Imaging

New technologies that solve some old problems could make cardiovascular CT the go-to imaging tool to assess both anatomy and function.

Cardiovascular CT imaging has been a welcome tool in patient assessment due to its noninvasive nature, ease, and quickness. Likewise, cardiovascular CT angiography (CCTA) has provided noninvasive information about vessel stenoses, with lower costs and radiation exposure compared with invasive angiography.

Images courtesy Dr. James P. Earls

Perhaps the biggest criticism about cardiovascular CT is that, while it provides very good anatomic detail, functional information – a crucial piece to the overall picture – is not discernable.

"Historically, coronary CT angiography has been an extremely anatomic method for documenting the severity of coronary artery stenoses or luminal compromise," said Dr. James K. Min, immediate past president of SCCT. This has left CTA open to the criticism that the more useful evaluation of coronary artery disease is not only to document high-grade stenoses – as with coronary CT angiography – but also to determine the physiologic significance of those stenoses.

However, at this year’s meeting of the Society of Cardiovascular Computed Tomography in Baltimore, "we saw the emergence of two robust methods for physiologic assessment of coronary disease by cardiac CT," he said. These are fractional flow reserve CT and CT-based myocardial perfusion imaging.

Evidence regarding these methods was then bolstered at the annual congress of the European Society of Cardiology in Munich, with the presentation of two imaging trials. The DeFACTO study, comparing CT-based FFR with FFR obtained by conventional angiography, did not show diagnostic superiority of CT-based FFR over angiography, but it did enhance diagnoses compared with CT without FFR. The CORE320 trial, assessing the diagnostic accuracy CT-based myocardial perfusion imaging in patients with suspected coronary artery disease, showed that CT-based myocardial perfusion imaging significantly increased the diagnostic accuracy of CTA alone to delineate flow-limiting disease.

Cardiovascular CT also has been hamstrung by a number of technical limitations. Calcium blooming artifacts make it difficult to get an accurate measurement of calcium lesion components and lumen size and motion artifacts also limit the clarity of CT images, leaving some vessels simply unreadable.

Two new technological advances – dual-energy CT and intelligent motion correction using snapshot freeze – are already changing practice, according to leaders at this year’s annual meeting of the SCCT.

CT Fractional Flow Reserve

Fractional flow reserve (FFR) is defined as the maximal blood flow through a diseased artery to the blood flow in the hypothetical case that this artery is normal. CT-based FFR relies on the use of some complicated math and modeling to calculate FFR from CT data and actually traces its roots back to the air flow modeling that goes into designing airplane wings.

All of the data needed can be gleaned from a single-phase static CT image. Geometry can be extracted from CCTA anatomic data. Boundary conditions can also be determined. Resting coronary blood flow can be calculated from myocardial mass. Mean blood pressure can be estimated from brachial artery pressure. Coronary microcirculatory resistance can be derived from morphometry data. Lastly, fluid properties include the viscosity and density of blood. "Putting it all together, we can come out with a calculated assessment of things like coronary flow and FFR ... now, we can do anatomy and function," said Dr. Matthew J. Budoff, director of cardiology at the University of California at Los Angeles School of Medicine in Torrance.

Until now, FFR was determined through invasive coronary angiography, which was the only method for specific determination of coronary artery lesions (lesion-specific ischemia). Values of 0.80 and lower or 0.75 and lower are considered diagnostic of lesion-specific ischemia. "It tells us whether there is a physiologic significance of the lesion," Dr. Budoff said.

At the same time, stenosis seen on CCTA has been an unreliable predictor of lesion-specific ischemia in trials. "Just seeing that anatomical stenosis doesn’t mean it’s functionally significant," said Dr. Budoff. CCTA results in a lot of false positives when it comes to physiologic significance.

FFR estimates throughout the entire coronary tree. "Because it relies on the entire coronary anatomy, it’s actually less sensitive to artifacts and less sensitive to things like calcification than individual segment assessment."

The first trial of FFR-CT was in the Diagnosis of Ischemia-Causing Stenoses Obtained via Noninvasive Fractional Flow Reserve (DISCOVER-FLOW) trial. In the study, the researchers compared the accuracy of CCTA with FFR-CT (invasive FFR served as the reference).

The results showed that the coronary stenoses that cause ischemia can be identified noninvasively with computer analysis of CCTA to construct FFR for specific lesions (Eur. Heart J. Cardiovasc. Imaging 2012 Jul 15 [doi: 10.1093/ehjci/jes130]).

The upshot of this study is that "when we think it’s a high-grade stenosis [with FFR-CT], it is a physiologically significant stenosis," Dr. Budoff said. "So we’ve dramatically improved the ability of CT to correlate with the most invasive and probably the most definitive way, currently, of assessing physiologic significance, and that’s FFR."

CT-based fractional flow reserve (FFR) is now a step closer to clinical use with the results of the Determination of FFR by Anatomic CT Angiography (DeFACTO) trial presented at the ESC meeting and simultaneously published (JAMA 2012 Aug. 26 [doi:10.1001/2012.jama.11274]). The addition of CT-based FFR information to CT alone improved diagnostic accuracy of stenoses, compared with invasive angiography and FFR.

"We’ve dramatically improved the ability of CT to correlate with ... FFR," said Dr. Matthew J. Budoff.

Although FFR-CT plus CT narrowly failed to meet the trial’s primary end point – diagnostic accuracy greater than 70% for the lower bound of the 95% confidence interval, the per-patient performance diagnostic accuracy of FFR-CT plus CT was 73% with a 95% CI of 67%-78%.

Nevertheless, the addition of FFR-CT "demonstrated superior diagnostic performance characteristics, as compared with CT stenosis alone in all patients, in all vessels and also in vessels of intermediate stenosis severity," Dr. Min said during a press conference.

Myocardial Perfusion

"The second method of physiologic assessment of coronary disease, which is emerging, is myocardial perfusion imaging – performing a typical stress test with a CT angiogram," said Dr. Min.

This allows the visualization of perfusion/ischemia at specific lesions identified by CTA, providing functional and anatomic information. The data for perfusion images are extracted from a standard CTA scan.

With CT perfusion, a rest CT angiogram is performed to document the coronary artery stenoses that are within the coronary artery bed and also to look at the rest perfusion of the myocardium to determine whether it’s normal or abnormal, according to Dr. Min.

Before or after the rest CTA, a stress CT would be performed via pharmacologic means using a traditional 64-row cardiac CT.

It’s known that patients who have a normal SPECT myocardial perfusion examination have a very low rate of cardiovascular events over the next year, according to Dr. Richard T. George. "However, those patients with an abnormal nuclear scan actually have a quite high event rate over the next year."

In addition, it’s also known that CCTA has great prognostic value "and probably for a longer period than SPECT does, but SPECT myocardial perfusion imaging probably tells you more about the intermediate time period in the future about the event rate in the patient," he said.

Several studies have looked at the additional value of CT perfusion testing.

One of the first studies that compared CCTA and CT perfusion (CTP) with quantitative coronary angiography and SPECT perfusion showed a sensitivity with CTA/CTP of 88% and a specificity of 91% (Circ. Cardiovasc. Imaging 2009;2:174-82). "This study demonstrates some of the additional value of stress CT myocardial perfusion imaging," said Dr. George, assistant professor of medicine at the Heart and Vascular Institute at Johns Hopkins Hospital in Baltimore.

In another study, researchers assessed the additional value of dipyridamole stress myocardial perfusion by 64-row CT in patients with coronary stents (J. Cardiovasc. Comput. Tomogr. 2011;5:449-58). It is often difficult in many of these patients to assess whether in-stent restenosis is present, said Dr. George. The researchers in this study found that the addition of CT myocardial perfusion imaging to CCTA improved accuracy.

In a study targeting reversible ischemia, researchers assessed CT myocardial perfusion imaging with 320-row detector CT in 50 patients with an intermediate- to high-risk for CAD (Circ. Cardiovasc. Imaging 2012;5:333-40).

"The important part of this study is that they actually looked at reversible ischemia. A lot of our studies with CT perfusion imaging just lump all perfusion deficits together." In it, 40% of patients had an abnormal SPECT scan; 90% of those abnormal scans were reversible ischemia," said Dr. George.

In a per-patient analysis of CT perfusion imaging vs. CTA stenosis greater than 50% in the setting of a territorial SPECT myocardial perfusion deficit, sensitivity was 100% and specificity was 81%. The study shows the effectiveness of CT perfusion for assessing lesion-specific ischemia, Dr. George noted.

"What we’re finding is that CT perfusion or stress testing with CT can be as accurate, if not more accurate, than the conventional stress testing methods that we’ve used until this day," Dr. Min said.

"CT perfusion or stress testing with CT can be as accurate, if not more accurate, than the conventional stress testing method," said Dr. James K. Min.

In the Combined Non-invasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography (Core320) trial, researchers compared the diagnostic accuracy of CTA plus CT-based myocardial perfusion against ICA plus SPECT myocardial perfusion imaging in 381 patients with suspected or diagnosed coronary artery disease with a clinical indication for coronary angiography.

"When we add perfusion [to CTA alone] we gain power to diagnose flow-limiting stenosis," lead author Dr. Joao A.C. Lima said at the ESC meeting. Together, "they have the same power as invasive angiography and SPECT MPI in defining who are the patients who end up going through revascularization," he said.

The area under the receiver operating characteristic curve (ROC) – an effective method of evaluating the performance of diagnostic tests – was 0.79 for CTA-CTP and 0.81 for ICA-SPECT.

"At this point, the [CT perfusion] technology could be used precisely to find the patients who have flow-limiting disease and, therefore, are going to need revascularization," said Dr. Lima, director of cardiovascular imaging at the Johns Hopkins University in Baltimore.

Dual-Energy CT

Dual-energy CT (also known as dual-source CT) "interleaves sets of high- and low-keV images. The energy alternates between two energies (80 keV to 140 keV) every 0.5 msec," said Dr. James P. Earls. The result is two competing sets that can be used simultaneously. The importance of this dual-energy approach is that with higher energies and a software algorithm, calcium blooming is decreased. This means a more accurate size of calcium in lesions and lumen size.

Images courtesy Dr. Jonathon Leipsic, St. Paul\'s Hospital in Vancouver

Back-end software produces a range of monochromatic images (images at a single energy). "In terms of calcium reduction, the monochromatic images are probably more important," said Dr. Earls, codirector of the cardiac CT program at Inova Heart and Vascular Institute in Falls Church, Va.

Monochromatic images range from 40 keV to 140 keV. "At 40 keV you’re very close to the k-edge of iodine, so you have significant attenuation of anything that is enhancing ... at about 75 keV you have something that looks akin to a 120-keV image that we would normally get." As the energy increases, "you get away from what we would do on a routine clinical basis."

The ATLANTA I study (Assessment of Tissue Characteristics, Lesion Morphology, and Hemodynamics by Angiography With Fractional Flow Reserve, Intravascular Ultrasound and Virtual Histology, and Noninvasive Computed Tomography in Atherosclerotic Plaques) showed that with conventional single-energy CT calcium, plaque is overestimated and lumen size is therefore underestimated (J. Am. Coll. Cardiol. Intv. 2011;4:198-208 [doi:10.1016/j.jcin.2010.10.008]).

The ATLANTA I study tells us that "when we do routine single-energy CT, calcium plaques are significantly overportrayed." In this study, researchers found that calcified plaque volume is 104% greater than its true volume as determined by intravascular ultrasound. As a result, the minimal luminal diameter is underestimated by 21% and the percentage diameter stenosis is overrepresented by 39%. "Lots of false positives [are] caused by calcified plaque in the area," Dr. Earls observed.

