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Editorial
ONLINE FIRST
September 26, 2012

Detecting Obstructive Coronary Disease With CT Angiography and Noninvasive Fractional Flow Reserve

Author Affiliations

Author Affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.

JAMA. 2012;308(12):1269-1270. doi:10.1001/2012.jama.11383

Physicians commonly encounter patients reporting chest discomfort. In these cases, the physician needs to determine whether the patient has obstructive coronary artery disease (CAD), and if so, whether the patient is at increased risk of future cardiovascular events. The ultimate goal of this evaluation is to direct optimal medical therapy and potentially lead to ischemia-driven coronary revascularization. The fractional flow reserve (FFR) performed during invasive coronary angiography has been shown to provide lesion-specific data on ischemia, which, when used to direct revascularization, leads to improved clinical outcomes.1,2 Fractional flow reserve is the ratio of the mean coronary artery pressure distal to an obstructive coronary lesion relative to the mean aortic pressure during maximal coronary blood flow and represents a physiologic measure of coronary stenosis.

Current guidelines recommend that this evaluation should be differential based on patient pretest risk assessment. Low-risk patients should receive only expectant management, intermediate-risk patients should be referred for noninvasive testing, and high-risk patients should undergo invasive cardiac catheterization.3 To date, noninvasive tests have performed this evaluation by taking either an anatomic approach such as computed tomographic (CT) angiography to identify obstructive CAD or a functional approach to determine ischemia by perfusion or wall motion function via a variety of stress and imaging modes. Therefore, technologies that provide both a highly sensitive anatomic evaluation for obstructive disease and a highly specific physiologic evaluation for ischemia represent the “holy grail” for noninvasive imaging for CAD.

It is with this background that Min et al4 report the findings of the DeFACTO study in this issue of JAMA evaluating CT angiography with a novel noninvasive FFR computed from CT (FFRCT) compared with the reference standard of invasive FFR determined by conventional coronary angiography. The investigators performed a multicenter (17 centers in 5 countries) diagnostic performance study involving 288 stable patients with known or suspected CAD, of whom 252 patients had evaluable images that were compared with invasive FFR. The study's prespecified aim was to determine if FFRCT plus CT could improve the per-patient diagnostic accuracy such that the lower boundary of the 95% confidence interval exceeded 70%. The investigators went to great lengths to ensure blinding, such as using core laboratories for CT angiography evaluation, FFRCT evaluation, and invasive coronary angiography as well as an integration core laboratory that helped register the images and identify locations for FFRCT vs reference FFR analysis.

The investigators report that 137 patients (54.4%) had an abnormal FFR based on invasive angiography. In the per-patient analysis, FFRCT had an accuracy of 73% (95% CI, 67%-78%) arising from a sensitivity of 90% (95% CI, 84%-95%) and specificity of 54% (95% CI, 46%-83%). However, this level of diagnostic accuracy did not meet the prespecified primary end point because the lower bound of the 95% CI for accuracy was 67%. For lesions of 50% or greater, CT angiography had an accuracy of 64% (95% CI, 58%-70%) with a sensitivity of 84% (95% CI, 77%-90%) and a specificity of 42% (95% CI, 34%-51%). The investigators rightly conclude that FFRCT plus CT was associated with improved diagnostic accuracy and discrimination compared with CT angiography alone.

This well-conducted multicenter study provides important data about the performance both of FFRCT plus CT and CT angiography. Additionally, beyond the sheer novelty of the FFRCT technology, the investigators raise the bar by comparing this diagnostic technology with a reference standard of both invasive angiography and invasive FFR. This change in reference standard may in part explain some of the accuracy findings. So how should these findings be considered with regard to current clinical evaluation for chest pain?

First, the findings on the performance of CT angiography should be put in context. Several recent multicenter studies have reported diagnostic performance of CT angiography to have high sensitivity (ie, between 85%-95%) compared with conventional invasive angiography for stenoses of 50% or greater.5,6 The high sensitivity of CT angiography for anatomic stenosis has been used to triage low-risk patients in acute settings such as the emergency department,7,8 where currently the technology may be most used. However, in stable intermediate-risk patients, for whom a higher degree of specificity (low rate of false-positive results) may be desirable to reduce referrals for invasive angiography, concerns exist about the specificity of CT angiography. In the current study, with the more rigorous reference standard, CT angiography had a sensitivity of 84% but a specificity of only 42%.

It is in this context that FFRCT represents a novel and important innovation, with the possibility not only to diagnose but also to help direct invasive treatment. Initial reports found FFRCT to have a sensitivity of 88% and a specificity of 82% compared with the invasive FFR reference standard.9 However, the current larger multicenter report by Min et al4 confirms a high sensitivity (90%) but demonstrates modest specificity (54%), albeit better than CTA alone.

At first glance, readers of the study may consider FFRCT technology to be limited based on the results presented. However, this would be a naive conclusion, likely based on the published diagnostic performance of noninvasive tests compared only with invasive angiography. If the existing noninvasive imaging technologies were compared with invasive angiography plus FFR, it is highly likely that the published diagnostic performance would be reduced. In fact, in clinical practice, the sole use of invasive angiography for lesion evaluation has decreased. Additionally, in real-world practice, the current noninvasive technologies used for diagnosis and risk stratification in stable elective patients prior to invasive angiography do not perform at the published diagnostic levels, as evidenced by the low rates of obstructive CAD at elective catheterization.10 Hence, the current report describes an important noninvasive technology that may improve existing care and has the potential to outperform established noninvasive technologies.

Undoubtedly, investigators and innovators will continue to work on improving the FFRCT technology and should continue to evaluate it rigorously. To provide meaningful data, future studies should be aimed at diagnostic strategies involving patients with varying pretest risks, thereby providing information on the incremental benefit from the test. Additionally, important comparison technologies beyond invasive angiography are needed, although improved access techniques and safety of invasive FFR may make it a plausible comparator. In addition to diagnostic performance, other outcomes of interest such as resource utilization and clinical outcomes should be captured. Finally, future studies will need to have local sites rather than core laboratories perform, analyze, and interpret the images to provide a sense of real-world function. It is with these types of continued rigorous studies that noninvasive technologies such as FFRCT plus CT may move the clinical community closer to the holy grail of a high-quality combined anatomic and functional test for detection of CAD that improves efficiency and patient outcomes.

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Article Information

Corresponding Author: Manesh R. Patel, MD, Duke Clinical Research Institute, Duke University Medical Center, 2400 Pratt St, Durham, NC 27710 (manesh.patel@duke.edu).

Published Online: August 26, 2012. doi:10.1001/2012.jama.11383

Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Patel reports consultancy for Bayer, Jansen, Baxter, and Otsuka and grants from Johnson and Johnson and AstraZeneca.

Editorials represent the opinions of the authors and JAMA and not those of the American Medical Association.

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