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Anatomy Meets Function
Journal of the American College of Cardiology © 2011 by the American College of Cardiology Foundation Published by Elsevier Inc.
EDITORIAL COMMENT
Anatomy Meets Function Modeling Coronary Flow Reserve on the Basis of Coronary Computed Tomography Angiography* Stephan Achenbach, MD Giessen, Germany
Coronary computed tomography angiography (CCTA) allows noninvasive visualization of coronary anatomy and is increasingly used to detect and rule out coronary artery stenoses. Seemingly, it has made possible what cardiologists had dreamed of in the past: the ability to perform “noninvasive coronary angiography” and to identify coronary artery narrowing without having to proceed to invasive cardiac catheterization. Ironically, the time period during which CCTA matured (starting in the early 1990s and continuing into the second decade of the new millennium) coincides with another very prominent development in cardiology: decreasing enthusiasm with coronary “luminology.” On one hand, it is now widely recognized that acute coronary syndromes are not necessarily linked to pre-existing highgrade coronary artery stenoses (1–3). Much rather, the majority of acute events are caused by the rupture of plaques See page 1989
that are not associated with severe luminal narrowing (which does not imply that a high-grade stenosis is always harmless: per-lesion, a severe stenosis has a higher likelihood of rupture than a lesion without severe obstruction, but mild lesions are substantially more frequent, which explains why they cause the majority of events). On the other hand, several landmark studies have demonstrated rather convincingly that coronary revascularization on the basis of stenosis degree alone, let alone on the basis of visual estimation of stenosis severity in invasive coronary angiography, is not a suitable strategy to minimize event rates or to spend healthcare dollars. Obviously, there is a close correlation between the degree of ischemia a given *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 Department of Cardiology, University of Giessen, Giessen, Germany. Dr. Achenbach has received research grants from Siemens and Bayer Heathcare; has received lecture honoraria from Siemens; is a consultant to Guerbet, Servier, and Circle; and is supported by research grant BMBF 01 EV 0708 from Bundesministerium für Bildung und Forschung (BMBF), Bonn, Germany.
Vol. 58, No. 19, 2011 ISSN 0735-1097/$36.00 doi:10.1016/j.jacc.2011.09.006
stenosis causes and the benefit that can be derived from its revascularization (4 –7). Obviously, both of these issues—which have had dramatic consequences with regard to the understanding and perception of coronary artery disease, its clinical manifestations, and optimal treatment—substantially influence the way in which cardiologists view the potential use of CCTA. High-quality CCTA datasets permit visualization not only of the coronary artery lumen and its narrowing but also of the atherosclerotic plaque itself—incremental information to what invasive coronary angiography can provide. In fact, it has been shown that CCTA and the analysis of coronary plaque burden provides incremental prognostic information beyond the analysis of conventional cardiovascular risk factors (8 –12). Potentially, computed tomography (CT) might thus be a much more comprehensive anatomic imaging modality than invasive coronary angiography could ever be. In a different way, there are understandable concerns that the option to noninvasively obtain information on coronary morphology and the presence of coronary stenoses, often displayed in a 3-dimensional and visually pleasing way further enhanced by the liberal use of color, might entice physicians—and patients—to forget what the cardiology community has painfully learned in the past years: that detecting luminal narrowing is, in fact, not the “holy grail” and that not every stenotic coronary segment requires invasive angiography and revascularization. This issue is further complicated because coronary CT angiograms have a tendency to overestimate the presence and severity of coronary luminal obstruction, especially if image quality is impaired. The “positive predictive value” has been the greatest problem of CCTA. It is limited in the purely anatomic comparisons with invasive coronary angiography (and