The reason for this is that as energy increases, the calcium blooming decreases. This accounts for the enlargement of the lumen.

Noncalcified plaques don’t show as dramatic an effect, though. Soft plaque size does not change much when seen at different energies, Dr. Earls noted. "Ultimately it may be that we use a combination of monochromatic images and material density images, as we approach this going forward. These are both available every time that you do a scan," said Dr. Earls.

Dual-source CT does have limitations, though. There is no retrospective gating; there are limited milliAmpere (electrical charge) presets, and there is no high-resolution mode.

Intelligent Motion Correction

Motion artifacts make it difficult or impossible to evaluate vessels, leaving clinicians to treat the vessels as narrowed by default. A new technology is designed to overcome the problem of motion artifacts in cardiovascular CT.

"The images are acquired in a standard fashion, but instead of reconstructing them in a standard fashion, there is integration of this intelligent motion correction that tracks the motion of the vessel over two or three phases of the cardiac cycle," Dr. Jonathon A. Leipsic said in an interview. "When we acquire the study, we get a couple of phases beyond just the minimal acquisition – which is standard. It sees where the vessel is over a couple of phases and how it looks. Based on the known velocity of the artery, how it appears, and the patient’s known heart rate, [the algorithm] then corrects for the expected motion."

The technology is already changing practice. It is used on Europe and Japan; it is also being used in many centers in the United States. The motion correction algorithm has wide range of applications. "Anywhere there is motion, anyone with a sudden ectopic pace or premature ventricular contraction, anyone with an arrhythmia – all of those patients will benefit from this motion correction," said Dr. Leipsic, chairman of the department of radiology for Providence Health Care and vice chairman of research for the department of radiology at the University of British Columbia, Vancouver.

Importantly, the scan time and radiation dose don’t increase appreciably with the acquisition of vessel velocity data. "It doesn’t change the acquisition. You can just wait and see. If you have a study that has no motion, then you don’t need to use [motion correction]. But if you have a study with motion, then you can use it. You can make that choice after you see the initial data," Dr. Leipsic explained.

Dr. Leipsic was the lead author on one of the first studies to assess the accuracy this of this method (J. Cardiovasc. Comput. Tomography 2012;6:164-71. Epub 2012 Apr 6). In the study, "we looked at a population of convenience patients that happened to be going to the cath lab. We chose very difficult patients – patients undergoing transcatheter valve replacement – who have very high heart rates. We saw a significant improvement in interpretability, overall image quality, and diagnostic accuracy" with this technology. The researchers also noted significant improvements in right coronary evaluation, as well as other coronary territories.

Some have argued that all that is needed to avoid motion artifacts is to rate-control patients. However, "we aggressively rate-controlled patients ... there’s just too much motion," Dr. Leipsic countered. "It’s hard to anticipate some problems – an irregular beat or some irregular rhythm – and having this in your back pocket ... has exciting potential."

Additional trials to assess accuracy are expected, perhaps most prominently the VICTORY trial (Validation of an Intracycle CT Motion Correction Algorithm for Diagnostic Accuracy: A Prospective Multicenter Study). In the study, CCTA will be compared with invasive coronary angiography (ICA) for diagnostic sensitivity and specificity, positive predictive value, negative predictive value, diagnostic accuracy, and positive and negative likelihood ratios.

Coronary segments will be assessed for "significance" of coronary artery luminal diameter obstruction. Individual segments will be graded based on image quality, with the third reader used to achieve consensus. Dr. Leipsic and Dr. James Min are the principal investigators for the study.

For now, the intelligent motion correction algorithm, called SnapShot Freez4e, is available only from GE Healthcare, as part of its Discovery CT750 HD FREEdom Edition, which was granted 510(k) clearance in June. "I think that other companies are going to come up with something similar but I think that each type will be adequately different enough that [these technologies] will require their own validation studies," said Dr. Leipsic.

Siemens is reportedly developing a similar technology.

Dr. Min is a speaker for GE Healthcare. Dr. Budoff receives grant support from HeartFlow. Dr. George has received research support from Toshiba Medical Systems and GE Healthcare, is on the advisory board of GE Healthcare, and is a consultant to ICON Medical Imaging. Dr. Earls is on the speakers bureau for and has research funded by GE Healthcare. Dr. Leipsic is a consultant/speaker for Edwards Lifesciences and GE Healthcare.

New technologies that solve some old problems could make cardiovascular CT the go-to imaging tool to assess both anatomy and function.

Cardiovascular CT imaging has been a welcome tool in patient assessment due to its noninvasive nature, ease, and quickness. Likewise, cardiovascular CT angiography (CCTA) has provided noninvasive information about vessel stenoses, with lower costs and radiation exposure compared with invasive angiography.

Images courtesy Dr. James P. Earls

Perhaps the biggest criticism about cardiovascular CT is that, while it provides very good anatomic detail, functional information – a crucial piece to the overall picture – is not discernable.

"Historically, coronary CT angiography has been an extremely anatomic method for documenting the severity of coronary artery stenoses or luminal compromise," said Dr. James K. Min, immediate past president of SCCT. This has left CTA open to the criticism that the more useful evaluation of coronary artery disease is not only to document high-grade stenoses – as with coronary CT angiography – but also to determine the physiologic significance of those stenoses.

However, at this year’s meeting of the Society of Cardiovascular Computed Tomography in Baltimore, "we saw the emergence of two robust methods for physiologic assessment of coronary disease by cardiac CT," he said. These are fractional flow reserve CT and CT-based myocardial perfusion imaging.

Evidence regarding these methods was then bolstered at the annual congress of the European Society of Cardiology in Munich, with the presentation of two imaging trials. The DeFACTO study, comparing CT-based FFR with FFR obtained by conventional angiography, did not show diagnostic superiority of CT-based FFR over angiography, but it did enhance diagnoses compared with CT without FFR. The CORE320 trial, assessing the diagnostic accuracy CT-based myocardial perfusion imaging in patients with suspected coronary artery disease, showed that CT-based myocardial perfusion imaging significantly increased the diagnostic accuracy of CTA alone to delineate flow-limiting disease.

Cardiovascular CT also has been hamstrung by a number of technical limitations. Calcium blooming artifacts make it difficult to get an accurate measurement of calcium lesion components and lumen size and motion artifacts also limit the clarity of CT images, leaving some vessels simply unreadable.

Two new technological advances – dual-energy CT and intelligent motion correction using snapshot freeze – are already changing practice, according to leaders at this year’s annual meeting of the SCCT.

CT Fractional Flow Reserve

Fractional flow reserve (FFR) is defined as the maximal blood flow through a diseased artery to the blood flow in the hypothetical case that this artery is normal. CT-based FFR relies on the use of some complicated math and modeling to calculate FFR from CT data and actually traces its roots back to the air flow modeling that goes into designing airplane wings.

All of the data needed can be gleaned from a single-phase static CT image. Geometry can be extracted from CCTA anatomic data. Boundary conditions can also be determined. Resting coronary blood flow can be calculated from myocardial mass. Mean blood pressure can be estimated from brachial artery pressure. Coronary microcirculatory resistance can be derived from morphometry data. Lastly, fluid properties include the viscosity and density of blood. "Putting it all together, we can come out with a calculated assessment of things like coronary flow and FFR ... now, we can do anatomy and function," said Dr. Matthew J. Budoff, director of cardiology at the University of California at Los Angeles School of Medicine in Torrance.

Until now, FFR was determined through invasive coronary angiography, which was the only method for specific determination of coronary artery lesions (lesion-specific ischemia). Values of 0.80 and lower or 0.75 and lower are considered diagnostic of lesion-specific ischemia. "It tells us whether there is a physiologic significance of the lesion," Dr. Budoff said.

At the same time, stenosis seen on CCTA has been an unreliable predictor of lesion-specific ischemia in trials. "Just seeing that anatomical stenosis doesn’t mean it’s functionally significant," said Dr. Budoff. CCTA results in a lot of false positives when it comes to physiologic significance.

FFR estimates throughout the entire coronary tree. "Because it relies on the entire coronary anatomy, it’s actually less sensitive to artifacts and less sensitive to things like calcification than individual segment assessment."

The first trial of FFR-CT was in the Diagnosis of Ischemia-Causing Stenoses Obtained via Noninvasive Fractional Flow Reserve (DISCOVER-FLOW) trial. In the study, the researchers compared the accuracy of CCTA with FFR-CT (invasive FFR served as the reference).

The results showed that the coronary stenoses that cause ischemia can be identified noninvasively with computer analysis of CCTA to construct FFR for specific lesions (Eur. Heart J. Cardiovasc. Imaging 2012 Jul 15 [doi: 10.1093/ehjci/jes130]).

The upshot of this study is that "when we think it’s a high-grade stenosis [with FFR-CT], it is a physiologically significant stenosis," Dr. Budoff said. "So we’ve dramatically improved the ability of CT to correlate with the most invasive and probably the most definitive way, currently, of assessing physiologic significance, and that’s FFR."

CT-based fractional flow reserve (FFR) is now a step closer to clinical use with the results of the Determination of FFR by Anatomic CT Angiography (DeFACTO) trial presented at the ESC meeting and simultaneously published (JAMA 2012 Aug. 26 [doi:10.1001/2012.jama.11274]). The addition of CT-based FFR information to CT alone improved diagnostic accuracy of stenoses, compared with invasive angiography and FFR.

"We’ve dramatically improved the ability of CT to correlate with ... FFR," said Dr. Matthew J. Budoff.

Although FFR-CT plus CT narrowly failed to meet the trial’s primary end point – diagnostic accuracy greater than 70% for the lower bound of the 95% confidence interval, the per-patient performance diagnostic accuracy of FFR-CT plus CT was 73% with a 95% CI of 67%-78%.

Nevertheless, the addition of FFR-CT "demonstrated superior diagnostic performance characteristics, as compared with CT stenosis alone in all patients, in all vessels and also in vessels of intermediate stenosis severity," Dr. Min said during a press conference.

Myocardial Perfusion

"The second method of physiologic assessment of coronary disease, which is emerging, is myocardial perfusion imaging – performing a typical stress test with a CT angiogram," said Dr. Min.

This allows the visualization of perfusion/ischemia at specific lesions identified by CTA, providing functional and anatomic information. The data for perfusion images are extracted from a standard CTA scan.

With CT perfusion, a rest CT angiogram is performed to document the coronary artery stenoses that are within the coronary artery bed and also to look at the rest perfusion of the myocardium to determine whether it’s normal or abnormal, according to Dr. Min.

Before or after the rest CTA, a stress CT would be performed via pharmacologic means using a traditional 64-row cardiac CT.

It’s known that patients who have a normal SPECT myocardial perfusion examination have a very low rate of cardiovascular events over the next year, according to Dr. Richard T. George. "However, those patients with an abnormal nuclear scan actually have a quite high event rate over the next year."

In addition, it’s also known that CCTA has great prognostic value "and probably for a longer period than SPECT does, but SPECT myocardial perfusion imaging probably tells you more about the intermediate time period in the future about the event rate in the patient," he said.

Several studies have looked at the additional value of CT perfusion testing.

One of the first studies that compared CCTA and CT perfusion (CTP) with quantitative coronary angiography and SPECT perfusion showed a sensitivity with CTA/CTP of 88% and a specificity of 91% (Circ. Cardiovasc. Imaging 2009;2:174-82). "This study demonstrates some of the additional value of stress CT myocardial perfusion imaging," said Dr. George, assistant professor of medicine at the Heart and Vascular Institute at Johns Hopkins Hospital in Baltimore.

