Coronary CT Angiography in Acute Chest Pain is a Cost Effective Risk Stratification Strategy
Coronary CT Angiography in Acute Chest Pain is a Cost Effective Risk Stratification Strategy
This study will evaluate the impact of adding coronary computed tomographic angiography (CTA)
 on health care costs for diagnosing patients with acute chest pain.
Background and Significance

 Standard-of-care risk-stratification algorithm (SOC):

 In the past 20 years since Goldman et al4 described a clinical algorithm to predict MI in ED
 patients, the clinical ability to decrease the false-negative rate for myocardial events has
 not improved. Hence, the emergency physician (EP) is compelled to admit to the hospital the
 majority of patients who present with acute chest pain for further observation and
 investigation due to inconclusive evidence of ACS or MI during the index ED visit;
 false-negatives are still sent home with CAD; and false-positives are admitted without CAD;
 accounting for a significant consumption of resources every year in the US1.

 The current state of the art for EPs includes clinical data, electrocardiograms (ECGs) and
 cardiac biomarkers5 (Fig. 1). The limitations of using the Goldman prediction rule and the
 ECG is that they are insensitive indicators of myocardial injury in patients with MI4-9. The
 sensitivity and specificity of cardiac biomarkers is proportional to the time from onset of
 chest pain. Cardiac troponin begins to rise within 3-4 hours after the onset of myocardial
 injury and may remain increased for up to 4-7 days for cTnI and 10-14 days for cTnT10. There
 is enthusiasm for myoglobin as an early marker; however, myoglobin is non-specific11-16 In ED
 based trials; cardiac biomarkers have performed well but have not changed the cost and
 admission rate (false-positives). In 1999, McCord et al9 published a single center
 prospective cohort study that examined point-of-care cardiac biomarkers during the first 90
 minutes and if they could help to exclude AMI in the ED chest pain patient. The post-hoc
 analysis and resultant negative predictive value (NPV) was 98 to 99% at time 0 minutes, 90
 minutes, and 3-hours with various combinations of the three biomarkers including Myoglobin,
 Troponin I and CK-MB. These results demonstrated a consistency of negative predictive values
 with both combinations of CK-MB with myoglobin equal to Troponin with myoglobin. In 2004,
 Fesmire, et al17 reported in another prospective ED cohort study that a 2-hour delta CK-MB
 level outperforms myoglobin level in the early identification and exclusion of acute MI and
 can effectively risk-stratify patients for 30-day adverse outcomes. In both of these ED based
 trials, despite the impressive post-hoc NPV in the McCord et al trial, the cost and admission
 rate (false-positives) remains the same since the rule-out MI process requires admission and
 24 hours of serial cardiac enzyme testing.

 Patients presenting to the ED with acute chest pain undergo the SOC risk-stratification
 algorithm to determine the etiology of the complaint (Figure 1). The SOC risk-stratification
 initially includes the clinical assessment and an ECG. If the ECG reveals an ST elevation MI
 (STEMI) the patient is treated immediately in the cardiac catheterization laboratory. If the
 ECG is normal or indeterminate, and there are clinical risk factors, the patient will undergo
 cardiac biomarker testing. If the cardiac biomarkers are negative, the patient will then be
 admitted to the hospital for further testing. If the cardiac biomarkers are positive, the
 patient will be admitted to the cardiac care unit (CCU) for further testing. If the clinical
 risk factors are absent and the ECG is normal, the patient may be discharged without further
 testing4-8, however this is practiced in a small percentage (11%) of patients9. This practice
 risk-stratification algorithm continues to be the SOC. However, the combination of the
 Goldman predictor risk algorithm (ECG and symptoms) with a Troponin I (cTnI) < 0.3 was not
 able to identify a group of chest pain patients at <1% risk for the composite outcome of
 death, AMI or revascularization18. Further demonstrating the need for integration of
 additional testing that will decrease the false-positive and false-negative rates.

