All patients presenting to the Emergency Department with symptoms suggestive of



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APPENDIX: Online Data Supplements Clinical Trial Inclusion and Exclusion Criteria All patients presenting to the Emergency Department with symptoms suggestive of acute coronary syndrome (ACS) were screened for the clinical trial. The inclusion criteria included low to intermediate risk of ACS and a TIMI ACS Risk Score 4; chest pain or other symptoms suggestive of ACS within 24 hours; male 30 years or female 45 years old; at least one cardiac risk factor (known vascular disease, hypertension, dyslipidemia, diabetes, family history with 1st degree relative with CAD diagnosis < 55 years old, current or recent smoking within one month); and no obvious cause for symptoms. Exclusion criteria included known CAD with a coronary stenosis >50%; prior coronary revascularization; ST segment elevation, new left bundle branch block or dynamic ECG changes with presenting ECG, creatinine 1.8 mg/dl or estimated glomerular filtration rate of less than 40 ml/min/1.73 m 2 ; pregnant or lactating female; hemodynamic or respiratory instability determined by the treating physician; ongoing bronchospasm; iodinated contrast allergy; atrial fibrillation or heart rate variability of >10 bpm. Patients were enrolled between 7am and 6pm Monday through Friday, as well as the morning following overnight or weekend arrival in the ED. Model Inputs and Cost Parameters. Costs from ED Billing Records Page 20 of 28

After the ED evaluation, all ED billing were reviewed by Medicare billing specialists at our center. To obtain patient costs, all items and services were assigned the appropriate 2007 Medicare reimbursement based on CPT or APC billing codes. Professional fees were obtained from the 2007 Medicare tables for our region. Due to significant changes in stress imaging reimbursement since 2007, we used the 2010 Medicare reimbursement for these data (Table 3 in the manuscript). When billed items did not have a corresponding code or were not Medicare reimbursed, the charges were not used for calculations. Observation charges were not included for this analysis as these are not commonly reimbursed at our center. Table e1 lists all Medicare-adjusted costs used for the base case calculations with corresponding CPT or APC codes. ED visit costs were were summed for each individual to obtain the standard of care (SOC) cost for each patient. The mean and 95% CI cost per patient were used for the SOC model base case cost. Base case costs were calculated similarly to the SOC, but only used costs within a 6 hours of arrival to the ED. After the ED visit, patients were followed up by telephone contact at 3, 6 and 12 months. Any further ED visits or other evaluations were recorded. If the patient returned to our center, costs were again obtained from the billing data and adjusted to 2007 Medicare costs as outlined above. However, most patients did not return to our center, but were followed up outside our hospital system. Costs for these further evaluations used the most likely CPT or APC codes to estimate patient costs based on the telephone follow up. These data are shown in Table e2. Page 21 of 28

Data Ranges for Variables Some model inputs require further clarification. Variables taken from the clinical data typically used 95% confidence intervals for the range of data. To reflect an anticipated variability in some centers, we increased the range of a few variables to more extreme values than those reported in the literature. These were ACS prevalence and probability of cardiac reevaluation for recurrent ACS symptoms. The prevalence of ACS ranged from 0 to 0.2 in the model to reflect the use of CT either in exclusively very low risk patients to those centers that may use CT scans in all suspected ACS patients, including those at high risk. The incidence of non-cardiac findings with CT was also doubled to account for patients with larger thoracic field of view, whole chest scans versus those with smaller field of view, dedicated cardiac CT. Whenever possible, we used the lowest and the highest 95% confidence interval or three standard deviations from the mean for literature based data to estimate the uncertainty in the measure. For variables where only a single point estimate for cost was available, the range of data was defined by the point estimate ± 20%. For some values in Table 1 in the manuscript, more than one literature reference was used to estimate the baseline mean and range of values. A mean of the average values weighted for the number of patients reported in the study was calculated to obtain the model point estimates. Page 22 of 28

Table e1: All Billed Patient Items Used for Base Case Cost Calculation SOC CCT Item Name APC/CPT Code Total Billed Mean per Patient* Total Billed Mean per Patient* Mean Cost ($) Profee Cost ($) 12 LEAD ECG 93005 163 1.3 159 0.6 41.58 8.65 TRACING ABDOMEN, SINGLE 74000 1 1.0 1 1.0 46.90 -- AP VIEW AMYLASE 82150 23 1.0 23 1.0 9.06 -- APOLIPOPROTEIN A- 82172 1 1.0 1 1.0 21.65 -- 1 APOLIPOPROTEIN B 82172 1 1.0 1 1.0 21.65 -- BASIC METABOLIC 80048 52 1.2 52 0.8 10.30 -- PANEL BILIRUBIN, DIRECT 82248 3 1.0 3 1.0 6.45 -- BLOOD CULTURE 87040 1 1.0 1 0.0 14.42 -- BLOOD GLUCOSE-ER 82962 4 2.8 4 0.8 6.96 -- B-NATRIURETIC 83880 21 1.0 21 1.0 47.43 -- PEPTIDE CBC, DIFFERENTIAL, 85025 41 1.0 41 0.9 10.86 -- SMEAR CBC HEMOGRAM 85027 1 1.0 1 1.0 9.04 -- COMPREHENSIVE 80053 60 1.0 60 0.9 11.92 -- METABOLIC PANEL COMPLETE BLOOD 85027 70 1.2 70 0.8 10.46 -- COUNT Page 23 of 28

