Geoffrey D. Rubin, M.D.George B. Geller Professor of Radiology & Biomedical Engineering

Chairman, Department of RadiologyDuke University

Coronary CT Angiography: Available And Pending Evidence

Asymptomaticactive

59 y.o. man

Accuracy TrialProspective, multi-center (16 site) trial

Supported and coordinated by G.E. Healthcare

230 subjects (59% male, 57±10 y.)

Presentation: chest pain & referral for non-emergent invasive coronary angiography

Retrospective gating with target HR <65 bpm

3 readers, result (per subject and per artery) based upon consensus (! 2)

EXPEDITED PUBLICATION

Diagnostic Performance of 64-Multidetector RowCoronary Computed Tomographic Angiography forEvaluation of Coronary Artery Stenosis in IndividualsWithout Known Coronary Artery DiseaseResults From the Prospective Multicenter ACCURACY (Assessmentby Coronary Computed Tomographic Angiography of IndividualsUndergoing Invasive Coronary Angiography) Trial

Matthew J. Budoff, MD,* David Dowe, MD,† James G. Jollis, MD,‡ Michael Gitter, MD,§John Sutherland, MD,! Edward Halamert, MD,¶ Markus Scherer, MD,# Raye Bellinger, MD,**Arthur Martin, MD,†† Robert Benton, MD,‡‡ Augustin Delago, MD,‡‡ James K. Min, MD§§

Torrance and Sacramento, California; Atlantic City, New Jersey; Durham and Concord, North Carolina; Appleton,Wisconsin; Phoenix, Arizona; Indianapolis, Indiana; Hattiesburg, Mississippi; and Albany and New York, New York

Objectives The purpose of this study was to evaluate the diagnostic accuracy of electrocardiographically gated 64-multidetectorrow coronary computed tomographic angiography (CCTA) in individuals without known coronary artery disease (CAD).

Background CCTA is a promising method for detection and exclusion of obstructive coronary artery stenosis. To date, no pro-spective multicenter trial has evaluated the diagnostic accuracy of 64-multidetector row CCTA in populationswith intermediate prevalence of CAD.

Methods We prospectively evaluated subjects with chest pain at 16 sites who were clinically referred for invasive coronaryangiography (ICA). CCTAs were scored by consensus of 3 independent blinded readers. The ICAs were evaluatedfor coronary stenosis based on quantitative coronary angiography (QCA). No subjects were excluded for baselinecoronary artery calcium score or body mass index.

Results A total of 230 subjects underwent both CCTA and ICA (59.1% male; mean age: 57 ! 10 years). On a patient-based model, the sensitivity, specificity, and positive and negative predictive values to detect !50% or !70%stenosis were 95%, 83%, 64%, and 99%, respectively, and 94%, 83%, 48%, 99%, respectively. No differences insensitivity and specificity were noted for nonobese compared with obese subjects or for heart rates "65 beats/min compared with "65 beats/min, whereas calcium scores "400 reduced specificity significantly.

Conclusions In this prospective multicenter trial of chest pain patients without known CAD, 64-multidetector row CCTA pos-sesses high diagnostic accuracy for detection of obstructive coronary stenosis at both thresholds of 50% and70% stenosis. Importantly, the 99% negative predictive value at the patient and vessel level establishes CCTA as aneffective noninvasive alternative to ICA to rule out obstructive coronary artery stenosis. (A Study of Computed Tomog-raphy [CT] for Evaluation of Coronary Artery Blockages in Typical or Atypical Chest Pain; NCT00348569) (J Am CollCardiol 2008;52:000–000) © 2008 by the American College of Cardiology Foundation

*From the Department of Medicine, Los Angeles Biomedical Research Institute atHarbor-UCLA, Torrance, California; †Department of Radiology, Atlantic MedicalImaging, Atlantic City, New Jersey; ‡Department of Medicine, Duke University MedicalCenter, Durham, North Carolina; §Appleton Cardiology, Appleton, Wisconsin;!Arizona Heart Institute, Phoenix, Arizona; ¶Indiana Heart Hospital, Indianapolis,Indiana; #Northeast Medical Center, Concord, North Carolina; **Sacramento Heartand Vascular Research Center, Sacramento, California; ††Southern Heart Center,Hattiesburg, Mississippi; ‡‡Capital Cardiology Associates, Albany, New York; andthe §§Departments of Medicine and Radiology, Weill Medical College of Cornell

University and New York Presbyterian Hospital, New York, New York. Supported byGeneral Electric (GE); GE Healthcare sponsored and coordinated the study andprovided recommendations for computed tomography X-ray dosing and injectionprotocols, site training, and logistical support for data transfer from individual sites tothe core laboratories; GE Healthcare allowed the principal investigators to direct thedata analysis, manuscript preparation, and review or authorization for submission.Drs. Budoff and Min are on the Speakers’ Bureau for General Electric.

