Non-invasive fractional flow reserve estimation in coronary arteries using angiographic images.

Coronary artery disease is the leading global cause of mortality and Fractional Flow Reserve (FFR) is widely regarded as the gold standard for assessing coronary artery stenosis severity. However, due to the limitations of invasive FFR measurements, there is a pressing need for a highly accurate virtual FFR calculation framework. Additionally, it's essential to consider local haemodynamic factors such as time-averaged wall shear stress (TAWSS), which play a critical role in advancement of atherosclerosis. This study introduces an innovative FFR computation method that involves creating five patient-specific geometries from two-dimensional coronary angiography images and conducting numerical simulations using computational fluid dynamics with a three-element Windkessel model boundary condition at the outlet to predict haemodynamic distribution. Furthermore, four distinct boundary condition methodologies are applied to each geometry for comprehensive analysis. Several haemodynamic features, including velocity, pressure, TAWSS, and oscillatory shear index are investigated and compared for each case. Results show that models with average boundary conditions can predict FFR values accurately and observed errors between invasive FFR and virtual FFR are found to be less than 5%.

Evaluation of models of sequestration flow in coronary arteries-Physiology versus anatomy?

BACKGROUND: Myocardial ischaemia results from insufficient coronary blood flow. Computed virtual fractional flow reserve (vFFR) allows quantification of proportional flow loss without the need for invasive pressure-wire testing. In the current study, we describe a novel, conductivity model of side branch flow, referred to as 'leak'. This leak model is a function of taper and local pressure, the latter of which may change radically when focal disease is present. This builds upon previous techniques, which either ignore side branch flow, or rely purely on anatomical factors. This study aimed to describe a new, conductivity model of side branch flow and compare this with established anatomical models. METHODS AND RESULTS: The novel technique was used to quantify vFFR, distal absolute flow (Qd) and microvascular resistance (CMVR) in 325 idealised 1D models of coronary arteries, modelled from invasive clinical data. Outputs were compared to an established anatomical model of flow. The conductivity model correlated and agreed with the reference model for vFFR (r = 0.895, p < 0.0001; ＋0.02, 95% CI 0.00 to ＋ 0.22), Qd (r = 0.959, p < 0.0001; -5.2 mL/min, 95% CI -52.2 to ＋13.0) and CMVR (r = 0.624, p < 0.0001; ＋50 Woods Units, 95% CI -325 to ＋2549). CONCLUSION: Agreement between the two techniques was closest for vFFR, with greater proportional differences seen for Qd and CMVR. The conductivity function assumes vessel taper was optimised for the healthy state and that CMVR was not affected by local disease. The latter may be addressed with further refinement of the technique or inferred from complementary image data. The conductivity technique may represent a refinement of current techniques for modelling coronary side-branch flow. Further work is needed to validate the technique against invasive clinical data.

Prognostic Value of Post-PCI Angiography-Derived Fractional Flow Reserve: A Systematic Review and Meta-Analysis of Cohort Studies.

The post-percutaneous coronary intervention (post-PCI) fractional flow reserve (FFR) can detect suboptimal PCI or residual ischemia and potentially lead to fewer adverse clinical outcomes. We sought to investigate the predictive value of the angiography-derived FFR for adverse cardiovascular events in patients after PCI. We conducted a comprehensive search of electronic databases, MEDLINE, EMBASE, and the Cochrane Library, for studies published until March 2023 that investigated the prognostic role of angiography-derived fractional flow reserve values after PCI. We investigated the best predictive ability of the post-PCI angiography-derived FFR and relative risk (RR) estimates with 95% confidence intervals (CIs) between post-PCI angiography-derived FFR values and adverse events. Thirteen cohort studies involving 6961 patients (9719 vascular lesions; mean follow-up: 2.2 years) were included in this meta-analysis. The pooled HR of the studies using specific cut-off points for post-PCI angiography-derived FFR was 4.13 (95% CI, 2.92-5.82) for total cardiovascular events, while the pooled HRs for target vessel revascularization, cardiac death, target vessel myocardial infarction, and target lesion revascularization were 6.87 (95% CI, 4.93-9.56), 6.17 (95% CI, 3.52-10.80), 3.98 (95% CI, 2.37-6.66) and 6.27 (95% CI, 3.08-12.79), respectively. In a sensitivity analysis of three studies with 1789 patients assessing the predictive role of the post-PCI angiography-derived FFR as a continuous variable, we found a 58% risk reduction for future adverse events per 0.1 increase in the post-PCI angiography-derived FFR value. In conclusion, post-PCI angiography-derived FFR is an effective tool for predicting adverse cardiovascular events and could be potentially used in decision making, both during PCI and in the long-term follow-up.

