Int J Cardiovasc Imaging DOI 10.1007/s10554-015-0763-2

ORIGINAL PAPER

Cardiac CT angiography for evaluation of acute chest pain Nam Ju Lee1 • Harold Litt1

Received: 4 August 2015 / Accepted: 31 August 2015 Ó Springer Science+Business Media Dordrecht 2015

Abstract Chest pain is the second most common emergency department (ED) presentation in the United States. Cardiac computed tomography angiography (CCTA) now plays an important role in the evaluation of patients with suspected acute coronary syndrome in the ED setting. In this article, we review the available techniques focused on the use of CCTA to evaluate patients fosr coronary atherosclerosis for timely triage of acute chest pain. Keywords Acute coronary syndrome
Chest pain
Coronary CT angiography
Atherosclerosis
Emergency department

present with unstable angina, acute myocardial infarction, or sudden coronary death [5], therefore, timely triage of ACS is important as it effects treatment and prognosis. Also timely triage may save significant costs. Using coronary CTA to clear patients instead of admitting patients for a rule out approach with serial troponin has the potential to save significant costs to the health care system. In this article, we review the role of cardiac CT angiography (CCTA) in patients with acute chest pain to diagnose and manage ACS caused by coronary atherosclerosis in the setting of the emergency department.

Risk assessment Introduction There is nearly one death from heart disease every 38 s in the United States [1]. Acute chest pain is the single most common complaint of patients older than 15 years of age presenting to the emergency department (ED) [2] and accounts for about 4 % of ED visits in the United States [3]. Origins of chest pain include diseases of the heart, aorta, pulmonary system, esophagus, upper abdomen, chest wall, and even psychiatric disorders. Determination of the etiology of the chest pain is often difficult, although different types of chest pain are classically ascribed to different corresponding diseases. Acute coronary syndrome (ACS) is estimated to be responsible for 20 % of all clinical encounters for acute chest pain [4]. Patients with ACS & Harold Litt [email protected] 1

Department of Radiology, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA

The initial step in evaluation of potential ACS in the ED is assessment of patient risk; this may be performed using scales such as the Thrombosis in Myocardial Infarction (TIMI) score, including clinical and medical history, coronary artery disease risk factors, electrocardiogram (ECG) results, and serum cardiac enzyme levels [6]. In approximately 10 % of all ED chest pain patients, with a TIMI risk score of zero combined with negative serial cardiac biomarker testing, the patient may be considered at low risk and discharged directly from the ED [7]. The presence or absence of specific symptoms is not reliable when used to rule out myocardial ischemia [8], and risk factors (hypercholesterolemia, hypertension, family history, and tobacco use) remain poor predictors of ACS [9, 10]. The standard 12-lead ECG cannot exclude ACS conclusively because diagnostic ECG findings are present only in a minority of patients, although it is the single best test to identify ST-segment elevation MI (STEMI) [11, 12]. Despite improvement in cardiac biomarkers (Creatine kinase, CK-MB, Myoglobin, Troponin I, Troponin T) for

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early diagnosis and risk stratification of acute MI [13–16], they are not universally elevated in patients with unstable angina or transient myocardial ischemia [17]. Therefore, negative markers cannot exclude ACS entirely and evaluation is still needed according to their clinical presentations. Patients with low-intermediate TIMI score without initial enzyme level elevation or ECG changes are typically admitted for complete evaluation with further enzyme analysis and often for myocardial stress imaging, whereas patients with a high-risk score are referred for intravenous (IV) heparin and further investigation with catheterization for intervention [18]. However, the reported 2–4 % rate of missed diagnosis of ACS [19–21] may expand the number of tests and hospitalizations in relatively low-risk populations with chest pain without definite evidence of ACS [22].

Evidence for CCTA in the ED The application of CCTA in the ED is based on trial data and observation from a limited number of centers [23–28] and CCTA is now seen as a viable alternative to functional testing in the evaluation of patients with acute chest pain in the ED [29–31]. Early utilization of CCTA in the ED for appropriately selected patients with a low to intermediate risk of ACS identifies low-risk patients quickly without the added delay of serial biomarkers or prolonged observation. It facilitates more rapid discharge from the ED compared to those undergoing non-CCTA standard care including serial ECGs, cardiac biomarkers, and subsequent cardiac testing such as exercise testing, stress perfusion imaging, or cardiac catheterization without a statistically significant difference in major adverse cardiac events (MACE) [25, 29– 34]. CCTA has shown its safety and efficiency in excluding coronary artery disease or relevant stenosis for advanced risk stratification over the past decade in the setting of ambiguous acute chest pain of a low to intermediate risk of ACS with 86–100 % sensitivity, 92–98 % specificity, 93–100 % negative predictive value, 50–90 % positive predictive value [23, 35–38]. Gallagher and colleagues [24] showed that CCTA is comparable to myocardial stress perfusion imaging in terms of safety and accuracy for excluding or diagnosing ACS. In a prospective cohort trial of 568 patients in the ED with low TIMI score, 84 % of patients were discharged based on a negative CCTA without adverse outcomes in 30 days with only one potential cardiac death at 1-year follow-up [27, 39]. ACRIN PA 4005 was a randomized controlled study of CCTA versus usual care for low-to-intermediate-risk patients presenting with a possible acute coronary syndrome. Of 640 patients with a negative CCTA

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examination, none died or had a myocardial infarction within 30 days and patients in the CCTA group had a higher rate of discharge from the ED (49.6 vs. 22.7 %), a shorter length of stay (LOS) (median, 18.0 vs. 24.8 h), and a higher rate of detection of coronary disease (9.0 vs. 3.5 %) compared with patients receiving traditional care [30]. CCTA also reduces cost in addition to reduction in diagnostic time in the intermediate-risk population [23, 39]. However, patients with indeterminate lesions or nondiagnostic CCTA will be referred for stress testing to evaluate the physiologic relevance of intermediate lesions. There are a small number of uninterpretable cases due to patient motion or unexpected heart rate variability. Our goal is that fewer than 5 % of studies will be deemed uninterpretable; this is accomplished only with strict heart rate control and patient education about what will happen during the test. The Computed Tomographic Angiography for the Systematic Triage of Acute Chest Pain Patients to Treatment (CT-STAT) trial showed that CCTA and stress SPECT myocardial perfusion imaging led to a similar number of patients referred to invasive coronary angiography, 6.9 and 6.2 %, respectively, similar to findings in ACRIN PA 4005. Time to diagnosis and hospital costs were significantly reduced with CCTA, to an average of 3 h compared with 7 h for those who received stress SPECT MPI; direct costs were reduced by 38 %, from roughly $3500 to $2000. In the ROMICAT II trial, 1000 patients with symptoms suggestive of ACS were randomized to an early CCTA or standard ED evaluation. Similar to the other studies, ROMICAT II demonstrated a shorter LOS for patients who underwent CCTA than standard evaluation and ED costs were lower. However, catheterization and revascularization rates were higher in the CCTA arm, leading to higher inpatient costs and overall cost neutrality. Women in the CCTA arm had greater reduction in LOS, lower hospital admission rates, and a smaller increase in cumulative radiation dose than men when comparing ED strategies (pinteractions B 0.02) [40]. While women had lower ACS rates than men, sex differences in LOS persisted after adjustment for baseline differences including ACS rate (pinteraction \ 0.03). LOS was similar between sexes with normal CCTA findings (p = 0.11).

