Diagnostic Accuracy of Fast Computational Approaches to Derive Fractional Flow Reserve From Diagnostic Coronary Angiography : The International Multicenter FAVOR Pilot Study
TL;DR: The QFR computation improved the diagnostic accuracy of 3-dimensional quantitative coronary angiography-based identification of stenosis significance and bears the potential of a wider adoption of FFR-based lesion assessment through a reduction in procedure time, risk, and costs.
Abstract: Objectives The aim of this prospective multicenter study was to identify the optimal approach for simple and fast fractional flow reserve (FFR) computation from radiographic coronary angiography, called quantitative flow ratio (QFR).
Background A novel, rapid computation of QFR pullbacks from 3-dimensional quantitative coronary angiography was developed recently.
Methods QFR was derived from 3 flow models with: 1) fixed empiric hyperemic flow velocity (fixed-flow QFR [fQFR]); 2) modeled hyperemic flow velocity derived from angiography without drug-induced hyperemia (contrast-flow QFR [cQFR]); and 3) measured hyperemic flow velocity derived from angiography during adenosine-induced hyperemia (adenosine-flow QFR [aQFR]). Pressure wire-derived FFR, measured during maximal hyperemia, served as the reference. Separate independent core laboratories analyzed angiographic images and pressure tracings from 8 centers in 7 countries.
Results The QFR and FFR from 84 vessels in 73 patients with intermediate coronary lesions were compared. Mean angiographic percent diameter stenosis (DS%) was 46.1 ± 8.9%; 27 vessels (32%) had FFR ≤ 0.80. Good agreement with FFR was observed for fQFR, cQFR, and aQFR, with mean differences of 0.003 ± 0.068 (p = 0.66), 0.001 ± 0.059 (p = 0.90), and −0.001 ± 0.065 (p = 0.90), respectively. The overall diagnostic accuracy for identifying an FFR of ≤0.80 was 80% (95% confidence interval [CI]: 71% to 89%), 86% (95% CI: 78% to 93%), and 87% (95% CI: 80% to 94%). The area under the receiver-operating characteristic curve was higher for cQFR than fQFR (difference: 0.04; 95% CI: 0.01 to 0.08; p < 0.01), but did not differ significantly between cQFR and aQFR (difference: 0.01; 95% CI: -0.04 to 0.06; p = 0.65). Compared with DS%, both cQFR and aQFR increased the area under the receiver-operating characteristic curve by 0.20 (p < 0.01) and 0.19 (p < 0.01). The positive likelihood ratio was 4.8, 8.4, and 8.9 for fQFR, cQFR, and aQFR, with negative likelihood ratio of 0.4, 0.3, and 0.2, respectively.
Conclusions The QFR computation improved the diagnostic accuracy of 3-dimensional quantitative coronary angiography-based identification of stenosis significance. The favorable results of cQFR that does not require pharmacologic hyperemia induction bears the potential of a wider adoption of FFR-based lesion assessment through a reduction in procedure time, risk, and costs.
Citations
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TL;DR: The study met its prespecified primary performance goal for the level of diagnostic accuracy of QFR in identifying hemodynamically significant coronary stenosis.
302 citations
Cites background or methods or result from "Diagnostic Accuracy of Fast Computa..."
...The contrast flow model, which uses a frame count method to derive contrast flow velocity from coronary angiography (9), was used in this study for QFR computation....
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...The FAVOR (Functional Assessment by Various Flow Reconstructions) pilot study showed promising results for core laboratory– based QFR computation in identifying the presence of functionally significant stenosis in selected patients (9)....
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...Quantitative flow ratio (QFR) is a novel method for evaluating the functional significance of coronary stenosis by computation of FFR in the vessel based on 3-dimensional angiographic reconstruction and fluid dynamics algorithms (9,10)....
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...The target goal was chosen to be higher than the upper boundary of the diagnostic accuracy of QCA, which was 74% in the FAVOR pilot study (9)....
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...The results of this study expand on findings and reported clinical potentials from the previous FAVOR pilot study (9), in which QFR was assessed by core laboratories and compared with wire-based FFR in 84 vessels from 73 patients....
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TL;DR: Online computation of QFR in the catheterization laboratory is clinically feasible and is superior to angiographic assessment for evaluation of intermediary coronary artery stenosis using FFR as a reference standard.
Abstract: Background Quantitative flow ratio (QFR) is a novel modality for physiological lesion assessment based on 3‐dimensional vessel reconstructions and contrast flow velocity estimates. We evaluated the...
224 citations
Erasmus University Rotterdam1, University of Amsterdam2, Northern Hospital3, University of Melbourne4, Queen Mary University of London5, University College London6, Brigham and Women's Hospital7, Leiden University8, Massachusetts Institute of Technology9, University of Sheffield10, Norwegian University of Science and Technology11, Seoul National University12, Seoul National University Hospital13, Stanford University14, Polytechnic University of Milan15, Erasmus University Medical Center16, Emory University17, Worcester Polytechnic Institute18, Harvard University19, University of Utah20, Scientific Computing and Imaging Institute21, Imperial College London22
TL;DR: In this paper, the authors proposed a method to solve the problem of the problem: this paper ] of "uniformity" of the distribution of data points in the data set.
Abstract: Abstract
152 citations
TL;DR: FFRangio measured from the coronary angiogram alone has a high sensitivity, specificity, and accuracy compared with pressure wire–derived FFR, and has the promise to substantially increase physiological coronary lesion assessment in the catheterization laboratory, thereby potentially leading to improved patient outcomes.
