Curr Cardiovasc Imaging Rep (2013) 6:197–202 DOI 10.1007/s12410-013-9196-2

CARDIAC COMPUTED TOMOGRAPHY (TC VILLINES AND S ACHENBACH, SECTION EDITORS)

Coronary CT Angiography in the Emergency Department: Current Status Abhay N. Bilolikar & Kavitha M. Chinnaiyan

Published online: 13 March 2013 # Springer Science+Business Media New York 2013

Abstract In the United States alone, nearly 7 million patients present annually to emergency departments (ED) with complaints of chest pain suspicious for acute coronary ischemia. Acute chest pain represents a clinical as well as economic challenge, resulting in elaborate, time-consuming, and expensive work-ups to avoid litigation related to missed diagnoses of acute coronary syndromes (ACS). Coronary CT angiography (CTA) is an attractive noninvasive technique with promising data for use in the ED due to its high accuracy and negative predictive value. Recent studies have demonstrated that coronary CTA can aid in safe, rapid, and cost-efficient triage of patients with acute chest pain. Additional applications of plaque characterization, fractional flow analysis, and CT perfusion imaging hold promise in providing incremental data in patients with suspected ACS. Keywords Coronary CT angiography . Emergency department . Chest pain . Acute coronary syndrome

Introduction Appropriate and timely triage of patients presenting to the emergency department (ED) with acute chest pain remains challenging. Of all patients presenting to the ED with acute chest pain, nearly 75 % are diagnosed with non-cardiac or non-ischemic cardiac problems and less than 20 % of the remaining meet the criteria for acute coronary syndromes (ACS) [1••, 2••, 3••]. In general, although patients at either end of the spectrum, that is, those with ACS and those with very low probability for coronary ischemia, can be A. N. Bilolikar : K. M. Chinnaiyan (*) Department of Cardiology, William Beaumont Hospital, 3601 W. 13 Mile Road, Royal Oak, MI 48073, USA e-mail: [email protected]

identified and triaged in an expedited manner, those with low-to-intermediate cardiac risk present a diagnostic dilemma. Frequently, these patients are admitted to the hospital or specialized ‘chest pain’ units for extended observation with various diagnostic strategies including serial EKGs, cardiac enzymes, and often, noninvasive stress testing.[4–9]. In the United States alone, 7 million patients present annually to the ED with complaints of chest pain suspicious for acute coronary ischemia [1••]. Though recent data suggest that ED visits for chest pain have decreased over the past decade, they result in aggregate costs of $10–$14 billion to the U.S. healthcare system annually [1••, 3••, 9–11]. Even with an approach of extensive testing at such high costs, 2 %–8 % of patients have a missed diagnosis of ACS or are inappropriately discharged home, leading to a doubling of mortality, and resulting in the majority of malpractice suits against ED physicians [10, 11]. Thus, a safe, rapid, and accurate testing modality that can detect the presence of coronary artery disease in patients with acute chest pain and help facilitate clinical decision-making is highly attractive.

Accuracy of Coronary CTA in the ED The accuracy of coronary CTA for assessing the presence and severity of coronary atherosclerosis compared with invasive angiography has been reported in over 30 published studies encompassing more than 2000 patients. A meta-analysis of 29 studies (16 to 64-slice systems, in 2024 patients) revealed a per patient sensitivity of 96 %, specificity of 74 %, and positive and negative predictive values of 68 % and 97 % respectively [12] when compared with invasive angiography. Two prospective, multicenter studies the CORE 64 and ACCURACY studies [13, 14] demonstrated similar results, with the diagnostic

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performance of coronary CTA being somewhat dependent on the prevalence of coronary disease in the population studied. More recently, a meta-analysis was published on the accuracy of coronary CTA in patients presenting to the ED with chest pain including updated CT scanning technology, and encompassing 9 studies demonstrated excellent diagnostic accuracy for ACS, with a sensitivity of 95 %, specificity of 87 %, and negative and positive likelihood ratios of 0.006 and 7.4, respectively [15]. Overall, this meta-analysis reaffirms the known body of literature concerning the diagnostic accuracy of CTA, both as applied to the general population and specifically in this case as applied to a low-intermediate cardiac risk population.

