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Cardiac Tests

  • Author: Richard S Krause, MD; Chief Editor: Barry E Brenner, MD, PhD, FACEP  more...
 
Updated: Dec 18, 2014
 

Practice Essentials

Cardiac testing is used to help stratify patients thought to be at risk for symptomatic coronary artery disease (CAD), specifically for short-term complications such as myocardial infarction (MI) or sudden cardiac death.

The image below depicts Wellens syndrome, a preinfarction stage of CAD that often progresses to a devastating anterior wall MI.

Classic Wellens syndrome T-wave changes. This ECG Classic Wellens syndrome T-wave changes. This ECG represents a patient after becoming pain free secondary to medications. Notice the deep T waves in V3-V5 and slight biphasic T wave in V6 in this chest pain free ECG. The patient had negative cardiac enzyme levels and later had a stent placed in the proximal left anterior descending (LAD) artery.

Types of tests

Cardiac testing encompasses diagnostic coronary angiography (invasive) or a variety of noninvasive tests. Noninvasive tests include the following:

  • Exercise stress testing
  • Pharmacologic stress testing
  • Myocardial perfusion imaging
  • Stress echocardiography
  • Cardiac computed tomography (CT) scanning

These noninvasive tests can be performed in an outpatient setting, in a physician's office, in a hospital, or in an observation unit, as well as for admitted inpatients. The American Heart Association recommends that in nonemergency settings, patients should be informed of the risks (including those associated with radiation) and benefits involved in the use of cardiac CT scanning, radiopharmaceuticals, and fluoroscopy.[1]

Exercise stress test

Multiple protocols exist for exercise tolerance tests. A bicycle ergometer or treadmill is most often used. The goal is to increase workload incrementally to induce ischemia or until a predetermined workload is reached. The goal of exercise testing in the setting of acute chest pain is typically to evaluate for coronary ischemia and not for exercise capacity per se.

Pharmacologic stress test

Pharmacologic stress testing, established after exercise testing, is a diagnostic procedure in which cardiovascular stress induced by pharmacologic agents is demonstrated in patients with decreased functional capacity or in patients who cannot exercise. The most widely available pharmacologic agents for stress testing are dipyridamole (Persantine), adenosine, regadenoson (Lexiscan), and dobutamine. However, the US Food and Drug Administration (FDA) warns against the use of adenosine and regadenoson in patients with signs or symptoms of unstable angina or cardiovascular instability.[2, 3]

Myocardial perfusion imaging

A myocardial perfusion SPECT (single photon emission computed tomography) test is a procedure that illustrates the function of the myocardium. It is the test of choice for patients with active chest pain, an ECG with no ischemic changes, and an initial negative troponin result, according to the American College of Radiology guidelines.[4]

Stress echocardiography

Another method of detecting coronary artery disease is to perform echocardiography while the heart is undergoing exercise or pharmacologically induced ischemia. The exercise is performed using a treadmill or a bicycle ergometer. If a treadmill is used, images are obtained prior to exercise and then within 60-90 seconds of completing exercise. Bicycle ergometry has the advantage of being able to perform the echocardiogram at different stages of exercise. Supine ergometry provides the most information, since 4 cardiac views can be obtained.

Computed tomography

Calcium deposits are commonly found in atherosclerotic coronary plaques. The total amount of coronary calcium is predictive of future cardiac events. Cardiac computed tomography (CCT) can measure the density and extent of calcifications in coronary artery walls. The technique relies on ECG "gating" to compensate for cardiac motion.

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Overview

The goal of cardiac testing is to help stratify patients thought to be at risk for symptomatic coronary artery disease, specifically for short-term complications such as myocardial infarction (MI) or sudden cardiac death. Risk stratification of chest pain patients in the emergency department (ED) or other outpatient settings also includes interpretation of the history, physical examination, ECG, and, when indicated, cardiac biomarkers. Cardiac testing encompasses diagnostic coronary angiography (invasive) or a variety of noninvasive tests.

This article focuses on the noninvasive testing modalities and their role in risk-stratifying ED patients and other outpatients. The tests reviewed include exercise stress testing; pharmacologic stress testing; myocardial perfusion imaging; stress echocardiography; and cardiac CT, MRI, and positron emission tomography (PET) scanning. These noninvasive tests can be performed in an outpatient setting, in a physician's office, in a hospital, or in an observation unit, as well as for admitted inpatients.

An understanding of these tests is important to for 2 primary reasons. First, patients frequently present that have undergone prior noninvasive testing. Knowing the value and limitations of that testing can be valuable in the care of such patients. Second, with the recent expansion of observation medicine, it has become the responsibility of emergency physicians to choose and utilize the results of noninvasive cardiac testing in many hospitals. Noninvasive cardiac testing is an important adjunct to the broader scheme used to risk stratify chest pain patients. Use of cardiac biomarkers alone without additional noninvasive testing has not been shown to confer a low-enough risk to safely discharge a large proportion of emergency department chest pain patients.[5, 6, 7]

Explicitly or implicitly physicians use a Bayesian model to interpret results of cardiac tests. They generate a pretest probability of disease for an individual patient based on history, ECG, laboratory results, and other clinical factors. Then by using the sensitivity and specificity of a given test for the population of interest, a post-test probability is calculated which can guide decision making. In day-to-day practice, this is performed more qualitatively than quantitatively. In addition, this process is reflected in diagnostic protocols for chest pain.

This article discusses the physiology, technique, interpretation, and utility of the most common noninvasive cardiac tests.

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Exercise Tolerance Test

Test physiology and technique

Physical exercise places stress on the cardiopulmonary system. The physiologic response to exercise stress increases myocardial oxygen demand in response to increased heart rate and systolic blood pressure. The ECG response and development of angina in response to exercise closely correlates with myocardial ischemia due to obstructive coronary artery disease. Exercise capacity is reduced by myocardial ischemia but is also influenced by many other factors. The goal of exercise testing in the setting of acute chest pain is typically to evaluate for coronary ischemia and not for exercise capacity per se. A typical clinical paradigm anticipates discharge to home of patients with a negative initial evaluation (H+P, ECG, chest radiograph, negative cardiac biomarkers), and a negative exercise test.

Multiple protocols exist for exercise tolerance tests. A bicycle ergometer or treadmill is most often used. The goal is to increase workload incrementally to induce ischemia or until a predetermined workload is reached. 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, the heart rate or blood pressure reaches preset limits, or the patient reaches a predetermined metabolic workload.

Multiple studies have validated the safety and efficacy of exercise testing in low-risk chest pain patients. Low risk, in this context, is defined as patients presenting with chest pain who remain pain-free during a 6- to 12-hour period of observation and have normal initial and repeat cardiac biomarker levels.[8] It is also assumed that other serious diagnoses such as pulmonary embolism or aortic dissection are not present. Studies have also reported on the safety and efficacy of "immediate" exercise testing in low-risk patients who have normal initial ECG findings and initial biomarker levels and are not serially evaluated prior to stress testing.[9]

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 ≥1 mm ST depressions at rest), inability to exercise, and others. Test interpretation may be compromised in patients taking certain medications such as digoxin, beta-blockers, certain calcium channel blockers, and other antihypertensive medications. Other tests, such as nuclear cardiac scanning, may be useful in this subgroup. In addition, clinicians should be familiar with contraindications to stress testing prior to ordering or performing the test. Contraindications include the following.

  • Acute MI
  • Sustained ventricular arrhythmias, SVT, high-grade heart block
  • Wellens syndrome (highly correlated with CAD and sudden death), shown in the image below
    Classic Wellens syndrome T-wave changes. This ECG Classic Wellens syndrome T-wave changes. This ECG represents a patient after becoming pain free secondary to medications. Notice the deep T waves in V3-V5 and slight biphasic T wave in V6 in this chest pain free ECG. The patient had negative cardiac enzyme levels and later had a stent placed in the proximal left anterior descending (LAD) artery.
  • Aortic stenosis (hemodynamically significant)*
  • Severe hypertension*
  • Serious coexisting illness (eg, pneumonia, DKA)
  • Symptomatic CHF
  • Active venous thromboembolic disease (DVT, PE)
  • Pericarditis, myocarditis, endocarditis

*May be candidates for pharmacologic stress testing

Test interpretation

Exercise tolerance test (ETT) results are centered on the ST response, with ST depression greater than or equal to 1 mm signifying a positive test result. 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 is a rare finding, which signifies significant ischemia. ST-segment elevation in leads with previous Q waves appears to be related to the presence of dyskinetic areas or ventricular aneurysms, which does not signify acute ischemia.

Clinical responses

Patients are instructed to terminate the test for significant chest pain, as chest pain consistent with angina constitutes a positive 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 in 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). METs 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. In patients with CAD, exercise capacity of at least 10 METs signifies a good prognosis with medical therapy, similar to that of coronary artery bypass surgery. An exercise capacity of 13 METs indicates a good prognosis even with an abnormal exercise ECG response.[10]

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 ventricular dysfunction, ischemia, cardioactive drugs, or autonomic dysfunction. Chronotropic incompetence, defined as 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.[11] 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.

Test utility

The American College of Cardiology and the American Heart Association performed a 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 mean specificity of 72% of 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%.[12] However, the purpose of stress testing in the context of the ED evaluation of chest pain is not to definitively rule coronary artery disease in or out. Rather, it is a short-term prognostic tool to aid in the safe disposition of patients. Studies have shown excellent short-term (1-6 mo) cardiovascular prognosis for patients discharged from the ED or observation unit after a negative exercise test result.[13]

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Myocardial Perfusion Imaging

The American College of Radiology guidelines for imaging state that in patients with active chest pain, an ECG with no ischemic changes, and an initial negative troponin result, rest SPECT has been demonstrated to be the "test of choice." However, it has been shown to be less sensitive than stress SPECT imaging if performed after the chest pain has subsided. Abundant literature describes the use of SPECT in suspected ACS. The absence of a perfusion defect on an acute rest study is associated with a very high negative predictive value for ACS evaluation. A perfusion defect that becomes apparent or becomes larger during exercise stress or pharmacologic stress defines ischemic myocardium.[4]

One difficulty that arises is when the electrocardiographic evidence and myocardial perfusion imaging on a stress test disagree. Soman et al studied 473 patients with chest pain, and two thirds of whom had abnormal ST segment response to exercise. In this study, normal technetium-99 sestamibi SPECT study results were associated with an annual mortality rate of 0.2%.[14] When interpreting stress tests, more importance is generally placed on the myocardial perfusion results than the electrocardiographic results.

Test limitations

A technetium-99 sestamibi scan exposes a patient to approximately 8 millisieverts of radiation. This is roughly half the radiation exposure from a chest or abdomen CT. The thallium test exposure is approximately equal to that of a CT.

Equivocal results can result from poor image quality. Interference by breast tissue or the diaphragm can impair image quality in some patients.

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Stress Echocardiography

Test physiology and technique

Another method of detecting coronary artery disease is to perform echocardiography while the heart is undergoing exercise or pharmacologically induced ischemia. Wall motion abnormalities can be visualized with the technique. The exercise is performed using a treadmill or a bicycle ergometer. If a treadmill is used, images are obtained prior to exercise and then within 60-90 seconds of completing exercise. Bicycle ergometry has the advantage of being able to perform the echocardiogram at different stages of exercise. Supine ergometry provides the most information since 4 cardiac views can be obtained. Dobutamine is the most common pharmacologic agent used in conjunction with echocardiography. Image quality can be enhanced by injection of echogenic microbubbles.

Test interpretation

A positive stress echocardiogram is defined by stress-induced decrease in regional wall motion, decreased wall thickening, or regional compensatory hyperkinesis. In experienced hands, this can have a diagnostic accuracy similar to that of nuclear stress testing. However, results are operator dependent.[15]

Test utility

Advantages to stress echocardiography are that it is a faster test to perform than a nuclear stress test because delayed images are obtained much sooner. It has no associated radiation exposure. It is less costly than nuclear stress testing, and therefore performs well on cost analysis studies. The test can be more readily performed in an office setting.

In a meta-analysis that included data from 24 studies, Fleischmann et al found that exercise echocardiography had a sensitivity of 85% and a specificity of 77% when compared with coronary angiography. The results were felt to be similar to those for SPECT imaging.[16]

Test limitations

As stated above, the test is dependent on the experience of the operator. Obesity, lung disease, and tachycardia can limit image quality. Up to 10% of cases have inadequate image quality.

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Computed Tomography

Test methodology

Calcium deposits are commonly found in atherosclerotic coronary plaques. The total amount of coronary calcium is predictive of future cardiac events. Cardiac computed tomography (CCT) can measure the density and extent of calcifications in coronary artery walls. The technique of CCT was established with electron beam scanners, but it has been refined and made more widely available with the introduction of multidetector scanners. The technique relies on ECG "gating" to compensate for cardiac motion. No contrast is used. The coronary lumen itself is not visualized. A related technique is cardiac CT angiography (CCTA). CCTA uses intravenous contrast material to provide direct visualization of the coronary lumen. Gating is also used to decrease motion artifact. CCTA has been shown to have good correlation with the criterion standard of conventional coronary angiography.

Coronary CTA techniques are under rapid development. A low and regular heart rate (typically sinus rhythm) is necessary for optimal imaging, and it is often necessary to administer beta-blockers to achieve an adequately low heart rate (approximately 60-65 bpm or less). Studies have shown that if a patient's heart rate can be brought below 60 bpm, only about 3% of coronary segments will be unevaluable by the CCTA, while at 61-65 bpm, over 21% are unevaluable. Obtaining optimal images with the least radiation exposure depends on control of the heart rate.[17]

Test interpretation requires special training and is usually performed by a radiologist or cardiologist.

Test outcomes and interpretation

The amount of calcium seen in coronary vessels on CT is usually expressed as an "Agatston score," which is based on the area and the density of the calcified plaques. A typical report provides an Agatston score for the major coronary arteries as well as a total Agatston score. A test result is considered to be positive if any calcification is detected within the coronary arteries. A positive test result is nearly 100% specific for atheromatous coronary plaque but not highly correlated with obstructive disease. A negative test result has a 96-100% negative predictive value for obstructive lesions. Agatston scores of less than 10, 11-99, 100-400, and above 400 have been proposed to categorize individuals into groups having minimal, moderate, increased, or extensive amounts of calcification, respectively.

Conversely, a study by Rosen et al found that "although there is a significant relationship between the extent of calcification and mean degree of stenosis in individual coronary vessels, 16% of the coronary arteries with significant stenoses had no calcification at baseline."[18]

Calcium scores greater than 1000 have been associated with significant increases in morbidity and mortality independent of other risk factors. Scores greater than 100 are consistent with a high risk (>2% annually) of a coronary event within 5 years. The amount of calcification can give, to some extent, an indication of the overall amount of atherosclerosis. In addition, a greater amount of calcification and a higher Agatston score increase the likelihood that coronary angiography will detect significant coronary artery stenosis. However, there is not a 1-to-1 relationship between a high score and the presence of coronary artery stenosis. In other words, a positive scan result indicates atherosclerosis but not necessarily significant stenosis.[19]

Individuals with Agatston scores greater than 400 have an increased occurrence of coronary procedures (bypass, stent placement, angioplasty) and events (myocardial infarction and cardiac death) within the 2-5 years after the test. Individuals with very high Agatston scores (>1000) have a 20% chance of suffering a myocardial infarction or cardiac death within a year. Even among elderly patients (>70 y), who frequently have calcification, an Agatston score greater than 400 was associated with a higher risk of death. 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% confidence interval [CI], 2.52-6.40). However, calcium scores reflect overall risk and cannot be used to diagnose the presence of an obstructing lesion.[20]

Test utility

Studies have investigated the use of CCT in the ED. These studies report a negative predictive value (NPV) of 97-100%. For example, in one study, CCT was performed in 192 patients presenting to the ED with chest pain, with an average follow-up interval of 50 months. The negative predictive value of the test was 99%. Patients with the absence of coronary artery calcium (CAC) had a 0.6% annual cardiovascular event rate. In another study of ED chest pain patients, a negative test result (absence of coronary calcification) was associated with a very low adverse event rate over a 7-year follow-up period. Increasing score quartiles were strongly correlated with risk (p< 0.001).[21] Another recent study evaluated 1,031 patients admitted to an observation unit with CCT. Only 2 events occurred in 625 patients with a calcium score of 0 (0.3%; 95% confidence interval, 0.04-1.1%).[22]

The absence of detectable calcium has a very high negative predictive value for ruling out obstructive coronary artery disease and confers an excellent long-term prognosis for future cardiac events. Thus, use in low-risk patients is the most important application of CCT. A negative predictive value of 98% has been reported for coronary chest pain or myocardial infarction in patients with acute symptoms and nonspecific ECG results.[23, 24]

As with other noninvasive techniques, CCT cannot be used to identify or rule out the presence of an unstable plaque. A problem with the use of CCT is that calcification is present much more often than significant stenosis. Most patients with coronary calcification who go on to conventional invasive catheter angiography will therefore not have significant obstructive disease. CCTA may be a less invasive alternative in these cases, but there are limitations of the currently available data for CCTA. These include the fact that most reports have been based on single-center experiences and have been conducted with a subset of symptomatic middle-aged white men who had a high prevalence of CAD. Multicenter trials and studies with intermediate-risk populations are warranted.

Cardiac CT angiography (CCTA)

The studies evaluating CCTA are relatively small. They have found good negative predictive value of CCTA compared with the criterion standard of catheter angiography. A normal CCTA study reliably rules out significant stenosis.

Large outcome-based studies of CCTA in acutely symptomatic patients are presently lacking. In one study of CCTA in low-risk ED patients published in abstract form, CCTA result was considered negative if no vessel had more than a 50% stenosis and the calcium score was less than 100. Patients with a negative study result were discharged. Of the 407 discharged patients, 402 had 30-day follow up. None (0%) died from a cardiovascular cause, needed revascularization, or had an MI. This result has a 95% confidence interval of 0-0.9%. The authors concluded that low-risk chest pain patients with a negative CCTA result can be safely discharged.[25]

Another representative study of 1,127 low- to intermediate-risk patients followed for 15 months showed that there were just 1 in 333 all-cause deaths in the group with no visualized coronary plaque.[26]

Further studies in various populations will define the role of CCTA. However, it appears that enough evidence exists to allow safe discharge of patients without acute ECG changes, elevated markers, and benign CCTA examinations. Of course, this assumes other serious causes of chest pain have been considered and excluded as needed.

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Future Directions in Testing

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.

A 2010 publication reported on the use of stress MRI in an observation unit compared to routine inpatient care in a group of non–low-risk patients. Thirty day outcomes were the same in both the admitted group and the observation/MRI patients. Observation/MRI patients had significantly lower costs ($336-$811; 95% CI).[27]

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.

Combined CT studies for chest pain evaluation: the "triple rule out"

Conceptually, a CT scan with intravenous contrast can combine imaging of the coronary arteries, ascending aorta, and pulmonary arteries. This allows assessment of coronary artery disease, pulmonary embolism, and disease of the thoracic aorta (dissection) with a single study. Technical aspects of the study differ than for CCTA with a wider field of view and a different protocol for the administration of intravenous contrast. The technique involves substantial cost and radiation exposure. This type of evaluation has been called the "triple rule out (TRO)."

