Introduction
Previous chapters have detailed the important roles of clinical presentation (see Chapter 6 ), cardiovascular risk factors, electrocardiography (ECG), and biomarkers (see Chapter 7 and Chapter 8 ) in the initial assessment of patients who present with acute chest pain to the emergency department (ED). However, even all of this information does not allow accurate exclusion or diagnosis of acute myocardial infarction (MI) in a substantial proportion of patients. This chapter reviews the clinical utility, strengths, and weaknesses of the major imaging modalities that have been studied in this setting.
The use of imaging techniques in the evaluation of patients with chest pain in the ED has increased steadily. Between 1999 and 2008, the use of advanced medical imaging in the ED increased more than fourfold beyond standard x-ray testing. Because less than 10% of patients with an inconclusive initial ED evaluation are subsequently diagnosed with MI, the primary goal is to safely and efficiently identify those without MI. In the United States, the standard of safety for patients and ED physicians has been defined as a risk of an adverse event of less than 1% within 30 days after discharge. However, imaging should be held to a higher standard than this and not only provide diagnostic information, but also prognostic information that may help tailor medical therapy even in those without acute MI.
Available tests include functional testing at rest and stress, anatomic coronary assessment by computed tomographic angiography (CTA), and myocardial perfusion and viability by cardiac magnetic resonance imaging (CMR). Currently, the role of CTA and anatomic assessment is restricted to de novo acute chest pain presentations, whereas stress test–based assessment of myocardial ischemia is favorable in those who have had previous events. It is further important to emphasize that it is a small proportion of patients who present with chest pain that have a final diagnosis of acute coronary syndrome (ACS), and that most patients who undergo imaging are classified as having unstable angina (85%) with few non–ST-elevation MIs (NSTEMIs) (15%), although this epidemiology is shifting (see Chapter 1 and Chapter 6 ).
Rationale for Functional and Anatomic Assessment
Functional Imaging
In the so-called “ischemic cascade,” the earliest manifestation of ischemia is a perfusion abnormality. As supply–demand mismatch worsens, left ventricular diastolic abnormalities develop, and then later, systolic wall motion abnormalities. Ischemic changes on the ECG, increases in troponin, and onset of angina are late events. The ability to use imaging to detect regional differences in myocardial blood flow (with perfusion imaging) and regional variation in systolic function allows for identification of myocardial ischemia in patients before, or even in the absence of, ECG changes.
Anatomic Assessment of Coronary Artery Disease
Overall, most ACS occur as a result of rupture of an atherosclerotic plaque (see Chapter 3 ). However, most patients in whom plaque rupture occurs in a large, previously nonobstructive vessel will present with STEMI and will be referred immediately to the catheterization laboratory. In contrast, candidates for imaging will more likely present with an acute exacerbation of an already existing luminal narrowing. A minority of patients referred for imaging will eventually develop troponin elevation and be diagnosed with an MI.
Functional Imaging
Gathered over 40 years, data that have assessed functional imaging for the evaluation of patients with chest symptoms presenting to the ED are predominantly observational in nature. However, some randomized comparative effectiveness trials have been performed.
Rest Radionuclide Myocardial Perfusion Imaging
Early reports of rest radionuclide myocardial perfusion imaging (MPI) to assess patients with chest pain in the ED using thallium-201 planar imaging in patients with unstable angina and suspected MI date back to the 1970s. Because the redistribution of thallium-201 requires imaging to be completed relatively quickly after injection, this tracer is challenging for imaging ED patients. Subsequently, technetium-99 (Tc99m)–based agents with only minimal redistribution, such as sestamibi and tetrofosmin, have enabled rest perfusion imaging in the ED setting.
Rest-Only Myocardial Perfusion Imaging in Suspected Acute Coronary Syndromes
During the 1990s, a series of studies that used Tc99m-sestamibi at rest established that hypoperfused myocardium before thrombolysis in patients with STEMI represented the area-at-risk of infarct. Subsequently, Tc99m-sestamibi imaging was established as a marker of infarct size in clinical trials of therapeutic agents for patients with MI. Tc99m-sestamibi imaging at rest demonstrated a high negative predictive value in patients who presented to the ED with suspicion for ACS to exclude MI, as well as had a higher sensitivity than the ECG recorded during symptoms for predicting the presence of a coronary stenosis on subsequent angiography. In addition, a normal perfusion study identified patients at low risk for subsequent cardiovascular events. Examples of normal and abnormal studies are shown for applications of rest-only MPI in Figures 9-1 and 9-2 . Examples of stress MPI are shown in Figures 9-e1 and 9-e2 .
Subsequently, in a larger study in which approximately 1200 ED patients with ECGs that were nondiagnostic for ischemia or infarction and possible or probable unstable angina had perfusion scans performed; the sensitivity of MPI for MI was 100% (95% confidence interval [CI], 64% to 100%), and the negative predictive value for MI or revascularization over 1 year of follow-up was 97% (95% CI, 95% to 98%). Including revascularization, the total event rate at 12-month follow-up was 0.9% in patients with a normal resting scan and 42% in those with abnormal findings. These data added weight to the concept that a normal perfusion study when performed immediately in the ED identified a low-risk group that were potentially eligible for early discharge.
Randomized Trials of Myocardial Perfusion Imaging in the Emergency Department
To critically assess the application of single-photon emission computed tomography (SPECT) MPI in the ED, several randomized effectiveness trials were conducted to study the effect on clinical decision-making when using the test versus when not using the test in a more real-life setting, where clinicians were not directed in their decisions by protocol ( Table 9-1 ).
| Author/Reference | No. of Pts | Intervention | Control | Timing of Intervention | Effectiveness? ∗ | Endpoint(s) | Results |
|---|---|---|---|---|---|---|---|
| Stowers (2000) | 46 | Rest MPI | SOC | After ED | No, clinical decisions driven by protocol | In-hospital costs and length of stay | Rest MPI-guided strategy had lower median in-hospital costs and shorter median LOS |
| Udelson (2002) | 2475 | Rest MPI | SOC | In ED | Yes | % Unnecessary admissions | Group randomized to rest MPI had fewer unnecessary admissions (in those without ACS) |
| Lim (2013) | 1508 | Stress/rest MPI | SOC | After 6 h of negative serial biomarkers/ECGs | Yes | Admission rate | Stress MPI group had lower admission rate |
∗ “Effectiveness” refers to whether the clinical decisions that followed knowledge of the randomized test results were protocol-driven. In the trial by Stowers and colleagues, the steps of care after the initial imaging results (or control group without imaging) were directed by the research study protocol. In the trials by Udelson and colleagues and Lim and colleagues, the test results were given to clinicians who then incorporated the results into their own decision-making, not directed by protocol. This latter, more real-life scenario is consistent with an effectiveness trial.
The ERASE Chest Pain (Emergency Room Assessment of Sestamibi for the Evaluation of Chest Pain) multicenter trial enrolled approximately 2500 patients in an effectiveness trial to test whether providing results of rest MPI to ED clinicians for patients with low-to-intermediate likelihood of ACS would improve clinical decision-making, which was defined as the appropriateness of an admitting decision. An appropriate admission was defined as admission of a patient who was ultimately found to have a final diagnosis of ACS (blindly adjudicated), whereas an unnecessary admission was defined as the admission of a patient who was ultimately found to have a final diagnosis of “not ACS.” Among patients randomized to the imaging strategy who ultimately were found to not have ACS, unnecessary admissions were significantly reduced (relative risk, 0.84; 95% CI, 0.77 to 0.92), whereas there was no change in appropriate admission for those with ACS. The results of this large, multicenter randomized effectiveness trial provided strong evidence that incorporating rest MPI in this setting could improve triage decisions.
Appropriate Use Criteria, Guidelines, and Clinical Role
Appropriate use criteria for the use of radionuclide imaging from the American College of Cardiology Foundation (ACCF), the American Society of Nuclear Cardiology (ASNC), the American College of Radiology (ACR), the American Heart Association (AHA), and the Society of Nuclear Medicine (SNR), among others, rate the use of rest-only MPI as appropriate in the setting of acute chest pain suspicious for ACS, provided that the initial ECG is nondiagnostic or normal, the initial troponin is negative, and pain is ongoing or recent.
Resting Echocardiography
A major strength of resting two-dimensional (2-D) echocardiography in the evaluation of acute chest pain is its widespread availability and portability; however, a skilled operator is needed to acquire images, and experience is required for expert interpretation of images. Similarly to MPI, evaluation of suspected ACS by resting 2-D echocardiography is based on the concept that a perfusion abnormality will result in abnormal regional wall motion and myocardial thickening. Because regional wall motion abnormalities may resolve relatively soon after resolution of angina, 2-D echocardiography should be performed as early as possible, optimally in patients with ongoing symptoms, to provide high sensitivity (up to 90%). Although the exact time frame during which regional wall motion abnormalities will resolve after the offset of myocardial ischemia is unknown, studies suggest that the high sensitivity can be maintained within a window of 4 hours of arriving to the ED, and will drop to 64% sensitivity after resolution of chest pain.
Echocardiography in Acute Coronary Syndrome
ED providers often use ultrasound in their initial evaluation, including for those patients with chest pain. The focused cardiac ultrasound examination is intended to rapidly identify pericardial effusion, assess global systolic function, discover significant left or right ventricular enlargement, and assess intravascular volume through identification of the diameter and degree of collapse of the inferior vena cava. The American Society of Echocardiography (ASE) consensus statement reports that the examination is not intended to replace a comprehensive echocardiogram, and most providers who perform the test will not be vigorously trained in the acquisition and interpretation of ultrasound imaging to identify regional wall motion abnormalities. As of yet, there are no strong data to support the use of handheld ultrasound in the initial evaluation of suspected MI, without concomitant high suspicion of dissection or pericardial effusion.
Echocardiographic Imaging with Contrast
Echocardiographic contrast consists of gas microbubbles that are encapsulated and create a nonlinear vibration from contact with the ultrasound wave emitted from the transducer. The use of contrast echocardiography for opacification of the left ventricular cavity is safe in the setting of ACS. In the left ventricle, this opacification provides a contrast to the surrounding myocardium and allows for improved identification of the endocardial border, enhancing the assessment of regional wall motion abnormalities especially when imaging is technically difficult.
Beyond the use of contrast for left ventricular cavity opacification, it has also been investigated for evaluation of myocardial perfusion. The gas microbubbles of echocardiographic contrast also enter the myocardial circulation. The bubbles are fragile, and if a strong ultrasound pulse is generated, they will burst. Careful imaging of the myocardium in the cycles after the ultrasound pulse will demonstrate a new contrast agent entering the myocardial microvasculature. This influx can be visualized and analyzed based on the time to reperfuse, and correlates with myocardial blood flow to various segments.
Although not approved by the Food and Drug Administration (FDA) for the indication of assessing myocardial perfusion, myocardial contrast echocardiography has been extensively studied, and the data suggest that its use is safe and may provide useful and simultaneous data regarding myocardial perfusion and wall motion. The perfusion and wall motion data derived from contrast perfusion echocardiography in the setting of ACS correlate with radionuclide MPI. Specifically, both wall motion and perfusion with echocardiographic contrast show a more than 80% agreement with SPECT imaging of perfusion. When results of the two imaging modalities are discordant, contrast echocardiography is typically abnormal and SPECT is normal, probably because of the destruction of bubbles closest to the ultrasound transducer often causing the appearance of a perfusion defect in the anterior wall and apex.
Appropriate Use Criteria, Guidelines, and Clinical Role
The 2011 appropriate use criteria for echocardiography rate the evaluation of acute chest pain with suspected MI and nondiagnostic ECG when a resting echocardiogram can be performed during pain as appropriate. In the absence of pain, but with other features of an ischemic equivalent or positive biomarkers, the use of echocardiography is similarly appropriate.
Stress Testing with or without Imaging in the Emergency Department
Stress Radionuclide Myocardial Perfusion Imaging
In patients unable to exercise, or those with an uninterpretable ECG, the addition of an imaging modality to stress is warranted. One study for the evaluation of chest pain in the ED reported a protocol that used a multistep process, including history and physical, 2-hour biomarker levels, serial ECGs, and stress MPI for select patients based on risk category. The sensitivity and specificity for the diagnosis of ACS at 30 days for those patients who underwent stress testing was 99% and 87%, respectively.
In a randomized trial that incorporated stress MPI into the evaluation pathway, following a negative observation period involving serial ECG monitoring and serial biomarkers, 1508 patients were allocated to the use of stress MPI in the ED or to complete a standard clinical evaluation. Overall, fewer patients who had stress imaging performed were admitted (18.5% vs. 10.2%). However, event rates were low in both groups, and most patients were able to exercise and had an interpretable ECG. The predictive value of exercise ECG was similar to stress MPI, so although it is effective, the additional costs of imaging should be considered in such a situation under clinical conditions.
Stress Echocardiography
A study of 377 patients with a normal or nondiagnostic ECG and negative serial biomarker levels at 6 hours examined the ability of early dobutamine stress echocardiography in the ED to predict outcomes. Testing was not possible in 23 of 404 patients because of poor acoustic windows, a proportion similar to the general population. With dobutamine stress testing, 39 patients tested were unable to complete the protocol because of intolerable side effects, such as arrhythmia, severe hypertension, or hypotension. The overall event rate, including death, MI, rehospitalization, or revascularization, was 31% in patients with a positive stress echocardiogram and 4% in patients with a negative study. The negative predictive value was 96%, slightly lower than that reported in studies of radionuclide imaging.
Dobutamine stress echocardiography may be a cost-effective strategy compared with exercise treadmill testing alone. Nucifora and colleagues reported on 190 patients with chest pain, serial negative biomarkers, and nondiagnostic ECG results who were randomized to undergo either dobutamine stress echocardiography or exercise ECG testing. There was a higher event rate in patients who were discharged after negative exercise ECG testing compared with dobutamine stress echocardiography (11% vs. 0%; P = .004). Costs were lower in the dobutamine echocardiography group at both 1- and 2-month follow-up compared with exercise ECG testing ($1026 ± $253 vs. $1329 ± $1288; P = .03 at 1 month and $1029 ± $253 vs. $1684 ± $2149; P = .005 at 2 months). Lower costs in the dobutamine stress echocardiography group were believed to be caused by shorter length of stay and less need for follow-up testing for indeterminate results, which are more likely with exercise ECG testing alone.
Appropriate Use Criteria, Guidelines, and Clinical Role
The 2011 ACC/AHA guidelines present a class I recommendation, that in patients with suspected ACS, if the follow-up 12-lead ECG and cardiac biomarkers measurements are normal, a stress test (exercise or pharmacological) to provoke ischemia should be performed in the ED, in a chest pain unit, or on an outpatient basis in a timely fashion as an alternative to inpatient admission. Also, patients with possible ACS and negative cardiac biomarkers who are unable to exercise or who have an abnormal resting ECG should undergo a pharmacological stress test with imaging. The 2009 appropriate use criteria for cardiac radionuclide imaging rate the use of stress MPI in the setting of possible ACS with a (1) normal or nondiagnostic ECG; (2) either low or high clinical risk based on Thrombolysis In Myocardial Infarction (TIMI) score; and (3) either negative, borderline, equivocal, or minimally elevated troponin all as appropriate. The 2008 appropriate use criteria for stress echocardiography rate the use of stress echocardiography as appropriate for the indication of acute chest pain in the setting of an intermediate pretest probability of coronary artery disease (CAD) and an ECG without dynamic ST changes when serial cardiac enzymes are negative.
Figure 9-3 illustrates points in the triage algorithm when rest and stress functional imaging could be used. Although the efficacy and effectiveness, especially of rest perfusion imaging, has been demonstrated, these techniques are not widely deployed. Rather, the more common strategy has been to assess serial biomarkers in the ED or in an Observation Unit, followed by stress testing (see Chapter 12 ).
Cardiac Computed Tomography Angiography
In most patients who are ultimately diagnosed with ACS, acute chest pain develops because of myocardial ischemia after the erosion or rupture of a coronary atherosclerotic plaque (see Figure 3-5 ). Moreover, a significant coronary stenosis can be detected by invasive coronary angiography in most patients with ACS (>80%), whereas ACS is rare in the absence of coronary atherosclerosis. To assess for obstructive CAD and reach a confident diagnosis, clinicians have typically relied on the patient’s history and presentation, followed by noninvasive stress testing, and in some cases, invasive coronary angiography. For the first time, the advent of high-quality cardiac computed tomography angiography (CCTA) has provided clinicians with the ability to visualize the coronary arteries without the risks of invasive angiography. During the preceding decades of care for patients with acute chest pain, such insight into coronary anatomy has been considered the holy grail of cardiac imaging. However, now that CCTA is available, the benefits of this technology have been vigorously disputed. Because of the low efficiency of functional testing as a gatekeeper, proponents have argued that CTA allows more precision and individually tailored care, because, on one hand, CCTA is be able to exclude the most common reason for ACS in many patients. On the other hand, CCTA can identify patients potentially needing urgent revascularization, whereas the patients without significant obstructive disease could avoid a test that, for them, provides risk but no possibility of benefit. Greater efficiency might well also lead to lower total costs of care. Skeptics counter that CTA is too sensitive and will detect many patients with bystander CAD, and that it is lacks sufficient specificity. For example, in the presence of severe calcification and in the absence of information on the hemodynamic significance of CAD, it could potentially lead to more referrals for additional stress imaging and invasive angiography. Patients in this scenario would actually receive more radiation, and care would be more costly. Because of this controversy, adoption of CTA into practice has been variable, as has been reimbursement policies for U.S. payers.
Accuracy of Cardiac Computed Tomography Angiography for Detection of Coronary Artery Disease
Over the past two decades, CT has rapidly evolved. State-of-the-art scanners acquire 64 to 320 cross sections per rotation, depicting vascular details with a spatial resolution of less than 0.5 mm. Fast scanner technology combined with heart rate–reducing medication now makes it possible to image the coronary arteries without motion artifacts in most patients. ECG-synchronized, contrast-enhanced images of the heart and coronary arteries can be acquired in one to five heart cycles. With that, CCTA has evolved into a robust and reliable technique for detection and assessment of coronary stenosis and atherosclerotic plaque. A wealth of single and multicenter trials have established CCTA as a noninvasive diagnostic test with excellent sensitivity (97.2%; 95% CI, 96.2% to 98.0%) and good specificity (87.4%; 95% CI, 84.5% to 89.8%) for the detection of more than 50% coronary artery stenosis compared with the gold standard of invasive coronary angiography. The major strength of CCTA is its high negative predictive value (typically approaching 99%), and thus, CCTA permits confident exclusion of significant coronary stenosis. In addition, CCTA accurately detects nonobstructive calcified and noncalcified atherosclerotic plaque (accuracy, 92%; 95% CI, 90% to 93%) compared with the gold standard of intravascular ultrasound. The reproducibility of CCTA for both the detection of coronary plaque and stenosis is high (κ, 0.85 to 0.93).
