Reproducibility of quantitative flow ratio: An inter-core laboratory variability study

Background: Quantitative flow ratio (QFR) is a novel approach to derive fractional flow reserve (FFR) from coronary angiography. This study sought to evaluate the reproducibility of QFR when analyzed in independent core laboratories. Methods: All interrogated vessels in the FAVOR II China Study were separately analyzed using the AngioPlus system (Pulse medical imaging technology, Shanghai) by two independent core laboratories, following the same standard operation procedures. The analysts were blinded to the FFR values and online QFR values. For each interrogated vessel, two identical angiographic image runs were used by two core laboratories for QFR computation. In both core laboratories QFR was successfully obtained in 330 of 332 vessels, in which FFR was available in 328 vessels. Thus, 328 vessels ended in the present statistical analysis. Results: The mean difference in contrast-flow QFR between the two core laboratories was 0.004 ± 0.03 (p = 0.040), which was slightly smaller than that between the online analysis and the two core laboratories (0.01 ± 0.05, p < 0.001 and 0.01 ± 0.05, p = 0.038). The mean difference of QFR with re­spect to FFR were comparable between the two core laboratories (0.002 ± 0.06, p = 0.609, and 0.002 ± 0.06, p = 0.531). Receiver operating characteristic curve analysis showed that diagnostic accuracies of QFR analyzed by the two core laboratories were both excellent (area under the curve: 0.970 vs. 0.963, p = 0.142), when using FFR as the reference standard. Conclusions: The present study showed good inter-core laboratory reproducibility of QFR in assessing functionally-significant stenosis. It suggests that QFR analyses can be carried out in different core labo­ratories if, and only if, highly standardized conditions are maintained

Diagnostic accuracy and reproducibility of optical flow ratio for functional evaluation of coronary stenosis in a prospective series

Background: Evaluating prospectively the feasibility, accuracy and reproducibility of optical flow ratio (OFR), a novel method of computational physiology based on optical coherence tomography (OCT).Methods and results: Sixty consecutive patients (76 vessels) underwent prospectively OCT, angiography- based quantitative flow ratio (QFR) and fractional flow ratio (FFR). OFR was computed offline in a central core-lab by analysts blinded to FFR. OFR was feasible in 98.7% of the lesions and showed excellent agreement with FFR (ICCa = 0.83, r = 0.83, slope = 0.80, intercept = 0.17, kappa = 0.84). The area under curve to predict an FFR ≤ 0.80 was 0.95, higher than for QFR (0.91, p = 0.115) and for minimal lumen area (0.64, p < 0.001). Diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 93%, 92%, 93%, 88%, 96%, 13.8, 0.1, respectively. Median time to obtain OFR was 1.07 (IQR: 0.98–1.16) min, with excellent intraobserver and interobserver reproducibility (0.97 and 0.95, respectively). Pullback speed had negligible impact on OFR, provided the same coronary segment were imaged (ICCa = 0.90, kappa = 0.697).Conclusions: The prospective computation of OFR is feasible and reproducible in a real-world series,resulting in excellent agreement with FFR, superior to other image-based methods

Optimal diagnostic approach for using CT-derived quantitative flow ratio in patients with stenosis on coronary computed tomography angiography

Background: Coronary computed tomography angiography (CCTA)-derived quantitative flow ratio (CT-QFR) is an on-site non-invasive technique estimating invasive fractional flow reserve (FFR). This study assesses the diagnostic performance of using most distal CT-QFR versus lesion-specific CT-QFR approach for identifying hemodynamically obstructive coronary artery disease (CAD).Methods: Prospectively enrolled de novo chest pain patients (n ​= ​445) with ≥50 ​% visual diameter stenosis on CCTA were referred for invasive evaluation. On-site CT-QFR was analyzed post-hoc blinded to angiographic data and obtained as both most distal (MD-QFR) and lesion-specific CT-QFR (LS-QFR). Abnormal CT-QFR was defined as ≤0.80. Hemodynamically obstructive CAD was defined as invasive FFR ≤0.80 or ≥70 ​% diameter stenosis by 3D-quantitative coronary angiography.Results: In total 404/445 patients had paired CT-QFR and invasive analyses of whom 149/404 (37 ​%) had hemodynamically obstructive CAD. MD-QFR and LS-QFR classified 188 (47 ​%) and 165 (41 ​%) patients as abnormal, respectively. Areas under the receiver-operating characteristic curve for MD-QFR was 0.83 vs. 0.85 for LS-QFR, p ​= ​0.01. Sensitivities for MD-QFR and LS-QFR were 80 ​% (95%CI: 73-86) vs. 77 ​% (95%CI: 69-83), p ​= ​0.03, respectively, and specificities were 73 ​% (95%CI: 67-78) vs. 80 ​% (95%CI: 75-85), p ​< ​0.01, respectively. Positive predictive values for MD-QFR and LS-QFR were 63 ​% vs. 69 ​%, p ​< ​0.01, respectively, and negative predictive values for MD-QFR and LS-QFR were 86 ​% vs. 85 ​%, p ​= ​0.39, respectively).Conclusion: Using a lesion-specific CT-QFR approach has superior discrimination of hemodynamically obstructive CAD compared to a most distal CT-QFR approach. CT-QFR identified most cases of hemodynamically obstructive CAD while a normal CT-QFR excluded hemodynamically obstructive CAD in the majority of patients