Performing CCTA in the ED Patients with a low to intermediate risk of ACS are usually judged clinically according to initial risk assessment data including clinical history, ECG, biomarkers, and TIMI score of 0–2. CCTA may be performed for patients with negative prior stress test or even for those with TIMI score 3–4 and this allows cardiac CTA to be ordered for

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approximately 60–70 % of patients [41, 42]. Previously, the North American Society of Cardiovascular Imaging (NASCI) and the European Society of Cardiac Radiology (ESCR) published interim guidance for utilization of CCTA in the ED [43]. Multiple societies, including the American College of Cardiology and the American College of Radiology, are currently collaborating to create appropriate use criteria for the imaging of ED patients presenting with chest pain (Rybicki, et al. JACR, in press). Patients with a serum creatinine level of greater than 1.5 mg/dL or a severe allergy to iodinated contrast material and those who are pregnant are not eligible for CCTA. Conditions that may be not suitable for CCTA are active asthma or other contraindications to b-blocker administration, irregular heart rhythms such as atrial fibrillation, and weight more than 150 kg, depending on the specific CT technology in use. Heart rate control to \70 bpm is required for high quality CCTA, depending upon the technology in use [44]. A fast-acting b-blocker with a short half-life, typically oral metoprolol, is given at least 1 h before imaging for patients with fast heart rates when there is no contraindications, e.g., active or unstable small airways disease, hypotension, sinus bradycardia, or recent cocaine use. The initial dose is 50–100 mg with additional doses up to 200 mg if needed [45]. IV metoprolol can be administered in the CT suite, and the effect occurs typically in 5–10 min; 5 mg IV can be given initially, with additional doses up to 20 mg if required. For patients with contraindications to b-blockers, calcium channel blockers, preferably diltiazem with the least negative inotropic effect, can be considered as an alternative (initial IV bolus of up to 0.25 mg/kg). Careful monitoring of vital signs is required with IV medication. Utilizing sublingual nitroglycerin before contrast-enhanced images is valuable for improving the contrast-to-noise ratio and vessel visualization by vasodilation of the coronary arteries [46, 47]. Contraindications to nitroglycerin include recent phosphodiesterase inhibitor therapy, commonly used for erectile dysfunction or pulmonary hypertension, hypotension, and critical aortic stenosis.

Alternative tests In patients with low to intermediate pretest probability, other tests with high negative predictive value to rule in or rule out ACS or myocardial infarct (MI) to enable early discharge include rest CMR, echocardiography, and SPECT MPI, though these must be performed while the patient is experiencing chest pain. Resting SPECT MPI with technetium-99m sestamibi is useful in the setting of suspected ACS [48–51] and its use in the ED setting resulted in earlier discharge, lower cost, and fewer

unnecessary admissions [52–54]. Observational studies demonstrated its high negative predictive value to rule out MI or short-term cardiac events. However, a considerable limitation of resting SPECT MPI in ED patients is the limited availability of tracers and interpreting personnel as well as decreased accuracy when not performed during an episode of chest pain. Resting 2-dimensional (2D) echocardiography provides information by evaluating wall motion and ejection fraction rapidly and noninvasively [55, 56]. However, the positive predictive value is only 0–44 % [55, 57, 58] with difficulty distinguishing acute from chronic ischemia. In addition, coronary stenosis cannot be evaluated unless the patient has a wall motion abnormality; as with multiphase CCTA, rest echo may be useful for evaluation nonischemic causes of chest pain. Cardiac MR (CMR) can image coronary anatomy, ventricular function, myocardial perfusion, and myocardial fibrosis/scar. In observational studies, CMR has a sensitivity of 70–85 % to detect ischemic heart disease [59–61] and coronary MR angiography showed 72 % accuracy detecting stenosis. Although a normal CMR is associated with good prognosis and a very low risk, lower spatial resolution and limited availability compared to CCTA limit its clinical application in the ED setting [62]. Conventional catheter angiography, considered a gold standard for diagnosis of coronary artery disease, should be reserved for use as a confirmative test and for intervention for patients with significant stenosis or occlusion who will undergo intervention with certain likelihood rather than for initial evaluation of patients at less than high risk for ACS. Hence, invasive catheterization should be a purely therapeutic option. Coronary artery calcification (CAC) can be seen in most patients with ACS or sudden cardiac death and it has been established as a quantitative marker and indicator of atherosclerosis using the Agatston-score [63–66]. The role of calcium scoring in ED patients with suspected ACS continues to be debated, because it has been shown that calcium scores alone cannot be used to determine risk in patients presenting with potential ACS in the ED and does not add prognostic value for acute events although it may be useful for long-term management of cardiac risk in outpatients. One study showed that a significant number of patients with a zero CAC had CTA findings [67], therefore, CTA is better than CAC scoring in determining the atheroma burden, especially in patients with risk factors. However, higher Agatston score is correlated with increased risk of cardiac events and worse overall prognosis [68]. Framingham risk score combined with coronary calcium score can improve 10-year risk stratification of asymptomatic people, especially those with intermediate risk (Framingham risk score 10–20 %) [69]. Calcium scoring may be recommended in this group to support clinical decision making, particularly whether to start

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aggressive medical therapy. The risk is highest when the Agatston score is above 400. Cardiovascular risk increases proportionally to the amount of calcium and an annual progression of more than 15 % enhances the risk of myocardial infarctions although positive predictive value of CAC progression is low as a marker of risk [70–72]. After myocardial infarction, patients have higher CAC progression than event-free subjects [73]. CAC scoring does not necessarily add relevant information in high or low risk populations [35]. While an unenhanced series may be useful to customize the CCTA scan field and other parameters to reduce doses, the effective dose of a calcium scoring acquisition is now similar to CCTA doses obtained with lower tube voltage technique, and therefore its value in the ED is uncertain. [74].

Stenosis and plaque in ED CCTA studies A study from Miller et al., showed that a diameter stenosis of 25–50 % on cardiac CTA is unlikely to be related to ACS and there is a very low MACE rate (0.5 %) after ED presentation in the following 30 days in those patients [75]. The result is different than the ROMICAT-I trial, in which 2.6 % of ED patients with visible atherosclerosis but less than 50 % stenosis at CCTA experienced ACS, as identified by serial cardiac markers but not by stress testing [28]. All patients had small vessel disease, which is associated with a low incidence of adverse events and mortality, and is not generally amenable to revascularization [76–80]. Nonetheless, small vessels are a limitation of CCTA evaluation [81], and therefore, serial cardiac makers may be beneficial in patients with less than 50 % stenosis on CCTA but further testing such as stress testing is not indicated during the index visit [75]. Short-interval outpatient follow-up is important to establish strategies for primary prevention. The ROMICAT-I trial demonstrated a 77 % sensitivity of a stenosis C50 % for detection of ACS [28]. In the ROMICAT-II study, a stenosis C50 % was detected in 78 % of patients with ACS, which is similar to invasive angiography studies that observed an absence of significant stenosis in 12–14 % of patients with ACS [82]. A clinical registry by van Velzen et al. [83] showed sensitivity, specificity, and positive and negative predictive values to detect significant CAD on CTA were 100, 87, 93, and 100 %, respectively. During mean follow-up of 13.7 months, no cardiovascular events occurred in patients with a normal CTA examination. In patients with nonsignificant CAD on CTA, no cardiac deaths or myocardial infarctions occurred and only 1 patient underwent revascularization due to unstable angina. In patients presenting with acute chest pain, an excellent clinical performance for the non-invasive assessment of significant CAD was

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demonstrated using CTA. Normal or non-significant CAD on CTA predicted a low rate of adverse cardiovascular events and favorable outcome during follow-up [83]. ROMICAT-I demonstrated limited positive value of a stenosis [50 % at CCTA for ACS because matching perfusion abnormalities on SPECT MPI testing were seen in only 46 % of these patients [84]. The optimal management of patients with intermediate lesions at CCTA remains uncertain and may result in an increased frequency of downstream testing and interventions [29–31, 85]. However, patients with significant stenosis on CTA cannot be discharged from the ED after initial troponin and ECG [29– 31, 85]. Coronary artery plaque features may assist in further stratifying risk beyond that obtained using percent stenosis [86–88]. Atherosclerotic lesions can be characterized as calcified, non-calcified and partially calcified (mixed plaques) on CT (Fig. 1). A lack of coronary calcium does not definitely exclude coronary stenosis and a high amount of calcium does not necessarily correlate with angiographic luminal stenosis or vulnerability of plaques [89, 90]. Frequently ACS develops from relatively mild or moderate lesions angiographically in the relatively early stage of atherosclerosis [91–93]. Reported features of high risk plaque are large plaque volume, positive remodeling (Fig. 2), spotty calcium, greater proportion of non-calcified plaque, low mean and minimal CT attenuation value (Hounsfield units, HU), and contrast-enhanced rim seen around the central filling defect (napkin-ring sign) [87, 94– 100], which are similar to high risk findings on intravascular imaging (positive remodeling, larger plaque area, spotty calcium, and large necrotic core) [101, 102] as well as histology. These changes can directly be visualized on CCTA but will not appear on invasive angiography because the vessel wall is invisible [35]. Multi-energy imaging techniques may assess plaque composition [103] and myocardial perfusion providing prognostic information [104]. Dual energy CT may assist in distinguishing densely calcified plaques from other plaque types although further plaque discrimination such as fibrous versus lipid rich plaque is not currently possible [105]. High-risk plaque features have been associated with an increased risk for future cardiovascular events in patients with stable chest pain syndromes [88, 106, 107]. Pflederer et al. showed that these findings are more often seen with culprit lesions in patients with ACS compared with similarly stenotic plaques in patients with stable angina [63]. Studies reported 5–15 % prevalence of high-risk plaque features in the acute chest pain population, patients undergoing invasive coronary angiography, and in nonculprit vessels of patients with ACS (Providing Regional Observations to Study Predictors of Events in the Coronary Tree, PROSPECT trial) [85– 88, 97, 98]. The value of high-risk plaque features for the