Observational Studies with Cardiac Computed Tomography Angiography in Evaluation of Acute Chest Pain
The ability to rapidly image coronary arteries with a noninvasive technique with strong performance characteristics is a potentially attractive option in the setting of evaluating patients with suspected ACS in the ED. With substantial technical developments and wide availability, CCTA has evolved into a viable alternative to standard of care (SOC) management in patients presenting to the ED with acute chest pain.
The prospective observational cohort ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) trial, published in 2009, was the first large clinical trial that assessed the potential role of CCTA in the ED. The ROMICAT trial had a unique blinded observational cohort study design. The trial included 368 patients with acute chest pain from the ED with an initial inconclusive assessment who underwent CCTA. Care providers were blinded to the CCTA results, and therefore, the diagnostic performance of CCTA for ACS and its association with other test findings could be studied in a truly unbiased fashion. Among the more notable findings of this study were the following: (1) the distribution of CAD in patients presenting with acute chest pain—50% had no evidence of CAD, 30% had nonobstructive plaque, and approximately 20% of patients had obstructive CAD; (2) the absence of CAD had 100% negative predictive value for ACS, whereas the presence of obstructive CAD (>50% luminal narrowing) only had 77% sensitivity (and 87% specificity) for ACS; and (3) not surprisingly, the presence and extent of coronary plaque and stenosis were superior in their discriminative capacity for ACS compared with clinical risk scores such as TIMI or Goldman.
Takakuwa and colleagues performed a meta-analysis of available observational studies that evaluated the accuracy of CCTA to detect ACS in 1559 acute chest pain patients (42% women, mean age 52 years, low-to-intermediate likelihood of ACS) ( Table 9-2 ). The pooled results confirmed the excellent negative predictive value (99.3%; 95% CI, 98.7% to 99.6%), but also confirmed a low positive predictive value (48.1%; 95% CI, 42.5% to 53.8%) of the presence of 50% stenosis to identify patients with ACS during the index hospitalization and major cardiovascular events during 30-day follow-up. Hence, the absence of CAD on CCTA may allow for immediate hospital discharge ( Figure 9-e3 ).
| Study | N | Population | Scanner | ACS Definition | ACS Rate (MI rate) | CT Criterion | Sens | Spec |
|---|---|---|---|---|---|---|---|---|
| Rubinshtein (2007) | 58 | Higher risk (including history of CAD) | 64-CT | Positive troponins, or >50% stenosis by invasive angiography, or positive ischemia test | 34% | Stenosis | 100% | 92% |
| Gallagher (2007) | 92 | Low-risk ED | 64-CT | MI, UA | 13% | Stenosis | 86% | 92% |
| ROMICAT I (2009) | 368 | Low-risk ED | 64-CT ∗ | MI (8), UA (23) | 8.4% (2%) | Plaque Stenosis | 100% 77% | 54% 87% |
| Hansen (2010) | 89 | Low-risk ED | 64-DSCT | MI | 4% (4%) | Plaque Stenosis | 100% 75% | 41% 86% |
| Dedic (2013) | 111 | Any-risk ED (including low-positive troponins) | 64-DSCT ∗ | MI (13), UA (6) | 17% (12%) | Calcium Plaque Stenosis | 89% 100% 89% | 41% 40% 79% |
∗ Blinded cardiac CT examination, without affecting management.
However, the studies demonstrated that the mere detection of obstructive CAD by CCTA does not equate to a diagnosis of ACS ( Figure 9-4 ). In the ROMICAT trial, only 20 of 34 patients with obstructive CAD were clinically diagnosed with ACS. In the study by Hollander and colleagues, only 7 of 54 patients with obstructive CAD by CCTA had a stenosis confirmed by invasive coronary angiography (i.e., underwent invasive angiography on clinical grounds) or a major cardiovascular event within 30 days. However, the low positive predictive value (35% to 50%) of obstructive CAD combined with the low prevalence of ACS (2% to 8%) represents a major challenge for the management of acute chest pain patients. Hence, a finding of 50% has similar importance as a finding that indicates an increased likelihood for future cardiovascular events and an indicator of an ACS.
