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Can Coronary Computed Tomographic Angiography Trigger Coronary Revascularization?

Questioning the Appropriateness of the Question^_*

Daniel S. Berman, MD^,_*, James K. Min, MD

Departments of Imaging (Division of Nuclear Medicine), Department of Medicine (Division of Cardiology), and CSMC Burns & Allen Research Institute, Cedars-Sinai Medical Center; Department of Medicine, University of California at Los Angeles, School of Medicine, Los Angeles, California
Department of Medicine and Radiology, Weill Medical College of Cornell University, The New York Presbyterian Hospital, New York, New York

Key Words: appropriateness • fractional flow reserve • multidetector computed tomography

In this study, concordance between MDCTA and CA was good (kappa = 0.74). However, diagnostic performance of both MDCTA and CA to detect a functionally significant stenosis was poor with per-patient sensitivity and specificity of 80% and 65%, and 67% and 75%, respectively. With a strict anatomic definition by MDCT at the 50% stenosis threshold, rates of inappropriate revascularization (22%) and inappropriate deferral of revascularization (7%) based on MDCTA alone were non-negligible. While combined evaluation of both anatomic severity of coronary artery stenosis by MDCTA and flow limitation as assessed by FFR resulted in a much higher proportion of "appropriate" decision-making (91%), the authors concluded that MDCTA does not reliably predict functional significance of coronary artery stenoses or need for revascularization. The findings of Sarno et al. (4) are very similar to those from a study by Gaemperli et al. (5), who evaluated 79 patients undergoing MDCTA, CA, and FFR. Within this latter study, the diagnostic accuracy of MDCTA to detect a coronary lesion with an FFR <0.75 was only 49%.

The findings by Sarno et al. are in accord with the recently-published FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) study of 1,005 patients with multivessel CAD randomized to FFR-guided percutaneous coronary intervention (PCI) versus angiographically-guided PCI on the basis of CA (6). This study demonstrated a 28% relative risk reduction in adverse CAD event rates with the FFR-guided PCI—defined by death, myocardial infarction, or repeat coronary revascularization—at a 1-year follow-up, although no differences were noted for symptomatic anginal status. The results of the FAME trial suggests that CA identification of anatomic coronary artery stenosis is insufficient for identifying suitability for coronary revascularization and that identification of lesion-specific ischemia is necessary for determining future clinical benefit from coronary revascularization.

Traditionally, diagnostic performance studies of MDCTA have assessed stenosis severity, comparing it with quantitative coronary angiography (QCA) as a reference standard. The use of QCA as a comparator with MDCTA is a logical one, because intraluminal stenosis severity is assessed by both approaches. By this criterion, MDCTA has performed well (1–3).

The QCA threshold for "significant" coronary artery stenosis detection in prior MDCTA diagnostic accuracy studies has been variable, with some using 50% stenosis and some using 70% stenosis as a cutoff of anatomic significance. These data arise from landmark studies using positron emission tomography that demonstrate significant reductions in myocardial blood flow at the 50% stenosis threshold, which became much more dramatic at the 70%-stenosis threshold (7,8). In this regard, the 70%-stenosis threshold has now become the generally accepted angiographic measure of anatomic significance, given the wide variability of functional reduction in myocardial blood flow within the 50% to 69% stenosis range. In this regard, the recent Appropriateness Criteria for Coronary Revascularization (9) state that a 70% stenosis is the angiographic standard for consideration of revascularization. Furthermore, because prior studies (10) indicate that MDCTA tends toward overestimation of plaque stenosis severity—in particular, for calcified plaque—it would seem that a 70% stenosis severity criterion rather than the 50% criterion would have been more "appropriate" for use in the Sarno et al. study (4).