In another study, researchers assessed the additional value of dipyridamole stress myocardial perfusion by 64-row CT in patients with coronary stents (J. Cardiovasc. Comput. Tomogr. 2011;5:449-58). It is often difficult in many of these patients to assess whether in-stent restenosis is present, said Dr. George. The researchers in this study found that the addition of CT myocardial perfusion imaging to CCTA improved accuracy.

In a study targeting reversible ischemia, researchers assessed CT myocardial perfusion imaging with 320-row detector CT in 50 patients with an intermediate- to high-risk for CAD (Circ. Cardiovasc. Imaging 2012;5:333-40).

"The important part of this study is that they actually looked at reversible ischemia. A lot of our studies with CT perfusion imaging just lump all perfusion deficits together." In it, 40% of patients had an abnormal SPECT scan; 90% of those abnormal scans were reversible ischemia," said Dr. George.

In a per-patient analysis of CT perfusion imaging vs. CTA stenosis greater than 50% in the setting of a territorial SPECT myocardial perfusion deficit, sensitivity was 100% and specificity was 81%. The study shows the effectiveness of CT perfusion for assessing lesion-specific ischemia, Dr. George noted.

"What we’re finding is that CT perfusion or stress testing with CT can be as accurate, if not more accurate, than the conventional stress testing methods that we’ve used until this day," Dr. Min said.

"CT perfusion or stress testing with CT can be as accurate, if not more accurate, than the conventional stress testing method," said Dr. James K. Min.

In the Combined Non-invasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography (Core320) trial, researchers compared the diagnostic accuracy of CTA plus CT-based myocardial perfusion against ICA plus SPECT myocardial perfusion imaging in 381 patients with suspected or diagnosed coronary artery disease with a clinical indication for coronary angiography.

"When we add perfusion [to CTA alone] we gain power to diagnose flow-limiting stenosis," lead author Dr. Joao A.C. Lima said at the ESC meeting. Together, "they have the same power as invasive angiography and SPECT MPI in defining who are the patients who end up going through revascularization," he said.

The area under the receiver operating characteristic curve (ROC) – an effective method of evaluating the performance of diagnostic tests – was 0.79 for CTA-CTP and 0.81 for ICA-SPECT.

"At this point, the [CT perfusion] technology could be used precisely to find the patients who have flow-limiting disease and, therefore, are going to need revascularization," said Dr. Lima, director of cardiovascular imaging at the Johns Hopkins University in Baltimore.

Dual-Energy CT

Dual-energy CT (also known as dual-source CT) "interleaves sets of high- and low-keV images. The energy alternates between two energies (80 keV to 140 keV) every 0.5 msec," said Dr. James P. Earls. The result is two competing sets that can be used simultaneously. The importance of this dual-energy approach is that with higher energies and a software algorithm, calcium blooming is decreased. This means a more accurate size of calcium in lesions and lumen size.

Images courtesy Dr. Jonathon Leipsic, St. Paul\'s Hospital in Vancouver

Back-end software produces a range of monochromatic images (images at a single energy). "In terms of calcium reduction, the monochromatic images are probably more important," said Dr. Earls, codirector of the cardiac CT program at Inova Heart and Vascular Institute in Falls Church, Va.

Monochromatic images range from 40 keV to 140 keV. "At 40 keV you’re very close to the k-edge of iodine, so you have significant attenuation of anything that is enhancing ... at about 75 keV you have something that looks akin to a 120-keV image that we would normally get." As the energy increases, "you get away from what we would do on a routine clinical basis."

The ATLANTA I study (Assessment of Tissue Characteristics, Lesion Morphology, and Hemodynamics by Angiography With Fractional Flow Reserve, Intravascular Ultrasound and Virtual Histology, and Noninvasive Computed Tomography in Atherosclerotic Plaques) showed that with conventional single-energy CT calcium, plaque is overestimated and lumen size is therefore underestimated (J. Am. Coll. Cardiol. Intv. 2011;4:198-208 [doi:10.1016/j.jcin.2010.10.008]).

The ATLANTA I study tells us that "when we do routine single-energy CT, calcium plaques are significantly overportrayed." In this study, researchers found that calcified plaque volume is 104% greater than its true volume as determined by intravascular ultrasound. As a result, the minimal luminal diameter is underestimated by 21% and the percentage diameter stenosis is overrepresented by 39%. "Lots of false positives [are] caused by calcified plaque in the area," Dr. Earls observed.

The reason for this is that as energy increases, the calcium blooming decreases. This accounts for the enlargement of the lumen.

Noncalcified plaques don’t show as dramatic an effect, though. Soft plaque size does not change much when seen at different energies, Dr. Earls noted. "Ultimately it may be that we use a combination of monochromatic images and material density images, as we approach this going forward. These are both available every time that you do a scan," said Dr. Earls.

Dual-source CT does have limitations, though. There is no retrospective gating; there are limited milliAmpere (electrical charge) presets, and there is no high-resolution mode.

Intelligent Motion Correction

Motion artifacts make it difficult or impossible to evaluate vessels, leaving clinicians to treat the vessels as narrowed by default. A new technology is designed to overcome the problem of motion artifacts in cardiovascular CT.

"The images are acquired in a standard fashion, but instead of reconstructing them in a standard fashion, there is integration of this intelligent motion correction that tracks the motion of the vessel over two or three phases of the cardiac cycle," Dr. Jonathon A. Leipsic said in an interview. "When we acquire the study, we get a couple of phases beyond just the minimal acquisition – which is standard. It sees where the vessel is over a couple of phases and how it looks. Based on the known velocity of the artery, how it appears, and the patient’s known heart rate, [the algorithm] then corrects for the expected motion."

The technology is already changing practice. It is used on Europe and Japan; it is also being used in many centers in the United States. The motion correction algorithm has wide range of applications. "Anywhere there is motion, anyone with a sudden ectopic pace or premature ventricular contraction, anyone with an arrhythmia – all of those patients will benefit from this motion correction," said Dr. Leipsic, chairman of the department of radiology for Providence Health Care and vice chairman of research for the department of radiology at the University of British Columbia, Vancouver.

Importantly, the scan time and radiation dose don’t increase appreciably with the acquisition of vessel velocity data. "It doesn’t change the acquisition. You can just wait and see. If you have a study that has no motion, then you don’t need to use [motion correction]. But if you have a study with motion, then you can use it. You can make that choice after you see the initial data," Dr. Leipsic explained.

Dr. Leipsic was the lead author on one of the first studies to assess the accuracy this of this method (J. Cardiovasc. Comput. Tomography 2012;6:164-71. Epub 2012 Apr 6). In the study, "we looked at a population of convenience patients that happened to be going to the cath lab. We chose very difficult patients – patients undergoing transcatheter valve replacement – who have very high heart rates. We saw a significant improvement in interpretability, overall image quality, and diagnostic accuracy" with this technology. The researchers also noted significant improvements in right coronary evaluation, as well as other coronary territories.

Some have argued that all that is needed to avoid motion artifacts is to rate-control patients. However, "we aggressively rate-controlled patients ... there’s just too much motion," Dr. Leipsic countered. "It’s hard to anticipate some problems – an irregular beat or some irregular rhythm – and having this in your back pocket ... has exciting potential."

Additional trials to assess accuracy are expected, perhaps most prominently the VICTORY trial (Validation of an Intracycle CT Motion Correction Algorithm for Diagnostic Accuracy: A Prospective Multicenter Study). In the study, CCTA will be compared with invasive coronary angiography (ICA) for diagnostic sensitivity and specificity, positive predictive value, negative predictive value, diagnostic accuracy, and positive and negative likelihood ratios.

Coronary segments will be assessed for "significance" of coronary artery luminal diameter obstruction. Individual segments will be graded based on image quality, with the third reader used to achieve consensus. Dr. Leipsic and Dr. James Min are the principal investigators for the study.

For now, the intelligent motion correction algorithm, called SnapShot Freez4e, is available only from GE Healthcare, as part of its Discovery CT750 HD FREEdom Edition, which was granted 510(k) clearance in June. "I think that other companies are going to come up with something similar but I think that each type will be adequately different enough that [these technologies] will require their own validation studies," said Dr. Leipsic.

Siemens is reportedly developing a similar technology.

Dr. Min is a speaker for GE Healthcare. Dr. Budoff receives grant support from HeartFlow. Dr. George has received research support from Toshiba Medical Systems and GE Healthcare, is on the advisory board of GE Healthcare, and is a consultant to ICON Medical Imaging. Dr. Earls is on the speakers bureau for and has research funded by GE Healthcare. Dr. Leipsic is a consultant/speaker for Edwards Lifesciences and GE Healthcare.

New technologies that solve some old problems could make cardiovascular CT the go-to imaging tool to assess both anatomy and function.

Cardiovascular CT imaging has been a welcome tool in patient assessment due to its noninvasive nature, ease, and quickness. Likewise, cardiovascular CT angiography (CCTA) has provided noninvasive information about vessel stenoses, with lower costs and radiation exposure compared with invasive angiography.

Images courtesy Dr. James P. Earls

Perhaps the biggest criticism about cardiovascular CT is that, while it provides very good anatomic detail, functional information – a crucial piece to the overall picture – is not discernable.

"Historically, coronary CT angiography has been an extremely anatomic method for documenting the severity of coronary artery stenoses or luminal compromise," said Dr. James K. Min, immediate past president of SCCT. This has left CTA open to the criticism that the more useful evaluation of coronary artery disease is not only to document high-grade stenoses – as with coronary CT angiography – but also to determine the physiologic significance of those stenoses.

However, at this year’s meeting of the Society of Cardiovascular Computed Tomography in Baltimore, "we saw the emergence of two robust methods for physiologic assessment of coronary disease by cardiac CT," he said. These are fractional flow reserve CT and CT-based myocardial perfusion imaging.

Evidence regarding these methods was then bolstered at the annual congress of the European Society of Cardiology in Munich, with the presentation of two imaging trials. The DeFACTO study, comparing CT-based FFR with FFR obtained by conventional angiography, did not show diagnostic superiority of CT-based FFR over angiography, but it did enhance diagnoses compared with CT without FFR. The CORE320 trial, assessing the diagnostic accuracy CT-based myocardial perfusion imaging in patients with suspected coronary artery disease, showed that CT-based myocardial perfusion imaging significantly increased the diagnostic accuracy of CTA alone to delineate flow-limiting disease.

Cardiovascular CT also has been hamstrung by a number of technical limitations. Calcium blooming artifacts make it difficult to get an accurate measurement of calcium lesion components and lumen size and motion artifacts also limit the clarity of CT images, leaving some vessels simply unreadable.

Two new technological advances – dual-energy CT and intelligent motion correction using snapshot freeze – are already changing practice, according to leaders at this year’s annual meeting of the SCCT.

CT Fractional Flow Reserve

Fractional flow reserve (FFR) is defined as the maximal blood flow through a diseased artery to the blood flow in the hypothetical case that this artery is normal. CT-based FFR relies on the use of some complicated math and modeling to calculate FFR from CT data and actually traces its roots back to the air flow modeling that goes into designing airplane wings.

All of the data needed can be gleaned from a single-phase static CT image. Geometry can be extracted from CCTA anatomic data. Boundary conditions can also be determined. Resting coronary blood flow can be calculated from myocardial mass. Mean blood pressure can be estimated from brachial artery pressure. Coronary microcirculatory resistance can be derived from morphometry data. Lastly, fluid properties include the viscosity and density of blood. "Putting it all together, we can come out with a calculated assessment of things like coronary flow and FFR ... now, we can do anatomy and function," said Dr. Matthew J. Budoff, director of cardiology at the University of California at Los Angeles School of Medicine in Torrance.

