Computed Tomography Assessment of Hemodynamic Significance of Coronary Artery Disease: CT Perfusion, Contrast Gradients by Coronary CTA, and Fractional Flow Reserve Review

Loewe, Christian MD*; Stadler, Alfred MD, Msc

Journal of Thoracic Imaging:
doi: 10.1097/RTI.0000000000000073
Symposium Review Articles

The need for functional estimation of the relevance of stenosis to guide appropriate treatment in coronary artery disease has recently been shown. Invasive coronary angiography (CA) with invasive measurement of the pressure gradient in patients with coronary stenoses becomes the method of choice for treatment decision-making in invasive cardiology. Coronary computed tomography angiography (CCTA) was established several years ago as a noninvasive alternative to invasive CA; it is used primarily to exclude coronary artery disease and has shown a very high negative predictive value in this regard. During the last several years, in an effort to obtain functional information, CCTA has received much attention. The rationale for this is that with the functional information provided by CT, the positive predictive value for “relevant” stenoses should be improved. In this article, the history and limitations of anatomic grading of coronary stenoses will be discussed. Furthermore, shifts in the treatment paradigm in modern cardiology will be introduced, as well as an overview of the currently used invasive methods to assess the “relevance” of stenosis. The current role and still-existing limitations of CCTA, as well as the systematic problems in comparing CA and CCTA, are addressed. As CCTA is a highly innovative technique, new innovations are currently under clinical evaluation, including myocardial perfusion imaging, attenuation gradient measurement, and assessment of fractional flow reserve with CT. This review article will mainly focus on the technical background of these techniques and the status of their clinical implementation and will attempt to provide some suppositions about the possible future role of these new innovations.

Author Information

*Section of Cardiovascular and Interventional Radiology, Department of Biomedical Imaging and Inmage-guided Therapy, Medical University of Vienna

Department of Radiology, General Hospital Hietzing with Neurological Department Rosenhügel, Vienna, Austria

The authors declare no conflicts of interest.

Reprints: Christian Loewe, MD, Section of Cardiovascular and Interventional Radiology, Department of Biomedical Imaging and Inmage-guided Therapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria (e-mail:

Article Outline

For decades, clinical decision-making in invasive cardiology depended on the anatomic grading of coronary stenosis and the personal preference of the treating physician. Lesions appearing to be “relevant” were treated by percutaneous balloon dilatation, later by stent implantation, and finally by implantation of drug-eluting stents as the method of choice. However, it has been shown that the visual grading or even the quantification of the anatomic relevance of a stenosis—as described by the luminal narrowing—is not a good indicator of the severity of disease and not a good predictor of patient outcomes. The usefulness of measuring the flow gradients in a coronary stenosis and the superiority of these flow gradient measurements to anatomic grading has been demonstrated. A similar evolution could be observed with coronary computed tomography angiography (CCTA), traditionally compared with and measured against coronary angiography (CA). After the clinical introduction of this innovative, noninvasive alternative to diagnostic invasive CA, the primary aim was to show the noninferiority of CCTA compared with CA, with regard to anatomic stenosis quantification. Given the already known limitations of CA in this regard, the assessment of the relevance of stenosis with CCTA remains the critical issue. Thus, new CT techniques, such as CT perfusion (CTP) imaging, CT contrast gradient assessment, and computing the fractional flow reserve (FFR) among stenoses from CT images, are currently under clinical evaluation. These techniques are promising, and some of them are more or less ready to be implemented in clinical applications. These techniques also have the potential to fundamentally change the clinical value and use of CT for the management of patients suffering from coronary artery disease (CAD). Given all the technological innovations during the past decade, it was clearly the “decade of CT”; with the recently published new techniques, it seems that even the next decade will be another landmark one for CT.

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Clinical Significance of Stenosis Relevance in CAD

The relationship between coronary stenosis and the clinical symptoms of angina are well known. Myocardial ischemia is an important factor in an unfavorable outcome,1 and prognosis can be improved by revascularization of relevant stenosis that causes the myocardial ischemia, although even this beneficial effect of percutaneous coronary intervention (PCI) in cases of relevant stenosis has recently been called into question.2 However, it is known that treatment of a functionally nonsignificant lesion by means of stent placement will not benefit the patient with regard to either symptoms or outcome.3 Thus, the exact definition of the “relevance” of a stenosis is crucial for treatment indications and recommendations.

