AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Exercise Tolerance Test
• Myocardial Perfusion Imaging
• Stress Echocardiography
• Computed Tomography
• Future Directions in Testing
• Cardiac Testing in Women
• Summary
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Exercise Tolerance Test
• Myocardial Perfusion Imaging
• Stress Echocardiography
• Computed Tomography
• Future Directions in Testing
• Cardiac Testing in Women
• Summary
• References

During the course of an emergency department evaluation, the results of previous cardiac testing may become available. These tests may provide valuable information that can influence decisions affecting the treatment and disposition of patients. Physicians rely on a Bayesian model in interpreting the results of cardiac tests, generating a pretest probability of disease for an individual patient based on history, laboratory results, or other clinical factors, and then using the sensitivity and specificity of a given test for the population of interest to calculate the posttest probability of disease that will guide their decision making.

This article discusses the mechanism, sensitivity, and specificity of several common noninvasive cardiac tests, including exercise stress testing, cardiac radionuclide imaging, exercise echocardiography, electron beam computed tomography, and magnetic resonance imaging. Special considerations for interpreting the results of these tests in female patients are addressed as well.

EXERCISE TOLERANCE TEST

Section 3 of 10  

• Authors and Editors
• Introduction
• Exercise Tolerance Test
• Myocardial Perfusion Imaging
• Stress Echocardiography
• Computed Tomography
• Future Directions in Testing
• Cardiac Testing in Women
• Summary
• References

Testing methodology

The major hemodynamic consequence of coronary artery disease is decreased cardiac output resulting in decreased exercise capacity. During exercise, acute reduction of left ventricular function leading to decreased stroke volume and heart rate and increasing pulmonary artery pressure appears to be the mechanism limiting cardiac output. Multiple protocols exist for exercise tolerance tests; their common goal is to induce ischemia by pushing a patient to his or her maximum exercise level and then to measure the physiologic response. One common protocol is to have the patient start walking on a treadmill and then to increase the treadmill speed and gradient until the patient experiences symptoms or ECG changes, heart rate, or blood pressure reaches preset limits, or the patient reaches a predetermined metabolic workload.

Test outcomes and interpretation

Electrocardiographic responses

ST-segment depression: Standard criterion for this response is horizontal or down-sloping ST-segment depression of 0.1 mV or more for 80 milliseconds. The probability and severity of coronary artery disease is related directly to the amount of depression and to the down-slope of the ST segment. Severity of coronary artery disease and prognosis is correlated with the lower workload at which ST-segment depression occurs.

ST-segment elevation: In patients with no Q waves on the resting ECG, severe transmural ischemia is signified, and the site of ischemia is pinpointed. ST-segment elevation over areas of previous Q waves appears to be related to the presence of dyskinetic areas or ventricular aneurysms. Approximately 50% of patients with anterior MI and 15% of patients with inferior MI demonstrate this response.

Exercise tolerance test (ETT) results are centered on the ST response, with a ST depression greater than or equal to 1 mm signifying a positive test result. The American College of Cardiology and the American Heart Association performed meta-analysis of the diagnostic accuracy of exercise stress testing on 147 consecutively published reports involving 24,045 patients who underwent coronary angiography and ETT. The results indicated a mean sensitivity of 68% (range, 23-100%; standard deviation, 17%) and a mean specificity of 77% (range, 17-100%; standard deviation, 17%). When the studies that included patients with a previous MI were excluded, the meta-analysis involving 11,691 patients showed a mean sensitivity of 67% and a mean specificity of 72% for exercise stress testing for diagnosing coronary artery disease. The few studies that removed workup bias by having patients agree to undergo both procedures beforehand showed a sensitivity of 50% and a specificity of 90%.

The ETT is used to estimate prognosis of future cardiac events. However, available data show that test results offer a better guide to the likelihood of a fatal ruptured plaque than the likelihood of a nonfatal MI. In separate studies, ST-segment depression and exercise capacity were not correlated with an increased probability of a nonfatal MI.

However, a normal ECG during an exercise tolerance test should not necessarily be interpreted as a negative stress test. Other outcomes, including pain, workload, and vital sign abnormalities, are important clinical indicators as well.