Coronary Angiography Upgraded by Imaging Post-Processing: Present and Future Directions.

Advances in computer technology and image processing now allow us to obtain from angiographic images a large variety of information on coronary physiology without the use of a guide-wire as a diagnostic information equivalent to FFR and iFR but also information allowing for the performance of a real virtual percutaneous coronary intervention (PCI) and finally the ability to obtain information to optimize the results of PCI. With specific software, it is now possible to have a real upgrading of invasive coronary angiography. In this review, we present the different advances in this field and discuss the future perspectives offered by this technology.

Association Between 3D-Angiography Based Fractional Flow Reserve and Non-Invasive Myocardial Ischemia Testing: The FAST ISCHEMIA Study.

BACKGROUND: In order to facilitate fractional flow reserve (FFR)-guided lesion assessment, several 3-dimensional (3D)-angiography-based physiological indices have been recently validated. Thus far, limited data are available on the association of these indices with conventional forms of ischemia testing. AIM: The aim of the study was to determine the association between 3D-angiography-based vessel-FFR (vFFR) and myocardial ischemia as assessed by exercise electrocardiography (ECG) testing, dobutamine stress echocardiography, single photon emission computed tomography myocardial perfusion imaging (SPECTMPI), and stress cardiovascular magnetic resonance imaging (stress CMR). METHODS: FAST ISCHEMIA is a retrospective, single-center cohort study including patients who underwent non-invasive myocardial ischemia testing and subsequent coronary angiography (≤3 months). A total of 145 patients (340 vessels) were analyzed. The overall patient-based sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of vFFR ≤0.80 in any vessel for ischemia was 64% (95% confidence interval [CI], 53-74), 71% (95% CI, 54-84), 83% (95% CI, 72-91), 46% (95% CI, 33-60), 2.16 (95% CI, 1.25-3.74), and 0.52 (95% CI, 0.36-0.74), respectively. Multivariable logistic regression showed that vFFR ≤0.80 was significantly associated with ischemia on a patient level (odds ratio, 8.13; 95% CI, 2.51-30.06; P<.001) and on a vascular territory level (odds ratio, 2.75; 95% CI, 1.17-6.44; P<.01). CONCLUSION: Our study suggests that vFFR ≤0.80 has a modest association with non-invasive myocardial ischemia testing using either exercise ECG or stress imaging modalities. After correcting for independent confounders, vFFR was independently associated with ischemia on a non-invasive myocardial ischemia detection test.

Correlation of 3D Quantitative Coronary-Angiography Based Vessel FFR With Diastolic Pressure Ratio: A Single-Center Pooled Analysis of the FAST EXTEND and FAST II Studies.

BACKGROUND: Vessel fractional flow reserve (vFFR) has a high diagnostic accuracy in assessing functional lesion significance compared with FFR. Nonhyperemic pressure ratios (NHPRs) were noninferior to FFR to guide revascularization of intermediate lesions. Therefore, the diagnostic performance of vFFR compared with NHPR warrants interest. AIM: To evaluate the diagnostic performance of vFFR with a generic diastolic pressure ratio (dPR) as a reference. METHODS: The study population was derived from the FAST EXTEND and FAST II studies. Between January 2016 and September 2020, a total of 475 patients were enrolled. RESULTS: Median dPR was 0.92 (interquartile range [IQR], 0.87-0.95), median vFFR was 0.86 (IQR, 0.80-0.90). The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of vFFR ≤0.80 for dPR ≤0.89 were 66%, 92%, 79%, 85%, and 84%, respectively. Vessel FFR showed a good agreement with dPR (r=0.68), consistent among specific clinical lesion subsets and a high diagnostic accuracy for dPR ≤0.89 (area under the curve=0.89). Discordance between vFFR and dPR was observed in 78/492 cases (15.6%) and logistic regression analysis did not reveal any clinical, angiographic, or hemodynamic variables associated with vFFR and dPR discordance. CONCLUSION: Vessel FFR shows a good agreement with dPR and a high diagnostic accuracy for dPR ≤0.89.

