Prognostic value of pre-revascularization fractional flow reserve mediated by the post-revascularization level: a causal mediation analysis

Abstract Background The prognostic value of pre-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) can depend on that of the post-PCI FFR and their interaction. To correctly interpret the prognostic value of pre-PCI FFR, it is essential to understand to what extent the relationship between pre-PCI FFR and clinical outcome is explained by pre-PCI FFR-related post-PCI FFR. Purpose The aim of this study is to investigate the extent to which post-PCI FFR mediates the relationship between pre-PCI FFR and vessel-related outcomes using a global, multicenter collaboration registry. Methods Patient data from 4 global FFR registries were pooled and 1488 patients with pre-PCI FFR ≤0.80 were analyzed. The primary outcome was target vessel failure (TVF) during 2-years of follow-up. We evaluated the extent to which post-PCI FFR <0.90 mediated the association between pre-PCI FFR <0.75 and TVF employing a causal mediation analysis in a counterfactual framework. Results Among 1488 patients, the mean (standard deviation) age was 63.5 (9.9) years and 78% (1161 patients) were male. The median (IQR) pre-PCI and post-PCI FFR were 0.71 (0.62–0.76) and 0.88 (0.83–0.92), respectively. The direct effect of low pre-PCI FFR (<0.75) on TVF was significantly elevated (OR: 1.81, 95% CI: 1.03–3.18, p=0.038), and was not mediated by post-PCI FFR<0.90 (indirect effect, OR: 1.01, 95% CI: 0.98–1.05, p=0.39). In the model, post-PCI FFR explained only 2.2% of the association between pre-PCI FFR and TVF. The subgroup analysis implicated that the prognostic information of pre-PCI FFR was mainly for diffuse lesions. Conclusions The prognostic information of pre-PCI FFR did not greatly depend on the results of PCI assessed by post-PCI FFR. Pre-PCI FFR, as a prognostic marker, may mainly reflect the global atherosclerotic burden of the artery, not the extent of the modifiable epicardial stenosis, thus providing independent information from post-PCI FFR. Interpretation Funding Acknowledgement Type of funding source: None