Sex Differences in Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve: Lessons From ADVANCE.

Objectives: This study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFR _CT ) according to sex.
Background: Women are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFR _CT improves sex-based patient management decisions compared to CCTA alone is unknown.
Methods: Subjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFR _CT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFR _CT management plans, incidence of ICA demonstrating obstructive CAD (≥50% stenosis) and revascularization rates.
Results: A total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFR _CT . Women were older (age 68 ± 10 years vs. 65 ± 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFR _CT (0.76 ± 0.10 vs. 0.73 ± 0.10; p < 0.0001), and lower likelihood of positive FFR _CT ≤ 0.80 for the same degree stenosis (p < 0.0001). A positive FFR _CT ≤0.80 resulted in equal referral to ICA (n = 510 [54.5%] vs. n = 1,249 [56.5%]; p = 0.31), but more nonobstructive CAD (n = 208 [32.1%] vs. n = 354 [24.5%]; p = 0.0003) and less revascularization (n = 294 [31.4%] vs. n = 800 [36.2%]; p < 0.0001) in women, unless the FFR _CT was ≤0.75 where revascularization rates were similar (n = 253 [41.9%] vs. n = 715 [46.4%]; p = 0.06). Women have a higher V/M ratio (26.17 ± 7.58 mm ³ /g vs. 24.76 ± 7.22 mm ³ /g; p < 0.0001) that is associated with higher FFR _CT independent of degree stenosis (p < 0.001). Predictors of revascularization included stenosis severity, FFR _CT, symptoms, and V/M ratio (p < 0.001) but not female sex (p = 0.284).
Conclusions: FFR _CT differs between the sexes, as women have a higher FFR _CT for the same degree of stenosis. In FFR _CT -positive CAD, women have less obstructive CAD at ICA and less revascularization, which is associated with higher V/M ratio. The findings suggest that CAD and FFR _CT variations by sex need specific interpretation as these differences may affect therapeutic decision making and clinical outcomes. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care [ADVANCE]; NCT02499679).
Competing Interests: Author Disclosures This study was supported by HeartFlow, Inc., Redwood City, California, via individual Clinical Study Agreements with each enrolling institution and with the Duke Clinical Research Institute (DCRI) for Core Laboratory activities and Clinical Event Committee adjudication of adverse events. Dr. Fairbairn is on the Speakers Bureau for Heartflow. Dr. Hurwitz-Koweek is on the Speakers Bureau for Heartflow; and has unrestricted grant funding from Siemens and Heartflow. Dr. Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr. Nieman has received unrestricted institutional research grants from Siemens, Bayer, GE, and HeartFlow. Dr. Bax has received unrestricted research grants from Edwards Lifescience, Medtronic, Boston Scientific, Biotronik, and GE Healthcare; and is on the Speakers Bureau with Abbott. Dr. Pontone is a consultant for GE Healthcare; and has research grants from GE Healthcare and Heartflow. Dr. Raff has received institutional grants from HeartFlow. Dr. Chinnaiyan has received institutional grants from HeartFlow. Dr. Rabbat has received institutional grants from HeartFlow. Dr. Binukrishnan is on the Speakers Bureau for Heartflow. Dr. Rogers is an employee of and has equity in Heartflow. Dr. Berman has received unrestricted research support from Heartflow. Dr. Patel has received grants from HeartFlow, Jansen, Bayer, AstraZeneca, and NHLBI; and has served as a consultant for Jansen, Bayer, AstraZeneca, Genzyme, and Merck. Dr. Douglas has received institutional grants from HeartFlow. Dr. Leipsic is a consultant for and has stock options in Circle CVI and Heartflow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)