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European Journal of Radiology 81 (2012) 3719– 3725

Contents lists available at ScienceDirect

European Journal of Radiology

jo ur n al hom epage: www.elsev ier .com/ locate /e j rad

ost-effectiveness of substituting dual-energy CT for SPECT in the assessmentf myocardial perfusion for the workup of coronary artery disease

athias Meyera,c, John W. Nance Jr. a, U. Joseph Schoepfa,b,∗, Antonio Moscarielloa,d,arkus Weiningera, Garrett W. Rowea, Balazs Ruzsicsa, Doo Kyoung Kanga,e,

alvatore A. Chiaramidab, Stefan O. Schoenbergc, Christian Finkc, Thomas Henzlera,c

Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USADepartment of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston, SC, USAInstitute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim–Heidelberg University, Mannheim, GermanyDepartment of Bioimaging and Radiological Sciences, Catholic University of Sacred Heart, “A. Gemelli” Hospital, Rome, ItalyDepartment of Radiology, Ajou University School of Medicine, Suwon, South Korea

r t i c l e i n f o

rticle history:eceived 21 December 2010ccepted 22 December 2010

eywords:ual-energy computed tomographyingle photon emission computedomography

yocardial perfusionost effectiveness

a b s t r a c t

Purpose: We compared cost-effectiveness and potential lifetime benefits of using dual-energy computedtomography (DECT) for myocardial perfusion assessment instead of single photon emission computedtomography (SPECT) for the workup of coronary artery disease (CAD).Materials and methods: A decision and simulation model was developed to estimate cost and healtheffects of using DECT myocardial perfusion imaging instead of SPECT for identifying patients in needof invasive imaging and possible revascularization. The model was based on the performance indicesof stress/rest DECT compared with stress/rest SPECT for detecting myocardial perfusion deficits in 50patients (mean age 61 ± 10 years) with CAD. Stress/rest perfusion and delayed enhancement cardiac MRIserved as reference standard. For DECT a reimbursement of US$1700 was assumed but costs of cardiacMRI were not included in the model. All other actual healthcare costs in these patients were derived fromMUSC’s hospital billing system.Results: Compared with cardiac MRI, DECT (versus SPECT) had 90% (85%) sensitivity and 71% (58%) speci-ficity for identifying patients with obstructive CAD. Compared with the no imaging and no treatmentstrategy, routine SPECT gained 13.49 quality-adjusted life-years (QALYs) with an incremental cost-

effectiveness ratio (ICER) of US$3557 (in 2010) per QALY. In comparison, DECT ICER was lower (US$3.191per QALY, p = 0.0002) and an additional 0.64 QALYs was obtained (total of 14.13 QALYs) if compared withthe SPECT strategy as well as the no imaging and no treatment strategy.Conclusion: Using DECT as the first-line imaging test for myocardial perfusion for the workup of patientswith CAD has the potential to provide gains in QALYs, while lowering costs if compared to routine

CT.

myocardial perfusion SPE

. Introduction

Conventional diagnostic workup of patients with suspectedoronary artery disease (CAD) is based on physiological versusnatomical testing, or a combination of both [1]. While cardiac mag-etic resonance imaging (cMRI) [2] has demonstrated superiority in

etecting physiologically significant perfusion defects due to coro-ary artery stenosis, single photon emission computed tomographySPECT) [3] is still the most widely used test for this purpose. Yet

∗ Corresponding author at: Heart & Vascular Center, Medical University of Southarolina, Ashley River Tower, 25 Courtenay Drive, MSC 226, Charleston, SC 29401,SA. Tel.: +1 843 876 7146; fax: +1 843 876 3157.

E-mail address: schoepf@musc.edu (U.J. Schoepf).

720-048X/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.oi:10.1016/j.ejrad.2010.12.055

© 2010 Elsevier Ireland Ltd. All rights reserved.

the specificity of SPECT is limited, resulting in a relatively highfalse-positive rate (FPR) when the pre-test probability of diseaseis low [4] leading to unnecessary referrals for diagnostic catheterangiography.

While anatomical testing, such as invasive coronary angiog-raphy, can directly visualize and grade coronary artery stenosis,it has limitations for grading the hemodynamic effect of lesionson myocardial perfusion [5]. Consequently, a single test for thecomprehensive evaluation of both disease components would befavorable. Coronary computed tomography angiography (cCTA) indual-energy mode recently emerged and has been reported to pro-

vide good diagnostic accuracy in the detection of physiologicallysignificant stenoses via material differentiation and quantifica-tion of myocardial iodine distribution [6]. Dual-energy computedtomography (DECT) may therefore serve as a possible stand-alone

3720 M. Meyer et al. / European Journal of R

Table 1Patients characteristics.