Clinical responses

Chest pain consistent with angina is important, particularly if it terminates the test. Chest pain becomes more predictive of coronary artery disease if it is associated with ST depression. Signs of poor perfusion, such as a drop of skin temperature or peripheral cyanosis and symptoms of lightheadedness or vertigo, may indicate inadequate cardiac output.

Exercise capacity

Exercise capacity frequently is reported in metabolic equivalents of task (METs), which indicate units equivalent to the metabolic equivalent of resting oxygen uptake while sitting. An exercise capacity of 5 METs or less is associated with a poor prognosis in patients younger than 65 years. Exercise capacity of 10 METs signifies a prognosis with medical therapy similar to that of coronary artery bypass surgery. An exercise capacity of 13 METs indicates a good prognosis despite abnormal exercise test responses.

Exercise capacity correlates poorly with left ventricular function in patients with clinically normal heart function. Exercise capacity also does not identify patients with moderate left ventricular dysfunction.

Hemodynamic responses

Systolic blood pressure at peak exertion is considered a clinically useful estimation of the inotropic capacity of the heart. A drop of systolic blood pressure below that at rest is associated with increased risk in patients with a prior myocardial infarction (MI) or myocardial ischemia. Heart rate response to exercise can be affected by left ventricle dysfunction, ischemia, cardioactive drugs, or autonomic dysfunction. Chronotropic incompetence, or failure to achieve 80% of the age-predicted maximum exercise heart rate, was associated with an 84% increase in all-cause mortality over 2 years in a 1996 Cleveland Clinic Study. The heart rate recovery pattern, or change in heart rate after the patient stops exercising, also has prognostic significance, as do changes in blood pressure, with a slower reversion to the patient's baseline vital signs associated with higher long-term mortality.

Clinicians can combine multiple variables to give an overall evaluation of the patient's performance on the exercise tolerance using published equations such as the Duke Treadmill Score and the Long Beach Veterans Administration score.

Test utility

Exercise testing is indicated to evaluate patients with low risk or intermediate risk for coronary artery disease, including patients presenting to the emergency department with chest pain who remain pain-free during a period of observation and have normal cardiac enzyme levels. Certain patients do not benefit from exercise electrocardiography; this group includes patients with resting ECG abnormalities (left bundle-branch block, paced rhythm, preexcitation syndromes, or ST depressions at rest), inability to exercise, or angina and a history of revascularization. In addition, patients who take medications including digoxin, beta-blockers, vasodilators, and other antihypertensive medications may find that these medications affect their physiologic response to exercise.

MYOCARDIAL PERFUSION IMAGING

Section 4 of 10  

• Authors and Editors
• Introduction
• Exercise Tolerance Test
• Myocardial Perfusion Imaging
• Stress Echocardiography
• Computed Tomography
• Future Directions in Testing
• Cardiac Testing in Women
• Summary
• References

Test methodology

Myocardial perfusion imaging is used to visualize myocardial blood flow distribution using radionuclides such as thallium and technetium. Myocardial perfusion imaging is commonly used during exercise stress, but it can also be performed at rest. Rest imaging relies on the administration of the inotrope dobutamine or drugs that cause cardiac hyperemia (eg, dipyridamole, adenosine) for patients who are unable to exercise.

Thallium 201 is an intracellular cation that behaves similarly to potassium and has a half-life of 73 hours. After intravenous administration, thallium distributes in cardiac tissue in proportion to regional blood flow and is taken up by viable myocytes. During a thallium stress test, thallium 201 is injected while the patient is at peak exercise, and the patient continues to exercise for another minute afterwards. Images are taken immediately after administration of the thallium and again 3-4 hours later. Areas of decreased blood flow and nonviable myocardium have decreased thallium uptake and show up as defects on the initial images. Over time, the defects related to ischemic myocardium resolve on the subsequent images as myocardial blood flow normalizes. Persistent defects represent regions of scar from previous MI.

