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Journal of the American College of Cardiology Vol. 52, No. 16, 2008© 2008 by the American College of Cardiology Foundation ISSN 0735-1097/08/$34.00Published by Elsevier Inc. doi:10.1016/j.jacc.2008.07.022

EDITORIAL COMMENT

ssessing the Prognosticalue of Coronary Computedomography Angiography*

tephan Achenbach, MD, FACC, FESC

rlangen, Germany

omputed tomography (CT) imaging of the coronaryrteries is challenging. The coronary vessels are small, andhey move very rapidly, so that tremendously high spatialnd temporal resolution are necessary to obtain sharpmages of the coronary tree. The first CT system success-ully used to visualize the coronary arteries was the electroneam tomography (EBT) scanner, which became availablen the late 1980s and early 1990s and was also calledultrafast CT” because of its ability to acquire images atnprecedented speed. With an exposure time of 100 ms/mage, the EBT scanner allowed faster imaging than most

ultidetector CT systems in use today, but limitationsncluded a spatial resolution much lower than that of currentT scanners, rather high image noise, and a long overall

mage acquisition time (patients typically had to hold theirreath for more than 30 s).

See page 1335

The main application of EBT was the detection anduantification of coronary artery calcification. In addition,BT first demonstrated the ability of CT imaging to obtain

noninvasive coronary angiograms” after injection of aontrast agent. In the mid 1990s, this new developmenteceived tremendous interest and fueled the surprisinglyapid evolution of CT technology, much of which wasriven by the desire to improve the ability of CT to visualizehe coronary arteries. Today, 64-slice CT systems, whichllow rather stable imaging of the coronary vessels, areidely available. Coronary computed tomography angiog-

aphy (CTA) is considered an “appropriate” clinical tool inelected situations, including ruling out coronary stenoses inymptomatic patients with intermediate likelihood of coro-

Editorials published in the Journal of the American College of Cardiology reflect theiews of the authors and do not necessarily represent the views of JACC or themerican College of Cardiology.From the Department of Cardiology, University of Erlangen, Erlangen, Germany.r. Achenbach receives research grants from Siemens Healthcare and Bayer Schering

fharma, and is supported by a grant (01 EV 0708) from Bundesministerium fürildung und Forschung, Germany.

ary artery disease (1). Although numerous comparisons ofT imaging to invasive angiography have been published

nd demonstrate a high accuracy for the detection ofobstructive” coronary artery lesions, very little is knownbout the prognostic implications of coronary CTA.

The study presented by Ostrom et al. (2) in this issue ofhe Journal provides data concerning the prognostic value ofontrast-enhanced CT visualization of the coronary arteries.he investigators followed up 2,538 patients studied by

ontrast-enhanced EBT for up to 15 years. Based on theirarge number of patients, complete follow-up, and longbservation period, they are able to demonstrate that theresence of obstructive and nonobstructive coronary artery

esions seen in contrast-enhanced EBT is predictive ofortality above and beyond traditional risk factors. Dem-

nstration of lesions is also a better predictor than the meressessment of coronary calcification. The severity of coro-ary lesions and the extent of disease (e.g., 1 affected vessels. several affected vessels) were associated with mortalityates. After adjustment for risk factors and coronary calciumcore, patients with obstructive lesions seen in EBT angiog-aphy had an approximately 2-fold risk of death as com-ared to patients without detectable atherosclerosis. Inter-stingly, noncalcified, nonstenotic plaque was found to beredictive only if its extent was substantial: only patientsho had all 3 vessels affected had an increased mortality.Obviously, the study by Ostrom et al. (2) has some

imitations—for example, it is unclear how many patientsere symptomatic and what treatment was initiated basedn the EBT results—but it does provide very interestingarly data concerning the prognostic implications of coro-ary plaque detected in contrast-enhanced CT imaging. As