Manuscript received May 13, 2008; revised manuscript received July 11, 2008,accepted July 30, 2008.

Journal of the American College of Cardiology Vol. 52, No. xx, 2008© 2008 by the American College of Cardiology Foundation ISSN 0735-1097/08/$34.00Published by Elsevier Inc. doi:10.1016/j.jacc.2008.07.031

ARTICLE IN PRESS

by on September 12, 2008 content.onlinejacc.orgDownloaded from

ACCURACY Trial. JACC 2008:52

Per SubjectPer Subject Per ArteryPer Artery

Se 0.95 52/55 0.84 73/87

Sp 0.83 142/172 0.90 744/823

PPV 0.64 52/81 0.51 73/143

NPV 0.99 142/143 0.99 744/754

CORE 64 TrialProspective, multi-center (9 site, 7 country) trial

Supported by Toshiba Medical Systems

291 subjects (74% male, 59 y.) with CAC " 600

Presentation: symptomatic & referral for non-emergent invasive coronary angiography

Retrospective gating with target HR <70 bpm

2 readers, if disagreement, then adjudication by a third reader

N Engl J Med 2008;359:2324-36.

Per SubjectPer Subject Per ArteryPer Artery

Threshold ! 50% 163/291 subjects (56%) 271/868 arteries (31%)Threshold ! 50% 163/291 subjects (56%) 271/868 arteries (31%)Threshold ! 50% 163/291 subjects (56%) 271/868 arteries (31%)Threshold ! 50% 163/291 subjects (56%) 271/868 arteries (31%)Threshold ! 50% 163/291 subjects (56%) 271/868 arteries (31%)Threshold ! 50% 163/291 subjects (56%) 271/868 arteries (31%)

C64 C64

Se 0.83 0.75

Sp 0.90 0.93

PPV 0.91 0.83

NPV 0.83 0.89

Accuracy Accuracy

0.95 0.84

0.83 0.90

0.64 0.51

0.99 0.99

• technical competence• site dominance• spectrum bias• prevalence: 56% (C64) vs.

25% (ACCURACY)

TPTP + FN

TNTN + FPTP

TP + FPTN

TN + FN

Undercall

Overcall

The Dutch TrialProspective, multi-center (3 site, 1 country) trial

Supported by Dutch government grant

3 different manufacturer’s CT scanners used

360 subjects (74% male, 50-70 y.), no CAC cut-off

Presentation: symptomatic & referral for non-emergent invasive coronary angiography

2 readers, if disagreement, then adjudication by a third reader

JACC 2008;52:2135-44

Per SubjectPer SubjectPer SubjectPer Subject

Dutch C64 Accuracy

Prev 0.68 0.56 0.25

Se 0.99 0.83 0.95

Sp 0.64 0.90 0.83

PPV 0.86 0.91 0.64

NPV 0.97 0.83 0.99

0

0.25

0.5

0.75

1

0 0.25 0.5 0.75 1

Sen

siti

vity

1-Specificity

DutchAccuracy

Core 64

6 million patients in U.S. each year

55-85% without cardiac disease

Most are admitted to observation units serial serum markers & EKGs, stress testing with possible radionuclide imaging

2-10% with ACS are inappropriately sent home

Cost of negative exams is $10-13 billion/yr

Chest Pain in the Emergency Dept. ROMICAT I Trial

368 patients with chest pain, negative initial troponin& nonischemic ECG

All had CTA and results not initially disclosed

50% negative CTA, 31% non-obstructive, 19% positive or inconclusive

31 patients had ACS

Sensitivity and NPV for ACS was 100%

Hoffmann, et al., JACC 2009; 53:1642

Feasibility

Diagnostic Performance

Health Outcomes

Societal ImpactsCost-effectiveness, risk

Interventional RCTsPROMISE – Impact of functional vs. anatomic testing for CP on ACS, death, & major complications 3,177 of 10,000 recruited

RESCUE – Equivalent results & more cost-effective than SPECT MPI measured by revasc., MI, & cardiac death. Rx based upon *COURAGE trial.4300 subjects to be recruited

ROMICAT II – Impact of CT vs. standard w/u for acute CP on length of stay, time to dx, MACE, CE, healthcare utilization. 1000 subjects to be recruited

*N Engl J Med 2007;35:1503–16

SummaryThe high NPV appears ideal for excluding disease in low to intermediate risk patients, but low PPV may result in unnecessary work-up. This could change

Trials are underway (PROMISE, RESCUE) to determine effect of management of patients based upon CCTA

Based upon expert opinion in 2010, the use of CCTA is appropriate for those with non-acute chest pain and an intermediate level of risk