Technetium Tc 99m sestamibi, a calcium analog, is another commonly used radionuclide for perfusion imaging. Technetium Tc 99m sestamibi has a shorter half-life (6 h) than thallium 201, so a larger dose may be administered, improving count statistics and allowing evaluation of left ventricle function. Imaging characteristics are also more favorable, such as higher emission energy and less scattered radiation. Uptake of technetium Tc 99m sestamibi is clinically insignificant after the initial myocardial uptake, so 2 separate injections (one during exercise and one at rest) are necessary to distinguish between stress-induced perfusion defects and fixed perfusion defects. Most of the available data on myocardial perfusion imaging have involved the use of thallium 201, but the evidence suggests that technetium Tc 99m sestamibi yields similar accuracy in diagnosing coronary artery disease.

Most myocardial perfusion imaging procedures use a single crystal gamma camera that rotates around the body, obtaining single-photon emission computed tomography (SPECT) images after intravenous administration of a radionuclide. SPECT images are tomographic reconstructions that can distinguish myocardial from nonmyocardial structures and individual coronary artery territories.

Myocardial perfusion imaging can also be performed using planar techniques. SPECT imaging is preferable to planar imaging because of higher accuracy in diagnosing coronary artery disease, localizing hypoperfused vascular territories, identifying left anterior descending and left circumflex coronary artery stenoses, and predicting the presence of multivessel coronary artery disease.

Test outcomes and interpretation

A reversible perfusion defect on SPECT imaging is defined as a positive test. According to the 2003 AHA/ACC/ASCH Guidelines for the Clinical Use of Cardiac Radionuclide Imaging, the sensitivity of exercise and vasodilator stress perfusion SPECT for detecting clinically significant (>50% stenosis) coronary artery disease average 87% and 89%; specificities average 73% and 75%. In general, computer analysis of SPECT images is associated with improved sensitivity.

Stress radionuclide tests also provide some prognostic information. In patients with suspected or known coronary artery disease, qualitative and quantitative assessment of the number or extent of perfusion defects and the magnitude of defect reversibility are predictive of cardiac events during follow-up. Quantitatively normal planar or SPECT stress perfusion images, even in the presence of documented coronary artery disease, indicates a favorable prognosis with a 0.6% yearly nonfatal MI rate and a 0.5% yearly mortality rate.

Test utility

SPECT imaging is indicated for patients with intermediate pretest probability of coronary artery disease based on clinical history or results of a previous exercise tolerance test. It is also indicated in patients who cannot exercise and in patients for whom exercise electrocardiography is not helpful because of resting ECG abnormalities or exertional ST depressions associated with left ventricular hypertrophy (LVH). SPECT imaging has been found to be less sensitive and specific in patients with single-vessel disease (particularly isolated disease in the circumflex artery), significant collateral formation, cardiomyopathy, and significant attenuation from breast or diaphragm tissue.

STRESS ECHOCARDIOGRAPHY

Section 5 of 10  

• Authors and Editors
• Introduction
• Exercise Tolerance Test
• Myocardial Perfusion Imaging
• Stress Echocardiography
• Computed Tomography
• Future Directions in Testing
• Cardiac Testing in Women
• Summary
• References

Test methodology

Stress echocardiography is used to diagnose coronary artery disease by detecting cardiac wall motion abnormalities during exercise-induced myocardial ischemia. This test relies on the occurrence of ischemia, so sufficient cardiovascular stress must be achieved to detect wall motion abnormalities.

The different exercise modalities include treadmill and supine or upright bicycle ergometry. Echocardiography is not possible during treadmill exercise, so imaging is performed before and immediately after exercise. Four views are typically captured for treadmill testing; these are the parasternal long and short axes and the apical 4- and 2-chamber views. Postexercise images need to be obtained within 60-90 seconds or diagnostic accuracy falls.

Bicycle ergometry has a significant advantage in that echocardiographic imaging can be performed at each stage of exercise. Apical imaging is continued actively throughout most of the exercise. For supine ergometry, most laboratories configure the studies to include 4 views and 4 stages. Usual images included are 4 views of a predetermined cardiac site on a single quad screen at rest, low stress, peak stress, and either recovery or intermediate stress. Upright bicycle ergometry provides images with quality between that of the treadmill and supine bicycle because parasternal views are frequently not possible because of the upright position.

