Non-invasive fractional flow reserve (FFR) from anatomic CT angiography.

Posted On 2012-10-24 14:24:46

Standard, invasive fractional flow reserve (FFR) is a physiologic measure of coronary stenosis severity, allowing identification of hemodynamic significant lesions during cardiac catheterization. The recently published ‘FAME 2’ trial has provided evidence that PCI of such lesions is a safe and effective therapeutic approach to obtain symptom relief and to decrease the rate of urgent revascularizations in patients with stable coronary artery disease (1).

Noninvasive coronary computed tomographic angiography (CTA) is a noninvasive anatomic test for diagnosis of coronary stenosis. Typically, lesions with >50% diameter stenosis are defined as ‘significant’, but assessment of hemodynamic significant requires additional stress testing. Recent papers have described noninvasive FFR computed from CT (FFR-CT) as a method for determining the physiologic significance of coronary artery disease. This method is based on computational fluid dynamic applied to the CTA images obtained at rest. (2) Prior clinical papers describe diagnostic accuracy based on per-vessel basis. (3) However, its ability to identify ischemia and clinical value is incompletely understood.

A recent paper in JAMA examines the diagnostic performance of FFR-CT plus CTA for diagnosis of hemodynamically significant coronary stenosis on a per-patient basis. (4) In this multicenter diagnostic performance study, 252 stable patients with suspected or known CAD from 17 centers in 5 countries who underwent CT, invasive coronary angiography (ICA), FFR, and FFR-CT between October 2010 and October 2011 were included. Computed tomography, ICA, FFR, and FFR-CT were interpreted in blinded fashion by independent core laboratories (the core laboratory for the FFR-CT analysis is located with the company HeartFlow Inc.). Accuracy of FFR-CT plus CT for diagnosis of ischemia was compared with an invasive FFR reference standard. Ischemia was defined by an FFR or FFR-CT of 0.80 or less, while anatomically obstructive CAD was defined by a stenosis of 50% or larger on CT and ICA. The primary study outcome assessed whether FFR-CT 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%.

Among the 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 FFR-CT 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), FFR-CT was associated with improved discrimination (AUC, 0.81; 95% CI, 0.75-0.86; P < .001).

The authors point out that the use of noninvasive FFR-CT 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. However, the authors acknowledge that the study did not achieve its pre-specified primary outcome goal for the level of per-patient diagnostic accuracy. Further evaluation will be necessary to define its potential clinical role.

1. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med 2012;367:991-1001. 
2. Serruys PW, Girasis C, Papadopoulou S-L, Onuma Y. Non-invasive fractional flow reserve: scientific basis, methods and perspectives. EuroIntervention 2012;8:511-19.
3. Koo BK, Erglis A, Doh JH, et al. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study. J Am Coll Cardiol 2011;58:1989-97.
4. Min JK, Leipsic J, Pencina MJ, Berman DS, Koo BK, van Mieghem C, Erglis A, Lin FY, Dunning AM, Apruzzese P, Budoff MJ, Cole JH, Jaffer FA, Leon MB, Malpeso J, Mancini GB, Park SJ, Schwartz RS, Shaw LJ, Mauri L. Diagnostic accuracy of fractional flow reserve from anatomic CT angiography. JAMA. 2012 Sep 26;308(12):1237-45.