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Original Research |
1 Department of Diagnostic Radiology, University of Maryland School of Medicine,
22 S Greene St., Baltimore, MD 21201.
2 Division of Emergency Medicine, Department of Surgery, University of Maryland
School of Medicine, Baltimore, MD 21201.
3 Division of Cardiology, Department of Internal Medicine, University of
Maryland School of Medicine, Baltimore, MD 21201.
4 Clinical Scientist, Philips Medical Systems, Department of Radiology,
University of Maryland School of Medicine, Baltimore, MD.
Received March 1, 2005; accepted after revision April 22, 2005.
Supported by a grant from Philips Medical Systems.
OBJECTIVE. The purpose of our study was to determine whether MDCT can provide a comprehensive assessment of cardiac and noncardiac causes of chest pain in stable emergency department patients.
SUBJECTS AND METHODS. Patients with chest pain who presented to the emergency department without definitive findings of acute myocardial infarction based on history, physical examination, and ECG were recruited immediately after the initial clinical assessment. For each patient, the emergency department physician was asked whether a CT scan would normally have been ordered on clinical grounds (e.g., to exclude pulmonary embolism). Each consenting patient underwent enhanced ECG-gated 16-MDCT. Ten cardiac phases were reconstructed. The images were evaluated for cardiac (coronary calcium and stenosis, ejection fraction, and wall motion and perfusion) and significant noncardiac (pulmonary embolism, dissection, pneumonia, and so forth) causes of chest pain. Correlation was made between the presence of significant cardiac and noncardiac findings on CT and the final clinical diagnosis based on history, examination, and any subsequent cardiac workup at the 1-month follow-up by a consensus of three physicians.
RESULTS. Sixty-nine patients met all criteria for enrollment in the study, of whom 45 (65%) would not otherwise have undergone CT. Fifty-two patients (75%) had no significant CT findings and a final diagnosis of clinically insignificant chest pain. Thirteen patients (19%) had significant CT findings (cardiac, 10; noncardiac, 3) concordant with the final diagnosis. CT failed to suggest a diagnosis in two patients (3%), both of whom proved to have clinically significant coronary artery stenoses. In two patients (3%), CT overdiagnosed a coronary stenosis. Sensitivity and specificity for the establishment of a cardiac cause of chest pain were 83% and 96%, respectively. Overall sensitivity and specificity for all other cardiac and noncardiac causes were 87% and 96%, respectively.
CONCLUSION. ECG-gated MDCT appears to be logistically feasible and shows promise as a comprehensive method for evaluating cardiac and noncardiac chest pain in stable emergency department patients. Further hardware and software improvements will be necessary for adoption of this paradigm in clinical practice.
Diagnosing the cause of acute chest pain in the emergency department remains a formidable task because of extensive etiology that ranges from benign to potentially lethal. The evaluation of many of these conditions, particularly the conventional assessment for the presence of cardiac disease in the acute setting, is often inconclusive and may require further invasive testing. MDCT has been shown to be effective for the delineation of many causes of chest pain that may be inapparent on initial clinical or radiographic evaluation, including pneumonia, aortic dissection, and pulmonary embolism [1, 2]. More recently, promising results have been obtained with the use of MDCT in the evaluation of coronary artery stenosis [3, 4]. Our study was undertaken for two purposes: to determine the logistic feasibility of using MDCT in the emergency department setting to assess chest pain, and to assess sensitivity and specificity of the MDCT technology in providing an evaluation of cardiac and noncardiac causes of acute chest pain in stable emergency department patients.
Subjects and Methods
Patients
Patients presenting in our emergency department with acute chest pain
between November 2003 and July 2004 were approached for recruitment in this
prospective study. Acute chest pain in the University of Maryland emergency
department is typically classified on a scale of 1 to 5 on the basis of the
initial clinical impression. These are clinical categories based on the
patient's chief complaint, symptoms and signs, risk factors, and ECG. Category
1 is an acute myocardial infarction. Category 2 is considered definite angina
with uncertainty regarding acute myocardial infarction. Categories 3, 4, and 5
are probable angina, probably not angina, and not angina, respectively.
Patients in whom there is less concern for angina but suspicion of clinically
significant noncoronary chest pain (e.g., pulmonary embolism) are usually
graded as category 3 or 4 rather than category 5, conferring a nonanginal
component to the classification system. These are not final diagnoses but
rather simple, practical, and functional categories along a continuum adopted
broadly by emergency physicians and advocated by the Society of Chest Pain
Centers [5].