s typically the case with new and exciting research results,he study answers some questions, but also raises many newnes, some of which are outlined below.ymptomatic patients or asymptomatic individuals? Iny opinion, it is important to carefully distinguish 2 clinical

cenarios. The first scenario is the use of coronary CTA forymptomatic patients. For some subgroups of patients whoo not have a high likelihood of coronary artery stenoses,his is currently considered appropriate (1). Clinically, theim of CT will be ruling out coronary artery stenoses tovoid invasive catheterization. Prognostic studies are neededo clarify whether it is safe to replace invasive angiographyy CT, and also to determine whether patients in whom CTules out the presence of obstructive lesions (thus avoidingnvasive angiography) but demonstrates the presence ofonobstructive plaque are at higher risk of cardiac eventshan are patients with entirely normal coronary arteries onT. This determination is important in order to make

ppropriate recommendations regarding risk modificationn such patients. The study by Ostrom et al. (2) providesome data in this respect.

The second scenario is that of the asymptomatic patient

or whom coronary CTA is performed for the sole purpose

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1345JACC Vol. 52, No. 16, 2008 AchenbachOctober 14, 2008:1344–6 Prognostic Value of Coronary CTA

f “risk stratification” in a primary prevention context. Thiss quite a different setting. Most patients in the study by

strom et al. (2) probably had symptoms, and similarly, theew other available studies that have investigated prognosticmplications of coronary CTA were all conducted in pa-ients who were largely symptomatic (3–7). It is importantot to use results obtained from such patient groups to

ustify coronary CT “screening” of asymptomatic patients.retest likelihoods and future event risks are substantially

ower, and the balance between test benefit and associatedisks (and costs) may be profoundly different from that ofymptomatic patients. The use of contrast-enhanced coro-ary CTA for risk stratification for asymptomatic patients isurrently considered an “inappropriate” application (1), andn my opinion, the study by Ostrom et al. (2) will nothange that.

id technology matter? The study by Ostrom et al. (2)as conducted using EBT, which is not widely available

nymore. The EBT data collected by Ostrom et al. (2) arextremely valuable because they allow a long follow-uperiod, but EBT has meanwhile been replaced by multide-ector computed tomography (MDCT), which has higherpatial resolution and, in general, better image quality thanBT. However, this does not mean that detection of plaquey MDCT is easy. Data sets of impeccable quality areequired to assess the presence or absence of nonobstructivelaque, and even in expert hands, neither sensitivity norpecificity is perfect (8). With adequate image quality,owever, it should be expected that more noncalcifiedlaque will be identified in MDCT as compared to EBT—aouble-edged sword. On the one hand, it will make it less

ikely that a patient with a future event will be missed byDCT. On the other hand, I suspect that even more plaqueay be detected by MDCT, and that may lead to a larger

umber of patients being placed in a “high risk” category.gain, it is important to keep in mind that only plaque in allvessels was predictive of future events in the study by Ostrom

t al. (2). Small, localized plaques have so far not been tied ton increased event risk.

ould the mere detection of plaque be enough? Ostromt al. (2) used a “yes/no” model to assess the presence ofbstructive and nonobstructive coronary lesions by CT.ost likely, that will not be sufficient in the future (Fig. 1).ot all “nonobstructive lesions” are alike—for example, theyay be small, confined to the vessel wall, and predominantly

alcified, or they can be large, positively remodelled, andargely noncalcified. However, as noncalcified plaque isbserved very frequently by contrast-enhanced coronaryTA (more than one-half of all patients in the study bystrom et al. [2], and about 30% of patients in a different

tudy [9]), merely evaluating the presence of plaque maylace too many individuals in a “high-risk” category, withhe consequence of (expensive) risk modification treatments well as considerable emotional stress. Efforts will have toe undertaken to identify characteristics that are associatedith increased risk of future events, whether this may be

lobal features (such as plaque volume), specific aspects of a

Figure 1 Visualization of Proximal and MidLAD by Contrast-Enhanced MDCT in 3 Patients