typically ranges between roughly 70% and 95%) (13–15). In comparison with tests for ischemia, it is even lower (16). For this reason, investigators have tried to obtain additional information from cardiac CT: to reduce the number of false positive interpretations and to obtain information on the functional relevance of a given coronary narrowing detected by CT. For example, 1 approach has been to measure the gradient of intraluminal attenuation along the course of a coronary artery, in an attempt to extract information somehow related to “flow” within the coronary vessel (17,18). Alternatively, several investigators have looked at myocardial enhancement, both at rest (19) and during pharmacological stress (20 –23), to analyze the impact of coronary stenoses in myocardial blood flow. This has been shown to improve specificity and the positive predictive value of CCTA (24), but as compared with morphological imaging alone, it requires additional contrast and radiation. In this issue of the Journal, Koo et al. (25) present a fascinating new approach to extract additional information on ischemia from anatomic CCTA datasets. With theories of fluid dynamics and massive computing
JACC Vol. 58, No. 19, 2011 November 1, 2011:1998–2000
power, the effect of coronary narrowing identified by CT on blood flow in the coronary arteries during stress is predicted, and results are expressed in a way very similar to the invasively obtained “fractional flow reserve” (FFR), which describes the difference in intracoronary blood pressure proximal and distal to a coronary lesion during hyperemia. Fractional flow reserve has been shown to be extremely valuable for the distinction between lesions that benefit from revascularization and lesions in which revascularization can safely be deferred (6). Notably, the value is not measured by CT—CT is unable to measure flow or pressure inside the coronary arteries. Much rather, modeling of theoretical coronary artery flow is used to derive the necessary parameters from the shape of the coronary lesions, taking into account the entire anatomy of the coronary vessels and aortic root, all obtained in a single dataset at rest. One wonders intuitively how this is possible, considering the relatively limited spatial resolution of CT, which can very crudely be assumed at approximately 0.5 mm. However, in a selected cohort of 103 patients, in whom 153 vessels were analyzed, the authors demonstrate a relatively close agreement between computation of fractional flow reserve from coronary computed tomographic angiography data (“FFRCT”) with the invasively determined “true FFR” and a significantly better performance of FFRCT to identify lesions with a true FFR ⱕ0.80 than the mere anatomic evaluation of CCTA datasets by an independent, expert interpreter. Accuracies were 84% versus 59%, and the areas under the receiver-operator characteristic curves were 0.92 versus 0.70 (p ⫽ 0.0001). The trial was well-performed, with a multicenter design and independent core laboratories, and the presented results clearly demonstrate the potential added value of a completely new (albeit computationally elaborate) way of analyzing CCTA datasets. It is an impressive first step into what needs to follow, the painstakingly detailed workup of whether this method will translate into clinical benefit when applied on a broader scale and which patient groups are the ones to most likely benefit from this additional analysis. Some shortcomings of this current trial deserve mentioning, without diminishing the accomplishment of the investigators. As in prior trials, which used additional analyses (transluminal attenuation) or even additional examinations (stress myocardial perfusion), it was mainly specificity that was improved. Although sensitivity for stenosis detection slightly decreased from 91% to 88% (2 additional “missed lesions” on the basis of FFRCT), specificity improved dramatically from 40% to 82% if FFRCT was used instead of mere visual analysis. Potentially, the simplified 50% threshold commonly used to define relevant diameter stenosis in visual analysis is too low and might not be fully appropriate. The potential of visually analyzing coronary CT datasets might not have been fully used. For example, Cheng et al. (26) have previously demonstrated that accuracy of CCTA can be increased by introducing higher stenosis thresholds.
