FUnctional diagnoSIs of corONary Stenosis (FUSION)

Study Overview
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Brief Summary
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The purpose of the FUSION study is to validate the diagnostic performance of Virtual Flow Reserve (VFR) by comparing it against a reference standard, fractional flow reserve (FFR).

Detailed Description
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This study is a single-arm, prospective, multi-center study collecting OCT pullback images of lesions pre-percutaneous coronary intervention (PCI) and (optional) post-PCI procedure, and the corresponding pressure tracings and physiology indices. Up to 30 centers in the US will enroll approximately 310 patients. The expected duration of enrollment is approximately 15 months. The total duration of the clinical investigation is expected to be approximately 27 months.

Official Title
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Validation of OCT-based FUnctional diagnoSIs of corONary Stenosis (FUSION)

Conditions
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Coronary Artery Disease, Coronary Stenosis

Intervention / Treatment
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* Procedure: ICA (Invasive Coronary Angiography)
* Procedure: OCT
* Procedure: FFR
* Other: VFR Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Patient provides written informed consent Scheduled for clinically indicated coronary catheterization with the intent to perform physiologic assessment to guide physician clinical course (in lesions with visual % diameter stenosis 40-90%), if clinically indicated Subject is undergoing invasive FFR with Adenosine (high-dose intra-coronary (IC) [200 μg for the left and or 100 μg for the right coronary artery] or 140 μg/kg/min for intravenous (IV)) used as hyperemic stimulus Clinical presentation with or history of stable angina, unstable angina, or silent ischemia (defined as abnormal stress test or abnormal invasive physiology assessment) that has led to the procedure General Exclusion Criteria: Prior history of myocardial infarction (MI) in the target vessel Presence of acute ST Elevation Myocardial Infarction (STEMI) Culprit vessel of Non-ST Elevation Myocardial Infarction (NSTEMI) TIMI flow < Grade 3 at baseline or visible thrombus Prior history of coronary artery bypass grafting (CABG) Prior heart transplant Severe valvular heart disease or history of valve repair or replacement Prior history of PCI with stent in target vessel, or target vessel involves in-stent restenosis. Target coronary vessel is supplied by major collaterals or is supplying major collaterals to a CTO (chronic total occlusion) CTO in the target vessel Severe diffuse disease observed in target vessel defined as the presence of diffuse, serial gross luminal irregularities present in the majority of the coronary tree Presence of myocardial bridge (MB), regardless of vessel location Contraindication for FFR examination or administration of vasodilators Known LVEF ≤45% Target lesion involves Left Main coronary artery or ostial right coronary artery Known renal insufficiency (eGFR < 30 ml/kg/m^2 or serum creatinine ≥ 2.5 mg/dL) unless patient is on dialysis Heart Failure NYHA Class III or IV Subject is pregnant (For a female subject of childbearing potential, a pregnancy test must be performed within 14 days (≤14 days) prior to the index procedure per site standard test) Subject has or had active COVID-19 symptoms and/or a positive test result within the prior 2 months Participation in another clinical study of an investigational drug or device Presence of aneurysm in the target vessel Imaging and Pressure Tracing Exclusion Criteria: Artifact in pre-PCI OCT for the target lesion or in the event of multiple target lesions, artifact in pre-PCI OCT for ALL target lesions Target lesion requires any preparation (including but not limited to balloon dilatation, atherectomy, etc.) prior to pre-PCI OCT and physiology measurement, or in case of multiple target lesions, ALL target lesions require-any preparation (including but not limited to balloon dilatation, atherectomy, etc.) prior to pre-PCI OCT and physiology measurement Severe vessel tortuosity or calcification in the target vessel such that it is unlikely that the OCT catheter can be delivered Target lesion not imaged by OCT or in the event of multiple target lesions, ALL target lesions not imaged by OCT Pressure drift of > 0.03; i.e. Pd and Pa ratio value < 0.97 or > 1.03, unless physiology measurements are repeated after re-equalization Target lesion or significant CAD beyond 60mm from coronary ostium; i.e. not able to clearly image and capture all disease segment with OCT in 1 run Incorrectly done or unsuccessful catheter purge and/or contrast flush Presence of plaque rupture and/or intravascular hematoma in target vessel (visual % diameter stenosis ≥ 40%) Inability to receive intracoronary nitroglycerin prior to OCT or FFR Use of flush media other than radiographic contrast

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Standard of Care: Angiography, OCT, FFR, and VFR<br>Patients will have Pre-OCT Angiography, OCT pullbacks, a FFR measurement and a VFR analysis | Procedure: ICA (Invasive Coronary Angiography)<br>* Patients will undergo a Pre-PCI Angiography<br>Procedure: OCT<br>* OCT pullback images will be collected pre-PCI and (optional) post-PCI procedure<br>Procedure: FFR<br>* FFR will be measured<br>Other: VFR Analysis<br>* VFR will be calculated offline using the OCT pullback images<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of Virtual Flow Reserve (VFR) against Fractional Flow Reserve (FFR) | Sensitivity and specificity of the VFR compared with FFR each of which will be tested against a prespecified performance goal. FFR with a binary cut-off of 0.80 will be used as the reference standard for comparison. FFR or VFR value ≤ 0.80 will be considered positive (ischemia-causing), and FFR or VFR value > 0.80 will be considered negative (non-ischemia-causing) Sensitivity is defined as the proportion of VFR positive lesions, in the group of FFR positive lesions. Sensitivity=TP/(TP+FN), where TP denotes the number of True Positives (both VFR and FFR positive) and FN denotes the number of False Negatives (VFR negative but FFR positive). Specificity is defined as the proportion of VFR negative lesions in the group of FFR negative lesions. Specificity=TN/(TN+FP), where TN denotes the number of True Negatives (both VFR and FFR negatives) and FP denotes the number of False Positives (VFR positive but FFR negative). | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall diagnostic accuracy | Overall diagnostic accuracy is defined as the proportion of correctly classified lesions among all lesions. Overall Diagnostic Accuracy= (TP+TN)/(TP+TN+FP+FN), where TP denotes the number of True Positives, FN denotes the number of False Negatives, TN denotes the number of True Negatives, and FN denotes the number of False Negatives. | 1 hour | 
| Positive predictive value (PPV) | PPV is defined as the proportion of lesions with the disease and with a positive test result among the group of lesions with a positive test result. PPV= TP/(TP+FP), where TP denotes the number of True Positives and FP denotes the number of False Positives. | 1 hour | 
| Negative predictive value (NPV) | NPV is defined as the proportion of lesions without the disease and with a negative test result among the group of lesions with negative test results. NPV= TN/(TN+FN), where TN denotes the number of True Negatives and FN denotes the number of False Negatives. | 1 hour | 
| Correlation between VFR and FFR | The correlation between VFR and FFR will be estimated as the R^2 correlation coefficient from the simple linear regression model using VFR value as the independent variable and FFR as the dependent variable. | 1 hour | 
| Area under curve (AUC) against FFR | AUC will be estimated as the area under the ROC curve. ROC curve will be constructed using specificity on the x-axis and sensitivity on the y-axis. Sensitivity and specificity are calculated at various values of VFR and FFR, and the AUC curve will be drawn using logistic regression. | 1 hour | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Virtual Flow Reserve (VFR), Optical Coherence Tomography (OCT), Fractional Flow Reserve (FFR), Percutaneous Coronary Intervention (PCI), OPTIS System, Dragonfly, PressureWire X