Int J Cardiovasc Imaging (2009) 25:319–326 DOI 10.1007/s10554-008-9375-4

ORIGINAL PAPER

Coronary CT angiography in emergency department patients with acute chest pain: triple rule-out protocol versus dedicated coronary CT angiography Hwa Yeon Lee Æ Seung Min Yoo Æ Charles S. White

Received: 13 June 2008 / Accepted: 23 September 2008 / Published online: 14 October 2008 Ó Springer Science+Business Media, B.V. 2008

Abstract Immediate coronary catheterization is mandatory for high risk patients with typical chest pain in the emergency department (ED). In contrast, in ED patients with acute chest pain but low to intermediate risk, traditional management protocol includes serial ECG, cardiac troponins and radionuclide perfusion imaging. However, this protocol is time-consuming and expensive, and definite treatment of unstable angina is often delayed. Due to advances of multi-detector CT (MDCT) technology, dedicated coronary CT angiography provides the potential to rapidly and reliably diagnose or exclude acute coronary syndrome in ED patients with acute chest pain. Moreover, major life-threatening causes of ED chest pain (i.e., acute aortic syndrome and pulmonary embolism as well as acute coronary syndrome) can simultaneously be assessed by the so-called ‘‘triple rule-out’’ protocol with a single scan. In ED patients with atypical chest pain and low to intermediate risk, the triple rule-out protocol may be preferred, especially in older patients who have relatively lower risk of lifelong radiation-induced cancer. However, the

H. Y. Lee Department of Diagnostic Radiology, Chung-Ang University College of Medicine, Seoul, South Korea S. M. Yoo
C. S. White (&) Department of Diagnostic Radiology, University of Maryland Medical Center, 22 South Greene Street, Baltimore, MD 21201, USA e-mail: [email protected]

increased radiation dose resulting from the extended volume coverage with this protocol should be fully considered prior to performing this protocol. Therefore, in ED patients who have a low clinical suspicion of pulmonary embolism and acute aortic syndrome, especially younger patients, dedicated coronary CT angiography accompanied by modifications to reduce radiation dose is recommended. Keywords Computed tomography
Acute coronary syndrome
Acute aortic syndrome
Pulmonary embolism

Introduction of acute chest pain Acute chest pain is the second most common presentation to emergency department (ED) after abdominal pain [1]. More than six million patients annually present to the ED for the evaluation of acute chest pain in the United States and the number of annual hospitalizations due to chest pain approximates two million [2]. About 60% of patients who are admitted with acute chest pain eventually prove not to have acute coronary syndrome (ACS), incurring an estimated annual cost of eight billion dollars in the United States. Although ED physicians tend to have a low threshold for admission, 2–5% of ACS overall is missed at initial evaluation. Approximately 25% of patients with undiagnosed ACS who are inappropriately discharged die [3–7].

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As the traditional triage protocol for the ED patients with acute chest pain is neither accurate nor cost-effective, there has been a strong incentive to develop additional effective noninvasive imaging tools. A total of 64-slice MDCT is increasingly being used in the evaluation of ED chest pain. Several recent reports suggest that the presence of high-grade coronary artery stenosis can reliably be excluded by dedicated coronary CT angiography (Fig. 1) [8–10]. In addition, the so-called ‘‘triple rule-out protocol’’ which can simultaneously evaluate major life-threatening causes of ED chest pain (i.e., acute aortic syndrome (AAS) and pulmonary embolism (PE) as well as ACS) is technically feasible within a single breathhold in most patients using 64-slice MDCT. This article reviews the role and technical considerations of dedicated coronary CT angiography in the evaluation of ACS and also discusses the pros and cons of dedicated coronary CT angiography as compared to the triple rule-out protocol.

Current role of dedicated coronary CT angiography in the evaluation of ACS The term ACS encompasses ST-segment elevation myocardial infarction (STEMI), non ST-segment

Fig. 1 Curved multi-planar reformatted image shows normal left main, left anterior descending artery (a) and right coronary arteries (b) (arrowheads). Normal coronary CTA in a patient

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elevation myocardial infarction (NSTEMI), and unstable angina (UA). The diagnosis of ACS is straightforward in high risk patients who have typical chest pain, characteristic ECG changes, and elevation of serum cardiac troponin, whereas it is notoriously difficult in patients with atypical chest pain, nonspecific or normal ECG changes and normal initial cardiac biomarkers. Immediate reperfusion therapy is required to save ischemic but viable myocardium from further damage in high risk patients with a classic presentation. MDCT and other non-invasive imaging strategies have no role in the evaluation of these patients [11, 12]. The current role of MDCT in the triage of ACS is mainly limited to evaluation of low to intermediate risk patients. Low to intermediate risk patients are those with nonspecific or negative ECG change and normal initial serum cardiac biomarkers without evidence of cardiac failure. In these patients, the risk of a short term major adverse cardiac event (MACE) is relatively low [3, 13]. Many of these patients are admitted to dedicated cardiac units to rule out ACS, and the conventional management protocol includes serial ECGs, serum cardiac biomarkers over 12–24 h and radionuclide perfusion imaging, often with single photon emission computed tomography (SPECT) or less frequently, positron emission tomography (PET).

presenting to emergency department with acute chest pain virtually excludes acute coronary syndrome

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Radionuclide perfusion imaging tends to be performed at a later period of observation to ensure patient safety because the examination time is relatively long and the department of nuclear medicine is usually not located nearby to the ED in most hospitals. Therefore, a definite treatment of UA with nonspecific ECG change and normal troponin level is often delayed using the conventional triage protocol. Conversely, MDCT has a very short examination time of less than 20 min and is located close to or in the ED in many institutions. Incorporation of MDCT into the triage protocol shortly after presentation provides the potential to expedite early discharge of patients who do not have ACS and also facilitate early intervention for ACS, especially UA, if this is diagnosed. Recent studies indicate that 64-slice MDCT may be a good alternative to radionuclide perfusion imaging in the evaluation of low to intermediate risk patients with acute chest pain [14, 15]. A single center, prospective study compared a 64-slice MDCT protocol (i.e., dedicated coronary CT angiography) with a traditional protocol using radionuclide perfusion imaging for the evaluation of low risk patients with acute chest pain. Ninety-nine and ninety-eight patients, respectively, were randomly assigned to either MDCT or traditional protocols. MDCT patients with significant stenosis ([70%) were referred for an invasive coronary angiography. Those with minimal stenosis (B25%) or a low calcium score (B100 Agatston U) were discharged without further work up, whereas patients with intermediate stenosis (26– 70%), a calcium score greater than 100 Agatston U, or a non-diagnostic CT scan (e.g., motion artifact, severe calcifications or obesity) underwent radionuclide perfusion imaging. MDCT excluded or established coronary artery disease as the cause of acute chest pain in 75.8% of patients (67.8% were immediately discharged and 8% were referred for invasive coronary angiography). Additional stress testing was required in 24.2% patients who underwent MDCT due to either indeterminate coronary stenosis (13.1%) or a non-diagnostic CT scan (11.1%). Notably, the MDCT protocol demonstrated a decrease in overall cost and diagnostic time compared with traditional protocol. No case was complicated by a subsequent major cardiac event among patients discharged immediately in the MDCT protocol group over a 6 month follow-up. However,

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the study did reveal some disadvantages of MDCT protocol; additional radionuclide stress testing or coronary angiogram were required in cases with intermediate coronary artery stenosis (Fig. 2) to evaluate hemodynamic significance, and with nondiagnostic CT scans, resulting in greater radiation exposure [15]. A recent study demonstrates that the correlation between significant coronary artery stenosis ([50%) diagnosed by 64-slice MDCT and functional flow reserve is poor. Therefore, like conventional angiography, 64-slice coronary CT angiography can reliably assess high-grade anatomic stenosis but the evaluation of hemodynamic significance is limited [16]. Stress echocardiography or magnetic resonance imaging may be options to avoid further radiation exposure. Application of strict MDCT indications is mandatory to reduce nondiagnostic CT scans. In patients with severe coronary artery calcification ([1,000 Agatston U), inability to maintain breathhold, irregular heart rate, and obesity, obtaining a diagnostic coronary CT angiography is problematic. In the near future, it may be possible to decrease non-diagnostic CT scans and to assess myocardial perfusion directly with MDCT.