Since the clinical introduction of CA, the associated picture of chest pain causing lesions had become common sense. However, recently published papers have demonstrated that we might have believed the wrong image, and it may have been a mistake to rely solely on angiographic images to guide treatment decisions.4 The identification of the “relevant” stenosis, historically defined as a percentage of luminal diameter or area narrowing, has become more complex than previously thought.5

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Why Anatomy Is Not Enough

Again, the “relevance” of a stenosis from the point of view of the patient, and with regard to outcome, is determined by the presence or absence of myocardial ischemia, and only lesions that cause such myocardial ischemia should be treated by stent implantation. The situation at the level of the epicardial vessels is, however, only one side of the problem, and the presence or absence of ischemia mainly depends on the function of the microcirculation.6 There are angiographically relevant stenoses that do not cause a relevant reduction in coronary flow and coronary flow reserve, and there are fixed mild stenoses that lead to a relevant flow reduction.7 Current knowledge about the fluid dynamics in the coronary arteries has been derived from animal and experimental models begun about 40 years ago. The “70% cutoff value” for “relevant” coronary stenosis is based on these early experimental models.8 However, the limitations of this anatomic grading have been known for almost the same period of time, although this grading approach is still commonly used in clinical practice.5 The discrepancy between “anatomic” and “physiological” stenosis severity is the most important issue in modern cardiology. In addition to the technical limitations, as reflected by the inability to obtain accurate measurements of vessel diameters, the methodological weaknesses of anatomic grading are several, including limited documentation in diffuse disease, the lack of a “normal” reference vessel, the presence of multiple stenoses, or the remodeling process.9 It has been shown that PCI, on the basis of anatomic grading only, was unable to reduce coronary events compared with a control group treated by the best medical treatment only without revascularization.2 The reasons for the lack of reduction of events after PCI include the insufficient anatomic grading of stenosis severity and the inability to treat all the lesions in case of diffuse disease and/or multiple vulnerable plaques.9 Most of the limitations of the “anatomy-only” grading can be overcome by functional assessments, which is why “physiology” is superior to “anatomy” in this regard.

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How the “Physiological” Assessment Works

Currently, the FFR is used as the “real” physiological gold standard to assess the relevance of a coronary artery stenosis. FFR is defined as the ratio of maximal blood flow in a stenotic artery to the normal maximal flow.4,10 FFR is determined during CA, just before planned intervention. An FFR of 1.0 is defined as normal, and an FFR <0.75 is considered relevant, which is defined as a stenosis-associated inducible ischemia.11,12 Coronary blood pressure is measured after inducing maximal hyperemia by injection of adenosine either intravenously or intracoronarily. The pressure measurement within the coronary artery is obtained using a pressure wire that is advanced over the stenosis, and this pressure is compared with the intra-aortic pressure as measured using the guiding catheter. FFR is calculated by the ratio of maximal hyperemic coronary pressure distally from the stenosis to the intra-aortic pressure, and a ratio <0.75 is an indicator of hemodynamic relevance. The superiority of the physiological method, as represented by the FFR, to anatomic guidance for decision-making in interventional cardiology has been shown by several randomized prospective trials thus far.4,13,14 These trials demonstrated both better outcomes and event prevention. A prospective, randomized evaluation about the possible advantage of establishing the treatment indication for bypass graft surgery solely on physiological means rather than anatomy has not been carried out as yet; however, it seems that, even in this application, physiological information about the hemodynamic relevance of stenosis might be superior compared with anatomy only.

However, as shown, for example, by the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, and as pointed out in the discussion of the results,9 the prevention of events requires more than just exact grading of stenosis. In addition to all these important discussions and improvements in defining the “relevance” of stenosis, and all the efforts to adapt the guidelines for CAD treatment based on functional stenosis assessment, other factors are important as well. Information about the morphology of disease, the morphology of plaques, and changes within the vessel wall—potentially responsible for future events—are significant considerations in clinical decision making in CAD patients.15 This information is currently not a part of current treatment guidelines.

