DeFACTO: Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography

List of Authors:
James K. Min, MD; Jonathon Leipsic, MD; Michael J. Pencina, PhD; Daniel S. Berman, MD; Bon-Kwon Koo, MD; Carlos van Mieghem, MD; Andrejs Erglis, MD; Fay Y. Lin, MD; Allison M. Dunning, MS; Patricia Apruzzese, MS; Matthew J. Budoff, MD; Jason H. Cole, MD; Farouc A. Jaffer, MD; Martin B. Leon, MD; Jennifer Malpeso, MD8; G.B. John Mancini, MD; Seung-Jung Park, MD, Robert S. Schwartz, MD; Leslee J. Shaw, PhD, Laura Mauri, MD

Coronary CT angiography (CT) is a non-invasive anatomic test for diagnosis of coronary stenosis, but 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 requires an invasive procedure. Non-invasive fractional flow reserve (FFR) computed from CT (FFRCT) is a novel method for determining the physiologic significance of coronary artery disease (CAD), but its ability to identify patients with ischemia has not been adequately examined to date.

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 five countries who underwent CT, invasive coronary angiography (ICA), FFR and FFRCT between October 2010 and October 2011. CT, ICA, FFR and FFRCT were interpreted in blinded fashion by independent core laboratories. Accuracy of FFRCT and CT for diagnosis of ischemia was compared against an invasive FFR reference standard. Ischemia was defined by an FFR or FFRCT < 0.80, while anatomically obstructive CAD was defined by a stenosis > 50% 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 one-sided 95% confidence interval of this estimate exceeded 70%.

Among study participants, 137 (54.4%) had an abnormal FFR. On a per-patient basis, diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of FFRCT were 73% (95% confidence interval [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 to obstructive CAD by CT alone (area under the receiver operating characteristics 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 for comparison].

Although the study did not achieve its pre-specified primary outcome goal for the level of per-patient diagnostic accuracy, use of non-invasive FFRCT plus CT among stable patients with suspected or known CAD was associated with improved diagnostic accuracy and discrimination compared to CT alone for the diagnosis of hemodynamically-significant CAD when FFR determined at the time of ICA served as the reference standard. (Diagnostic Accuracy of Fractional Flow Reserve from Anatomic Computed TOmographic Angiography, or DeFACTO study, number NCT01233518)