Until now, FFR was determined through invasive coronary angiography, which was the only method for specific determination of coronary artery lesions (lesion-specific ischemia). Values of 0.80 and lower or 0.75 and lower are considered diagnostic of lesion-specific ischemia. "It tells us whether there is a physiologic significance of the lesion," Dr. Budoff said.

At the same time, stenosis seen on CCTA has been an unreliable predictor of lesion-specific ischemia in trials. "Just seeing that anatomical stenosis doesn’t mean it’s functionally significant," said Dr. Budoff. CCTA results in a lot of false positives when it comes to physiologic significance.

FFR estimates throughout the entire coronary tree. "Because it relies on the entire coronary anatomy, it’s actually less sensitive to artifacts and less sensitive to things like calcification than individual segment assessment."

The first trial of FFR-CT was in the Diagnosis of Ischemia-Causing Stenoses Obtained via Noninvasive Fractional Flow Reserve (DISCOVER-FLOW) trial. In the study, the researchers compared the accuracy of CCTA with FFR-CT (invasive FFR served as the reference).

The results showed that the coronary stenoses that cause ischemia can be identified noninvasively with computer analysis of CCTA to construct FFR for specific lesions (Eur. Heart J. Cardiovasc. Imaging 2012 Jul 15 [doi: 10.1093/ehjci/jes130]).

The upshot of this study is that "when we think it’s a high-grade stenosis [with FFR-CT], it is a physiologically significant stenosis," Dr. Budoff said. "So we’ve dramatically improved the ability of CT to correlate with the most invasive and probably the most definitive way, currently, of assessing physiologic significance, and that’s FFR."

CT-based fractional flow reserve (FFR) is now a step closer to clinical use with the results of the Determination of FFR by Anatomic CT Angiography (DeFACTO) trial presented at the ESC meeting and simultaneously published (JAMA 2012 Aug. 26 [doi:10.1001/2012.jama.11274]). The addition of CT-based FFR information to CT alone improved diagnostic accuracy of stenoses, compared with invasive angiography and FFR.

"We’ve dramatically improved the ability of CT to correlate with ... FFR," said Dr. Matthew J. Budoff.

Although FFR-CT plus CT narrowly failed to meet the trial’s primary end point – diagnostic accuracy greater than 70% for the lower bound of the 95% confidence interval, the per-patient performance diagnostic accuracy of FFR-CT plus CT was 73% with a 95% CI of 67%-78%.

Nevertheless, the addition of FFR-CT "demonstrated superior diagnostic performance characteristics, as compared with CT stenosis alone in all patients, in all vessels and also in vessels of intermediate stenosis severity," Dr. Min said during a press conference.

Myocardial Perfusion

"The second method of physiologic assessment of coronary disease, which is emerging, is myocardial perfusion imaging – performing a typical stress test with a CT angiogram," said Dr. Min.

This allows the visualization of perfusion/ischemia at specific lesions identified by CTA, providing functional and anatomic information. The data for perfusion images are extracted from a standard CTA scan.

With CT perfusion, a rest CT angiogram is performed to document the coronary artery stenoses that are within the coronary artery bed and also to look at the rest perfusion of the myocardium to determine whether it’s normal or abnormal, according to Dr. Min.

Before or after the rest CTA, a stress CT would be performed via pharmacologic means using a traditional 64-row cardiac CT.

It’s known that patients who have a normal SPECT myocardial perfusion examination have a very low rate of cardiovascular events over the next year, according to Dr. Richard T. George. "However, those patients with an abnormal nuclear scan actually have a quite high event rate over the next year."

In addition, it’s also known that CCTA has great prognostic value "and probably for a longer period than SPECT does, but SPECT myocardial perfusion imaging probably tells you more about the intermediate time period in the future about the event rate in the patient," he said.

Several studies have looked at the additional value of CT perfusion testing.

One of the first studies that compared CCTA and CT perfusion (CTP) with quantitative coronary angiography and SPECT perfusion showed a sensitivity with CTA/CTP of 88% and a specificity of 91% (Circ. Cardiovasc. Imaging 2009;2:174-82). "This study demonstrates some of the additional value of stress CT myocardial perfusion imaging," said Dr. George, assistant professor of medicine at the Heart and Vascular Institute at Johns Hopkins Hospital in Baltimore.

In another study, researchers assessed the additional value of dipyridamole stress myocardial perfusion by 64-row CT in patients with coronary stents (J. Cardiovasc. Comput. Tomogr. 2011;5:449-58). It is often difficult in many of these patients to assess whether in-stent restenosis is present, said Dr. George. The researchers in this study found that the addition of CT myocardial perfusion imaging to CCTA improved accuracy.

In a study targeting reversible ischemia, researchers assessed CT myocardial perfusion imaging with 320-row detector CT in 50 patients with an intermediate- to high-risk for CAD (Circ. Cardiovasc. Imaging 2012;5:333-40).

"The important part of this study is that they actually looked at reversible ischemia. A lot of our studies with CT perfusion imaging just lump all perfusion deficits together." In it, 40% of patients had an abnormal SPECT scan; 90% of those abnormal scans were reversible ischemia," said Dr. George.

In a per-patient analysis of CT perfusion imaging vs. CTA stenosis greater than 50% in the setting of a territorial SPECT myocardial perfusion deficit, sensitivity was 100% and specificity was 81%. The study shows the effectiveness of CT perfusion for assessing lesion-specific ischemia, Dr. George noted.

"What we’re finding is that CT perfusion or stress testing with CT can be as accurate, if not more accurate, than the conventional stress testing methods that we’ve used until this day," Dr. Min said.

"CT perfusion or stress testing with CT can be as accurate, if not more accurate, than the conventional stress testing method," said Dr. James K. Min.

In the Combined Non-invasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography (Core320) trial, researchers compared the diagnostic accuracy of CTA plus CT-based myocardial perfusion against ICA plus SPECT myocardial perfusion imaging in 381 patients with suspected or diagnosed coronary artery disease with a clinical indication for coronary angiography.

"When we add perfusion [to CTA alone] we gain power to diagnose flow-limiting stenosis," lead author Dr. Joao A.C. Lima said at the ESC meeting. Together, "they have the same power as invasive angiography and SPECT MPI in defining who are the patients who end up going through revascularization," he said.

The area under the receiver operating characteristic curve (ROC) – an effective method of evaluating the performance of diagnostic tests – was 0.79 for CTA-CTP and 0.81 for ICA-SPECT.

"At this point, the [CT perfusion] technology could be used precisely to find the patients who have flow-limiting disease and, therefore, are going to need revascularization," said Dr. Lima, director of cardiovascular imaging at the Johns Hopkins University in Baltimore.

Dual-Energy CT

Dual-energy CT (also known as dual-source CT) "interleaves sets of high- and low-keV images. The energy alternates between two energies (80 keV to 140 keV) every 0.5 msec," said Dr. James P. Earls. The result is two competing sets that can be used simultaneously. The importance of this dual-energy approach is that with higher energies and a software algorithm, calcium blooming is decreased. This means a more accurate size of calcium in lesions and lumen size.

Images courtesy Dr. Jonathon Leipsic, St. Paul\'s Hospital in Vancouver

Back-end software produces a range of monochromatic images (images at a single energy). "In terms of calcium reduction, the monochromatic images are probably more important," said Dr. Earls, codirector of the cardiac CT program at Inova Heart and Vascular Institute in Falls Church, Va.

Monochromatic images range from 40 keV to 140 keV. "At 40 keV you’re very close to the k-edge of iodine, so you have significant attenuation of anything that is enhancing ... at about 75 keV you have something that looks akin to a 120-keV image that we would normally get." As the energy increases, "you get away from what we would do on a routine clinical basis."

The ATLANTA I study (Assessment of Tissue Characteristics, Lesion Morphology, and Hemodynamics by Angiography With Fractional Flow Reserve, Intravascular Ultrasound and Virtual Histology, and Noninvasive Computed Tomography in Atherosclerotic Plaques) showed that with conventional single-energy CT calcium, plaque is overestimated and lumen size is therefore underestimated (J. Am. Coll. Cardiol. Intv. 2011;4:198-208 [doi:10.1016/j.jcin.2010.10.008]).

The ATLANTA I study tells us that "when we do routine single-energy CT, calcium plaques are significantly overportrayed." In this study, researchers found that calcified plaque volume is 104% greater than its true volume as determined by intravascular ultrasound. As a result, the minimal luminal diameter is underestimated by 21% and the percentage diameter stenosis is overrepresented by 39%. "Lots of false positives [are] caused by calcified plaque in the area," Dr. Earls observed.

The reason for this is that as energy increases, the calcium blooming decreases. This accounts for the enlargement of the lumen.

Noncalcified plaques don’t show as dramatic an effect, though. Soft plaque size does not change much when seen at different energies, Dr. Earls noted. "Ultimately it may be that we use a combination of monochromatic images and material density images, as we approach this going forward. These are both available every time that you do a scan," said Dr. Earls.

Dual-source CT does have limitations, though. There is no retrospective gating; there are limited milliAmpere (electrical charge) presets, and there is no high-resolution mode.

Intelligent Motion Correction

Motion artifacts make it difficult or impossible to evaluate vessels, leaving clinicians to treat the vessels as narrowed by default. A new technology is designed to overcome the problem of motion artifacts in cardiovascular CT.

"The images are acquired in a standard fashion, but instead of reconstructing them in a standard fashion, there is integration of this intelligent motion correction that tracks the motion of the vessel over two or three phases of the cardiac cycle," Dr. Jonathon A. Leipsic said in an interview. "When we acquire the study, we get a couple of phases beyond just the minimal acquisition – which is standard. It sees where the vessel is over a couple of phases and how it looks. Based on the known velocity of the artery, how it appears, and the patient’s known heart rate, [the algorithm] then corrects for the expected motion."

The technology is already changing practice. It is used on Europe and Japan; it is also being used in many centers in the United States. The motion correction algorithm has wide range of applications. "Anywhere there is motion, anyone with a sudden ectopic pace or premature ventricular contraction, anyone with an arrhythmia – all of those patients will benefit from this motion correction," said Dr. Leipsic, chairman of the department of radiology for Providence Health Care and vice chairman of research for the department of radiology at the University of British Columbia, Vancouver.

Importantly, the scan time and radiation dose don’t increase appreciably with the acquisition of vessel velocity data. "It doesn’t change the acquisition. You can just wait and see. If you have a study that has no motion, then you don’t need to use [motion correction]. But if you have a study with motion, then you can use it. You can make that choice after you see the initial data," Dr. Leipsic explained.

Dr. Leipsic was the lead author on one of the first studies to assess the accuracy this of this method (J. Cardiovasc. Comput. Tomography 2012;6:164-71. Epub 2012 Apr 6). In the study, "we looked at a population of convenience patients that happened to be going to the cath lab. We chose very difficult patients – patients undergoing transcatheter valve replacement – who have very high heart rates. We saw a significant improvement in interpretability, overall image quality, and diagnostic accuracy" with this technology. The researchers also noted significant improvements in right coronary evaluation, as well as other coronary territories.

Some have argued that all that is needed to avoid motion artifacts is to rate-control patients. However, "we aggressively rate-controlled patients ... there’s just too much motion," Dr. Leipsic countered. "It’s hard to anticipate some problems – an irregular beat or some irregular rhythm – and having this in your back pocket ... has exciting potential."

Additional trials to assess accuracy are expected, perhaps most prominently the VICTORY trial (Validation of an Intracycle CT Motion Correction Algorithm for Diagnostic Accuracy: A Prospective Multicenter Study). In the study, CCTA will be compared with invasive coronary angiography (ICA) for diagnostic sensitivity and specificity, positive predictive value, negative predictive value, diagnostic accuracy, and positive and negative likelihood ratios.