Angiography-based superficial wall strain of de novo stenotic coronary arteries:serial assessment of vessels treated with bioresorbable scaffold or drug-eluting stent

Objectives: This study sought to present an angiography-based computational model for serial assessment of superficial wall strain (SWS, dimensionless) of de-novo coronary stenoses treated with either bioresorbable scaffold (BRS) or drug-eluting stent (DES). Background: A novel method for SWS allows the assessment of the mechanical status of arteries in-vivo, which may help for predicting cardiovascular outcomes. Methods: Patients with arterial stenosis treated with BRS (n = 21) or DES (n = 21) were included from ABSORB Cohort B1 and AIDA trials. The SWS analyses were performed along with quantitative coronary angiography (QCA) at pre-PCI, post-PCI, and 5-year follow-up. Measurements of QCA and SWS parameters were quantified at the treated segment and adjacent 5-mm proximal and distal edges. Results: Before PCI, the peak SWS on the ‘to be treated’ segment (0.79 ± 0.36) was significantly higher than at both virtual edges (0.44 ± 0.14 and 0.45 ± 0.21; both p &lt; 0.001). The peak SWS in the treated segment significantly decreased by 0.44 ± 0.13 (p &lt; 0.001). The surface area of high SWS decreased from 69.97mm2 to 40.08mm2 (p = 0.002). The peak SWS in BRS group decreased to a similar extent (p = 0.775) from 0.81 ± 0.36 to 0.41 ± 0.14 (p &lt; 0.001), compared with DES group from 0.77 ± 0.39 to 0.47 ± 0.13 (p = 0.001). Relocation of high SWS to device edges was often observed in both groups after PCI (35 of 82 cases, 41.7 %). At follow-up of BRS, the peak SWS remained unchanged compared to post-PCI (0.40 ± 0.12 versus 0.36 ± 0.09, p = 0.319). Conclusion: Angiography-based SWS provided valuable information about the mechanical status of coronary arteries. Device implantation led to a significant decrease of SWS to a similar extent with either polymer-based scaffolds or permanent metallic stents.</p

Novel computational functional assessment of coronary stenosis and its clinical applications in predicting and evaluating procedural results

