Diagnostic Accuracy of On-line Quantitative Flow Ratio (QFR). FAVOR II Europe-Japan

Study Overview
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Brief Summary
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Quantitative Flow Ratio (QFR) is a novel method for evaluating the functional significance of coronary stenosis. QFR is assessed by calculation of the pressure in the vessel based on two angiographic projections. The purpose of the FAVOR II study is to evaluate the diagnostic accuracy of on-line QFR compared to 2D Quantitative Coronary Angiography (QCA) with FFR as gold standard.

Detailed Description
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Background: Patients at high risk of having one or more coronary stenosis are evaluated routinely by invasive coronary angiography (CAG). Lesions are often quantified by QCA, but fractional flow reserve is increasingly used to assess functional significance of identified stenosis. FFR is assessed during CAG by advancing a wire with a pressure transducer towards the stenosis and measure the ratio in pressure between the two sides of the stenosis during medical induced maximum blood flow (hyperaemia). The solid evidence for FFR evaluation of coronary stenosis and the relative simplicity in performing the measurements have supported adoption of an FFR based strategy in many centers but the need for interrogating the stenosis by a pressure wire, the cost of the wire, and the drug inducing hyperaemia limits more widespread adoption. Quantitative Flow Ratio is a novel method for evaluating the functional significance of coronary stenosis by calculation of the pressure drop in the vessel based on two angiographic projections. The FAVOR I study (Tu et al.), showed promising results for core laboratory QFR analysis in selected patients. The purpose of the FAVOR II study is to evaluate the feasibility and diagnostic precision of in-procedure QFR during CAG in comparison to QCA with FFR as gold standard for physiological lesion evaluation. Hypothesis: QFR has superior sensitivity and specificity for detection of functional significant lesions in comparison to QCA with FFR as gold standard Methods: Prospective, observational, multicenter study with inclusion of 310 patients. Patients with indication for FFR are enrolled. At least two angiographic projections are acquired during resting conditions. QFR is calculated in-procedure using the Medis Suite application and simultaneously to the operator performing the FFR measurement. The QFR observer is blinded to the FFR measurement. QFR is reassessed off-line by the Interventional Coronary Imaging Core Laboratory, Aarhus University, Denmark, blinded to FFR and in-procedure QFR results. FFR is assessed by core laboratory reading, blinded to QFR results. All data are entered and stored in a protected and logged trial management system (TrialPartner, Aarhus University, Denmark).

Official Title
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Diagnostic Accuracy of On-line Quantitative Flow Ratio. Functional Assessment by Virtual Online Reconstruction (The FAVOR II Europe-Japan Study)

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Other: QFR (observational)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable angina pectoris or secondary evaluation of stenosis after acute MI Age > 18 years Able to provide signed informed consent Angiographic inclusion criteria: Indication for FFR in at least one stenosis: Diameter stenosis of 30%-90% by visual estimate Reference vessel size > 2 mm in stenotic segment by visual estimate Exclusion Criteria: Myocardial infarction within 72 hours Severe asthma or severe chronic obstructive pulmonary disease Severe heart failure (NYHA≥III) S-creatinine>150µmol/L or GFR<45 ml/kg/1.73m2 Allergy to contrast media or adenosine Atrial fibrillation Angiographic exclusion criteria: Lesion specific Below 30% and above 90% diameter stenosis by visual estimate. Reference size of vessel below 2 mm by visual estimation. Ostial LMCA lesions Ostial RCA lesions Distal LMCA lesions in combination with proximal Cx lesions Other bifurcation stenosis with lesions on both sides of a major shift (>1mm) in reference diameter Angiographic quality Poor image quality precluding contour detection Good contrast filling not possible Severe overlap of stenosed segments Severe tortuosity of target vessel

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: QFR (observational)|QFR assessment by Medis Suite, Medis medical imaging B.V., The Netherlands|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity: Proportion of Patients With Positive QFR of FFR Positive Patients (True Positives) Compared to Proportion of Patients With Positive Percentual Diameter Stenosis (DS%) Assessed by 2D QCA of FFR Positive Patients (True Positives) | Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80. Positive DS% is defined as DS% > 50% | 1 hour | 
| Specificity: Proportion of Patients With Negative QFR of FFR Negative Patients (True Negatives) Compared to Proportion of Patients With Negative DS% Assessed by 2D QCA of FFR Negative Patients (True Negatives) | Negative FFR is defined as FFR>0.80. Negative QFR is defined as QFR>0.80. Negative DS% is defined as DS% ≤ 50%. | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Successful QFR in Patients With Successful FFR (Feasibility) |  | 1 hour | 
| Proportion of Patients With Positive QFR of FFR Positive Patients (True Positives) (Sensitivity) | Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80 | 1 hour | 
| Proportion of Patients With Negative QFR of FFR Negative Patients (True Negatives) (Specificity) | Negative FFR is defined as FFR>0.80. Negative QFR is defined as QFR>0.80 | 1 hour | 
| Proportion of Patients With Positive FFR (True Positives) of Patients With Positive QFR (Positive Predictive Value) | Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80 | 1 hour | 
| Proportion of Patients With Negative FFR (True Negatives) of Patients With Negative QFR (Negative Predictive Value) | Negative FFR is defined as FFR>0.80. Negative QFR is defined as QFR>0.80 | 1 hour | 
| Diagnostic Performance of QFR in Comparison to FFR Reported as Positive and Negative Likelihood Ratio | Positive likelihood ratio is defined as sensitivity/(1-specificity). Negative likelihood ratio is defined as (1-sensitivty)/specificity | 1 hour | 
| Diagnostic Grey Zone Calculation. QFR Limits for Achieving 95% Sensitivity and Specificity in Comparison to FFR | QFR limits to yield 95% sensitivity and specificity. The QFR limits are identified by Area under the receiver operating curve analysis. QFR limits are defined as the numerical QFR ratios (0-1.00). | 1 hour | 
| Diagnostic Accuracy of TIMI-flow Based QFR in Comparison to 2D QCA (>50% Diameter Stenosis) | Comparison of proportion of participants correctly classified by QFR and 2D QCA using FFR as reference standard. Diagnostic accuracy is defined as (true positives + false negatives) / (true positives+false positives+true negatives+false negatives). Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80. Negative FFR is defines as FFR>0.80. Negative QFR is defines as QFR>0.80. Positive 2D QCA is defined as 2D-QCA % percent diameter stenosis >50. Negative 2D QCA is defined as 2D-QCA % diameter stenosis≤50. | 1 hour | 
| Participants With Myocardial Infarction (Number of Patients) | Peri-procedural myocardial infarction | 1 day | 
| All-cause Mortality (Number of Patients) | Peri-procedural mortality | 1 day | 
| Time to FFR | Time from starting preparations to do FFR (e.g. ordering assistants to prepare pressure wire, adenosine infusion etc.) to FFR value is obtained and drift has been verified to be within the prespecified limits | 1 hour | 
| Time to QFR After Receiving Angiographic Images | Time from first image evaluation on QFR computer until TIMI frame count based QFR value is obtained | 1 hour | 
| Contrast Use | Volume of contrast for total procedure | 1 hour | 
| Fluoroscopy Time | Fluoroscopy time for total procedure | 1 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fractional Flow Reserve, Quantitative Coronary Analysis, Stable coronary artery disease, Angina pectoris