Case Report: Invasive and Non-invasive Hemodynamic Assessment of Coronary Artery Disease: Strengths and Weaknesses.

Coronary angiography has been the gold standard for assessment of coronary artery disease (CAD) and guidance for percutaneous coronary interventions (PCI). Physiology-guided PCI has shown increased safety and efficacy, improved resource utilization, and better clinical outcomes in patients with stable angina and acute coronary syndromes. The three cases presented and discussed in this report illustrate the strengths and weaknesses of the available invasive and non-invasive methods for the physiological assessment of CAD. As technology evolves, invasive non-wire-based (angiography-derived FFR) and non-invasive (FFRCT) modalities for the hemodynamic assessment of CAD appear to provide reliable and user-friendly alternatives to the gold standard invasive wire-based techniques. Interventional cardiologists and cardiovascular healthcare providers should be familiar with the strengths and weaknesses of the available hemodynamic assessment modalities.

Diagnostic Accuracy of Coronary Angiography-Based Vessel Fractional Flow Reserve (vFFR) Virtual Stenting.

3D coronary angiography-based vessel fractional flow reserve (vFFR) proved to be an accurate diagnostic alternative to invasively measured pressure wire based fractional flow reserve (FFR). The ability to compute post-PCI vFFR using pre-PCI vFFR virtual stent analysis is unknown. We aimed to assess the feasibility and diagnostic accuracy of pre-PCI vFFR virtual stenting analysis (residual vFFR) with post-PCI FFR as a reference. This is an observational, single-center retrospective cohort study including consecutive patients from the FFR-SEARCH registry. We blindly calculated residual vFFR from pre-PCI angiograms and compared them to invasive pressure-wire based post-PCI FFR. Inclusion criteria involved presentation with either stable or unstable angina or non-ST elevation myocardial infarction (NSTEMI), ≥1 significant stenosis in one of the epicardial coronary arteries (percentage diameter stenosis of >70% by QCA or hemodynamically relevant stenosis with FFR ≤0.80) and pre procedural angiograms eligible for vFFR analysis. Exclusion criteria comprised patients with ST elevation myocardial infarction (STEMI), coronary bypass grafts, cardiogenic shock or severe hemodynamic instability. Eighty-one pre-PCI residual vFFR measurements were compared to post-PCI FFR and post-PCI vFFR measurements. Mean residual vFFR was 0.91 ± 0.06, mean post-PCI FFR 0.91 ± 0.06 and mean post-PCI vFFR was 0.92 ± 0.05. Residual vFFR showed a high linear correlation (r = 0.84) and good agreement (mean difference (95% confidence interval): 0.005 (−0.002−0.012)) with post-PCI FFR, as well as with post-PCI-vFFR (r = 0.77, mean difference −0.007 (−0.015−0.0003)). Residual vFFR showed good accuracy in the identification of lesions with post-PCI FFR < 0.90 (sensitivity 94%, specificity 71%, area under the curve (AUC) 0.93 (95% CI: 0.86−0.99), p < 0.001). Virtual stenting using vFFR provided an accurate estimation of post-PCI FFR and post-PCI vFFR. Further studies are needed to prospectively validate a vFFR-guided PCI strategy.

Virtual (Computed) Fractional Flow Reserve: Future Role in Acute Coronary Syndromes.

