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/Title (Use of the Corus� CAD Gene Expression Test for Assessment of Obstructive Coronary Artery Disease Likelihood in Symptomatic Non-Diabetic Patients � PLOS Currents Evidence on Genomic Tests)
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BT 15.000 718.042 Td /F2 21.0 Tf  [(Use of the Corus� CAD Gene Expression Test for Assessment )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(of Obstructive Coronary Artery Disease Likelihood in )] TJ ET
BT 15.000 668.146 Td /F2 21.0 Tf  [(Symptomatic Non-Diabetic Patients)] TJ ET
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BT 15.000 650.140 Td /F3 9.8 Tf  [(August 26, 2013)] TJ ET
BT 83.523 650.140 Td /F3 9.8 Tf  [(�)] TJ ET
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BT 88.398 650.140 Td /F3 9.8 Tf  [(Diagnostic)] TJ ET
BT 26.250 638.299 Td /F1 9.8 Tf  [(Jose Vargas)] TJ ET
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BT 80.441 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 85.862 638.299 Td /F1 9.8 Tf  [(Joao A.C. Lima)] TJ ET
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BT 152.512 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 157.933 638.299 Td /F1 9.8 Tf  [(William E. Kraus)] TJ ET
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BT 229.440 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 234.861 638.299 Td /F1 9.8 Tf  [(Pamela S Douglas)] TJ ET
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BT 315.601 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
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BT 321.022 638.299 Td /F1 9.8 Tf  [(Steven Rosenberg)] TJ ET
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BT 26.250 626.394 Td /F1 9.8 Tf  [(Vargas J, Lima JA, Kraus WE, Douglas PS, Rosenberg S. Use of the Corus� CAD Gene Expression Test for Assessment of )] TJ ET
BT 26.250 614.490 Td /F1 9.8 Tf  [(Obstructive Coronary Artery Disease Likelihood in Symptomatic Non-Diabetic Patients. PLOS Currents Evidence on Genomic )] TJ ET
BT 26.250 602.585 Td /F1 9.8 Tf  [(Tests. 2013 Aug 26 . Edition 1. doi: 10.1371/currents.eogt.0f04f6081905998fa92b99593478aeab.)] TJ ET
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BT 26.250 573.482 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 553.528 Td /F1 9.8 Tf  [(The determination of the underlying etiology of symptoms suggestive of obstructive coronary artery disease \(CAD, ?50% )] TJ ET
BT 26.250 541.623 Td /F1 9.8 Tf  [(stenosis in a major coronary artery\) is a common clinical challenge in both primary care and cardiology clinics. Usual care in low )] TJ ET
BT 26.250 529.719 Td /F1 9.8 Tf  [(to medium risk patients often involves a family history, risk factor assessment, and then stress testing with or without non-)] TJ ET
BT 26.250 517.814 Td /F1 9.8 Tf  [(invasive imaging. If positive, this is often followed by invasive coronary angiography \(ICA\). Despite extensive adoption of this )] TJ ET
BT 26.250 505.909 Td /F1 9.8 Tf  [(usual care paradigm, more than 60% of patients referred for angiography do not have obstructive CAD. In order to robustly )] TJ ET
BT 26.250 494.004 Td /F1 9.8 Tf  [(identify those symptomatic patients without obstructive CAD, who can avoid subsequent cardiac testing and look elsewhere for )] TJ ET
BT 26.250 482.100 Td /F1 9.8 Tf  [(the cause of their symptoms, a recently described whole blood gene expression score \(GES: Corus� CAD, CardioDx, Inc., Palo )] TJ ET
BT 26.250 470.195 Td /F1 9.8 Tf  [(Alto, CA\) has been developed and validated in two multi-center trials. This paper reviews the published literature and )] TJ ET
BT 26.250 458.290 Td /F1 9.8 Tf  [(assessments by independent parties regarding the analytical and clinical validity as well as the clinical utility of the Corus� CAD )] TJ ET
BT 26.250 446.385 Td /F1 9.8 Tf  [(test.)] TJ ET
BT 26.250 409.783 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 389.829 Td /F1 9.8 Tf  [(No outside funding was provided for this review. Drs. Lima and Vargas report no competing interests. Dr. Kraus has received )] TJ ET
BT 26.250 377.924 Td /F1 9.8 Tf  [(research funding from CardioDx, Inc. Dr. Douglas reports stock ownership and consulting fees from CardioDx, Inc. Dr. )] TJ ET
BT 26.250 366.019 Td /F1 9.8 Tf  [(Rosenberg is an employee of CardioDx, Inc.)] TJ ET
BT 26.250 336.917 Td /F4 12.0 Tf  [(Clinical Scenarios)] TJ ET
BT 26.250 316.962 Td /F1 9.8 Tf  [(Coronary artery disease \(CAD\) and its clinical sequelae, including myocardial infarction and heart failure, are the leading causes )] TJ ET
BT 26.250 305.058 Td /F1 9.8 Tf  [(of morbidity and mortality in the developed and developing world. Symptoms consistent with CAD are common, variable and )] TJ ET
BT 26.250 293.153 Td /F1 9.8 Tf  [(quite diverse with significant gender-specific differences and overlap with other common conditions. Symptomatic patients are )] TJ ET
BT 26.250 281.248 Td /F1 9.8 Tf  [(often first seen by primary care physicians who determine if a referral to a cardiology service is warranted, prior to investigation )] TJ ET
BT 26.250 269.343 Td /F1 9.8 Tf  [(of other causes for the symptoms. In cardiology practices, current practice guidelines suggest non-invasive imaging for medium )] TJ ET
BT 26.250 257.439 Td /F1 9.8 Tf  [(risk patients and invasive coronary angiography for high risk patients )] TJ ET
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BT 324.834 258.946 Td /F4 8.7 Tf  [(1)] TJ ET
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BT 329.653 257.439 Td /F1 9.8 Tf  [(. Despite the utilization of non-invasive imaging in most )] TJ ET
BT 26.250 245.534 Td /F1 9.8 Tf  [(patients prior to ICA, the yield for obstructive CAD was <40% in a recent large national study )] TJ ET
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BT 427.531 247.041 Td /F4 8.7 Tf  [(2)] TJ ET
0.271 0.267 0.267 rg
BT 432.349 245.534 Td /F1 9.8 Tf  [(. In addition, the prevalence of )] TJ ET
BT 26.250 233.629 Td /F1 9.8 Tf  [(positive myocardial perfusion imaging studies, has decreased significantly over the last two decades, from 40% to 10% in a )] TJ ET
BT 26.250 221.724 Td /F1 9.8 Tf  [(recent report )] TJ ET
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BT 84.233 223.232 Td /F4 8.7 Tf  [(3)] TJ ET
0.271 0.267 0.267 rg
BT 89.052 221.724 Td /F1 9.8 Tf  [(. Ruling out obstructive CAD in symptomatic women is particularly problematic as currently used diagnostic tests, )] TJ ET
BT 26.250 209.820 Td /F1 9.8 Tf  [(such as EKG, myocardial perfusion imaging \(MPI\), and echocardiography, perform less well in women than in men )] TJ ET
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BT 523.139 211.327 Td /F4 8.7 Tf  [(4)] TJ ET
0.271 0.267 0.267 rg
BT 527.958 209.820 Td /F1 9.8 Tf  [(. The )] TJ ET
BT 26.250 197.915 Td /F1 9.8 Tf  [(Agency for Healthcare Research and Quality highlighted the need for a better diagnostic test for women in a recent report by )] TJ ET
BT 26.250 186.010 Td /F1 9.8 Tf  [(stating that physicians evaluating women at low to intermediate risk of CAD may want to rule-out disease with a non-invasive )] TJ ET
BT 26.250 174.105 Td /F1 9.8 Tf  [(test with a high negative predictive value )] TJ ET
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BT 204.002 175.613 Td /F4 8.7 Tf  [(5)] TJ ET
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BT 208.821 174.105 Td /F1 9.8 Tf  [(. In addition, despite the common use of stress testing prior to coronary angiography, )] TJ ET
BT 26.250 162.201 Td /F1 9.8 Tf  [(practice utilization varies significantly across different regions )] TJ ET
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BT 292.298 163.708 Td /F4 8.7 Tf  [(6)] TJ ET
0.271 0.267 0.267 rg
BT 297.117 162.201 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 125.598 Td /F4 12.0 Tf  [(Test Description)] TJ ET
BT 26.250 105.644 Td /F1 9.8 Tf  [(When a clinician suspects obstructive CAD as a cause of patient symptoms, a standard venous blood draw is performed into a )] TJ ET
BT 26.250 93.739 Td /F1 9.8 Tf  [(PAXgene)] TJ ET
BT 67.444 97.627 Td /F1 8.7 Tf  [(TM )] TJ ET
BT 82.368 93.739 Td /F1 9.8 Tf  [(RNA preservation tube \(Pre-analytix, Valencia, CA\). The sample and accompanying test requisition form are sent )] TJ ET
BT 26.250 81.834 Td /F1 9.8 Tf  [(under temperature controlled conditions to the CLIA and College of American Pathologist�s certified CardioDx laboratory. The )] TJ ET
BT 26.250 69.930 Td /F1 9.8 Tf  [(sample is then accessioned, and RNA purification, cDNA synthesis, and quantitative real-time polymerase chain reaction \(qRT-)] TJ ET
BT 26.250 58.025 Td /F1 9.8 Tf  [(PCR\) are performed. Test results are calculated based on the age and sex of the patient and the expression levels of the 23 )] TJ ET
BT 26.250 46.120 Td /F1 9.8 Tf  [(genes in the Corus CAD algorithm and reported on a 1-40 scale )] TJ ET
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BT 304.252 47.627 Td /F4 8.7 Tf  [(7)] TJ ET
0.271 0.267 0.267 rg
BT 309.070 46.120 Td /F1 9.8 Tf  [(. The test algorithm differs between men and women based )] TJ ET
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15.000 659.406 577.500 78.594 re W n
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BT 15.000 718.042 Td /F2 21.0 Tf  [(Use of the Corus� CAD Gene Expression Test for Assessment )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(of Obstructive Coronary Artery Disease Likelihood in )] TJ ET
BT 15.000 668.146 Td /F2 21.0 Tf  [(Symptomatic Non-Diabetic Patients)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 650.140 Td /F3 9.8 Tf  [(August 26, 2013)] TJ ET
BT 83.523 650.140 Td /F3 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
BT 88.398 650.140 Td /F3 9.8 Tf  [(Diagnostic)] TJ ET
BT 26.250 638.299 Td /F1 9.8 Tf  [(Jose Vargas)] TJ ET
0.271 0.267 0.267 rg
BT 80.441 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 85.862 638.299 Td /F1 9.8 Tf  [(Joao A.C. Lima)] TJ ET
0.271 0.267 0.267 rg
BT 152.512 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 157.933 638.299 Td /F1 9.8 Tf  [(William E. Kraus)] TJ ET
0.271 0.267 0.267 rg
BT 229.440 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 234.861 638.299 Td /F1 9.8 Tf  [(Pamela S Douglas)] TJ ET
0.271 0.267 0.267 rg
BT 315.601 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 321.022 638.299 Td /F1 9.8 Tf  [(Steven Rosenberg)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 626.394 Td /F1 9.8 Tf  [(Vargas J, Lima JA, Kraus WE, Douglas PS, Rosenberg S. Use of the Corus� CAD Gene Expression Test for Assessment of )] TJ ET
BT 26.250 614.490 Td /F1 9.8 Tf  [(Obstructive Coronary Artery Disease Likelihood in Symptomatic Non-Diabetic Patients. PLOS Currents Evidence on Genomic )] TJ ET
BT 26.250 602.585 Td /F1 9.8 Tf  [(Tests. 2013 Aug 26 . Edition 1. doi: 10.1371/currents.eogt.0f04f6081905998fa92b99593478aeab.)] TJ ET
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0.271 0.267 0.267 rg
BT 26.250 573.482 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 553.528 Td /F1 9.8 Tf  [(The determination of the underlying etiology of symptoms suggestive of obstructive coronary artery disease \(CAD, ?50% )] TJ ET
BT 26.250 541.623 Td /F1 9.8 Tf  [(stenosis in a major coronary artery\) is a common clinical challenge in both primary care and cardiology clinics. Usual care in low )] TJ ET
BT 26.250 529.719 Td /F1 9.8 Tf  [(to medium risk patients often involves a family history, risk factor assessment, and then stress testing with or without non-)] TJ ET
BT 26.250 517.814 Td /F1 9.8 Tf  [(invasive imaging. If positive, this is often followed by invasive coronary angiography \(ICA\). Despite extensive adoption of this )] TJ ET
BT 26.250 505.909 Td /F1 9.8 Tf  [(usual care paradigm, more than 60% of patients referred for angiography do not have obstructive CAD. In order to robustly )] TJ ET
BT 26.250 494.004 Td /F1 9.8 Tf  [(identify those symptomatic patients without obstructive CAD, who can avoid subsequent cardiac testing and look elsewhere for )] TJ ET
BT 26.250 482.100 Td /F1 9.8 Tf  [(the cause of their symptoms, a recently described whole blood gene expression score \(GES: Corus� CAD, CardioDx, Inc., Palo )] TJ ET
BT 26.250 470.195 Td /F1 9.8 Tf  [(Alto, CA\) has been developed and validated in two multi-center trials. This paper reviews the published literature and )] TJ ET
BT 26.250 458.290 Td /F1 9.8 Tf  [(assessments by independent parties regarding the analytical and clinical validity as well as the clinical utility of the Corus� CAD )] TJ ET
BT 26.250 446.385 Td /F1 9.8 Tf  [(test.)] TJ ET
BT 26.250 409.783 Td /F4 12.0 Tf  [(Funding Statement)] TJ ET
BT 26.250 389.829 Td /F1 9.8 Tf  [(No outside funding was provided for this review. Drs. Lima and Vargas report no competing interests. Dr. Kraus has received )] TJ ET
BT 26.250 377.924 Td /F1 9.8 Tf  [(research funding from CardioDx, Inc. Dr. Douglas reports stock ownership and consulting fees from CardioDx, Inc. Dr. )] TJ ET
BT 26.250 366.019 Td /F1 9.8 Tf  [(Rosenberg is an employee of CardioDx, Inc.)] TJ ET
BT 26.250 336.917 Td /F4 12.0 Tf  [(Clinical Scenarios)] TJ ET
BT 26.250 316.962 Td /F1 9.8 Tf  [(Coronary artery disease \(CAD\) and its clinical sequelae, including myocardial infarction and heart failure, are the leading causes )] TJ ET
BT 26.250 305.058 Td /F1 9.8 Tf  [(of morbidity and mortality in the developed and developing world. Symptoms consistent with CAD are common, variable and )] TJ ET
BT 26.250 293.153 Td /F1 9.8 Tf  [(quite diverse with significant gender-specific differences and overlap with other common conditions. Symptomatic patients are )] TJ ET
BT 26.250 281.248 Td /F1 9.8 Tf  [(often first seen by primary care physicians who determine if a referral to a cardiology service is warranted, prior to investigation )] TJ ET
BT 26.250 269.343 Td /F1 9.8 Tf  [(of other causes for the symptoms. In cardiology practices, current practice guidelines suggest non-invasive imaging for medium )] TJ ET
BT 26.250 257.439 Td /F1 9.8 Tf  [(risk patients and invasive coronary angiography for high risk patients )] TJ ET
0.267 0.267 0.267 rg
BT 324.834 258.946 Td /F4 8.7 Tf  [(1)] TJ ET
0.271 0.267 0.267 rg
BT 329.653 257.439 Td /F1 9.8 Tf  [(. Despite the utilization of non-invasive imaging in most )] TJ ET
BT 26.250 245.534 Td /F1 9.8 Tf  [(patients prior to ICA, the yield for obstructive CAD was <40% in a recent large national study )] TJ ET
0.267 0.267 0.267 rg
BT 427.531 247.041 Td /F4 8.7 Tf  [(2)] TJ ET
0.271 0.267 0.267 rg
BT 432.349 245.534 Td /F1 9.8 Tf  [(. In addition, the prevalence of )] TJ ET
BT 26.250 233.629 Td /F1 9.8 Tf  [(positive myocardial perfusion imaging studies, has decreased significantly over the last two decades, from 40% to 10% in a )] TJ ET
BT 26.250 221.724 Td /F1 9.8 Tf  [(recent report )] TJ ET
0.267 0.267 0.267 rg
BT 84.233 223.232 Td /F4 8.7 Tf  [(3)] TJ ET
0.271 0.267 0.267 rg
BT 89.052 221.724 Td /F1 9.8 Tf  [(. Ruling out obstructive CAD in symptomatic women is particularly problematic as currently used diagnostic tests, )] TJ ET