Coronary CTA vs Standard of Care A large body of evidence exists to support the use of noninvasive stress testing to discharge patients effectively from the ED, delineating it as a standard of care in those with low-to-intermediate cardiac risk [16]. The advent of coronary CTA and its expanding clinical applications, including to those with acute chest pain has resulted in international interest in this modality as an alternative to stress testing in the ED. To this end, 3 recent randomized, controlled studies have examined the value of coronary CTA vs standard of care in the ED, with or without stress testing [17–19]. The first of these, the CT-STAT trial randomized 749 low-risk patients to coronary CTA or to standard of care with stress myocardial perfusion imaging (MPI) [17]. Compared with those in the MPI arm, patients undergoing coronary CTA as the first test had a significantly shorter time to diagnosis (2.9 vs 6.2 hours, P<0.0001), as well as significant reduction in total ED costs by nearly 40 %. Importantly, both approaches were equally safe, with similar rates of major adverse cardiac events (MACE) in those with normal index tests (0.8 % vs 0.4 %, P=0.29). These findings were expounded upon in 2 studies published in tandem, the ROMICAT II [18] and the ACRIN [19] studies. The ROMICAT II trial randomized 1000 patients with acute chest pain to coronary CTA or standard ED evaluation, with the intent to determine if the former would result in decreased hospital length of stay. Patients in the CTA arm had significantly shorter lengths of stay (23.2 vs 30.8 hours, P= 0.001), almost 3-fold higher rate of direct discharge from the ED (46.7 % vs 12.4 %, P=0.001) and significant reduction in time to diagnosis (10.4 vs 18.7 hours, P=0.0001). Among patients with a positive coronary CTA, increased downstream testing was noted; however there was no significant difference in total costs related to the increased testing. The ACRIN study randomized 1392 low-risk patients (TIMI risk scores of 0–2) to coronary CTA or traditional care (with or

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without stress testing), with safety as the primary outcome [19]. Among the 640 patients with negative coronary CTA, no death or MI was reported at 30 days. Patients undergoing coronary CTA had nearly 2-fold rate of direct ED discharge (49.6 % vs 22.7 %, P<0.0001), with significantly shorter lengths of stay (18 vs 24.8 hours, P<0.001). Coronary artery disease was diagnosed more frequently in the CTA group compared with the traditional care group (9 % vs 3.5 %). In the ED, having a test that can accurately detect coronary disease is the first half of the challenge; determining what to do with those results is a larger quandary. When the coronary CTA demonstrates normal coronary arteries, the disposition is clear; the etiology for the patient’s symptoms is not ACS and if other serious diagnoses have been considered and excluded, discharge is appropriate [20]. Similarly, when “severe disease” (>70 % stenoses) is demonstrated on coronary CTA, the disposition is also clear: admission and further invasive or non-invasive work-up is warranted. Disposition is not as clear in those with intermediate disease noted on CTA, ie, stenosis in the 25 %–70 % range, with concern regarding outcomes in the intermediateand long-term range. Although several studies have examined the prognostic value of coronary CTA in patients with or without known coronary disease [21, 22], comparative studies of long-term outcomes in large ED populations triaged via different approaches has not been evaluated. Overall, there is mounting evidence from large studies demonstrating the safety of a coronary CTA-based triage of low-to-intermediate risk patients with acute chest pain presenting to the ED. This approach is also found to be rapid, resulting in more frequent direct discharge and lower lengths of stay, and associated with lower costs of care. Importantly, coronary CTA detects subclinical coronary disease with larger implications for application of preventive measures. Thus, many EDs across the country have embraced coronary CTA as a reliable means with which to safely exclude coronary artery disease as a cause of a patient’s symptoms.

“Triple Rule Out” Protocols in the ED Nearly 1 in 6 patients without CAD detected on coronary CTA have non-cardiac findings that could explain their presenting symptoms [23]. In the process of acquiring CTA images, 3-dimensional data is acquired from the entire thorax within the field of view. This routine acquisition results in the ability to examine other non-cardiac structures, providing the possibility for ruling out the 3 most potentially fatal causes of chest pain: coronary disease, acute aortic dissection, and pulmonary embolism, ie, the “triple rule out” protocol. These protocols employ the use of a triphasic contrast injection and a caudal-cranial, or cranialcaudal (or in succession) acquisition. Such an acquisition

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results in excellent contrast opacification of the 3 vascular beds in question: the pulmonary and coronary arteries, and the aorta [24–26]. However, the very low incidence of occult pulmonary or aortic disease in acute chest pain patients without clinical signs or symptoms does not warrant routine use of the triple rule out protocols despite its excellent ability to diagnose a myriad of cardiac and non-cardiac pathology [27–29]. Triple rule out protocols are very useful in clinical scenarios where 1 or more of the “big 3” diagnoses may be equally likely; in such situations, expedited protocols intuitively decrease time-to-diagnosis, costs, and cumulative radiation dose. However, such clinical situations must still be assessed on a case-by-case basis. Comparative effectiveness research is much needed in the arena of triple rule out cardiac CT scans. Until further evidence, it remains an “uncertain” indication in the current appropriate use criteria for cardiac CT [30].