For patients who are not able to exercise, echocardiography can also be performed with pacing or with pharmacologic agents to increase heart rate. In cases where patients are difficult to image because of body habitus, lung disease, or tachycardia, the introduction of IV contrast or microbubbles can improve visualization. In all cases, however, stress echocardiography is relatively operator-dependent compared with other modalities, and as many as 10% of patients may have inadequate images. Despite this, however, cost analysis has shown that stress echocardiography offers the greatest improvement in health outcomes relative to expenditures when compared with standard exercise testing and thallium imaging.

Test outcomes and interpretation

Observation of an ischemia-induced regional wall motion abnormality on echocardiography is considered a positive test result. Analysis is based on regional wall motion abnormalities. The ventricle is divided into a 16-segment model as recommended by the American Society of Echocardiography, and each of the 16 segments is graded with respect to wall motion as normal, hypokinetic, akinetic, dyskinetic, or aneurysmal. Comparison of wall motion scores at rest and varying levels of stress provides a quantitative measure of the severity of ischemia. In addition, stress echocardiography can also be used to generate information about LV function and valve function.

Fleischmann et al performed a recent meta-analysis that compared exercise echocardiography with exercise SPECT (thallium 201 or technetium Tc 99m sestamibi) imaging using coronary angiography as the reference for diagnosing coronary artery disease. It showed that exercise echocardiography had a sensitivity of 85% (95% confidence interval [CI], 83-87%) with a specificity of 77% (95% CI, 74-80%); it showed that exercise SPECT had a sensitivity of 87% (95% CI, 86-88%) with a lower specificity of 64% (95% CI, 60-68%).

A recent study on 463 patients with known or suspected coronary artery disease who were then followed for 44 +/- 11 months by Marwick et al showed that positive test results for ischemia are highly predictive of coronary events. A negative exercise ECHO was associated with a 7% (20/293) event rate (eg, late revascularization, angina, MI, fatality) during this follow-up period.

Test utility

Stress echocardiography may be useful in patients with significant cardiomyopathies for whom SPECT will be less sensitive, or in patients for whom echocardiography is desired for other reasons. It is less useful when practitioners have limited experience performing the test.

COMPUTED TOMOGRAPHY

Section 6 of 10  

• Authors and Editors
• Introduction
• Exercise Tolerance Test
• Myocardial Perfusion Imaging
• Stress Echocardiography
• Computed Tomography
• Future Directions in Testing
• Cardiac Testing in Women
• Summary
• References

Test methodology

Calcium is commonly found in plaques and particularly in healing plaques that have ruptured. Computed tomography (CT), when used to image the heart and coronary vessels, can detect plaques obstructing the lumen as well as the increased density of these calcifications in coronary artery walls. Although coronary calcium is associated with the presence of unstable plaques, the calcium is frequently not present in the unstable plaque itself; some plaques are destabilized due to erosion rather than calcification. Instead, high levels of calcification are a marker for overall disease burden. The technique was established with electron beam scanners, but it has been refined and made more widely available with the introduction of multidetector scanners.

Test outcomes and interpretations

Electron beam CT has been compared to invasive angiography in the detection of coronary artery luminal obstructions greater than 50% and has been found to have a sensitivity of 92% and a specificity of 94%; for multidetector CT scanners, the sensitivity and specificity are 82% and 96%. The amount of calcium seen in coronary vessels on CT can also be quantified in a calcium score according to one of several algorithms. In multiple large studies, calcium scores greater than 1000 have been associated with significant increases in morbidity and mortality independent of other risk factors. In one study, patients with calcium scores greater than 1000 were found to have a relative risk of death at 5 years of 4.03 (95% CI, 2.52-6.40). Unlike CT angiography, however, calcium scores reflect overall risk and cannot be used to diagnose the presence of an obstructing lesion.

Test utility

CT angiography is a modality that continues to improve with the introduction of 32- and 64-slice CT scanners and may eventually equal invasive angiography in the diagnosis of obstructing lesions.