Achenbach Coronary Flow Reserve and Coronary CT Angiography
1999
Also, this study suffers from a certain selection bias. Only patients with “at least 1 stenosis ⱖ50% in a major coronary artery” in CCTA were included in the trial. This artificially lowers the specificity of anatomic evaluation, because there are fewer “true negative” cases than in an unselected population. Six very-high-grade lesions were excluded because invasive FFR was not safely possible. This again introduces a slight bias, because the number of “true positive” counts of CT was reduced. In a completely nonselected collective of individuals undergoing CCTA, the incremental value of FFRCT determination might therefore be less than suggested by the analysis presented here, and if speculations about the best clinical applications were appropriate at this early stage at all, applications would probably be most interesting in lesions that visually seem of questionable severity. In spite of these limitations, which are due to technical requirements and necessities of trial design and not uncommon in the early reports of a new technique, the overall result of the study remains an impressive one: we learn that modern computational methods enable the simulation of complex disease manifestations during stress or exercise on the basis of 3-dimensional morphology imaging obtained at rest and under baseline nonstress conditions. In general terms: it seems to be possible to derive very detailed functional information from purely anatomic datasets— anatomy meets function. This concept deserves and requires further investigation on a much broader scale and will most likely not remain limited to the relatively confined area of CCTA. Reprint requests and correspondence: Dr. Stephan Achenbach, Department of Cardiology, University of Giessen, Klinikstrasse 33, 35392 Giessen, Germany. E-mail: stephan.achenbach@ innere.med.uni-giessen.de. REFERENCES
1. Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation 1988;78:1157– 66. 2. Little WC, Applegate RJ. Role of plaque size and degree of stenosis in acute myocardial infarction. Cardiol Clin 1996;14:221– 8. 3. Giroud D, Li JM, Urban P, Meier B, Rutishauer W. Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography. Am J Cardiol 1992;69:729 –32. 4. Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation 2003;107: 2900 –7. 5. Shaw LJ, Berman DS, Maron DJ, et al., for the COURAGE Investigators. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation 2008; 117:1283–91. 6. 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.
2000
Achenbach Coronary Flow Reserve and Coronary CT Angiography
7. Pijls NH, Fearon WF, Tonino PA, et al., for the FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME study. J Am Coll Cardiol 2010;56:1778 – 84. 8. Hadamitzky M, Freissmuth B, Meyer T, et al. Prognostic value of coronary computed tomographic angiography for prediction of cardiac events in patients with suspected coronary artery disease. J Am Coll Cardiol Img 2009;2:404 –11. 9. Min JK, Shaw LJ, Devereux RB, et al. Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality. J Am Coll Cardiol 2007;50:1161–70. 10. van Werkhoven JM, Schuijf JD, Gaemperli O, et al. Incremental prognostic value of multi-slice computed tomography coronary angiography over coronary artery calcium scoring in patients with suspected coronary artery disease. Eur Heart J 2009;30:2622–9. 11. Min JK, Dunning A, Lin FY, et al. Rationale and design of the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) Registry. J Cardiovasc Comput Tomogr 2011;5:84 –92. 12. Ostrom MP, Gopal A, Ahmadi N, et al. Mortality incidence and the severity of coronary atherosclerosis assessed by computed tomography angiography. J Am Coll Cardiol 2008;52:1335– 43. 13. Meijboom WB, Meijs MF, Schuijf JD, et al. Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study. J Am Coll Cardiol 2008;52:2135– 44. 14. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol 2008;52:1724 –32. 15. Mowatt G, Cummins E, Waugh N, et al. Systematic review of the clinical effectiveness and cost-effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of coronary artery disease. Health Technol Assess 2008;12:iii–iv, ix–143. 16. Min JK, Shaw LJ, Berman DS. The present state of coronary computed tomography angiography a process in evolution. J Am Coll Cardiol 2010;55:957– 65.
