In addition, a truly negative catheterization result 2 weeks earlier does not exclude the possibility that a patient could be having an acute MI in your emergency department today.

Coronary artery plaque may grow into the wall of a vessel and not produce significant luminal narrowing, a phenomenon known as coronary artery remodeling.[1,2] Because cardiac catheterization provides only 2-dimensional visualization, such coronary lesions may not be readily apparent using this technique. However, coronary computed tomographic angiography (CCTA) now allows 3-dimensional visualization of coronary plaque, which provides valuable information on the content and composition of the plaque and on the extent of remodeling, information that standard cardiac catheterization does not provide.[3]

Coronary plaques with significant remodeling have a high lipid content and macrophage count and a thin fibrous cap, all of which are markers for plaque vulnerability.[4] This may explain why plaque rupture is common in coronary segments with minimal luminal narrowing but significant coronary remodeling.[4] In fact, in a recent study, more than 50% of coronary segments negative for CAD by cardiac catheterization were found to be positively remodeled when examined by CCTA, with vulnerable plaque at risk for erosion or rupture.[4]

Use of intravascular ultrasonongraphy (IVUS) as well as CCTA may identify areas of extraluminal growth of lipid- rich vulnerable coronary plaques, which are highly prone to rupture but may not be visualized by traditional cardiac catheterization.[5] Rupture of vulnerable, lipid-rich coronary plaques identified by CCTA and IVUS have been implicated as a risk factor in patients who present with acute MI but have no cardiac catheterization-based evidence of significant (> 50%) luminal narrowing.[5]

Coronary spasm may also cause fatal ST-elevation MI and can occur by various mechanisms. The first mechanism is Prinzmetal’s angina, a syndrome in which patients who have normal exercise tolerances develop acute MI or angina at rest owing to coronary vasospasm, often in the early morning hours.[6] Coronary vasospasm can be a result of dysfunctional coronary endothelium, or it may be caused by release of local vasoconstrictors from platelets (serotonin or thromboxane A2). Cocaine use is also a well-established cause of coronary vasospasm.[7,8,9]

Myocardial bridging is another mechanism by which MI can occur in patients with negative findings on cardiac catheterization. This term refers to a large coronary vessel that generally is epicardial but may submerge under the myocardial surface for short segments. In this situation, bridging may lead to compression of a coronary vessel by the surrounding muscle during systole, thereby depriving the heart muscle of oxygen and blood flow. Myocardial bridging is seen in vivo in only about 5% of patients with normal vessels, but the incidence in autopsy series is quoted as 5% to 86%.[10,11,12]

Myocardial bridging most often occurs in the middle segment of the left anterior descending coronary artery, and a recent study using IVUS suggested that this phenomenon is more frequent than previously thought. The study found an incidence of 23% in a patient sample with a high incidence of CAD, suggesting that most bridging lesions are angiographically silent.[13]

Negative catheterization results may be seen in 10%-30% of patients referred for clinical suspicion of angina.[14] Many more women than men (nearly 3 times) with suspected angina have negative catheterization results or lesions smaller than 50% of luminal diameter.[14] About 3% of patients who undergo cardiac catheterization for acute MI have normal coronary arteries.[15]

Some patients who have typical angina, multiple coronary risk factors (hypertension, diabetes, elevated cholesterol level, abdominal obesity), and ST-segment depression on exercise electrocardiography, are referred to as having "cardiac syndrome X." The source of pain in these patients has been debated in the past, but newer studies suggest that they are experiencing subendocardial ischemia.[16,17] Coronary endothelial dysfunction and subsequent microvascular ischemia is the probable mechanism in patients with cardiac syndrome X, which results in angina-like chest pain.[18] This occurs not from large-vessel obstructions, but from flow limitation in relatively small vessels or microvascular angina. In the past, prognosis of these patients was thought to be excellent.[16,17] At least one recent study, however, found that in patients in whom microvascular angina was demonstrated, 14% had cardiac death, MI, or coronary artery bypass grafting over28-months.[19]

Finally, patients with significant left ventricular hypertrophy can develop mild, diffuse subendocardial ischemia. Essentially, the heart muscle becomes thick enough that the blood supply to the subendocardium cannot keep pace with demand. In times of increased demand, small areas can infarct, but subsequent catheterization will reveal no blockage.


  • Most patients who have had a truly negative cardiac catheterization in the recent past (up to 12 months previously) are less likely to be having acute MI than someone whose arteries have not been studied. However, the scenarios described above can occur, and a negative catheterization result alone does not rule out acute MI.

  • Coronary artery remodeling with evaluation of plaque vulnerability may play a larger role in the future evaluation of patients who may be at risk for acute coronary syndromes with evolution to acute MI.

  • Any patient with multiple risk factors, especially diabetes and a history of smoking, who presents with concerning features for angina should be evaluated for possible acute MI or unstable angina.

  • Overall, patients with negative catheterization reports have a low mortality rate. A recent study of survival rates for patients with normal catheterizations found that 96% were alive after 7 years, compared with 92% of patients who had mild coronary lesions (< 50%).[20]


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: