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Cardiac Imaging for Patients with Acute Chest Pain in the Emergency Department
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 ).
TABLE 9-1
Randomized Controlled Trials Incorporating Rest and/or Stress Myocardial Perfusion Imaging into Clinical Decision-Making for Emergency Department Chest Pain Patients
| 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 |
ACS , Acute coronary syndrome; ECGs , electrocardiograms; ED , emergency department; LOS , length of stay; MPI , myocardial perfusion imaging; SOC , standard of care.
∗ “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.
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