Coronary segments will be assessed for "significance" of coronary artery luminal diameter obstruction. Individual segments will be graded based on image quality, with the third reader used to achieve consensus. Dr. Leipsic and Dr. James Min are the principal investigators for the study.

For now, the intelligent motion correction algorithm, called SnapShot Freez4e, is available only from GE Healthcare, as part of its Discovery CT750 HD FREEdom Edition, which was granted 510(k) clearance in June. "I think that other companies are going to come up with something similar but I think that each type will be adequately different enough that [these technologies] will require their own validation studies," said Dr. Leipsic.

Siemens is reportedly developing a similar technology.

Dr. Min is a speaker for GE Healthcare. Dr. Budoff receives grant support from HeartFlow. Dr. George has received research support from Toshiba Medical Systems and GE Healthcare, is on the advisory board of GE Healthcare, and is a consultant to ICON Medical Imaging. Dr. Earls is on the speakers bureau for and has research funded by GE Healthcare. Dr. Leipsic is a consultant/speaker for Edwards Lifesciences and GE Healthcare.

The use of fractional flow reserve to guide percutaneous coronary intervention, along with best medical management, sharply reduced the need for urgent revascularization in patients with stable coronary artery disease and at least one physiologically significant lesion.

However, FFR-guided percutaneous coronary intervention (PCI) had little effect on deaths or myocardial infarctions, when compared with best medical management alone, according to the results of the FAME 2 (Fractional Flow Reserve vs. Angiography for Multivessel Evaluation 2) trial, which was conducted at 28 sites in Europe and North America and halted early.

The percentage of patients who had an MI, death, or urgent revascularization (the combined primary end point) was significantly lower in the PCI group than in the medical therapy group (4.3% vs.12.7%; hazard ratio with PCI, 0.32). This difference was driven by a 13-fold increase in the need for urgent revascularization in the medical-therapy group. Notably, the rate of death from any cause and the rate of MI did not differ significantly between the PCI group and the medical therapy group.

Importantly, patient recruitment was stopped on Jan. 15, 2012, at the recommendation of an independent data and safety monitoring board because of the highly significant difference in the incidence rates of the primary end point between the PCI and medical-therapy groups.

The results of the study were released in the New England Journal of Medicine on Aug. 28 to coincide with the presentation of the study at the annual congress of the European Society of Cardiology (N. Engl. J. Med. 2012 Aug. 28 [doi:10.1056/NEJMoa1205361]).

A total of 1,220 patients out a planned 1,832 were enrolled. Of those, 888 patients had at least one stenosis with an FFR of 0.80 or less: 447 patients were randomly assigned to FFR-guided PCI plus the best available medical therapy, and 441 patients to the best available medical therapy alone. The 332 patients with angiographically significant stenoses, but none with an FFR of 0.80 or less were enrolled in the registry and received the best available medical therapy alone. The mean duration of follow-up was 212 days.

Patients in stable condition who were appropriate candidates for PCI and who had angiographically assessed one-, two-, or three-vessel coronary artery disease suitable for PCI were included in the trial.

All patients were prescribed aspirin at a dose of 80-325 mg daily, metoprolol at a dose of 50 mg-200 mg daily (or any other beta-blocker), lisinopril (at least 5 mg daily, or another ACE inhibitor or an angiotensin receptor blocker)and atorvastatin (20-80 mg daily, or another statin).

All PCI patients were treated with second-generation drug-eluting stents.

Among the 56 patients who underwent urgent revascularization, the procedure was triggered by a MI in 12 patients (21%), by unstable angina accompanied by evidence of ischemia on ECG in 15 patients (27%), and by unstable angina diagnosed on the basis of clinical features in 29 patients (52%).

Patients in the PCI group were 86% less likely to undergo any revascularization and 83% less likely to undergo or nonurgent revascularization than were those in the medical therapy group.

The researchers identified several factors that may explain the differences between results in the present study and those in previous trials involving patients with stable coronary disease. "First, in previous trials in which various revascularization methods were compared with the best available medical therapy, patient enrollment was based primarily on angiographic findings, with or without noninvasive documentation of ischemia. It is likely that a sizable proportion of the patients had only limited ischemia," wrote lead investigator Dr. Bernard B. De Bruyne and his coinvestigators. Dr. De Bruyne is the codirector of the Cardiovascular Center at OLV Hospital in Aalst, Belgium.

"Even in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, in which noninvasive testing was performed in 85% of the patients, less than one-third of the patients had more than 10% ischemia on myocardial perfusion imaging. In daily clinical practice, less than half of patients undergo noninvasive stress testing before elective PCI. In the current trial, all the patients who underwent randomization had at least one functionally significant stenosis," they observed (N. Engl. J. Med. 2007;356:1503-16).

Second, PCI was performed only in lesions with an FFR of 0.80 or less. "This FFR-guided approach is associated with a better clinical outcome than that with PCI performed on the basis of angiographic results alone. These features probably explain the similarity of event rates between patients who were treated with PCI plus the best available medical therapy and patients with equivalent baseline characteristics but no functionally significant lesions who were enrolled in the registry and treated with the best available medical therapy alone," according to the investigators.

Third, second-generation drug-eluting stents were used in PCIs. This strategy is associated with a low number of repeat revascularizations. Finally, the primary end point included urgent revascularization, a component that was not included in the primary end point of previous trials.

The study was sponsored by St. Jude Medical, which makes the two pressure wires used in the trial. The company was involved in the collection and source verification of the data but not in the conduct of the trial. Dr. De Bruyne reported receiving consulting/honorarium and travel fees from St. Jude Medical. Most of the investigators had significant financial relationships with St. Jude Medical, as well as with other device and pharmaceutical companies. One author is an employee of St. Jude Medical.

The use of fractional flow reserve to guide percutaneous coronary intervention, along with best medical management, sharply reduced the need for urgent revascularization in patients with stable coronary artery disease and at least one physiologically significant lesion.

However, FFR-guided percutaneous coronary intervention (PCI) had little effect on deaths or myocardial infarctions, when compared with best medical management alone, according to the results of the FAME 2 (Fractional Flow Reserve vs. Angiography for Multivessel Evaluation 2) trial, which was conducted at 28 sites in Europe and North America and halted early.

The percentage of patients who had an MI, death, or urgent revascularization (the combined primary end point) was significantly lower in the PCI group than in the medical therapy group (4.3% vs.12.7%; hazard ratio with PCI, 0.32). This difference was driven by a 13-fold increase in the need for urgent revascularization in the medical-therapy group. Notably, the rate of death from any cause and the rate of MI did not differ significantly between the PCI group and the medical therapy group.

Importantly, patient recruitment was stopped on Jan. 15, 2012, at the recommendation of an independent data and safety monitoring board because of the highly significant difference in the incidence rates of the primary end point between the PCI and medical-therapy groups.

The results of the study were released in the New England Journal of Medicine on Aug. 28 to coincide with the presentation of the study at the annual congress of the European Society of Cardiology (N. Engl. J. Med. 2012 Aug. 28 [doi:10.1056/NEJMoa1205361]).

A total of 1,220 patients out a planned 1,832 were enrolled. Of those, 888 patients had at least one stenosis with an FFR of 0.80 or less: 447 patients were randomly assigned to FFR-guided PCI plus the best available medical therapy, and 441 patients to the best available medical therapy alone. The 332 patients with angiographically significant stenoses, but none with an FFR of 0.80 or less were enrolled in the registry and received the best available medical therapy alone. The mean duration of follow-up was 212 days.

Patients in stable condition who were appropriate candidates for PCI and who had angiographically assessed one-, two-, or three-vessel coronary artery disease suitable for PCI were included in the trial.

All patients were prescribed aspirin at a dose of 80-325 mg daily, metoprolol at a dose of 50 mg-200 mg daily (or any other beta-blocker), lisinopril (at least 5 mg daily, or another ACE inhibitor or an angiotensin receptor blocker)and atorvastatin (20-80 mg daily, or another statin).

All PCI patients were treated with second-generation drug-eluting stents.

Among the 56 patients who underwent urgent revascularization, the procedure was triggered by a MI in 12 patients (21%), by unstable angina accompanied by evidence of ischemia on ECG in 15 patients (27%), and by unstable angina diagnosed on the basis of clinical features in 29 patients (52%).

Patients in the PCI group were 86% less likely to undergo any revascularization and 83% less likely to undergo or nonurgent revascularization than were those in the medical therapy group.

The researchers identified several factors that may explain the differences between results in the present study and those in previous trials involving patients with stable coronary disease. "First, in previous trials in which various revascularization methods were compared with the best available medical therapy, patient enrollment was based primarily on angiographic findings, with or without noninvasive documentation of ischemia. It is likely that a sizable proportion of the patients had only limited ischemia," wrote lead investigator Dr. Bernard B. De Bruyne and his coinvestigators. Dr. De Bruyne is the codirector of the Cardiovascular Center at OLV Hospital in Aalst, Belgium.

"Even in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, in which noninvasive testing was performed in 85% of the patients, less than one-third of the patients had more than 10% ischemia on myocardial perfusion imaging. In daily clinical practice, less than half of patients undergo noninvasive stress testing before elective PCI. In the current trial, all the patients who underwent randomization had at least one functionally significant stenosis," they observed (N. Engl. J. Med. 2007;356:1503-16).

Second, PCI was performed only in lesions with an FFR of 0.80 or less. "This FFR-guided approach is associated with a better clinical outcome than that with PCI performed on the basis of angiographic results alone. These features probably explain the similarity of event rates between patients who were treated with PCI plus the best available medical therapy and patients with equivalent baseline characteristics but no functionally significant lesions who were enrolled in the registry and treated with the best available medical therapy alone," according to the investigators.

Third, second-generation drug-eluting stents were used in PCIs. This strategy is associated with a low number of repeat revascularizations. Finally, the primary end point included urgent revascularization, a component that was not included in the primary end point of previous trials.

The study was sponsored by St. Jude Medical, which makes the two pressure wires used in the trial. The company was involved in the collection and source verification of the data but not in the conduct of the trial. Dr. De Bruyne reported receiving consulting/honorarium and travel fees from St. Jude Medical. Most of the investigators had significant financial relationships with St. Jude Medical, as well as with other device and pharmaceutical companies. One author is an employee of St. Jude Medical.

The use of fractional flow reserve to guide percutaneous coronary intervention, along with best medical management, sharply reduced the need for urgent revascularization in patients with stable coronary artery disease and at least one physiologically significant lesion.

However, FFR-guided percutaneous coronary intervention (PCI) had little effect on deaths or myocardial infarctions, when compared with best medical management alone, according to the results of the FAME 2 (Fractional Flow Reserve vs. Angiography for Multivessel Evaluation 2) trial, which was conducted at 28 sites in Europe and North America and halted early.

The percentage of patients who had an MI, death, or urgent revascularization (the combined primary end point) was significantly lower in the PCI group than in the medical therapy group (4.3% vs.12.7%; hazard ratio with PCI, 0.32). This difference was driven by a 13-fold increase in the need for urgent revascularization in the medical-therapy group. Notably, the rate of death from any cause and the rate of MI did not differ significantly between the PCI group and the medical therapy group.

Importantly, patient recruitment was stopped on Jan. 15, 2012, at the recommendation of an independent data and safety monitoring board because of the highly significant difference in the incidence rates of the primary end point between the PCI and medical-therapy groups.

The results of the study were released in the New England Journal of Medicine on Aug. 28 to coincide with the presentation of the study at the annual congress of the European Society of Cardiology (N. Engl. J. Med. 2012 Aug. 28 [doi:10.1056/NEJMoa1205361]).