JACC Vol. 58, No. 19, 2011 November 1, 2011:1998–2000 17. Steigner ML, Mitsouras D, Whitmore AG, et al. Iodinated contrast opacification gradients in normal coronary arteries imaged with prospectively ECG-gated single heart beat 320-detector row computed tomography. Circ Cardiovasc Imaging 2010;3:179 – 86. 18. Choi J-H, Min JK, Labounty TM, et al. Intracoronary transluminal attenuation gradient in 64-slice coronary computed tomographic angiography: a novel method of determining coronary artery stenosis. J Am Coll Cardiol Img 2011. In press. 19. Ruzsics B, Schwarz F, Schoepf UJ, et al. Comparison of dual-energy computed tomography of the heart with single photon emission computed tomography for assessment of coronary artery stenosis and of the myocardial blood supply. Am J Cardiol 2009;104:318 –26. 20. Blankstein R, Shturman LD, Rogers IS, et al. Adenosine-induced stress myocardial perfusion imaging using dual-source cardiac computed tomography. J Am Coll Cardiol 2009;54:1072– 84. 21. Ho KT, Chua KC, Klotz E, Panknin C. Stress and rest dynamic myocardial perfusion imaging by evaluation of complete timeattenuation curves with dual-source CT. J Am Coll Cardiol Img 2010;3:811–20. 22. Bamberg F, Becker A, Schwarz F, et al. Detection of hemodynamically significant coronary artery stenosis: incremental diagnostic value of dynamic CT-Based myocardial perfusion imaging. Radiology 2011; 260:689 –98. 23. Techasith T, Cury RC. Stress myocardial CT perfusion: an update and future perspective. J Am Coll Cardiol Img 2011;4:905–16. 24. Rocha-Filho JA, Blankstein R, Shturman LD, et al. Incremental value of adenosine-induced stress myocardial perfusion imaging with dualsource CT at cardiac CT angiography. Radiology 2010;254:410 –9. 25. Koo B-K, Erglis A, Doh J-H, et al. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms: results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenosis Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol 2011;58:1989 –97. 26. Cheng V, Gutstein A, Wolak A, et al. Moving beyond binary grading of coronary arterial stenoses on coronary computed tomographic angiography: insights for the imager and referring clinician. J Am Coll Cardiol Img 2008;1:460 –71. Key Words: computational fluid dynamics y coronary CT angiography y coronary ischemia y fractional flow reserve.
EDITORIAL COMMENT
Anatomy Meets Function Modeling Coronary Flow Reserve on the Basis of Coronary Computed Tomography Angiography* Stephan Achenbach, MD Giessen, Germany
Coronary computed tomography angiography (CCTA) allows noninvasive visualization of coronary anatomy and is increasingly used to detect and rule out coronary artery stenoses. Seemingly, it has made possible what cardiologists had dreamed of in the past: the ability to perform “noninvasive coronary angiography” and to identify coronary artery narrowing without having to proceed to invasive cardiac catheterization. Ironically, the time period during which CCTA matured (starting in the early 1990s and continuing into the second decade of the new millennium) coincides with another very prominent development in cardiology: decreasing enthusiasm with coronary “luminology.” On one hand, it is now widely recognized that acute coronary syndromes are not necessarily linked to pre-existing highgrade coronary artery stenoses (1–3). Much rather, the majority of acute events are caused by the rupture of plaques See page 1989
that are not associated with severe luminal narrowing (which does not imply that a high-grade stenosis is always harmless: per-lesion, a severe stenosis has a higher likelihood of rupture than a lesion without severe obstruction, but mild lesions are substantially more frequent, which explains why they cause the majority of events). On the other hand, several landmark studies have demonstrated rather convincingly that coronary revascularization on the basis of stenosis degree alone, let alone on the basis of visual estimation of stenosis severity in invasive coronary angiography, is not a suitable strategy to minimize event rates or to spend healthcare dollars. Obviously, there is a close correlation between the degree of ischemia a given *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 Department of Cardiology, University of Giessen, Giessen, Germany. Dr. Achenbach has received research grants from Siemens and Bayer Heathcare; has received lecture honoraria from Siemens; is a consultant to Guerbet, Servier, and Circle; and is supported by research grant BMBF 01 EV 0708 from Bundesministerium für Bildung und Forschung (BMBF), Bonn, Germany.
