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Journal of the American College of Cardiology
Ó 2013 by the American College of Cardiology Foundation
Published by Elsevier Inc.
EDITORIAL COMMENT
Computed Tomography
Perfusion to Assess
Physiological Significance of
Coronary Stenosis in the
Post-FAME Era (Fractional Flow
Reserve Versus Angiography for
Multivessel Evaluation)*
Andrew E. Arai, MD
Bethesda, Maryland
Goldstein et al. (1) documented that it takes a severe
coronary stenosis before myocardial perfusion is compromised. Both invasive and noninvasive cardiologists should
consider a few lessons from the FAME (Fractional Flow
Reserve versus Angiography for Multivessel Evaluation)
studies and other contemporary analyses. First, it is safer and
better to manage a coronary stenosis based on physiological
significance than angiographic severity, at least as determined by fractional flow reserve (FFR) (2). Second, when
compared with optimal medical therapy, stenting reduces
major adverse cardiac events when FFR is used to determine
the physiological significance of stenoses (3). Third, too
See page 1476
many patients underwent invasive coronary for stable angina
without prior stress testing in the United States in 2004 (4).
Fourth, our most commonly selected stress tests (electrocardiography, single-photon emission computed tomography, and echocardiography) do not localize ischemia and
do not quantify the severity of ischemia in a way that looks
interchangeable with the invasive FFR stress test of specific
coronary stenoses. This probably contributes to why interventional cardiologists have relied so heavily on severity of
*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood
Institute, National Institutes of Health, Department of Health and Human Services,
Bethesda, Maryland. This work was funded by the Division of Intramural Research of
the National, Heart, Lung, and Blood Institute (ZIA HL006137-03 and ZIA
HL006138-03). Dr. Arai has received research support from Siemens and Toshiba.
Vol. 62, No. 16, 2013
ISSN 0735-1097/$36.00
http://dx.doi.org/10.1016/j.jacc.2013.05.056
coronary stenosis for many years and have now developed
FFR as their reference standard. However, if FFR is the new
reference standard, one can expect that noninvasive imaging
should be able to assess the physiological significance of
stenosis and may someday replace invasive FFR.
The work by Rief et al. (5) from the Charite Medical
School in Berlin in this issue of the Journal nicely documents
how the combination of coronary computed tomography
angiography (CTA) and adenosine stress computed
tomography perfusion (CTP) can be used to assess the
severity of coronary stenosis. The protocol is a noninvasive
analogue to the 2 steps used in the cardiac catheterization
laboratory: CT coronary angiography followed by an adenosine stress perfusion physiological assessment of stenosis.
The population in the study by Rief et al. (5) tackles a set
of patients that challenges CTA. Blooming artifact from
coronary stents can make it difficult to accurately assess for instent restenosis and reduces the diagnostic accuracy of CTA
alone. Patients with severe coronary disease often have heavily
calcified coronary arteries that can also compromise the ability
to accurately predict the presence or severity of native coronary stenoses. The CTA provides accurate anatomic localization of stenoses, stents, heavily calcified coronary arteries,
and the myocardium served by the coronary arteries affected
by these apparent or possible stenoses. The stress CTP then
assesses the physiological significance of the stenoses. The
current study documents that CTP improves diagnostic
accuracy over CTA alone in this population of patients. Such
results would be difficult to achieve by CTA alone.
CTA combined with stress CTP is not the only strategy for
improving the accuracy of noninvasive evaluation of coronary
artery disease. CT-FFR has been studied as a computerized
analysis of the coronary arteries that can make a determination
of the predicted physiological significance of stenoses.
Computational fluid dynamics, or complex modeling of blood
flow through the imaged coronary arteries combined with
assessments of the amount of myocardium served by the
coronary, and a few assumptions such as the stress coronary
blood flow, can provide a CT-based estimate of FFR. The
DeFACTO (Determination of Fractional Flow Reserve by
Anatomic Computed Tomographic Angiography) study (6)
showed improved area under the curve for CT-FFR than
for CTA alone, but the study did not quite meet predetermined diagnostic accuracy thresholds. Nonetheless,
there is a lot of interest in CT-FFR because this approach
avoids a CT stress test and the associated additional radiation
exposure. Finally, quantitative positron emission tomography
perfusion and quantitative stress magnetic resonance imaging
theoretically could also make measurements of myocardial
perfusion reserve and substitute for the invasive FFR,
assuming adequate clinical trials prove that hypothesis.
Despite what had seemed like a long period of wellestablished approaches to diagnosing and managing coronary artery disease, there have been a remarkable number of
developments since 2009 that are shaking dogma. There is
reason to believe that the fundamental approach to detecting
JACC Vol. 62, No. 16, 2013
October 15, 2013:1486–7
Arai
CT Perfusion in the Post-FAME Era
1487
REFERENCES
2. Tonino PA, De Bruyne B, Pijls NH, et al., for the FAME Study
Investigators. Fractional flow reserve versus angiography for guiding
percutaneous coronary intervention. N Engl J Med 2009;360:
213–24.
3. De Bruyne B, Pijls NH, Kalesan B, et al., for the FAME 2 Trial
Investigators. Fractional flow reserve-guided PCI versus medical therapy
in stable coronary disease. N Engl J Med 2012;367:991–1001.
4. Lin GA, Dudley RA, Lucas FL, Malenka DJ, Vittinghoff E,
Redberg RF. Frequency of stress testing to document ischemia prior
to elective percutaneous coronary intervention. JAMA 2008;300:
1765–73.
5. Rief M, Zimmermann E, Stenzel F, et al. Computed tomography
angiography and myocardial computed tomography perfusion in patients
with coronary stents: prospective intraindividual comparison with
conventional angiography. J Am Coll Cardiol 2013;62:1476–85.
6. Min JK, Leipsic J, Pencina MJ, et al. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA 2012;
308:1237–45.
7. Dattilo PB, Prasad A, Honeycutt E, Wang TY, Messenger JC.
Contemporary patterns of fractional flow reserve and intravascular
ultrasound use among patients undergoing percutaneous coronary
intervention in the United States: insights from the National Cardiovascular Data Registry. J Am Coll Cardiol 2012;60:2337–9.
1. Goldstein RA, Kirkeeide RL, Demer LL, et al. Relation between
geometric dimensions of coronary artery stenoses and myocardial
perfusion reserve in man. J Clin Invest 1987;79:1473–8.
Key Words: computed tomography - coronary angiography
coronary vessels - diagnostic accuracy - stents.
and diagnosing coronary disease is changing. Economic
pressures and outcome-based research are pushing us to use
fewer stents and to reserve them for those patients that have
physiologically significant stenoses. Although we have a long
way to go in adopting FFR in the cardiac catheterization
laboratory in the United States (7), one can be confident that
either invasive FFR or noninvasive equivalent metrics will
play an increasingly important role in selecting patients for
stenting versus medical therapy.
Reprint requests and correspondence: Dr. Andrew E. Arai,
National Institutes of Health, National Heart, Lung, and Blood
Institute, Building 10, Room B1D416, MSC 1061, 10 Center
Drive, Bethesda, Maryland 20892-1061. E-mail: [email protected].
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