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CCTA and Stenosis Quantification

The “classic” CCTA suffers from limitations similar to those of diagnostic CA alone. Technical improvements during the last few years have improved the spatial resolution16,17 and have reduced the risk for motion-induced artifacts and, thus, the number of nonassessable coronary artery segments. However, the methodological limitations of providing either anatomic or morphologic information only remain unaffected by these technical innovations. For this reason, CCTA becomes predominantly used and recommended for patients with low to intermediate pretest probability of CAD, wherein the exclusion of any coronary stenosis is the main target. In this indication, extremely high negative predictive values (NPVs), close to 100%, have been published thus far,15,18–20 leading to endorsement of the use of CCTA for this indication by many societies.21 Thus, the above-mentioned limitations of accurate quantification and/or grading of a coronary stenosis are negligible in a negative CCTA that shows patent coronary arteries.

In case of positive findings, things become more critical, and the positive predictive values (PPVs), as published, are significantly lower compared with the NPV. The PPV in 3 large multicenter trials ranged from 64% to 91%.22–25 There are different reasons for this limited accuracy in stenosis assessment with CCTA, including technical and methodological limitations, which lead to the limited PPVs.

From a technical point of view, the spatial resolution of CCTA—although significantly improved during the last decade—is still too low. Given the diameter of the main epicardial coronary vessels, which ranges between 1.5 and 3.5 mm, it is obvious that a spatial resolution of 0.5 mm is not high enough to accurately measure diameters and is significantly lower compared with CA (0.2 mm).26 Partial volume effects lead to overestimation of stenosis, and this limitation becomes more severe in the case of calcified lesions, in which blooming, due to calcified tissue, masks the arterial border.26–28 Although recently published techniques for image reconstruction have shown the potential to overcome or at least to reduce this limitation,29 calcified plaques still represent an important factor for the low PPV of CCTA. These technical limitations enhance the above-mentioned problems in assessing the hemodynamic significance of coronary lesions.

Another important reason for the low accuracy of CCTA in stenosis assessment is the lack of clearly defined guidelines about how a coronary lesion should be graded with CCTA. Although recommendations about grading stenoses have been published by some societies,30 different categorizations can be found in the literature.26 The fact that a relevant stenosis can be defined by a 50% diameter reduction or by a 70% area reduction is another frequent cause of confusion when comparing CCTA and CA findings. Traditionally, CCTA is compared with CA, as CA represents the so-called gold standard. In addition to the limitations of this reference standard as addressed above, the attempt of such a comparison seems to be inappropriate because of the technical differences between these 2 methods. The assessment of luminal narrowing heavily depends on the relation between a “normal” vessel and the residuary lumen at the level of the lesion (stenosis). It is obvious that, especially in diffuse atherosclerotic disease, this reference vessel diameter would be defined differently by CA, which provides a luminography only, and CCTA, which demonstrates wall irregularities and positive remodeling. Particularly in the case of diffuse atherosclerotic disease, overestimation of stenosis severity by CCTA is much more frequent compared with singular, well-defined stenosis. However, the information about extensive disease, described by diffuse wall irregularities, seems to be important additional information about a patient’s vascular status, although this information is not taken into account in the actual guidelines for treatment. It seems surprising that one of the most promising advantages of “classic” CCTA—the potential to describe changes within the vessel wall—is counted as a disadvantage when comparing CCTA with the luminographic technique, CA. Although the potential of CCTA to detect plaques at risk for rupture and to differentiate them from stable plaques has been shown by different studies, to date, this application remains an academic one.15,31,32 Given these promising results and the knowledge about atherosclerosis as a systemic disease, the focus on the relevance of a stenosis seems to be 1-dimensional and somehow outdated. Furthermore, “relevance” is historically focused on the relevance for myocardial ischemia but not the relevance for potential future events. However, many attempts are currently underway to add functional information to the morphologic information obtained with CCTA, to make CCTA equivalent to CA, and to increase the PPV of CCTA compared with CA (Fig. 1).

