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 mm³/g vs. 24.76 ± 7.22 mm³/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).