BT 26.250 209.820 Td /F1 9.8 Tf  [(such as EKG, myocardial perfusion imaging \(MPI\), and echocardiography, perform less well in women than in men )] TJ ET
0.267 0.267 0.267 rg
BT 523.139 211.327 Td /F4 8.7 Tf  [(4)] TJ ET
0.271 0.267 0.267 rg
BT 527.958 209.820 Td /F1 9.8 Tf  [(. The )] TJ ET
BT 26.250 197.915 Td /F1 9.8 Tf  [(Agency for Healthcare Research and Quality highlighted the need for a better diagnostic test for women in a recent report by )] TJ ET
BT 26.250 186.010 Td /F1 9.8 Tf  [(stating that physicians evaluating women at low to intermediate risk of CAD may want to rule-out disease with a non-invasive )] TJ ET
BT 26.250 174.105 Td /F1 9.8 Tf  [(test with a high negative predictive value )] TJ ET
0.267 0.267 0.267 rg
BT 204.002 175.613 Td /F4 8.7 Tf  [(5)] TJ ET
0.271 0.267 0.267 rg
BT 208.821 174.105 Td /F1 9.8 Tf  [(. In addition, despite the common use of stress testing prior to coronary angiography, )] TJ ET
BT 26.250 162.201 Td /F1 9.8 Tf  [(practice utilization varies significantly across different regions )] TJ ET
0.267 0.267 0.267 rg
BT 292.298 163.708 Td /F4 8.7 Tf  [(6)] TJ ET
0.271 0.267 0.267 rg
BT 297.117 162.201 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 125.598 Td /F4 12.0 Tf  [(Test Description)] TJ ET
BT 26.250 105.644 Td /F1 9.8 Tf  [(When a clinician suspects obstructive CAD as a cause of patient symptoms, a standard venous blood draw is performed into a )] TJ ET
BT 26.250 93.739 Td /F1 9.8 Tf  [(PAXgene)] TJ ET
BT 67.444 97.627 Td /F1 8.7 Tf  [(TM )] TJ ET
BT 82.368 93.739 Td /F1 9.8 Tf  [(RNA preservation tube \(Pre-analytix, Valencia, CA\). The sample and accompanying test requisition form are sent )] TJ ET
BT 26.250 81.834 Td /F1 9.8 Tf  [(under temperature controlled conditions to the CLIA and College of American Pathologist�s certified CardioDx laboratory. The )] TJ ET
BT 26.250 69.930 Td /F1 9.8 Tf  [(sample is then accessioned, and RNA purification, cDNA synthesis, and quantitative real-time polymerase chain reaction \(qRT-)] TJ ET
BT 26.250 58.025 Td /F1 9.8 Tf  [(PCR\) are performed. Test results are calculated based on the age and sex of the patient and the expression levels of the 23 )] TJ ET
BT 26.250 46.120 Td /F1 9.8 Tf  [(genes in the Corus CAD algorithm and reported on a 1-40 scale )] TJ ET
0.267 0.267 0.267 rg
BT 304.252 47.627 Td /F4 8.7 Tf  [(7)] TJ ET
0.271 0.267 0.267 rg
BT 309.070 46.120 Td /F1 9.8 Tf  [(. The test algorithm differs between men and women based )] TJ ET
Q
q
15.000 659.406 577.500 78.594 re W n
0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(Use of the Corus� CAD Gene Expression Test for Assessment )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(of Obstructive Coronary Artery Disease Likelihood in )] TJ ET
BT 15.000 668.146 Td /F2 21.0 Tf  [(Symptomatic Non-Diabetic Patients)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 650.140 Td /F3 9.8 Tf  [(August 26, 2013)] TJ ET
BT 83.523 650.140 Td /F3 9.8 Tf  [(�)] TJ ET
0.267 0.267 0.267 rg
BT 88.398 650.140 Td /F3 9.8 Tf  [(Diagnostic)] TJ ET
BT 26.250 638.299 Td /F1 9.8 Tf  [(Jose Vargas)] TJ ET
0.271 0.267 0.267 rg
BT 80.441 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 85.862 638.299 Td /F1 9.8 Tf  [(Joao A.C. Lima)] TJ ET
0.271 0.267 0.267 rg
BT 152.512 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 157.933 638.299 Td /F1 9.8 Tf  [(William E. Kraus)] TJ ET
0.271 0.267 0.267 rg
BT 229.440 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 234.861 638.299 Td /F1 9.8 Tf  [(Pamela S Douglas)] TJ ET
0.271 0.267 0.267 rg
BT 315.601 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 321.022 638.299 Td /F1 9.8 Tf  [(Steven Rosenberg)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 626.394 Td /F1 9.8 Tf  [(Vargas J, Lima JA, Kraus WE, Douglas PS, Rosenberg S. Use of the Corus� CAD Gene Expression Test for Assessment of )] TJ ET
BT 26.250 614.490 Td /F1 9.8 Tf  [(Obstructive Coronary Artery Disease Likelihood in Symptomatic Non-Diabetic Patients. PLOS Currents Evidence on Genomic )] TJ ET
BT 26.250 602.585 Td /F1 9.8 Tf  [(Tests. 2013 Aug 26 . Edition 1. doi: 10.1371/currents.eogt.0f04f6081905998fa92b99593478aeab.)] TJ ET
q
15.000 31.834 577.500 568.370 re W n
0.271 0.267 0.267 rg
BT 26.250 573.482 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 553.528 Td /F1 9.8 Tf  [(The determination of the underlying etiology of symptoms suggestive of obstructive coronary artery disease \(CAD, ?50% )] TJ ET
BT 26.250 541.623 Td /F1 9.8 Tf  [(stenosis in a major coronary artery\) is a common clinical challenge in both primary care and cardiology clinics. Usual care in low )] TJ ET
BT 26.250 529.719 Td /F1 9.8 Tf  [(to medium risk patients often involves a family history, risk factor assessment, and then stress testing with or without non-)] TJ ET
BT 26.250 517.814 Td /F1 9.8 Tf  [(invasive imaging. If positive, this is often followed by invasive coronary angiography \(ICA\). Despite extensive adoption of this )] TJ ET
BT 26.250 505.909 Td /F1 9.8 Tf  [(usual care paradigm, more than 60% of patients referred for angiography do not have obstructive CAD. In order to robustly )] TJ ET
BT 26.250 494.004 Td /F1 9.8 Tf  [(identify those symptomatic patients without obstructive CAD, who can avoid subsequent cardiac testing and look elsewhere for )] TJ ET
BT 26.250 482.100 Td /F1 9.8 Tf  [(the cause of their symptoms, a recently described whole blood gene expression score \(GES: Corus� CAD, CardioDx, Inc., Palo )] TJ ET
BT 26.250 470.195 Td /F1 9.8 Tf  [(Alto, CA\) has been developed and validated in two multi-center trials. This paper reviews the published literature and )] TJ ET
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BT 516.110 627.586 Td /F1 9.8 Tf  [(. Despite the )] TJ ET
BT 26.250 615.681 Td /F1 9.8 Tf  [(significant resources expended only 10% of patients presenting to primary care with chest pain are ultimately diagnosed with )] TJ ET
BT 26.250 603.777 Td /F1 9.8 Tf  [(stable obstructive CAD )] TJ ET
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BT 26.250 584.372 Td /F4 9.8 Tf  [(Recommendations by independent groups.)] TJ ET
BT 226.700 584.372 Td /F1 9.8 Tf  [( As part of the Clinical Laboratory Improvement Act \(CLIA\) licensure process, the )] TJ ET
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BT 26.250 481.634 Td /F1 9.8 Tf  [(practice once specific molecular and clinically meaningful CVD signatures are developed� )] TJ ET
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BT 194.213 462.229 Td /F1 9.8 Tf  [(. A number of recent independent review articles have described the scientific work )] TJ ET
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BT 26.250 279.125 Td /F1 9.8 Tf  [(units. A comparison of overall process variability to biological dynamic range across 21,000 clinical samples showed that the )] TJ ET
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0.271 0.267 0.267 rg
BT 380.878 663.300 Td /F1 9.8 Tf  [(. Patients with symptoms suggestive of CAD )] TJ ET
BT 26.250 651.396 Td /F1 9.8 Tf  [(undergo extensive non-invasive and invasive testing to exclude the presence of CAD as the cause and, in the process are )] TJ ET
BT 26.250 639.491 Td /F1 9.8 Tf  [(exposed to risks of iatrogenic side effects such as those from ionizing radiation and contrast dye. The annual U.S. cost of non-)] TJ ET
BT 26.250 627.586 Td /F1 9.8 Tf  [(invasive imaging tests used in the cardiac work-up of stable symptomatic patients is approximately $7 billion )] TJ ET
0.267 0.267 0.267 rg
BT 494.425 629.093 Td /F4 8.7 Tf  [(11)] TJ ET
0.271 0.267 0.267 rg
BT 504.063 631.474 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 506.472 629.093 Td /F4 8.7 Tf  [(12)] TJ ET
0.271 0.267 0.267 rg
BT 516.110 627.586 Td /F1 9.8 Tf  [(. Despite the )] TJ ET
BT 26.250 615.681 Td /F1 9.8 Tf  [(significant resources expended only 10% of patients presenting to primary care with chest pain are ultimately diagnosed with )] TJ ET
BT 26.250 603.777 Td /F1 9.8 Tf  [(stable obstructive CAD )] TJ ET
0.267 0.267 0.267 rg
BT 128.118 605.284 Td /F4 8.7 Tf  [(8)] TJ ET
0.271 0.267 0.267 rg
BT 132.937 603.777 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 584.372 Td /F4 9.8 Tf  [(Recommendations by independent groups.)] TJ ET
BT 226.700 584.372 Td /F1 9.8 Tf  [( As part of the Clinical Laboratory Improvement Act \(CLIA\) licensure process, the )] TJ ET
BT 26.250 572.467 Td /F1 9.8 Tf  [(analytical and clinical validation data for the Corus CAD test were independently evaluated by reviewers from the California and )] TJ ET
BT 26.250 560.562 Td /F1 9.8 Tf  [(New York Departments of Publish Health. In both cases these reviews resulted in positive recommendations and the CardioDx )] TJ ET
BT 26.250 548.658 Td /F1 9.8 Tf  [(laboratory is licensed in all 50 states. In addition, as of April, 2013, the CardioDx laboratory is now accredited by the College of )] TJ ET
BT 26.250 536.753 Td /F1 9.8 Tf  [(American Pathologists \(CAP\).)] TJ ET
BT 26.250 517.348 Td /F4 9.8 Tf  [(Guidelines.)] TJ ET
BT 78.812 517.348 Td /F1 9.8 Tf  [( A recent policy statement from the American College of Cardiology and American Heart Association discussed the )] TJ ET
BT 26.250 505.443 Td /F1 9.8 Tf  [(role of genetics and cardiovascular disease treatment and diagnosis but did not address gene expression as is measured in the )] TJ ET
BT 26.250 493.539 Td /F1 9.8 Tf  [(Corus CAD Test )] TJ ET
0.267 0.267 0.267 rg
BT 99.931 495.046 Td /F4 8.7 Tf  [(13)] TJ ET
0.271 0.267 0.267 rg
BT 109.568 493.539 Td /F1 9.8 Tf  [(. An earlier scientific statement suggested: �Gene expression profiling has potential application in clinical )] TJ ET
BT 26.250 481.634 Td /F1 9.8 Tf  [(practice once specific molecular and clinically meaningful CVD signatures are developed� )] TJ ET
0.267 0.267 0.267 rg
BT 414.222 483.141 Td /F4 8.7 Tf  [(14)] TJ ET
0.271 0.267 0.267 rg
BT 423.859 481.634 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 462.229 Td /F4 9.8 Tf  [(Recent Independent Review Articles)] TJ ET
BT 194.213 462.229 Td /F1 9.8 Tf  [(. A number of recent independent review articles have described the scientific work )] TJ ET
BT 26.250 450.324 Td /F1 9.8 Tf  [(underpinning the Corus CAD test )] TJ ET
0.267 0.267 0.267 rg
BT 172.022 451.832 Td /F4 8.7 Tf  [(15)] TJ ET
0.271 0.267 0.267 rg
BT 181.660 454.213 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 184.069 451.832 Td /F4 8.7 Tf  [(16)] TJ ET
0.271 0.267 0.267 rg
BT 193.706 450.324 Td /F1 9.8 Tf  [(. A very recent review article in Nature Reviews Cardiology was solely focused on Corus )] TJ ET
BT 26.250 438.420 Td /F1 9.8 Tf  [(CAD )] TJ ET
0.267 0.267 0.267 rg
BT 49.543 439.927 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 59.180 438.420 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 401.817 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 381.863 Td /F4 9.8 Tf  [(Analytical Validity)] TJ ET
BT 26.250 362.458 Td /F1 9.8 Tf  [(A large study utilizing more than 800 whole blood control samples was performed to assess the intra and inter-batch variability )] TJ ET
BT 26.250 350.553 Td /F1 9.8 Tf  [(and inherent reproducibility of the Corus CAD test in the CardioDx commercial laboratory as a function of time, reagent batches, )] TJ ET
BT 26.250 338.649 Td /F1 9.8 Tf  [(operators, and equipment )] TJ ET
0.267 0.267 0.267 rg
BT 140.062 340.156 Td /F4 8.7 Tf  [(18)] TJ ET
0.271 0.267 0.267 rg
BT 149.699 338.649 Td /F1 9.8 Tf  [(. A total of 11 variables were assessed for their contribution to inter-batch variability, including four )] TJ ET
BT 26.250 326.744 Td /F1 9.8 Tf  [(individual steps in the process \(RNA purification, cDNA synthesis, sample addition, and qRT-PCR\) across multiple operator, )] TJ ET
BT 26.250 314.839 Td /F1 9.8 Tf  [(equipment, and reagent lots. Intra-batch variability estimated from 132 samples was 0.092 Cp units, dominated by inherent PCR )] TJ ET
BT 26.250 302.934 Td /F1 9.8 Tf  [(stochastic variance, and represented approximately 70% of overall variance. Inter-batch variability was estimated across 895 )] TJ ET
BT 26.250 291.030 Td /F1 9.8 Tf  [(samples over a two-year time frame; the largest sources of variances were reagent lots, and the overall variance was 0.11 Cp )] TJ ET
BT 26.250 279.125 Td /F1 9.8 Tf  [(units. A comparison of overall process variability to biological dynamic range across 21,000 clinical samples showed that the )] TJ ET
BT 26.250 267.220 Td /F1 9.8 Tf  [(biological variability was more than 10 times the process variability, demonstrating that the signal to noise was excellent. Overall )] TJ ET
BT 26.250 255.315 Td /F1 9.8 Tf  [(process variance standard deviation corresponded to 1 unit on the Corus CAD 1-40 scale, corresponding to a clinically )] TJ ET
BT 26.250 243.411 Td /F1 9.8 Tf  [(insignificant 1.7% change in obstructive CAD likelihood.)] TJ ET
BT 26.250 224.006 Td /F4 9.8 Tf  [(Clinical Validity)] TJ ET
BT 26.250 204.601 Td /F1 9.8 Tf  [(Two prospective multi-center trials evaluated the performance of the Corus CAD test across populations of different disease )] TJ ET
BT 26.250 192.696 Td /F1 9.8 Tf  [(prevalence. The PREDICT trial evaluated test performance in a patient population \(N=526\) referred for invasive coronary )] TJ ET
BT 26.250 180.792 Td /F1 9.8 Tf  [(angiography, the gold standard for obstructive disease evaluation )] TJ ET
0.267 0.267 0.267 rg
BT 310.774 182.299 Td /F4 8.7 Tf  [(19)] TJ ET
0.271 0.267 0.267 rg
BT 320.412 180.792 Td /F1 9.8 Tf  [(. Disease prevalence was 37%, as measured by core )] TJ ET
BT 26.250 168.887 Td /F1 9.8 Tf  [(laboratory quantitative coronary angiography, and very similar to that observed in a very large registry study )] TJ ET
0.267 0.267 0.267 rg
BT 492.817 170.394 Td /F4 8.7 Tf  [(2)] TJ ET
0.271 0.267 0.267 rg
BT 497.635 168.887 Td /F1 9.8 Tf  [(. A gender specific )] TJ ET
BT 26.250 156.982 Td /F1 9.8 Tf  [(analysis of the PREDICT results showed the obstructive CAD prevalence in women was only 22%, indicating a need for better )] TJ ET
BT 26.250 145.077 Td /F1 9.8 Tf  [(non-invasive diagnostic tools specifically in women )] TJ ET
0.267 0.267 0.267 rg
BT 247.868 146.585 Td /F4 8.7 Tf  [(20)] TJ ET
0.271 0.267 0.267 rg
BT 257.505 145.077 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 125.673 Td /F1 9.8 Tf  [(The COMPASS study evaluated test performance in symptomatic patients \(N=431\) referred for myocardial perfusion imaging, a )] TJ ET
BT 26.250 113.768 Td /F1 9.8 Tf  [(procedure used prior to angiography )] TJ ET
0.267 0.267 0.267 rg
BT 186.121 115.275 Td /F4 8.7 Tf  [(21)] TJ ET
0.271 0.267 0.267 rg
BT 195.758 113.768 Td /F1 9.8 Tf  [(. The gold standard was a combination of either invasive angiography and CT-)] TJ ET
BT 26.250 101.863 Td /F1 9.8 Tf  [(angiography, both determined in core laboratories, so that all patients, independent of their MPI results, had gold standard data )] TJ ET
BT 26.250 89.958 Td /F1 9.8 Tf  [(on their coronary anatomy. Obstructive CAD prevalence was only 15%, lower than seen in PREDICT. Positive MPI scans were )] TJ ET