 Adding nuclear perfusion cardiac testing to the SOC risk-stratification in the ED:

 Investigators have studied adding exercise stress testing and echocardiograms in the ED in
 the SOC risk-stratification of acute chest pain. Both the exercise stress test and the
 echocardiogram can be enhanced with the addition of nuclear perfusion that can define recent
 reduction in arterial flow to specific segments of the myocardium. Due to the known weakness
 of exercise testing 19 and the cost of adding nuclear perfusion enhancement to both the
 exercise stress test and the echocardiogram, neither study findings have informed the
 standard-of-care risk-stratification algorithm20-22. Furthermore, no apriori clinical
 research had performed a cost-analysis to confirm the obvious excessive expense of adding
 nuclear study in chest pain patients. However, stress testing is considered a worthy test to
 include in the risk-stratification algorithm because it is capable of detecting flow limiting
 stenosis, though does not establish the presence or absence of coronary artery disease.

 Adding non-invasive cardiac imaging: Coronary CT angiography (CTA) to the SOC (CTA + SOC)
 risk-stratification in the ED:

 Appropriate decision-making in the low to intermediate-risk subgroup of patients presenting
 with acute chest pain requires new tools. We postulate that perhaps the incorporation of
 coronary CTA can, by providing an anatomical window that defines the amount of
 atherosclerotic burden within the coronary tree, advance the risk-stratification algorithm in
 low to intermediate-risk acute chest pain in a cost-effective manner. In recent years, there
 has been much interest in noninvasive imaging techniques that allow direct visualization and
 assessment of the coronary arteries (Image A). The coronary tree is challenging to image due
 to the continuous motion of the coronary arteries. This motion necessitates both high spatial
 and temporal resolution. Recent advances in computed tomography (CT) techniques have made
 imaging of the coronary arteries possible. The introduction of electron-beam CT (EBCT) in
 1984 first allowed for ECG-synchronized imaging of the heart. In 1998, the first multiple
 detector spiral CT (MDCT) system with 4 detector rows was introduced, allowing for greater
 volume of coverage with each rotation of the CT gantry than EBCT. 23 Since that time, gantry
 rotation times have decreased, resulting in improved temporal resolution. An increase in
 number of detectors has allowed for sub-millimeter spatial resolution. At this time, 64 slice
 MDCT (Image A) is considered the "state of the art" technology for performance of coronary
 CTA, although the next generation of scanners, including dual source and 256 slice MDCT are
 currently under evaluation. Several small studies in the literature have shown the utility of
 coronary CTA in the safe and rapid triage of low to intermediate-risk acute chest pain
 patients presenting to the ED24-29. One of the clinical advantages of the coronary CTA is
 that, unlike stress testing that can detect flow limiting stenosis but not CAD; it can detect
 flow limiting stenosis in addition to the presence or absence of coronary artery disease. The
 disadvantage of coronary CTA is the exposure to radiation.

 Multiple small trials comparing coronary CTA with invasive coronary angiography have
 demonstrated sensitivities ranging from 86-99% and specificities ranging from 93-97% for the
 detection of hemodynamically significant CAD. The negative predictive value (NPV) of coronary
 CTA in these studies was uniformly high, ranging from 95-99%, while rates of non-evaluable
 segments were low, ranging from 0-12%23, 30-34. Results of the multicenter, international
 CORE-64 trial were discussed at the 2007 American Heart Association Scientific Sessions
 evaluating the diagnostic performance of coronary CTA as compared with interventional
 coronary angiography in 291 patients with suspected or known CAD and Agatston calcium score
 <600. On a per patient basis, the sensitivity and specificity of coronary CTA for detection
 of significant CAD were 85% and 90%, while positive and NPV were 91% and 83%35. Moreover, in
 2007, Meijboom et al36 reported on the utility of the coronary CTA in symptomatic patients
 with low, intermediate, or high estimated pretest probability of having significant CAD. Of
 the 254 patients enrolled in the study, the authors determined that all of the patients in
 both the low and intermediate-risk groups that were found to not have disease by coronary CTA
 were later determined to not have disease by invasive coronary angiography. Patients
 presenting to the ED with acute chest pain could potentially undergo more rapid triage with
 coronary CTA, speeding diagnosis, lowering hospital and further cost of testing.

 Additional reports on cost-analyses in populations when adding coronary CTA to the SOC
 risk-stratification algorithm (CTA + SOC):

 In a study by Goldstein et al published in 2007 in Journal of the American College of
 Cardiology, the authors reported that ED cost during the index visit was significantly lower
 in the group that received the coronary CTA versus the group that did not receive the
 coronary CTA. However, this cost difference was primarily due to a decrease in length of stay
 in the ED rather than the cost associated with other testing, specifically nuclear imaging.
 This cost analysis was limited to the index ED visits alone; since the study was powered for
 outcomes, not cost. No additional cost data was gathered, although outcome follow-up was
 6-months.

