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Detecting obstructive coronary disease with CT angiography and noninvasive fractional flow reserve.

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 ischemiadriven 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. 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. Lowrisk patients should receive only expectant management, intermediate-risk patients should be referred for noninvasive testing, and high-risk patients should undergo invasive cardiac catheterization. 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 al 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 perpatient 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?