Coronary Artery Disease
Conditions
Keywords
Fractional Flow Reserve, Quantitative Coronary Analysis, Stable coronary artery disease, Angina pectoris
Brief summary
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
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).
Interventions
OTHERQFR (observational)
QFR assessment by Medis Suite, Medis medical imaging B.V., The Netherlands
Sponsors
Aarhus University Hospital Skejby
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 1 hour | Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80. Positive DS% is defined as DS% \> 50% |
| 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) | 1 hour | Negative FFR is defined as FFR\>0.80. Negative QFR is defined as QFR\>0.80. Negative DS% is defined as DS% ≤ 50%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Negative QFR of FFR Negative Patients (True Negatives) (Specificity) | 1 hour | Negative FFR is defined as FFR\>0.80. Negative QFR is defined as QFR\>0.80 |
| Proportion of Patients With Positive FFR (True Positives) of Patients With Positive QFR (Positive Predictive Value) | 1 hour | Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80 |
| Proportion of Patients With Negative FFR (True Negatives) of Patients With Negative QFR (Negative Predictive Value) | 1 hour | Negative FFR is defined as FFR\>0.80. Negative QFR is defined as QFR\>0.80 |
| Diagnostic Performance of QFR in Comparison to FFR Reported as Positive and Negative Likelihood Ratio | 1 hour | Positive likelihood ratio is defined as sensitivity/(1-specificity). Negative likelihood ratio is defined as (1-sensitivty)/specificity |
| Diagnostic Grey Zone Calculation. QFR Limits for Achieving 95% Sensitivity and Specificity in Comparison to FFR | 1 hour | 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). |
| Diagnostic Accuracy of TIMI-flow Based QFR in Comparison to 2D QCA (>50% Diameter Stenosis) | 1 hour | 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. |
| Percentage of Patients With Successful QFR in Patients With Successful FFR (Feasibility) | 1 hour | — |
| All-cause Mortality (Number of Patients) | 1 day | Peri-procedural mortality |
| Time to FFR | 1 hour | 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 |
| Time to QFR After Receiving Angiographic Images | 1 hour | Time from first image evaluation on QFR computer until TIMI frame count based QFR value is obtained |
| Contrast Use | 1 hour | Volume of contrast for total procedure |
| Fluoroscopy Time | 1 hour | Fluoroscopy time for total procedure |
| Participants With Myocardial Infarction (Number of Patients) | 1 day | Peri-procedural myocardial infarction |
| Proportion of Patients With Positive QFR of FFR Positive Patients (True Positives) (Sensitivity) | 1 hour | Positive FFR is defined as FFR≤0.80. Positive QFR is defined as QFR≤0.80 |
Countries
Denmark, France, Germany, Italy, Japan, Netherlands, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients With Paired QFR, FFR and 2D-QCA Patients with stable angina pectoris or secondary evaluation of stenosis after acute MI reffered to invasive coronary angiography (ICA). ICA revealed at least one lesion with 30-90 % diameter stenosis with indication for fractional flow reserve (FFR). No lesions were excluded by the FFR, 2D-QCA nor angiographic criteria | 272 |
| Total | 272 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Excluded based on anatomical criteria | 2 |
| Overall Study | Excluded based on diagnostic angiography | 16 |
| Overall Study | Excluded by FFR core-lab | 24 |
| Overall Study | FFR not measured | 2 |
| Overall Study | In-procedure QFR not computed | 6 |
| Overall Study | Protocol Violation | 7 |
Baseline characteristics
| Characteristic | Patients With Paired QFR, FFR and 2D-QCA | — |
|---|---|---|
| Age, Continuous | 67 years STANDARD_DEVIATION 10 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 76 Participants | — |
| Sex: Female, Male Male | 196 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 329 |
| other Total, other adverse events | 0 / 329 |
| serious Total, serious adverse events | 0 / 329 |
Outcome results
Primary
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%
Time frame: 1 hour
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | 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) | 2D-QCA | 0.442 Proportion |
| Patients With Paired QFR, FFR and 2D-QCA | 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) | QFR | 0.865 Proportion |
Primary
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%.