BT 26.250 78.054 Td /F1 9.8 Tf  [(seen in 11% of patients, very similar to that seen in a recent study reporting MPI positivity over the last two decades of 10% )] TJ ET
0.267 0.267 0.267 rg
BT 560.579 79.561 Td /F4 8.7 Tf  [(3)] TJ ET
0.271 0.267 0.267 rg
BT 565.398 78.054 Td /F1 9.8 Tf  [(. )] TJ ET
BT 26.250 66.149 Td /F1 9.8 Tf  [(Results of the two Corus CAD validation studies representing 58 centers in the US were very consistent.)] TJ ET
BT 26.250 46.744 Td /F1 9.8 Tf  [(� The primary endpoint of the area under the receiver-operating characteristics curve \(AUC for ROC\) analysis for discriminating )] TJ ET
Q
q
15.000 32.458 577.500 744.542 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(on age-dependent risk, specific genes, and relative gene weighting )] TJ ET
0.267 0.267 0.267 rg
BT 317.278 768.983 Td /F4 8.7 Tf  [(7)] TJ ET
0.271 0.267 0.267 rg
BT 322.096 767.476 Td /F1 9.8 Tf  [(. Increasing score is associated with increasing likelihood )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(of obstructive CAD and increasing disease burden. A pre-specified threshold of ?15 has been prospectively evaluated as a low )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(risk boundary. Approximately 95% of samples received result in a valid test result and of more than 40,000 patients evaluated )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(since launch, 47% have scores below the pre-specified threshold of ?15.)] TJ ET
BT 26.250 695.159 Td /F4 12.0 Tf  [(Public Health Importance/Prevalence)] TJ ET
BT 26.250 675.205 Td /F1 9.8 Tf  [(The evaluation of undiagnosed stable but symptomatic chest pain is associated with as many as 2% of all office visits or 2-3 )] TJ ET
BT 26.250 663.300 Td /F1 9.8 Tf  [(million visits to primary care outpatient clinics each year in the United States )] TJ ET
0.267 0.267 0.267 rg
BT 356.785 664.808 Td /F4 8.7 Tf  [(8)] TJ ET
0.271 0.267 0.267 rg
BT 361.603 667.189 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 364.013 664.808 Td /F4 8.7 Tf  [(9)] TJ ET
0.271 0.267 0.267 rg
BT 368.831 667.189 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 371.241 664.808 Td /F4 8.7 Tf  [(10)] TJ ET
0.271 0.267 0.267 rg
BT 380.878 663.300 Td /F1 9.8 Tf  [(. Patients with symptoms suggestive of CAD )] TJ ET
BT 26.250 651.396 Td /F1 9.8 Tf  [(undergo extensive non-invasive and invasive testing to exclude the presence of CAD as the cause and, in the process are )] TJ ET
BT 26.250 639.491 Td /F1 9.8 Tf  [(exposed to risks of iatrogenic side effects such as those from ionizing radiation and contrast dye. The annual U.S. cost of non-)] TJ ET
BT 26.250 627.586 Td /F1 9.8 Tf  [(invasive imaging tests used in the cardiac work-up of stable symptomatic patients is approximately $7 billion )] TJ ET
0.267 0.267 0.267 rg
BT 494.425 629.093 Td /F4 8.7 Tf  [(11)] TJ ET
0.271 0.267 0.267 rg
BT 504.063 631.474 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 506.472 629.093 Td /F4 8.7 Tf  [(12)] TJ ET
0.271 0.267 0.267 rg
BT 516.110 627.586 Td /F1 9.8 Tf  [(. Despite the )] TJ ET
BT 26.250 615.681 Td /F1 9.8 Tf  [(significant resources expended only 10% of patients presenting to primary care with chest pain are ultimately diagnosed with )] TJ ET
BT 26.250 603.777 Td /F1 9.8 Tf  [(stable obstructive CAD )] TJ ET
0.267 0.267 0.267 rg
BT 128.118 605.284 Td /F4 8.7 Tf  [(8)] TJ ET
0.271 0.267 0.267 rg
BT 132.937 603.777 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 584.372 Td /F4 9.8 Tf  [(Recommendations by independent groups.)] TJ ET
BT 226.700 584.372 Td /F1 9.8 Tf  [( As part of the Clinical Laboratory Improvement Act \(CLIA\) licensure process, the )] TJ ET
BT 26.250 572.467 Td /F1 9.8 Tf  [(analytical and clinical validation data for the Corus CAD test were independently evaluated by reviewers from the California and )] TJ ET
BT 26.250 560.562 Td /F1 9.8 Tf  [(New York Departments of Publish Health. In both cases these reviews resulted in positive recommendations and the CardioDx )] TJ ET
BT 26.250 548.658 Td /F1 9.8 Tf  [(laboratory is licensed in all 50 states. In addition, as of April, 2013, the CardioDx laboratory is now accredited by the College of )] TJ ET
BT 26.250 536.753 Td /F1 9.8 Tf  [(American Pathologists \(CAP\).)] TJ ET
BT 26.250 517.348 Td /F4 9.8 Tf  [(Guidelines.)] TJ ET
BT 78.812 517.348 Td /F1 9.8 Tf  [( A recent policy statement from the American College of Cardiology and American Heart Association discussed the )] TJ ET
BT 26.250 505.443 Td /F1 9.8 Tf  [(role of genetics and cardiovascular disease treatment and diagnosis but did not address gene expression as is measured in the )] TJ ET
BT 26.250 493.539 Td /F1 9.8 Tf  [(Corus CAD Test )] TJ ET
0.267 0.267 0.267 rg
BT 99.931 495.046 Td /F4 8.7 Tf  [(13)] TJ ET
0.271 0.267 0.267 rg
BT 109.568 493.539 Td /F1 9.8 Tf  [(. An earlier scientific statement suggested: �Gene expression profiling has potential application in clinical )] TJ ET
BT 26.250 481.634 Td /F1 9.8 Tf  [(practice once specific molecular and clinically meaningful CVD signatures are developed� )] TJ ET
0.267 0.267 0.267 rg
BT 414.222 483.141 Td /F4 8.7 Tf  [(14)] TJ ET
0.271 0.267 0.267 rg
BT 423.859 481.634 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 462.229 Td /F4 9.8 Tf  [(Recent Independent Review Articles)] TJ ET
BT 194.213 462.229 Td /F1 9.8 Tf  [(. A number of recent independent review articles have described the scientific work )] TJ ET
BT 26.250 450.324 Td /F1 9.8 Tf  [(underpinning the Corus CAD test )] TJ ET
0.267 0.267 0.267 rg
BT 172.022 451.832 Td /F4 8.7 Tf  [(15)] TJ ET
0.271 0.267 0.267 rg
BT 181.660 454.213 Td /F1 8.7 Tf  [(,)] TJ ET
0.267 0.267 0.267 rg
BT 184.069 451.832 Td /F4 8.7 Tf  [(16)] TJ ET
0.271 0.267 0.267 rg
BT 193.706 450.324 Td /F1 9.8 Tf  [(. A very recent review article in Nature Reviews Cardiology was solely focused on Corus )] TJ ET
BT 26.250 438.420 Td /F1 9.8 Tf  [(CAD )] TJ ET
0.267 0.267 0.267 rg
BT 49.543 439.927 Td /F4 8.7 Tf  [(17)] TJ ET
0.271 0.267 0.267 rg
BT 59.180 438.420 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 401.817 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 381.863 Td /F4 9.8 Tf  [(Analytical Validity)] TJ ET
BT 26.250 362.458 Td /F1 9.8 Tf  [(A large study utilizing more than 800 whole blood control samples was performed to assess the intra and inter-batch variability )] TJ ET
BT 26.250 350.553 Td /F1 9.8 Tf  [(and inherent reproducibility of the Corus CAD test in the CardioDx commercial laboratory as a function of time, reagent batches, )] TJ ET
BT 26.250 338.649 Td /F1 9.8 Tf  [(operators, and equipment )] TJ ET
0.267 0.267 0.267 rg
BT 140.062 340.156 Td /F4 8.7 Tf  [(18)] TJ ET
0.271 0.267 0.267 rg
BT 149.699 338.649 Td /F1 9.8 Tf  [(. A total of 11 variables were assessed for their contribution to inter-batch variability, including four )] TJ ET
BT 26.250 326.744 Td /F1 9.8 Tf  [(individual steps in the process \(RNA purification, cDNA synthesis, sample addition, and qRT-PCR\) across multiple operator, )] TJ ET
BT 26.250 314.839 Td /F1 9.8 Tf  [(equipment, and reagent lots. Intra-batch variability estimated from 132 samples was 0.092 Cp units, dominated by inherent PCR )] TJ ET
BT 26.250 302.934 Td /F1 9.8 Tf  [(stochastic variance, and represented approximately 70% of overall variance. Inter-batch variability was estimated across 895 )] TJ ET
BT 26.250 291.030 Td /F1 9.8 Tf  [(samples over a two-year time frame; the largest sources of variances were reagent lots, and the overall variance was 0.11 Cp )] TJ ET
BT 26.250 279.125 Td /F1 9.8 Tf  [(units. A comparison of overall process variability to biological dynamic range across 21,000 clinical samples showed that the )] TJ ET
BT 26.250 267.220 Td /F1 9.8 Tf  [(biological variability was more than 10 times the process variability, demonstrating that the signal to noise was excellent. Overall )] TJ ET
BT 26.250 255.315 Td /F1 9.8 Tf  [(process variance standard deviation corresponded to 1 unit on the Corus CAD 1-40 scale, corresponding to a clinically )] TJ ET
BT 26.250 243.411 Td /F1 9.8 Tf  [(insignificant 1.7% change in obstructive CAD likelihood.)] TJ ET
BT 26.250 224.006 Td /F4 9.8 Tf  [(Clinical Validity)] TJ ET
BT 26.250 204.601 Td /F1 9.8 Tf  [(Two prospective multi-center trials evaluated the performance of the Corus CAD test across populations of different disease )] TJ ET
BT 26.250 192.696 Td /F1 9.8 Tf  [(prevalence. The PREDICT trial evaluated test performance in a patient population \(N=526\) referred for invasive coronary )] TJ ET
BT 26.250 180.792 Td /F1 9.8 Tf  [(angiography, the gold standard for obstructive disease evaluation )] TJ ET
0.267 0.267 0.267 rg
BT 310.774 182.299 Td /F4 8.7 Tf  [(19)] TJ ET
0.271 0.267 0.267 rg
BT 320.412 180.792 Td /F1 9.8 Tf  [(. Disease prevalence was 37%, as measured by core )] TJ ET
BT 26.250 168.887 Td /F1 9.8 Tf  [(laboratory quantitative coronary angiography, and very similar to that observed in a very large registry study )] TJ ET
0.267 0.267 0.267 rg
BT 492.817 170.394 Td /F4 8.7 Tf  [(2)] TJ ET
0.271 0.267 0.267 rg
BT 497.635 168.887 Td /F1 9.8 Tf  [(. A gender specific )] TJ ET
BT 26.250 156.982 Td /F1 9.8 Tf  [(analysis of the PREDICT results showed the obstructive CAD prevalence in women was only 22%, indicating a need for better )] TJ ET
BT 26.250 145.077 Td /F1 9.8 Tf  [(non-invasive diagnostic tools specifically in women )] TJ ET
0.267 0.267 0.267 rg
BT 247.868 146.585 Td /F4 8.7 Tf  [(20)] TJ ET
0.271 0.267 0.267 rg
BT 257.505 145.077 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 125.673 Td /F1 9.8 Tf  [(The COMPASS study evaluated test performance in symptomatic patients \(N=431\) referred for myocardial perfusion imaging, a )] TJ ET
BT 26.250 113.768 Td /F1 9.8 Tf  [(procedure used prior to angiography )] TJ ET
0.267 0.267 0.267 rg
BT 186.121 115.275 Td /F4 8.7 Tf  [(21)] TJ ET
0.271 0.267 0.267 rg
BT 195.758 113.768 Td /F1 9.8 Tf  [(. The gold standard was a combination of either invasive angiography and CT-)] TJ ET
BT 26.250 101.863 Td /F1 9.8 Tf  [(angiography, both determined in core laboratories, so that all patients, independent of their MPI results, had gold standard data )] TJ ET
BT 26.250 89.958 Td /F1 9.8 Tf  [(on their coronary anatomy. Obstructive CAD prevalence was only 15%, lower than seen in PREDICT. Positive MPI scans were )] TJ ET
BT 26.250 78.054 Td /F1 9.8 Tf  [(seen in 11% of patients, very similar to that seen in a recent study reporting MPI positivity over the last two decades of 10% )] TJ ET
0.267 0.267 0.267 rg
BT 560.579 79.561 Td /F4 8.7 Tf  [(3)] TJ ET
0.271 0.267 0.267 rg
BT 565.398 78.054 Td /F1 9.8 Tf  [(. )] TJ ET
BT 26.250 66.149 Td /F1 9.8 Tf  [(Results of the two Corus CAD validation studies representing 58 centers in the US were very consistent.)] TJ ET
BT 26.250 46.744 Td /F1 9.8 Tf  [(� The primary endpoint of the area under the receiver-operating characteristics curve \(AUC for ROC\) analysis for discriminating )] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(2)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Evidence on Genomic Tests)] TJ ET

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BT 26.250 767.476 Td /F1 9.8 Tf  [(patients with and without obstructive CAD \(50% stenosis by quantitative angiography or core-lab CT-angiography\) yielded )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(AUCs of 0.70 and 0.79, for PREDICT and COMPASS, respectively \(p<0.001 in both cases\).)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(� In both studies Corus CAD demonstrated excellent sensitivity \(85 and 89%\) and moderate specificity \(43 and 52%\), )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(respectively, at a threshold of ?15 which was derived from the PREDICT study and pre-specified for the COMPASS study)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(� Corus CAD showed high negative predictive values of 83 and 96%, respectively, in the PREDICT and COMPASS studies, )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(consistent with the differences in obstructive CAD prevalence.)] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(� In the subset of PREDICT patients who had MPI and in the entire COMPASS study Corus CAD showed superior diagnostic )] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(performance to MPI driven by much greater sensitivity and diagnostic accuracy \(ROC curve AUC\). In the COMPASS study the )] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(AUCs were 0.79, 0.59, and 0.63 for Corus CAD, site-read, and core-lab read MPI, respectively.)] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(� In both studies increasing Corus CAD score was significantly associated with increasing maximum percent stenosis.)] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(� In both studies clinical follow-up for subsequent revascularization and major adverse cardiovascular events was performed. In )] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(PREDICT this was for 1 year post-index catheterization and showed a very significant association of Corus CAD score and the )] TJ ET
BT 26.250 587.119 Td /F1 9.8 Tf  [(composite revascularization and event endpoint )] TJ ET
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BT 234.890 588.626 Td /F4 8.7 Tf  [(22)] TJ ET
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BT 244.528 587.119 Td /F1 9.8 Tf  [(. In the COMPASS trial 6 month follow-up also showed significantly fewer )] TJ ET
BT 26.250 575.214 Td /F1 9.8 Tf  [(revascularization and events with low \(?15\) Corus CAD scores )] TJ ET
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BT 298.792 576.722 Td /F4 8.7 Tf  [(21)] TJ ET
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BT 308.429 575.214 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 555.810 Td /F4 9.8 Tf  [(Clinical Utility)] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(Three studies of the clinical utility of Corus CAD have been reported: a multi-center retrospective chart review in primary care, a )] TJ ET
BT 26.250 524.500 Td /F1 9.8 Tf  [(prospective single center study of change in behavior in cardiology, and a prospective multi-center change in behavior study in )] TJ ET
BT 26.250 512.595 Td /F1 9.8 Tf  [(primary care.)] TJ ET
BT 26.250 493.191 Td /F5 9.8 Tf  [(Retrospective Chart Review in Primary Care)] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(To document the impact of Corus CAD in real-world primary care practice, a retrospective chart review study was completed in )] TJ ET
BT 26.250 461.881 Td /F1 9.8 Tf  [(four primary care practices currently using Corus CAD, located in Arizona, Georgia, Louisiana, and North Carolina )] TJ ET
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BT 519.883 463.388 Td /F4 8.7 Tf  [(23)] TJ ET
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BT 529.520 461.881 Td /F1 9.8 Tf  [(. A total of )] TJ ET
