Abstract Background In the Complete Revascularization with Multivessel PCI for Myocardial Infarction (COMPLETE) trial, patients with ST-segment-elevation myocardial infarction (MI) who underwent staged revascularization of non-culprit coronary stenoses experienced fewer major adverse cardiovascular events than those who underwent a culprit-only approach (1). Inclusion was, however, based on angiographic and not physiological criteria. Purpose To analyse, using computational modelling, the physiological significance of non-culprit lesions included in the COMPLETE trial, to compare these against angiographic measures of severity, and investigate interactions between physiology and the benefits of complete revascularization. Methods Angiograms with appropriate digital imaging and communications in medicine (DICOM) data from the COMPLETE trial (n=1327) underwent software-based 3-dimensional (3D) arterial reconstruction and analysis of 3D-quantitative coronary angiography (QCA) and virtual fractional flow reserve (vFFR) using computational fluid dynamics software. Physiological lesion significance was defined as vFFR ≤0.80 and was compared with operators’ visual angiographic analysis, core-laboratory 2D-QCA and 3D-QCA. Results vFFR was computed successfully in 635 patients (710 lesions). The median vFFR was 0.82 (interquartile range 0.73–0.91). 302 patients (48%) had at least one physiologically significant lesion and 333 (52%) had none. 321 (45%) lesions were physiologically significant and 389 (55%) were not. Physiologically significant lesions were angiographically more severe than non-significant lesions according to the operator’s visual angiographic assessment (mean stenosis 80% vs. 75%, P<0.0001), 2D-QCA (69% vs. 59%, p<0.0001), and 3D-QCA (56% vs. 43, P<0.0001). Percentage lesion stenosis was significantly different when measured visually, with 2D-QCA and with 3D-QCA (80% vs 62% vs 49%, P<0.0001). vFFR was weakly correlated with operators’ visual angiographic severity (Figure 1) and 2D-QCA, but more strongly with 3D-QCA (r=-0.21, -0.21, and -0.60, respectively; all p<0.0001). 3D-QCA predicted vFFR significance more accurately than visual and 2D-QCA (concordance 73% vs 49% vs 59%, respectively). There was no statistically significant interaction between physiological lesion significance and any of the trial coprimary or key secondary clinical outcomes, or on an exploratory outcome of ischaemia-driven revascularization without preceding MI (all interactions P>0.30) (Figure 2). Conclusions In this virtual physiological substudy of the COMPLETE trial, 52% of patients lacked any physiologically-significant lesions, 3D-QCA was a better predictor of physiological significance than either 2D-QCA or operator visual analysis, and the benefits of complete revascularization appeared to be independent of physiological lesion significance. Further research is warranted to compare angiography-guided and physiology-guided complete revascularization strategies.Figure 1.Figure 2.
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