Clinically stable patients with chest pain classified from 2 to 4 were eligible for inclusion based on the assessment of the emergency department physician and other inclusion and exclusion criteria. Inclusion criteria included age greater than 18 years and the ability to understand and sign a consent form. Exclusion criteria were clinical instability (such as arrhythmia, congestive heart failure, and hypotension), compromised renal function, allergies to contrast material, and pregnancy. Category 1 patients were excluded because of clinical instability. Category 5 patients were deemed unlikely to have a significant cause of chest pain and were also excluded. The emergency department physician was asked in each case before the study whether CT would have been performed for the conventional workup. The CT study was done early in the clinical evaluation of the patient in the interval immediately after the ECG was done and blood samples drawn and before a decision was made as to further care or studies for the patient and before results of cardiac enzymes were available. Patient demographics are summarized in Table 1.
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Seventy-eight patients with chest pain were enrolled. Nine patients were excluded before completing the protocol. In four patients, the CT was performed but the raw projection data were erased from the scanner hard drive before multiple phases of the cardiac cycle could be reconstructed. In three patients, no CT was performed because the patients were undergoing evaluation elsewhere and could not be scheduled for CT. The other two patients left the emergency department against medical advice before CT scanning. Ultimately, 69 patients participated in the chest pain protocol.
The study protocol was approved by our institutional review board (IRB) and informed consent was given by each patient. All Health Insurance Portability and Accountability Act procedures were followed. As part of the study protocol, all patients enrolled in the study received a consultation with a cardiologist.
Image Acquisition
CT scans were acquired on each patient using a 16-MDCT scanner (MX8000IDT,
Philips Medical Systems). The CT scanner is located adjacent to the emergency
suite, and thus patients could be monitored as necessary by emergency
department personnel while undergoing CT. For each patient, retrospective
ECG-gated images were obtained through the entire chest during a single
breath-hold beginning at the inferior margin of the heart and extending to the
top of the lung apices. Patients were advised to exhale slowly if they could
not maintain breath-holding throughout the scanning. The scanning protocol
included collimation of 0.75 x 16 mm with reconstructed axial image
thickness of 1 mm. Scanning technique was 140 kVp and 350–500 mAs. A
pitch of 0.2–0.3 was used with a scanner rotation time of 0.42 sec.
Iodinated contrast material, 120–150 mL, was injected through an 18- to
20-gauge angiocatheter into an antecubital vein at 3–4 mL/sec. Automated
bolus timing was performed using a threshold value of 150 H and a region of
interest placed over the ascending aorta. After additional IRB approval was
obtained, a ß-blocker (Lopressor [metoprolol, Novartis], 5 mg IV) was
used to control heart rates greater than 70 beats per minute. Of the final 32
patients, 10 received ß-blockers.
The average scanning time was 30 sec with an additional 3–4 min for preprocedure placement and adjustment of the ECG leads. A large field of view (350–400 mm) was used to encompass the entire chest at 75% of the R-R interval. The raw data were used to reconstruct axial images as well as coronal and sagittal maximum-intensity-projection reformations. Axial images were also subsequently reconstructed in a smaller field of view (250 mm) targeted to the heart. These reconstructions were obtained at 10% intervals for a total of 10 phases.
Image Interpretation
An initial assessment was made of noncardiac disease and for the
contrast-enhanced presence of coronary artery calcification using the large
field-of-view images (ECG-gated 75% R-R interval). Specific noncardiac
entities that were evaluated included, but were not limited to, aortic
dissection, pulmonary embolism, pneumonia, pneumothorax, pericardial effusion,
and rib fracture. A qualitative assessment of the presence and extent of
coronary artery calcifications was made. No quantitative software was used
because all scans were obtained after the administration of IV contrast
material. Coronary artery calcification was characterized as none, mild,
moderate, or severe. All of this information was immediately communicated to
the clinical team in the emergency department using a preliminary report form
(Fig. 1A). This abbreviated
initial evaluation was necessitated by the time required to reconstruct the 10
cardiac phases consisting of 2,500–3,500 images, which ranged from 15
min if all images were reconstructed immediately to several hours, depending
on other duties of the technologists and the clinical demands made on the CT
scanner.