BT 26.250 449.976 Td /F1 9.8 Tf  [(317 patients who presented to four primary care physician sites with signs and symptoms suggestive of obstructive CAD and )] TJ ET
BT 26.250 438.072 Td /F1 9.8 Tf  [(underwent Corus CAD testing from January 2011 to September 2011 were determined to be evaluable by medical records )] TJ ET
BT 26.250 426.167 Td /F1 9.8 Tf  [(review and were included in this retrospective study. The objective of this study was to determine if there was a relationship )] TJ ET
BT 26.250 414.262 Td /F1 9.8 Tf  [(between Corus CAD score and referral decision to the cardiologist: specifically, if patients with low Corus CAD scores were less )] TJ ET
BT 26.250 402.357 Td /F1 9.8 Tf  [(likely to be referred to a cardiologist than patients with non-low scores.)] TJ ET
BT 26.250 382.953 Td /F1 9.8 Tf  [(In this study, 41% \(129/317\) of the Corus CAD patients had low scores \(?15\), a rate consistent with the broader commercial )] TJ ET
BT 26.250 371.048 Td /F1 9.8 Tf  [(population receiving the test and the COMPASS clinical trial population. Based upon physician self-reported referral rates, the )] TJ ET
BT 26.250 359.143 Td /F1 9.8 Tf  [(expected referral rate to cardiology was 56.5%. The data show that the average referral rate to a cardiologist following Corus )] TJ ET
BT 26.250 347.238 Td /F1 9.8 Tf  [(CAD testing was reduced to 30% \(p<0.001\). In addition, the referral rate was just 9% \(12/129\) in the Corus CAD low scoring )] TJ ET
BT 26.250 335.334 Td /F1 9.8 Tf  [(patient population. In multivariate analysis, after controlling for age, gender, type of symptoms, and practice site, patients with )] TJ ET
BT 26.250 323.429 Td /F1 9.8 Tf  [(low Corus CAD scores had a relative reduction in referral likelihood of 73% \(p=0.01\).)] TJ ET
BT 26.250 304.024 Td /F5 9.8 Tf  [(IMPACT-Cardiology)] TJ ET
BT 26.250 284.619 Td /F1 9.8 Tf  [(The IMPACT-Cardiology \(Investigation of a Molecular Personalized Coronary Gene Expression Test on Cardiology Practice )] TJ ET
BT 26.250 272.715 Td /F1 9.8 Tf  [(Pattern\)\(IMPACT-CARD\) trial sought to assess the impact of Corus CAD use on clinical decision-making during the assessment )] TJ ET
BT 26.250 260.810 Td /F1 9.8 Tf  [(of stable chest pain patients in the cardiology setting. The study included a prospective cohort of 83 patients eligible for )] TJ ET
BT 26.250 248.905 Td /F1 9.8 Tf  [(analysis. These patients were referred to six cardiologists for evaluation of suspected CAD in the Vanderbilt University health )] TJ ET
BT 26.250 237.000 Td /F1 9.8 Tf  [(care system and were matched by clinical factors to 83 patients in a historical cohort )] TJ ET
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BT 392.021 238.508 Td /F4 8.7 Tf  [(24)] TJ ET
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BT 401.659 237.000 Td /F1 9.8 Tf  [(. The IMPACT-Cardiology protocol was )] TJ ET
BT 26.250 225.096 Td /F1 9.8 Tf  [(designed to evaluate and compare the cardiologists� diagnostic strategies before and after receiving the Corus CAD results for )] TJ ET
BT 26.250 213.191 Td /F1 9.8 Tf  [(their patients. Clinicians performed a pre-Corus CAD assessment of patients� CAD probability and noted their preliminary )] TJ ET
BT 26.250 201.286 Td /F1 9.8 Tf  [(management decision \(no intervention/medical management, referral for non-invasive imaging, or referral for invasive )] TJ ET
BT 26.250 189.381 Td /F1 9.8 Tf  [(angiography\). This pre-Corus CAD assessment was compared to physicians� assessment of CAD probability after seeing the )] TJ ET
BT 26.250 177.477 Td /F1 9.8 Tf  [(Corus CAD result \(post-Corus CAD assessment\) and determining a final management decision.)] TJ ET
BT 26.250 158.072 Td /F1 9.8 Tf  [(In this study following communication of Corus CAD results, a change in diagnostic testing \(e.g. myocardial perfusion imaging, )] TJ ET
BT 26.250 146.167 Td /F1 9.8 Tf  [(CTA and cardiac catheterization\) was noted in 48 patients [58%, 95% CI \(46%, 69%\)]. More patients had a decreased versus )] TJ ET
BT 26.250 134.262 Td /F1 9.8 Tf  [(increased level of testing \(n=32 \(39%\) vs n=16 \(19%\), p=0.03\). In particular, 91% \(29 of 32\) of patients with decreased testing )] TJ ET
BT 26.250 122.358 Td /F1 9.8 Tf  [(had low Corus CAD \(? 15\), while 100% \(16 of 16\) of patients with increased testing had elevated Corus CAD \(p<0.001\). The )] TJ ET
BT 26.250 110.453 Td /F1 9.8 Tf  [(most common change was among patients considered for referral to non-invasive imaging or invasive angiography prior to the )] TJ ET
BT 26.250 98.548 Td /F1 9.8 Tf  [(Corus CAD test who were then referred to either no intervention or medical management after receiving a low Corus CAD )] TJ ET
BT 26.250 86.643 Td /F1 9.8 Tf  [(score. Furthermore, none of the patients with low scores \(?15\) saw an increase in testing.)] TJ ET
BT 26.250 67.239 Td /F1 9.8 Tf  [(The IMPACT-CARD trial demonstrated that among patients with a low Corus CAD score, the management decisions of )] TJ ET
BT 26.250 55.334 Td /F1 9.8 Tf  [(cardiologists change, leading to a decrease in non-invasive cardiac imaging and invasive angiography.)] TJ ET
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15.000 26.048 577.500 750.952 re W n
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BT 26.250 767.476 Td /F1 9.8 Tf  [(patients with and without obstructive CAD \(50% stenosis by quantitative angiography or core-lab CT-angiography\) yielded )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(AUCs of 0.70 and 0.79, for PREDICT and COMPASS, respectively \(p<0.001 in both cases\).)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(� In both studies Corus CAD demonstrated excellent sensitivity \(85 and 89%\) and moderate specificity \(43 and 52%\), )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(respectively, at a threshold of ?15 which was derived from the PREDICT study and pre-specified for the COMPASS study)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(� Corus CAD showed high negative predictive values of 83 and 96%, respectively, in the PREDICT and COMPASS studies, )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(consistent with the differences in obstructive CAD prevalence.)] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(� In the subset of PREDICT patients who had MPI and in the entire COMPASS study Corus CAD showed superior diagnostic )] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(performance to MPI driven by much greater sensitivity and diagnostic accuracy \(ROC curve AUC\). In the COMPASS study the )] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(AUCs were 0.79, 0.59, and 0.63 for Corus CAD, site-read, and core-lab read MPI, respectively.)] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(� In both studies increasing Corus CAD score was significantly associated with increasing maximum percent stenosis.)] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(� In both studies clinical follow-up for subsequent revascularization and major adverse cardiovascular events was performed. In )] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(PREDICT this was for 1 year post-index catheterization and showed a very significant association of Corus CAD score and the )] TJ ET
BT 26.250 587.119 Td /F1 9.8 Tf  [(composite revascularization and event endpoint )] TJ ET
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BT 234.890 588.626 Td /F4 8.7 Tf  [(22)] TJ ET
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BT 244.528 587.119 Td /F1 9.8 Tf  [(. In the COMPASS trial 6 month follow-up also showed significantly fewer )] TJ ET
BT 26.250 575.214 Td /F1 9.8 Tf  [(revascularization and events with low \(?15\) Corus CAD scores )] TJ ET
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BT 298.792 576.722 Td /F4 8.7 Tf  [(21)] TJ ET
0.271 0.267 0.267 rg
BT 308.429 575.214 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 555.810 Td /F4 9.8 Tf  [(Clinical Utility)] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(Three studies of the clinical utility of Corus CAD have been reported: a multi-center retrospective chart review in primary care, a )] TJ ET
BT 26.250 524.500 Td /F1 9.8 Tf  [(prospective single center study of change in behavior in cardiology, and a prospective multi-center change in behavior study in )] TJ ET
BT 26.250 512.595 Td /F1 9.8 Tf  [(primary care.)] TJ ET
BT 26.250 493.191 Td /F5 9.8 Tf  [(Retrospective Chart Review in Primary Care)] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(To document the impact of Corus CAD in real-world primary care practice, a retrospective chart review study was completed in )] TJ ET
BT 26.250 461.881 Td /F1 9.8 Tf  [(four primary care practices currently using Corus CAD, located in Arizona, Georgia, Louisiana, and North Carolina )] TJ ET
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BT 519.883 463.388 Td /F4 8.7 Tf  [(23)] TJ ET
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BT 529.520 461.881 Td /F1 9.8 Tf  [(. A total of )] TJ ET
BT 26.250 449.976 Td /F1 9.8 Tf  [(317 patients who presented to four primary care physician sites with signs and symptoms suggestive of obstructive CAD and )] TJ ET
BT 26.250 438.072 Td /F1 9.8 Tf  [(underwent Corus CAD testing from January 2011 to September 2011 were determined to be evaluable by medical records )] TJ ET
BT 26.250 426.167 Td /F1 9.8 Tf  [(review and were included in this retrospective study. The objective of this study was to determine if there was a relationship )] TJ ET
BT 26.250 414.262 Td /F1 9.8 Tf  [(between Corus CAD score and referral decision to the cardiologist: specifically, if patients with low Corus CAD scores were less )] TJ ET
BT 26.250 402.357 Td /F1 9.8 Tf  [(likely to be referred to a cardiologist than patients with non-low scores.)] TJ ET
BT 26.250 382.953 Td /F1 9.8 Tf  [(In this study, 41% \(129/317\) of the Corus CAD patients had low scores \(?15\), a rate consistent with the broader commercial )] TJ ET
BT 26.250 371.048 Td /F1 9.8 Tf  [(population receiving the test and the COMPASS clinical trial population. Based upon physician self-reported referral rates, the )] TJ ET
BT 26.250 359.143 Td /F1 9.8 Tf  [(expected referral rate to cardiology was 56.5%. The data show that the average referral rate to a cardiologist following Corus )] TJ ET
BT 26.250 347.238 Td /F1 9.8 Tf  [(CAD testing was reduced to 30% \(p<0.001\). In addition, the referral rate was just 9% \(12/129\) in the Corus CAD low scoring )] TJ ET
BT 26.250 335.334 Td /F1 9.8 Tf  [(patient population. In multivariate analysis, after controlling for age, gender, type of symptoms, and practice site, patients with )] TJ ET
BT 26.250 323.429 Td /F1 9.8 Tf  [(low Corus CAD scores had a relative reduction in referral likelihood of 73% \(p=0.01\).)] TJ ET
BT 26.250 304.024 Td /F5 9.8 Tf  [(IMPACT-Cardiology)] TJ ET
BT 26.250 284.619 Td /F1 9.8 Tf  [(The IMPACT-Cardiology \(Investigation of a Molecular Personalized Coronary Gene Expression Test on Cardiology Practice )] TJ ET
BT 26.250 272.715 Td /F1 9.8 Tf  [(Pattern\)\(IMPACT-CARD\) trial sought to assess the impact of Corus CAD use on clinical decision-making during the assessment )] TJ ET
BT 26.250 260.810 Td /F1 9.8 Tf  [(of stable chest pain patients in the cardiology setting. The study included a prospective cohort of 83 patients eligible for )] TJ ET
BT 26.250 248.905 Td /F1 9.8 Tf  [(analysis. These patients were referred to six cardiologists for evaluation of suspected CAD in the Vanderbilt University health )] TJ ET
BT 26.250 237.000 Td /F1 9.8 Tf  [(care system and were matched by clinical factors to 83 patients in a historical cohort )] TJ ET
0.267 0.267 0.267 rg
BT 392.021 238.508 Td /F4 8.7 Tf  [(24)] TJ ET
0.271 0.267 0.267 rg
BT 401.659 237.000 Td /F1 9.8 Tf  [(. The IMPACT-Cardiology protocol was )] TJ ET
BT 26.250 225.096 Td /F1 9.8 Tf  [(designed to evaluate and compare the cardiologists� diagnostic strategies before and after receiving the Corus CAD results for )] TJ ET
BT 26.250 213.191 Td /F1 9.8 Tf  [(their patients. Clinicians performed a pre-Corus CAD assessment of patients� CAD probability and noted their preliminary )] TJ ET
BT 26.250 201.286 Td /F1 9.8 Tf  [(management decision \(no intervention/medical management, referral for non-invasive imaging, or referral for invasive )] TJ ET
BT 26.250 189.381 Td /F1 9.8 Tf  [(angiography\). This pre-Corus CAD assessment was compared to physicians� assessment of CAD probability after seeing the )] TJ ET
BT 26.250 177.477 Td /F1 9.8 Tf  [(Corus CAD result \(post-Corus CAD assessment\) and determining a final management decision.)] TJ ET
BT 26.250 158.072 Td /F1 9.8 Tf  [(In this study following communication of Corus CAD results, a change in diagnostic testing \(e.g. myocardial perfusion imaging, )] TJ ET
BT 26.250 146.167 Td /F1 9.8 Tf  [(CTA and cardiac catheterization\) was noted in 48 patients [58%, 95% CI \(46%, 69%\)]. More patients had a decreased versus )] TJ ET
BT 26.250 134.262 Td /F1 9.8 Tf  [(increased level of testing \(n=32 \(39%\) vs n=16 \(19%\), p=0.03\). In particular, 91% \(29 of 32\) of patients with decreased testing )] TJ ET
BT 26.250 122.358 Td /F1 9.8 Tf  [(had low Corus CAD \(? 15\), while 100% \(16 of 16\) of patients with increased testing had elevated Corus CAD \(p<0.001\). The )] TJ ET
BT 26.250 110.453 Td /F1 9.8 Tf  [(most common change was among patients considered for referral to non-invasive imaging or invasive angiography prior to the )] TJ ET
BT 26.250 98.548 Td /F1 9.8 Tf  [(Corus CAD test who were then referred to either no intervention or medical management after receiving a low Corus CAD )] TJ ET
BT 26.250 86.643 Td /F1 9.8 Tf  [(score. Furthermore, none of the patients with low scores \(?15\) saw an increase in testing.)] TJ ET
BT 26.250 67.239 Td /F1 9.8 Tf  [(The IMPACT-CARD trial demonstrated that among patients with a low Corus CAD score, the management decisions of )] TJ ET
BT 26.250 55.334 Td /F1 9.8 Tf  [(cardiologists change, leading to a decrease in non-invasive cardiac imaging and invasive angiography.)] TJ ET
Q
q