A review of the topic suggests that this approach may have utility under relatively limited circumstances.[28] A 2013 study evaluated 100 intermediate-risk patients with acute chest pain. All had D-dimer testing. Those with a positive D-dimer result were imaged with a TRO protocol and the others with CCTA. Sixty of 100 had a negative CCTA and were discharged. No adverse events occurred in this group at 90-day follow-up. Nineteen of 100 had positive CCTA, of which 17 were true positive based on catheter angiography. A TRO-CCTA protocol was performed in 36 patients because they had elevated D-dimer levels. Pulmonary embolism was present in 5, pleural effusion of unknown etiology in 3, severe right-sided ventricular dysfunction with pericardial effusion in 1, and an incidental bronchial carcinoma was diagnosed in 1 patient.[29]

In current practice, this type of imaging exposes patients to significant radiation but shows promise in appropriately selected patients. Improved scanning hardware and imaging algorithms have shown promise for reducing radiation exposure without compromising accuracy. To date, no consensus has been reached on which patients are most appropriate for TRO imaging.

Cardiac PET scanning for diagnosis of coronary artery disease

There are 2 specific clinical applications of PET that have been proposed for the evaluation of patients with known or suspected coronary artery disease. Detection of coronary artery disease and estimation of severity is performed using a PET perfusion agent at rest and during pharmacologic vasodilation. The second clinical application of PET is the assessment of myocardial viability in patients with coronary artery disease and left ventricular dysfunction. The most common approach is to determine whether metabolic activity is preserved in regions with reduced perfusion as a marker of glucose utilization and, thus, tissue viability.

The combined technique of PET/CT of the coronary arteries was shown in one study to compare favorably with the criterion standard of catheter coronary angiography. One hundred seven patients with an intermediate pretest likelihood of coronary artery disease were enrolled. All patients underwent PET/CT, and the results were compared with invasive angiography. PET and CT angiography alone both demonstrated 97% negative predictive value, CT angiography alone was suboptimal in assessing the severity of stenosis (positive predictive value, 81%). Perfusion imaging alone could not always separate microvascular disease from epicardial stenoses, but hybrid PET/CT significantly improved this accuracy to 98%.[30]

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Cardiac Testing in Women

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%, respectively, for women compared with 72% and 77%, respectively, for men.[31]

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 exercise tolerance testing as the initial noninvasive test of choice for symptomatic woman who are at intermediate risk for ischemic heart disease, have a normal baseline ECG, and are able to exercise.[32]

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Pharmacologic Stress Testing

Test physiology and technique

Pharmacologic stress testing differs from exercise testing in that it does not rely on the patient's own ability to increase cardiac oxygen demand. Rather, the patient can remain at rest while the heart's response to a drug is measured. The most widely available pharmacologic agents for stress testing are dipyridamole (Persantine), adenosine, regadenoson (Lexiscan), and dobutamine. The adenosine analog regadenoson has a longer half-life than adenosine. This allows for simpler bolus versus continuous administration.

Pharmacologic agents

For patients unable to exercise, pharmacologic agents are used to stress the myocardium and produce the characteristic ECG or nuclear imaging findings. Pharmacologic stress testing is indicated for patients who would be unable to adequately perform an exercise stress test. An exercise test is considered inadequate when a patient cannot reach 85% of predicted maximum heart rate or reach a workload of 5 metabolic equivalents of task (METs) for 3 minutes. A pharmacologic test is preferred over an exercise test in patients with aortic stenosis, left bundle branch block, a paced rhythm, recent myocardial infarction, and severe hypertension, even if they were able to exercise adequately.[33]

Adenosine, regadenoson (Lexiscan), and dipyridamole (Persantine) are coronary vasodilators. In terms of blood flow, normal vessels are up to 400% more responsive to the vasodilatory effect than stenotic vessels. This difference in response leads to differential flow, and perfusion defects appear in cardiac nuclear imaging or as ST-segment changes on the ECG.

Contraindications to adenosine include active asthma, high-grade heart block, and hypotension. Caffeine or theophylline should be stopped 12 hours before adenosine is given. Regadenoson and dipyridamole have similar contraindications (although studies have indicated that regadenoson is relatively safe in asthma).[34] In addition, in November 2013, the US Food and Drug Administration (FDA) issued a warning that regadenoson and adenosine should not be used for cardiac nuclear stress tests in patients with signs or symptoms of unstable angina or cardiovascular instability, because they may increase the risk for a fatal heart attack.[2, 3]

Dobutamine is a direct cardiac inotrope and chromotrope. It consequently increases myocardial oxygen demand similar to exercise and allows ischemic areas to become visible on nuclear scanning or apparent as ST depression on the ECG.

