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Computed Tomography Perfusion to Assess Physiological Significance of Coronary Stenosis in the Post-FAME Era (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation)∗
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].
-
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].
-