Patients demographicsAge (years) 61 ± 10Female (%) 26Male (%) 74

Risk factors (%)Diabetes mellitus 28Hypertension 92Dyslipidemia 80Family history of CAD (%) 62BMI (kg/m2) 27.3 ± 9.3Weight (kg) 84 ± 19

Prior medical history (%)Angina pectoris 88Myocardial infarct 48PCI 48CABG 22Cerebrovascular event 10

Post-medical procedures within 2 months (%)PCI 30CABG 5

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ote: CAD, coronary artery disease; PCI, percutaneous coronary intervention; CABG,oronary artery bypass graft.

est for comprehensive assessment of cardiac anatomy (includingoronary artery morphology), function, perfusion, and viability inatients with acute chest pain or known CAD [6,7].

Until now no comparative data is available on the effective-ess of SPECT versus DECT for myocardial perfusion assessment

n terms of lifetime benefits and health care expenditures. Pur-ose of this study was to compare diagnostic accuracy, incrementalost-effectiveness and gain in quality-adjusted life-years (QALYs)f SPECT versus DECT imaging for myocardial perfusion in workupf patients with CAD.

. Materials and methods

.1. Patients

The study protocol was approved by MUSC’s Institutionaleview Board and each patient gave written informed consentrior to examination and study inclusion. Prospectively 50 patientsere clinically referred for stress/rest SPECT for the workup of CAD.

atient demographic data are displayed in Table 1. Study popula-ion consisted of 74% (37/50) male patients with an average agef 61 ± 10 years and an average body weight of 83 ± 21 kg. Historyf prior myocardial infarction (MI) was observed in 24 patients.ixteen patients did not have any past medical history of heart dis-ase. Ten of 50 patients underwent coronary artery bypass graftithin the next 2 months after imaging due to severe two or three

essel disease. In addition to SPECT imaging, each patient under-ent adenosine stress/rest perfusion and delayed enhancement

MRI and adenosine stress/rest and delayed enhancement DECT ofhe heart. Afterwards all patients were classified as true-positives,alse-positives, true-negatives, or false-negatives for perfusionefects using cMRI results as reference standard.

.2. SPECT procedures

SPECT was performed after intravenous administration of Tetro-osmin (99mTechnetium), based on a one-day protocol. An activityf 370 MBq at rest and 1110 MBq immediately after peak stressere injected. Ergometric stress testing was carried out using theruce treadmill protocol. Pharmacological stress testing during

eak adenosine (140 �g/min/kg Adenoscan, Astellas, Deerfield, IL)tress was used if there were contraindications for ergometric test-ng. A triple-head camera (Vertex 60+, collimator VXGP, Philips,leveland, OH) with attenuation correction was used for ECG-gated

adiology 81 (2012) 3719– 3725

data acquisition. Studies were interpreted for perfusion defects byconsensus of two experienced observers using the AHA 17 segmentmodel [8].

2.3. cMRI

All patients underwent cMRI on a 1.5T scanner (Avanto,Siemens, Erlangen, Germany). Contrast (Gd-DTPA, Magnevist,Bayer, Wayne, NJ) enhanced perfusion studies were acquiredduring peak adenosine stress (140 g/kg/min Adenoscan, Astellas,Tokyo, Japan) and at rest. Delayed enhancement studies wereacquired 15 min after the last contrast injection. Perfusion anddelayed enhancement imaging used single shot SR-trueFISP andT1 weighted sequences with TI of 250 ms (adjusted to null viablemyocardium) and a TR of 2 cardiac cycles. Studies were interpretedfor perfusion defects and delayed enhancement by consensus oftwo experienced observers using the AHA 17 segment model [8].

2.4. DECT procedures

All patients were examined using a 64-sction dual-source CTsystem (SOMATON Definition FLASH, Siemens Healthcare Sector,Forchheim, Germany) in dual-energy mode.

CT assessment started with single heart-beat CT calcium scoringusing the following parameters: 2 mm × 128 mm × 0.6 mm sec-tions, 280 ms gantry rotation time, 120 kV tube potential and73 mAs per rotation tube current time product. Subsequentlyprospectively ECG-triggered coronary CT angiography was per-formed. Contrast medium enhancement was achieved using atriphasic injection protocol with injection of 70 ml of pure, undi-luted iodinated contrast material (Iopromide, Ultravist 370 mgI/ml,Bayer-Schering Pharma AG, Berlin, Germany) followed by a con-stant volume of 50 ml of a 70%:30% saline-to-contrast mediummixture and 30 ml of pure saline, all injected at 6 ml/s throughan 18G intravenous antecubital catheter using a dual-syringeinjector (Stellant D, Medrad, Indianola, PA, USA) and automaticbolus triggering using a threshold of 100 Hounsfield Unites. Thestudy acquisition delay time was estimated by injection of a15 ml contrast medium test bolus at 6 ml/s, followed by 50 mlof saline. The actual delay time was calculated as the time ofpeak contrast medium attenuation in a region of interest inthe ascending aorta plus four seconds. For prospectively ECG-triggered coronary CT angiography, acquisition parameters were2 mm × 128 mm × 0.6 mm sections, 280 ms gantry rotation time,120 kV tube potential, and 320 mAs per rotation tube current timeproduct. Acquisition was cranio-caudal from above the origin ofthe coronary arteries to below the dome of the diaphragm. Adap-tive prospective ECG-triggering was used with the full radiationdose window set at 70% of the R–R′ interval in two patients withheart rates ≤70 beats per minute (bpm), and 40% of the R–R′