Dobutamine contraindications include hemodynamically significant left ventricular outflow tract obstruction, tachyarrhythmias (including prior history of ventricular tachycardia), uncontrolled hypertension (blood pressure >200/110 mm Hg), aortic dissection or large aortic aneurysm. Beta-blockers should be discontinued so that response to dobutamine will not be attenuated.

Test interpretation

The pharmacologic stress test is interpreted in a manner similar to the exercise stress test (see above). Additionally, myocardial perfusion imaging is advisable in all patients undergoing pharmacologic stress testing.

Test utility

Pharmacologic stress testing with nuclear imaging is equivalent to an exercise stress test with nuclear imaging at detecting coronary artery disease. Note, however, that since patients undergoing pharmacologic stress testing tend to have more comorbidities, the posttest probability of disease is higher in patients who have undergone a pharmacologic test. A normal pharmacologic stress test result confers a 1-2% per year cardiac event rate, whereas a normal exercise test result with nuclear imaging has a rate less than 1% per year.[35]

Test limitations

Theophylline can reduce ischemic changes on the ECG with vasodilator stress testing. Caffeine has been reported to have a similar effect. However, one study demonstrated that one cup of coffee, one hour prior to stress testing did not attenuate the results of adenosine nuclear imaging.[36] Calcium channel blockers, beta-blockers, and nitrates can also alter perfusion defects on pharmacologic stress tests and therefore ideally should be withheld for 24 hours prior to pharmacologic stress testing. Dipyridamole and adenosine can lead to bronchospasm; they are generally avoided in patients with severe reactive airway disease or active wheezing. Dobutamine is safe to use in these patients.

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Summary

Noninvasive cardiac testing is used as part of a broader scheme of risk stratification for patients with possible acute coronary syndromes. Many tests exist, and each has unique advantages and disadvantages. Patient characteristics and local resources dictate which of the cardiac tests are chosen. Variability exists in how well noninvasive cardiac tests correlate with angiographic findings. Despite this variability, most of the tests are useful for determining short-term risk of myocardial infarction and death.

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

As with all diagnostic tests, no single cardiac test is ideal. They are useful as part of a risk stratification scheme, but, with the current state of diagnostic testing, some cases of serious coronary disease will always be missed.

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Contributor Information and Disclosures
Author

Richard S Krause, MD Senior Clinical Faculty/Clinical Assistant Professor, Department of Emergency Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Benjamin O Koenig, MD Assistant Professor of Emergency Medicine, State University of New York at Buffalo; Director of Chest Pain Center, Department of Emergency Medicine, Buffalo General Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Eddy S Lang, MDCM, CCFP(EM), CSPQ Associate Professor, Senior Researcher, Division of Emergency Medicine, Department of Family Medicine, University of Calgary Faculty of Medicine; Assistant Professor, Department of Family Medicine, McGill University Faculty of Medicine, Canada

Eddy S Lang, MDCM, CCFP(EM), CSPQ is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine, Canadian Association of Emergency Physicians

Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director for Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, Society for Academic Emergency Medicine, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians

Disclosure: Nothing to disclose.

Additional Contributors

David A Peak, MD Associate Residency Director of Harvard Affiliated Emergency Medicine Residency; Attending Physician, Massachusetts General Hospital; Assistant Professor, Harvard Medical School

David A Peak, MD is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, American Medical Association

Disclosure: Partner received salary from Pfizer for employment.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Emily Carrier, MD, Corita Gruzden, MD, Peter Ro, MD, and David FM Brown, MD, to the development and writing of this article.

References
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Classic Wellens syndrome T-wave changes. This ECG represents a patient after becoming pain free secondary to medications. Notice the deep T waves in V3-V5 and slight biphasic T wave in V6 in this chest pain free ECG. The patient had negative cardiac enzyme levels and later had a stent placed in the proximal left anterior descending (LAD) artery.
 
 
 
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