The current management of acute coronary syndromes (ACS) is with an invasive strategy to guide treatment. However, identifying the lesions which are physiologically significant can be challenging. Non-invasive imaging is generally not appropriate or timely in the acute setting, so the decision is generally based upon visual assessment of the angiogram, supplemented in a small minority by invasive pressure wire studies using fractional flow reserve (FFR) or related indices. Whilst pressure wire usage is slowly increasing, it is not feasible in many vessels, patients and situations. Limited evidence for the use of FFR in non-ST elevation (NSTE) ACS suggests a 25% change in management, compared with traditional assessment, with a shift from more to less extensive revascularisation. Virtual (computed) FFR (vFFR), which uses a 3D model of the coronary arteries constructed from the invasive angiogram, and application of the physical laws of fluid flow, has the potential to be used more widely in this situation. It is less invasive, fast and can be integrated into catheter laboratory software. For severe lesions, or mild disease, it is probably not required, but it could improve the management of moderate disease in 'real time' for patients with non-ST elevation acute coronary syndromes (NSTE-ACS), and in bystander disease in ST elevation myocardial infarction. Its practicability and impact in the acute setting need to be tested, but the underpinning science and potential benefits for rapid and streamlined decision-making are enticing.

Non-invasive imaging software to assess the functional significance of coronary stenoses: a systematic review and economic evaluation.

BACKGROUND: QAngio® XA 3D/QFR® (three-dimensional/quantitative flow ratio) imaging software (Medis Medical Imaging Systems BV, Leiden, the Netherlands) and CAAS® vFFR® (vessel fractional flow reserve) imaging software (Pie Medical Imaging BV, Maastricht, the Netherlands) are non-invasive technologies to assess the functional significance of coronary stenoses, which can be alternatives to invasive fractional flow reserve assessment. OBJECTIVES: The objectives were to determine the clinical effectiveness and cost-effectiveness of QAngio XA 3D/QFR and CAAS vFFR. METHODS: We performed a systematic review of all evidence on QAngio XA 3D/QFR and CAAS vFFR, including diagnostic accuracy, clinical effectiveness, implementation and economic analyses. We searched MEDLINE and other databases to January 2020 for studies where either technology was used and compared with fractional flow reserve in patients with intermediate stenosis. The risk of bias was assessed with quality assessment of diagnostic accuracy studies. Meta-analyses of diagnostic accuracy were performed. Clinical and implementation outcomes were synthesised narratively. A simulation study investigated the clinical impact of using QAngio XA 3D/QFR. We developed a de novo decision-analytic model to estimate the cost-effectiveness of QAngio XA 3D/QFR and CAAS vFFR relative to invasive fractional flow reserve or invasive coronary angiography alone. Scenario analyses were undertaken to explore the robustness of the results to variation in the sources of data used to populate the model and alternative assumptions. RESULTS: Thirty-nine studies (5440 patients) of QAngio XA 3D/QFR and three studies (500 patients) of CAAS vFFR were included. QAngio XA 3D/QFR had good diagnostic accuracy to predict functionally significant fractional flow reserve (≤ 0.80 cut-off point); contrast-flow quantitative flow ratio had a sensitivity of 85% (95% confidence interval 78% to 90%) and a specificity of 91% (95% confidence interval 85% to 95%). A total of 95% of quantitative flow ratio measurements were within 0.14 of the fractional flow reserve. Data on the diagnostic accuracy of CAAS vFFR were limited and a full meta-analysis was not feasible. There were very few data on clinical and implementation outcomes. The simulation found that quantitative flow ratio slightly increased the revascularisation rate when compared with fractional flow reserve, from 40.2% to 42.0%. Quantitative flow ratio and fractional flow reserve resulted in similar numbers of subsequent coronary events. The base-case cost-effectiveness results showed that the test strategy with the highest net benefit was invasive coronary angiography with confirmatory fractional flow reserve. The next best strategies were QAngio XA 3D/QFR and CAAS vFFR (without fractional flow reserve). However, the difference in net benefit between this best strategy and the next best was small, ranging from 0.007 to 0.012 quality-adjusted life-years (or equivalently £140-240) per patient diagnosed at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. LIMITATIONS: Diagnostic accuracy evidence on CAAS vFFR, and evidence on the clinical impact of QAngio XA 3D/QFR, were limited. CONCLUSIONS: Quantitative flow ratio as measured by QAngio XA 3D/QFR has good agreement and diagnostic accuracy compared with fractional flow reserve and is preferable to standard invasive coronary angiography alone. It appears to have very similar cost-effectiveness to fractional flow reserve and, therefore, pending further evidence on general clinical benefits and specific subgroups, could be a reasonable alternative. The clinical effectiveness and cost-effectiveness of CAAS vFFR are uncertain. Randomised controlled trial evidence evaluating the effect of quantitative flow ratio on clinical and patient-centred outcomes is needed. FUTURE WORK: Studies are required to assess the diagnostic accuracy and clinical feasibility of CAAS vFFR. Large ongoing randomised trials will hopefully inform the clinical value of QAngio XA 3D/QFR. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019154575. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 56. See the NIHR Journals Library website for further project information.