Given that the definitions of "appropriate" and "inappropriate" in the Sarno study are based upon treatment decisions from functional rather than anatomic significance, it is perhaps not surprising that MDCTA performed poorly. Even when CA is the standard, the recently published American College of Cardiology Appropriateness Criteria of Coronary Revascularization judge appropriateness not only by summary measures of coronary anatomy (including the 70% definition of stenosis) but also by patient symptoms and, in certain cases, noninvasive testing results (9). How could MDCTA, with lower resolution than CA be held to a higher standard? In this regard, Sarno et al. seem to have set up MDCTA to be a "strawman." If functional significance as measured by FFR is to be the criteria for which lesions are judged, then any anatomic measure of stenosis that cannot assess coronary flow reserve will invariably fail. Indeed, in this study, CA also fails to identify appropriate lesions for revascularization, and the probabilistic likelihood of MDCTA to identify functionally significant lesions is not different from CA.

Furthermore, underlying this study is a presupposition that the purpose of noninvasive cardiac imaging should be to determine the appropriateness of coronary revascularization. This is in direct contrast with the tenets that the fields of noninvasive imaging have followed for the past 30 years. At its core, the principal purposes of noninvasive cardiac imaging are two-fold, namely, to diagnose or exclude coronary artery disease by defining its extent and severity, and to predict outcomes on the basis of image-specific findings (11).

For the first of these criteria, MDCTA has performed excellently, with sensitivity and specificity for CAD by CA clearly higher than those of any other noninvasive test. Beyond diagnostic performance, however, an accruing growing evidence base indicates that MDCTA permits risk stratification as robust as that associated with other noninvasive tests, such as myocardial perfusion scintigraphy (MPS). Individuals with greater extent and severity of CAD as identified by MDCTA are at greater risk for future adverse CAD events. In contrast, those individuals identified as having no or minimal CAD by MDCTA have a long "warranty" period that seems to extend to at least 7 years (12).

This characteristic of MDCTA should not be overlooked. Indeed, the most "appropriate" patient cohort for noninvasive cardiac imaging evaluation is the intermediate-risk population, because patients with low and high pre-test risk—in accordance with Bayes' theorem—will not be sufficiently reclassified by positive or negative testing, respectively. In this regard, in an intermediate-risk population, the majority of individuals evaluated by noninvasive testing will not have severe CAD, and a test that can safely exclude CAD is useful for identification of individuals in whom no further testing—including CA—is necessary.

Although it might be then tempting to extrapolate the FFR findings of this study and the FAME trial to noninvasive methods that are capable of assessing the functional significance of CAD, to date there are limited data to suggest that these tests—including electrocardiography, MPS, positron emission tomography, and stress echocardiography—in conjunction with coronary anatomy are able to determine "appropriateness" of coronary revascularization. In the recent nuclear substudy of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, there was suggestive evidence that patients with moderate-to-severe ischemia by MPS and angiographic coronary artery stenoses of anatomic significance might benefit from PCI plus optimal medical therapy versus optimal medical therapy alone (13). However, this substudy of 314 patients was insufficiently powered to fully address this possibility. Further study of the use of noninvasive studies to guide decisions for CA and coronary revascularization is needed.

Thus, the criteria for using noninvasive tests for determining appropriateness of coronary revascularization are a work-in-progress. Whether similar results to the FAME study can be derived with noninvasive testing rather than invasive FFR remains unknown. Until then, no noninvasive test—including MDCTA—should be used in isolation for the determination of appropriateness of coronary revascularization. Similarly, no invasive test—including FFR—should be used alone for the determination of appropriateness of coronary revascularization. Instead, defining appropriateness of coronary revascularization is best left to societal consensus, which at present requires careful consideration of a complex interplay between patient symptoms, coronary anatomy, and the results of functional tests.

	Footnotes

 
Drs. Berman and Min have received grant support from GE.

^_* Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.

^_* Reprint requests and correspondence: Dr. Daniel S. Berman, Director, Cardiac Imaging Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 1258, Los Angeles, California 90048 (Email: bermand{at}cshs.org).

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