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CT of Myocardial Perfusion

The detection of a coronary stenosis based only on anatomic information cannot define the extent of the resulting myocardial perfusion deficit, which is the physiological equivalent of the stenosis. The presence of anatomic lesions does not necessarily correlate with functional deficits.25

However, the identification of myocardial ischemia is critical for evaluating the hemodynamic significance of a coronary stenosis to guide clinical management and long-term prognosis. Three different imaging modalities are typically used to assess the functional or perfusion abnormalities in patients with myocardial ischemia: echocardiography, magnetic resonance imaging (MRI), and nuclear imaging [including positron emission tomography and single-photon emission computed tomography (SPECT)].33

Pharmacological stress agents are vasodilators and work by means of the coronary “steal phenomenon,” according to which the normal coronary arteries dilate more than the diseased arteries. This results in a different flow in the dependent myocardial segments and unmasks the perfusion deficit in the territory of the stenosed artery. The pharmacological stress agents used include adenosine, dipyridamole, and regadenoson. Dobutamine works through a different physiological pathway by increasing the oxygen consumption in the myocardium.34

CT-perfusion measurement is facilitated by the fact that reduced perfusion of myocardial tissue results in reduced concentration of contrast media and, thus, to a lower attenuation in these areas. The measurement has to be performed in the first pass of the circulation, in which the amount of intravascular iodine reflects myocardial perfusion. If the measurement is performed too late, the extravascular iodine in the tissue can mask the perfusion effects.35

There are 2 strategies for performing a stress-rest protocol: stress first, followed by rest, or vice versa. The first scan has the main advantage of a pure effect of the contrast media, without interference of the effects of previous contrast administration.34 Thus, it must be decided whether the main focus is on the detection of a perfusion deficit at stress, representing a reversible perfusion deficit, on the detection of a perfusion deficit at rest, which usually is indicative of myocardial infarction but can also be seen in the presence of high-grade stenosis.

To avoid interference from β-blockers and stress agents, the CT angiography (CTA) must be performed at the rest scan. Performing the rest scan first provides the opportunity to stop the protocol after the first scan if no stenoses are detected.34 To avoid contrast contamination a time interval between rest and stress scan of about 30 minutes is recommended.

Several recent studies were conducted using the various new CT technologies: a 64-detector CT, a 64-detector dual-source CT (DSCT), a 128-detector DSCT using dynamic shuttle mode and high pitch spiral mode, and a 320-detector scanner.34,36

Rocha-Filho et al37 showed, using a 64-detector DSCT, an increase in sensitivity from 83% to 91% and an increase in specificity from 71% to 91%, with invasive angiography as a reference standard.

A study by Feuchtner et al,38 using prospectively triggered high-pitch dual-source CTP imaging, showed a sensitivity of 96% and a specificity of 95% for imaging of reversible ischemia, compared with cardiac MRI. The accuracy improved from 84% to 95% after adding stress CTP to CTA. The radiation dose of the entire stress/rest CT examination was 2.5 mSv.

A recent study by Nasis et al39 determined the diagnostic accuracy of combined 320-detector CTA and adenosine stress CTP in detecting perfusion abnormalities, finding a sensitivity of 94% and a specificity of 98%, with invasive CA combined with SPECT as the gold standard. The morphologic evaluation of stenosis based on CTA alone had a sensitivity of 100% and a specificity of 84%. The mean CTA/CTP radiation dose was 9.2±7.4 mSv.

The potential for high temporal resolution of the newer, faster scanners, for example, a 320-detector scanner or a 128-detector dual-source scanner with shuttle mode acquisition, has gained attention for performing dynamic CTP to quantify myocardial blood flow (MBF).

In the shuttle mode acquisition of 128-detector dual-source scanners, images are acquired in 2 alternating table positions with the table moving back and forth, resulting in an anatomic coverage of 73 mm for every single heartbeat. Thus, a dynamic image acquisition of the contrast wash-in and wash-out, with time points at every consecutive heartbeat, can be performed.

In a study by Weininger et al,40 using a 128-detector DSCT, dynamic perfusion CT had 86% sensitivity and 98% specificity, compared with perfusion MRI, for the detection of myocardial perfusion defects. The radiation dose of the dynamic perfusion study resulted in a mean radiation dose of 12.8±2.4 mSv.

