Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia

Study Overview
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Brief Summary
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The study seeks to determine the accuracy of using anatomic and physiologic information measurable by computed tomography features of stenosis, plaque, fractional flow reserve-CT and to compare this measure to stress testing for the detection of myocardial ischemia against the gold standard of cardiac catheterization with fractional flow reserve. The hypothesis of this proposal is that integrating anatomic plaque features with physiologic fractional flow reserve-CT will optimize identification of coronary lesions that are ischemia-causing by computed tomography .

Detailed Description
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The CREDENCE trial will be a prospective multicenter cross-sectional study of 618 individuals (n=309 [derivation cohort]; n=309 [validation cohort]) who will undergo stress test, computed tomography, cardiac catheterization and fractional flow reserve. For the purposes of the study, either stress test or computed tomography will have been performed for clinical purposes, with the other test being performed as part of trial procedure. Study analyses will focus on the diagnostic performance of the information derived by stress test versus computed tomography against an invasive gold standard of cardiac catheterization and fractional flow reserve for an endpoint of vessel territory-specific ischemia. In keeping with prior studies, vessel territories will be comprised of the left anterior descending artery (and diagonal branches), the left circumflex artery (and obtuse marginal branches) and the right coronary artery (and posterolateral branch and posterior descending artery). To date, the relative performance of traditional stress imaging testing compared to the entirety of information proffered by CT has not been assessed compared to an unbiased gold standard. The study proposed herein will directly address this unmet need.

Official Title
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Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia (The CREDENCE Trial)

Conditions
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Myocardial Ischemia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Scheduled to undergo clinically-indicated non-emergent invasive coronary angiography Exclusion Criteria: Known CAD (myocardial infarction [MI], percutaneous coronary interventions [PCIs], coronary artery bypass graft [CABG],) Hemodynamic instability Inability to provide written informed consent Concomitant participation in another clinical trial in which subject is subject to investigational drug or device Pregnant state Absolute contraindication to iodinated contrast due to prior near-fatal anaphylactoid reaction (laryngospasm, bronchospasm, cardiorespiratory collapse, or equivalent) Serum creatinine ≥1.7 mg/dl or Glomerular Filtration Rate <30 ml/min Baseline irregular heart rhythm (e.g., atrial fibrillation, etc.) Heart rate ≥100 beats per minute Systolic blood pressure ≤90 mm Hg Contraindications to β blockers or nitroglycerin or adenosine BMI >40 kg/m2

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 |
| --- | --- |
| derivation cohort<br>n = 309 | |
| validation cohort<br>n = 309 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy of vessel territory-specific ischemia of an integrated stenosis-APC-FFRCT measure by CT | The primary endpoint is the diagnostic accuracy of an integrated stenosis-APC-FFRCT metric by CT, as compared to perfusion or perfusion-MBF stress imaging testing for vessel territory-specific ischemia as determined by FFR (gold standard). | 48-60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Individual comparisons of APCs or FFRCT to MPI vessel-specific perfusion deficits or reduced MBF. | To compare the accuracy of the individual components of APCs or FFRCT to MPI vessel-specific perfusion deficits or reduced MBF against ischemia by FFR. | 48-60 months | 
| Post-PCI FFR prediction by FFRCT virtual stenting | To determine the accuracy of FFRCT virtual stenting to post-PCI FFR value of >0.80 and determine the correlation between the FFRCT virtual stenting to post-PCI FFR. | 48-60 months |