Stable angina is a type of chest pain; left untreated, it can lead to heart failure, heart attack and sudden death. To avoid these outcomes, patients may require surgical intervention to open obstructed arteries, known as 'revascularisation'. Patients who might need revascularisation undergo tests to identify blocked arteries. The last line of testing is called invasive fractional flow reserve assessment. This is an invasive measurement of blood flow that involves inserting a wire into an artery after the patient has taken drugs to dilate the artery. It carries some risks and may have side effects. Non-invasive tests have been proposed to precede or replace invasive fractional flow reserve assessments. These include QAngio^® XA 3D/QFR^® (three-dimensional/quantitative flow ratio) (Medis Medical Imaging Systems BV, Leiden, the Netherlands) and CAAS^® vFFR^® (vessel fractional flow reserve) (Pie Medical Imaging BV, Maastricht, the Netherlands) imaging software. This project investigated whether or not these technologies can provide accurate assessments of blood pressure, and if they are a reasonable use of NHS resources. A thorough review of all the literature on the technologies was performed. All data were combined and re-analysed to determine whether or not the tests accurately predict the need for revascularisation and to consider their clinical benefits. An economic analysis was conducted to investigate whether or not using either of these technologies is economically viable. The project found that QAngio XA 3D/QFR can accurately measure blood flow, may be a reasonable alternative to fractional flow reserve, pending more evidence on benefits to patients' health, and is a reasonable use of NHS resources. The current evidence for CAAS vFFR is too limited to draw any firm conclusions.

Effect of Patient-Specific Coronary Flow Reserve Values on the Accuracy of MRI-Based Virtual Fractional Flow Reserve.

The purpose of this study is to investigate the effect of varying coronary flow reserve (CFR) values on the calculation of computationally-derived fractional flow reserve (FFR). CFR reflects both vessel resistance due to an epicardial stenosis, and resistance in the distal microvascular tissue. Patients may have a wide range of CFR related to the tissue substrate that is independent of epicardial stenosis levels. Most computationally based virtual FFR values such as FFRCT do not measure patient specific CFR values but use a population-average value to create hyperemic flow conditions. In this study, a coronary arterial computational geometry was constructed using magnetic resonance angiography (MRA) data acquired in a patient with moderate CAD. Coronary flow waveforms under rest and stress conditions were acquired in 13 patients with phase-contrast magnetic resonance (PCMR) to calculate CFR, and these flow waveforms and CFR values were applied as inlet flow boundary conditions to determine FFR based on computational fluid dynamics (CFD) simulations. The stress flow waveform gave a measure of the functional significance of the vessel when evaluated with the physiologically-accurate behavior with the patient-specific CFR. The resting flow waveform was then scaled by a series of CFR values determined in the 13 patients to simulate how hyperemic flow and CFR affects FFR values. We found that FFR values calculated using non-patient-specific CFR values did not accurately predict those calculated with the true hyperemic flow waveform. This indicates that both patient-specific anatomic and flow information are required to accurately non-invasively assess the functional significance of coronary lesions.