Bamberg et al41 reported a significant increase in the accuracy of predicting hemodynamically significant stenosis. Although the sensitivity and specificity of defining a coronary stenosis of >50% was high (94% and 97%), the ability to predict a hemodynamically significant stenosis, defined as an FFR≤75, was low, with a PPV of 49%. The combination of an MBF of <75 mL/100 mL/min, with a CTA stenosis of >50%, raised the PPV of predicting an FFR from ≤75% to 78% (sensitivity 93%, specificity 87%). The radiation dose of the dynamic perfusion study was 10.0±2 mSv, and the additional dose of the CTA was 3.1±1 mSv.

In a more recent study,42 dynamic stress perfusion CT with a 128-detector DSCT was compared with invasive FFR measurement. Dynamic myocardial perfusion imaging (MPI) showed a significant increase in specificity and PPV for the detection of hemodynamically relevant stenoses (66% and 74%, respectively), with high sensitivity and NPV for ruling out hemodynamically relevant stenoses (97% and 96%, respectively). However, in that study, the combination of CTA and CT-MPI showed no further increase in the detection of hemodynamically significant stenoses, compared with CT-MPI alone. CT-MPI had a mean effective radiation dose of 9.7±2.2 mSv.

DSCT with dual-energy mode can provide an “iodine map” for the assessment of myocardial perfusion status by analyzing iodine distribution within the myocardium.36 The mapping of the iodine distribution, on the basis of the specific absorption characteristics of iodine, is possible by the simultaneous acquisition of 2 data sets with different x-ray energy levels within 1 measurement.

Weininger et al40 compared dual-energy MPI CT SPECT and obtained 93% sensitivity, 99% specificity, 92% PPV, and 96% NPV for detecting hypoperfused myocardial segments. The resulting radiation dose was 15.2±2.7 mSv.

A study by Ko et al43 obtained stress/rest iodine maps using dual-energy CTP, which resulted in a sensitivity of 89% and a specificity of 76% for the detection of ischemic defects in vessel territories with coronary stenoses of <50%. The radiation dose of the dual-energy measurement was 8.6 mSv.

Compared with these stress/rest studies investigating patients with reversible ischemia, there are a few studies that obtained only rest perfusion.

In a study by Iwasaki and Matsumoto,44 a significant percentage of patients with angiographically proven significant coronary artery stenosis showed a myocardial perfusion defect on 64-multidetector CT at rest; the size of these defects correlated with the stenosis grade. Furthermore, most of these perfusion defects improved after coronary revascularization therapy.

The focus of the recent work by Feuchtner et al45 was the evaluation of low-risk to intermediate-risk patients with acute chest pain. The analysis of rest perfusion myocardial defects, combined with stenosis detection of CTA, improved the PPV from 67% to 90% compared with CTA evaluation alone; the false positive rate was also significantly reduced (Figs. 2–4).

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Intracoronary Transluminal Attenuation Gradient (TAG)

In coronary arteries imaged in the arterial phase, there is a difference in the contrast opacification between the proximal and the distal portions of the vessel. In theory, opacification of the coronary artery lumen and luminal contrast density is dependent upon contrast bolus geometry, which is the result of several parameters—for example, iodine concentration, contrast infusion rate volume, acquisition timing, and cardiac output coronary flow.

In first approximation, differences in opacification are linked to the coronary blood flow. Flow is linked to the resistance and, thus, depends on the minimum vessel diameter. Normal coronary arteries do not have a measurable decrease in pressure along their course, but stenosed arteries should show a pressure drop and, as a result, a measurable decrease in the mean density of the mean vessel Hounsfield units (HU) distal to the stenosis or, in other words, an alteration of the contrast gradient. Coronary contrast opacification gradients are defined as coronary HU differences divided by a property of the coronary artery, such as distance from the ostium or the coronary short axis diameter.

Early studies with a 360-slice scanner showed a linear relationship between the coronary mean HU and the distance to the coronary ostium, the coronary vessel diameter, and the coronary vessel short axis diameter in normal coronary arteries.46 The obtained gradients were not significantly influenced by patient characteristics, such as heart rates or body mass index, and were also independent of the cardiac phases.

