Rationale and design of the DeFACTO (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic AngiOgraphy) study

Abstract

Background: Coronary computed tomographic angiography (CTA) allows for noninvasive identification of anatomic coronary artery disease (CAD) severity but does not discriminate whether a stenosis causes ischemia. Computational fluid dynamic techniques applied to CTA images now permit noninvasive computation of fractional flow reserve (FFR), a measure of lesion-specific ischemia, but the diagnostic performance of computed FFR (FFR(CT)) as compared with measured FFR at the time of invasive coronary angiography remains unexplored.

Objective: We determined the diagnostic accuracy of noninvasive FFR(CT) for the detection and exclusion of ischemia-causing stenoses.

Methods: DeFACTO (NCT01233518) is a prospective, international, multicenter study of 238 patients designed to evaluate the diagnostic performance of FFR(CT) for the detection of hemodynamically significant coronary artery stenoses identified by CTA, compared with invasive FFR as a reference standard. FFR values ≤ 0.80 will be considered hemodynamically significant. Patients enrolled in the DeFACTO study will undergo CTA, invasive coronary angiography, and 3-vessel FFR in the left anterior descending artery, left circumflex artery, and right coronary artery distributions. FFR(CT) will be computed with acquired CTA images, without modification to CTA image acquisition protocols and without additional image acquisition. Blinded core laboratory interpretation will be performed for CTA, invasive coronary angiography, FFR, and FFR(CT).

Results: The primary endpoint of the DeFACTO study is the per-patient diagnostic accuracy of FFR(CT) for noninvasive assessment of the hemodynamic significance of CAD, compared with FFR during invasive coronary angiography as a reference standard. The secondary endpoints include additional per-patient as well as per-vessel diagnostic performance characteristics, including sensitivity, specificity, positive predictive value, and negative predictive value.

Conclusion: The DeFACTO study will determine whether the addition of FFR(CT) to conventional CTA improves the diagnosis of hemodynamically significant CAD.