interval in one patient with a heart rate of >70 bpm. Reduceddose (25% of the nominal tube current) was applied between30% and 90% of the R–R′ interval to obtain functional informa-tion. Coronary artery evaluation datasets were reconstructed using0.75 mm section thickness and 0.3 mm reconstruction incrementat 40% or 70% R–R′ depending on the heart rate. An additionalreconstruction was performed during systole at 250 ms after theR-peak to plan the coverage range for the myocardial perfusionacquisition.

Myocardial perfusion imaging was performed in the “shuttle”mode during peak adenosine (140 �g/kg/min Adenoscan, Astel-las Pharma Inc., Tokyo, Japan) stress. Data were acquired during

end systole (250 ms after the R-peak). The anatomic extensionof the scan range was planned based on the systolic reconstruc-tion of the previously performed coronary CT angiography suchas to encompass most of the myocardium, starting at the ante-

M. Meyer et al. / European Journal of Radiology 81 (2012) 3719– 3725 3721

Fig. 1. 65 year-old man with a fixed perfusion defect of the inferior wall. First-pass rest and stress perfusion DECT demonstrates inferior perfusion defect (arrows),wk

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Fig. 2. Decision pathways for patients with chest pain presenting to emer-gency department and managed under a modified standard-of-care algorithm.True/False+ = SPECT/DECT reveals significant perfusion defect compared to cardiac

nostics in patients with acute chest pain, and the rate of missedcases of myocardial perfusion defects (Fig. 3).

hich was confirmed by rest/stress SPECT. This perfusion defect corresponds tonown chronic infarction, as confirmed by delayed enhancement CT (arrows).

ior and superior portions of the left ventricle and extending tohe inferior wall along the 73 mm coverage. The study range forhe volumetric myocardial perfusion data acquisition was plannedy the CT technologist, without knowledge of the SPECT or car-iac MRI results. Image acquisition parameters were 100 kV tubeoltage and 300 mAs. The image acquisition sequence was initiatedour seconds prior to the arrival of the contrast medium bolus fronts determined by the initial test bolus injection in order to ensureaseline acquisition of non-contrast images prior to the onset ofrst-pass perfusion. Myocardial perfusion studies were contrastedium enhanced with 50 ml of contrast medium, followed by

0 ml of saline, injected at 6 ml/s. Including test bolus acquisitionnd coronary CTA angiography, each patient thus received a totalolume of 150 ml contrast medium and 135 ml saline. Studies werebtained during end-inspiration with a standardized acquisitionime of 30 s.

If patients could not hold their breath for 30 s, they werenstructed to slowly release their breath and continue breath-ng shallowly. Images were reconstructed with 3 mm slice

idth every 2 mm with a medium sharpness convolutionlgorithm.

Finally, delayed enhancement studies were performed 6 minfter perfusion imaging using a regular prospectively ECG-triggeredode with image acquisition at 70% of the R–R′ interval at 80 kV

nd 320 mAs. DECT image post-processing was performed as pre-iously described [9]. Briefly, from each set of DECT raw data, onemage series was reconstructed based only on the 80 kV X-raypectrum and another only on the 140 kV X-ray spectrum usinghe routine Heart Perfusion Blood Volume and General Viewingpplication of the DECT reconstruction algorithm. The myocar-ial iodine distribution was analyzed based on the unique X-raybsorption characteristics of this element at different kV levels. Theesulting color coded “iodine maps” were then superimposed ontorayscale multiplanar reformats of the myocardium in short- andong-axis views of the left ventricle (Fig. 1). The resulting images

ere displayed using the DECT image post-processing software of Multi-Modality Workstation (Syngo, Siemens Healthcare, Erlan-en, Germany). Two experienced observers who were blinded tohe results of other imaging tests independently evaluated all DECTtudies for myocardial iodine deficits and delayed enhancementsing the AHA 17 segment model [8]. Interobserver variability andgreement were evaluated. A final consensus read with arbitra-ion by a third experienced observer was performed to resolveiscrepant observations; these data were then used for furthernalysis.