A total of 1,220 patients out a planned 1,832 were enrolled. Of those, 888 patients had at least one stenosis with an FFR of 0.80 or less: 447 patients were randomly assigned to FFR-guided PCI plus the best available medical therapy, and 441 patients to the best available medical therapy alone. The 332 patients with angiographically significant stenoses, but none with an FFR of 0.80 or less were enrolled in the registry and received the best available medical therapy alone. The mean duration of follow-up was 212 days.

Patients in stable condition who were appropriate candidates for PCI and who had angiographically assessed one-, two-, or three-vessel coronary artery disease suitable for PCI were included in the trial.

All patients were prescribed aspirin at a dose of 80-325 mg daily, metoprolol at a dose of 50 mg-200 mg daily (or any other beta-blocker), lisinopril (at least 5 mg daily, or another ACE inhibitor or an angiotensin receptor blocker)and atorvastatin (20-80 mg daily, or another statin).

All PCI patients were treated with second-generation drug-eluting stents.

Among the 56 patients who underwent urgent revascularization, the procedure was triggered by a MI in 12 patients (21%), by unstable angina accompanied by evidence of ischemia on ECG in 15 patients (27%), and by unstable angina diagnosed on the basis of clinical features in 29 patients (52%).

Patients in the PCI group were 86% less likely to undergo any revascularization and 83% less likely to undergo or nonurgent revascularization than were those in the medical therapy group.

The researchers identified several factors that may explain the differences between results in the present study and those in previous trials involving patients with stable coronary disease. "First, in previous trials in which various revascularization methods were compared with the best available medical therapy, patient enrollment was based primarily on angiographic findings, with or without noninvasive documentation of ischemia. It is likely that a sizable proportion of the patients had only limited ischemia," wrote lead investigator Dr. Bernard B. De Bruyne and his coinvestigators. Dr. De Bruyne is the codirector of the Cardiovascular Center at OLV Hospital in Aalst, Belgium.

"Even in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, in which noninvasive testing was performed in 85% of the patients, less than one-third of the patients had more than 10% ischemia on myocardial perfusion imaging. In daily clinical practice, less than half of patients undergo noninvasive stress testing before elective PCI. In the current trial, all the patients who underwent randomization had at least one functionally significant stenosis," they observed (N. Engl. J. Med. 2007;356:1503-16).

Second, PCI was performed only in lesions with an FFR of 0.80 or less. "This FFR-guided approach is associated with a better clinical outcome than that with PCI performed on the basis of angiographic results alone. These features probably explain the similarity of event rates between patients who were treated with PCI plus the best available medical therapy and patients with equivalent baseline characteristics but no functionally significant lesions who were enrolled in the registry and treated with the best available medical therapy alone," according to the investigators.

Third, second-generation drug-eluting stents were used in PCIs. This strategy is associated with a low number of repeat revascularizations. Finally, the primary end point included urgent revascularization, a component that was not included in the primary end point of previous trials.

The study was sponsored by St. Jude Medical, which makes the two pressure wires used in the trial. The company was involved in the collection and source verification of the data but not in the conduct of the trial. Dr. De Bruyne reported receiving consulting/honorarium and travel fees from St. Jude Medical. Most of the investigators had significant financial relationships with St. Jude Medical, as well as with other device and pharmaceutical companies. One author is an employee of St. Jude Medical.

The addition of CT-based fractional flow reserve information to CT alone improved the diagnostic accuracy of stenoses, allowing noninvasive assessment of the physiologic consequences of lesions, according to the long-awaited results of the Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography (DeFACTO) study.

However, CT fractional flow reserve (FFR-CT) plus CT narrowly failed to meet the trial’s primary end point – diagnostic accuracy greater than 70% for the lower bound of the 95% confidence interval. Per-patient performance diagnostic accuracy of FFR-CT plus CT was 73% with a 95% CI of 67%-78%.

Nevertheless, the addition of FFR-CT "demonstrated superior diagnostic performance characteristics, as compared with CT stenosis alone, in all patients, in all vessels, and also in vessels of intermediate stenosis severity," lead author Dr. James K. Min said during a press conference.

The results of the study were released in JAMA on Aug. 26th to coincide with the presentation of the study at the European Society of Cardiology meeting (JAMA 2012;308 [doi: 10.1001/2012.jama.11274]).

Fractional flow reserve (FFR) is currently assessed during invasive coronary angiography (ICA) to determine whether a coronary stenosis results in ischemia, and is the currently accepted reference standard for determining lesion-specific ischemia. FFR is the ratio of the mean coronary pressure distal to a coronary stenosis to the mean aortic pressure during maximal coronary blood flow. This value describes coronary flow still attainable despite the presence of a stenotic lesion.

While CT angiography has long been used to accurately and noninvasively assess the anatomic severity of stenoses, the technique has been criticized because it does not yield functional information about the hemodynamic effect of lesions.

Noninvasive calculation of FFR from CT "is a novel method that applies computational fluid dynamics to determine the physiologic significance of CAD [coronary artery disease]. Fractional flow reserve from CT enables calculation of rest and hyperemic pressure fields in coronary arteries without additional imaging, modification of CT acquisition protocols, or administration of medications," the investigators wrote.

"Taken together, these study results suggest the potential of FFR-CT as a promising noninvasive method for identification of individuals with ischemia. The present study findings can be considered proof of concept of the feasibility of this novel technology."

A total of 252 patients were included in the final analysis of the DeFACTO study. These patients had CAD and underwent clinically indicated ICA after CT with no intervening coronary event. Patients were not eligible if they had a history of coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention. About 77% of patients had experienced angina within the past month.

Among 615 study vessels, 271 had less than 30% stenosis and 101 had at least 90% stenosis. In all, 407 vessels were directly assessed by both FFR and FFR-CT.

Computed tomographic angiography was performed on 64- or greater detector scanners with prospective or retrospective electrocardiographic gating.

The investigators evaluated CTs for maximal patient-, vessel-, and segment-based diameter stenosis (characterized as 0%, 1%-29%, 30%-49%, or 50% or larger).

Per-patient and per-vessel CAD stenosis were the maximal stenoses identified in all segments or in all segments within a vessel distribution, respectively. Vessel distributions were categorized for the left anterior descending, left circumflex, and right coronary artery. Computed tomographic angiograms (CTAs) were judged as excellent, good, adequate, or nondiagnostic.

Selective ICA was performed by standard protocol, and FFR was performed at the time of ICA. Fractional flow reserve was considered diagnostic of ischemia at a threshold of 0.80 or less. Computation of FFR-CT was performed in blinded fashion by the FFR-CT core laboratory at HeartFlow, the study’s sponsor.

Per-patient diagnostic accuracy for FFR-CT plus CT was 73%. By comparison, diagnostic accuracy of CT alone was 64%.

FFR-CT also demonstrated greater discriminatory power than CT alone for vessels directly assessed by invasive FFR. For these vessels, the diagnostic sensitivity and specificity of FFR-CT alone were 80% and 61%, respectively.

Importantly, the researchers performed a secondary analysis of patients with an intermediate stenosis ranging from 30% to 70%, "wherein the clinical utility of FFR-CT would be most commonly expected for use." Diagnostic accuracy (73% for FFR-CT and 57% for CT), sensitivity (82% and 37%, respectively), positive predictive value (54% and 34%) and negative predictive value (88% and 68%) were greater for FFR-CT than for CT, though specificity was similar at 66%.

This intermediate group is an important patient population. "We know that patients with 30%-70% stenosis – even though they don’t look high-risk anatomically – actually, some of them experience ischemia and physiologic consequences of their coronary artery disease," said Dr. Min, director of cardiac imaging research and co-director of cardiac imaging at the Cedars-Sinai Heart Institute in Los Angeles.

High sensitivity/low specificity among patients with intermediate stenoses suggests "a low false-negative rate if assessments by FFR-CT were used to identify ischemia causing intermediate lesions, with negligible effects on reductions of false positive results. In this regard, the use of FFR-CT may significantly advance clinical assessment of patients without conventional measures of anatomic high-grade coronary stenosis, largely by proper identification of a significantly greater proportion of patients with manifest ischemia rather than as a safeguard to further invasive evaluation," the researchers noted.

They also pointed out that the prespecified primary end point for FFR-CT – a lower bound of the 95% confidence interval greater than 70% – "represents a 15% increase over traditional noninvasive histologic imaging methods, including myocardial perfusion imaging by SPECT or stress echocardiography," Dr. Min said.

Dr. Min and several of his coauthors reported significant financial relationships with GE Healthcare and Philips Medical, as well as other medical imaging/pharmaceutical companies. Dr. Jason H. Cole reported a grant for research support from HeartFlow. Dr. John Mancini reported a grant to his institution from HeartFlow. This study was funded by HeartFlow.

The addition of CT-based fractional flow reserve information to CT alone improved the diagnostic accuracy of stenoses, allowing noninvasive assessment of the physiologic consequences of lesions, according to the long-awaited results of the Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography (DeFACTO) study.

However, CT fractional flow reserve (FFR-CT) plus CT narrowly failed to meet the trial’s primary end point – diagnostic accuracy greater than 70% for the lower bound of the 95% confidence interval. Per-patient performance diagnostic accuracy of FFR-CT plus CT was 73% with a 95% CI of 67%-78%.

Nevertheless, the addition of FFR-CT "demonstrated superior diagnostic performance characteristics, as compared with CT stenosis alone, in all patients, in all vessels, and also in vessels of intermediate stenosis severity," lead author Dr. James K. Min said during a press conference.

The results of the study were released in JAMA on Aug. 26th to coincide with the presentation of the study at the European Society of Cardiology meeting (JAMA 2012;308 [doi: 10.1001/2012.jama.11274]).

Fractional flow reserve (FFR) is currently assessed during invasive coronary angiography (ICA) to determine whether a coronary stenosis results in ischemia, and is the currently accepted reference standard for determining lesion-specific ischemia. FFR is the ratio of the mean coronary pressure distal to a coronary stenosis to the mean aortic pressure during maximal coronary blood flow. This value describes coronary flow still attainable despite the presence of a stenotic lesion.

While CT angiography has long been used to accurately and noninvasively assess the anatomic severity of stenoses, the technique has been criticized because it does not yield functional information about the hemodynamic effect of lesions.

Noninvasive calculation of FFR from CT "is a novel method that applies computational fluid dynamics to determine the physiologic significance of CAD [coronary artery disease]. Fractional flow reserve from CT enables calculation of rest and hyperemic pressure fields in coronary arteries without additional imaging, modification of CT acquisition protocols, or administration of medications," the investigators wrote.

"Taken together, these study results suggest the potential of FFR-CT as a promising noninvasive method for identification of individuals with ischemia. The present study findings can be considered proof of concept of the feasibility of this novel technology."

A total of 252 patients were included in the final analysis of the DeFACTO study. These patients had CAD and underwent clinically indicated ICA after CT with no intervening coronary event. Patients were not eligible if they had a history of coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention. About 77% of patients had experienced angina within the past month.

Among 615 study vessels, 271 had less than 30% stenosis and 101 had at least 90% stenosis. In all, 407 vessels were directly assessed by both FFR and FFR-CT.

Computed tomographic angiography was performed on 64- or greater detector scanners with prospective or retrospective electrocardiographic gating.

The investigators evaluated CTs for maximal patient-, vessel-, and segment-based diameter stenosis (characterized as 0%, 1%-29%, 30%-49%, or 50% or larger).