CONTINUOUS 94660 1 1.0 1 0.0 101.51 -- POSITIVE PRESSURE (CPAP) CPK MB FRACTION 82553 25 1.8 25 0.6 27.74 -- CREATINE KINASE, 82550 22 1.6 22 0.6 14.48 -- BLOOD D-DIMER, 85379 53 1.0 53 1.0 14.22 -- QUANTITATIVE EXTREMITY VEIN 93970 1 1.0 1 0.0 162.69 -- DUPLEX COMPLETE EMERGENCY DRUG 80101 5 1.0 5 1.0 19.24 -- SCREEN EMERGENCY LEVEL 99281 1 1.0 1 1.0 53.79 -- 1 EMERGENCY LEVEL 99284 5 1.0 5 1.0 334.77 108.89 4 EMERGENCY LEVEL 99285 95 1.0 95 1.0 512.87 163.00 5 ERYTHROCYTE SED 85651 1 1.0 1 1.0 4.96 -- RATE EST PT VISIT LEVEL 4 99214 2 1.0 1 1.0 90.23 -- FIBRINOGEN 85384 4 1.5 4 0.0 11.23 -- ACTIVITY FREE THYROXINE 84439 5 1.0 5 1.0 12.22 -- HCG-PREGNANCY- 84702 1 1.0 1 1.0 21.03 -- SERUM HEMOGLOBIN A1C 83036 4 1.0 4 0.3 13.56 -- Page 24 of 28

HEPATIC FUNCTION 80076 1 1.0 1 1.0 8.93 -- PANEL A HYDRATION IV 90760 4 1.0 4 0.8 119.61 -- INF,31-60M INHALATION 94640 1 2.0 1 1.0 46.64 -- TREATMENT INJECTION-SUBQ/IM 90772 2 1.5 2 0.5 39.13 -- IV HYDR EA ADD HR 90761 12 1.3 12 0.5 32.61 -- IV INF TX/DX TO 1 HR 90767 1 1.0 1 1.0 26.08 -- SEQ IV PUSH 1ST/INIT 90774 45 1.0 45 0.8 52.51 -- DRUG 96374 5 1.0 5 0.8 52.51 -- C8952 4 1.0 4 0.8 52.51 -- IV PUSH EA ADD NEW 90775 20 1.4 20 0.7 73.52 -- DRUG 96375 1 2.0 1 0.0 105.02 -- LIPASE, BLOOD 83690 4 1.0 4 1.0 9.62 -- LIPID PANEL 80061 11 1.0 11 0.3 18.72 -- MAGNESIUM, BLOOD 83735 47 1.1 47 0.7 9.96 -- PARTIAL 85730 56 1.1 56 0.8 9.28 -- THROMBOPLASTIN PHOSPHORUS- 84100 26 1.1 26 0.7 7.14 -- BLOOD PROTHROMBIN 85610 55 1.1 55 0.9 5.89 -- RAD.EXAM,CHEST,1 71010 2 1.0 2 1.0 66.40 19.50 V,PA Page 25 of 28

RADEX,CHEST,1V, PA 71010 84 1.0 84 0.9 66.40 19.50 RADEX,CHEST,2V, 71020 22 1.0 22 1.0 57.90 11.00 PA&LAT RAPID STREP A TEST 87880 1 1.0 1 1.0 16.76 -- STREP CULTURE 87081 1 1.0 1 1.0 9.26 -- ONLY FREE T3 - BLOOD 84481 1 1.0 1 1.0 10.14 -- THROMBIN TIME 85670 1 1.0 1 0.0 8.07 -- THYROID 84443 10 1.0 10 0.8 23.39 -- STIMULATING HORMONE TROPONIN-I 84484 126 2.2 126 0.8 30.56 -- TRANSTHORACIC 93307 5 1.0 5 0.0 261.73 49.13 ECHOCARDIOGRAM, COMPLETE DOPPLER COLOR 93325 5 1.0 5 0.0 109.51 3.90 FLOW DOPPLER ECHO- 93320 5 1.0 5 0.0 125.85 20.24 SPECTRAL URINALYSIS,W/O 81003 1 0.0 1 1.0 4.43 -- MICRO URINALYSIS AUTO W/ 81001 21 1.0 21 1.0 4.43 -- MICRO VENIPUNCTURE 36415 79 1.0 79 0.9 3.08 -- The mean number per patient are for those patients that received at least 1 billing code. Page 26 of 28

Table e2: Costs and Billing Codes for Further Cardiac Evaluation in Patients with Recurrent Symptoms Item Name APC/CPT Billing Codes N Medicare 2007 Costs* Cardiac catheterization 93545 2 $2,773 Primary care outpatient clinic visit (Level 4) Outpatient cardiology evaluation (Level 4) 99204 2 $256 99204 3 $256 Emergency Department visit 80053, 85027, 71010, 85730, 85610, 84484, 99285, 93005, 36415, 93005 6 $768 Hospital admission with cardiac catheterization DRG 124 2 $5,524 *Costs include technical and professional fees. Mean Medicare reimbursement for all patients hospitalized for cardiac catheterization. N=number of patients. Page 27 of 28