15.000 26.048 577.500 750.952 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(patients with and without obstructive CAD \(50% stenosis by quantitative angiography or core-lab CT-angiography\) yielded )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(AUCs of 0.70 and 0.79, for PREDICT and COMPASS, respectively \(p<0.001 in both cases\).)] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(� In both studies Corus CAD demonstrated excellent sensitivity \(85 and 89%\) and moderate specificity \(43 and 52%\), )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(respectively, at a threshold of ?15 which was derived from the PREDICT study and pre-specified for the COMPASS study)] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(� Corus CAD showed high negative predictive values of 83 and 96%, respectively, in the PREDICT and COMPASS studies, )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(consistent with the differences in obstructive CAD prevalence.)] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(� In the subset of PREDICT patients who had MPI and in the entire COMPASS study Corus CAD showed superior diagnostic )] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(performance to MPI driven by much greater sensitivity and diagnostic accuracy \(ROC curve AUC\). In the COMPASS study the )] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(AUCs were 0.79, 0.59, and 0.63 for Corus CAD, site-read, and core-lab read MPI, respectively.)] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(� In both studies increasing Corus CAD score was significantly associated with increasing maximum percent stenosis.)] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(� In both studies clinical follow-up for subsequent revascularization and major adverse cardiovascular events was performed. In )] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(PREDICT this was for 1 year post-index catheterization and showed a very significant association of Corus CAD score and the )] TJ ET
BT 26.250 587.119 Td /F1 9.8 Tf  [(composite revascularization and event endpoint )] TJ ET
0.267 0.267 0.267 rg
BT 234.890 588.626 Td /F4 8.7 Tf  [(22)] TJ ET
0.271 0.267 0.267 rg
BT 244.528 587.119 Td /F1 9.8 Tf  [(. In the COMPASS trial 6 month follow-up also showed significantly fewer )] TJ ET
BT 26.250 575.214 Td /F1 9.8 Tf  [(revascularization and events with low \(?15\) Corus CAD scores )] TJ ET
0.267 0.267 0.267 rg
BT 298.792 576.722 Td /F4 8.7 Tf  [(21)] TJ ET
0.271 0.267 0.267 rg
BT 308.429 575.214 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 555.810 Td /F4 9.8 Tf  [(Clinical Utility)] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(Three studies of the clinical utility of Corus CAD have been reported: a multi-center retrospective chart review in primary care, a )] TJ ET
BT 26.250 524.500 Td /F1 9.8 Tf  [(prospective single center study of change in behavior in cardiology, and a prospective multi-center change in behavior study in )] TJ ET
BT 26.250 512.595 Td /F1 9.8 Tf  [(primary care.)] TJ ET
BT 26.250 493.191 Td /F5 9.8 Tf  [(Retrospective Chart Review in Primary Care)] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(To document the impact of Corus CAD in real-world primary care practice, a retrospective chart review study was completed in )] TJ ET
BT 26.250 461.881 Td /F1 9.8 Tf  [(four primary care practices currently using Corus CAD, located in Arizona, Georgia, Louisiana, and North Carolina )] TJ ET
0.267 0.267 0.267 rg
BT 519.883 463.388 Td /F4 8.7 Tf  [(23)] TJ ET
0.271 0.267 0.267 rg
BT 529.520 461.881 Td /F1 9.8 Tf  [(. A total of )] TJ ET
BT 26.250 449.976 Td /F1 9.8 Tf  [(317 patients who presented to four primary care physician sites with signs and symptoms suggestive of obstructive CAD and )] TJ ET
BT 26.250 438.072 Td /F1 9.8 Tf  [(underwent Corus CAD testing from January 2011 to September 2011 were determined to be evaluable by medical records )] TJ ET
BT 26.250 426.167 Td /F1 9.8 Tf  [(review and were included in this retrospective study. The objective of this study was to determine if there was a relationship )] TJ ET
BT 26.250 414.262 Td /F1 9.8 Tf  [(between Corus CAD score and referral decision to the cardiologist: specifically, if patients with low Corus CAD scores were less )] TJ ET
BT 26.250 402.357 Td /F1 9.8 Tf  [(likely to be referred to a cardiologist than patients with non-low scores.)] TJ ET
BT 26.250 382.953 Td /F1 9.8 Tf  [(In this study, 41% \(129/317\) of the Corus CAD patients had low scores \(?15\), a rate consistent with the broader commercial )] TJ ET
BT 26.250 371.048 Td /F1 9.8 Tf  [(population receiving the test and the COMPASS clinical trial population. Based upon physician self-reported referral rates, the )] TJ ET
BT 26.250 359.143 Td /F1 9.8 Tf  [(expected referral rate to cardiology was 56.5%. The data show that the average referral rate to a cardiologist following Corus )] TJ ET
BT 26.250 347.238 Td /F1 9.8 Tf  [(CAD testing was reduced to 30% \(p<0.001\). In addition, the referral rate was just 9% \(12/129\) in the Corus CAD low scoring )] TJ ET
BT 26.250 335.334 Td /F1 9.8 Tf  [(patient population. In multivariate analysis, after controlling for age, gender, type of symptoms, and practice site, patients with )] TJ ET
BT 26.250 323.429 Td /F1 9.8 Tf  [(low Corus CAD scores had a relative reduction in referral likelihood of 73% \(p=0.01\).)] TJ ET
BT 26.250 304.024 Td /F5 9.8 Tf  [(IMPACT-Cardiology)] TJ ET
BT 26.250 284.619 Td /F1 9.8 Tf  [(The IMPACT-Cardiology \(Investigation of a Molecular Personalized Coronary Gene Expression Test on Cardiology Practice )] TJ ET
BT 26.250 272.715 Td /F1 9.8 Tf  [(Pattern\)\(IMPACT-CARD\) trial sought to assess the impact of Corus CAD use on clinical decision-making during the assessment )] TJ ET
BT 26.250 260.810 Td /F1 9.8 Tf  [(of stable chest pain patients in the cardiology setting. The study included a prospective cohort of 83 patients eligible for )] TJ ET
BT 26.250 248.905 Td /F1 9.8 Tf  [(analysis. These patients were referred to six cardiologists for evaluation of suspected CAD in the Vanderbilt University health )] TJ ET
BT 26.250 237.000 Td /F1 9.8 Tf  [(care system and were matched by clinical factors to 83 patients in a historical cohort )] TJ ET
0.267 0.267 0.267 rg
BT 392.021 238.508 Td /F4 8.7 Tf  [(24)] TJ ET
0.271 0.267 0.267 rg
BT 401.659 237.000 Td /F1 9.8 Tf  [(. The IMPACT-Cardiology protocol was )] TJ ET
BT 26.250 225.096 Td /F1 9.8 Tf  [(designed to evaluate and compare the cardiologists� diagnostic strategies before and after receiving the Corus CAD results for )] TJ ET
BT 26.250 213.191 Td /F1 9.8 Tf  [(their patients. Clinicians performed a pre-Corus CAD assessment of patients� CAD probability and noted their preliminary )] TJ ET
BT 26.250 201.286 Td /F1 9.8 Tf  [(management decision \(no intervention/medical management, referral for non-invasive imaging, or referral for invasive )] TJ ET
BT 26.250 189.381 Td /F1 9.8 Tf  [(angiography\). This pre-Corus CAD assessment was compared to physicians� assessment of CAD probability after seeing the )] TJ ET
BT 26.250 177.477 Td /F1 9.8 Tf  [(Corus CAD result \(post-Corus CAD assessment\) and determining a final management decision.)] TJ ET
BT 26.250 158.072 Td /F1 9.8 Tf  [(In this study following communication of Corus CAD results, a change in diagnostic testing \(e.g. myocardial perfusion imaging, )] TJ ET
BT 26.250 146.167 Td /F1 9.8 Tf  [(CTA and cardiac catheterization\) was noted in 48 patients [58%, 95% CI \(46%, 69%\)]. More patients had a decreased versus )] TJ ET
BT 26.250 134.262 Td /F1 9.8 Tf  [(increased level of testing \(n=32 \(39%\) vs n=16 \(19%\), p=0.03\). In particular, 91% \(29 of 32\) of patients with decreased testing )] TJ ET
BT 26.250 122.358 Td /F1 9.8 Tf  [(had low Corus CAD \(? 15\), while 100% \(16 of 16\) of patients with increased testing had elevated Corus CAD \(p<0.001\). The )] TJ ET
BT 26.250 110.453 Td /F1 9.8 Tf  [(most common change was among patients considered for referral to non-invasive imaging or invasive angiography prior to the )] TJ ET
BT 26.250 98.548 Td /F1 9.8 Tf  [(Corus CAD test who were then referred to either no intervention or medical management after receiving a low Corus CAD )] TJ ET
BT 26.250 86.643 Td /F1 9.8 Tf  [(score. Furthermore, none of the patients with low scores \(?15\) saw an increase in testing.)] TJ ET
BT 26.250 67.239 Td /F1 9.8 Tf  [(The IMPACT-CARD trial demonstrated that among patients with a low Corus CAD score, the management decisions of )] TJ ET
BT 26.250 55.334 Td /F1 9.8 Tf  [(cardiologists change, leading to a decrease in non-invasive cardiac imaging and invasive angiography.)] TJ ET
Q
q
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BT 291.710 19.825 Td /F1 11.0 Tf  [(3)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Evidence on Genomic Tests)] TJ ET

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15.000 29.583 577.500 747.417 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F5 9.8 Tf  [(IMPACT-PCP)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(The IMPACT-PCP \(Investigation of a Molecular Personalized Coronary Gene Expression Test on Primary Care Practice )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Pattern\) trial assessed the impact of Corus CAD use on clinical decision-making around the assessment of patients with )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(symptoms of obstructive CAD in the primary care setting. The study included a prospective cohort of 251 patients, eligible for )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(analysis, assessed by 8 community based practitioners at four sites. Clinicians performed a pre-Corus CAD assessment of )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(patients� CAD probability and noted their preliminary management decisions \(no intervention/medical management, referral for )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(non-invasive imaging, or referral for invasive angiography\). This pre-Corus CAD assessment was compared to the clinician�s )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(assessment of CAD probability after seeing the Corus CAD results \(post-Corus CAD assessment\) and determining a final )] TJ ET
BT 26.250 664.738 Td /F1 9.8 Tf  [(management decision.)] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(In this study, a change in diagnostic testing \(e.g. myocardial perfusion imaging, CTA and cardiac catheterization\) was noted in )] TJ ET
BT 26.250 633.429 Td /F1 9.8 Tf  [(145 patients following Corus CAD testing \(58% observed vs 10% expected change, p<0.001\). More patients had decreased )] TJ ET
BT 26.250 621.524 Td /F1 9.8 Tf  [(\(n=93, 37%\) versus increased \(n=52, 21%\) intensity of testing \(p<0.001\). In particular, among the 127 low score Corus CAD )] TJ ET
BT 26.250 609.619 Td /F1 9.8 Tf  [(patients \(51% of study patients\), 60% \(76/127\) had decreased testing, and only 2% \(3/127\) had increased testing. After more )] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(than 30 days of follow-up of 247 \(98%\) patients, there has been one MACE event \(hemorrhagic stroke in a low score Corus )] TJ ET
BT 26.250 585.810 Td /F1 9.8 Tf  [(CAD patient\) reported.)] TJ ET
BT 26.250 566.405 Td /F1 9.8 Tf  [(In summary, Corus CAD was associated with a statistically significant and clinically relevant change in clinical decision-making )] TJ ET
BT 26.250 554.500 Td /F1 9.8 Tf  [(among patients evaluated for suspected symptomatic CAD. In addition, the utilization of Corus CAD showed clinical utility above )] TJ ET
BT 26.250 542.595 Td /F1 9.8 Tf  [(and beyond conventional decision-making by optimizing the patient�s diagnostic evaluation, particularly around the reduction in )] TJ ET
BT 26.250 530.691 Td /F1 9.8 Tf  [(the intensity of diagnostic testing among low Corus CAD patients.)] TJ ET
BT 26.250 511.286 Td /F4 9.8 Tf  [(Systematic Evidence Reviews)] TJ ET
BT 26.250 491.881 Td /F1 9.8 Tf  [(Palmetto Government Benefits Administrators \(Palmetto, GBA\), the CMS Medicare Administrative Contractor with oversight for )] TJ ET
BT 26.250 479.976 Td /F1 9.8 Tf  [(Corus CAD, has published its assessment of the test. This review determined that the test meets standards for analytical and )] TJ ET
BT 26.250 468.072 Td /F1 9.8 Tf  [(clinical validity, and clinical utility and is a reasonable and necessary Medicare benefit, effective January 1, 2012 )] TJ ET
0.267 0.267 0.267 rg
BT 512.336 469.579 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 521.974 468.072 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 448.667 Td /F1 9.8 Tf  [(Overall Analysis of Evidence. The Evaluation of Genomic Applications in Practice and Prevention \(EGAPP\) working group has )] TJ ET
BT 26.250 436.762 Td /F1 9.8 Tf  [(published a framework for evaluation of evidence of genomic testing, comprising analytical and clinical validity and clinical utility )] TJ ET
0.267 0.267 0.267 rg
BT 26.250 426.365 Td /F4 8.7 Tf  [(26)] TJ ET
0.271 0.267 0.267 rg
BT 35.887 424.857 Td /F1 9.8 Tf  [(. For Corus CAD with respect to analytic validity, an extensive study demonstrating very good score reproducibility and the )] TJ ET
BT 26.250 412.953 Td /F1 9.8 Tf  [(ability to result >95% of samples, suggests a Level 1 evidence category in our judgement, for the performance of the test in the )] TJ ET
BT 26.250 401.048 Td /F1 9.8 Tf  [(CardioDx clinical laboratory. For clinical validity it is our assessment that the two prospective multi-center trials with core )] TJ ET
BT 26.250 389.143 Td /F1 9.8 Tf  [(laboratory definition of disease status, representing almost 1000 patients, also correspond to Level 1 evidence according to )] TJ ET
BT 26.250 377.238 Td /F1 9.8 Tf  [(EGAPP criteria )] TJ ET
0.267 0.267 0.267 rg
BT 94.519 378.746 Td /F4 8.7 Tf  [(26)] TJ ET
0.271 0.267 0.267 rg
BT 104.157 377.238 Td /F1 9.8 Tf  [(. The clinical utility data from the IMPACT and retrospective chart review studies are of relatively small size )] TJ ET
BT 26.250 365.334 Td /F1 9.8 Tf  [(and limited follow-up suggesting a level 2-3 evidence determination.)] TJ ET
BT 26.250 328.731 Td /F4 12.0 Tf  [(Limitations)] TJ ET
BT 26.250 308.777 Td /F1 9.8 Tf  [(Although the results of the evaluation of the Corus CAD test are very promising, its results should be interpreted carefully as )] TJ ET
BT 26.250 296.872 Td /F1 9.8 Tf  [(patients with diabetes mellitus and chronic inflammatory or autoimmune disorders were excluded from test development and )] TJ ET
BT 26.250 284.967 Td /F1 9.8 Tf  [(validation. Furthermore, this test was derived and tested in predominantly Caucasian patient populations. Given the known )] TJ ET
BT 26.250 273.063 Td /F1 9.8 Tf  [(variations in the prevalence of CAD in different ethnic/racial backgrounds )] TJ ET
0.267 0.267 0.267 rg
BT 343.262 274.570 Td /F4 8.7 Tf  [(27)] TJ ET
0.271 0.267 0.267 rg
BT 352.899 273.063 Td /F1 9.8 Tf  [(, results of this test in non-Caucasian populations )] TJ ET
BT 26.250 261.158 Td /F1 9.8 Tf  [(should be interpreted with caution.)] TJ ET
BT 26.250 224.555 Td /F4 12.0 Tf  [(Conclusions)] TJ ET
BT 26.250 204.601 Td /F1 9.8 Tf  [(The Corus CAD test has been extensively evaluated since it was first derived, including with two prospective multi-center trials. )] TJ ET
BT 26.250 192.696 Td /F1 9.8 Tf  [(Given the scope of the deleterious effects of CAD and the considerable costs involved in diagnosing obstructive CAD, a blood )] TJ ET
BT 26.250 180.792 Td /F1 9.8 Tf  [(test that can help in this determination is certainly valuable. The Corus CAD test promises to have an important role in this )] TJ ET
BT 26.250 168.887 Td /F1 9.8 Tf  [(regard particularly if it continues to perform this well in larger, more diverse cohorts.)] TJ ET
BT 26.250 132.284 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 112.330 Td /F1 9.8 Tf  [(We thank the team at CardioDx and all the investigators, clinical research staff, and patients who participated in the clinical )] TJ ET