Per-patient and per-vessel CAD stenosis were the maximal stenoses identified in all segments or in all segments within a vessel distribution, respectively. Vessel distributions were categorized for the left anterior descending, left circumflex, and right coronary artery. Computed tomographic angiograms (CTAs) were judged as excellent, good, adequate, or nondiagnostic.

Selective ICA was performed by standard protocol, and FFR was performed at the time of ICA. Fractional flow reserve was considered diagnostic of ischemia at a threshold of 0.80 or less. Computation of FFR-CT was performed in blinded fashion by the FFR-CT core laboratory at HeartFlow, the study’s sponsor.

Per-patient diagnostic accuracy for FFR-CT plus CT was 73%. By comparison, diagnostic accuracy of CT alone was 64%.

FFR-CT also demonstrated greater discriminatory power than CT alone for vessels directly assessed by invasive FFR. For these vessels, the diagnostic sensitivity and specificity of FFR-CT alone were 80% and 61%, respectively.

Importantly, the researchers performed a secondary analysis of patients with an intermediate stenosis ranging from 30% to 70%, "wherein the clinical utility of FFR-CT would be most commonly expected for use." Diagnostic accuracy (73% for FFR-CT and 57% for CT), sensitivity (82% and 37%, respectively), positive predictive value (54% and 34%) and negative predictive value (88% and 68%) were greater for FFR-CT than for CT, though specificity was similar at 66%.

This intermediate group is an important patient population. "We know that patients with 30%-70% stenosis – even though they don’t look high-risk anatomically – actually, some of them experience ischemia and physiologic consequences of their coronary artery disease," said Dr. Min, director of cardiac imaging research and co-director of cardiac imaging at the Cedars-Sinai Heart Institute in Los Angeles.

High sensitivity/low specificity among patients with intermediate stenoses suggests "a low false-negative rate if assessments by FFR-CT were used to identify ischemia causing intermediate lesions, with negligible effects on reductions of false positive results. In this regard, the use of FFR-CT may significantly advance clinical assessment of patients without conventional measures of anatomic high-grade coronary stenosis, largely by proper identification of a significantly greater proportion of patients with manifest ischemia rather than as a safeguard to further invasive evaluation," the researchers noted.

They also pointed out that the prespecified primary end point for FFR-CT – a lower bound of the 95% confidence interval greater than 70% – "represents a 15% increase over traditional noninvasive histologic imaging methods, including myocardial perfusion imaging by SPECT or stress echocardiography," Dr. Min said.

Dr. Min and several of his coauthors reported significant financial relationships with GE Healthcare and Philips Medical, as well as other medical imaging/pharmaceutical companies. Dr. Jason H. Cole reported a grant for research support from HeartFlow. Dr. John Mancini reported a grant to his institution from HeartFlow. This study was funded by HeartFlow.

The addition of CT-based fractional flow reserve information to CT alone improved the diagnostic accuracy of stenoses, allowing noninvasive assessment of the physiologic consequences of lesions, according to the long-awaited results of the Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography (DeFACTO) study.

However, CT fractional flow reserve (FFR-CT) plus CT narrowly failed to meet the trial’s primary end point – diagnostic accuracy greater than 70% for the lower bound of the 95% confidence interval. Per-patient performance diagnostic accuracy of FFR-CT plus CT was 73% with a 95% CI of 67%-78%.

Nevertheless, the addition of FFR-CT "demonstrated superior diagnostic performance characteristics, as compared with CT stenosis alone, in all patients, in all vessels, and also in vessels of intermediate stenosis severity," lead author Dr. James K. Min said during a press conference.

The results of the study were released in JAMA on Aug. 26th to coincide with the presentation of the study at the European Society of Cardiology meeting (JAMA 2012;308 [doi: 10.1001/2012.jama.11274]).

Fractional flow reserve (FFR) is currently assessed during invasive coronary angiography (ICA) to determine whether a coronary stenosis results in ischemia, and is the currently accepted reference standard for determining lesion-specific ischemia. FFR is the ratio of the mean coronary pressure distal to a coronary stenosis to the mean aortic pressure during maximal coronary blood flow. This value describes coronary flow still attainable despite the presence of a stenotic lesion.

While CT angiography has long been used to accurately and noninvasively assess the anatomic severity of stenoses, the technique has been criticized because it does not yield functional information about the hemodynamic effect of lesions.

Noninvasive calculation of FFR from CT "is a novel method that applies computational fluid dynamics to determine the physiologic significance of CAD [coronary artery disease]. Fractional flow reserve from CT enables calculation of rest and hyperemic pressure fields in coronary arteries without additional imaging, modification of CT acquisition protocols, or administration of medications," the investigators wrote.

"Taken together, these study results suggest the potential of FFR-CT as a promising noninvasive method for identification of individuals with ischemia. The present study findings can be considered proof of concept of the feasibility of this novel technology."

A total of 252 patients were included in the final analysis of the DeFACTO study. These patients had CAD and underwent clinically indicated ICA after CT with no intervening coronary event. Patients were not eligible if they had a history of coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention. About 77% of patients had experienced angina within the past month.

Among 615 study vessels, 271 had less than 30% stenosis and 101 had at least 90% stenosis. In all, 407 vessels were directly assessed by both FFR and FFR-CT.

Computed tomographic angiography was performed on 64- or greater detector scanners with prospective or retrospective electrocardiographic gating.

The investigators evaluated CTs for maximal patient-, vessel-, and segment-based diameter stenosis (characterized as 0%, 1%-29%, 30%-49%, or 50% or larger).

Per-patient and per-vessel CAD stenosis were the maximal stenoses identified in all segments or in all segments within a vessel distribution, respectively. Vessel distributions were categorized for the left anterior descending, left circumflex, and right coronary artery. Computed tomographic angiograms (CTAs) were judged as excellent, good, adequate, or nondiagnostic.

Selective ICA was performed by standard protocol, and FFR was performed at the time of ICA. Fractional flow reserve was considered diagnostic of ischemia at a threshold of 0.80 or less. Computation of FFR-CT was performed in blinded fashion by the FFR-CT core laboratory at HeartFlow, the study’s sponsor.

Per-patient diagnostic accuracy for FFR-CT plus CT was 73%. By comparison, diagnostic accuracy of CT alone was 64%.

FFR-CT also demonstrated greater discriminatory power than CT alone for vessels directly assessed by invasive FFR. For these vessels, the diagnostic sensitivity and specificity of FFR-CT alone were 80% and 61%, respectively.

Importantly, the researchers performed a secondary analysis of patients with an intermediate stenosis ranging from 30% to 70%, "wherein the clinical utility of FFR-CT would be most commonly expected for use." Diagnostic accuracy (73% for FFR-CT and 57% for CT), sensitivity (82% and 37%, respectively), positive predictive value (54% and 34%) and negative predictive value (88% and 68%) were greater for FFR-CT than for CT, though specificity was similar at 66%.

This intermediate group is an important patient population. "We know that patients with 30%-70% stenosis – even though they don’t look high-risk anatomically – actually, some of them experience ischemia and physiologic consequences of their coronary artery disease," said Dr. Min, director of cardiac imaging research and co-director of cardiac imaging at the Cedars-Sinai Heart Institute in Los Angeles.

High sensitivity/low specificity among patients with intermediate stenoses suggests "a low false-negative rate if assessments by FFR-CT were used to identify ischemia causing intermediate lesions, with negligible effects on reductions of false positive results. In this regard, the use of FFR-CT may significantly advance clinical assessment of patients without conventional measures of anatomic high-grade coronary stenosis, largely by proper identification of a significantly greater proportion of patients with manifest ischemia rather than as a safeguard to further invasive evaluation," the researchers noted.

They also pointed out that the prespecified primary end point for FFR-CT – a lower bound of the 95% confidence interval greater than 70% – "represents a 15% increase over traditional noninvasive histologic imaging methods, including myocardial perfusion imaging by SPECT or stress echocardiography," Dr. Min said.

Dr. Min and several of his coauthors reported significant financial relationships with GE Healthcare and Philips Medical, as well as other medical imaging/pharmaceutical companies. Dr. Jason H. Cole reported a grant for research support from HeartFlow. Dr. John Mancini reported a grant to his institution from HeartFlow. This study was funded by HeartFlow.

The use of cardiac computed tomography angiography (CCTA) can help emergency department physicians make better decisions about which patients with symptoms suggestive of acute coronary syndromes can safely be sent home.

There were no undetected cases of acute coronary syndromes (ACS) in patients assessed with CCTA or standard evaluation, suggesting that the earlier and greater number of discharges in the CCTA group did not result in any missed diagnoses in a prospective, randomized trial of 1,000 patients.

"It’s really about what is the minimum testing that you can do to safely send someone home if you’re an emergency department physician," senior author Dr. James E. Udelson said in an interview. Each ED and each ED physician had their own criteria for when a patient could be discharged based on CCTA findings. "We’re really measuring not the performance of the test, but how the test affects decision making," he said.

Previous studies have suggested that CCTA may aid in safer and earlier triage of low-risk patients and that it can rule out coronary artery disease faster than stress myocardial-perfusion imaging. However, CCTA often can involve more follow-up procedures and greater costs than functional testing.

While the accuracy of CCTA was roughly equivalent to that of standard ED evaluation, the imaging technique also cost about the same. There was no difference in total costs between the two groups for the index visit and during 28-day follow-up in a subgroup of 649 patients from five of nine sites, in which complete billing data were available. Costs for patients with CCTA appeared to be driven by a greater use of additional diagnostic testing.

In ROMICAT-II (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography II), researchers pitted CCTA – as a first diagnostic test, performed as early as possible – against standard ED evaluation in 1,000 patients with acute chest pain suggestive of ACS (N. Engl. J. Med. 2012;367:299-308).

The average length of the hospital stay – the primary end point – for patients who underwent CCTA was 7.6 hours less than that of the standard evaluation group.

Patient enrollment began in April 2010 and ended in January 2012 at nine U.S. hospitals. All sites were required to use at least 64-slice CT. Eligible patients were 40-74 years of age, and presented to the ED with chest pain (or the anginal equivalent) of at least 5 minutes’ duration within 24 hours before presentation in the ED. They also had to be in sinus rhythm and warranted further risk stratification to rule out acute coronary syndromes.

Patient care was not mandated by the study protocol in either group, but instead was at the discretion of local physicians. The discharge diagnosis also was based on the local physicians’ assessment.

Of 1,000 enrolled patients, 501 were randomized to CCTA and 499 were assigned to a standard evaluation. All patients were included in the intention-to-treat analysis. Overall, 987 patients (99%) had complete follow-up at 28 days.

After a complete evaluation, 75 patients (8%) had a final diagnosis of an acute coronary syndrome. In this subgroup of patients with a final diagnosis of ACS, the length of stay in the hospital was similar after CCTA and after standard evaluation in the ED.

In the overall cohort and also in patients without a final diagnosis of ACS, the mean time to diagnosis was significantly decreased with CCTA, compared with a standard evaluation. Patients in the CCTA group were more often directly discharged from the ED (47%, compared with 12% of patients in the standard-evaluation group), with fewer admissions to an observation unit.

Overall, there were eight major adverse cardiovascular events during the 28-day follow-up: six after standard evaluation in the ED and two after CCTA.

The results have important implications for some EDs. Not all EDs are the same: Some are overflowing with patients, while others have light traffic. For directors of busy and crowded EDs, the findings provide "an opportunity to get people out a lot sooner," said Dr. Udelson, chief of the cardiology division at Tufts Medical Center in Boston.

Half of patients who presented to the ED with symptoms suggestive of ACS and who underwent CCTA were discharged within 8.6 hours. In contrast, it took more than a day (26.7 hours) for half of the patients in the standard-evaluation group to be discharged. "If you’re in a supercrowded ED, that’s really worth something," he said.