Volume CT dose index (CTDIvol), dose-length product (DLP),

atient weight, kV and mAs were recorded. Effective dose (ED) waserived by multiplying the DLP with a chest specific conversionoefficient (� = 0.014 mSv × Gy−1 × cm−1).

MRI, True/False− = SPECT/DECT reveals mild or no perfusion defect compared tocardiac MRI.

2.5. Decision analytic model

A Monte Carlo simulation model was developed to compareSPECT with DECT in the triage of patients with known or suspectedCAD or chest pain. Patients were evaluated with a SPECT or DECTstress test and only three diagnostic outcomes were considered,patients with evidence of normal coronary arteries, patients withmoderate perfusion defects (in form of moderate one vessel dis-ease) and patients with severe perfusion defects (in forms of severeone vessel disease or two to three vessel disease). Depending onthose results patients were either discharged from the emergencydepartment with no further testing or were referred for coronarycatheterization (Fig. 2).

After being discharged from the emergency department or inpa-tient hospital service, patients return to a baseline state of health, inwhich health risks are determined by age, sex, ACS history, and car-diac medication. The primary outcome measurements were gainedyears in QALYs due to a correct diagnosis, health care costs for diag-

Fig. 3. Acceptability curves for the short-term analysis illustrate the probability thata certain diagnostic strategy is cost-effective at different willingness to pay (WTP)per QALY threshold levels.

3722 M. Meyer et al. / European Journal of Radiology 81 (2012) 3719– 3725

Table 2Health state, mortality risk for disease condition and procedures for patients withCAD.

Variable Base–caseestimates

Range Reference

Health state (scale of 0–1)Healthy 0.95 Not varied [10]CAD with chest pain 0.7725 Not varied [10]No CAD with chest pain 0.895 Not varied [10]

ACS 1-year mortality riskNon-ST segment myocardial infarctionPatients with CAD 0.111 Not varied [13]Risk ratio for missed cases (30 days) 1.9 1–5.2 [12]

Unstable anginaPatients with CAD 0.07 Not varied [13]Risk ratio for missed cases (30 days) 1.7 1–17.0 [12]

Annual mortality risk ratios for CADLeft main artery disease 9.6 Not varied [10]

Three-vessel disease 3.6 Not varied [10]Annual mortality risk reduction for CAD treatment

CABG left main artery disease 0.67 Not varied [9]CABG three-vessel disease 0.48 Not varied [9]PCI 0.15 Not varied [10]

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Table 3Patient, diagnostic test characteristics and cost for patients with CAD.

Variable Base–caseestimate

Range Reference

Patients (n) 50 Not varied This studyAge 61 45–72 This studySensitivity (%)

SPECT 85 75–95 This studyDECT 90 80–100 This study

Specivity %SPECT 57 47–67 This studyDECT 71 61–81 This study

Accuracy %SPECT 79 69–89 This studyDECT 87 77–97 This study

Cost (US$)Reimbursement forSPECT

1987 Not varied This study

modalities without adverse events. Effective radiation dose equiv-

ote: ACS, acute coronary syndrome; CABG, coronary artery bypass graft; CAD,oronary artery disease; PCI, percutaneous coronary intervention.

.6. Quality of life

CAD may be associated with chronic chest discomfort. There-ore, health-related quality of life in this study was based on thexistence cardiac or non-cardiac chest pain. Effects of test-basedreatments were estimated in agreement with those that haveeen reported for the Clinical Outcomes Using Revascularizationnd Aggressive Evaluation (COURAGE) quality-of-life study [9–11]Table 2). Patients with CAD who were correctly diagnosed andere treated obtained a quality-of-life improvement relative to

heir counterparts who did not receive a diagnosis and were notreated.

Patients wrongfully discharged from the emergency depart-ent with undiagnosed CAD faced an elevated risk of mortality

12]. Overall mortality risk over time was based on age, sex, exis-ence and severity of CAD, history of coronary artery bypass graftr percutaneous coronary interventional treatment, and history ofI [13,14] (Table 2).

.7. Definition of cost effectiveness

For the purpose of this study, first criterion for effectiveness ofiagnostic tests was the ability to identify accurately a patient whoas cardiac perfusion defects if patients are selected for testing from

group presenting to a physician because of possible CAD. Addi-ional criteria for CAD in terms of the clinical outcome for patientsndergoing the tests were developed, i.e. an increase in the num-er of QALYs for a patient. Numbers of years of life extended byherapy were multiplied by the adjusted quality of life, expresseds a fraction of full quality of life (1.0).