Int J Cardiovasc Imaging Fig. 1 Coronary atherosclerotic disease. A Noncalcified plaque in the proximal LAD, which is difficult to differentiate from thrombosis by CT. B Mixed plaque with a small focus of calcification peripherally in the main coronary bifurcation. C Mixed plaque, predominantly noncalcified plaque in the proximal LAD. D Predominantly calcified plaques in the LAD and LCx

diagnosis of ACS in patients with significant stenosis was demonstrated in the ROMICAT-I trial [108]. In the ROMICAT II trial, high-risk plaques on coronary CTA increased the likelihood of ACS independent of stenotic CAD and clinical risk assessment (age, sex, and number of cardiovascular risk factors) in patients presenting to the ED with acute chest pain but negative initial electrocardiogram and troponin [85]. Interestingly, nonalcoholic fatty liver disease (NAFLD) was reported to be associated with advanced high-risk coronary plaque, independent of traditional cardiovascular risk factors and the extent and severity of coronary artery disease [109]. Chronic total occlusions (CTOs) of a coronary artery is defined as the total occlusion of the vessel on invasive angiography with complete interruption of antegrade blood flow and an age of the occlusion C3 months proven by prior angiography or estimated from the clinical course [110]. CCTA can directly visualize morphological characteristics of CTOs, which influence the success rates of PCI for and it is useful to predict the likelihood of successful recanalization [111–113]. CCTA is also useful for planning other interventions by providing evaluation of total lesion length (calcified plus non-calcified plaque), reference segment diameter, angulation of the aortic root, and better visualization of ostial lesions than catheter angiography. This information may assist in selection of appropriate stent length and diameter and result in shortened procedure times and improved outcomes [114, 115].

Blooming artifact from densely calcified plaque limits the accurate evaluation of stenosis and the degree of stenosis is often overestimated [116]. Despite concerns about image quality in patients with calcium score over 400, a recent study showed that only a small percentage of these studies in ED patients are uninterpretable [117]. Newer dual-energy technology using simultaneous or alternating imaging at two different x-ray tube potentials allows improved quantification of calcified plaque by reducing tissue blooming and beam hardening beyond single-energy MDCT [103]. At our institution, we have no threshold set for aborting CCTA, and a radiologist may decide to proceed with scanning based on the likelihood of a diagnostic study even in patients with high calcium score. Evaluation of coronary stent patency is limited due to blooming artifacts similar to dense calcium [118]. However, stents are unlikely to be present in a patient with low to intermediate risk of ACS presenting to the ED.

Non-atherosclerotic causes of chest pain Myocardial bridging, an intramyocardial segment of an epicardial coronary artery coursing within the myocardium, is present in about one-third of adults [119]. In the majority of cases, systolic compression of the tunneled segment remains clinically silent. With provocative testing in

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Int J Cardiovasc Imaging Fig. 2 48 year-old male with intermittent breif chest pain. High cholesterol, nonsmoker, normal troponin. There is long segmental noncalcified plaque with high grade stenosis in the LAD with positive remodeling (A). Stent was placed. Note increased diameter of the stenotic artery (C) compared to the proximal (B) and distal (D) to the stenosis

patients with angiographically normal coronary arteries, myocardial bridges are revealed in B40 % of cases by increasing systolic compression [120]. Rare complications of myocardial bridging include angina, myocardial ischemia, myocardial infarction, left ventricular dysfunction, myocardial stunning, paroxysmal AV blockade, exerciseinduced ventricular tachycardia and sudden cardiac death [121–124]. The likelihood of ischemia also increases with the intramyocardial depth of the tunneled segment, however, there is no consistent association between the patient’s symptom and the length, depth of the tunneled segment or the degree of systolic compression [125, 126]. CCTA is ideal to demonstrate the anatomic course of coronaries and caliber change throughout the cardiac cycle when retrospectively ECG gated CCTA is employed. About 80 % of coronary artery anomalies are benign and incidental findings at the time of catheterization [127]. Although the significance of coronary anomalies is mostly unclear, potentially serious anomalies which include ectopic coronary origin from the pulmonary artery or opposite aortic sinus, single coronary artery, and large coronary fistulae can result in

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angina pectoris, myocardial infarction, heart failure, arrhythmias, and sudden cardiac arrest [127]. Younger patients in their first three decades with isolated coronary artery anomalies are at risk of dying, especially with exercise [128]. Sudden cardiac arrest (SCA) secondary to congenital anomalous coronary artery disease occurs due to insufficient coronary flow by the anomalous LCA to meet elevated left ventricular myocardial metabolic demand, usually during exertion or exercise. In a majority of previously reported cases, SCA was triggered by exertion and most of these patients have a positive exercise stress test [129]. Contributing factors to an increased resistance in the LCA include compression between the great vessels, a slit-like ostium, myocardial bridging, or unfavorable geometry [130]. High risk defects include those involved with the proximal coronary artery or coursing of the anomalous artery between the aorta and pulmonary trunk [128]. Left anterior descending coronary arteries arising from the right cusp with an inter-arterial course have been considered malignant and anomalous coronary origins can be associated with acute chest pain [128].

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Conclusions CCTA has demonstrated its safety and efficiency in the ED setting to evaluate patients with suspected ACS related to coronary atherosclerosis. Evaluation of the association between plaque features and risk of ACS and outcomes is ongoing. Compliance with ethical standards Conflict of interest Nam Ju Lee declares that he has no conflict of interest. Harold Litt grants funding from Siemens Medical Solutions for unrelated CT research.

References 1. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Thom T, WasserthielSmoller S, Wong ND, Wylie-Rosett J (2010) Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation 121(7):e46–e215. doi:10.1161/ CIRCULATIONAHA.109.192667 2. Pitts SR, Niska RW, Xu J, Burt CW (2008) National Hospital Ambulatory Medical Care Survey: 2006 emergency department summary. Natl Health Stat Report 7:1–38 3. McCaig LF, Burt CW (2004) National Hospital Ambulatory Medical Care Survey: 2002 emergency department summary. Adv Data 340:1–34 4. Pozen MW, D’Agostino RB, Selker HP, Sytkowski PA, Hood WB Jr (1984) A predictive instrument to improve coronary-careunit admission practices in acute ischemic heart disease. A prospective multicenter clinical trial. N Engl J Med 310(20):1273–1278. doi:10.1056/NEJM198405173102001 5. Virmani R, Burke AP, Farb A, Kolodgie FD (2006) Pathology of the vulnerable plaque. J Am Coll Cardiol 47(8 Suppl):C13–C18. doi:10.1016/j.jacc.2005.10.065 6. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, Mautner B, Corbalan R, Radley D, Braunwald E (2000) The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA 284(7):835–842 7. Than M, Cullen L, Reid CM, Lim SH, Aldous S, Ardagh MW, Peacock WF, Parsonage WA, Ho HF, Ko HF, Kasliwal RR, Bansal M, Soerianata S, Hu D, Ding R, Hua Q, Seok-Min K, Sritara P, Sae-Lee R, Chiu TF, Tsai KC, Chu FY, Chen WK, Chang WH, Flaws DF, George PM, Richards AM (2011) A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet 377(9771):1077–1084. doi:10. 1016/S0140-6736(11)60310-3 8. Hickam DH, Sox HC Jr, Sox CH (1985) Systematic bias in recording the history in patients with chest pain. J Chronic Dis 38(1):91–100 9. Jayes RL Jr, Beshansky JR, D’Agostino RB, Selker HP (1992) Do patients’ coronary risk factor reports predict acute cardiac ischemia in the emergency department? A multicenter study. J Clin Epidemiol 45(6):621–626