Another study using a 64-slice scanner obtained the linear regression coefficient between luminal attenuation and axial distance.47 The TAG decreased consistently and significantly with maximum stenosis severity on a per-vessel basis. The addition of TAG to the visual estimate of CCTA resulted in reclassification of stenosis severity to another grade in a significant number of calcified lesions but not in noncalcified lesions. Adding TAG to the interpretation of CCTA improved diagnostic accuracy (P=0.001), especially in vessels with calcified lesions.

Using a 320-detector row CT scanner has some theoretical advantages. The differences in proximal versus distal coronary artery lumen enhancement obtained at one point in time within a single heartbeat reflects the pure TAG, whereas the lack of temporal uniformity from the combined measurement over multiple heartbeats using a 64-slice scanner can result in an artificial drop in coronary HU.

One study tried to overcome these drawbacks of a 64-slice scanner by normalizing the coronary artery density with the HU of the aorta in the same slice.48 The authors found that changes in coronary opacification across coronary stenoses seem to predict abnormal (TIMI flow grade <3) resting coronary blood flow.

In another study49 using a 64-slice scanner, TAG did not improve the diagnostic accuracy [receiver operator characteristic: area under the curve (AUC) TAG 0.63, AUC CCTA 0.73] compared with the CCTA stenosis grade.

A recent study50 reported that combined 320-detector row CT TAG and CCTA assessment may have an incremental predictive value over CCTA alone for detecting functionally significant coronary arterial stenosis, with a sensitivity of 77%, a specificity of 74%, a PPV of 67%, and an NPV of 86%. Thus, TAG provides acceptable prediction of invasive FFR and may provide a noninvasive modality for detecting functionally significant coronary stenoses.

All these studies showed that gradients across lesions are larger than across normal coronary arteries, giving a morphologically based surrogate for additional, functional information. However, measuring TAG at rest, which would entail measuring abnormal resting coronary flow, is of limited value. Like other functional tests (eg, cardiac MRI stress perfusion) in the diagnosis of ischemic heart disease, functional relevant stenosis can only be evaluated using stress examinations. Pharmacological stress examinations can augment coronary flow in normal arteries and decrease the flow in stenosed arteries to measure the functional relevance of morphologic stenosis. Further studies are needed to evaluate the value of measuring TAG in this context.

However, TAG measurements may be useful in the assessment of morphologically unevaluable segments (eg, heavy calcification, stents).

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Measurement of FFR From CCTA

FFR is defined as the ratio of maximal MBF through a stenosed artery versus the hypothetical flow in the normal vessel. The FFR is obtained invasively and has been shown to be a highly valuable method to differentiate between lesions and determine who would benefit from a revascularization and who would not.51

The simulation of flow dynamics through a stenosis on the basis of noninvasively obtained morphologic information could theoretically provide valuable physiological information with which to derive the FFR. This technique, called FFRCT, uses a 3D model of the coronary vessels obtained from a normal coronary CT. On the basis of these morphologic data, a mathematical model is used to simulate the pulsatile flow in the coronary vessels.52 This complex numerical simulation necessitates high computational power and high-quality morphologic data.

In the prospective multicenter Diagnosis of Ischemia-Causing Stenoses Obtained Via Non-invasive Fractional Flow Reserve study, the computation of FFRCT from CCTA data was performed on 159 vessels in 103 patients undergoing CCTA. The FFRCT was modeled to simulate the conditions of adenosine-induced hyperemia. The computation time was about 5 hours per examination.

The diagnostic performance of FFRCT and CCTA for relevant stenoses was assessed with invasive FFR as the reference standard.53 The FFRCT and FFR correlated well, with a slight underestimation by FFRCT. On a per-vessel basis, the sensitivity was 87.9% and the specificity was 82.2%.

A multicenter study by Min et al54 investigated 252 patients to assess the diagnostic performance of FFRCT plus CT for the diagnosis of hemodynamically significant coronary stenosis. Noninvasive FFRCT plus CT was associated with improved diagnostic accuracy compared with CT alone. FFRCT plus CT showed a sensitivity of 90% and a specificity of 54%.