Costs of a diagnostic test strategy were calculated by using theollowing components: reimbursement rates for modalities multi-lied by number of patients plus cost of subsequent tests, and costesulting from diagnosis of a patient as false negative, multipliedy the respective number of patients. As DECT perfusion imaging isot yet used as a routine strategy reimbursement rates were esti-ated by using a sensitivity analysis. Maximal possible costs forECT were calculated to avoid random effects if compared to the

PECT imaging strategy. All costs were derived from MUSC’s hospi-al billing system using its business calculation software CranwareCranware Inc., Atlanta, GA, USA) and are expressed in US dollars.

Reimbursement for DECT 1700 Not varied This studyReimbursement for leftventricle catheterization

4837 Not varied This study

2.8. Model analysis

Costs and outcomes (in QALYs) were calculated for both diag-nostic strategies. Strategies were ranked according to increasingcosts and eliminated strategies by using simple dominance (i.e.strategies that were less effective and more costly) and extendeddominance (i.e. strategies that were less effective and had ahigher incremental cost-effectiveness ratio [ICER]). Of the remain-ing strategy, ICERs were calculated relative to no therapy. 1,000,000first-order Monte Carlo simulations were ran for the study patientpopulation.

One-way sensitivity analyses on model parameters were per-formed to evaluate their unique effects on clinical and costoutcomes. In addition, a probabilistic sensitivity analysis was con-ducted to evaluate the effect of all sources of uncertainty in themodel. Monte Carlo simulation was performed to derive mean val-ues for costs, cost per correct diagnose and QALYs at a perfusiondefects prevalence of 40%, 60%, and 80%. Ranges and distributionalassumptions for model variables were based on actual data or liter-ature values if available; otherwise, they were constructed by usingresearch data (Table 3). For example, sensitivity and specificity forDECT and SPECT were varied on the basis of their actual 95% con-fidence intervals. Mean diagnostic test costs were varied at 20% byusing a gamma distribution.

Study parameters are displayed as mean ± standard deviationor percentage (%). Comparisons between patient groups were per-formed using a Spearman �2 or Fisher exact test for categoricalvariables and non-parametric Wilcoxon rank sum test for continu-ous variables. Interobserver agreement was assessed using Cohen’sKappa statistics. Good agreement was reported when Cohen’skappa (�) values was in between 0.6 and 0.8. Kappa value above0.8 was considered as excellent agreement. For all analysis, a p-value <0.05 was considered significant. The model was built withTreeAge Pro 2008 (TreeAge Software, Williamstown, MA, USA), andresults were analyzed using SAS 9.0 (SAS Institute, Raleigh, NC,USA).

3. Results

3.1. Patient demographics

Images of all patients were successfully obtained with all three

alent from the three DECT scans was 13.4 ± 2.6 mSv.Of 50 patients, 43 (86%) patients had perfusion defects on cMRI.

Thirty-two patients had fixed and 11 patients had reversible per-

M. Meyer et al. / European Journal of Radiology 81 (2012) 3719– 3725 3723

Table 4Mean costs, health outcomes, and cost-effectiveness for patients with CAD at different pre-test likelihoods.

Pre-test likelihood Cost (US$)per patient

QALY 80% ICER per QALY ICER/correctdiagnose 80%

ICER/QALYs 40% ICER/QALYs 60%

SPECT $2938 13.49 $3557 $3625 $5922 $5183

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p-Value 0.0002 0.0004

usion defects at cMRI. Intermodality agreement for detection ofxed and reversible perfusion defects at cMRI with DECT was good� = 0.656 and 0.738, respectively). Compared with cMRI as refer-nce standard, DECT (versus SPECT) had 90% (85%) sensitivity, 71%57%) specificity and 87% (79%) accuracy for diagnosing patientsith perfusion defects (Table 3). In comparison SPECT had 85% sen-

itivity, 57% specificity and 79% accuracy for diagnosing patientsith perfusion defects (Table 3).

.2. Base–case analysis

Myocardial perfusion DECT had better diagnostic accuracy thanPECT, with accuracy of 87% compared to cMRI. DECT was alsoess expensive, with an average cost of $2631 per patient. Com-ared with no treatment patients gained 14.13 QALYs, resulting

n an ICER of $3191 per QALY (p = 0.0004) and $2922 per correctiagnose (p = 0.0001). Myocardial perfusion SPECT had a signifi-ant higher average cost of $2938 per patient (p = 0.0002) and aain in QALY of 13.49 compared to no treatment. It was signif-cant less effective if compared to DECT with an ICER of $3557er QALY (p = 0.0004) and $3625 per correct diagnose (p = 0.0001)Table 4).

.3. Sensitivity analysis

Using sensitivity analysis, most important parameters con-ributing to cost-effectiveness outcomes were accuracy of diag-ostic test and prevalence of perfusion defects in the patientopulation. Other important factors included patient age and base-

ine costs of the test. Only accuracy and cost of DECT versus SPECTffected dominance of DECT over the range of values assessed inhis study. Probabilistic sensitivity analysis showed that SPECT was

ore cost-effective up to a threshold level of $4600 per QALYssuming a DECT accuracy of as low as 40% and a SPECT accuracy of0%. At higher accuracies, DECT seems to be a more cost-effectivetrategy.