10. Han JH, Lindsell CJ, Storrow AB, Luber S, Hoekstra JW, Hollander JE, Peacock WFT, Pollack CV, Gibler WB (2007) The role of cardiac risk factor burden in diagnosing acute coronary syndromes in the emergency department setting. Ann Emerg Med 49(2):145–152. doi:10.1016/j.annemergmed.2006. 09.027 e141 11. Lloyd-Jones DM, Camargo CA Jr, Lapuerta P, Giugliano RP, O’Donnell CJ (1998) Electrocardiographic and clinical predictors of acute myocardial infarction in patients with unstable angina pectoris. Am J Cardiol 81(10):1182–1186 12. Chase M, Brown AM, Robey JL, Pollack CV Jr, Shofer FS, Hollander JE (2006) Prognostic value of symptoms during a normal or nonspecific electrocardiogram in emergency department patients with potential acute coronary syndrome. Acad Emerg Med 13(10):1034–1039. doi:10.1197/j.aem.2006.06.051 13. Green GB, Beaudreau RW, Chan DW, DeLong D, Kelley CA, Kelen GD (1998) Use of troponin T and creatine kinase-MB subunit levels for risk stratification of emergency department patients with possible myocardial ischemia. Ann Emerg Med 31(1):19–29 14. Newby LK (2001) The emerging role of myoglobin for risk stratification. Am Heart J 142(1):4–6. doi:10.1067/mhj.2001. 116069 15. Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, Biedert S, Schaub N, Buerge C, Potocki M, Noveanu M, Breidthardt T, Twerenbold R, Winkler K, Bingisser R, Mueller C (2009) Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 361(9):858–867. doi:10.1056/NEJMoa0900428 16. Keller T, Zeller T, Peetz D, Tzikas S, Roth A, Czyz E, Bickel C, Baldus S, Warnholtz A, Frohlich M, Sinning CR, Eleftheriadis MS, Wild PS, Schnabel RB, Lubos E, Jachmann N, Genth-Zotz S, Post F, Nicaud V, Tiret L, Lackner KJ, Munzel TF, Blankenberg S (2009) Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med 361(9):868–877. doi:10.1056/NEJMoa0903515 17. Januzzi JL Jr, Bamberg F, Lee H, Truong QA, Nichols JH, Karakas M, Mohammed AA, Schlett CL, Nagurney JT, Hoffmann U, Koenig W (2010) High-sensitivity troponin T concentrations in acute chest pain patients evaluated with cardiac computed tomography. Circulation 121(10):1227–1234. doi:10. 1161/CIRCULATIONAHA.109.893826 18. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J, Levin TN, Pepine CJ, Schaeffer JW, Smith EE 3rd, Steward DE, Theroux P, Gibbons RJ, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Hiratzka LF, Jacobs AK, Smith SC Jr (2002) ACC/ AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation 106(14):1893–1900 19. Pope JH, Aufderheide TP, Ruthazer R, Woolard RH, Feldman JA, Beshansky JR, Griffith JL, Selker HP (2000) Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 342(16):1163–1170. doi:10.1056/ NEJM200004203421603 20. Goldberg A, Litt HI (2010) Evaluation of the patient with acute chest pain. Radiol Clin N Am 48(4):745–755. doi:10.1016/j.rcl. 2010.05.003 21. Lee TH, Rouan GW, Weisberg MC, Brand DA, Acampora D, Stasiulewicz C, Walshon J, Terranova G, Gottlieb L, GoldsteinWayne B et al (1987) Clinical characteristics and natural history of patients with acute myocardial infarction sent home from the emergency room. Am J Cardiol 60(4):219–224

123

Int J Cardiovasc Imaging 22. Fineberg HV, Scadden D, Goldman L (1984) Care of patients with a low probability of acute myocardial infarction. Cost effectiveness of alternatives to coronary-care-unit admission. N Engl J Med 310(20):1301–1307. doi:10.1056/ NEJM198405173102006 23. Rubinshtein R, Halon DA, Gaspar T, Jaffe R, Karkabi B, Flugelman MY, Kogan A, Shapira R, Peled N, Lewis BS (2007) Usefulness of 64-slice cardiac computed tomographic angiography for diagnosing acute coronary syndromes and predicting clinical outcome in emergency department patients with chest pain of uncertain origin. Circulation 115(13):1762–1768. doi:10. 1161/CIRCULATIONAHA.106.618389 24. Goldstein JA, Gallagher MJ, O’Neill WW, Ross MA, O’Neil BJ, Raff GL (2007) A randomized controlled trial of multi-slice coronary computed tomography for evaluation of acute chest pain. J Am Coll Cardiol 49(8):863–871. doi:10.1016/j.jacc.2006.08.064 25. Hoffmann U, Nagurney JT, Moselewski F, Pena A, Ferencik M, Chae CU, Cury RC, Butler J, Abbara S, Brown DF, Manini A, Nichols JH, Achenbach S, Brady TJ (2006) Coronary multidetector computed tomography in the assessment of patients with acute chest pain. Circulation 114(21):2251–2260. doi:10.1161/ CIRCULATIONAHA.106.634808 26. Gallagher MJ, Ross MA, Raff GL, Goldstein JA, O’Neill WW, O’Neil B (2007) The diagnostic accuracy of 64-slice computed tomography coronary angiography compared with stress nuclear imaging in emergency department low-risk chest pain patients. Ann Emerg Med 49(2):125–136. doi:10.1016/j.annemergmed. 2006.06.043 27. Hollander JE, Chang AM, Shofer FS, McCusker CM, Baxt WG, Litt HI (2009) Coronary computed tomographic angiography for rapid discharge of low-risk patients with potential acute coronary syndromes. Ann Emerg Med 53(3):295–304. doi:10.1016/j. annemergmed.2008.09.025 28. Hoffmann U, Bamberg F, Chae CU, Nichols JH, Rogers IS, Seneviratne SK, Truong QA, Cury RC, Abbara S, Shapiro MD, Moloo J, Butler J, Ferencik M, Lee H, Jang IK, Parry BA, Brown DF, Udelson JE, Achenbach S, Brady TJ, Nagurney JT (2009) Coronary computed tomography angiography for early triage of patients with acute chest pain: the ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) trial. J Am Coll Cardiol 53(18):1642–1650. doi:10.1016/j. jacc.2009.01.052 29. Hoffmann U, Truong QA, Schoenfeld DA, Chou ET, Woodard PK, Nagurney JT, Pope JH, Hauser TH, White CS, Weiner SG, Kalanjian S, Mullins ME, Mikati I, Peacock WF, Zakroysky P, Hayden D, Goehler A, Lee H, Gazelle GS, Wiviott SD, Fleg JL, Udelson JE (2012) Coronary CT angiography versus standard evaluation in acute chest pain. N Engl J Med 367(4):299–308. doi:10.1056/NEJMoa1201161 30. Litt HI, Gatsonis C, Snyder B, Singh H, Miller CD, Entrikin DW, Leaming JM, Gavin LJ, Pacella CB, Hollander JE (2012) CT angiography for safe discharge of patients with possible acute coronary syndromes. N Engl J Med 366(15):1393–1403. doi:10.1056/NEJMoa1201163 31. Goldstein JA, Chinnaiyan KM, Abidov A, Achenbach S, Berman DS, Hayes SW, Hoffmann U, Lesser JR, Mikati IA, O’Neil BJ, Shaw LJ, Shen MY, Valeti US, Raff GL (2011) The CTSTAT (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment) trial. J Am Coll Cardiol 58(14):1414–1422. doi:10.1016/j.jacc. 2011.03.068 32. Cook TS, Galperin-Aizenberg M, Litt HI (2013) Coronary and cardiac computed tomography in the emergency room: current status and future directions. J Thorac Imaging 28(4):204–216. doi:10.1097/RTI.0b013e3182956bbf