Vol. 58, No. 19, 2011 ISSN 0735-1097/$36.00 doi:10.1016/j.jacc.2011.09.006
stenosis causes and the benefit that can be derived from its revascularization (4 –7). Obviously, both of these issues—which have had dramatic consequences with regard to the understanding and perception of coronary artery disease, its clinical manifestations, and optimal treatment—substantially influence the way in which cardiologists view the potential use of CCTA. High-quality CCTA datasets permit visualization not only of the coronary artery lumen and its narrowing but also of the atherosclerotic plaque itself—incremental information to what invasive coronary angiography can provide. In fact, it has been shown that CCTA and the analysis of coronary plaque burden provides incremental prognostic information beyond the analysis of conventional cardiovascular risk factors (8 –12). Potentially, computed tomography (CT) might thus be a much more comprehensive anatomic imaging modality than invasive coronary angiography could ever be. In a different way, there are understandable concerns that the option to noninvasively obtain information on coronary morphology and the presence of coronary stenoses, often displayed in a 3-dimensional and visually pleasing way further enhanced by the liberal use of color, might entice physicians—and patients—to forget what the cardiology community has painfully learned in the past years: that detecting luminal narrowing is, in fact, not the “holy grail” and that not every stenotic coronary segment requires invasive angiography and revascularization. This issue is further complicated because coronary CT angiograms have a tendency to overestimate the presence and severity of coronary luminal obstruction, especially if image quality is impaired. The “positive predictive value” has been the greatest problem of CCTA. It is limited in the purely anatomic comparisons with invasive coronary angiography (and typically ranges between roughly 70% and 95%) (13–15). In comparison with tests for ischemia, it is even lower (16). For this reason, investigators have tried to obtain additional information from cardiac CT: to reduce the number of false positive interpretations and to obtain information on the functional relevance of a given coronary narrowing detected by CT. For example, 1 approach has been to measure the gradient of intraluminal attenuation along the course of a coronary artery, in an attempt to extract information somehow related to “flow” within the coronary vessel (17,18). Alternatively, several investigators have looked at myocardial enhancement, both at rest (19) and during pharmacological stress (20 –23), to analyze the impact of coronary stenoses in myocardial blood flow. This has been shown to improve specificity and the positive predictive value of CCTA (24), but as compared with morphological imaging alone, it requires additional contrast and radiation. In this issue of the Journal, Koo et al. (25) present a fascinating new approach to extract additional information on ischemia from anatomic CCTA datasets. With theories of fluid dynamics and massive computing
JACC Vol. 58, No. 19, 2011 November 1, 2011:1998–2000
power, the effect of coronary narrowing identified by CT on blood flow in the coronary arteries during stress is predicted, and results are expressed in a way very similar to the invasively obtained “fractional flow reserve” (FFR), which describes the difference in intracoronary blood pressure proximal and distal to a coronary lesion during hyperemia. Fractional flow reserve has been shown to be extremely valuable for the distinction between lesions that benefit from revascularization and lesions in which revascularization can safely be deferred (6). Notably, the value is not measured by CT—CT is unable to measure flow or pressure inside the coronary arteries. Much rather, modeling of theoretical coronary artery flow is used to derive the necessary parameters from the shape of the coronary lesions, taking into account the entire anatomy of the coronary vessels and aortic root, all obtained in a single dataset at rest. One wonders intuitively how this is possible, considering the relatively limited spatial resolution of CT, which can very crudely be assumed at approximately 0.5 mm. However, in a selected cohort of 103 patients, in whom 153 vessels were analyzed, the authors demonstrate a relatively close agreement between computation of fractional flow reserve from coronary computed tomographic angiography data (“FFRCT”) with the invasively determined “true FFR” and a significantly better performance of FFRCT to identify lesions with a true FFR ⱕ0.80 than the mere anatomic evaluation of CCTA datasets by an independent, expert interpreter. Accuracies were 84% versus 59%, and the areas under the receiver-operator characteristic curves were 0.92 versus 0.70 (p ⫽ 0.0001). The trial was well-performed, with a multicenter design and independent core laboratories, and the presented results clearly demonstrate the potential added value of a completely new (albeit computationally elaborate) way of analyzing CCTA datasets. It is an impressive first step into what needs to follow, the painstakingly detailed workup of whether this method will translate into clinical benefit when applied on a broader scale and which patient groups are the ones to most likely benefit from this additional analysis. Some shortcomings of this current trial deserve mentioning, without diminishing the accomplishment of the investigators. As in prior trials, which used additional analyses (transluminal attenuation) or even additional examinations (stress myocardial perfusion), it was mainly specificity that was improved. Although sensitivity for stenosis detection slightly decreased from 91% to 88% (2 additional “missed lesions” on the basis of FFRCT), specificity improved dramatically from 40% to 82% if FFRCT was used instead of mere visual analysis. Potentially, the simplified 50% threshold commonly used to define relevant diameter stenosis in visual analysis is too low and might not be fully appropriate. The potential of visually analyzing coronary CT datasets might not have been fully used. For example, Cheng et al. (26) have previously demonstrated that accuracy of CCTA can be increased by introducing higher stenosis thresholds.