Coronary CTA and the Hemodynamics of Coronary Stenosis An important consideration of coronary CTA, particularly relevant in the ED, is that it delineates only anatomy, and can therefore only infer the impact of any given luminal narrowing on coronary blood flow. Anatomical assessment of the coronaries is most clinically reassuring when the vessels are normal or have minimal disease, and may reliably predict the physiological significance of very severe stenoses. However, anatomic data by itself is limited in assessing the physiological significance of stenoses of “intermediate severity” (25 %–70 % diameter stenoses). Recent post hoc analyses of the FAME study data have shown poor correlation between perceived angiographic percent stenosis, and confirmed hemodynamic significance via fractional flow reserve [31]. Thus, whether such anatomically defined lesions are responsible for symptoms, or are “innocent bystanders” requires adjudication by physiological determination of coronary blood flow [32]. In attempting to adjudicate this nonFig. 1 A “2-feature positive” atherosclerotic plaque with low attenuation and positive remodeling seen on coronary CTA (left) and invasive coronary angiography (right) in the left circumflex artery in a patient with acute chest pain (a). Ulceration and plaque disruption are suggested on coronary CTA (left), with complex, disrupted, and a “hazy” appearing lesion on invasive angiography in a patient with acute chest pain (b)

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invasively, a recent prospective study showed that compared with MPI, the addition of contrast enhanced CT perfusion (CTP) to standard coronary CTA can provide excellent anatomic and functional data [33]. CTP has the potential to provide incremental information to the angiographic images to help guide diagnosis and treatment of patients presenting to the ED with acute chest pain, with a significant improvement in the positive predictive value of CTA alone. Similar promising findings are seen with coronary fractional flow reserve CT (FFRct) studies, wherein advanced mathematical flow modeling of static CT images can be used to create a hemodynamic image at various lesion locations [34]. FFRct is shown to improve the diagnostic accuracy of coronary CTA, with decreased false positive rate. However, more data on the economics and time to decision is needed to support the routine use of such a technique to help guide decision-making in patients with acute chest pain. Also, further studies are needed to assess the functional significance of non-obstructive lesions, which have previously been implicated in acute myocardial infarctions [35]. As the field of coronary CTA has evolved, there is increasing interest in identifying features of plaques at “high risk” for causing ACS: features such as positive remodeling and low lesion attenuation. Patients with 2feature positive plaques have been shown to have a significant increase in the incidence of future ACS [36, 37] (Fig. 1). Other high-risk plaque features that have been identified are ulceration and intra-plaque dye penetration, with excellent correlation with invasive angiography (Fig. 1). Although neither high-risk plaque features nor their clinical implications have been specifically studied in large ED populations, the ability to identify vulnerable patients may soon be of clinical importance.

Best Practice and Limitations of Coronary CTA Coronary CTA has several important limitations that affect its usefulness in the triage of ED patients with acute chest

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pain. The advent of newer CT technology has resulted in major breakthroughs in scanning protocols, radiation dose, and resolution of artifacts. However, the lack of availability

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of up to date scanning equipment may require additional attention to patient preparation and choosing appropriate protocols (Table 1).

Table 1 Best practice model for patient selection and scanning for coronary CTA in the emergency department Pre-scan, patient selection, and preparation: A. Instructions to ED physician: 1. Ensure that the scan is appropriate for the patient’s symptoms and presentation. 2. Select patients based on pre-test probability of disease which would place them in a low-to-intermediate risk category based on TIMI risk score1 and historical presentation. For very low risk patients or simply low risk patients, consider no further advanced testing, or gated exercise treadmill testing (if ECG is interpretable and patient is able to exercise). 3. Prescribe beta-blockers if appropriate, with the intent to achieve a target heart rate of 60 bpm. 4. Evaluate renal function and prescribe hydration protocol when indicated. Prescribe medications to counter intolerance to iodinated contrast when indicated. B. Instructions to patients: 1. Hydrate liberally pre- and post-scan to avoid dehydration. C. Nursing assessment on arrival: 1. Assess heart rate variability and blood pressure, and effects of breath hold on heart rate. 2. Administer beta-blockers to achieve target heart rate (if no contraindication such as reactive airway disease, severe aortic stenosis etc.). D. *Administration of beta-blockers: 1. Baseline heart rates over 65 bpm, blood pressure over 90 mmHg systolic, body mass index over 18 kg/m2: Administer 100 mg of oral metoprolol or comparable dose equivalent, 30 min to 1 h prior to the procedure, or comparable intravenous doses with telemetric monitoring. 2. Baseline heart rates over 50 bpm, but less than 65 bpm, blood pressure over 90 mmHg: administer 50 mg of oral metoprolol to block heart rate acceleration during scan, or comparable intravenous doses with telemetric monitoring. Scan protocol: A. Nitroglycerin administration: 1. Provided blood pressure is over 90 mmHg, nitroglycerin generally improves image quality, yielding a lower frequency of repeat scans. 2. Avoided in patients with contraindications (for example, aortic stenosis, intake of phosphodiesterase inhibitors in preceding 12 h, etc.) B. *Scan field of view (FOV): 1. FOV should be consistently restricted to mid-pulmonary artery to the diaphragm. 2. Extended FOV “triple rule out” scans should be limited to patients with clinical likelihood of either a pulmonary embolus or aortic dissection based on generally accepted diagnostic criteria. C. **Tube potential: 1. Reduce tube potential from the standard 120 to100kVp in patients with a body weight of 85 kg or less and a body mass index of under 30 kg/ m2, subject to physician discretion. 2. In selected cases, tube potential may further be reduced to 80 kVp (pediatric or body mass index <18 kg/m2). D. *Tube current modulation (Retrospective Gating): 1. Tube current modulation by “EKG pulsing” should be used in all patients unless atrial fibrillation or frequent premature contractions are present. 2. Highly variable heart rates or atrial fibrillation may preclude the use of ECG dose modulation, but this should be weighed against the patient’s age and the suitability of other diagnostic options. 3. Tube output outside of the ECG modulation window. If scanner model allows tube current adjustment, the lowest available tube current outside the window should be utilized (eg, 5 % of maximal). This is equally applicable in obese patients, since the data during systole will not be used. E. Acquisition window: 1. For scanners with adjustable acquisition windows during EKG pulsing the following adjustments are recommended: • Heart rate <65 bpm: 65 % to 75 %. • Heart rate 66 bpm to 70 bpm: 60 % to 80 %. • Heart rate >70 bpm: 35 % to 80 %. F. Newer Technologies: 1. Prospective gating: every effort must be made to adopt prospective gating. 2. Adaptive statistical iterative reconstruction: per physician discretion. *Educational strategies found most effective for dose reduction. 1

