Journal of the American College of Cardiology Vol. 58, No. 8, 2011© 2011 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00Published by Elsevier Inc. doi:10.1016/j.jacc.2011.03.051

EDITORIAL COMMENT

Coronary ComputedTomography AngiographyCONFIRMations and Perspectives*

Bernard De Bruyne, MD, PHD,Carlos Van Mieghem, MD, PHD

Aalst, Belgium

The explosive growth of coronary computed tomographyangiography (CCTA) is related to several factors, amongwhich are the widespread availability of computed tomog-raphy machines, the financial incentive associated with theiruse, the strong appeal of a noninvasive visualization of thecoronary anatomy, and the clinical usefulness of the highnegative predictive value of CCTA. No other imagingtechnique in cardiology has undergone a higher degree ofscrutiny for demonstration of effectiveness in the scientificliterature, nor received the level of media coverage in the laypress. The enthusiastic adoption of CCTA contrasts withthe persisting debate on effective radiation doses associatedwith CCTA (1,2) and, more importantly, on the exact role,if any, of CCTA in the diagnostic work-up of individualswith suspected coronary artery disease (CAD). Until now,the prognostic significance of CAD detection by CCTA hasbeen limited to relatively small patient cohorts (3).

See page 849

In this issue of the Journal, Min et al. (4) convincinglydemonstrate the significance of CCTA-derived anatomicfindings on total mortality in patients without known CAD.The sample size is almost 1 order of magnitude larger thanall previous studies on CCTA-related outcome, and thestudy focuses on the “hardest” possible endpoint. Theauthors report that regardless of treatment: 1) individualswithout detectable coronary atherosclerosis at CCTA have avery favorable prognosis, and better than those with non-obstructive CAD; 2) total mortality increases with both thedegree and extent of coronary obstruction as detected onCCTA; and 3) the significance of these findings is moremarked in young patients and in women. It is likely that

*Editorials published in the Journal of the American College of Cardiology reflect theviews of the authors and do not necessarily represent the views of JACC or theAmerican College of Cardiology.

From the Cardiovascular Center Aalst, OLV-Clinic, Aalst, Belgium. The authors

have reported that they have no relationships relevant to the contents of this paper todisclose.

further analysis of this large cohort of patients will provideus with information regarding the impact of CCTA find-ings on therapeutic decision making. Grouches will objectthat what was old is new again—that most of this informa-tion derived from noninvasive angiography has already beendescribed by conventional angiography (5) and myocardialperfusion imaging (6) studies. However, in the presentstudy, selection biases are less likely, as more than 90% ofpatients had a low or intermediate pre-test likelihood ofCAD. In addition, the large sample size permits generalizedapplicability of the findings as well as risk stratification ofindividuals as categorized by age and sex. With this land-mark study, CCTA unquestionably overcomes a significantevidence gap: Not only is it feasible and accurate inpredicting the presence of coronary atherosclerosis, but itsfindings also predict clinical outcome.

To what extent is this important for our patient? Not forthe 23,854 patients reported by Min et al. (4); rather, whatdoes it change for the obese 62-year-old woman with a leftbundle branch block whose mother died from a “heartattack” at the age of 55 and who presented at the outpatientclinic with atypical angina? Min et al. (4) CONFIRM thatstrictly normal CCTA findings would be an enormousrelief. It is even likely that the favorable prognostic value ofa normal CCTA is higher than that of normal myocardialperfusion imaging, as functional testing does not distinguishbetween normal coronary arteries and nonobstructive dis-ease. Accordingly, the hope of belonging to this verylow-risk group will continue to entice both physicians andpatients and will keep triggering a large number of CCTAprocedures. The ever-decreasing doses of radiation usedwith the most recent CCTA protocols (7) will furthercontribute to lowering the threshold to perform CCTA,but, paradoxically, will contribute to increasing the numberof diagnostic conundrums in patients with suspected CAD.The likelihood that we will discover that our patient hassome degree of coronary atherosclerosis is substantial.Whether it is considered nonobstructive, more than 50%, ormore than 70%, in 1, 2, or 3 vessels will barely temper thepatient’s worries and will continue to convey an ambiguousmessage to the physician. It has long been recognized thatthe angiographic delineation of the arterial lumen and of itsnarrowing poorly correlates with its effect on myocardialblood flow (8). This relates not only to the intrinsicinaccuracies of a luminogram to depict the true dimensionsof the narrowing, but also to the fact that the metrics of thenarrowing (the “anatomy”)—even if they were to be per-fectly accurate—are only one of the many factors that definepatients’ symptoms and prognosis. Myocardial mass, micro-vascular function (and hence maximal myocardial flow),endothelial function, and coronary vasomotion are at least asimportant in shaping the “physiology” of the coronaryartery. Nevertheless, the visual impression of the lumino-gram and the sacred threshold of 50% diameter stenosis

remain pivotal to the very definition of the presence of

ati6TiaImc

862 De Bruyne and Van Mieghem JACC Vol. 58, No. 8, 2011CCTA: Confirmations and Perspectives August 16, 2011:861–2

coronary artery disease; for the description of its extent in1-, 2-, or 3-vessel disease; and constitute the basis for thevast majority of individual clinical decisions regarding re-vascularization.