123

33. Cury RC, Feuchtner GM, Batlle JC, Pena CS, Janowitz W, Katzen BT, Ziffer JA (2013) Triage of patients presenting with chest pain to the emergency department: implementation of coronary CT angiography in a large urban health care system. AJR Am J Roentgenol 200(1):57–65. doi:10.2214/AJR.12.8808 34. Hoffmann U, Pena AJ, Moselewski F, Ferencik M, Abbara S, Cury RC, Chae CU, Nagurney JT (2006) MDCT in early triage of patients with acute chest pain. AJR Am J Roentgenol 187(5):1240–1247. doi:10.2214/AJR.05.2240 35. Eckert J, Schmidt M, Magedanz A, Voigtlander T, Schmermund A (2015) Coronary CT angiography in managing atherosclerosis. Int J Mol Sci 16(2):3740–3756. doi:10.3390/ijms16023740 36. Fazel P, Peterman MA, Schussler JM (2009) Three-year outcomes and cost analysis in patients receiving 64-slice computed tomographic coronary angiography for chest pain. Am J Cardiol 104(4):498–500. doi:10.1016/j.amjcard.2009.04.011 37. Romero J, Husain SA, Holmes AA, Kelesidis I, Chavez P, Mojadidi MK, Levsky JM, Wever-Pinzon O, Taub C, Makani H, Travin MI, Pina IL, Garcia MJ (2015) Non-invasive assessment of low risk acute chest pain in the emergency department: a comparative meta-analysis of prospective studies. Int J Cardiol 187:565–580. doi:10.1016/j.ijcard.2015.01.032 38. Beigel R, Oieru D, Goitein O, Chouraqui P, Konen E, Shamiss A, Hod H, Or J, Matetzky S (2009) Usefulness of routine use of multidetector coronary computed tomography in the ‘‘fast track’’ evaluation of patients with acute chest pain. Am J Cardiol 103(11):1481–1486. doi:10.1016/j.amjcard.2009.02.009 39. Rubinshtein R, Halon DA, Gaspar T, Jaffe R, Goldstein J, Karkabi B, Flugelman MY, Kogan A, Shapira R, Peled N, Lewis BS (2007) Impact of 64-slice cardiac computed tomographic angiography on clinical decision-making in emergency department patients with chest pain of possible myocardial ischemic origin. Am J Cardiol 100(10):1522–1526. doi:10.1016/j.amj card.2007.06.052 40. Truong QA, Hayden D, Woodard PK, Kirby R, Chou ET, Nagurney JT, Wiviott SD, Fleg JL, Schoenfeld DA, Udelson JE, Hoffmann U (2013) Sex differences in the effectiveness of early coronary computed tomographic angiography compared with standard emergency department evaluation for acute chest pain: the rule-out myocardial infarction with Computer-Assisted Tomography (ROMICAT)-II Trial. Circulation 127(25):2494–2502. doi:10.1161/CIRCULATIONAHA.113. 001736 41. Galperin-Aizenberg M, Cook TS, Hollander JE, Litt HI (2015) Cardiac CT angiography in the emergency department. AJR Am J Roentgenol 204(3):463–474. doi:10.2214/AJR.14.12657 42. Hollander JE, Chang AM, Shofer FS, Collin MJ, Walsh KM, McCusker CM, Baxt WG, Litt HI (2009) One-year outcomes following coronary computerized tomographic angiography for evaluation of emergency department patients with potential acute coronary syndrome. Acad Emerg Med 16(8):693–698. doi:10.1111/j.1553-2712.2009.00459.x 43. Stillman AE, Oudkerk M, Ackerman M, Becker CR, Buszman PE, de Feyter PJ, Hoffmann U, Keadey MT, Marano R, Lipton MJ, Raff GL, Reddy GP, Rees MR, Rubin GD, Schoepf UJ, Tarulli G, van Beek EJ, Wexler L, White CS (2007) Use of multidetector computed tomography for the assessment of acute chest pain: a consensus statement of the North American Society of Cardiac Imaging and the European Society of Cardiac Radiology. Int J Cardiovasc Imaging 23(4):415–427. doi:10. 1007/s10554-007-9226-8 44. Shim SS, Kim Y, Lim SM (2005) Improvement of image quality with beta-blocker premedication on ECG-gated 16-MDCT coronary angiography. AJR Am J Roentgenol 184(2):649–654. doi:10.2214/ajr.184.2.01840649

Int J Cardiovasc Imaging 45. Abbara S, Arbab-Zadeh A, Callister TQ, Desai MY, Mamuya W, Thomson L, Weigold WG (2009) SCCT guidelines for performance of coronary computed tomographic angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee. J Cardiovasc Comput Tomogr 3(3):190–204. doi:10.1016/j.jcct.2009.03.004 46. Dewey M, Hoffmann H, Hamm B (2006) Multislice CT coronary angiography: effect of sublingual nitroglycerine on the diameter of coronary arteries. Rofo 178(6):600–604. doi:10. 1055/s-2006-926755 47. Decramer I, Vanhoenacker PK, Sarno G, Van Hoe L, Bladt O, Wijns W, Parizel PM (2008) Effects of sublingual nitroglycerin on coronary lumen diameter and number of visualized septal branches on 64-MDCT angiography. AJR Am J Roentgenol 190(1):219–225. doi:10.2214/AJR.07.2648 48. Hilton TC, Fulmer H, Abuan T, Thompson RC, Stowers SA (1996) Ninety-day follow-up of patients in the emergency department with chest pain who undergo initial single-photon emission computed tomographic perfusion scintigraphy with technetium 99m-labeled sestamibi. J Nucl Cardiol 3(4):308–311 49. Conti A, Gallini C, Costanzo E, Ferri P, Matteini M, Paladini B, Francois C, Grifoni S, Migliorini A, Antoniucci D, Pieroni C, Berni G (2001) Early detection of myocardial ischaemia in the emergency department by rest or exercise (99m)Tc tracer myocardial SPET in patients with chest pain and non-diagnostic ECG. Eur J Nucl Med 28(12):1806–1810. doi:10.1007/ s002590100647 50. Schaeffer MW, Brennan TD, Hughes JA, Gibler WB, Gerson MC (2007) Resting radionuclide myocardial perfusion imaging in a chest pain center including an overnight delayed image acquisition protocol. J Nucl Med Technol 35(4):242–245. doi:10.2967/jnmt.107.042796 51. Kontos MC, Haney A, Ornato JP, Jesse RL, Tatum JL (2008) Value of simultaneous functional assessment in association with acute rest perfusion imaging for predicting short- and long-term outcomes in emergency department patients with chest pain. J Nucl Cardiol 15(6):774–782. doi:10.1007/BF03007358 52. Radensky PW, Hilton TC, Fulmer H, McLaughlin BA, Stowers SA (1997) Potential cost effectiveness of initial myocardial perfusion imaging for assessment of emergency department patients with chest pain. Am J Cardiol 79(5):595–599 53. Udelson JE, Beshansky JR, Ballin DS, Feldman JA, Griffith JL, Handler J, Heller GV, Hendel RC, Pope JH, Ruthazer R, Spiegler EJ, Woolard RH, Selker HP (2002) Myocardial perfusion imaging for evaluation and triage of patients with suspected acute cardiac ischemia: a randomized controlled trial. JAMA 288(21):2693–2700 54. Kontos MC, Schmidt KL, McCue M, Rossiter LF, Jurgensen M, Nicholson CS, Jesse RL, Ornato JP, Tatum JL (2003) A comprehensive strategy for the evaluation and triage of the chest pain patient: a cost comparison study. J Nucl Cardiol 10(3):284–290 55. Kontos MC, Arrowood JA, Paulsen WH, Nixon JV (1998) Early echocardiography can predict cardiac events in emergency department patients with chest pain. Ann Emerg Med 31(5):550–557 56. Muscholl MW, Oswald M, Mayer C, von Scheidt W (2002) Prognostic value of 2D echocardiography in patients presenting with acute chest pain and non-diagnostic ECG for ST-elevation myocardial infarction. Int J Cardiol 84(2–3):217–225 57. Lim SH, Sayre MR, Gibler WB (2003) 2-D echocardiography prediction of adverse events in ED patients with chest pain. Am J Emerg Med 21(2):106–110. doi:10.1053/ajem.2003.50036 58. Weston P, Alexander JH, Patel MR, Maynard C, Crawford L, Wagner GS (2004) Hand-held echocardiographic examination of patients with symptoms of acute coronary syndromes in the

59.