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Clinical Follow-Up and Assessment
Emergency department data and all available medical records were reviewed
for each patient between 1 and 2 months after the emergency department visit.
Data were collected as to whether the patient left against medical advice from
the emergency department and whether the patient required either
hospitalization or a subsequent emergency department visit. In addition to the
CT, information on other relevant diagnostic tests was recorded, including
coronary angiography, stress echocardiography, or radionuclide stress testing
obtained within 1 month of presentation to the emergency department.
A consensus group consisting of one emergency department physician, one cardiologist, and one radiologist was convened to determine a final diagnosis. The consensus group used the following guidelines to adjudicate each case: For patients who were discharged from the emergency department and who did not receive further testing, the diagnosis provided at the time of discharge from the emergency department by the emergency department physician was deemed definitive. For patients who had coronary angiography, stress echocardiography, or radionuclide stress testing, the results of these tests were used to arrive at a final judgment. Positive coronary angiography was defined as showing a stenosis greater than 50% in a major vessel. For clinically significant diagnoses for which CT is considered a standard reference technique (e.g., pulmonary embolism, aortic dissection), the CT findings were regarded as definitive. Using these guidelines based on the best available clinical and testing information, a final diagnosis for the emergency department visit was determined. Finally, results of invasive coronary angiography, stress echocardiography, and radionuclide stress testing were correlated with their respective findings on CT angiography.
Statistical Analysis
Sensitivity, specificity, positive predictive value, and negative
predictive value were calculated for the emergency department CT using the
final clinical diagnosis as the reference standard. Separate values were
calculated for the diagnosis of cardiac chest pain only and for the full
assessment of cardiac and noncardiac diagnoses. For differences between
ejection fractions as calculated on MDCT and radionuclide testing, an unpaired
t test was used. A p value of less than 0.05 was considered
to indicate statistical significance.
Results
Overall Clinical Assessment
The 69 patients who completed the chest pain protocol included 35 men (51%)
and 34 women (49%) with a mean age of 51 years (range, 33–81 years).
Forty-five patients (65%) would not otherwise have undergone CT, according to
the judgment of the emergency physician caring for the patient. Seventeen
patients (25%) presented with chest pain that was classified as category 2, 32
(46%) with category 3, and 18 (26%) with category 4. In two patients (3%), no
category was assigned by the emergency physician. Twentynine patients (42%)
required hospital admission for further evaluation, including 13 (76%) of
those with category 2 pain, 11 (32%) with category 3 pain, and three (17%)
with category 4 pain. Both patients for whom no category was assigned were
also admitted. One patient was ruled in for an acute myocardial infarction and
a second was diagnosed with acute coronary syndrome.
Fifty-two (75%) of the 69 patients had no significant CT findings and a final diagnosis of clinically insignificant chest pain (Fig. 2A, 2B). Thirteen patients (19%) had significant CT findings concordant with the final diagnosis (cardiac, 10; noncardiac, 3). Each of the 10 patients with cardiac disease and a positive CT diagnosis was deemed to have a diagnosis of angina due to coronary artery disease (Fig. 3A, 3B). The three noncardiac diagnoses were pericarditis with a moderately large pericardial effusion, subtle pneumonia, and pulmonary embolism (Figs. 4 and 5). In two patients (3%), CT failed to suggest a clinically significant diagnosis. Both of those were clinically significant coronary artery stenoses identified on angiography in the left anterior descending and first diagonal branches, respectively. In both patients, image quality was adversely affected by motion (Fig. 6A, 6B, 6C). In two additional instances (3%), CT overdiagnosed a coronary stenosis. Both incorrectly identified lesions were in the mid left anterior descending artery. The decision on final diagnosis was based on clinical data in 34 patients (49%), radionuclide testing in 15 (22%), coronary angiography in 11(16%), stress echocardiography in six (9%), and CT alone in three (4%). The diagnoses made on CT alone were those with noncardiac causes, for which CT is a standard reference technique.
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Coronary Artery Calcification
Qualitative analysis of the extent of coronary artery calcification on the
contrast-enhanced study revealed no calcification in 42 patients. Mild,
moderate, or severe amounts of calcification were present in 19, four, and
four patients, respectively. Of the 10 patients with significant coronary
artery disease found on CT, coronary artery calcification was graded
qualitatively as mild in one, moderate in six, and severe in three. Of the two
patients with negative CT findings who proved to have coronary artery disease,
one had no visible coronary artery calcification and the second had mild
coronary artery calcification.