 Preliminary cost-outcome data presented at the Chicago 2008 American College of Cardiology
 meeting reported that; when including coronary CT calcium scores in the protocol to screen
 495 asymptomatic firefighters, researchers were able to effectively triage subjects into
 follow-up coronary CTA or send them back to work without further workup, thus, decreasing
 cost. In another report presented, researchers concluded that cost was decreased in an
 out-patient cardiology clinic by incorporating coronary CTA in the risk-stratification of
 cardiac patients leading to reduced need for myocardial perfusion imaging and exercise
 treadmill testing over a 6-month period. Moreover, doctors were able to identify more
 coronary artery disease and provide more aggressive lipid management.

 These data illustrate how cost and outcome studies are at the forefront of the research that
 is measuring and defining the role of coronary CTA. The coronary CTA is so innovative in the
 domain of acute chest pain, there is a paucity of published work that looks at the cost;
 instead, the majority of the literature examines outcomes and is produced primarily by
 cardiology.

 Healthcare cost implications when adding coronary CTA to the SOC (CTA + SOC); and the
 coronary CTA demonstrates normal coronary arteries:

 The cost implications of potentially discharging patients from the ED that are found to be
 free of CAD without further testing are impressive. In May of 2008, data in abstract form
 were presented in Academic EM where authors reported good NPV in 568 prospective patients who
 received coronary CTA in the ED at 30-days. These reports lacked a description of design,
 methodology, and a stated power calculation of an a priori hypothesis. Thus, the need for
 more definitive apriori cost and outcome clinical research in the application of coronary CTA
 in acute chest pain is warranted. The effect of this work will define and change the clinical
 practice landscape when applying this innovation to the cardiac risk-stratification model,
 particularly in acutely presenting chest pain. Embracing the incorporation of coronary CTA in
 acute chest pain is an innovation that will require well performed clinical trials to define
 the patients who will benefit most; whether it should be applied to asymptomatic patients,
 low, intermediate, and/or high-risk acute chest pain patients remains the question.
Inclusion Criteria:

 -  patients who complain of typical or atypical chest pain (that is compatible with
 ischemia during the past 12 hrs);

 -  patients a prediction of low to intermediate risk of myocardial infarction and/or
 complications according to established criteria;

 -  patients who have normal or non-diagnostic electrocardiograms;

 -  patients who have negative cardiac biomarker including creatine kinase-MB, myoglobin,
 and/or cardiac troponin I at initial testing; patients who require admission to the
 hospital by the EP at the time of risk-stratification;

 -  patients who require cardiology consultation in the ED 7. patients who are age 35
 years or older;

 -  patients who are able to hold their breath for ≥ 15 seconds (to obtain a quality
 static anatomical image, scanning requires at least fifteen seconds of breath holding;

 -  patients who have heart rate of < 70 beats per minute before or after the
 administration of beta-blocker medication

 Exclusion Criteria:

 -  patients who have a contraindication to iodinated and/ or beta-blocking drugs;
 patients who have compromised renal function defined as creatinine ≥ 1.2 mg/dl;

 -  patients who are pregnant, suspected pregnant or other vulnerable populations e.g.,
 incarcerated patients;

 -  patients who have documented CAD by prior invasive coronary angiography or coronary CT
 angiography and/or patients with coronary artery stents, prior angioplasty, or prior
 coronary artery bypass grafts (CABG);

 -  patients who have had prior cardiac imaging (within the past year) with normal result
 including invasive coronary angiography, coronary CT angiography, or nuclear stress
 testing;

 -  patients who are unstable; patients who have an electrocardiogram diagnostic of
 ischemia or myocardial infarction (significant Q waves, ST -segment deviations > 0.5
 mm, or T wave inversions);

 -  patients in atrial fibrillation or have markedly irregular rhythm 9. patients who have
 had contrast administration within the past 24hrs;

 -  patients without an 18 gauge antecubital intravenous access; patients who have a
 medical home outside of the UTSWMC/Parkland Medical system.