60.

61.

62.

63.

64.

65.

66.

67.

68.

69.

emergency department: the 30-day outcome associated with normal left ventricular wall motion. Am Heart J 148(6):1096–1101. doi:10.1016/j.ahj.2004.05.026 Kwong RY, Schussheim AE, Rekhraj S, Aletras AH, Geller N, Davis J, Christian TF, Balaban RS, Arai AE (2003) Detecting acute coronary syndrome in the emergency department with cardiac magnetic resonance imaging. Circulation 107(4):531–537 Ingkanisorn WP, Kwong RY, Bohme NS, Geller NL, Rhoads KL, Dyke CK, Paterson DI, Syed MA, Aletras AH, Arai AE (2006) Prognosis of negative adenosine stress magnetic resonance in patients presenting to an emergency department with chest pain. J Am Coll Cardiol 47(7):1427–1432. doi:10.1016/j. jacc.2005.11.059 Cury RC, Shash K, Nagurney JT, Rosito G, Shapiro MD, Nomura CH, Abbara S, Bamberg F, Ferencik M, Schmidt EJ, Brown DF, Hoffmann U, Brady TJ (2008) Cardiac magnetic resonance with T2-weighted imaging improves detection of patients with acute coronary syndrome in the emergency department. Circulation 118(8):837–844. doi:10.1161/CIRCU LATIONAHA.107.740597 Kim WY, Danias PG, Stuber M, Flamm SD, Plein S, Nagel E, Langerak SE, Weber OM, Pedersen EM, Schmidt M, Botnar RM, Manning WJ (2001) Coronary magnetic resonance angiography for the detection of coronary stenoses. N Engl J Med 345(26):1863–1869. doi:10.1056/NEJMoa010866 Pohle K, Ropers D, Maffert R, Geitner P, Moshage W, Regenfus M, Kusus M, Daniel WG, Achenbach S (2003) Coronary calcifications in young patients with first, unheralded myocardial infarction: a risk factor matched analysis by electron beam tomography. Heart 89(6):625–628 Schmermund A, Schwartz RS, Adamzik M, Sangiorgi G, Pfeifer EA, Rumberger JA, Burke AP, Farb A, Virmani R (2001) Coronary atherosclerosis in unheralded sudden coronary death under age 50: histo-pathologic comparison with ‘healthy’ subjects dying out of hospital. Atherosclerosis 155(2):499–508 Budoff MJ, Achenbach S, Blumenthal RS, Carr JJ, Goldin JG, Greenland P, Guerci AD, Lima JA, Rader DJ, Rubin GD, Shaw LJ, Wiegers SE (2006) Assessment of coronary artery disease by cardiac computed tomography: a scientific statement from the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology. Circulation 114(16):1761–1791. doi:10. 1161/CIRCULATIONAHA.106.178458 O’Rourke RA, Brundage BH, Froelicher VF, Greenland P, Grundy SM, Hachamovitch R, Pohost GM, Shaw LJ, Weintraub WS, Winters WL Jr (2000) American College of Cardiology/ American Heart Association Expert Consensus Document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. J Am Coll Cardiol 36(1):326–340 Ergun E, Kosar P, Ozturk C, Basbay E, Koc F, Kosar U (2011) Prevalence and extent of coronary artery disease determined by 64-slice CTA in patients with zero coronary calcium score. Int J Cardiovasc Imaging 27(3):451–458. doi:10.1007/s10554-0109681-5 Sarwar A, Shaw LJ, Shapiro MD, Blankstein R, Hoffmann U, Cury RC, Abbara S, Brady TJ, Budoff MJ, Blumenthal RS, Nasir K (2009) Diagnostic and prognostic value of absence of coronary artery calcification. JACC Cardiovasc Imaging 2(6):675–688. doi:10.1016/j.jcmg.2008.12.031 Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC (2004) Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA 291(2):210–215. doi:10.1001/jama.291.2.210

123

Int J Cardiovasc Imaging 70. Raggi P, Cooil B, Ratti C, Callister TQ, Budoff M (2005) Progression of coronary artery calcium and occurrence of myocardial infarction in patients with and without diabetes mellitus. Hypertension 46(1):238–243. doi:10.1161/01.HYP. 0000164575.16609.02 71. Greenland P, Bonow RO, Brundage BH, Budoff MJ, Eisenberg MJ, Grundy SM, Lauer MS, Post WS, Raggi P, Redberg RF, Rodgers GP, Shaw LJ, Taylor AJ, Weintraub WS (2007) ACCF/ AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol 49(3):378–402. doi:10.1016/j.jacc.2006.10.001 72. Budoff MJ, Hokanson JE, Nasir K, Shaw LJ, Kinney GL, Chow D, Demoss D, Nuguri V, Nabavi V, Ratakonda R, Berman DS, Raggi P (2010) Progression of coronary artery calcium predicts all-cause mortality. JACC Cardiovasc Imaging 3(12):1229–1236. doi:10.1016/j.jcmg.2010.08.018 73. Raggi P, Callister TQ, Shaw LJ (2004) Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy. Arterioscler Thromb Vasc Biol 24(7):1272–1277. doi:10.1161/01.ATV.0000127024. 40516.ef 74. Herzog C, Britten M, Balzer JO, Mack MG, Zangos S, Ackermann H, Schaechinger V, Schaller S, Flohr T, Vogl TJ (2004) Multidetector-row cardiac CT: diagnostic value of calcium scoring and CT coronary angiography in patients with symptomatic, but atypical, chest pain. Eur Radiol 14(2):169–177. doi:10.1007/s00330-003-2197-9 75. Miller CD, Litt HI, Askew K, Entrikin D, Carr JJ, Chang AM, Kilkenny J, Weisenthal B, Hollander JE (2012) Implications of 25 % to 50 % coronary stenosis with cardiac computed tomographic angiography in ED patients. Am J Emerg Med 30(4):597–605. doi:10.1016/j.ajem.2011.02.015 76. Wu E, Ortiz JT, Tejedor P, Lee DC, Bucciarelli-Ducci C, Kansal P, Carr JC, Holly TA, Lloyd-Jones D, Klocke FJ, Bonow RO (2008) Infarct size by contrast enhanced cardiac magnetic resonance is a stronger predictor of outcomes than left ventricular ejection fraction or end-systolic volume index: prospective cohort study. Heart 94(6):730–736. doi:10.1136/hrt.2007. 122622 77. Miller TD, Christian TF, Hopfenspirger MR, Hodge DO, Gersh BJ, Gibbons RJ (1995) Infarct size after acute myocardial infarction measured by quantitative tomographic 99mTc sestamibi imaging predicts subsequent mortality. Circulation 92(3):334–341 78. Elezi S, Kastrati A, Neumann FJ, Hadamitzky M, Dirschinger J, Schomig A (1998) Vessel size and long-term outcome after coronary stent placement. Circulation 98(18):1875–1880 79. Togni M, Eber S, Widmer J, Billinger M, Wenaweser P, Cook S, Vogel R, Seiler C, Eberli FR, Maier W, Corti R, Roffi M, Luscher TF, Garachemani A, Hess OM, Wandel S, Meier B, Juni P, Windecker S (2007) Impact of vessel size on outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents: a subgroup analysis of the SIRTAX trial. J Am Coll Cardiol 50(12):1123–1131. doi:10.1016/j.jacc.2007.06.015 80. Schunkert H, Harrell L, Palacios IF (1999) Implications of small reference vessel diameter in patients undergoing percutaneous coronary revascularization. J Am Coll Cardiol 34(1):40–48