BT 26.250 100.425 Td /F1 9.8 Tf  [(studies in the development, clinical validation, and clinical utilization of Corus CAD.)] TJ ET
BT 26.250 71.323 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 43.869 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 43.869 Td /F1 9.8 Tf  [(Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS )] TJ ET
Q
q
15.000 29.583 577.500 747.417 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F5 9.8 Tf  [(IMPACT-PCP)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(The IMPACT-PCP \(Investigation of a Molecular Personalized Coronary Gene Expression Test on Primary Care Practice )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Pattern\) trial assessed the impact of Corus CAD use on clinical decision-making around the assessment of patients with )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(symptoms of obstructive CAD in the primary care setting. The study included a prospective cohort of 251 patients, eligible for )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(analysis, assessed by 8 community based practitioners at four sites. Clinicians performed a pre-Corus CAD assessment of )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(patients� CAD probability and noted their preliminary management decisions \(no intervention/medical management, referral for )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(non-invasive imaging, or referral for invasive angiography\). This pre-Corus CAD assessment was compared to the clinician�s )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(assessment of CAD probability after seeing the Corus CAD results \(post-Corus CAD assessment\) and determining a final )] TJ ET
BT 26.250 664.738 Td /F1 9.8 Tf  [(management decision.)] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(In this study, a change in diagnostic testing \(e.g. myocardial perfusion imaging, CTA and cardiac catheterization\) was noted in )] TJ ET
BT 26.250 633.429 Td /F1 9.8 Tf  [(145 patients following Corus CAD testing \(58% observed vs 10% expected change, p<0.001\). More patients had decreased )] TJ ET
BT 26.250 621.524 Td /F1 9.8 Tf  [(\(n=93, 37%\) versus increased \(n=52, 21%\) intensity of testing \(p<0.001\). In particular, among the 127 low score Corus CAD )] TJ ET
BT 26.250 609.619 Td /F1 9.8 Tf  [(patients \(51% of study patients\), 60% \(76/127\) had decreased testing, and only 2% \(3/127\) had increased testing. After more )] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(than 30 days of follow-up of 247 \(98%\) patients, there has been one MACE event \(hemorrhagic stroke in a low score Corus )] TJ ET
BT 26.250 585.810 Td /F1 9.8 Tf  [(CAD patient\) reported.)] TJ ET
BT 26.250 566.405 Td /F1 9.8 Tf  [(In summary, Corus CAD was associated with a statistically significant and clinically relevant change in clinical decision-making )] TJ ET
BT 26.250 554.500 Td /F1 9.8 Tf  [(among patients evaluated for suspected symptomatic CAD. In addition, the utilization of Corus CAD showed clinical utility above )] TJ ET
BT 26.250 542.595 Td /F1 9.8 Tf  [(and beyond conventional decision-making by optimizing the patient�s diagnostic evaluation, particularly around the reduction in )] TJ ET
BT 26.250 530.691 Td /F1 9.8 Tf  [(the intensity of diagnostic testing among low Corus CAD patients.)] TJ ET
BT 26.250 511.286 Td /F4 9.8 Tf  [(Systematic Evidence Reviews)] TJ ET
BT 26.250 491.881 Td /F1 9.8 Tf  [(Palmetto Government Benefits Administrators \(Palmetto, GBA\), the CMS Medicare Administrative Contractor with oversight for )] TJ ET
BT 26.250 479.976 Td /F1 9.8 Tf  [(Corus CAD, has published its assessment of the test. This review determined that the test meets standards for analytical and )] TJ ET
BT 26.250 468.072 Td /F1 9.8 Tf  [(clinical validity, and clinical utility and is a reasonable and necessary Medicare benefit, effective January 1, 2012 )] TJ ET
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BT 512.336 469.579 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 521.974 468.072 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 448.667 Td /F1 9.8 Tf  [(Overall Analysis of Evidence. The Evaluation of Genomic Applications in Practice and Prevention \(EGAPP\) working group has )] TJ ET
BT 26.250 436.762 Td /F1 9.8 Tf  [(published a framework for evaluation of evidence of genomic testing, comprising analytical and clinical validity and clinical utility )] TJ ET
0.267 0.267 0.267 rg
BT 26.250 426.365 Td /F4 8.7 Tf  [(26)] TJ ET
0.271 0.267 0.267 rg
BT 35.887 424.857 Td /F1 9.8 Tf  [(. For Corus CAD with respect to analytic validity, an extensive study demonstrating very good score reproducibility and the )] TJ ET
BT 26.250 412.953 Td /F1 9.8 Tf  [(ability to result >95% of samples, suggests a Level 1 evidence category in our judgement, for the performance of the test in the )] TJ ET
BT 26.250 401.048 Td /F1 9.8 Tf  [(CardioDx clinical laboratory. For clinical validity it is our assessment that the two prospective multi-center trials with core )] TJ ET
BT 26.250 389.143 Td /F1 9.8 Tf  [(laboratory definition of disease status, representing almost 1000 patients, also correspond to Level 1 evidence according to )] TJ ET
BT 26.250 377.238 Td /F1 9.8 Tf  [(EGAPP criteria )] TJ ET
0.267 0.267 0.267 rg
BT 94.519 378.746 Td /F4 8.7 Tf  [(26)] TJ ET
0.271 0.267 0.267 rg
BT 104.157 377.238 Td /F1 9.8 Tf  [(. The clinical utility data from the IMPACT and retrospective chart review studies are of relatively small size )] TJ ET
BT 26.250 365.334 Td /F1 9.8 Tf  [(and limited follow-up suggesting a level 2-3 evidence determination.)] TJ ET
BT 26.250 328.731 Td /F4 12.0 Tf  [(Limitations)] TJ ET
BT 26.250 308.777 Td /F1 9.8 Tf  [(Although the results of the evaluation of the Corus CAD test are very promising, its results should be interpreted carefully as )] TJ ET
BT 26.250 296.872 Td /F1 9.8 Tf  [(patients with diabetes mellitus and chronic inflammatory or autoimmune disorders were excluded from test development and )] TJ ET
BT 26.250 284.967 Td /F1 9.8 Tf  [(validation. Furthermore, this test was derived and tested in predominantly Caucasian patient populations. Given the known )] TJ ET
BT 26.250 273.063 Td /F1 9.8 Tf  [(variations in the prevalence of CAD in different ethnic/racial backgrounds )] TJ ET
0.267 0.267 0.267 rg
BT 343.262 274.570 Td /F4 8.7 Tf  [(27)] TJ ET
0.271 0.267 0.267 rg
BT 352.899 273.063 Td /F1 9.8 Tf  [(, results of this test in non-Caucasian populations )] TJ ET
BT 26.250 261.158 Td /F1 9.8 Tf  [(should be interpreted with caution.)] TJ ET
BT 26.250 224.555 Td /F4 12.0 Tf  [(Conclusions)] TJ ET
BT 26.250 204.601 Td /F1 9.8 Tf  [(The Corus CAD test has been extensively evaluated since it was first derived, including with two prospective multi-center trials. )] TJ ET
BT 26.250 192.696 Td /F1 9.8 Tf  [(Given the scope of the deleterious effects of CAD and the considerable costs involved in diagnosing obstructive CAD, a blood )] TJ ET
BT 26.250 180.792 Td /F1 9.8 Tf  [(test that can help in this determination is certainly valuable. The Corus CAD test promises to have an important role in this )] TJ ET
BT 26.250 168.887 Td /F1 9.8 Tf  [(regard particularly if it continues to perform this well in larger, more diverse cohorts.)] TJ ET
BT 26.250 132.284 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 112.330 Td /F1 9.8 Tf  [(We thank the team at CardioDx and all the investigators, clinical research staff, and patients who participated in the clinical )] TJ ET
BT 26.250 100.425 Td /F1 9.8 Tf  [(studies in the development, clinical validation, and clinical utilization of Corus CAD.)] TJ ET
BT 26.250 71.323 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 43.869 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 43.869 Td /F1 9.8 Tf  [(Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS )] TJ ET
Q
q
15.000 29.583 577.500 747.417 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F5 9.8 Tf  [(IMPACT-PCP)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(The IMPACT-PCP \(Investigation of a Molecular Personalized Coronary Gene Expression Test on Primary Care Practice )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Pattern\) trial assessed the impact of Corus CAD use on clinical decision-making around the assessment of patients with )] TJ ET
BT 26.250 724.262 Td /F1 9.8 Tf  [(symptoms of obstructive CAD in the primary care setting. The study included a prospective cohort of 251 patients, eligible for )] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(analysis, assessed by 8 community based practitioners at four sites. Clinicians performed a pre-Corus CAD assessment of )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(patients� CAD probability and noted their preliminary management decisions \(no intervention/medical management, referral for )] TJ ET
BT 26.250 688.548 Td /F1 9.8 Tf  [(non-invasive imaging, or referral for invasive angiography\). This pre-Corus CAD assessment was compared to the clinician�s )] TJ ET
BT 26.250 676.643 Td /F1 9.8 Tf  [(assessment of CAD probability after seeing the Corus CAD results \(post-Corus CAD assessment\) and determining a final )] TJ ET
BT 26.250 664.738 Td /F1 9.8 Tf  [(management decision.)] TJ ET
BT 26.250 645.333 Td /F1 9.8 Tf  [(In this study, a change in diagnostic testing \(e.g. myocardial perfusion imaging, CTA and cardiac catheterization\) was noted in )] TJ ET
BT 26.250 633.429 Td /F1 9.8 Tf  [(145 patients following Corus CAD testing \(58% observed vs 10% expected change, p<0.001\). More patients had decreased )] TJ ET
BT 26.250 621.524 Td /F1 9.8 Tf  [(\(n=93, 37%\) versus increased \(n=52, 21%\) intensity of testing \(p<0.001\). In particular, among the 127 low score Corus CAD )] TJ ET
BT 26.250 609.619 Td /F1 9.8 Tf  [(patients \(51% of study patients\), 60% \(76/127\) had decreased testing, and only 2% \(3/127\) had increased testing. After more )] TJ ET
BT 26.250 597.714 Td /F1 9.8 Tf  [(than 30 days of follow-up of 247 \(98%\) patients, there has been one MACE event \(hemorrhagic stroke in a low score Corus )] TJ ET
BT 26.250 585.810 Td /F1 9.8 Tf  [(CAD patient\) reported.)] TJ ET
BT 26.250 566.405 Td /F1 9.8 Tf  [(In summary, Corus CAD was associated with a statistically significant and clinically relevant change in clinical decision-making )] TJ ET
BT 26.250 554.500 Td /F1 9.8 Tf  [(among patients evaluated for suspected symptomatic CAD. In addition, the utilization of Corus CAD showed clinical utility above )] TJ ET
BT 26.250 542.595 Td /F1 9.8 Tf  [(and beyond conventional decision-making by optimizing the patient�s diagnostic evaluation, particularly around the reduction in )] TJ ET
BT 26.250 530.691 Td /F1 9.8 Tf  [(the intensity of diagnostic testing among low Corus CAD patients.)] TJ ET
BT 26.250 511.286 Td /F4 9.8 Tf  [(Systematic Evidence Reviews)] TJ ET
BT 26.250 491.881 Td /F1 9.8 Tf  [(Palmetto Government Benefits Administrators \(Palmetto, GBA\), the CMS Medicare Administrative Contractor with oversight for )] TJ ET
BT 26.250 479.976 Td /F1 9.8 Tf  [(Corus CAD, has published its assessment of the test. This review determined that the test meets standards for analytical and )] TJ ET
BT 26.250 468.072 Td /F1 9.8 Tf  [(clinical validity, and clinical utility and is a reasonable and necessary Medicare benefit, effective January 1, 2012 )] TJ ET
0.267 0.267 0.267 rg
BT 512.336 469.579 Td /F4 8.7 Tf  [(25)] TJ ET
0.271 0.267 0.267 rg
BT 521.974 468.072 Td /F1 9.8 Tf  [(.)] TJ ET
BT 26.250 448.667 Td /F1 9.8 Tf  [(Overall Analysis of Evidence. The Evaluation of Genomic Applications in Practice and Prevention \(EGAPP\) working group has )] TJ ET
BT 26.250 436.762 Td /F1 9.8 Tf  [(published a framework for evaluation of evidence of genomic testing, comprising analytical and clinical validity and clinical utility )] TJ ET
0.267 0.267 0.267 rg
BT 26.250 426.365 Td /F4 8.7 Tf  [(26)] TJ ET
0.271 0.267 0.267 rg
BT 35.887 424.857 Td /F1 9.8 Tf  [(. For Corus CAD with respect to analytic validity, an extensive study demonstrating very good score reproducibility and the )] TJ ET
BT 26.250 412.953 Td /F1 9.8 Tf  [(ability to result >95% of samples, suggests a Level 1 evidence category in our judgement, for the performance of the test in the )] TJ ET
BT 26.250 401.048 Td /F1 9.8 Tf  [(CardioDx clinical laboratory. For clinical validity it is our assessment that the two prospective multi-center trials with core )] TJ ET
BT 26.250 389.143 Td /F1 9.8 Tf  [(laboratory definition of disease status, representing almost 1000 patients, also correspond to Level 1 evidence according to )] TJ ET
BT 26.250 377.238 Td /F1 9.8 Tf  [(EGAPP criteria )] TJ ET
0.267 0.267 0.267 rg
BT 94.519 378.746 Td /F4 8.7 Tf  [(26)] TJ ET
0.271 0.267 0.267 rg
BT 104.157 377.238 Td /F1 9.8 Tf  [(. The clinical utility data from the IMPACT and retrospective chart review studies are of relatively small size )] TJ ET
BT 26.250 365.334 Td /F1 9.8 Tf  [(and limited follow-up suggesting a level 2-3 evidence determination.)] TJ ET
BT 26.250 328.731 Td /F4 12.0 Tf  [(Limitations)] TJ ET
BT 26.250 308.777 Td /F1 9.8 Tf  [(Although the results of the evaluation of the Corus CAD test are very promising, its results should be interpreted carefully as )] TJ ET
BT 26.250 296.872 Td /F1 9.8 Tf  [(patients with diabetes mellitus and chronic inflammatory or autoimmune disorders were excluded from test development and )] TJ ET
BT 26.250 284.967 Td /F1 9.8 Tf  [(validation. Furthermore, this test was derived and tested in predominantly Caucasian patient populations. Given the known )] TJ ET
BT 26.250 273.063 Td /F1 9.8 Tf  [(variations in the prevalence of CAD in different ethnic/racial backgrounds )] TJ ET
0.267 0.267 0.267 rg
BT 343.262 274.570 Td /F4 8.7 Tf  [(27)] TJ ET
0.271 0.267 0.267 rg
BT 352.899 273.063 Td /F1 9.8 Tf  [(, results of this test in non-Caucasian populations )] TJ ET
BT 26.250 261.158 Td /F1 9.8 Tf  [(should be interpreted with caution.)] TJ ET
BT 26.250 224.555 Td /F4 12.0 Tf  [(Conclusions)] TJ ET
BT 26.250 204.601 Td /F1 9.8 Tf  [(The Corus CAD test has been extensively evaluated since it was first derived, including with two prospective multi-center trials. )] TJ ET
BT 26.250 192.696 Td /F1 9.8 Tf  [(Given the scope of the deleterious effects of CAD and the considerable costs involved in diagnosing obstructive CAD, a blood )] TJ ET
BT 26.250 180.792 Td /F1 9.8 Tf  [(test that can help in this determination is certainly valuable. The Corus CAD test promises to have an important role in this )] TJ ET
BT 26.250 168.887 Td /F1 9.8 Tf  [(regard particularly if it continues to perform this well in larger, more diverse cohorts.)] TJ ET
BT 26.250 132.284 Td /F4 12.0 Tf  [(Acknowledgements)] TJ ET
BT 26.250 112.330 Td /F1 9.8 Tf  [(We thank the team at CardioDx and all the investigators, clinical research staff, and patients who participated in the clinical )] TJ ET
BT 26.250 100.425 Td /F1 9.8 Tf  [(studies in the development, clinical validation, and clinical utilization of Corus CAD.)] TJ ET