Functional Assessment
Twenty-one patients underwent stress nuclear medicine testing with
calculation of ejection fraction within 1 week of the MDCT. MDCT yielded a
significantly higher ejection fraction (mean, 63%; range, 47–82%) than
the radionuclide study (mean, 52%; range, 36–63%) in these patients
(p < 0.01). Twelve patients had a difference of 10% or less
between the radionuclide stress and MDCT ejection fraction, five and four
patients had discrepancies of 11–20% and 21–30%, respectively. One
patient showed a focal perfusion defect at the cardiac apex on CT
(Fig. 7). A wall motion
abnormality was identified in a similar location on stress
echocardiography.
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Discussion
Substantial advances have occurred in patient evaluation and triage over the past decade, but the assessment of chest pain in the emergency department remains a significant challenge. Although a cardiac or noncardiac diagnosis may be immediately apparent, initial clinical evaluation is often equivocal, resulting in a high proportion of hospital admissions [6]. Nevertheless, it is estimated that 4–8% of patients are inappropriately discharged from the emergency department and ultimately prove to have a myocardial infarction, the most important cause of acute chest pain [7, 8].
In the emergency department, the diagnosis of acute cardiac ischemia, which includes acute myocardial infarction and unstable angina, remains primarily clinical, and is guided by history, risk factors, and ECG results. This diagnostic pathway is known to lack sensitivity [9, 10]. Serum markers of myocardial injury (CK-MB [creatininekinase myoglobin] troponin, and myoglobin) also are a critical part of chest pain assessment but typically do not show elevations until more than 6 hr after the onset of the chest pain [11]. Thus, they may not be useful in the hyperacute setting when the administration of thrombolytics might lead to maximal preservation of myocardial tissue. Moreover, these markers do not allow rapid exclusion of myocardial ischemia, which would permit early discharge from the emergency department.
Other imaging-based diagnostic strategies have been attempted to assess cardiac causes of chest pain. Echocardiography with the patient at rest and after stress can show wall motion abnormalities due to ischemia and can assess valvular, pulmonary artery, and pericardial disease [12–14]. However, the technique is operator dependent and requires considerable experience. Moreover, poor acoustic windows may limit the study [12]. Nuclear scintigraphy using thallium or technetium-99m sestamibi may detect abnormalities of myocardial perfusion, but this may reflect remote infarction. These techniques have a high sensitivity and moderate specificity [15]. An important additional limitation is the need to transport the patient to a gamma camera, which is often in a remote location [13]. MRI is often impractical because of the need for specialized equipment that may not be available in the emergency department and a substantial prevalence of claustrophobia [16]. Each of these imaging techniques is also limited in its capability to detect extracardiac causes of chest pain.
CT, in particular electron beam CT, has been used to risk-stratify patients with acute chest pain by revealing coronary calcium [17]. The absence of calcification is associated with a very low likelihood of acute cardiac ischemia. The latest generation of MDCT scanners features ECG-gating, submillimeter spatial resolution, and relatively good temporal resolution that permit adequate assessment of coronary artery anatomy [18, 19].
Our pilot study shows that MDCT is a feasible approach to provide a
comprehensive chest pain evaluation in the emergency department. We selected
patients with chest pain levels of 2 to 4 who were deemed to be clinically
stable. It is this group of patients without definite evidence of myocardial
infarction in whom MDCT may have its greatest impact. None of our patients
ultimately proved to have myocardial infarction or unstable angina. Presumably
this is because of our restrictive inclusion criteria and the low prevalence
of myocardial infarction (
5%) that has been documented in our emergency
department. This low prevalence indicates the potential impact of the MDCT
protocol, if completed expeditiously, to rapidly triage patients, particularly
those with a negative study.