For patients with a pre-test likelihood of 40% for a perfusionefect, costs per patient of $3248 were lower by using DECT. Usinghe same assumption, SPECT had a significant higher cost of $5922er patient (p = 0.0051). The same was true with a pre-test likeli-ood of 60%; DECT had a lower cost of $2988 compared to $5183er patient using SPECT (p = 0.0094) (Table 4).

. Discussion

The management of patients with known or suspected CAD isdeally guided by documentation of myocardial ischemia for opti-

al planning of medical therapy and/or revascularization. Optimaliagnostic strategies for individuals who are suspected of havingyocardial perfusion defects are dependent on several variables

esides performance of the applied diagnostic test itself. Param-ters such as prevalence of myocardial perfusion defects, cost ofests, and social willingness to pay for additional correct diagnoses

r QALYs need to be considered.

Improved temporal resolution together with high spatial reso-ution of contemporary MRI technology has re-emphasized usingrst-pass perfusion cMRI for assessing hemodynamic significance

$2938 $3248 $29880.0001 0.0001 0.0001

of coronary artery stenosis. Analysis of global and regional myocar-dial function is enhanced by examination of myocardial viabilityand perfusion. This non-invasive diagnostic “triad” assumes cMRIa unique methodological strength for a comprehensive evaluationof CAD within one single examination. In particular, the high spa-tial resolution of perfusion cMRI allows detection of small, evensubendocardial perfusion deficits. Single and multicenter studieshave demonstrated the superiority of cMRI for detection of CAD incomparison with SPECT [4,15]. Recent studies suggest that coro-nary CT may serve as a stand alone test in patients with suspectedCAD due to its complex visibility of both the anatomic and phys-iological morphology of the heart and its coronary arteries [6,7].Moreover a CT scan could theoretically address other imaging chal-lenges in patients with acute chest pain, such as visualization ofpulmonary embolism and aortic dissection. Such a ‘triple rule-out’ is feasible within a single scan, but has not been sufficientlyevaluated and is currently not widely recommended since, for aparticular organ, image quality might be lower if compared tothe use of a dedicated scan protocol [16]. However, since coro-nary CT is capable of ruling out CAD in most cases it could beused in selected patients with acute chest pain for assessment ofCAD.

In this study, two different diagnostic strategies for symp-tomatic individuals with known or suspected CAD were examined.Costs per patient and long-term costs per saved QALY for bothSPECT and DECT imaging were compared. In addition, costs andoutcomes were evaluated from a payer perspective in relation totheir potential effects on downstream costs attributable to myocar-dial perfusion defects. However, until know there is now evidencefor cost-effectiveness of cardiac DECT imaging if compared to SPECTperfusion imaging. Considering that four out of five imaging stresstests performed in the United States are SPECT, a comparison of thenewly introduced DECT technique to the dominant ischemia-basedstrategy should be useful to ensure optimal health care delivery andoutcomes [17].

Our study results indicate that cardiac DECT imaging has ahigh sensitivity (90%) and a good specificity (71%) for the quali-tative assessment of myocardial perfusion. These findings are inagreement to previous reports. Ko et al. evaluated in 50 patientswith known CAD diagnostic accuracy of stress-DECT for detect-ing reversible myocardial perfusion defect compared with cardiacstress MRI (n = 28) and invasive coronary angiography (n = 41). Ona per-vascular territory basis, stress-DECT had a sensitivity of 91%,specificity of 72%, and accuracy of 83% if compared to cardiac stressMRI [18]. In another study with 7 patients with suspected CADNagao et al. compared ischemic and non-ischemic territories onstress-DECT with those of adenosine-stress myocardial perfusionscintigraphy. Stress-DECT was able to separate ischemic territoriesfrom non-ischemic territories with a sensitivity of 86% and a speci-ficity of 75% [19]. However, it has to be emphasized that there isyet only limited data available regarding the accuracy of this newintroduce imaging test.

Results for myocardial perfusion SPECT indicate a good sensitiv-

ity (85%) but only a poor specificity (57%) for qualitative assessmentof myocardial perfusion, with a high rate of false negative findings.Similar sensitivities of 77–85% and specificities of 44–58% have alsobeen reported in previous multicentre SPECT trials [4,20].

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724 M. Meyer et al. / European Journ

Findings of the cost effectiveness analysis suggest that a myocar-ial perfusion DECT based strategy for patients with known oruspected CAD led to lower costs per patient and seems to beore effective than myocardial perfusion SPECT in prolonging

ife and ICER per correct diagnosis. However, sensitivity analy-es suggest that results are applicable under various conditions.ven when several parameters such as accuracy or myocardial per-usion defects prevalence were modified (between 10–100% and0–80%, respectively), DECT remains cost-effective to SPECT in thistudy.

