Effect of smoking on the diagnostic performance of computational fluid dynamics-derived CT-derived fractional flow reserve: a cross-sectional study

Background: Previous studies have suggested that smoking may be associated with coronary microvascular dysfunction (CMD), which could theoretically impact computed tomography (CT)-derived fractional flow reserve (FFRct) reliability, but no direct evidence exists regarding FFRct performance in smoking populations. This study aimed to compare the diagnostic performance of FFRct between smokers and non-smokers using a personalized myocardial volume calibration approach in computational fluid dynamics (CFD) simulations.

Methods: This sub-study of the HBFlows trial included 298 patients (106 smokers and 192 non-smokers) with suspected coronary artery disease (CAD) who underwent coronary CT angiography (CCTA), invasive fractional flow reserve (FFR), and FFRct assessment. Smoking status was determined from lifestyle records. FFRct was calculated using CFD simulations with myocardial volume [measured via three-dimensional (3D) left ventricular segmentation] as a boundary condition, solved via the Newton-Krylov-Schwarz (NKS) method. Diagnostic performance was evaluated using sensitivity, specificity, accuracy, and area under the receiver operating characteristic (ROC) curve (AUC), with invasive FFR as the reference standard.

Results: Smokers had significantly larger myocardial volumes than non-smokers (193.4 vs. 157.9 mL, P<0.01), but no significant differences in FFR (0.85 vs. 0.85, P=0.496) or FFRct (0.86 vs. 0.86, P=0.466) values were observed between groups. FFRct showed strong correlation with invasive FFR in both smokers (r=0.730, P<0.0001) and non-smokers (r=0.726, P<0.0001). Diagnostic performance was comparable: sensitivity (87.50% vs. 90.00%), specificity (89.19% vs. 88.64%), accuracy (88.68% vs. 89.06%), and AUC (0.919 vs. 0.928) for smokers and non-smokers, respectively.

Conclusions: Smokers had significantly larger myocardial volumes than non-smokers, but no significant differences in FFRct values or diagnostic performance were observed between groups. FFRct demonstrates consistent diagnostic accuracy in both smokers and non-smokers, supporting its utility for CAD assessment in smoking populations.