In a study by Yoon and colleagues, the diagnostic performance of FFRCT in 53 patients was compared with CCTA, with invasive FFR as a reference standard. The results showed a sensitivity for FFRCT of 81% and a specificity of 94%. In the receiver operator characteristic analysis, FFRCT showed a significantly larger AUC, compared with CCTA alone, but this was not true for the subpopulation of patients with calcified plaques.49

The simulation of FFRCT on the basis of morphologic data from the coronaries alone has some limitations on the basis of the fact that the mathematical model has to deal with some simplifications—for example, the microcirculation at the level of the myocardium.55 The major increase in specificity has been shown for intermediate-grade stenosis, but the evaluation of calcified plaques showed some drawbacks. This new method demonstrated promising initial results; however, owing to the high computational demands, FFRCT cannot be included in the clinical routine as yet (Fig. 5).

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After decades of focusing on the optimized assessment and quantification of the “relevance” of coronary artery stenosis according to anatomic criteria and using the “70% cutoff rule,” there is obviously a need for functional information in modern cardiology. Not all stenoses that were thought to be relevant, and which were subsequently stented, turned out to be relevant with regard to the outcome of the patients. As a consequence, the assessment of FFR has been advocated to be the actual gold standard for treatment decision-making in modern cardiology, and an FFR<0.75 has become the new cutoff value for indicating the need for revascularization. The advantages of establishing treatment indications by functional means (as represented by the FFR), in terms of outcome and prevention of new events, rather than by anatomic grading, has been recently demonstrated by several prospective, randomized trials. Although the limitations of the anatomic grading of stenosis and the superiority of functional assessment have been known from the early beginnings of invasive cardiology, it has taken about 40 years to change the rules for treatment indications for revascularization. Compared with this slow implementation, cardiac CT has shown an excitingly fast evolution. Early after its initial introduction, the temporal and spatial resolution limitations could be partially overcome by further development of new techniques and new scanners. Furthermore, cardiac CT, not resting on the laurels of its already innovative advances and high clinical accuracy, is ever-evolving. CT has answered the challenge of providing functional information about coronary stenosis, and the adaption of new techniques has resulted in 3 different directions, which have been addressed in this review, namely, CT-MPI, intracoronary TAG, and CT-FFR. Of these 3 methods, in clinical evaluation, CT-MPI seems to be the most advanced. Incorporating all the tools and possibilities of dose reduction in modern state-of-the-art cardiac CT, CT-MPI seems to be ready to be implemented in clinical routine protocols. The high availability seems to be a great advantage of CT-MPI compared with MR-MPI and positron emission tomography. Compared with SPECT, the higher spatial resolution of CT could be an argument for the use of this technique in the future. These advantages, combined with the possibility of receiving combined information about lesion morphology and the situation at the level of the myocardium, promise a great potential for this modality in the management of CAD patients in the near future.

The value of TAG is difficult to establish right now; further studies seem to be mandatory to estimate the real position of these techniques within the tools currently becoming available. CT-FFR seems closer to possible implementation into the clinical routine. However, to date, only 1 company has been providing the (relatively expensive) service of these calculations, and patient inclusion is quite restricted. The sufficiency of the spatial resolution provided by coronary CT for such complex calculations must be confirmed in larger patient populations.

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For >10 years, CT has demonstrated its great potential and its enormous power for innovation. Different new and highly promising techniques for functional analysis in CAD with CT have been recently introduced, as described earlier in this review. Some of these techniques are ready to be implemented into clinical patient care, and others are close to that goal. If the promise can be fulfilled, the role of CT in the management of CAD patients will reach another level. Using a combination of “classical” CCTA with CT-MPI, and further analysis by advanced techniques like CT-FFR, for example, would allow for the combined assessment of anatomy and the functional relevance of stenosis, as well as myocardial viability within one extended examination. No other single method can match this! Let us hope that the great promise will be fulfilled.

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The authors would like to thank Fabian Bamberg, MD (Munich, D) and V. Sinitsyn (Moscow, RU) for their support and their contribution of image data.

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coronary artery disease; coronary computed tomography angiography; coronary stenoses; fractional flow reserve; myocardial perfusion imaging; coronary angiography

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