15

Ethan J. Halpern*

Essentials

1 The primary goal of “triple rule-out” (TRO) CT in the emergency department (ED) is to facilitate the safe, rapid discharge of patients judged to be at low to intermediate risk of acute coronary syndrome (ACS).

2 The detection of noncoronary lesions that explain the presenting complaint is a major advantage of the TRO-CT over nuclear stress testing.

3 TRO studies are most appropriate and cost-effective when there is a suspicion for ACS along with other diagnoses, such as pulmonary embolism, acute aortic syndrome, or nonvascular pathology in the thorax.

4 An optimized TRO protocol provides excellent image quality for aortic, coronary, and pulmonary arterial evaluation while minimizing contrast dose and radiation exposure.

5 Attention to the details of patient preparation, contrast administration, and timing of the scan is the key to high-quality TRO studies.

TRO-CT angiography (CTA) can provide cost-effective evaluation of the coronary arteries, aorta, pulmonary arteries, and adjacent intrathoracic structures for the patient with acute chest pain. It is most appropriate for the patient who is judged to be at low to intermediate risk for ACS and whose symptoms may also be attributed to acute pathology of the aorta or pulmonary arteries. Although a regular cardiac rhythm remains an important factor in coronary CT image quality, newer CT scanners with 64 or more detector rows afford rapid electrocardiographic (ECG)-gated imaging to provide high-quality TRO-CT in patients with heart rates up to 80 beats per minute. Injection of iodinated contrast material (≤100 mL) is tailored to provide simultaneous high levels of arterial enhancement in the coronary arteries and aorta (>300 Hounsfield units [HU]) as well as the pulmonary arteries (>200 HU). To limit radiation exposure, the TRO-CT does not include the entire chest but is constrained to incorporate the aortic arch down through the heart. Scan parameters, including prospective ECG tube current modulation and prospective ECG gating with the “step and shoot” technique, are tailored to reduce radiation exposure (optimally 5–9 mSv). When performed with appropriate attention to timing and technique, TRO-CT provides coronary image quality equal to that of a dedicated coronary CTA and pulmonary arterial evaluation that is free of motion artifact related to cardiac pulsation. In an appropriately selected ED patient population, TRO-CT can safely eliminate the need for further diagnostic testing in more than 75% of patients.

Evaluation of chest pain in the ED is a public health issue of great consequence. Based on the most recent available health statistics report from the Centers for Disease Control and Prevention, evaluation of acute chest pain and related symptoms was the second most common reason for a visit to the ED by adult women and the most common reason for a visit to the ED by adult men in the United States in 2006.¹ Chest pain accounted for 6,392,000 ED visits and 1,976,000 hospital admissions. Overall, suspected heart disease and chest pain were the most common reason for direct admission from the ED and accounted for 2,492,000 hospital admissions in 2006.

The differential diagnosis of chest pain is a complex problem for the ED physician. The diagnosis of ACS includes unstable angina, non–ST-elevation myocardial infarction, and ST-elevation myocardial infarction. Among patients presenting to the ED with symptoms of ACS, only 25% ultimately have a confirmed diagnosis of ACS on discharge.² The failure rate for diagnosis of ACS among patients presenting to the ED is in the range of 2 to 5%^3,4 but may be as high as 29% in low-volume centers.⁵ Patients in whom the diagnosis of ACS is missed tend to be younger, with an atypical presentation and a nondiagnostic ECG.⁶ The missed diagnosis of ACS is a common reason for litigation against ED physicians, accounting for up to 25% of the total malpractice liability of ED physicians.⁷ On the other hand, uncertainty in the diagnosis of ACS results in the practice of defensive medicine and begets an increased number of diagnostic tests and hospital admissions.⁸ The cost of negative inpatient cardiac evaluations is estimated at $6 billion in the United States each year.⁹

* Adapted with permission from Radiology. 2009 Aug;252(2):332–45

Clinical Role of TRO-CT

Numerous studies have demonstrated good to excellent diagnostic accuracy of dedicated coronary CT (cCTA) for evaluation of coronary disease,10 with excellent negative predictive value.^11,12 However, few reports have described the application of CT as part of the TRO examination with a dedicated TRO injection and scan protocol.¹³ TRO-CT is a tailored ECG-gated examination designed to evaluate the aorta, coronary circulation, pulmonary arteries, and the mid to lower portion of the chest with a single scan. Application of the TRO for evaluation of suspected ACS in the ED is possible because of advances in CT technology that provide greater z-axis coverage with improved temporal resolution and decreased radiation dose. A recent survey of radiology practices found that 33% used CT in the ED for the workup of chest pain and that 18% were using the TRO study.¹⁴

All patients with ACS require hospital admission, and many will benefit from rapid triage to cardiac catheterization and intervention. On the other hand, when the patient’s presentation clearly suggests a noncardiac diagnosis, coronary evaluation is not required and is not cost-effective. The remaining patients with suspected ACS must be cleared of this diagnosis before discharge. Given the potentially life-threatening consequences of missing the diagnosis of ACS, a high negative predictive value is critical for discharging patients with suspected ACS. The negative predictive value of cCTA for ACS will depend on the prevalence of coronary disease in the study population. A recent multicenter trial demonstrated a 99% negative predictive value of cCTA for coronary disease at both the patient and vessel level in a population with a disease prevalence of less than 25%, establishing cCTA as an effective noninvasive examination to rule out obstructive coronary artery stenosis.¹⁵ Although another recent multicenter trial demonstrated a negative predictive value of only 83% for cCTA, this study evaluated a population with a high (56%) prevalence of obstructive coronary disease.¹⁶ Based on these studies of dedicated cCTA, it is likely that TRO-CT will be most effective in a population with a low prevalence (<25%) of obstructive coronary disease.

For patients with low risk of ACS who are evaluated with conventional nuclear stress testing, only one third of patients with a positive or indeterminate stress test are found to have significant coronary disease on catheterization.¹⁷ For the evaluation of patients presenting to the ED who are judged to be at low risk of ACS, coronary CTA is at least as accurate as nuclear imaging,¹⁸ and it allows the safe, rapid discharge of low to intermediate risk ACS patients.^19–21 A recent study suggests that in low to moderate risk patients a CT triage model is less costly and more effective than strategies based on either stress echocardiography or stress ECG testing.²² Another recent study concludes that “compared to the other strategies, immediate CTA is safe, identified as many patients with coronary disease, had the lowest cost, had the shortest length of stay, and allowed discharge for the majority of patients.”²³ TRO-CT precludes the need for additional diagnostic testing in over 75% of patients with low to intermediate risk of ACS, and provides the additional advantage of finding noncoronary diagnoses that explain the presenting complaint in 11% of ED patients.²⁴ TRO-CT avoids the need for separate dedicated studies for coronary disease, aortic dissection, pulmonary embolism, and other acute chest pathology. In a properly selected population, coronary CT can provide cost-effective evaluation²⁵ with reduced diagnostic time, lower costs, and fewer repeat evaluations for recurrent chest pain compared with standard diagnostic evaluation.²⁶

Among patients who present to the ED with a low to moderate risk of ACS and who are evaluated with TRO-CT, a minority (<10%) are subsequently evaluated with conventional cardiac catheterization. Among those ED patients who are studied with both TRO-CT and cardiac catheterization, few normal cardiac catheterization studies would be expected.²⁴ Because it would not be ethical to subject most patients with a low to moderate risk of ACS to cardiac catheterization, there are no studies that confirm the negative predictive value of TRO-CT relative to conventional arteriography in the ED population. Nonetheless, if the quality of coronary imaging obtained with TRO-CT is equivalent to that of dedicated cCTA, one would expect the same high diagnostic accuracy and negative predictive value that has been documented with dedicated cCTA.

Injection and scanning techniques for TRO-CT studies vary considerably from one institution to another, resulting in inconsistent image quality. Some radiologists are reluctant to perform TRO studies because of an impression that the TRO is too technically challenging or that the quality of the coronary artery study is compromised in the TRO examination. The goal of this “how I do it” chapter is to discuss various approaches to patient preparation, bolus timing, contrast administration, and ECG gating and to describe a straightforward, optimized technique for performance of TRO-CT studies. An “optimized” TRO protocol should minimize contrast dose and radiation exposure to the patient while providing coronary arterial image quality equivalent to that of a dedicated cCTA, pulmonary arterial image quality equivalent to that of a dedicated CT pulmonary arteriogram, and high-quality imaging of the thoracic aorta without pulsation artifact.

Patient Selection

Appropriate patient selection is crucial to the cost-effective application of TRO-CT (Table 15.1). Patients who are at high risk for ACS with elevated cardiac biomarkers or acute ECG changes should be admitted to the hospital and are likely to benefit from direct triage to cardiac catheterization for diagnostic purposes and timely intervention. In the remaining patients with suspected ACS, the goal of TRO-CT is to exclude the diagnosis of coronary disease or to define an alternative diagnosis that might explain the presenting symptoms. Patients who are likely to have a high burden of calcified coronary plaque based on known coronary disease (previous myocardial infarction, chronic angina, stented patients, and post-bypass patients) are less likely to benefit from the coronary imaging performed with TRO-CT, although the TRO study may still be useful with respect to the aorta, pulmonary arteries, and other intrathoracic pathology. The degree of coronary disease is often overestimated in these patients as a result of blooming of calcified plaque such that it is impossible to exclude significant coronary disease. Older patients with multiple cardiac risk factors are more likely to have extensive coronary calcification.27 An indeterminate coronary CT evaluation is much more likely in patients with an elevated calcium score (above 400–1000).²⁸ In such patients, a calcium scoring study may be useful before performing TRO-CT to determine whether the patient is a candidate for TRO-CT.

An acceptable clinical history for TRO-CT includes a symptom complex that raises the suspicion of ACS, including symptoms such as chest pain; shortness of breath; syncope or near syncope; or neck, shoulder, back, or arm pain not appearing to be musculoskeletal in nature. Patients should have negative initial cardiac biomarkers (myoglobin and troponin-I) and should not have new ECG changes suggestive of myocardial ischemia. Ideally, these patients should have signs, symptoms, and laboratory data that might be interpreted as consistent with ACS or other causes of chest pain, including pulmonary embolism and acute aortic syndrome. In selected patients with low levels of positive biomarkers, TRO-CT may be appropriate when the clinical impression favors pulmonary embolism or acute aortic syndrome; there is a need to exclude ACS, but there is no immediate intention of sending the patient for invasive cardiac catheterization. When clinical suspicion is truly limited to ACS, a dedicated coronary CTA is preferred because it will use less contrast material and expose the patient to a lower radiation dose. Age, gender, and clinical presentation are well-validated parameters that can be used to define a population with suspected ACS that would be appropriate for TRO-CT.²⁹ Although traditional cardiac risk factors such as a family history of coronary disease, hypercholesterolemia, or hypertension are important long-term prognostic markers, such risk factors are of limited clinical value in diagnosing ACS in the ED setting and in triaging these patients.³⁰