Diagnostic accuracy of quantitative flow ratio (QFR) and vessel fractional flow reserve (vFFR) estimated retrospectively by conventional radiation saving X-ray angiography.

BACKGROUND: Angiography derived FFR reveals good performance in assessing intermediate coronary stenosis. However, its performance under contemporary low X-ray frame and pulse rate settings is unknown. We aim to validate the feasibility and performance of quantitative flow ratio (QFR) and vessel fractional flow reserve (vFFR) under such angiograms. METHODS: This was an observational, retrospective, single center cohort study. 134 vessels in 102 patients, with angiograms acquired under 7.5fps and 7pps mode, were enrolled. QFR (fQFR and cQFR) and vFFR were validated with FFR as the gold standard. A conventional manual and a newly developed algorithmic exclusion method (M and A group) were both evaluated for identification of poor-quality angiograms. RESULTS: Good agreement between QFR/vFFR and FFR were observed in both M and A group, except for vFFR in the M group. The correlation coefficients between fQFR/cQFR/vFFR and FFR were 0.6242, 0.5888, 0.4089 in the M group, with rvFFR significantly lower than rfQFR (p = 0.0303), and 0.7055, 0.6793, 0.5664 in the A group, respectively. AUCs of detecting lesions with FFR ≤ 0.80 were 0.852 (95% CI 0.722-0.913), 0.858 (95% CI 0.778-0.917), 0.682 (95% CI 0.586-0.768), for fQFR/cQFR/vFFR in the M group, while vFFR performed poorer than fQFR (p = 0.0063) and cQFR (p = 0.0054). AUCs were 0.898 (95% CI 0.811-0.945), 0.892 (95% CI 0.803-0.949), 0.843 (95% CI 0.746-0.914) for fQFR/cQFR/vFFR in the A group. AUCvFFR was significantly higher in the A group than that in the M group (p = 0.0399). CONCLUSIONS: QFR/vFFR assessment is feasible under 7.5fps and 7pps angiography, where cQFR showed no advantage compared to fQFR. Our newly developed algorithmic exclusion method could be a better method of selecting angiograms with adequate quality for angiography derived FFR assessment.

The effect of hemodynamic parameters in patient-based coronary artery models with serial stenoses: normal and hypertension cases.

The purpose of this study is to investigate the hemodynamic significance of various degrees of coronary area of stenosis (AS) and multiple sequential stenoses (MSS) in normal and hypertension pressure conditions. MSS in a single branch coronary artery pose challenges to determine the physiological assessment in the prevalent invasive intervention. The hemodynamic parameters of each stenosis are influenced by other stenoses in the single branch of MSS coronary artery. In this study, we entirely use open source tools and techniques for coronary computed tomography angiography (CCTA) image segmentation, 3D reconstruction, grid generation and hemodynamic simulations. The results yield different hemodynamic parameters such as velocity magnitude, mean arterial pressure difference, flow-pressure linear relation, wall shear stress (WSS) and eventually virtual fractional flow reserve (vFFR) allowing for the prediction and the assessment of lumen area severity conditions in MSS coronaries.

Fast Virtual Fractional Flow Reserve Based Upon Steady-State Computational Fluid Dynamics Analysis: Results From the VIRTU-Fast Study.

Fractional flow reserve (FFR)-guided percutaneous intervention is superior to standard assessment but remains underused. The authors have developed a novel "pseudotransient" analysis protocol for computing virtual fractional flow reserve (vFFR) based upon angiographic images and steady-state computational fluid dynamics. This protocol generates vFFR results in 189 s (cf >24 h for transient analysis) using a desktop PC, with <1% error relative to that of full-transient computational fluid dynamics analysis. Sensitivity analysis demonstrated that physiological lesion significance was influenced less by coronary or lesion anatomy (33%) and more by microvascular physiology (59%). If coronary microvascular resistance can be estimated, vFFR can be accurately computed in less time than it takes to make invasive measurements.