Time frame: 1 hour
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | 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) | 2D-QCA | 0.765 Proportion |
| Patients With Paired QFR, FFR and 2D-QCA | 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) | QFR | 0.869 Proportion |
Secondary
All-cause Mortality (Number of Patients)
Peri-procedural mortality
Time frame: 1 day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | All-cause Mortality (Number of Patients) | 0 Participants |
Secondary
Contrast Use
Volume of contrast for total procedure
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Contrast Use | 120 mL | Standard Deviation 76 |
Secondary
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.
Time frame: 1 hour
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Diagnostic Accuracy of TIMI-flow Based QFR in Comparison to 2D QCA (>50% Diameter Stenosis) | TIMI-FLOW based QFR | 0.868 Proportion |
| Patients With Paired QFR, FFR and 2D-QCA | Diagnostic Accuracy of TIMI-flow Based QFR in Comparison to 2D QCA (>50% Diameter Stenosis) | 2D-QCA | 0.659 Proportion |
Secondary
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).
Time frame: 1 hour
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Diagnostic Grey Zone Calculation. QFR Limits for Achieving 95% Sensitivity and Specificity in Comparison to FFR | 95% limit for sensitivity | 0.77 Ratio |
| Patients With Paired QFR, FFR and 2D-QCA | Diagnostic Grey Zone Calculation. QFR Limits for Achieving 95% Sensitivity and Specificity in Comparison to FFR | 95% limit for specificity | 0.87 Ratio |
Secondary
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
Time frame: 1 hour
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Diagnostic Performance of QFR in Comparison to FFR Reported as Positive and Negative Likelihood Ratio | Negative likelihood ratio | 0.16 Ratio |
| Patients With Paired QFR, FFR and 2D-QCA | Diagnostic Performance of QFR in Comparison to FFR Reported as Positive and Negative Likelihood Ratio | Positive likelihood ratio | 6.60 Ratio |
Secondary
Fluoroscopy Time
Fluoroscopy time for total procedure
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Fluoroscopy Time | 9.8 Minutes | Standard Deviation 7.2 |
Secondary
Participants With Myocardial Infarction (Number of Patients)
Peri-procedural myocardial infarction
Time frame: 1 day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Participants With Myocardial Infarction (Number of Patients) | 0 Participants |
Secondary
Percentage of Patients With Successful QFR in Patients With Successful FFR (Feasibility)
Time frame: 1 hour
Population: Patients with successful FFR Measurement before Exclusion based on missing QFR and/or 2D-QCA
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Percentage of Patients With Successful QFR in Patients With Successful FFR (Feasibility) | 296 Participants |
Secondary
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
Time frame: 1 hour
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Proportion of Patients With Negative FFR (True Negatives) of Patients With Negative QFR (Negative Predictive Value) | 0.930 Proportion |
Secondary
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
Time frame: 1 hour
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Proportion of Patients With Negative QFR of FFR Negative Patients (True Negatives) (Specificity) | 0.869 Proportion |
Secondary
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
Time frame: 1 hour
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Proportion of Patients With Positive FFR (True Positives) of Patients With Positive QFR (Positive Predictive Value) | 0.763 Proportion |
Secondary
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
Time frame: 1 hour
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Proportion of Patients With Positive QFR of FFR Positive Patients (True Positives) (Sensitivity) | 0.865 Proportion |
Secondary
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
Time frame: 1 hour
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Time to FFR | 7.0 Minutes |
Secondary
Time to QFR After Receiving Angiographic Images
Time from first image evaluation on QFR computer until TIMI frame count based QFR value is obtained
Time frame: 1 hour
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Patients With Paired QFR, FFR and 2D-QCA | Time to QFR After Receiving Angiographic Images | 5.0 Minutes |