Radiation exposure is a common and valid critique of car-iac CT imaging. The protocol used in this study is based on

number of dose-reduction strategies (i.e. by shortening theime of full radiation exposure and by narrowing the ECG puls-ng window) to lower radiation dose as much as possible. Thisllowed an average dose of ≈13 mSV, which is equivalent tohe dose of a single-day, single-isotope technetium SPECT scan21,22].

Analysis of cost effectiveness using the mathematical modelresented here includes few limitations: Although the model isased on real time clinical information, outcomes in some clin-

cal subgroups are sparse, thus, preventing conclusions on somelinical characteristics of interest. Data from CASS were used forost of the parameters on untreated patients which might be

utdated, although such data is no longer available from recenttudies.

In general, cost per QALYs saved might not be the best out-ome criteria for evaluating cost effectiveness of imaging tests.ne could apply additional parameters that represent an influencef imaging on subsequent management. In the current study, anttempt was made to balance this by calculating ICER per cor-ect diagnose. As the model is based on US data, results couldot directly be applied to other countries, in which epidemiology,reatment efficacy, medical costs and other sociomedical systemsiffer from those in the US. Nevertheless, as long as DECT is lessostly and accurate than SPECT, and as it provides enough reliableiagnostic performance, one would expect similar results in otherountries.

Variations in overall predictive accuracy as they were iden-ified in different meta-analyses do have a fairly large effectn corresponding results. The model applied here is based onata on sensitivity and specificity published in the most recenteta-analyses for SPECT. Accuracy for DECT and SPECT perfu-

ion was only varied in the 95% CI, i.e. avoiding any randomffects. Moreover, pre-test likelihood included in the model andaried between 10% and 100% for CAD to adjust for populationsith different CAD incidences. Finally, adenosine-induced-stressECT is a newly introduced imaging technique, so the underlying

maging protocol (amount and speed of contrast administra-ion, imaging delay time, etc.) and imaging post-processingechnique to normalize iodine in the iodine map to areas oformal myocardial perfusion might not be optimal. Further stud-

es might be able to review additional data in order to analyzetress DECT in context to similar and/or other managementlgorithms, e.g. multimodality approaches, i.e. combination of con-entional coronary CT angiogram and cMRI, which might haveower radiation exposure and even a higher diagnostic perfor-

ance compared to the approach used here. Further studiesre required to assess the potential of CT for integrative imag-ng of all pertinent aspects of coronary heart disease, includingoronary artery morphology, cardiac function, perfusion, andiability.

In conclusion, using myocardial perfusion DECT as a first-linemaging test for the workup of patients with CAD might provideains in QALYs while lowering costs if compared to routine myocar-ial perfusion SPECT.

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adiology 81 (2012) 3719– 3725

Disclosures

Dr. Schoepf receives research support from and is a consultantfor Bayer-Schering, Bracco, General Electric, Medrad, and Siemens.The other authors have no conflicts of interest to disclose.

References

[1] Schwarz F, Ruzsics B, Schoepf UJ, et al. Dual-energy CT of the heart – principlesand protocols. Eur J Radiol 2008;68(3):423–33.

[2] Hendel RC, Patel MR, Kramer CM, et al. ACCF/ACR/SCCT/SCMR/ASNC/NASCI/SCAI/SIR 2006 appropriateness criteria for cardiac com-puted tomography and cardiac magnetic resonance imaging: a report ofthe American College of Cardiology Foundation Quality Strategic DirectionsCommittee Appropriateness Criteria Working Group, American College ofRadiology, Society of Cardiovascular Computed Tomography, Society forCardiovascular Magnetic Resonance, American Society of Nuclear Cardiology,North American Society for Cardiac Imaging, Society for CardiovascularAngiography and Interventions, and Society of Interventional Radiology. J AmColl Cardiol 2006;48(7):1475–97.

[3] Hendel RC, Berman DS, Di Carli MF, et al. ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 appropriate use criteria for cardiac radionuclide imag-ing: a report of the American College of Cardiology Foundation Appropriate UseCriteria Task Force, the American Society of Nuclear Cardiology, the AmericanCollege of Radiology, the American Heart Association, the American Societyof Echocardiography, the Society of Cardiovascular Computed Tomography,the Society for Cardiovascular Magnetic Resonance, and the Society of NuclearMedicine. Circulation 2009;119(22):e561–87.

[4] Schwitter J, Wacker CM, van Rossum AC, et al. MR-IMPACT: compari-son of perfusion-cardiac magnetic resonance with single-photon emissioncomputed tomography for the detection of coronary artery disease ina multicentre, multivendor, randomized trial. Eur Heart J 2008;29(4):480–9.