Coronary angiography has limited efficacy in identifying patients with suboptimal results after percutaneous coronary intervention (PCI). Immediate post-procedural functional assessment, including fractional flow reserve (FFR), is emerging as an effective tool for this purpose whereas with limited clinical adoption. Image-based computational FFR has been recently developed as an alternative without the need for costly pressure wire or hyperaemia-inducing medications. This thesis investigated the utility of image-based computational FFR assessment in predicting and evaluating the physiological efficacy of PCI. In the first part of the thesis, the relationship between post-PCI wire-based FFR and clinical outcomes was investigated using a systematic review and study-level meta analysis, pooling 12340 patients and 12923 vessels from 62 studies. Mean post-PCI FFR was not continuously associated with 1-year major adverse cardiac events (MACE) including all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR). Still, risk ratio favoured high post-PCI FFR for reduced MACE, all-cause death, MI, TVR and better angina status under different cut-offs. The second part of the thesis focused on the utility of image-based FFR in post-PCI settings. The feasibility and accuracy of an optical coherence tomography (OCT)- based optical flow ratio (OFR) in predicting post-PCI FFR was evaluated. Post-PCI OFR was computed in 125 pullbacks from 119 patients with both OCT and FFR interrogation immediately after PCI. After eliminating the stenotic segment by virtual stenting, simulated residual OFR from pre-PCI OCT images was computed in 64 patients who had pre-PCI OCT. The accuracy in predicting post-PCI FFR ≤0.90 was 84% for post-PCI OFR and 80% for simulated residual OFR. Stent minimum expansion index was associated with in-stent pressure drop (r = -0.49, p<0.001). To overcome the restrictions of limited OCT pullback length, OFR was further incorporated with Murray law-based quantitative flow ratio (μQFR), a computational FFR from a single angiographic view, for a comprehensive physiological assessment of the entire interrogated vessel. The feasibility and accuracy of this OCT-modulated μQFR (OCT-μQFR) was validated in two datasets. Firstly, the diagnostic accuracy of single-view μQFR and two-view-based 3D-μQFR were compared in 280 vessels with two protocol-specified recommended angiographic views. μQFR computed from either angiographic view had similar diagnostic accuracy as compared with 3D-μQFR (92.1%, 92.5%, and 93.2%, respectively). μQFR from either angiographic view had excellent correlation (r = 0.95) and agreement (mean difference = 0.00 ± 0.03). Secondarily, the accuracy of OCT-μQFR as compared with μQFR was evaluated in 269 vessels with paired angiography, OCT, and FFR measurements. OCT-μQFR showed numerically higher diagnostic performance compared with μQFR (AUC = 0.95 versus 0.92, p = 0.057). The utility of OCT-μQFR for predicting physiological PCI efficacy was further investigated in 76 vessels from 74 patients undergoing OCT-guided PCI. Simulated residual OCT-μQFR was computed from pre-PCI co-registered angiography and OCT, by assuming full stent expansion to the intended-to-treat segment. Post-PCI OCT μQFR was computed from co-registered post-PCI angiography and OCT. Using actual post-PCI OCT-μQFR as reference, simulated residual OCT-μQFR showed good correlation (r = 0.80, p<0.001), agreement (mean difference = -0.02 ± 0.02, p<0.001) and diagnostic concordance (79%, using ≤0.90 for defining suboptimal functional stenting result). Post-PCI in-stent OCT-μQFR had a median value of 0.02 and was associated with LAD lesion location, higher baseline total plaque burden and fibrous plaque volume. To conclude, post-PCI wire-based FFR as a dichotomous variable was associated with clinical outcomes. Image-based computational FFR assessed immediately after PCI was feasible and accurate using FFR as reference. Estimating post-PCI physiology from baseline coronary images by virtual stenting was feasible and showed good concordance with post-PCI physiology. This thesis emphasized the potential application of image-based computational FFR in facilitating the achievement of optimal physiological efficacy of PCI

Diagnostic accuracy of intracoronary optical coherence tomography-derived fractional flow reserve for assessment of coronary stenosis severity

Aims: A novel method for computation of fractional flow reserve (FFR) from optical coherence tomography (OCT)was development recently. This study aimed to evaluate the diagnostic accuracy of a new OCT-based FFR (OFR) computational approach, using wire-based FFR as the reference standard.Methods and results: Patients who underwent both OCT and FFR prior to intervention were analysed. The lumen of the interrogated vessel and the ostia of the side branches were automatically delineated and used to compute OFR. Bifurcation fractal laws were applied to correct the change in reference lumen size due to the step-down phenomenon. OFR was compared with FFR, both using a cut-off value of 0.80 to define ischaemia. Computational analysis was performed in 125 vessels from 118 patients. Average FFR was 0.80 +/- 0.09. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for OFR to identify FF

Quantitative flow ratio-guided strategy versus angiography-guided strategy for percutaneous coronary intervention: Rationale and design of the FAVOR III China trial.

BACKGROUND Quantitative flow ratio (QFR) is a novel angiography-based approach enabling fast computation of fractional flow reserve without use of pressure wire or adenosine. The objective of this investigator-initiated, multicenter, patient- and clinical assessor-blinded randomized trial is to evaluate the efficacy and cost-effectiveness of a QFR-augmented angiography-guided (QFR-guided) strategy versus an angiography-only guided (angiography-guided) strategy for percutaneous coronary intervention (PCI) in patients with coronary artery disease. METHODS Approximately 3,830 patients will be randomized in a 1:1 ratio to a QFR-guided or an angiography-guided strategy. Included subjects scheduled for coronary angiography have at least 1 lesion eligible for PCI with 50%-90% stenosis in an artery with ≥2.5 mm reference diameter. Subjects assigned to the QFR-guided strategy will have QFR measured in each interrogated vessel and undergo PCI when QFR ≤0.80, with deferral for lesions with QFR >0.80. Those assigned to the angiography-guided strategy will undergo PCI based on angiography. Optimal medical therapy will be administered to all treated and deferred patients. The primary end point is the 1-year rate of major adverse cardiac events (MACE), a composite of all-cause mortality, any myocardial infarction, or any ischemia-driven revascularization. The major secondary end point is 1-year MACE excluding periprocedural myocardial infarction. Other secondary end points include the individual components of MACE and cost-effectiveness end points. The sample size affords 85% power to demonstrate superiority of QFR guidance compared with angiography guidance. CONCLUSIONS The FAVOR III China study will be the first randomized trial to examine the effectiveness and cost-effectiveness of a QFR-guided versus an angiography-guided PCI strategy in coronary artery disease patients