Fig. 2 Curved multi-planar reformatted image shows approximately 50–70% stenosis (arrowhead) by non-calcified plaque in proximal left anterior descending artery

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Technical considerations of dedicated coronary CT angiography in evaluation of ACS Certain prerequisites are required to ensure a diagnostic image quality of dedicated coronary CT angiography in the ED setting. Thorough shaving of the anterior chest in hirsute patients is necessary to allow the ECG leads to adhere firmly. A target heart rate of less than 65 beats per min is optimal to achieve a diagnostic image quality, although heart rate limitations may be less critical when using a dual source CT scanner, which has excellent temporal resolution (83 ms) [17, 18]. With 64-slice MDCT, beta blockers are routinely administered via an intravenous (5–20 mg of metoprotolol) or oral (50–100 mg of metoprolol) route before the examination unless a contraindication such as asthma, bradycardia or high grade AV block exists. Calcium channel blockers may be used as an alternative to beta blockers in patients with asthma. Short acting nitroglycerin (0.4 mg) should also be administered by a sublingual route to dilate the coronary arteries unless there is a history of having taken Viagra or low systolic blood pressure (\100 mm Hg). Instruction and explanation for proper breath-holding and potential side effects (e.g., heating sensation, nausea, or tingling sensation) after contrast injection should be given prior to MDCT examination. A test injection or bolus tracking method is required to determine the optimal starting point for MDCT scanning. It is also necessary to properly adjust CT parameters according to the patient’s body habitus. In obese patients, thicker collimation, increased radiation dose, slower gantry rotation time, and higher contrast volume are often necessary to avoid poor quality imaging. Contraindications for coronary CT angiography are renal insufficiency (creatinine level [ 1.5 mg l-1), allergy to contrast materials, severe arrhythmia, and hemodynamic instability. Adequate hydration is recommended to reduce the possibility of renal injury caused by the administration of contrast media. If calcium scoring is performed, some centers may choose to limit coronary CT angiography in patients with severe coronary calcification ([1,000 Agatston U) because of concern that it hinders the precise evaluation of coronary artery stenosis.

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The concept of the triple rule-out protocol In many clinical situations, a definite diagnosis of ED chest pain is not possible solely based on clinical symptoms and laboratory findings. In addition, most diagnostic modalities (i.e., ECG, cardiac enzymes, exercise treadmill testing, radionuclide perfusion imaging, and stress echocardiography) other than MDCT are focused on the diagnosis or exclusion of ACS but not other life-threatening causes of chest pain such as AAS and PE [19]. Therefore, there has been a strong interest to develop a noninvasive imaging tool to evaluate for multiple life-threatening causes of chest pain simultaneously. The triple ruleout protocol using MDCT is ideal for this goal. With faster gantry rotation time and the additional longitudinal coverage of the 64-slice scanner, imaging of the entire thorax is now feasible in approximately 15 s (i.e., within a single breathhold) in most patients. Proper timing in the performance of coronary CT angiography is important. Triple rule-out MDCT protocol should not be delayed if there is a high clinical suspicion of PE or AAS as well as ACS. Conversely, dedicated coronary CT angiography can be delayed until confirmation of normal initial cardiac biomarkers is received if ACS is the only clinical concern. Two types of cardiac protocols can be used in the ED setting: dedicated coronary CT angiography and the triple rule-out protocol. The two protocols have a different scanning range and field of view. A limited field of view focused on the heart is required to increase spatial resolution in dedicated coronary CT angiography, while a wider field of view to include the entire chest is necessary for simultaneous assessment of the coronary arteries, pulmonary arteries, and aorta in the triple rule-out protocol. The extent of scanning for the former ranges from the aortic root to the base of the heart, whereas that of the latter covers from above the aortic arch to the adrenal glands [20]. Because of extended volume coverage in the triple rule-out protocol, imaging is typically obtained in caudal-cranial direction to reduce artifact caused by respiratory motion (Table 1). The two protocols also have different contrast dynamics. With dedicated coronary CT angiography, the bolus of administered contrast materials is targeted to the left circulation and a major goal is