[5] Scanlon PJ, Faxon DP, Audet AM, et al. ACC/AHA guidelines for coronaryangiography: executive summary and recommendations. A report of the Amer-ican College of Cardiology/American Heart Association Task Force on PracticeGuidelines (Committee on Coronary Angiography) developed in collabora-tion with the Society for Cardiac Angiography and Interventions. Circulation1999;99(17):2345–57.

[6] Ruzsics B, Schwarz F, Schoepf UJ, et al. Comparison of dual-energy computedtomography of the heart with single photon emission computed tomographyfor assessment of coronary artery stenosis and of the myocardial blood supply.Am J Cardiol 2009;104(3):318–26.

[7] Heuschmid M, Burgstahler C, Reimann A, et al. Usefulness of noninvasivecardiac imaging using dual-source computed tomography in an unselectedpopulation with high prevalence of coronary artery disease. Am J Cardiol2007;100(4):587–92.

[8] Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardialsegmentation and nomenclature for tomographic imaging of the heart: a state-ment for healthcare professionals from the Cardiac Imaging Committee of theCouncil on Clinical Cardiology of the American Heart Association. Circulation2002;105(4):539–42.

[9] Coronary artery surgery study (CASS): a randomized trial of coronary arterybypass surgery. Quality of life in patients randomly assigned to treatmentgroups. Circulation 1983;68(5):951–60.

10] Lalonde L, Clarke AE, Joseph L, Mackenzie T, Grover SA. Comparingthe psychometric properties of preference-based and nonpreference-based health-related quality of life in coronary heart disease. Cana-dian Collaborative Cardiac Assessment Group. Qual Life Res 1999;8(5):399–409.

11] Weintraub WS, Spertus JA, Kolm P, et al. Effect of PCI on quality oflife in patients with stable coronary disease. N Engl J Med 2008;359(7):677–87.

12] Pope JH, Aufderheide TP, Ruthazer R, et al. Missed diagnoses of acute car-diac ischemia in the emergency department. N Engl J Med 2000;342(16):1163–70.

13] Armstrong PW, Fu Y, Chang WC, et al. Acute coronary syndromes in the GUSTO-IIb trial: prognostic insights and impact of recurrent ischemia. The GUSTO-IIbinvestigators. Circulation 1998;98(18):1860–8.

14] Roe MT, Harrington RA, Prosper DM, et al. Clinical and therapeutic profile ofpatients presenting with acute coronary syndromes who do not have significantcoronary artery disease. The Platelet Glycoprotein IIb/IIIa in Unstable Angina:Receptor Suppression Using Integrilin Therapy (PURSUIT) trial investigators.Circulation 2000;102(10):1101–6.

15] Ishida N, Sakuma H, Motoyasu M, et al. Noninfarcted myocardium: cor-relation between dynamic first-pass contrast-enhanced myocardial MRimaging and quantitative coronary angiography. Radiology 2003;229(1):209–16.

16] Shapiro MD. Is the “triple rule-out” study an appropriate indication for cardio-

vascular CT? J Cardiovasc Comput Tomogr 2009;3(2):100–3.

17] Bonow RO. Is appropriateness appropriate? J Am Coll Cardiol2008;51(13):1290–1.

18] Ko SM, Choi JW, Song MG, et al. Myocardial perfusion imaging using adenosine-induced stress dual-energy computed tomography of the heart: comparison

al of R

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M. Meyer et al. / European Journ

with cardiac magnetic resonance imaging and conventional coronary angiog-raphy. Eur Radiol 2011;21(1):26–35.

19] Nagao M, Kido T, Watanabe K, et al. Functional assessment of coronary artery

flow using adenosine stress dual-energy CT: a preliminary study. Int J Cardio-vasc Imaging. 2010 Aug 5. [Epub ahead of print].

20] He ZX, Iskandrian AS, Gupta NC, Verani MS. Assessing coronary artery diseasewith dipyridamole technetium-99m-tetrofosmin SPECT: a multicenter trial. JNucl Med 1997;38(1):44–8.

[

adiology 81 (2012) 3719– 3725 3725

21] Blankstein R, Shturman LD, Rogers IS, et al. Adenosine-induced stress myocar-dial perfusion imaging using dual-source cardiac computed tomography. J AmColl Cardiol 2009;54(12):1072–84.

22] Gerber TC, Carr JJ, Arai AE, et al. Ionizing radiation in cardiac imaging: a scienceadvisory from the American Heart Association Committee on Cardiac Imagingof the Council on Clinical Cardiology and Committee on Cardiovascular Imagingand Intervention of the Council on Cardiovascular Radiology and Intervention.Circulation 2009;119(7):1056–65.