Normal serial ECGs and myocardial marker measurements reduce the likelihood of AMI but do not exclude unstable angina, which still puts the patient at high risk for a subsequent adverse cardiac event. Therefore, patients with possible ACS should undergo some form of direct cardiac testing to evaluate coronary anatomy, cardiac function, or both. Common modalities used include stress electrocardiography, stress echocardiography, resting and/or stress nuclear medicine testing, stress cardiac MRI, and CT coronary angiography (CTCA).
Advanced cardiac testing is performed after normal biomarkers are present and no clear ischemic ECG changes exist; this happens either as an inpatient or during an observation unit stay, with the latter being less expensive. Another option proffered by the American College of Cardiology/American Heart Association guidelines is to do the advanced testing as an outpatient and within 72 hours of ED discharge if patients are at low risk for ACS, are pain free without recurrent symptoms, have no evidence of ischemia on their ECG, and have normal serial cardiac markers over 6 to 8 hours.12 This latter approach simply uses the ED stay as the observational interval.
Available data suggest that low-risk patients may safely undergo immediate stress testing. One center performed over 3000 immediate exercise stress tests in low-risk patients who had at least one negative serum cardiac marker, noting no adverse events.26
CARDIAC TESTING MODALITIES
ECG-Based Exercise Treadmill Testing
The accuracy of ED stress testing is particularly difficult to quantify, because test sensitivity and specificity are greatly influenced by characteristics of the population being tested. As the pretest probability of CAD increases, the likelihood of a false-negative test also increases. Conversely, when a population with a very low pretest probability of disease is tested, the likelihood of a false-positive result increases. Based on current data, diagnostic stress testing is recommended for patients with a low to moderate pretest probability of CAD but is unlikely to be helpful in those at very low risk or at high risk. Guidelines to assist with stress test selection are summarized in Figure 51–2.27
Stress testing decision making for patients with possible acute coronary syndrome (ACS). CAD = coronary artery disease; sig = significant.
ECG-based exercise treadmill testing is commonly used for patients without known coronary disease who are placed in an observation unit. Subjects exercise, most commonly on a treadmill, until a predetermined percentage of predicted maximum heart rate or other end points are reached. The most commonly used definition of a positive exercise test result from an ECG standpoint is ≥1 mm of horizontal or downsloping ST-segment depression or elevation for at least 60 to 80 milliseconds after the end of the QRS complex; ST-segment elevation is not sought because it defines acute ischemia.
Sensitivity of exercise treadmill testing depends on the risk and severity of disease of the patient population to which it is applied. Meta-analysis of 24,000 patient encounters notes that the sensitivity and specificity for significant coronary disease are 68% and 77%, respectively.27 Advantages of exercise treadmill testing are low cost, wide availability, and short test performance time. Exercise stress testing is contraindicated for various reasons (Table 51–4).27 Exercise testing may not be safe for patients at high risk for acute ischemia or those with other uncontrolled cardiovascular or pulmonary pathologies. Furthermore, patients with an abnormal baseline ECG, such as those with left ventricular hypertrophy, bundle-branch block, or digoxin effect, are less likely to benefit from standard exercise testing due to difficulties in interpretation of exercise-induced ECG changes.
Contraindications to Exercise Testing
||Download (.pdf) Table 51–4
Contraindications to Exercise Testing
Acute myocardial infarction (within 2 d)
High-risk unstable angina
Uncontrolled cardiac dysrhythmias causing symptoms or hemodynamic compromise
Symptomatic severe aortic stenosis
Uncontrolled symptomatic heart failure
Acute pulmonary embolus or pulmonary infarction
Acute myocarditis or pericarditis
Acute aortic dissection
Left main coronary stenosis
Moderate stenotic valvular heart disease
Severe arterial hypertension (>200 mm Hg systolic, >110 mm Hg diastolic)
Tachydysrhythmias or bradydysrhythmias
Hypertrophic cardiomyopathy and other forms of outflow tract obstruction
Mental or physical impairment leading to inability to exercise adequately
High-degree atrioventricular block
Echocardiography to evaluate wall motion at rest and while under stress (either exercise or pharmacologically induced) is widely used in patients with possible ACS. Advantages of stress echocardiography over exercise treadmill testing are improved accuracy for coronary disease and nondependence on the ECG. Compared with other cardiac imaging techniques, echocardiography is noninvasive, delivers no ionizing radiation, and provides information on myocardial function.
Detection of wall-thickening abnormalities defines acute ischemia; this is dependent on imaging technique and interpretative skills, with up to 10% of tests being technically inadequate. The echocardiogram cannot distinguish between myocardial ischemia and acute infarction, cannot reliably detect subendocardial ischemia, and may be falsely interpreted as positive in the presence of several conditions (notably conduction disturbances, volume overload, heart surgery, or trauma). Timing of the test relative to the onset of symptoms is critical, because transient wall motion abnormalities may resolve within minutes of an ischemic episode. Resting echocardiography within 12 hours of ED arrival does not provide additional predictive value for myocardial infarction over myocardial markers alone. Thus, a normal resting echocardiogram in the ED cannot exclude ACS, although it lowers the likelihood.
Stress echocardiography combines a standard ECG stress test with cardiac imaging at rest and after exercise or pharmacologically induced tachycardia. Overall, stress echocardiography is 80% sensitive and 84% specific for significant coronary disease, superior to ECG-based stress testing. In low-risk ED patients, three studies have reported negative predictive values for subsequent cardiac events to be 97% to 100%, comparable to that of stress testing using nuclear imaging techniques.
