title: Rationale and Design of the CREDENCE Trial: computed TomogRaphic evaluation of atherosclerotic DEtermiNants of myocardial IsChEmia.
abstract: Coronary computed tomography angiography (CCTA) allows for non-invasive assessment of obstructive coronary artery disease (CAD) beyond measures of stenosis severity alone. This assessment includes atherosclerotic plaque characteristics (APCs) and calculation of fractional flow reserve (FFR) from CCTA (FFRCT). Similarly, stress imaging by myocardial perfusion scintigraphy (MPS) provides vital information. To date, the diagnostic performance of integrated CCTA assessment versus integrated MPS assessment for diagnosis of vessel-specific ischemia remains underexplored.
  
  
  
  CREDENCE will enroll adult individuals with symptoms suspicious of CAD referred for non-emergent invasive coronary angiography (ICA), but without known CAD. All participants will undergo CCTA, MPS, ICA and FFR. FFR will be performed for lesions identified at the time of ICA to be ≥40 and <90 % stenosis, or those clinically indicated for evaluation. Study analyses will focus on diagnostic performance of CCTA versus MPS against invasive FFR reference standard. An integrated stenosis-APC-FFRCTmetric by CCTA for vessel-specific ischemia will be developed from derivation cohort and tested against a validation cohort. Similarly, integrated metric by MPS for vessel-specific ischemia will be developed, validated and compared. An FFR value of ≤0.80 will be considered as ischemia causing. The primary endpoint will be the diagnostic accuracy of vessel territory-specific ischemia of integrated stenosis-APC-FFRCTmeasure by CCTA, compared with perfusion or perfusion-myocardial blood flow stress imaging testing, against invasive FFR.
  
  
  
  CREDENCE will determine the performance of integrated CCTA metric compared to integrated MPS measure for diagnosis of vessel-specific ischemia. If proven successful, this study may reduce the number of missed diagnoses and help to optimally predict ischemia-causing lesions.
  
  
  
  ClinicalTrials.gov, NCT02173275 . Registered on June 23, 2014.
authors.affiliation: Dalio Institute of Cardiovascular Imaging, NewYork-Presbyterian Hospital, New York, NY, USA.
authors.forename: Asim
authors.initials: A
authors.lastname: Rizvi
authors.affiliation: Dalio Institute of Cardiovascular Imaging, NewYork-Presbyterian Hospital, New York, NY, USA.
authors.forename: Bríain Ó
authors.initials: BÓ
authors.lastname: Hartaigh
authors.affiliation: Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Knaapen
authors.affiliation: Department of Medical Imaging, University of British Columbia, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Jonathon
authors.initials: J
authors.lastname: Leipsic
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Leslee J
authors.initials: LJ
authors.lastname: Shaw
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Andreini
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Centro Cardiologico Monzino, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Pontone
authors.affiliation: Davis Heart and Lung Research Institute and Heart Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Subha
authors.initials: S
authors.lastname: Raman
authors.affiliation: The Cardiac Center of Texas, McKinney, TX, USA.
authors.forename: Muhammad Akram
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Heart Center Research, LLC, Huntsville, AL, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ridner
authors.affiliation: Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Faisal
authors.initials: F
authors.lastname: Nabi
authors.affiliation: Fondazione Toscana/CNR Gabriele Monasterio, Pisa, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Gimelli
authors.affiliation: Division of Cardiology, Kaiser Permanente San Jose Medical Center, San Jose, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Jang
authors.affiliation: Mobile Cardiology Associates, Mobile, AL, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Cole
authors.affiliation: Cardiovascular Imaging Lab, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakazato
authors.affiliation: Heart Flow, Inc., Redwood City, CA, USA.|Department of Surgery, Stanford University, Stanford, CA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Zarins
authors.affiliation: Dalio Institute of Cardiovascular Imaging, NewYork-Presbyterian Hospital, New York, NY, USA.
authors.forename: Donghee
authors.initials: D
authors.lastname: Han
authors.affiliation: Dalio Institute of Cardiovascular Imaging, NewYork-Presbyterian Hospital, New York, NY, USA.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Dalio Institute of Cardiovascular Imaging, NewYork-Presbyterian Hospital, New York, NY, USA.
authors.forename: Jackie
authors.initials: J
authors.lastname: Szymonifika
authors.affiliation: Dalio Institute of Cardiovascular Imaging, NewYork-Presbyterian Hospital, New York, NY, USA.
authors.forename: Millie J
authors.initials: MJ
authors.lastname: Gomez
authors.affiliation: Dalio Institute of Cardiovascular Imaging, NewYork-Presbyterian Hospital, New York, NY, USA.|Department of Medicine, Weill Cornell Medical College, New York, NY, USA.|Department of Radiology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Quynh A
authors.initials: QA
authors.lastname: Truong
authors.affiliation: Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University Health System, Seoul, South Korea.
authors.forename: Hyuk-Jae
authors.initials: HJ
authors.lastname: Chang
authors.affiliation: Dalio Institute of Cardiovascular Imaging, NewYork-Presbyterian Hospital, New York, NY, USA.|Department of Radiology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Fay Y
authors.initials: FY
authors.lastname: Lin
authors.affiliation: Dalio Institute of Cardiovascular Imaging, NewYork-Presbyterian Hospital, New York, NY, USA. jkm2001@med.cornell.edu.|Department of Medicine, Weill Cornell Medical College, New York, NY, USA. jkm2001@med.cornell.edu.|Department of Radiology, Weill Cornell Medical College, New York, NY, USA. jkm2001@med.cornell.edu.|Radiology and Medicine, New York-Presbyterian Hospital and Weill Cornell Medical College, 413 E. 69th Street, Suite 108, New York, NY, 10021, USA. jkm2001@med.cornell.edu.
authors.forename: James K
authors.initials: JK
authors.lastname: Min
mesh_terms: D000328:Adult; D017023:Coronary Angiography / Q000379:methods*; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D053805:Fractional Flow Reserve, Myocardial; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000503:physiopathology; D058226:Plaque, Atherosclerotic / Q000175:diagnosis* / Q000503:physiopathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed / Q000379:methods*
keywords: Coronary artery disease; Coronary computed tomography angiography; Fractional flow reserve; Myocardial blood flow; Myocardial perfusion scintigraphy