BT 26.250 71.323 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 43.869 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 43.869 Td /F1 9.8 Tf  [(Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS )] TJ ET
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BT 291.710 19.825 Td /F1 11.0 Tf  [(4)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Evidence on Genomic Tests)] TJ ET

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BT 26.250 767.476 Td /F1 9.8 Tf  [(Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2012;60\(24\):e44-e164.)] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 712.357 Td /F1 9.8 Tf  [(Patel MR, Peterson ED, Dai D, Brennan JM, Redberg RF, Anderson HV, et al. Low diagnostic yield of elective coronary )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(angiography. N Engl J Med. 2010;362\(10\):886-95.)] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 681.048 Td /F1 9.8 Tf  [(Rozanski A, Gransar H, Hayes SW, Min J, Friedman JD, Thomson LE, et al. Temporal trends in the frequency of inducible )] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(myocardial ischemia during cardiac stress testing: 1991 to 2009. J Am Coll Cardiol. 2013;61\(10\):1054-65.)] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 649.738 Td /F1 9.8 Tf  [(Kwok Y, Kim C, Grady D, Segal M, Redberg R. Meta-analysis of exercise testing to detect coronary artery disease in women. )] TJ ET
BT 26.250 637.833 Td /F1 9.8 Tf  [(Am J Cardiol. 1999;83\(5\):660-6.)] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 618.429 Td /F1 9.8 Tf  [(Dolor RJP, M.R.; Melloni, C.; Chatterjee, R.; McBroom, A.J.; Musty, M.D.; Wing, L.; Coeytaux, R.R.; Ross, A.K.; Bastian, )] TJ ET
BT 26.250 606.524 Td /F1 9.8 Tf  [(L.A.; Anderson, M.; Kosinski, A.S.; Sanders, G.D. Noninvasive Tecnologies for the Diagnosis of Coronary Artery Disease in )] TJ ET
BT 26.250 594.619 Td /F1 9.8 Tf  [(Women. Comparative Effectiveness Review No. 58. AHRQ. 2012;12\(EHCO34-EF\).)] TJ ET
BT 26.250 575.214 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 575.214 Td /F1 9.8 Tf  [(Lin GA, Dudley RA, Lucas FL, Malenka DJ, Vittinghoff E, Redberg RF. Frequency of stress testing to document ischemia )] TJ ET
BT 26.250 563.310 Td /F1 9.8 Tf  [(prior to elective percutaneous coronary intervention. Jama. 2008;300\(15\):1765-73.)] TJ ET
BT 26.250 543.905 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 543.905 Td /F1 9.8 Tf  [(Elashoff MR, Wingrove JA, Beineke P, Daniels SE, Tingley WG, Rosenberg S, et al. Development of a blood-based gene )] TJ ET
BT 26.250 532.000 Td /F1 9.8 Tf  [(expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients. BMC Med Genomics. )] TJ ET
BT 26.250 520.095 Td /F1 9.8 Tf  [(2011;4\(1\):26.)] TJ ET
BT 26.250 500.691 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 500.691 Td /F1 9.8 Tf  [(Cayley WE, Jr. Diagnosing the cause of chest pain. Am Fam Physician. 2005;72\(10\):2012-21.)] TJ ET
BT 26.250 481.286 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 481.286 Td /F1 9.8 Tf  [(Fook NU, P.; Agreus, L.; Karlson, B.W.; Nilsson, S.. Approach to managing undiagnosed chest pain. Can Fam Physician. )] TJ ET
BT 26.250 469.381 Td /F1 9.8 Tf  [(2007;53\(2\):261-6.)] TJ ET
BT 26.250 449.976 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 449.976 Td /F1 9.8 Tf  [(Nilsson S, Scheike M, Engblom D, Karlsson LG, Molstad S, Akerlind I, et al. Chest pain and ischaemic heart disease in )] TJ ET
BT 26.250 438.072 Td /F1 9.8 Tf  [(primary care. Br J Gen Pract. 2003;53\(490\):378-82.)] TJ ET
BT 26.250 418.667 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 418.667 Td /F1 9.8 Tf  [(Research XM.)] TJ ET
BT 26.250 399.262 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 399.262 Td /F1 9.8 Tf  [(Ayyad AE, Cole J, Syed A, Desai MY, Halliburton S, Schoenhagen P, et al. Temporal trends in utilization of cardiac )] TJ ET
BT 26.250 387.357 Td /F1 9.8 Tf  [(computed tomography. J Cardiovasc Comput Tomogr. 2009;3\(1\):16-21.)] TJ ET
BT 26.250 367.953 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 367.953 Td /F1 9.8 Tf  [(Ashley EA, Hershberger RE, Caleshu C, Ellinor PT, Garcia JG, Herrington DM, et al. Genetics and cardiovascular disease: )] TJ ET
BT 26.250 356.048 Td /F1 9.8 Tf  [(a policy statement from the American Heart Association. Circulation. 2012;126\(1\):142-57.)] TJ ET
BT 26.250 336.643 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 336.643 Td /F1 9.8 Tf  [(Arnett DK. Summary of the American Heart Association's scientific statement on the relevance of genetics and genomics for )] TJ ET
BT 26.250 324.738 Td /F1 9.8 Tf  [(prevention and treatment of cardiovascular disease. Arterioscler Thromb Vasc Biol. 2007;27\(8\):1682-6.)] TJ ET
BT 26.250 305.334 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 305.334 Td /F1 9.8 Tf  [(Cappola TP, Margulies KB. Functional genomics applied to cardiovascular medicine. Circulation. 2011;124\(1\):87-94.)] TJ ET
BT 26.250 285.929 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 285.929 Td /F1 9.8 Tf  [(Doring Y, Noels H, Weber C. The use of high-throughput technologies to investigate vascular inflammation and )] TJ ET
BT 26.250 274.024 Td /F1 9.8 Tf  [(atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32\(2\):182-95.)] TJ ET
BT 26.250 254.619 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 254.619 Td /F1 9.8 Tf  [(Vargas JD, Lima JA. Coronary artery disease: A gene-expression score to predict obstructive CAD. Nat Rev Cardiol. 2013.)] TJ ET
BT 26.250 235.215 Td /F1 9.8 Tf  [(18.)] TJ ET
BT 43.553 235.215 Td /F1 9.8 Tf  [(Elashoff MR, Nuttall R, Beineke P, Doctolero MH, Dickson M, Johnson AM, et al. Identification of factors contributing to )] TJ ET
BT 26.250 223.310 Td /F1 9.8 Tf  [(variability in a blood-based gene expression test. PLoS One. 2012;7\(7\):e40068.)] TJ ET
BT 26.250 203.905 Td /F1 9.8 Tf  [(19.)] TJ ET
BT 43.553 203.905 Td /F1 9.8 Tf  [(Rosenberg S, Elashoff MR, Beineke P, Daniels SE, Wingrove JA, Tingley WG, et al. Multicenter validation of the diagnostic )] TJ ET
BT 26.250 192.000 Td /F1 9.8 Tf  [(accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients. Ann )] TJ ET
BT 26.250 180.096 Td /F1 9.8 Tf  [(Intern Med. 2010;153\(7\):425-34.)] TJ ET
BT 26.250 160.691 Td /F1 9.8 Tf  [(20.)] TJ ET
BT 43.553 160.691 Td /F1 9.8 Tf  [(Lansky A, Elashoff MR, Ng V, McPherson J, Lazar D, Kraus WE, et al. A gender-specific blood-based gene expression )] TJ ET
BT 26.250 148.786 Td /F1 9.8 Tf  [(score for assessing obstructive coronary artery disease in nondiabetic patients: Results of the Personalized Risk Evaluation and )] TJ ET
BT 26.250 136.881 Td /F1 9.8 Tf  [(Diagnosis in the Coronary Tree \(PREDICT\) Trial. Am Heart J. 2012;164\(3\):320-6.)] TJ ET
BT 26.250 117.477 Td /F1 9.8 Tf  [(21.)] TJ ET
BT 43.553 117.477 Td /F1 9.8 Tf  [(Thomas GS, Voros S, McPherson JA, Lansky AJ, Winn ME, Bateman TM, et al. A blood-based gene expression test for )] TJ ET
BT 26.250 105.572 Td /F1 9.8 Tf  [(obstructive coronary artery disease tested in symptomatic nondiabetic patients referred for myocardial perfusion imaging the )] TJ ET
BT 26.250 93.667 Td /F1 9.8 Tf  [(COMPASS study. Circ Cardiovasc Genet. 2013;6\(2\):154-62.)] TJ ET
BT 26.250 74.262 Td /F1 9.8 Tf  [(22.)] TJ ET
BT 43.553 74.262 Td /F1 9.8 Tf  [(Rosenberg S, Elashoff MR, Lieu HD, Brown BO, Kraus WE, Schwartz RS, et al. Whole Blood Gene Expression Testing for )] TJ ET
BT 26.250 62.358 Td /F1 9.8 Tf  [(Coronary Artery Disease in Nondiabetic Patients: Major Adverse Cardiovascular Events and Interventions in the PREDICT Trial. )] TJ ET
BT 26.250 50.453 Td /F1 9.8 Tf  [(J Cardiovasc Transl Res. 2012;2012:7.)] TJ ET
Q
q
15.000 40.572 577.500 736.428 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2012;60\(24\):e44-e164.)] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 712.357 Td /F1 9.8 Tf  [(Patel MR, Peterson ED, Dai D, Brennan JM, Redberg RF, Anderson HV, et al. Low diagnostic yield of elective coronary )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(angiography. N Engl J Med. 2010;362\(10\):886-95.)] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 681.048 Td /F1 9.8 Tf  [(Rozanski A, Gransar H, Hayes SW, Min J, Friedman JD, Thomson LE, et al. Temporal trends in the frequency of inducible )] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(myocardial ischemia during cardiac stress testing: 1991 to 2009. J Am Coll Cardiol. 2013;61\(10\):1054-65.)] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 649.738 Td /F1 9.8 Tf  [(Kwok Y, Kim C, Grady D, Segal M, Redberg R. Meta-analysis of exercise testing to detect coronary artery disease in women. )] TJ ET
BT 26.250 637.833 Td /F1 9.8 Tf  [(Am J Cardiol. 1999;83\(5\):660-6.)] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 618.429 Td /F1 9.8 Tf  [(Dolor RJP, M.R.; Melloni, C.; Chatterjee, R.; McBroom, A.J.; Musty, M.D.; Wing, L.; Coeytaux, R.R.; Ross, A.K.; Bastian, )] TJ ET
BT 26.250 606.524 Td /F1 9.8 Tf  [(L.A.; Anderson, M.; Kosinski, A.S.; Sanders, G.D. Noninvasive Tecnologies for the Diagnosis of Coronary Artery Disease in )] TJ ET
BT 26.250 594.619 Td /F1 9.8 Tf  [(Women. Comparative Effectiveness Review No. 58. AHRQ. 2012;12\(EHCO34-EF\).)] TJ ET
BT 26.250 575.214 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 575.214 Td /F1 9.8 Tf  [(Lin GA, Dudley RA, Lucas FL, Malenka DJ, Vittinghoff E, Redberg RF. Frequency of stress testing to document ischemia )] TJ ET
BT 26.250 563.310 Td /F1 9.8 Tf  [(prior to elective percutaneous coronary intervention. Jama. 2008;300\(15\):1765-73.)] TJ ET
BT 26.250 543.905 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 543.905 Td /F1 9.8 Tf  [(Elashoff MR, Wingrove JA, Beineke P, Daniels SE, Tingley WG, Rosenberg S, et al. Development of a blood-based gene )] TJ ET
BT 26.250 532.000 Td /F1 9.8 Tf  [(expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients. BMC Med Genomics. )] TJ ET
BT 26.250 520.095 Td /F1 9.8 Tf  [(2011;4\(1\):26.)] TJ ET
BT 26.250 500.691 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 500.691 Td /F1 9.8 Tf  [(Cayley WE, Jr. Diagnosing the cause of chest pain. Am Fam Physician. 2005;72\(10\):2012-21.)] TJ ET
BT 26.250 481.286 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 481.286 Td /F1 9.8 Tf  [(Fook NU, P.; Agreus, L.; Karlson, B.W.; Nilsson, S.. Approach to managing undiagnosed chest pain. Can Fam Physician. )] TJ ET
BT 26.250 469.381 Td /F1 9.8 Tf  [(2007;53\(2\):261-6.)] TJ ET
BT 26.250 449.976 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 449.976 Td /F1 9.8 Tf  [(Nilsson S, Scheike M, Engblom D, Karlsson LG, Molstad S, Akerlind I, et al. Chest pain and ischaemic heart disease in )] TJ ET
BT 26.250 438.072 Td /F1 9.8 Tf  [(primary care. Br J Gen Pract. 2003;53\(490\):378-82.)] TJ ET
BT 26.250 418.667 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 418.667 Td /F1 9.8 Tf  [(Research XM.)] TJ ET
BT 26.250 399.262 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 399.262 Td /F1 9.8 Tf  [(Ayyad AE, Cole J, Syed A, Desai MY, Halliburton S, Schoenhagen P, et al. Temporal trends in utilization of cardiac )] TJ ET
BT 26.250 387.357 Td /F1 9.8 Tf  [(computed tomography. J Cardiovasc Comput Tomogr. 2009;3\(1\):16-21.)] TJ ET
BT 26.250 367.953 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 367.953 Td /F1 9.8 Tf  [(Ashley EA, Hershberger RE, Caleshu C, Ellinor PT, Garcia JG, Herrington DM, et al. Genetics and cardiovascular disease: )] TJ ET
BT 26.250 356.048 Td /F1 9.8 Tf  [(a policy statement from the American Heart Association. Circulation. 2012;126\(1\):142-57.)] TJ ET
BT 26.250 336.643 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 336.643 Td /F1 9.8 Tf  [(Arnett DK. Summary of the American Heart Association's scientific statement on the relevance of genetics and genomics for )] TJ ET
BT 26.250 324.738 Td /F1 9.8 Tf  [(prevention and treatment of cardiovascular disease. Arterioscler Thromb Vasc Biol. 2007;27\(8\):1682-6.)] TJ ET
BT 26.250 305.334 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 305.334 Td /F1 9.8 Tf  [(Cappola TP, Margulies KB. Functional genomics applied to cardiovascular medicine. Circulation. 2011;124\(1\):87-94.)] TJ ET
BT 26.250 285.929 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 285.929 Td /F1 9.8 Tf  [(Doring Y, Noels H, Weber C. The use of high-throughput technologies to investigate vascular inflammation and )] TJ ET
BT 26.250 274.024 Td /F1 9.8 Tf  [(atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32\(2\):182-95.)] TJ ET
BT 26.250 254.619 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 254.619 Td /F1 9.8 Tf  [(Vargas JD, Lima JA. Coronary artery disease: A gene-expression score to predict obstructive CAD. Nat Rev Cardiol. 2013.)] TJ ET
BT 26.250 235.215 Td /F1 9.8 Tf  [(18.)] TJ ET
BT 43.553 235.215 Td /F1 9.8 Tf  [(Elashoff MR, Nuttall R, Beineke P, Doctolero MH, Dickson M, Johnson AM, et al. Identification of factors contributing to )] TJ ET
BT 26.250 223.310 Td /F1 9.8 Tf  [(variability in a blood-based gene expression test. PLoS One. 2012;7\(7\):e40068.)] TJ ET
BT 26.250 203.905 Td /F1 9.8 Tf  [(19.)] TJ ET
BT 43.553 203.905 Td /F1 9.8 Tf  [(Rosenberg S, Elashoff MR, Beineke P, Daniels SE, Wingrove JA, Tingley WG, et al. Multicenter validation of the diagnostic )] TJ ET
BT 26.250 192.000 Td /F1 9.8 Tf  [(accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients. Ann )] TJ ET
BT 26.250 180.096 Td /F1 9.8 Tf  [(Intern Med. 2010;153\(7\):425-34.)] TJ ET
BT 26.250 160.691 Td /F1 9.8 Tf  [(20.)] TJ ET
BT 43.553 160.691 Td /F1 9.8 Tf  [(Lansky A, Elashoff MR, Ng V, McPherson J, Lazar D, Kraus WE, et al. A gender-specific blood-based gene expression )] TJ ET
BT 26.250 148.786 Td /F1 9.8 Tf  [(score for assessing obstructive coronary artery disease in nondiabetic patients: Results of the Personalized Risk Evaluation and )] TJ ET
BT 26.250 136.881 Td /F1 9.8 Tf  [(Diagnosis in the Coronary Tree \(PREDICT\) Trial. Am Heart J. 2012;164\(3\):320-6.)] TJ ET
BT 26.250 117.477 Td /F1 9.8 Tf  [(21.)] TJ ET
BT 43.553 117.477 Td /F1 9.8 Tf  [(Thomas GS, Voros S, McPherson JA, Lansky AJ, Winn ME, Bateman TM, et al. A blood-based gene expression test for )] TJ ET
BT 26.250 105.572 Td /F1 9.8 Tf  [(obstructive coronary artery disease tested in symptomatic nondiabetic patients referred for myocardial perfusion imaging the )] TJ ET
BT 26.250 93.667 Td /F1 9.8 Tf  [(COMPASS study. Circ Cardiovasc Genet. 2013;6\(2\):154-62.)] TJ ET
BT 26.250 74.262 Td /F1 9.8 Tf  [(22.)] TJ ET
BT 43.553 74.262 Td /F1 9.8 Tf  [(Rosenberg S, Elashoff MR, Lieu HD, Brown BO, Kraus WE, Schwartz RS, et al. Whole Blood Gene Expression Testing for )] TJ ET
BT 26.250 62.358 Td /F1 9.8 Tf  [(Coronary Artery Disease in Nondiabetic Patients: Major Adverse Cardiovascular Events and Interventions in the PREDICT Trial. )] TJ ET
BT 26.250 50.453 Td /F1 9.8 Tf  [(J Cardiovasc Transl Res. 2012;2012:7.)] TJ ET
Q
q