Abstract: Background: Measuring fractional flow reserve (FFR) with a pressure wire remains underutilized because of the invasiveness of guide wire placement or the need for a hyperemic stimulus FFR derived
140 citations
TL;DR: A QFR–FFR hybrid approach based on the present results enables wire-free and adenosine-free procedures in 68% of cases and shows good agreement and diagnostic accuracy compared with FFR.
Abstract: Background—Quantitative flow ratio (QFR) is a novel diagnostic modality for functional testing of coronary artery stenosis without the use of pressure wires and induction of hyperemia. QFR is based...
137 citations
References
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TL;DR: It is concluded that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity, and one or both should be presented in publishedMeta-an analyses in preference to the test for heterogeneity.
Abstract: The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity.
25,460 citations
"Diagnostic Accuracy of Fast Computa..." refers methods in this paper
...Heterogeneity between the study centers was assessed using the I(2) statistic (20); we assumed heterogeneity when the degree of inconsistency (using I(2) statistics) was >50% with an associated p value of <0....
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TL;DR: Routine measurement of FFR in patients with multivessel coronary artery disease who are undergoing PCI with drug-eluting stents significantly reduces the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year.
Abstract: Background In patients with multivessel coronary artery disease who are undergoing percutaneous coronary intervention (PCI), coronary angiography is the standard method for guiding the placement of the stent. It is unclear whether routine measurement of fractional flow reserve (FFR; the ratio of maximal blood flow in a stenotic artery to normal maximal flow), in addition to angiography, improves outcomes. Methods In 20 medical centers in the United States and Europe, we randomly assigned 1005 patients with multivessel coronary artery disease to undergo PCI with implantation of drug-eluting stents guided by angiography alone or guided by FFR measurements in addition to angiography. Before randomization, lesions requiring PCI were identified on the basis of their angiographic appearance. Patients assigned to angiography-guided PCI underwent stenting of all indicated lesions, whereas those assigned to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was 0.80 or less. The primary end point was the rate of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. Results The mean (±SD) number of indicated lesions per patient was 2.7±0.9 in the angiography group and 2.8±1.0 in the FFR group (P = 0.34). The number of stents used per patient was 2.7±1.2 and 1.9±1.3, respectively (P<0.001). The 1-year event rate was 18.3% (91 patients) in the angiography group and 13.2% (67 patients) in the FFR group (P = 0.02). Seventy-eight percent of the patients in the angiography group were free from angina at 1 year, as compared with 81% of patients in the FFR group (P = 0.20). Conclusions Routine measurement of FFR in patients with multivessel coronary artery disease who are undergoing PCI with drug-eluting stents significantly reduces the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. (ClinicalTrials.gov number, NCT00267774.)
3,479 citations
TL;DR: In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best Available medical therapy alone, decreased the need for urgent revascularization.
Abstract: A b s t r ac t Background The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone. Methods In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. Results Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary endpoint event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The difference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were triggered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001). Among patients in the registry, 3.0% had a primary end-point event. Conclusions In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.)
2,195 citations
TL;DR: Flow response and regional distribution during coronary hyperemia caused by Hypaque are quantitative measures for physiologically assessing critical coronary stenosis and flow reserve with potential applicability to patients.
Abstract: Quantitative hemodynamic assessment of coronary stenosis has not been previously reported. Resting coronary blood flow and its regional distribution are insensitive indexes for determining critical stenosis, but flow response to a hyperemic stimulus quantifies restrictions on maximal flow due to coronary arterial lesions. Coronary flow responses to temporary occlusion and to selective main coronary arterial injection of sodium diatrizoate (Hypaque-M 75 percent) were studied in 12 consecutive dogs with a surgically implanted electromagnetic flowmeter and separate micrometer constrictor on the left circumflex coronary artery. Selective Hypaque injection adequate for coronary cineangiography increased coronary flow to four times the resting base-line value, peaking at 6 seconds and lasting 3 minutes, a response equivalent to hyperemia after 10 seconds of circumflex arterial occlusion. With progressive micrometer constriction, resting flow measurements did not decrease until there was 85 percent stenosis. Hyperemia after intracoronary injection of Hypaque decreased when there was 30 to 45 percent stenosis and disappeared when there was 88 to 93 percent stenosis. Myocardial images obtained by gamma camera after left atrial injection of 131 iodine-macroaggregated albumin demonstrated uniform regional distribution of resting flow in spite of severe constriction. However, 6 seconds after selective Hypaque injection, left atrial injection of 99m technetium macroaggregates demonstrated distinct perfusion abnormalities in the region of circumflex stenosis. Thus, flow distribution with a severe lesion was normal at rest but showed marked differences due to restricted circumflex versus normal anterior descending hyperemic response after injection of Hypaque. Flow response and regional distribution during coronary hyperemia caused by Hypaque are quantitative measures for physiologically assessing critical coronary stenosis and flow reserve with potential applicability to patients.
1,508 citations
"Diagnostic Accuracy of Fast Computa..." refers background in this paper
...This factor should impact less on the computation of cQFR than aQFR, because resting flow will be restricted only by very tight epicardial stenoses (28)....
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TL;DR: In this paper, the diagnostic performance of noninvasive fractional flow reserve (FFR) derived from standard acquired coronary computed tomography angiography (CTA) datasets for the diagnosis of myocardial ischemia in patients with suspected stable coronary artery disease (CAD) was evaluated.
1,094 citations