Achenbach Coronary Flow Reserve and Coronary CT Angiography
1999
Also, this study suffers from a certain selection bias. Only patients with “at least 1 stenosis ⱖ50% in a major coronary artery” in CCTA were included in the trial. This artificially lowers the specificity of anatomic evaluation, because there are fewer “true negative” cases than in an unselected population. Six very-high-grade lesions were excluded because invasive FFR was not safely possible. This again introduces a slight bias, because the number of “true positive” counts of CT was reduced. In a completely nonselected collective of individuals undergoing CCTA, the incremental value of FFRCT determination might therefore be less than suggested by the analysis presented here, and if speculations about the best clinical applications were appropriate at this early stage at all, applications would probably be most interesting in lesions that visually seem of questionable severity. In spite of these limitations, which are due to technical requirements and necessities of trial design and not uncommon in the early reports of a new technique, the overall result of the study remains an impressive one: we learn that modern computational methods enable the simulation of complex disease manifestations during stress or exercise on the basis of 3-dimensional morphology imaging obtained at rest and under baseline nonstress conditions. In general terms: it seems to be possible to derive very detailed functional information from purely anatomic datasets— anatomy meets function. This concept deserves and requires further investigation on a much broader scale and will most likely not remain limited to the relatively confined area of CCTA. Reprint requests and correspondence: Dr. Stephan Achenbach, Department of Cardiology, University of Giessen, Klinikstrasse 33, 35392 Giessen, Germany. E-mail: stephan.achenbach@ innere.med.uni-giessen.de. REFERENCES
1. Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation 1988;78:1157– 66. 2. Little WC, Applegate RJ. Role of plaque size and degree of stenosis in acute myocardial infarction. Cardiol Clin 1996;14:221– 8. 3. Giroud D, Li JM, Urban P, Meier B, Rutishauer W. Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography. Am J Cardiol 1992;69:729 –32. 4. Hachamovitch R, Hayes SW, Friedman JD, Cohen I, Berman DS. Comparison of the short-term survival benefit associated with revascularization compared with medical therapy in patients with no prior coronary artery disease undergoing stress myocardial perfusion single photon emission computed tomography. Circulation 2003;107: 2900 –7. 5. Shaw LJ, Berman DS, Maron DJ, et al., for the COURAGE Investigators. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation 2008; 117:1283–91. 6. 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.