Visualization of the proximal artery and mid left anterior descending coronaryartery (LAD) by contrast-enhanced multidetector computed tomography (MDCT) in 3different patients. (A) Visualization of a small calcified plaque (large arrow) alongwith some noncalcified plaque (small arrow) in the mid left anterior descendingcoronary artery. (B) While nominally this patient also demonstrates calcified (largearrow) and noncalcified, nonobstructive plaque (small arrow), the lesion has differ-ent characteristics as compared with A. The noncalcified plaque component issubstantially larger, and the lesion displays pronounced positive remodeling.Potentially, this lesion may be more “vulnerable” than the lesion in A. (C) Not inall cases is image quality high enough to reliably rule in or rule out small noncalci-fied plaque. Although coronary stenoses can be ruled out, image noise preventsassessing the presence of noncalcified plaque in this low-dose image.

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1346 Achenbach JACC Vol. 52, No. 16, 2008Prognostic Value of Coronary CTA October 14, 2008:1344–6

iven plaque (such as remodeling), or a combination of both10). A small, noncalcified plaque may actually be prettyarmless and in fact, the absence of substantial amounts ofoncalcified plaque may at some point allow “downstaging” ofatients concerning their risk, but future research will need toddress this issue.

ow much can we afford to spend? Even when leavinghe economic implications of CT angiography for risktratification completely aside, this test comes at a cost: thenjection of contrast and the associated radiation exposurelace CTA in a completely different category as comparedo, for example, coronary calcium imaging. Low radiationose protocols are becoming increasingly available for CTA,ut flawless image quality is necessary to be able to assess theresence or absence of plaque with a reasonable degree ofertainty. Studies performed at very low dose or affected byther sorts of artifacts may be sufficient to rule out theresence of coronary stenosis, but not necessarily to visualizer even characterize plaque (Fig. 1). Contrast and radiationisks have to be assessed very carefully if ever considering these of CTA in primary prevention settings.In summary, the paper by Ostrom et al. (2) is helpful and

ery welcome as it provides more data on the prognosticmplications of coronary visualization using CT techniques.t contains the very reassuring message that the absence oftenosis and nonobstructive plaque is associated with a goodrognosis, even in a patient population that was most likely

argely symptomatic. However, the results do not justify these of CTA as a screening tool for asymptomatic, primaryrevention patients.

eprint requests and correspondence: Dr. Stephan Achenbach,epartment of Cardiology, University of Erlangen, Ulmenweg 18,rlangen 91054, Germany. E-mail: stephan.achenbach@uk-

rlangen.de. Kc

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2. Ostrom MP, Gopal A, Ahmadi N, et al. Mortality incidence and theseverity of coronary atherosclerosis assessed by computed tomographyangiography. J Am Coll Cardiol 2008;52:1335–43.

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7. Gaemperli O, Valenta I, Schepis T, et al. Coronary 64-slice CTangiography predicts outcome in patients with known or suspectedcoronary artery disease. Eur Radiol 2008;18:1162–73.

8. Schroeder S, Achenbach S, Bengel F, et al. Cardiac computedtomography: indications, applications, limitations, and training re-quirements: report of a writing group deployed by the Working GroupNuclear Cardiology and Cardiac CT of the European Society ofCardiology and the European Council of Nuclear Cardiology. EurHeart J 2008;29:531–56.

9. Hausleiter J, Meyer T, Hadamitzky M, Kastrati A, Martinoff S,Schömig A. Prevalence of noncalcified coronary plaques by 64-slicecomputed tomography in patients with an intermediate risk forsignificant coronary artery disease. J Am Coll Cardiol 2006;18:312–8.

0. Narula J, Finn AV, DeMaria AN. Picking plaques that pop. . . J AmColl Cardiol 2005;45:1970–3.

ey Words: coronary artery disease y electron beam tomography yomputed tomography y prognosis.