Diagnostic Accuracy of Fractional Flow Reserve From Anatomic CT Angiography

TitleDiagnostic Accuracy of Fractional Flow Reserve From Anatomic CT Angiography
Publication TypeJournal Article
Year of Publication2012
AuthorsMin, JK, Leipsic, J, Pencina, MJ, Berman, DS, Koo, B-W, van Mieghem, C, Erglis, A, Lin, FY, Dunning, AM, Apruzzese, P, Budoff, MJ, Cole, JH, Jaffer, FA, Leon, MB, Malpeso, J, Mancini, GBJ, Park, S-J, Schwartz, RS, Shaw, LJ, Mauri, L
Start Page1237-1245

Context Coronary computed tomographic (CT) angiography is a noninvasive anatomic test for diagnosis of coronary stenosis that does not determine whether a stenosis causes ischemia. In contrast, fractional flow reserve (FFR) is a physiologic measure of coronary stenosis expressing the amount of coronary flow still attainable despite the presence of a stenosis, but it requires an invasive procedure. Noninvasive FFR computed from CT (FFRCT) is a novel method for determining the physiologic significance of coronary artery disease (CAD), but its ability to identify ischemia has not been adequately examined to date.

Objective To assess the diagnostic performance of FFRCT plus CT for diagnosis of hemodynamically significant coronary stenosis.

Design, Setting, and Patients Multicenter diagnostic performance study involving 252 stable patients with suspected or known CAD from 17 centers in 5 countries who underwent CT, invasive coronary angiography (ICA), FFR, and FFRCT between October 2010 and October 2011. Computed tomography, ICA, FFR, and FFRCT were interpreted in blinded fashion by independent core laboratories. Accuracy of FFRCT plus CT for diagnosis of ischemia was compared with an invasive FFR reference standard. Ischemia was defined by an FFR or FFRCT of 0.80 or less, while anatomically obstructive CAD was defined by a stenosis of 50% or larger on CT and ICA.

Main Outcome Measures The primary study outcome assessed whether FFRCT plus CT could improve the per-patient diagnostic accuracy such that the lower boundary of the 1-sided 95% confidence interval of this estimate exceeded 70%.

Results Among study participants, 137 (54.4%) had an abnormal FFR determined by ICA. On a per-patient basis, diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFRCT plus CT were 73% (95% CI, 67%-78%), 90% (95% CI, 84%-95%), 54% (95% CI, 46%-83%), 67% (95% CI, 60%-74%), and 84% (95% CI, 74%-90%), respectively. Compared with obstructive CAD diagnosed by CT alone (area under the receiver operating characteristic curve [AUC], 0.68; 95% CI, 0.62-0.74), FFRCT was associated with improved discrimination (AUC, 0.81; 95% CI, 0.75-0.86; P < .001).

Conclusion Although the study did not achieve its prespecified primary outcome goal for the level of per-patient diagnostic accuracy, use of noninvasive FFRCT plus CT among stable patients with suspected or known CAD was associated with improved diagnostic accuracy and discrimination vs CT alone for the diagnosis of hemodynamically significant CAD when FFR determined at the time of ICA was the reference standard.


Coronary computed tomographic (CT) angiography is a noninvasive test that enables direct visualization of coronary artery disease (CAD) and correlates favorably with invasive coronary angiography (ICA) for measures of stenosis severity.1 However, CT cannot determine the hemodynamic significance of CAD, and even among CT-identified obstructive stenoses confirmed by ICA, fewer than half are ischemia-causing.2,3 These findings underscore an unreliable relationship of stenosis severity to ischemia and have raised concerns that use of CT may precipitate unnecessary ICA and coronary revascularization for patients who do not have ischemia.4,5

These concerns stem from recent randomized trials that have identified no survival benefit for patients who undergo angiographically based coronary revascularization.6,7 As an adjunct to ICA, fractional flow reserve (FFR) has served as a useful tool to determine the likelihood that a coronary stenosis hinders the delivery of oxygen to the heart muscle or causes myocardial ischemia. As the currently accepted reference standard for determining lesion-specific ischemia, FFR is an invasive procedure performed at the time of ICA and represents the ratio of the mean coronary pressure distal to a coronary stenosis to the mean aortic pressure during maximal coronary blood flow.8 This ratio expresses the coronary flow still attainable despite the presence of a coronary stenosis. The addition of physiologic measures of coronary flow by FFR to anatomic-based assessment of stenosis severity by ICA to guide decisions of coronary revascularization improves event-free survival in a manner that is long-lived and cost-effective.911 To date, however, this integrated anatomic-physiologic approach has not been available through noninvasive methods.

Noninvasive calculation of FFR from CT (FFRCT) is a novel method that applies computational fluid dynamics to determine the physiologic significance of CAD.12 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.13 In this multicenter international study, we evaluated the performance of noninvasive FFRCT compared with an invasive FFR reference standard for diagnosis of ischemia.