Because it does not allow for the possibility of intervention when a lesion is found, it is particularly useful in ruling out obstructing lesions in low-risk patients without exposing them to the potential hazards of catheterization and contrast dye. However, patients with a heavy calcium burden will have poorer quality CT images. Also, the thin slices necessary for CT angiography means that motion artifact can cause significant degradation. For this reason, patients are commonly treated with beta-blockers prior to CT angiography, and patients who are unable to tolerate the pretreatment will be less likely to generate useful images. Also, patients who have increased motion due to very large habitus (BMI >40) will likely have nondiagnostic images as well. Calcium scoring is indicated for further risk stratification of patients with an intermediate pretest probability for coronary artery disease. However, it cannot be used to identify or rule out the presence of an unstable plaque.

FUTURE DIRECTIONS IN TESTING

Section 7 of 10  

• Authors and Editors
• Introduction
• Exercise Tolerance Test
• Myocardial Perfusion Imaging
• Stress Echocardiography
• Computed Tomography
• Future Directions in Testing
• Cardiac Testing in Women
• Summary
• References

Magnetic resonance angiography

Cardiac magnetic resonance angiography (MRA) allows visualization of coronary vessels without radiation or contrast dye. With contrast and the addition of vasodilators or dobutamine, MRA can be used to assess myocardial viability as well. By synchronizing image acquisition with the patient's cardiac cycle, new protocols allow the patient to breathe during the test. While cardiac MRI/MRA continues to evolve, it shows promise as the only imaging modality that can combine angiography with perfusion and wall motion assessments.

Carotid intima-media thickness

Carotid artery ultrasonography and measurement of the intima-media thickness is another area of investigation. Observational studies have shown that intima-media thickness is an independent marker of cardiovascular risk, but whether it is more accurate than traditional risk factors is unclear. However, it could prove valuable as a rapid, low-cost, low-risk test easily obtainable in the emergency department.

CARDIAC TESTING IN WOMEN

Section 8 of 10  

• Authors and Editors
• Introduction
• Exercise Tolerance Test
• Myocardial Perfusion Imaging
• Stress Echocardiography
• Computed Tomography
• Future Directions in Testing
• Cardiac Testing in Women
• Summary
• References

Cardiovascular disease is the leading cause of death for women in the United States, but a considerable body of research has demonstrated that women have different patterns of coronary artery disease and different responses to cardiac testing than their male counterparts. Women are more likely to have nonobstructive or single-vessel disease when compared with men, which decreases the diagnostic accuracy of stress testing. For example, treadmill testing in one meta-analysis was shown to have a sensitivity and specificity of 61% and 70% for women compared with 72% and 77% for men.

Calcium scoring is limited because women tend to have 3- to 5-fold greater mortality rates for a given calcium score than men, suggesting that separate guidelines for interpreting scores in women should be developed.

SPECT imaging is technically limited in women because breast tissue and relatively small left ventricle size can generate false-positive results. Technetium is less prone to attenuation artifacts than thallium and thus has higher specificity. The American Heart Association has recommended that the exercise tolerance test is still the initial test of choice for a low-risk or intermediate-risk symptomatic woman with no contraindications.

SUMMARY

Section 9 of 10  

• Authors and Editors
• Introduction
• Exercise Tolerance Test
• Myocardial Perfusion Imaging
• Stress Echocardiography
• Computed Tomography
• Future Directions in Testing
• Cardiac Testing in Women
• Summary
• References

Noninvasive tests to diagnose coronary artery disease are improving as new diagnostic technologies and methods are being developed. As future studies reveal the true diagnostic characteristics and abilities of these tests, ED physicians can better assess patients' risk of coronary artery disease based on their previous test results and more effectively counsel them on future testing and interventions.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Exercise Tolerance Test
• Myocardial Perfusion Imaging
• Stress Echocardiography
• Computed Tomography
• Future Directions in Testing
• Cardiac Testing in Women
• Summary
• References

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• Mieres JH, Shaw LJ, Arai A, et al. Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: Consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Cou. Circulation. Feb 8 2005;111(5):682-96. [Medline].
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Article Last Updated: Jul 13, 2006