Nuclear medicine techniques use an IV-injected radioactive tracer. Local myocardial uptake and images depend on regional coronary flow and myocardial cell integrity. Tracer uptake occurs in direct proportion to regional myocardial blood flow.
Thallium-201 has been in use longest and is rapidly redistributed after initial uptake. The image generated after thallium injection represents blood flow at the moment of imaging. Areas of positive uptake reflect adequate coronary flow and viable myocardium, whereas areas without uptake represent infarcted or ischemic myocardium. On repeat imaging several hours later, continued lack of perfusion ("irreversible defect") indicates an area of infarction, and tracer uptake only on delayed images ("reversible defect") represents ischemic but not infarcted myocardium. Combined with conventional ECG-based stress testing, thallium imaging offers improved sensitivity and specificity for detection of significant CAD over ECG-based testing alone, and it is not hampered by baseline ECG abnormalities. Thallium-based imaging must be performed soon after injection, making it impractical for use in patients with ongoing chest pain. Also, the long half-life requires a lower injected dose to avoid excessive radiation exposure. This may impair imaging and create false-negative and false-positive results, especially in women and obese patients. Due to these limitations and the lack of ED-based outcome studies, thallium-201 imaging alone is not an ideal agent for use in the ED.
Myocardial perfusion imaging using technetium-99m (99mTc)-labeled agents such as sestamibi offers advantages over thallium for ED use. Because the half-life of 99mTc is much shorter than that of thallium (6 vs 73 hours), a larger dose is possible without harm to the patient. This produces superior image quality, decreased tissue attenuation–related artifacts, and higher ACS detection specificity for sestamibi imaging. In contrast to thallium, 99mTc is stable for several hours, allowing accurate imaging up to 3 hours after injection; the image represents the blood flow at the moment of injection. By using "gated" image acquisition technology, sestamibi scanning also estimates ejection fraction. As with thallium, resting and stress (exercise or pharmacologic) images can be compared to yield additional data.
Perfusion sestamibi imaging of patients with current or recent (within 30 minutes of injection) pain and no cardiac ischemia on ECG and biomarker analysis is very sensitive in detecting physiologic ischemia; a negative test would allow discharge to home. This latter approach requires broader study but is promising in select patients.
Dual-isotope stress testing using thallium and sestamibi is an increasingly common component of ED ACS evaluation protocols. In this technique, a resting thallium scan is first performed. Patients without resting defects can then immediately undergo stress testing with sestamibi imaging, thereby avoiding the delay usually required for isotope "washout" in single-isotope techniques. Dual-isotope stress testing in one trial reliably identified or excluded ACS.
Cardiac MRI assesses wall motion, perfusion, and coronary anatomy, either at rest or after pharmacologic stress. It is noninvasive and does not expose the patients to radiation. However, cardiac MRI cannot be performed on approximately 11% of ED patients with chest pain due to contraindications such as claustrophobia and implanted metallic objects. Another limit is the longer test performance time, although this is improving with newer scanners and software. Cardiac magnetic resonance stress imaging has excellent test performance but currently is not a common tool for early ACS evaluation.
CTCA allows gated images of the coronary arteries after rapid, peripheral (not central) IV contrast. Images are improved when the heart rate is <65 beats/min in 16-slice CT scanners, sometimes necessitating β-blocking medications; dual-source scanners (128-slice) can image adequately at higher heart rates but are less available. The advantages of CTCA are ready access to necessary equipment, rapid image acquisition, and the ability to image coronary structure. Notable disadvantages include ionizing radiation exposure, IV contrast exposure (and risk of allergy or kidney injury), need for specially trained technicians, and nondiagnostic scans due to nonvisualization of coronary segments. Additionally, CTCA provides a limited assessment of cardiac function. CTCA-detected lesions of >50% stenosis correlate with lesions on standard left-heart angiography; this means the test offers limited information in those with known coronary disease. Patients with positive scans require confirmation either with a cardiac catheterization or a functional advanced cardiac test.
Two recent clinical trials evaluated the usefulness of CTCA in decreasing ED length of stay and assessing for serious cardiac events within 30 days of discharge.28,29 Both studies included patients with low to intermediate risk for ACS and considered CTCA results of <50% stenosis as negative. These trials found that patients randomized to CTCA versus traditional care had a higher rate of discharge from the ED and a decreased overall length of stay. No significant coronary disease was missed on CTCA evaluation versus traditional stress testing, although one study found that patients with positive CTCA findings had more overall testing and increased radiation exposure. The cost of care was similar for both groups of patients. Overall, these studies provide evidence that CTCA allows for faster and safe discharge of patients from the ED.28,29
CTCA findings also have a strong correlation with 1-year prognosis as demonstrated in a meta-analysis that included 18 studies with 9592 patients. Researchers evaluated for major adverse cardiac events, including death, myocardial infarction, and need for revascularization. The overall event rate for patients with positive CTCA (>50% stenosis of any vessel) versus normal CTCA was 8.8% versus 0.17% per year, thus demonstrating that major adverse events in patients with negative CTCA imaging are rare.30
While ED CTCA helps deliver a prompt, safe disposition of patients in the ED, up to 24% of patients will have nondiagnostic CTCA imaging.2 The ideal approach to these patients is undefined and usually reverts to the previous strategies for evaluating low-risk ACS patients.