The presence of a cardiac arrhythmia presents a challenge for ECG-gated coronary imaging, but it is no longer an absolute contraindication. Sinus bradycardia is the preferred heart rhythm for TRO-CT. In the absence of a clinical contraindication, a β-blocker should be administered before performing TRO-CT. Both heart rate and ectopy are reduced after treatment with an intravenous β-blocker.^31,32 New scanner technology provides improved temporal resolution with the capability of scanning the entire heart in one or two heartbeats (compared with four to five beats for most 64-slice scanners). This new technology has reduced the required phase window for diagnostic imaging of the coronary arteries along with the impact of variability in heart rhythm on coronary image quality.³³ The decision as to whether a patient should be excluded from the TRO-CT on the basis of a cardiac arrhythmia must be based on an assessment of the magnitude of the arrhythmia and the specific capabilities of the scanner that will be used for the study. Regular heart rates up to 80 beats per minute are no longer a contraindication for many new scanners, including dual-source scanners and single-source scanners with gantry rotation times less than 300 msec. Irregular tachyarrhythmias pose a more difficult problem, but the degree of contraindication depends on the frequency of ectopic beats.

Allergies to contrast material and renal insufficiency are relative contraindications to administration of iodinated contrast for TRO studies. The presence of asthma, acute heart failure, severe cardiomyopathy, and hypotension may limit the use β-blockers to control heart rate and thus may reduce the quality of the TRO examination. A history of recent cocaine use or a positive drug screen for cocaine is also a relative contraindication to the use of β-blockers for the scan,³⁴ although this contraindication remains controversial.³⁵ Recent use of a phosphodiesterase inhibitor is a relative contraindication to the administration of nitroglycerin for coronary vasodilatation during CT, but this does not represent a contraindication to TRO-CT.

CT Hardware and Radiation Issues

TRO-CT studies require a longer scan length than dedicated coronary CTA. A mean scan length of 20 cm is required to image the chest from above the aortic arch through the caudal aspect of the heart. To perform this scan during a single breath-hold, the scanner should be capable of imaging the required volume with ECG-gated technique in no more than 15 seconds. This requirement limits TRO-CT studies to scanners with at least 64 detector rows.

TRO studies are associated with a higher radiation dose compared with dedicated coronary CTA examinations because of the longer scan length. Our typical scan parameters include a tube voltage of 120 kVp and a mean effective tube current of 600 mA per slice (where effective mA [= tube mA × gantry rotation time/pitch). Heavier patients weighing over 200 pounds are scanned with higher tube current of 800 to 1000 mA based on a subjective estimate of patient body habitus by the attending radiologist. In our experience, mean effective TRO radiation dose for patients evaluated in helical scan mode without tube current modulation averages 18 mSv and is decreased to 8.75 mSv among patients evaluated with tube current modulation.36 Mean effective tube current or tube voltage can be decreased in smaller patients to reduce radiation dose.

til recently all cCTA studies were performed with a helical scan acquisition (with or without tube current modulation). In patients with stable heart rates, newer scanners can acquire TRO-CT with prospective ECG gating using the “step and shoot” axial mode to further reduce radiation dose to 5–6 mSv. Prospective ECG gating should be reserved for patients with a stable heart rate because any change in cardiac rhythm will either prolong the scan time (as the scanner waits for the next “normal” heartbeat) or result in degraded image quality from cardiac motion. Images obtained with prospective ECG gating are more sensitive to minor variations in heart rate and cannot provide information about cardiac function and regional wall motion. Nonetheless, in appropriately selected patients evaluated with proper attention to technique, prospective ECG gating of coronary CTA can be used to reduce radiation dose while maintaining image quality.^37,38

CT imaging, and coronary CT in particular, have been criticized as an important source of radiation exposure to the population.^39,40 Recent advances in CT technology, however, allow a dramatic decrease in radiation dose with coronary CT. The effective radiation dose for a TRO-CT with a state-ofthe-art scanner compares favorably with the dose of a nuclear stress test, which has been reported to range from 10 to 17 mSv.⁴¹ When one considers that the conventional workup of a chest pain patient presenting to the ED is likely to include a negative nuclear stress test as well as another diagnostic radiologic examination such as a chest CT or VQ study, application of TRO-CT studies to an appropriate patient population may actually reduce the per patient radiation exposure for diagnostic studies during the ED evaluation.

TRO Technique and Image Quality

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