123

81. Herzog C, Zwerner PL, Doll JR, Nielsen CD, Nguyen SA, Savino G, Vogl TJ, Costello P, Schoepf UJ (2007) Significant coronary artery stenosis: comparison on per-patient and pervessel or per-segment basis at 64-section CT angiography. Radiology 244(1):112–120. doi:10.1148/radiol.2441060332 82. Roe MT, Harrington RA, Prosper DM, Pieper KS, Bhatt DL, Lincoff AM, Simoons ML, Akkerhuis M, Ohman EM, Kitt MM, Vahanian A, Ruzyllo W, Karsch K, Califf RM, Topol EJ (2000) Clinical and therapeutic profile of patients presenting with acute coronary syndromes who do not have significant coronary artery disease.The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators. Circulation 102(10):1101–1106 83. van Velzen JE, de Graaf FR, Kroft LJ, de Roos A, Reiber JH, Bax JJ, Jukema JW, Schuijf JD, Schalij MJ, van der Wall EE (2012) Performance and efficacy of 320-row computed tomography coronary angiography in patients presenting with acute chest pain: results from a clinical registry. Int J Cardiovasc Imaging 28(4):865–876. doi:10.1007/s10554-011-9889-z 84. Ahmed W, Schlett CL, Uthamalingam S, Truong QA, Koenig W, Rogers IS, Blankstein R, Nagurney JT, Tawakol A, Januzzi JL, Hoffmann U (2013) Single resting hsTnT level predicts abnormal myocardial stress test in acute chest pain patients with normal initial standard troponin. JACC Cardiovasc Imaging 6(1):72–82. doi:10.1016/j.jcmg.2012.08.014 85. Puchner SB, Liu T, Mayrhofer T, Truong QA, Lee H, Fleg JL, Nagurney JT, Udelson JE, Hoffmann U, Ferencik M (2014) High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial. J Am Coll Cardiol 64(7):684–692. doi:10.1016/j.jacc.2014.05.039 86. Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, Mehran R, McPherson J, Farhat N, Marso SP, Parise H, Templin B, White R, Zhang Z, Serruys PW (2011) A prospective natural-history study of coronary atherosclerosis. N Engl J Med 364(3):226–235. doi:10.1056/NEJMoa1002358 87. Pflederer T, Marwan M, Schepis T, Ropers D, Seltmann M, Muschiol G, Daniel WG, Achenbach S (2010) Characterization of culprit lesions in acute coronary syndromes using coronary dual-source CT angiography. Atherosclerosis 211(2):437–444. doi:10.1016/j.atherosclerosis.2010.02.001 88. Motoyama S, Sarai M, Harigaya H, Anno H, Inoue K, Hara T, Naruse H, Ishii J, Hishida H, Wong ND, Virmani R, Kondo T, Ozaki Y, Narula J (2009) Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol 54(1):49–57. doi:10.1016/j.jacc.2009.02.068 89. Marwan M, Ropers D, Pflederer T, Daniel WG, Achenbach S (2009) Clinical characteristics of patients with obstructive coronary lesions in the absence of coronary calcification: an evaluation by coronary CT angiography. Heart 95(13):1056–1060. doi:10.1136/hrt.2008.153353 90. Davies MJ (1997) The composition of coronary-artery plaques. N Engl J Med 336(18):1312–1314. doi:10.1056/ NEJM199705013361809 91. Nakamura M, Nishikawa H, Mukai S, Setsuda M, Nakajima K, Tamada H, Suzuki H, Ohnishi T, Kakuta Y, Nakano T, Yeung AC (2001) Impact of coronary artery remodeling on clinical presentation of coronary artery disease: an intravascular ultrasound study. J Am Coll Cardiol 37(1):63–69 92. Ambrose JA, Tannenbaum MA, Alexopoulos D, HjemdahlMonsen CE, Leavy J, Weiss M, Borrico S, Gorlin R, Fuster V (1988) Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 12(1):56–62

Int J Cardiovasc Imaging 93. Giroud D, Li JM, Urban P, Meier B, Rutishauer W (1992) Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography. Am J Cardiol 69(8):729–732 94. Hoffmann U, Moselewski F, Nieman K, Jang IK, Ferencik M, Rahman AM, Cury RC, Abbara S, Joneidi-Jafari H, Achenbach S, Brady TJ (2006) Noninvasive assessment of plaque morphology and composition in culprit and stable lesions in acute coronary syndrome and stable lesions in stable angina by multidetector computed tomography. J Am Coll Cardiol 47(8):1655–1662. doi:10.1016/j.jacc.2006.01.041 95. Gauss S, Achenbach S, Pflederer T, Schuhback A, Daniel WG, Marwan M (2011) Assessment of coronary artery remodelling by dual-source CT: a head-to-head comparison with intravascular ultrasound. Heart 97(12):991–997. doi:10.1136/hrt.2011. 223024 96. Motoyama S, Kondo T, Sarai M, Sugiura A, Harigaya H, Sato T, Inoue K, Okumura M, Ishii J, Anno H, Virmani R, Ozaki Y, Hishida H, Narula J (2007) Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol 50(4):319–326. doi:10.1016/j.jacc.2007.03. 044 97. Kashiwagi M, Tanaka A, Kitabata H, Tsujioka H, Kataiwa H, Komukai K, Tanimoto T, Takemoto K, Takarada S, Kubo T, Hirata K, Nakamura N, Mizukoshi M, Imanishi T, Akasaka T (2009) Feasibility of noninvasive assessment of thin-cap fibroatheroma by multidetector computed tomography. JACC Cardiovasc Imaging 2(12):1412–1419. doi:10.1016/j.jcmg.2009. 09.012 98. Kitagawa T, Yamamoto H, Horiguchi J, Ohhashi N, Tadehara F, Shokawa T, Dohi Y, Kunita E, Utsunomiya H, Kohno N, Kihara Y (2009) Characterization of noncalcified coronary plaques and identification of culprit lesions in patients with acute coronary syndrome by 64-slice computed tomography. JACC Cardiovasc Imaging 2(2):153–160. doi:10.1016/j.jcmg.2008.09.015 99. Obaid DR, Calvert PA, Gopalan D, Parker RA, Hoole SP, West NE, Goddard M, Rudd JH, Bennett MR (2013) Atherosclerotic plaque composition and classification identified by coronary computed tomography: assessment of computed tomographygenerated plaque maps compared with virtual histology intravascular ultrasound and histology. Circ Cardiovasc Imaging 6(5):655–664. doi:10.1161/CIRCIMAGING.112.000250 100. Pundziute G, Schuijf JD, Jukema JW, Decramer I, Sarno G, Vanhoenacker PK, Reiber JH, Schalij MJ, Wijns W, Bax JJ (2008) Head-to-head comparison of coronary plaque evaluation between multislice computed tomography and intravascular ultrasound radiofrequency data analysis. JACC Cardiovasc Interv 1(2):176–182. doi:10.1016/j.jcin.2008.01.007 101. Hong MK, Mintz GS, Lee CW, Suh J, Kim JH, Park DW, Lee SW, Kim YH, Cheong SS, Kim JJ, Park SW, Park SJ (2007) Comparison of virtual histology to intravascular ultrasound of culprit coronary lesions in acute coronary syndrome and target coronary lesions in stable angina pectoris. Am J Cardiol 100(6):953–959. doi:10.1016/j.amjcard.2007.04.034 102. Pundziute G, Schuijf JD, Jukema JW, Decramer I, Sarno G, Vanhoenacker PK, Boersma E, Reiber JH, Schalij MJ, Wijns W, Bax JJ (2008) Evaluation of plaque characteristics in acute coronary syndromes: non-invasive assessment with multi-slice computed tomography and invasive evaluation with intravascular ultrasound radiofrequency data analysis. Eur Heart J 29(19):2373–2381. doi:10.1093/eurheartj/ehn356 103. Boll DT, Merkle EM, Paulson EK, Mirza RA, Fleiter TR (2008) Calcified vascular plaque specimens: assessment with cardiac dual-energy multidetector CT in anthropomorphically moving heart phantom. Radiology 249(1):119–126. doi:10.1148/radiol. 2483071576

