Use of FFR-CT in Stable Intermediate Chest Pain Patients With Severe Coronary Calcium Score

Study Overview
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Brief Summary
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A prospective, blinded multicenter study for evaluation of chest pain patients with severe coronary calcium (Agatston score > 399). The objective is to evaluate if an initial non-invasive strategy with coronary computed tomography angiography (CCTA) including functional flow reserve derived from CCTA (FFR-CT) is as effective as invasive coronary angiography (ICA) including functional flow reserve (FFR) for the detection and exclusion of obstructive coronary artery disease (CAD). Study hypothesis: initial non-invasive anatomic and functional testing is non-inferior to an invasive anatomic and functional testing strategy.

Detailed Description
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Prospective, blinded multicenter study evaluating the diagnostic performance of coronary computed tomography angiography (CCTA) including functional flow reserve derived from CCTA (FFR-CT) for the detection and exclusion of significant obstructive coronary artery disease (CAD). The reference standard vil be invasive coronary angiography (ICA) including functional flow reserve (FFR). Patients referred for elective CCTA because of suspected stable CAD are considered. If the initial routine non-enhanced CT scan shows an Agatston score > 399, the patient is eligible for study inclusion. Four sites in the region of Southern Denmark will participate (Odense University Hospital, Svendborg Hospital, Vejle Hospital and Esbjerg Hospital). A total of 278 patients will be included.

Official Title
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Functional and Anatomical Testing in Intermediate Risk Chest Pain Patients With Severe Coronary Calcium Score

Conditions
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Observational

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years An estimated likelihood for the presence of significant CAD between 15% and 85% Clinical stable patients with symptoms of suspected CAD referred for CTTA Initial routine non-enhanced CT scan shows an Agatston score >399 Written informed consent Accept to undergo elective invasive coronary angiography (ICA) within 90 days Exclusion Criteria: Known prior myocardial infarction Prior percutaneous coronary intervention (PCI) Prior coronary artery bypass surgery (CABG) Pacemaker or internal defibrillator lead implantation Prosthetic heart valve Atrial fibrillation Renal Insufficiency (<40 mL/min) Known anaphylactic reaction to iodinated contrast Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with Agatston score > 399<br>Coronary computed tomography angiography with FFR-CT Invasive coronary angiography with FFR | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Per-patient diagnostic accuracy of functional flow reserve (FFR-CT) derived from standard coronary computed tomography angiography (CCTA) compared to invasive coronary angiography (ICA) including functional flow ratio (FFR) | The primary outcome measure is the per-patient diagnostic accuracy of functional flow reserve (FFR-CT) derived from standard coronary computed tomography angiography (CCTA) compared to invasive coronary angiography (ICA) including functional flow ratio (FFR), which is considered the gold standard in the detection or exclusion of obstructive coronary artery disease (CAD) | Comparison of the noninvasive and invasive diagnostic modalities is performed at least 90 days after enrollment of each of the included patients | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive coronary angiography (ICA) including functional flow ratio (FFR) without obstructive coronary artery disease | Percentage of patients with invasive coronary angiography (ICA) including functional flow reserve (FFR) measurement without evidence of obstructive coronary artery disease | 90 days after inclusion | 
| Coronary revascularization procedures | Percentage of coronary revascularization procedures (PCI and CABG) in patients with reduced FFR-CT vs. patients with normal FFR-CT | 90 day after inclusion | 
| Other clinical endpoints | Percentage of patients with the composite endpoint of all-cause mortality or myocardial infarction or unstable angina hospitalization | 90 days after inclusion | 
| Major complications from diagnostic invasive diagnostic procedures | Percentage of patients with major complications following invasive coronary angiography (ICA) including fractional flow reserve (FFR) measurement | Within 72 hours after invasive procedure | 
| Per-patient and per-vessel diagnostic performance of FFR-CT by means of accuracy, sensitivity, specificity, positive predictive value, and negative predictive value | Assessing per-patient and per-vessel diagnostic performance of FFR-CT by means of accuracy, sensitivity, specificity, positive predictive value, and negative predictive value | At least 90 days after patient inclusion | 
| Per-vessel correlation of FFR-CT numerical value with the FFR numerical value in patients undergoing FFR | The per-vessel correlation of FFRCT numerical value with the FFR numerical value in patients undergoing FFR | At least 90 days after patient inclusion | 
| The diagnostic accuracy of FFR-CT in subgroups of patients with high calcium score vs. patients with very high calcium score | Comparison of the diagnostic accuracy of FFR-CT in subgroups of patients with high calcium score (Agatston score 400-999) vs patients with very high calcium score (Agatston score ≥ 999) | At least 90 days after patient inclusion | 
| Costs and resource use. | Estimating the total costs of potentially unnecessary invasive coronary angiographies with functional flow ratio measurements | 90 days after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Angina, Chest pain, Diagnostic tests