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Table 1 Comparison of sample ED chest pain 64-Slice MDCT Protocols Protocol

Dedicated CT angiography

Triple rule-out

Field of view

220

400

Thickness (mm)

0.625–0.9

0.625–0.9

Increment (mm)

Half of slice thickness

Half of slice thickness

Direction

Cephalad-caudal

Caudal-cephalad

Time (s)

9–10

15

Z axis coverage

Aortic root-cardiac base

Aortic archadrenal gland

to avoid streaky artifacts caused by densely concentrated contrast in the right cardiac chambers, whereas in the triple rule-out both the right and left circulation must be well enhanced simultaneously to evaluate both the pulmonary arteries and coronary arteries [21]. In order to avoid diluting the contrast in the right heart, a triphasic injection is used in the triple rule-out protocol as follows: 100 ml of contrast injected at 5 ml s-1 to enhance the left circulation, then 30 ml of contrast at 3 ml s-1 to opacify the pulmonary arteries, followed by a saline flush. Using this protocol, satisfactory enhancement of both coronary and pulmonary arteries can be obtained without causing significant streak artifact into the right coronary artery [22].

Triple rule-out protocol versus dedicated coronary CT angiography It is crucial to understand the merits and deficiencies of the two competing cardiac CT protocols used to evaluate ED patients with acute chest pain. As noted, the major advantage of the triple rule-out protocol lies in its potential to diagnose major life-threatening thoracic diseases (i.e., ACS, PE, and AAS) with a single scan (Fig. 3) [19, 23, 24]. In addition, other diagnoses such as pneumonia, rib fracture, or lung cancer can also be established, suggesting that the term ‘‘triple rule-out’’ may underestimate the capabilities of the examination. One pilot study indicated that triple rule-out protocol may not only be a valuable method to identify or exclude ACS in low to intermediate risk patients who present to ED but also to assess extra-cardiac causes of acute chest pain that

Fig. 3 ECG-gated axial CT image performed with triple ruleout protocol shows an intra-vascular filling defect (arrow) in the right lower lobe pulmonary artery, consistent with pulmonary embolism

could not be evaluated by radionuclide stress test or stress echocardiography [23]. One advantage of the triple rule-out protocol compared with dedicated coronary CT angiography is the fact that only 35.5% of entire chest volume is evaluated using the field of view of a dedicated coronary CT angiography [25]. However, it should be kept in mind that the limited field of view in a dedicated coronary CT angiography is a step in the reconstruction not the acquisition. A dedicated coronary CT angiography contains the data for the entire width of the irradiated chest. The evaluation of approximately the lower two-thirds of whole chest is feasible in a dedicated coronary CT angiography without further radiation dose if one acquires the reconstruction images with a full field of view in addition to a small field of view for coronary arteries. Therefore, the diagnosis of central PE and most aortic dissection may be possible with a dedicated coronary CT angiography. However, a substantial number of cases of PE, especially peripheral PE, can still be missed with this protocol. Additional numbers of PE cases may also be missed with dedicated coronary CT angiography because washout of contrast material from the pulmonary arteries can lead to false negative results. There are also some important drawbacks to using the triple rule-out protocol. When compared with