In our study, several patients had chest pain caused by coronary artery disease, and MDCT showed coronary artery calcification or areas of coronary stenosis in most of these patients. However, in two patients, an area of significant coronary artery narrowing on coronary arteriography was not detected on CT. In part, this deficiency may have been due to the way the CT scan was acquired. Our protocol entailed a global evaluation of chest pain and thus represented a necessary compromise between evaluating the coronary arteries and the remainder of the chest. We used a larger focal spot and larger field of view than are typical for a dedicated coronary artery evaluation, and we subsequently reconstructed a smaller field of view centered around the heart. In addition, scanning was initiated at the bottom of the heart and extended cephalad for an uninterrupted acquisition through the entire chest, in contrast to the typical coronary artery protocol that progresses inferiorly from a level just above the coronary arteries. These modifications undoubtedly led to some degradation of coronary artery images. Moreover, ß-blockers were not used for the initial portion of the study. Despite the limitations of the technique, MDCT was able to diagnose clinically significant cardiac and noncardiac causes of chest pain in most cases.
Other aspects of the MDCT cardiac evaluation were less valuable. The assessment of coronary artery perfusion after enhancement was quite subjective. No quantitative threshold has been established to define such a defect. When a defect was conclusively present in the judgment of the two observers, its chronicity could not be determined. Similar considerations apply to the evaluation of wall motion abnormalities. Ejection fraction was depressed in a minority of patients, with a reasonable correlation with results from nuclear medicine testing when available.
Although the number of clinically significant abnormalities was low in this pilot study of an acute chest pain imaging protocol, MDCT showed the potential to be a valuable method for excluding significant cardiogenic causes of chest pain, including coronary artery stenoses greater than 50%, as evidenced by a high negative predictive value. Completely normal or not significantly abnormal MDCT findings was the most common result in our series and was confirmed in most cases by the final diagnosis. In addition, MDCT was valuable for suggesting noncardiac diagnoses such as pneumonia and pulmonary embolism. In this respect, MDCT has an advantage over other imaging techniques, such as perfusion radionuclide scintigraphy and echocardiography, that are sometimes used in the emergency department setting.
Several limitations of this study must be emphasized. First, because this was a feasibility study, the number of enrolled patients was small. Second, as described earlier, the goal of providing a complete thoracic assessment that included pulmonary embolism and aortic dissection necessitated a compromise protocol that was not optimized to the coronary arteries. Another technology-related shortcoming was that the time required for postprocessing necessitated an initial general evaluation followed by a more detailed cardiac evaluation, often separated by several hours or more. Thus, a real-time coronary artery assessment proved difficult or impossible. With the advent of the latest generation of 64-MDCT scanners, these limitations may be mitigated as a result of faster image acquisition, better spatial and temporal resolution, and more rapid postprocessing.
A fourth limitation was the lack of a standard end point to assess final diagnosis. As noted, the patients had variable clinical evaluations and some had no documented follow-up at our institution after their index emergency department visit. In particular, only a minority of patients ultimately underwent coronary angiography, the anatomic standard of reference. Thus, determination of a final diagnosis was necessarily subjective in many instances. This shortcoming is common in studies involving emergency department patients [20]. Finally, the design of the study did not permit assessment of high-risk or less stable patients, thereby limiting the number of subjects with clinically significant coronary artery stenoses. Further studies of this technique will need to assess its performance when evaluating patients with a higher likelihood of coronary artery disease.
An additional consideration is that CT may not be the best technique to diagnose certain causes of chest pain. For instance, musculoskeletal chest pain is often best evaluated on physical examination, gastrointestinal reflux disease may be assessed with manometric testing, and pneumonia is often better seen on chest radiography. Thus, although CT has potential value in the diagnosis of many life-threatening causes of chest pain, not every cause of chest pain can be diagnosed.
In summary, our pilot study suggests that a comprehensive evaluation of many cardiac and noncardiac causes of acute chest pain in the emergency department with MDCT is logistically feasible and may provide clinically meaningful data. The greatest potential impact appears to be in the exclusion of significant cardiac disease to supplement assessment of established indications in life-threatening noncardiac disease such as pulmonary embolism and aortic dissection. However, in patients with suspected coronary disease based on CT, further study is needed to more clearly elucidate its sensitivity for clinically significant coronary artery stenoses. Moreover, routine implementation of this technique will require further technologic advances, such as more rapid scanning and reconstruction, and greater ease of image postprocessing. The potential exists that these advances will lead to greater reliability of delineation of coronary artery anatomy and cardiac function, permitting contemporaneous clinical feedback of the entire MDCT examination to the emergency department team, thereby facilitating a more expeditious triage of the patient with chest pain.
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