15.000 40.572 577.500 736.428 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F1 9.8 Tf  [(Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of )] TJ ET
BT 26.250 755.571 Td /F1 9.8 Tf  [(Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of )] TJ ET
BT 26.250 743.667 Td /F1 9.8 Tf  [(Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for )] TJ ET
BT 26.250 731.762 Td /F1 9.8 Tf  [(Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2012;60\(24\):e44-e164.)] TJ ET
BT 26.250 712.357 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 712.357 Td /F1 9.8 Tf  [(Patel MR, Peterson ED, Dai D, Brennan JM, Redberg RF, Anderson HV, et al. Low diagnostic yield of elective coronary )] TJ ET
BT 26.250 700.452 Td /F1 9.8 Tf  [(angiography. N Engl J Med. 2010;362\(10\):886-95.)] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 681.048 Td /F1 9.8 Tf  [(Rozanski A, Gransar H, Hayes SW, Min J, Friedman JD, Thomson LE, et al. Temporal trends in the frequency of inducible )] TJ ET
BT 26.250 669.143 Td /F1 9.8 Tf  [(myocardial ischemia during cardiac stress testing: 1991 to 2009. J Am Coll Cardiol. 2013;61\(10\):1054-65.)] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 649.738 Td /F1 9.8 Tf  [(Kwok Y, Kim C, Grady D, Segal M, Redberg R. Meta-analysis of exercise testing to detect coronary artery disease in women. )] TJ ET
BT 26.250 637.833 Td /F1 9.8 Tf  [(Am J Cardiol. 1999;83\(5\):660-6.)] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 618.429 Td /F1 9.8 Tf  [(Dolor RJP, M.R.; Melloni, C.; Chatterjee, R.; McBroom, A.J.; Musty, M.D.; Wing, L.; Coeytaux, R.R.; Ross, A.K.; Bastian, )] TJ ET
BT 26.250 606.524 Td /F1 9.8 Tf  [(L.A.; Anderson, M.; Kosinski, A.S.; Sanders, G.D. Noninvasive Tecnologies for the Diagnosis of Coronary Artery Disease in )] TJ ET
BT 26.250 594.619 Td /F1 9.8 Tf  [(Women. Comparative Effectiveness Review No. 58. AHRQ. 2012;12\(EHCO34-EF\).)] TJ ET
BT 26.250 575.214 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 575.214 Td /F1 9.8 Tf  [(Lin GA, Dudley RA, Lucas FL, Malenka DJ, Vittinghoff E, Redberg RF. Frequency of stress testing to document ischemia )] TJ ET
BT 26.250 563.310 Td /F1 9.8 Tf  [(prior to elective percutaneous coronary intervention. Jama. 2008;300\(15\):1765-73.)] TJ ET
BT 26.250 543.905 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 543.905 Td /F1 9.8 Tf  [(Elashoff MR, Wingrove JA, Beineke P, Daniels SE, Tingley WG, Rosenberg S, et al. Development of a blood-based gene )] TJ ET
BT 26.250 532.000 Td /F1 9.8 Tf  [(expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients. BMC Med Genomics. )] TJ ET
BT 26.250 520.095 Td /F1 9.8 Tf  [(2011;4\(1\):26.)] TJ ET
BT 26.250 500.691 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 500.691 Td /F1 9.8 Tf  [(Cayley WE, Jr. Diagnosing the cause of chest pain. Am Fam Physician. 2005;72\(10\):2012-21.)] TJ ET
BT 26.250 481.286 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 481.286 Td /F1 9.8 Tf  [(Fook NU, P.; Agreus, L.; Karlson, B.W.; Nilsson, S.. Approach to managing undiagnosed chest pain. Can Fam Physician. )] TJ ET
BT 26.250 469.381 Td /F1 9.8 Tf  [(2007;53\(2\):261-6.)] TJ ET
BT 26.250 449.976 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 449.976 Td /F1 9.8 Tf  [(Nilsson S, Scheike M, Engblom D, Karlsson LG, Molstad S, Akerlind I, et al. Chest pain and ischaemic heart disease in )] TJ ET
BT 26.250 438.072 Td /F1 9.8 Tf  [(primary care. Br J Gen Pract. 2003;53\(490\):378-82.)] TJ ET
BT 26.250 418.667 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 418.667 Td /F1 9.8 Tf  [(Research XM.)] TJ ET
BT 26.250 399.262 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 399.262 Td /F1 9.8 Tf  [(Ayyad AE, Cole J, Syed A, Desai MY, Halliburton S, Schoenhagen P, et al. Temporal trends in utilization of cardiac )] TJ ET
BT 26.250 387.357 Td /F1 9.8 Tf  [(computed tomography. J Cardiovasc Comput Tomogr. 2009;3\(1\):16-21.)] TJ ET
BT 26.250 367.953 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 367.953 Td /F1 9.8 Tf  [(Ashley EA, Hershberger RE, Caleshu C, Ellinor PT, Garcia JG, Herrington DM, et al. Genetics and cardiovascular disease: )] TJ ET
BT 26.250 356.048 Td /F1 9.8 Tf  [(a policy statement from the American Heart Association. Circulation. 2012;126\(1\):142-57.)] TJ ET
BT 26.250 336.643 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 336.643 Td /F1 9.8 Tf  [(Arnett DK. Summary of the American Heart Association's scientific statement on the relevance of genetics and genomics for )] TJ ET
BT 26.250 324.738 Td /F1 9.8 Tf  [(prevention and treatment of cardiovascular disease. Arterioscler Thromb Vasc Biol. 2007;27\(8\):1682-6.)] TJ ET
BT 26.250 305.334 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 305.334 Td /F1 9.8 Tf  [(Cappola TP, Margulies KB. Functional genomics applied to cardiovascular medicine. Circulation. 2011;124\(1\):87-94.)] TJ ET
BT 26.250 285.929 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 285.929 Td /F1 9.8 Tf  [(Doring Y, Noels H, Weber C. The use of high-throughput technologies to investigate vascular inflammation and )] TJ ET
BT 26.250 274.024 Td /F1 9.8 Tf  [(atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32\(2\):182-95.)] TJ ET
BT 26.250 254.619 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 254.619 Td /F1 9.8 Tf  [(Vargas JD, Lima JA. Coronary artery disease: A gene-expression score to predict obstructive CAD. Nat Rev Cardiol. 2013.)] TJ ET
BT 26.250 235.215 Td /F1 9.8 Tf  [(18.)] TJ ET
BT 43.553 235.215 Td /F1 9.8 Tf  [(Elashoff MR, Nuttall R, Beineke P, Doctolero MH, Dickson M, Johnson AM, et al. Identification of factors contributing to )] TJ ET
BT 26.250 223.310 Td /F1 9.8 Tf  [(variability in a blood-based gene expression test. PLoS One. 2012;7\(7\):e40068.)] TJ ET
BT 26.250 203.905 Td /F1 9.8 Tf  [(19.)] TJ ET
BT 43.553 203.905 Td /F1 9.8 Tf  [(Rosenberg S, Elashoff MR, Beineke P, Daniels SE, Wingrove JA, Tingley WG, et al. Multicenter validation of the diagnostic )] TJ ET
BT 26.250 192.000 Td /F1 9.8 Tf  [(accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients. Ann )] TJ ET
BT 26.250 180.096 Td /F1 9.8 Tf  [(Intern Med. 2010;153\(7\):425-34.)] TJ ET
BT 26.250 160.691 Td /F1 9.8 Tf  [(20.)] TJ ET
BT 43.553 160.691 Td /F1 9.8 Tf  [(Lansky A, Elashoff MR, Ng V, McPherson J, Lazar D, Kraus WE, et al. A gender-specific blood-based gene expression )] TJ ET
BT 26.250 148.786 Td /F1 9.8 Tf  [(score for assessing obstructive coronary artery disease in nondiabetic patients: Results of the Personalized Risk Evaluation and )] TJ ET
BT 26.250 136.881 Td /F1 9.8 Tf  [(Diagnosis in the Coronary Tree \(PREDICT\) Trial. Am Heart J. 2012;164\(3\):320-6.)] TJ ET
BT 26.250 117.477 Td /F1 9.8 Tf  [(21.)] TJ ET
BT 43.553 117.477 Td /F1 9.8 Tf  [(Thomas GS, Voros S, McPherson JA, Lansky AJ, Winn ME, Bateman TM, et al. A blood-based gene expression test for )] TJ ET
BT 26.250 105.572 Td /F1 9.8 Tf  [(obstructive coronary artery disease tested in symptomatic nondiabetic patients referred for myocardial perfusion imaging the )] TJ ET
BT 26.250 93.667 Td /F1 9.8 Tf  [(COMPASS study. Circ Cardiovasc Genet. 2013;6\(2\):154-62.)] TJ ET
BT 26.250 74.262 Td /F1 9.8 Tf  [(22.)] TJ ET
BT 43.553 74.262 Td /F1 9.8 Tf  [(Rosenberg S, Elashoff MR, Lieu HD, Brown BO, Kraus WE, Schwartz RS, et al. Whole Blood Gene Expression Testing for )] TJ ET
BT 26.250 62.358 Td /F1 9.8 Tf  [(Coronary Artery Disease in Nondiabetic Patients: Major Adverse Cardiovascular Events and Interventions in the PREDICT Trial. )] TJ ET
BT 26.250 50.453 Td /F1 9.8 Tf  [(J Cardiovasc Transl Res. 2012;2012:7.)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(5)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Evidence on Genomic Tests)] TJ ET

Q
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0.271 0.267 0.267 rg
q
15.000 557.833 577.500 219.167 re W n
0.271 0.267 0.267 rg
BT 26.250 759.976 Td /F1 9.8 Tf  [(23.)] TJ ET
BT 43.553 759.976 Td /F1 9.8 Tf  [(Conlin MFH, L.; Mouton, M.; Wilson, L.; Yau, M.; Elashoff, M.; Monane, M.; McPherson, J.A. The Use of a Personalized )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(Gene Expression Test to Improve Decision Making in the Evaluation of Patients with Suspected Coronary Artery Disease. J )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Gen Intern Med. 2012;27:S540-1.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(24.)] TJ ET
BT 43.553 716.762 Td /F1 9.8 Tf  [(McPherson JA, Davis K, Yau M, Beineke P, Rosenberg S, Monane M, et al. The Clinical Utility of Gene Expression Testing )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(on the Diagnostic Evaluation of Patients Presenting to the Cardiologist With Symptoms of Suspected Obstructive Coronary )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(Artery Disease: Results From the IMPACT \(Investigation of a Molecular Personalized Coronary Gene Expression Test on )] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(Cardiology Practice Pattern\) Trial. Crit Pathw Cardiol. 2013;12\(2\):37-42.)] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(25.)] TJ ET
BT 43.553 661.643 Td /F1 9.8 Tf  [(MolDx Corus CAD Test Coding and Billing Guidelines. 2013. )] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(https://www.palmettogba.com/palmetto/providers.nsf/DocsCat/Providers~Ju )] TJ ET
BT 26.250 637.833 Td /F1 9.8 Tf  [(risdiction%201%20Part%20B~Browse%20by%20Topic~MolDx~Covered %20Tests~8WXQ5R5416?open&navmenu=%7C%7C)] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(26.)] TJ ET
BT 43.553 618.429 Td /F1 9.8 Tf  [(Teutsch SM, Bradley LA, Palomaki GE, Haddow JE, Piper M, Calonge N, et al. The Evaluation of Genomic Applications in )] TJ ET
BT 26.250 606.524 Td /F1 9.8 Tf  [(Practice and Prevention \(EGAPP\) Initiative: methods of the EGAPP Working Group. Genet Med. 2009;11\(1\):3-14.)] TJ ET
BT 26.250 587.119 Td /F1 9.8 Tf  [(27.)] TJ ET
BT 43.553 587.119 Td /F1 9.8 Tf  [(Bild DE, Detrano R, Peterson D, Guerci A, Liu K, Shahar E, et al. Ethnic differences in coronary calcification: the Multi-)] TJ ET
BT 26.250 575.214 Td /F1 9.8 Tf  [(Ethnic Study of Atherosclerosis \(MESA\). Circulation. 2005;111\(10\):1313-20.)] TJ ET
Q
q
15.000 557.833 577.500 219.167 re W n
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BT 26.250 759.976 Td /F1 9.8 Tf  [(23.)] TJ ET
BT 43.553 759.976 Td /F1 9.8 Tf  [(Conlin MFH, L.; Mouton, M.; Wilson, L.; Yau, M.; Elashoff, M.; Monane, M.; McPherson, J.A. The Use of a Personalized )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(Gene Expression Test to Improve Decision Making in the Evaluation of Patients with Suspected Coronary Artery Disease. J )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Gen Intern Med. 2012;27:S540-1.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(24.)] TJ ET
BT 43.553 716.762 Td /F1 9.8 Tf  [(McPherson JA, Davis K, Yau M, Beineke P, Rosenberg S, Monane M, et al. The Clinical Utility of Gene Expression Testing )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(on the Diagnostic Evaluation of Patients Presenting to the Cardiologist With Symptoms of Suspected Obstructive Coronary )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(Artery Disease: Results From the IMPACT \(Investigation of a Molecular Personalized Coronary Gene Expression Test on )] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(Cardiology Practice Pattern\) Trial. Crit Pathw Cardiol. 2013;12\(2\):37-42.)] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(25.)] TJ ET
BT 43.553 661.643 Td /F1 9.8 Tf  [(MolDx Corus CAD Test Coding and Billing Guidelines. 2013. )] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(https://www.palmettogba.com/palmetto/providers.nsf/DocsCat/Providers~Ju )] TJ ET
BT 26.250 637.833 Td /F1 9.8 Tf  [(risdiction%201%20Part%20B~Browse%20by%20Topic~MolDx~Covered %20Tests~8WXQ5R5416?open&navmenu=%7C%7C)] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(26.)] TJ ET
BT 43.553 618.429 Td /F1 9.8 Tf  [(Teutsch SM, Bradley LA, Palomaki GE, Haddow JE, Piper M, Calonge N, et al. The Evaluation of Genomic Applications in )] TJ ET
BT 26.250 606.524 Td /F1 9.8 Tf  [(Practice and Prevention \(EGAPP\) Initiative: methods of the EGAPP Working Group. Genet Med. 2009;11\(1\):3-14.)] TJ ET
BT 26.250 587.119 Td /F1 9.8 Tf  [(27.)] TJ ET
BT 43.553 587.119 Td /F1 9.8 Tf  [(Bild DE, Detrano R, Peterson D, Guerci A, Liu K, Shahar E, et al. Ethnic differences in coronary calcification: the Multi-)] TJ ET
BT 26.250 575.214 Td /F1 9.8 Tf  [(Ethnic Study of Atherosclerosis \(MESA\). Circulation. 2005;111\(10\):1313-20.)] TJ ET
Q
q
15.000 557.833 577.500 219.167 re W n
0.271 0.267 0.267 rg
BT 26.250 759.976 Td /F1 9.8 Tf  [(23.)] TJ ET
BT 43.553 759.976 Td /F1 9.8 Tf  [(Conlin MFH, L.; Mouton, M.; Wilson, L.; Yau, M.; Elashoff, M.; Monane, M.; McPherson, J.A. The Use of a Personalized )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(Gene Expression Test to Improve Decision Making in the Evaluation of Patients with Suspected Coronary Artery Disease. J )] TJ ET
BT 26.250 736.167 Td /F1 9.8 Tf  [(Gen Intern Med. 2012;27:S540-1.)] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(24.)] TJ ET
BT 43.553 716.762 Td /F1 9.8 Tf  [(McPherson JA, Davis K, Yau M, Beineke P, Rosenberg S, Monane M, et al. The Clinical Utility of Gene Expression Testing )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(on the Diagnostic Evaluation of Patients Presenting to the Cardiologist With Symptoms of Suspected Obstructive Coronary )] TJ ET
BT 26.250 692.952 Td /F1 9.8 Tf  [(Artery Disease: Results From the IMPACT \(Investigation of a Molecular Personalized Coronary Gene Expression Test on )] TJ ET
BT 26.250 681.048 Td /F1 9.8 Tf  [(Cardiology Practice Pattern\) Trial. Crit Pathw Cardiol. 2013;12\(2\):37-42.)] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(25.)] TJ ET
BT 43.553 661.643 Td /F1 9.8 Tf  [(MolDx Corus CAD Test Coding and Billing Guidelines. 2013. )] TJ ET
BT 26.250 649.738 Td /F1 9.8 Tf  [(https://www.palmettogba.com/palmetto/providers.nsf/DocsCat/Providers~Ju )] TJ ET
BT 26.250 637.833 Td /F1 9.8 Tf  [(risdiction%201%20Part%20B~Browse%20by%20Topic~MolDx~Covered %20Tests~8WXQ5R5416?open&navmenu=%7C%7C)] TJ ET
BT 26.250 618.429 Td /F1 9.8 Tf  [(26.)] TJ ET
BT 43.553 618.429 Td /F1 9.8 Tf  [(Teutsch SM, Bradley LA, Palomaki GE, Haddow JE, Piper M, Calonge N, et al. The Evaluation of Genomic Applications in )] TJ ET
BT 26.250 606.524 Td /F1 9.8 Tf  [(Practice and Prevention \(EGAPP\) Initiative: methods of the EGAPP Working Group. Genet Med. 2009;11\(1\):3-14.)] TJ ET
BT 26.250 587.119 Td /F1 9.8 Tf  [(27.)] TJ ET
BT 43.553 587.119 Td /F1 9.8 Tf  [(Bild DE, Detrano R, Peterson D, Guerci A, Liu K, Shahar E, et al. Ethnic differences in coronary calcification: the Multi-)] TJ ET
BT 26.250 575.214 Td /F1 9.8 Tf  [(Ethnic Study of Atherosclerosis \(MESA\). Circulation. 2005;111\(10\):1313-20.)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(6)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Evidence on Genomic Tests)] TJ ET

Q
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