EDITOR’S PAGE

CT angiography: Too much too soon?

George A. Beller, MD

A great deal of interest and enthusiasm for the earlyclinical adoption of cardiac computed tomography an-giography (CTA) for the noninvasive diagnosis of coro-nary artery disease (CAD) has emerged in recent years.This enthusiasm has been fueled by advocates for ananatomy-lumenology–based approach for assessing pa-tients with chest pain. The technique was rapidly ad-vanced technologically with the introduction of 64-slicecomputed tomography (CT) scanners and dual-sourceCT scanners (with 83 milliseconds of temporal resolu-tion). In an excellent recent review of cardiac CTtechnology, Di Carli and Hachamovitch1 show a sum-mary of published literature regarding the diagnosticaccuracy of CTA from 21 studies comprising 1,650patients. With a per-segment analysis, the sensitivity andspecificity for detecting a stenosis of greater than 50%were 83% and 92%, respectively, and the positive andnegative predictive values were 67% and 97%, respec-tively. The per-patient analyses showed a sensitivity,specificity, positive predictive value, and negative pre-dictive value of 94%, 77%, 84%, and 87%, respectively.The ability of CTA to accurately determine the degree ofluminal narrowing is a limitation, and correlation withquantitative coronary angiography is modest.2 True ste-nosis severity is overestimated by CTA. Coronary seg-ments of less than 2.0 mm are difficult to examine, andthe presence of calcium in plaques may prevent adequateluminal evaluation. Visualization of the lumen is alsodifficult in stented lesions. Most observers agree that themajor strength of CTA is its high negative predictivevalue in excluding CAD in patients with chest pain anda low likelihood of CAD. Such patients are frequentlyseen in chest pain units in emergency departments. Thequestion can be asked whether the enthusiasm for rapidintroduction into routine clinical care is “too much toosoon.”

The detection of coronary narrowing by an anatom-ic-based technology does not translate to prognosticationor even being sure that a stenosis seen on CTA is reallythe cause of a patient’s chest pain. Many years ago,studies in the field of nuclear cardiology showed thatknowing the anatomic information from coronary an-giography (ie, number of vessels with stenotic lesions of

�50% luminal narrowing) did not add prognostic infor-mation by Cox regression analysis to the cumulativeinformation derived from clinical, electrocardiographicstress testing, and radionuclide imaging variables.2-4

Many other studies with both planar thallium 201 andsingle photon emission computed tomography (SPECT)imaging with exercise or pharmacologic stress showedthe powerful prognostic value of the extent of hypoper-fusion and other findings, such as percent of the leftventricle rendered ischemic, transient ischemic cavitydilation, extent of regional wall motion abnormalities,and SPECT-derived left ventricular ejection fraction.5

From data extracted from 19 series in the literature in39,173 patients, the annualized rate of death or myocar-dial infarction was 0.6% in patients with normal scans. In69,655 patients collated from 39 published series in theliterature, the annual cardiac event rate was 0.8% forthose with low-risk stress SPECT studies versus 5.9% forthose with moderately or severely abnormal scans.5

Stress perfusion imaging with positron emission tomog-raphy (PET) may even yield a higher accuracy for CADdetection compared with SPECT. A recent study bySampson et al6 reported that the sensitivity of rubidium82 PET perfusion imaging was 93%, with a specificity of83%. For multivessel CAD patients, the sensitivity was95%. Bateman et al7 reported that PET correctly pre-dicted multivessel CAD in 71% of patients versus 48%of those undergoing SPECT.

This dichotomy between anatomy (CTA) and phys-iology (stress SPECT perfusion imaging) is graphicallypointed out by Di Carli and Hachamovitch,1 who showthat the frequency of inducible ischemia by myocardialperfusion imaging in myocardial territories supplied bystenoses of greater than 50% on CTA is rather low. Forexample, in the per-vessel analysis of 4 studies in theliterature, the positive predictive value of CTA foridentifying ischemia-producing lesions by SPECT was29%, 31%, 39%, and 40%. In the two studies in which aper-patient analysis was performed, the positive predic-tive value for CTA for inducible ischemia by perfusionimaging was 44% and 43%. In contrast, the negativepredictive value exceeded 90% in all per-vessel analyses.Few randomized studies have been published comparinga CTA-based strategy versus a standard stress imaging–based strategy in detecting significant CAD in patientspresenting with chest pain. One recent study by Gold-stein et al8 showed similar outcomes in patients random-

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ized to CTA versus a SPECT stress study. However,CTA was not considered adequate for diagnosis in 24 of99 patients (24%), because of either lesions of unclearhemodynamic significance (stenoses of 26%-70%) in 13patients or non–diagnostic-quality scans in 11. These 24patients had to undergo a stress perfusion study afterCTA; all 24 had normal scans and were sent home. Thehigher cost of the stress imaging strategy was solelyattributed to a longer length of stay in the emergencydepartment (15 hours vs 3.4 hours). Some observers havecommented that 15 hours to exclude CAD as a cause ofchest pain by use of a stress imaging strategy is on thelengthy side for most institutions. Regarding the afore-mentioned study, excessive radiation exposure occurredin the 24% of patients with inconclusive CTA scansnecessitating a physiologic nuclear stress study to com-plete the diagnostic evaluation.8

