Noninvasive FFR Derived From Coronary CT Angiography: Management and Outcomes in the PROMISE Trial

Abstract

Objectives: The purpose of this study was to determine whether noninvasive fractional flow reserve derived from computed tomography (FFR_CT) predicts coronary revascularization and outcomes and whether its addition improves efficiency of referral to invasive coronary angiography (ICA) after coronary computed tomography angiography (CTA).

Background: FFR_CT may improve the efficiency of an anatomic CTA strategy for stable chest pain.

Methods: This observational cohort study included patients with stable chest pain in the PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain) trial referred to ICA within 90 days after CTA. FFR_CT was measured at a blinded core laboratory, and FFR_CT results were unavailable to caregivers. We determined the agreement of FFR_CT (positive if ≤0.80) with stenosis on CTA and ICA (positive if ≥50% left main or ≥70% other coronary artery), and predictive value for a composite of coronary revascularization or major adverse cardiac events (death, myocardial infarction, or unstable angina). We retrospectively assessed whether adding FFR_CT ≤0.80 as a gatekeeper could improve efficiency of referral to ICA, defined as decreased rate of ICA without ≥50% stenosis and increased ICA leading to revascularization.

Results: FFR_CT was calculated in 67% (181 of 271) of eligible patients (mean age 62 years; 36% women). FFR_CT was discordant with stenosis in 31% (57 of 181) for CTA and 29% (52 of 181) for ICA. Most patients undergoing coronary revascularization had an FFR_CT of ≤0.80 (91%; 80 of 88). An FFR_CT of ≤0.80 was a significantly better predictor for revascularization or major adverse cardiac events than severe CTA stenosis (HR: 4.3 [95% confidence interval [CI]: 2.4 to 8.9] vs. 2.9 [95% CI: 1.8 to 5.1]; p = 0.033). Reserving ICA for patients with an FFR_CT of ≤0.80 could decrease ICA without ≥50% stenosis by 44%, and increase the proportion of ICA leading to revascularization by 24%.

Conclusions: In this hypothesis-generating study of patients with stable chest pain referred to ICA from CTA, an FFR_CT of ≤0.80 was a better predictor of revascularization or major adverse cardiac events than severe stenosis on CTA. Adding FFR_CT may improve efficiency of referral to ICA from CTA alone.

Keywords: computational fluid dynamics; coronary angiography; coronary artery disease; coronary computed tomography angiography; fractional flow reserve.

Figure 1. Flow Diagram

The analytic population included 181 subjects who had CTA, ICA, and FFR_CT.

Figure 2. Representative CTA, FFR_CT, and ICA

The first patient (A–C) was referred to ICA based on (A) CTA moderate stenosis in the left circumflex (white arrow). Severe stenosis in an obtuse marginal (red arrow) was missed by the CT reader, but detected by (B) FFR_CT of 0.76 and confirmed on (C) ICA showing severe stenosis, with subsequent PCI. Circumflex stenosis (white arrow) was mild and not revascularized. The second patient (D–F) was referred to ICA for (D) severe mid left anterior descending stenoses on CTA (red arrows). (E) FFR_CT of 0.83 suggests no hemodynamically significant stenosis; (F) ICA demonstrated mild stenosis that was not revascularized.

Figure 3. Box and Whisker Plots of Per-Patient FFR_CT by Categories of (A) CTA and (B) ICA Stenosis

The horizontal line corresponds to the FFR_CT threshold for a positive test (FFR_CT ≤0.80). FFR_CT decreased with increasing degrees of stenosis on CTA and ICA (both p<0.001).