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Background  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 (FFR CT ). 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.    Methods  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-FFR CT  metric 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-FFR CT  measure by CCTA, compared with perfusion or perfusion–myocardial blood flow stress imaging testing, against invasive FFR.    Discussion  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.    Trial registration  ClinicalTrials.gov,  NCT02173275 . Registered on June 23, 2014.     Electronic supplementary material  The online version of this article (doi:10.1186/s12872-016-0360-x) contains supplementary material, which is available to authorized users.

Rationale and Design of the CREDENCE Trial: computed TomogRaphic evaluation of atherosclerotic DEtermiNants of myocardial IsChEmia