Antman EM, Cohen M, Bernink PJLM, et al. The TIMI Risk Score for unstable angina/non–ST elevation MI: a method for prognostication and therapeutic decision making. JAMA. 2000;284:835–42.

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One frequent limitation of using coronary CTA in acute chest pain patients is the challenge of optimal heart rate control prior to the scan; prolonged preparation time in the real-world setting can result in much longer time-todiagnosis compared with published studies. In addition, because ECG-gating is critical to coronary imaging, any arrhythmias, ectopy, or ECG artifacts may result in degradation of image quality. Currently, scanning patients with atrial fibrillation is a challenge and requires specialized acquisition and reconstruction protocols. Extensive coronary calcification obscures the lumen and may substantially limit analysis of segments or even entire coronary arteries by CTA. Thus, this technique may be of limited application in patients with a high likelihood of significant coronary calcification, such as the elderly or in patients with prior calcium scores >1000 Agatston units [38–40]. Similarly, patients with pre-existing CAD often have extensive coronary calcifications, known intermediate severity coronary lesions, and/or coronary stents with resultant metal artifacts or prior coronary bypass grafting with extensively calcified native vessels and small caliber distal coronary arteries which make their studies very difficult to interpret. Obesity increases radiation scatter within the patient’s body and consequently degrades image quality due to a reduction of the signal-to-noise ratio. All of these factors diminish the diagnostic accuracy of coronary CTA, rendering it probably inappropriate for ED triage in patients with a body mass index over 40 kg/m2, although recent technical advances have enabled obtaining diagnostic quality images in the obese [41]. Radiation exposure is a significant consideration when performing coronary CTA, resulting in a non-negligible lifetime attributable risk of cancer and this should be weighed against potential benefits, especially in sensitive populations such as women under 45 years of age. Significant technological advances over the last few years have resulted in exponential decreases in total radiation exposure from cardiac CT [42]. Conscientious and meticulous patient preparation to lower heart rate, ECG dosemodulation, lowered tube voltage, prospective gating, and the use of newer technology such as the high-pitch or 320slice single heart beat volumetric acquisitions have resulted in in a >70 % dose reduction since the early and evolving application of CT for coronary angiography [42].

Conclusions Historically, ED evaluation of acute chest pain patients has entailed lengthy and expensive diagnostic testing. Recent studies provide robust data that coronary CTA has revolutionized the evaluation of appropriately selected patients, resulting in decreased time-to-diagnosis, expedited triage,

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and contributing to decreased downstream resource and cost utilization. Importantly, anatomic testing provides the ability to diagnose nonobstructive disease, which has important implications for application of judicious preventive measures. Further studies are needed to assess the functional significance of nonobstructive lesions, and long-term implications of such an approach. Finally, although this technology holds great promise, the limitations and risks, particularly that of radiation exposure must be considered carefully in its application in the ED.

Conflict of Interest Abhay N. Bilolikar declares no conflict of interest. Kavitha M. Chinnaiyan declares no conflict of interest.

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