Comparison of Optical Coherence Tomography-derived Minimal Lumen Area, Invasive Fractional Flow Reserve and FFRCT

Study Overview
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Brief Summary
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Significant left main (LM) stenosis is associated with a poor prognosis, therefore, adequate judgement of the prognostic significance of LM stenosis is essential to improve patients' prognosis. Recently, fractional flow reserve (FFR) has become widespread practice and carries a Class Ia recommendation to assess functional significance of intermediate coronary stenosis in patients with stable angina. Intravascular ultrasound (IVUS)-derived minimum lumen area (MLA) represents an accurate measure to determine LM significance as shown in multiple studies, while optical coherence tomography (OCT) ,which is a novel intracoronary imaging method with a greater spatial resolution (15μm vs. 100μm), faster image acquisition and facilitated image interpretation, OCT derived-MLA has never been validated against FFR and accordingly, it is not mentioned in the current guidelines for myocardial revascularization. Coronary computed tomography angiography (CTA) has emerged as a noninvasive alternative of coronary angiography with its excellent negative predictive value, while the positive predictive value of CTA is limited. Computational fluid dynamics is an emerging method that enables prediction of blood flow in coronary arteries and calculation of FFR from computed tomography (FFRCT) noninvasively. Noninvasive and accurate assessment of functional significance would bring a great benefit for patients with LM stenosis, however, there are no data to evaluate the diagnostic accuracy of FFRCT for LM stenosis in comparison with FFR and minimal lumen area derived by OCT. This study will investigate the optimal OCT-derived MLA cut-off point and the diagnostic performance of FFRCT for intermediate LM stenosis compared with FFR ≤0.8 as a reference standard.

Official Title
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Multimodality Assessment of Intermediate Left Main Stenosis: Comparison of Optical Coherence Tomography-derived Minimal Lumen Area, Invasive Fractional Flow Reserve and FFRCT

Conditions
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Coronary Stenosis

Intervention / Treatment
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* Diagnostic Test: OCT, FFR, CTA and FFRCT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unprotected LM lesion [midshaft, and distal bifurcation (Medina 1,1,1 or 1,1,0 or 1,0,1 or 1,0,0)] of 30% to 80% angiographic diameter stenosis (DS) on visual estimation or equivocal disease by angiography. Age ≥18 years. Ability to give preliminary oral consent witnessed by an independent physician or sign written informed consent prior to any study-specific procedures. Exclusion Criteria: Significant distal lesions (>50% angiographic DS on visual estimation within the left anterior descending artery [LAD] or left circumflex artery [LCX], except for ostium of LAD or LCX or diseased side branch [e.g. diagonal branch, obtuse marginal branch]) Ostial LM disease. Acute coronary syndrome (ACS) (non-ST-elevation ACS and ST-elevation MI). LM In-stent restenosis. Previous coronary stenting of the left coronary system. Chronic total occlusion. Previous coronary artery bypass graft. Previous MI related to the left coronary artery. Occurrence of ventricularization or hypotension during engagement of the LM ostial lesion. The presence of hemodynamic instability. Known renal insufficiency (serum creatinine >1.5mg/dL or receiving dialysis). Female of childbearing potential (age <50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy or hysterectomy. Life expectancy less than 1 year. Contraindication or known allergy against protocol-required medications including heparin, iodinated contrast, β-blocker, nitroglycerin, and adenosine. Body mass index >35kg/m2. Complex congenital heart disease other than anomalous coronary origins alone. Ventricular septal defect.

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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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Patient with left-main stenosis<br>Multimodality assessment of intermediate left main stenosis: Comparison of optical coherence tomography-derived minimal lumen area, invasive fractional flow reserve and FFRCT | Diagnostic Test: OCT, FFR, CTA and FFRCT<br>* Multimodality assessment of intermediate left main stenosis: Comparison of optical coherence tomography-derived minimal lumen area, invasive fractional flow reserve and FFRCT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OCT vs. FFR | - The area under the curve of OCT-derived MLA for FFR≤0.8 | Measurement at Procedure/ Baseline Visit | 
| OCT vs. FFR | -The optimal cut-off point of OCT-derived MLA from receiver-operator characteristics curves for FFR≤0.8 | Measurement at Procedure/ Baseline Visit | 
| FFRCT vs. FFR | Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FFRCT≤0.8 for FFR≤0.8 | Measurement at Procedure/ Baseline Visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OCT vs. FFR, RFR, resting Pd/Pa, FFRCT, QFR | - The area under the curve and the optimal cut-off point of OCT-derived MLA from receiver-operator characteristics curves for FFR≤0.75, RFR≤0.89, resting Pd/Pa≤0.91, and FFRCT≤0.80 and QFR≤0.80 | Measurement at Procedure/ Baseline Visit | 
| OCT vs. FFR, RFR, resting Pd/Pa, FFRCT | - Predictability of MLA, minimal lumen diameter, area stenosis, lesion length, eccentricity index, and plaque characteristics (plaque rupture, fibroatheroma, and calcification) for FFR ≤0.8, FFR≤0.75, RFR≤0.89, resting Pd/Pa≤0.91, and FFRCT≤0.80 and QFR≤0.80 | Measurement at Procedure/ Baseline Visit | 
| OCT vs. FFR, RFR, resting Pd/Pa, FFRCT | - Correlation among OCT-derived MLA, FFR, RFR, resting Pd/Pa, and FFRCT and QFR | Measurement at Procedure/ Baseline Visit | 
| OCT vs. CTA | - Correlation between luminal diameter stenosis of CTA and OCT-derived MLA | Measurement at Procedure/ Baseline Visit | 
| OCT vs. CTA | - Diagnostic accuracy of plaque characteristics with presumed high risk characteristics including napkin ring sign, low attenuation plaque (<30HU), positive remodelling (remodelling index >1.1), and spotty calcium (<3mm) for thin and thick cap fibroatheroma by OCT. | Measurement at Procedure/ Baseline Visit | 
| Clinical endpoint at 1 year | Death | 12 Month | 
| Clinical endpoint at 1 year | Myocardial infarction | 12 Month | 
| Clinical endpoint at 1 year | Target vessel myocardial infarction | 12 Month | 
| Clinical endpoint at 1 year | Target lesion revascularization | 12 Month | 
| Clinical endpoint at 1 year | Target vessel revascularization | 12 Month | 
| Clinical endpoint at 1 year | Any revascularization | 12 Month | 
| Clinical endpoint at 1 year | Stent thrombosis | 12 Month | 
| Clinical endpoint at 1 year | Stroke and transient ischemic attack | 12 Month | 
| Clinical endpoint at 1 year | Acute renal failure | 12 Month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary artery disease, Fractional flow reserve, Optical coherence tomography, Computed tomography angiography