The researchers did not measure additional follow-up in this study beyond major events that may have happened within 30 days. However, "one of the things about CT is that you identify early disease. You can potentially be comfortable that it doesn’t have anything to do with the chest pain." Primary care physicians should know about this early disease, in order to potentially start or change treatment.

One important question is what the yield is of subsequent testing following CCTA, said Dr. Udelson. "We’ll try to define the characteristics of the CT that mean that you’re not going to find anything else and not to test further."

In an accompanying editorial, Dr. Rita F. Redberg asserted that "with no evidence of benefit and definite risks, routine testing in the emergency department of patients with a low-to-intermediate risk of acute coronary syndromes should be avoided" (N. Engl. J. Med. 2012;367:375-6). Dr. Redberg is a professor of medicine and the director of Women’s Cardiovascular Services at the University of California, San Francisco. She is also on the editorial board of Cardiology News.

However, Dr. Udelson pointed out that "ED physicians struggle with this. They’re on the firing line. It’s their heads if they make a wrong decision."

"That’s our potential next step. ... Almost a quarter of the patients in the control group had no imaging tests. In other words, the physicians felt comfortable enough to discharge these patients with no [additional] testing." They will try to determine which individuals can safely go home and which patients need additional testing.

This study was supported by grants from the National Institutes of Health. Dr. Udelson reported that he is on the scientific advisory board of Lantheus Medical Imaging. Several of the coauthors reported financial ties to imaging and/or pharmaceutical companies and professional organizations.

The use of cardiac computed tomography angiography (CCTA) can help emergency department physicians make better decisions about which patients with symptoms suggestive of acute coronary syndromes can safely be sent home.

There were no undetected cases of acute coronary syndromes (ACS) in patients assessed with CCTA or standard evaluation, suggesting that the earlier and greater number of discharges in the CCTA group did not result in any missed diagnoses in a prospective, randomized trial of 1,000 patients.

"It’s really about what is the minimum testing that you can do to safely send someone home if you’re an emergency department physician," senior author Dr. James E. Udelson said in an interview. Each ED and each ED physician had their own criteria for when a patient could be discharged based on CCTA findings. "We’re really measuring not the performance of the test, but how the test affects decision making," he said.

Previous studies have suggested that CCTA may aid in safer and earlier triage of low-risk patients and that it can rule out coronary artery disease faster than stress myocardial-perfusion imaging. However, CCTA often can involve more follow-up procedures and greater costs than functional testing.

While the accuracy of CCTA was roughly equivalent to that of standard ED evaluation, the imaging technique also cost about the same. There was no difference in total costs between the two groups for the index visit and during 28-day follow-up in a subgroup of 649 patients from five of nine sites, in which complete billing data were available. Costs for patients with CCTA appeared to be driven by a greater use of additional diagnostic testing.

In ROMICAT-II (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography II), researchers pitted CCTA – as a first diagnostic test, performed as early as possible – against standard ED evaluation in 1,000 patients with acute chest pain suggestive of ACS (N. Engl. J. Med. 2012;367:299-308).

The average length of the hospital stay – the primary end point – for patients who underwent CCTA was 7.6 hours less than that of the standard evaluation group.

Patient enrollment began in April 2010 and ended in January 2012 at nine U.S. hospitals. All sites were required to use at least 64-slice CT. Eligible patients were 40-74 years of age, and presented to the ED with chest pain (or the anginal equivalent) of at least 5 minutes’ duration within 24 hours before presentation in the ED. They also had to be in sinus rhythm and warranted further risk stratification to rule out acute coronary syndromes.

Patient care was not mandated by the study protocol in either group, but instead was at the discretion of local physicians. The discharge diagnosis also was based on the local physicians’ assessment.

Of 1,000 enrolled patients, 501 were randomized to CCTA and 499 were assigned to a standard evaluation. All patients were included in the intention-to-treat analysis. Overall, 987 patients (99%) had complete follow-up at 28 days.

After a complete evaluation, 75 patients (8%) had a final diagnosis of an acute coronary syndrome. In this subgroup of patients with a final diagnosis of ACS, the length of stay in the hospital was similar after CCTA and after standard evaluation in the ED.

In the overall cohort and also in patients without a final diagnosis of ACS, the mean time to diagnosis was significantly decreased with CCTA, compared with a standard evaluation. Patients in the CCTA group were more often directly discharged from the ED (47%, compared with 12% of patients in the standard-evaluation group), with fewer admissions to an observation unit.

Overall, there were eight major adverse cardiovascular events during the 28-day follow-up: six after standard evaluation in the ED and two after CCTA.

The results have important implications for some EDs. Not all EDs are the same: Some are overflowing with patients, while others have light traffic. For directors of busy and crowded EDs, the findings provide "an opportunity to get people out a lot sooner," said Dr. Udelson, chief of the cardiology division at Tufts Medical Center in Boston.

Half of patients who presented to the ED with symptoms suggestive of ACS and who underwent CCTA were discharged within 8.6 hours. In contrast, it took more than a day (26.7 hours) for half of the patients in the standard-evaluation group to be discharged. "If you’re in a supercrowded ED, that’s really worth something," he said.

The researchers did not measure additional follow-up in this study beyond major events that may have happened within 30 days. However, "one of the things about CT is that you identify early disease. You can potentially be comfortable that it doesn’t have anything to do with the chest pain." Primary care physicians should know about this early disease, in order to potentially start or change treatment.

One important question is what the yield is of subsequent testing following CCTA, said Dr. Udelson. "We’ll try to define the characteristics of the CT that mean that you’re not going to find anything else and not to test further."

In an accompanying editorial, Dr. Rita F. Redberg asserted that "with no evidence of benefit and definite risks, routine testing in the emergency department of patients with a low-to-intermediate risk of acute coronary syndromes should be avoided" (N. Engl. J. Med. 2012;367:375-6). Dr. Redberg is a professor of medicine and the director of Women’s Cardiovascular Services at the University of California, San Francisco. She is also on the editorial board of Cardiology News.

However, Dr. Udelson pointed out that "ED physicians struggle with this. They’re on the firing line. It’s their heads if they make a wrong decision."

"That’s our potential next step. ... Almost a quarter of the patients in the control group had no imaging tests. In other words, the physicians felt comfortable enough to discharge these patients with no [additional] testing." They will try to determine which individuals can safely go home and which patients need additional testing.

This study was supported by grants from the National Institutes of Health. Dr. Udelson reported that he is on the scientific advisory board of Lantheus Medical Imaging. Several of the coauthors reported financial ties to imaging and/or pharmaceutical companies and professional organizations.

The use of cardiac computed tomography angiography (CCTA) can help emergency department physicians make better decisions about which patients with symptoms suggestive of acute coronary syndromes can safely be sent home.

There were no undetected cases of acute coronary syndromes (ACS) in patients assessed with CCTA or standard evaluation, suggesting that the earlier and greater number of discharges in the CCTA group did not result in any missed diagnoses in a prospective, randomized trial of 1,000 patients.

"It’s really about what is the minimum testing that you can do to safely send someone home if you’re an emergency department physician," senior author Dr. James E. Udelson said in an interview. Each ED and each ED physician had their own criteria for when a patient could be discharged based on CCTA findings. "We’re really measuring not the performance of the test, but how the test affects decision making," he said.

Previous studies have suggested that CCTA may aid in safer and earlier triage of low-risk patients and that it can rule out coronary artery disease faster than stress myocardial-perfusion imaging. However, CCTA often can involve more follow-up procedures and greater costs than functional testing.

While the accuracy of CCTA was roughly equivalent to that of standard ED evaluation, the imaging technique also cost about the same. There was no difference in total costs between the two groups for the index visit and during 28-day follow-up in a subgroup of 649 patients from five of nine sites, in which complete billing data were available. Costs for patients with CCTA appeared to be driven by a greater use of additional diagnostic testing.

In ROMICAT-II (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography II), researchers pitted CCTA – as a first diagnostic test, performed as early as possible – against standard ED evaluation in 1,000 patients with acute chest pain suggestive of ACS (N. Engl. J. Med. 2012;367:299-308).

The average length of the hospital stay – the primary end point – for patients who underwent CCTA was 7.6 hours less than that of the standard evaluation group.

Patient enrollment began in April 2010 and ended in January 2012 at nine U.S. hospitals. All sites were required to use at least 64-slice CT. Eligible patients were 40-74 years of age, and presented to the ED with chest pain (or the anginal equivalent) of at least 5 minutes’ duration within 24 hours before presentation in the ED. They also had to be in sinus rhythm and warranted further risk stratification to rule out acute coronary syndromes.

Patient care was not mandated by the study protocol in either group, but instead was at the discretion of local physicians. The discharge diagnosis also was based on the local physicians’ assessment.

Of 1,000 enrolled patients, 501 were randomized to CCTA and 499 were assigned to a standard evaluation. All patients were included in the intention-to-treat analysis. Overall, 987 patients (99%) had complete follow-up at 28 days.

After a complete evaluation, 75 patients (8%) had a final diagnosis of an acute coronary syndrome. In this subgroup of patients with a final diagnosis of ACS, the length of stay in the hospital was similar after CCTA and after standard evaluation in the ED.

In the overall cohort and also in patients without a final diagnosis of ACS, the mean time to diagnosis was significantly decreased with CCTA, compared with a standard evaluation. Patients in the CCTA group were more often directly discharged from the ED (47%, compared with 12% of patients in the standard-evaluation group), with fewer admissions to an observation unit.

Overall, there were eight major adverse cardiovascular events during the 28-day follow-up: six after standard evaluation in the ED and two after CCTA.

The results have important implications for some EDs. Not all EDs are the same: Some are overflowing with patients, while others have light traffic. For directors of busy and crowded EDs, the findings provide "an opportunity to get people out a lot sooner," said Dr. Udelson, chief of the cardiology division at Tufts Medical Center in Boston.

Half of patients who presented to the ED with symptoms suggestive of ACS and who underwent CCTA were discharged within 8.6 hours. In contrast, it took more than a day (26.7 hours) for half of the patients in the standard-evaluation group to be discharged. "If you’re in a supercrowded ED, that’s really worth something," he said.

The researchers did not measure additional follow-up in this study beyond major events that may have happened within 30 days. However, "one of the things about CT is that you identify early disease. You can potentially be comfortable that it doesn’t have anything to do with the chest pain." Primary care physicians should know about this early disease, in order to potentially start or change treatment.

One important question is what the yield is of subsequent testing following CCTA, said Dr. Udelson. "We’ll try to define the characteristics of the CT that mean that you’re not going to find anything else and not to test further."

In an accompanying editorial, Dr. Rita F. Redberg asserted that "with no evidence of benefit and definite risks, routine testing in the emergency department of patients with a low-to-intermediate risk of acute coronary syndromes should be avoided" (N. Engl. J. Med. 2012;367:375-6). Dr. Redberg is a professor of medicine and the director of Women’s Cardiovascular Services at the University of California, San Francisco. She is also on the editorial board of Cardiology News.

However, Dr. Udelson pointed out that "ED physicians struggle with this. They’re on the firing line. It’s their heads if they make a wrong decision."

"That’s our potential next step. ... Almost a quarter of the patients in the control group had no imaging tests. In other words, the physicians felt comfortable enough to discharge these patients with no [additional] testing." They will try to determine which individuals can safely go home and which patients need additional testing.

This study was supported by grants from the National Institutes of Health. Dr. Udelson reported that he is on the scientific advisory board of Lantheus Medical Imaging. Several of the coauthors reported financial ties to imaging and/or pharmaceutical companies and professional organizations.