In the future, an integrated approach with multimo-dality imaging via hybrid instrumentation or separateCTA scanners and nuclear cameras may emerge as themost effective approach for the noninvasive evaluationof patients with chest pain and a low to intermediatelikelihood of CAD by clinical, biomarker, and electro-cardiographic criteria. Such SPECT-CT or PET-CT tech-nology permits a significantly improved positive predic-tive value for identifying functionally important lesions.9

In this study in which SPECT/CTA was used for thedetection of hemodynamic significant coronary lesions,the positive predictive value increased from 31% withCTA alone to 77% with a SPECT/CTA combinedstrategy.9 The problems with using such a multimodalityapproach in all patients are radiation exposure and cost.If CTA is done first in low-risk patients with chest painand shows pristine normal coronary arteries, then theworkup ceases. If the anatomic study shows intermediatestenosis or exhibits unevaluable coronary segments (eg,dense calcium), a PET or SPECT stress study could thenbe performed to detect ischemia. Using a hybrid ap-proach in all patients would provide information on thepresence of subclinical plaques, which may have impli-cations for prevention therapy. Finally, PET imaging notonly has the ability to assess relative defects representingheterogeneous perfusion during vasodilator stress butcan be used to measure absolute flow reserve in coronarysupply regions by quantitative analysis. This provideseven more information than just plaque burden andflow-limiting stenoses, because some patients with CADrisk factors can manifest abnormal flow reserve in thepresence of angiographically normal coronary arteries.

What is needed now are well-designed clinical trials,some of which should be randomized, to convincinglydemonstrate the clinical accuracy and cost-effectivenessof CTA. Such outcome studies should ideally involvecomparing CTA strategies with nuclear and echocardio-graphic techniques that have proven their diagnostic andprognostic value in many thousands of patients. Theascertaining of the worth of multimodality hybrid imag-ing for evaluating anatomy by CTA and physiology bySPECT or PET would be extremely important beforesuch technology is accepted as appropriate for clinicalapplications to large numbers of patients. Good evidenceis required and not merely the continued reporting ofsingle-center observational studies conveying more sen-sitivity and specificity data.

References

1. Di Carli MF, Hachamovitch R. New technology for noninvasiveevaluation of coronary artery disease. Circulation 2007;115:1464-80.

2. Kaul S, Lilly DR, Gascho JA, Watson DD, Gibson RS, Oliner CA,et al. Prognostic utility of the exercise thallium-201 test in ambu-latory patients with chest pain: comparison with cardiac catheter-ization. Circulation 1988;77:745-58.

3. Iskandrian AS, Chae SC, Heo J, Stanberry CD, Wasserleben V,Cave V. Independent and incremental prognostic value of exercisesingle-photon emission computed tomographic (SPECT) thalliumimaging in coronary artery disease. J Am Coll Cardiol 1993;22:665-70.

4. Pancholy SB, Fattah AA, Kamal AM, Ghods M, Heo J, IskandrianAS. Independent and incremental prognostic value of exercisethallium single-photon emission computed tomographic imaging inwomen. J Nucl Cardiol 1995;2(Pt 1):110-6.

5. Shaw LJ, Iskandrian AE. Prognostic value of gated myocardialperfusion SPECT. J Nucl Cardiol 2004;11:171-85.

6. Sampson UK, Dorbala S, Limaye A, Kwong R, Di Carli MF.Diagnostic accuracy of rubidium-82 myocardial perfusion imagingwith hybrid positron emission tomography/computed tomography inthe detection of coronary artery disease. J Am Coll Cardiol2007;49:1052-8.

7. Bateman TM, Heller GV, McGhie AI, Friedman JD, Case JA,Bryngelson JR, et al. Diagnostic accuracy of rest/stress ECG-gatedRb-82 myocardial perfusion PET: comparison with ECG-gatedTc-99m sestamibi SPECT. J Nucl Cardiol 2006;13:24-33.

8. Goldstein JA, Gallagher MJ, O’Neill WW, Ross MA, O’Neil BJ,Raff GL. A randomized controlled trial of multi-slice coronarycomputed tomography for evaluation of acute chest pain. J Am CollCardiol 2007;49:863-71.

9. Rispler S, Keidar Z, Ghersin E, Roguin A, Soil A, Dragu R, et al.Integrated single-photon emission computed tomography and com-puted tomography coronary angiography for the assessment ofhemodynamically significant coronary artery lesions. J Am CollCardiol 2007;49:1059-67.

268 Beller Journal of Nuclear CardiologyCT angiography May/June 2007