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dedicated coronary CT angiography, the triple ruleout protocol requires an increase of volume coverage and field of view as well as prolonged contrast injection to guarantee adequate enhancement of both pulmonary and coronary arteries. Therefore, an increase of radiation dose and respiratory motion artifact, decrease of imaging resolution and higher risk of renal injury may be involved in this protocol. In the final analysis, there is a trade-off in using the triple rule-out protocol; a comprehensive evaluation of the chest can be obtained with potential compromise in the imaging quality of the coronary arteries. Radiation dose of cardiac CT angiography is an important consideration related to the use of MDCT in the ED. With 64-slice cardiac CT angiography (dedicated coronary CT angiography), radiation dosage is estimated to be 9.6–15.2 mSv in men and 13.5–21.4 mSv in women. It should be stressed that radiation dose of triple rule-out protocol is about 50% higher than that of dedicated coronary CT angiography because of the higher dose length product associated with greater longitudinal scanning [20]. On the other hand, the effective radiation doses of the competing techniques, selective coronary angiogram and radionuclide perfusion imaging using TC99 m SPECT, are 5–6 and 10–12 mSv, respectively [26, 27]. The dose with thallium SPECT often exceeds 20 mSv. One option to reduce radiation exposure is a tube current modulation technique in which radiation dose is automatically lowered during systolic phase. Using this method, reduction of radiation dose up to 44% is possible [28]. Therefore, tube current modulation should be considered for retrospective gating as a standard of care because of the associated high radiation exposure. A second option is a prospective gating technique that reduces radiation dose substantially by only obtaining images during part of diastole. A recent study indicates that image quality using prospective ECG-gating for coronary CT angiography is comparable to that of retrospective ECG-gating with substantially lower radiation dose ranging from 1.1 to 3.0 mSv [29]. With prospective gating, it is not possible to assess cardiac function because images are not obtained in systole. Moreover, heart rate should be less than 65 beats per min for optimal image quality. Although not widely used in clinical practice, it is possible for current MDCT scanners to change slice thickness as well as ECG gated/non-gated acquisition

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over the Z-range during the study. Therefore, the reduction of radiation dose is technically possible when performing triple rule-out protocol using this technology. For example, ECG non-gated acquisition with 1 or 2 mm thickness can be obtained in the upper one-third of the chest to exclude PE, with ECG-gated acquisition with sub-millimeter thickness over the heart to evaluate the coronary arteries. One study suggests the potential cancer risk approximates 1 per 1,000–2,000 patients exposed to triple rule-out protocol [30]. Therefore, the triple rule-out protocol should be avoided in younger patients, especially women except when there is a high clinical suspicion of other life-threatening illness in addition to ACS [20]. An additional disadvantage of the triple rule-out protocol is that it is not optimized to exclude AAS. It does not typically include a pre-contrast scan, thus making the diagnosis of intramural hematoma more difficult. The triple rule-out protocol also does not routinely assess the full extent of aortic dissection into the abdomen and pelvis, which is a considered a typical component of the AAS evaluation. Thus, in ED patients with atypical chest pain, nonspecific ECG changes and normal initial cardiac biomarkers in whom both ACS, PE and other etiologies are a consideration, the triple rule-out protocol may be appropriate, especially in older patients who have a relatively lower risk of radiationinduced cancer [24].

Future directions Recently, vendors have introduced 256 and 320-slice MDCT in the market. The detector coverage of 256 and 320-slice MDCT is up to five times as that of 64slice MDCT. With the extended 16 cm z-axis coverage of 320-slice MDCT, it is possible to image the entire heart in a one gantry rotation [31]. As the entire heart can be imaged approximately in 1-s with 320slice MDCT, there is greater potential to assess myocardial perfusion as part of the acute chest pain work-up as well as to optimize imaging quality. As a false positive diagnosis of myocardial ischemia using radionuclide perfusion imaging is not rare, the ability of new CT scanner to simultaneously assess the coronary arteries and myocardial perfusion may help reduce unnecessary cardiac catheterization. This new

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generation of CT scanners may substantially alter the paradigm of ED chest pain triage in the near future.

Conclusion Coronary CT angiography is useful to evaluate ED patients with atypical chest pain who are at low to intermediate risk. With 64-slice MDCT technology, major life-threatening thoracic diseases (i.e., ACS, PE, and AAS) can be diagnosed using the ‘‘triple rule-out’’ protocol within a single breathhold. However, the increased radiation dose resulting from the extended volume coverage should be fully considered prior to performing this protocol. Therefore, in ED patients who have a low clinical suspicion of PE and AAS, especially younger patients, dedicated coronary CT angiography accompanied by methods to reduce radiation dose is recommended.

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