Response to Letter Regarding Article, “Noninvasive Fractional Flow Reserve Derived From Computed Tomography Angiography for Coronary Lesions of Intermediate Stenosis Severity: Results From the DeFACTO Study”

Response:

We thank Mao et al¹ for their thoughtful letter and their interest in our prospective, multicenter study demonstrating the high diagnostic performance of fractional flow reserve derived from computed tomography (FFR_CT) to identify and exclude lesion-specific ischemia in intermediate stenosis.² Dr Mao et al¹ expressed 3 concerns with our study, which we address herein. First, Mao et al¹ assert that “the elasticity of arterial wall may greatly impact on the cardiac perfusion pressure in vivo, which was improperly neglected in the computation of FFR_CT.” Although the latter of these statements is true, the former is simply not. FFR_CT—similar to FFR itself—is a time-averaged quantity, and thus, arterial wall elasticity has negligible effects on the diagnostic performance of FFR_CT.

Second, for lesions of intermediate stenosis severity, which impart a non-negligible yet generally low rate of ischemia, a major goal of the diagnostic workup of patients with suspected ischemic heart disease is to effectively exclude patients who have ischemia-causing lesions. In the present study, the ability for FFR_CT—a diagnostically robust calculation that is less susceptible to CT artifacts than the CT stenosis alone³—to effectively exclude lesions that caused ischemia approached 100%. Indeed, these results remained consistent in a subsequent prospective, multicenter study of FFR_CT for lesions of intermediate stenosis severity, which demonstrated an overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 80%, 85%, 79%, 63%, and 92%, respectively.⁴ Importantly, lesion-specific ischemia of intermediate stenoses has not yet been evaluated for other noninvasive imaging tests to date.

Third, Mao et al¹ refer to a recent small, single-center, retrospective study of virtual FFR derived from 2-dimensional invasive coronary angiograms. The calculation of FFR from an invasive angiogram mitigates one major advantage of noninvasive FFR_CT. Beyond possessing high diagnostic performance for the identification of lesions that cause ischemia, a principal benefit of FFR_CT is to reduce unnecessary invasive procedures for patients without lesions that cause ischemia, a concept simply not achievable for any calculation that relies on the invasive procedure that noninvasive FFR_CT can effectively prevent.