104. Ruzsics B, Lee H, Zwerner PL, Gebregziabher M, Costello P, Schoepf UJ (2008) Dual-energy CT of the heart for diagnosing coronary artery stenosis and myocardial ischemia-initial experience. Eur Radiol 18(11):2414–2424. doi:10.1007/s00330-0081022-x 105. Barreto M, Schoenhagen P, Nair A, Amatangelo S, Milite M, Obuchowski NA, Lieber ML, Halliburton SS (2008) Potential of dual-energy computed tomography to characterize atherosclerotic plaque: ex vivo assessment of human coronary arteries in comparison to histology. J Cardiovasc Comput Tomogr 2(4):234–242. doi:10.1016/j.jcct.2008.05.146 106. Yamamoto H, Kitagawa T, Ohashi N, Utsunomiya H, Kunita E, Oka T, Urabe Y, Tsushima H, Awai K, Kihara Y (2013) Noncalcified atherosclerotic lesions with vulnerable characteristics detected by coronary CT angiography and future coronary events. J Cardiovasc Comput Tomogr 7(3):192–199. doi:10. 1016/j.jcct.2013.05.008 107. Versteylen MO, Kietselaer BL, Dagnelie PC, Joosen IA, Dedic A, Raaijmakers RH, Wildberger JE, Nieman K, Crijns HJ, Niessen WJ, Daemen MJ, Hofstra L (2013) Additive value of semiautomated quantification of coronary artery disease using cardiac computed tomographic angiography to predict future acute coronary syndrome. J Am Coll Cardiol 61(22):2296–2305. doi:10.1016/j.jacc.2013.02.065 108. Ferencik M, Schlett CL, Ghoshhajra BB, Kriegel MF, Joshi SB, Maurovich-Horvat P, Rogers IS, Banerji D, Bamberg F, Truong QA, Brady TJ, Nagurney JT, Hoffmann U (2012) A computed tomography-based coronary lesion score to predict acute coronary syndrome among patients with acute chest pain and significant coronary stenosis on coronary computed tomographic angiogram. Am J Cardiol 110(2):183–189. doi:10.1016/j.amj card.2012.02.066 109. Puchner SB, Lu MT, Mayrhofer T, Liu T, Pursnani A, Ghoshhajra BB, Truong QA, Wiviott SD, Fleg JL, Hoffmann U, Ferencik M (2015) High-risk coronary plaque at coronary CT angiography is associated with nonalcoholic fatty liver disease, independent of coronary plaque and stenosis burden: results from the ROMICAT II trial. Radiology 274(3):693–701. doi:10. 1148/radiol.14140933 110. Sianos G, Werner GS, Galassi AR, Papafaklis MI, Escaned J, Hildick-Smith D, Christiansen EH, Gershlick A, Carlino M, Karlas A, Konstantinidis NV, Tomasello SD, Di Mario C, Reifart N (2012) Recanalisation of chronic total coronary occlusions: 2012 consensus document from the EuroCTO club. EuroIntervention 8(1):139–145. doi:10.4244/EIJV8I1A21 111. Magro M, Schultz C, Simsek C, Garcia-Garcia HM, Regar E, Nieman K, Mollet N, Serruys PW, van Geuns RJ (2010) Computed tomography as a tool for percutaneous coronary intervention of chronic total occlusions. EuroIntervention 6(Suppl G):G123–G131 112. Soon KH, Cox N, Wong A, Chaitowitz I, Macgregor L, Santos PT, Selvanayagam JB, Farouque HM, Rametta S, Bell KW, Lim YL (2007) CT coronary angiography predicts the outcome of percutaneous coronary intervention of chronic total occlusion. J Interv Cardiol 20(5):359–366. doi:10.1111/j.1540-8183.2007. 00275.x 113. Martin-Yuste V, Barros A, Leta R, Ferreira I, Brugaletta S, Pujadas S, Carreras F, Pons G, Cinca J, Sabate M (2012) Factors determining success in percutaneous revascularization of chronic total coronary occlusion: multidetector computed tomography analysis. Rev Esp Cardiol (Engl Ed) 65(4):334–340. doi:10.1016/j.recesp.2011.11.009 114. Hecht HS (2008) Applications of multislice coronary computed tomographic angiography to percutaneous coronary intervention: How did we ever do without it? Catheter Cardiovasc Interv 71(4):490–503

123

Int J Cardiovasc Imaging 115. Rodriguez-Granillo GA, Rosales MA, Llaurado C, Ivanc TB, Rodriguez AE (2011) Guidance of percutaneous coronary interventions by multidetector row computed tomography coronary angiography. EuroIntervention 6(6):773–778 116. Lau GT, Ridley LJ, Schieb MC, Brieger DB, Freedman SB, Wong LA, Lo SK, Kritharides L (2005) Coronary artery stenoses: detection with calcium scoring, CT angiography, and both methods combined. Radiology 235(2):415–422. doi:10. 1148/radiol.2352031813 117. Chang AM, Le J, Matsuura AC, Litt HI, Hollander JE (2011) Does coronary artery calcium scoring add to the predictive value of coronary computed tomography angiography for adverse cardiovascular events in low-risk chest pain patients? Acad Emerg Med 18(10):1065–1071. doi:10.1111/j.1553-2712.2011. 01173.x 118. Boll DT, Merkle EM, Paulson EK, Fleiter TR (2008) Coronary stent patency: dual-energy multidetector CT assessment in a pilot study with anthropomorphic phantom. Radiology 247(3):687–695. doi:10.1148/radiol.2473070849 119. Mohlenkamp S, Hort W, Ge J, Erbel R (2002) Update on myocardial bridging. Circulation 106(20):2616–2622 120. Iversen S, Hake U, Mayer E, Erbel R, Diefenbach C, Oelert H (1992) Surgical treatment of myocardial bridging causing coronary artery obstruction. Scand J Thorac Cardiovasc Surg 26(2):107–111 121. Noble J, Bourassa MG, Petitclerc R, Dyrda I (1976) Myocardial bridging and milking effect of the left anterior descending coronary artery: Normal variant or obstruction? Am J Cardiol 37(7):993–999 122. Lee SS, Wu TL (1972) The role of the mural coronary artery in prevention of coronary atherosclerosis. Arch Pathol 93(1):32–35

123

123. Endo M, Lee YW, Hayashi H, Wada J (1978) Angiographic evidence of myocardial squeezing accompanying tachyarrhythmia as a possible cause of myocardial infarction. Chest 73(3):431–433 124. Tauth J, Sullebarger T (1997) Myocardial infarction associated with myocardial bridging: case history and review of the literature. Cathet Cardiovasc Diagn 40(4):364–367 125. Ferreira AG Jr, Trotter SE, Konig B Jr, Decourt LV, Fox K, Olsen EG (1991) Myocardial bridges: morphological and functional aspects. Br Heart J 66(5):364–367 126. Roberts WC, Dicicco BS, Waller BF, Kishel JC, McManus BM, Dawson SL, Hunsaker JC 3rd, Luke JL (1982) Origin of the left main from the right coronary artery or from the right aortic sinus with intramyocardial tunneling to the left side of the heart via the ventricular septum. The case against clinical significance of myocardial bridge or coronary tunnel. Am Heart J 104(2 Pt 1):303–305 127. Yamanaka O, Hobbs RE (1990) Coronary artery anomalies in 126,595 patients undergoing coronary arteriography. Cathet Cardiovasc Diagn 21(1):28–40 128. Taylor AJ, Rogan KM, Virmani R (1992) Sudden cardiac death associated with isolated congenital coronary artery anomalies. J Am Coll Cardiol 20(3):640–647 129. Basso C, Maron BJ, Corrado D, Thiene G (2000) Clinical profile of congenital coronary artery anomalies with origin from the wrong aortic sinus leading to sudden death in young competitive athletes. J Am Coll Cardiol 35(6):1493–1501 130. Bartoli CR, Wead WB, Giridharan GA, Prabhu SD, Koenig SC, Dowling RD (2012) Mechanism of myocardial ischemia with an anomalous left coronary artery from the right sinus of Valsalva. J Thorac Cardiovasc Surg 144(2):402–408. doi:10.1016/j.jtcvs. 2011.08.056