2000
Achenbach Coronary Flow Reserve and Coronary CT Angiography
7. Pijls NH, Fearon WF, Tonino PA, et al., for the FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention in patients with multivessel coronary artery disease: 2-year follow-up of the FAME study. J Am Coll Cardiol 2010;56:1778 – 84. 8. Hadamitzky M, Freissmuth B, Meyer T, et al. Prognostic value of coronary computed tomographic angiography for prediction of cardiac events in patients with suspected coronary artery disease. J Am Coll Cardiol Img 2009;2:404 –11. 9. Min JK, Shaw LJ, Devereux RB, et al. Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality. J Am Coll Cardiol 2007;50:1161–70. 10. van Werkhoven JM, Schuijf JD, Gaemperli O, et al. Incremental prognostic value of multi-slice computed tomography coronary angiography over coronary artery calcium scoring in patients with suspected coronary artery disease. Eur Heart J 2009;30:2622–9. 11. Min JK, Dunning A, Lin FY, et al. Rationale and design of the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) Registry. J Cardiovasc Comput Tomogr 2011;5:84 –92. 12. Ostrom MP, Gopal A, Ahmadi N, et al. Mortality incidence and the severity of coronary atherosclerosis assessed by computed tomography angiography. J Am Coll Cardiol 2008;52:1335– 43. 13. Meijboom WB, Meijs MF, Schuijf JD, et al. Diagnostic accuracy of 64-slice computed tomography coronary angiography: a prospective, multicenter, multivendor study. J Am Coll Cardiol 2008;52:2135– 44. 14. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol 2008;52:1724 –32. 15. Mowatt G, Cummins E, Waugh N, et al. Systematic review of the clinical effectiveness and cost-effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of coronary artery disease. Health Technol Assess 2008;12:iii–iv, ix–143. 16. Min JK, Shaw LJ, Berman DS. The present state of coronary computed tomography angiography a process in evolution. J Am Coll Cardiol 2010;55:957– 65.
JACC Vol. 58, No. 19, 2011 November 1, 2011:1998–2000 17. Steigner ML, Mitsouras D, Whitmore AG, et al. Iodinated contrast opacification gradients in normal coronary arteries imaged with prospectively ECG-gated single heart beat 320-detector row computed tomography. Circ Cardiovasc Imaging 2010;3:179 – 86. 18. Choi J-H, Min JK, Labounty TM, et al. Intracoronary transluminal attenuation gradient in 64-slice coronary computed tomographic angiography: a novel method of determining coronary artery stenosis. J Am Coll Cardiol Img 2011. In press. 19. Ruzsics B, Schwarz F, Schoepf UJ, et al. Comparison of dual-energy computed tomography of the heart with single photon emission computed tomography for assessment of coronary artery stenosis and of the myocardial blood supply. Am J Cardiol 2009;104:318 –26. 20. Blankstein R, Shturman LD, Rogers IS, et al. Adenosine-induced stress myocardial perfusion imaging using dual-source cardiac computed tomography. J Am Coll Cardiol 2009;54:1072– 84. 21. Ho KT, Chua KC, Klotz E, Panknin C. Stress and rest dynamic myocardial perfusion imaging by evaluation of complete timeattenuation curves with dual-source CT. J Am Coll Cardiol Img 2010;3:811–20. 22. Bamberg F, Becker A, Schwarz F, et al. Detection of hemodynamically significant coronary artery stenosis: incremental diagnostic value of dynamic CT-Based myocardial perfusion imaging. Radiology 2011; 260:689 –98. 23. Techasith T, Cury RC. Stress myocardial CT perfusion: an update and future perspective. J Am Coll Cardiol Img 2011;4:905–16. 24. Rocha-Filho JA, Blankstein R, Shturman LD, et al. Incremental value of adenosine-induced stress myocardial perfusion imaging with dualsource CT at cardiac CT angiography. Radiology 2010;254:410 –9. 25. Koo B-K, Erglis A, Doh J-H, et al. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms: results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenosis Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol 2011;58:1989 –97. 26. Cheng V, Gutstein A, Wolak A, et al. Moving beyond binary grading of coronary arterial stenoses on coronary computed tomographic angiography: insights for the imager and referring clinician. J Am Coll Cardiol Img 2008;1:460 –71. Key Words: computational fluid dynamics y coronary CT angiography y coronary ischemia y fractional flow reserve.