To understand cardiac disease and to apply the appro-priate treatment, cardiologists must primarily be physi-ologists. Morphology is essential but insufficient. Coro-nary atherosclerosis does not necessarily imply myocardialischemia, and myocardial ischemia does not necessarilyimply the presence of focal atherosclerosis (9). CCTA-derived luminology, with its lower resolution as com-pared with invasive angiography, has proven incapable ofavoiding the same anatomic misclassifications (10,11). Inrecognition of this weakness, several approaches havebeen proposed to integrate anatomy and function in thesame setting, including the combination of adenosinestress computed tomography myocardial perfusion imag-ing (12) and CCTA, and the superimposition of single-photon emission computed tomography or positron emis-sion tomography-derived perfusion imaging with CCTAimages (13). Another promising approach consists of thefusion of CCTA anatomic findings and color-codedcomputed tomography-derived fractional flow reserve(FFRCT) values. The method calculates FFR frompatient-specific CCTA data using computational fluiddynamics during rest and simulated maximal coronaryhyperemic conditions (14). Preliminary results in patientssuggest that noninvasive FFRCT accurately predicts thehemodynamic significance of coronary lesions when com-pared to directly measured FFR during cardiac catheter-ization (15). The method still needs to be validated inlarger patient cohorts. However, if this approach fulfillsits promises, a low radiation CCTA acquisition willprovide the clinician with anatomy (angiography) and physi-ology (FFRCT) simultaneously. This would spur CCTA to yetnother level and might drastically change our diagnostichinking in patients with suspected CAD. Expressions like “anntermediate lesion,” “a non–flow-limiting stenosis,” “a 40% to0% stenosis,” and many others expressions will fade away.he abundance of these expressions actually testifies to our

nability to act as physiologists when merely looking at anngiogram, whatever way this shadowgram has been produced.f cardiac imaging is to affect the individual clinical decision-aking process, it must reconnect us with a basic foundation of

ardiology that is, in fact, physiology (16).

Reprint requests and correspondence: Dr. Bernard De Bruyne,Cardiovascular Center Aalst, OLV-Clinic, Moorselbaan 164,

B-9300 Aalst, Belgium. E-mail: bernard.de.bruyne@olvz-aalst.be.

s

REFERENCES

1. Kaul P, Medvedev S, Hohmann SF, Douglas PS, Peterson ED, Patel,MR. Ionizing radiation exposure to patients admitted with acutemyocardial infarction in the United States. Circulation 2010;122:2160–69.

2. Wijns W, Popowski Y. Radiation exposure in patients with myocardialinfarction. Another false alarm? Circulation 2010;122:2113–15.

3. Hulten EA, Carbonaro S, Petrillo SP, Mitchell JD, Villines TC.Prognostic value of cardiac computed tomography angiography. J AmColl Cardiol 2011;57:1237–47.

4. Min JK, Dunning A, Lin FY, et al., for the CONFIRM Investigators.Age- and sex-related differences in all-cause mortality risk based oncoronary computed tomographic angiography findings: results fromthe international multicenter CONFIRM (Coronary CT AngiographyEvaluation for Clinical Outcomes: An International MulticenterRegistry) of 23,854 patients without know coronary artery disease.J Am Coll Cardiol 2011;58:849–60.

5. Coronary Artery Surgery Study (CASS): a randomized trial of coro-nary artery surgery. Survival data. Circulation 1983;68:939–50.

6. Shaw LJ, Narula J. Risk assessment and predictive value of coronaryartery disease testing. J Nucl Med 2009;50:1296–1306.

7. Buechel RR, Husmann L, Herzog BA, et al. Low-dose computedtomography coronary angiography with prospective electrocardiogramtriggering. Feasibility in a large population. J Am Coll Cardiol2011;57:332–36.

8. Bartunek J, Sys SU, Heyndrickx GR, Pijls NH, De Bruyne B.Quantitative coronary angiography in predicting functional signifi-cance of stenoses in an unselected patient cohort. J Am Coll Cardiol1995;26:328–34.

9. De Bruyne B, Hersbach F, Pijls NH, et al. Abnormal epicardialcoronary resistance in patients with diffuse atherosclerosis but “normal”coronary angiography. Circulation 2001;104:2401–6.

10. Meijboom WB, Van Mieghem C, van Pelt N, et al. Comprehensiveassessment of coronary artery stenoses: Computed tomography coro-nary angiography versus conventional coronary angiography and cor-relation with fractional flow reserve in patients with stable angina.J Am Coll Cardiol 2008;52:636–43.

11. Sarno G, Decraemer I, Vanhoenacker PK, et al. On the inappropri-ateness of noninvasive multidetector computed tomography coronaryangiography to trigger coronary revascularization: A comparison withinvasive angiography. J Am Coll Cardiol Intv 2009;2:550–57.

12. George RT, Arbab-Zadeh A, Miller JM, et al. Adenosine stress 64-and 256-row detector computed tomography angiography and perfu-sion imaging. A pilot study evaluating the transmural extent ofperfusion abnormalities to predict atherosclerosis causing myocardialischemia. Circ Cardiovasc Img 2009;2:174–82.

13. Kajander S, Joutsiniemi E, Saraste M, et al. Cardiac positron emissiontomography/computed tomography imaging accurately detects ana-tomically and functionally significant coronary artery disease. Circula-tion 2010;122:603–13.

14. Kim HJ, Vignon-Clementel IE, Coogan JS, Figueroa CA, Jansen KE,Taylor CA. Patient-specific modeling of blood flow and pressure inhuman coronary arteries. Ann Biomed Eng 2010;38:3195–3209.

15. Erglis A, Jegere S, Runkule Z, et al. Non-invasive FFR using coronaryCT angiography and computational fluid dynamics predicts thehemodynamic significance of coronary lesions (abstr). Eur Heart J2010;31:151–52.

16. Carabello BA. Cardiologists. Do we have the right to call ourselvesphysiologists? J Am Coll Cardiol Img 2008;1:12–14.

Key Words: coronary computed tomography angiography y coronarytenosis y fractional flow reserve y myocardial perfusion.