Danish study of Non-Invasive testing in Coronary Artery Disease (Dan-NICAD): study protocol for a randomised controlled trial

Abstract

BackgroundCoronary computed tomography angiography (CCTA) is an established method for ruling out coronary artery disease (CAD). Most patients referred for CCTA do not have CAD and only approximately 20–30 % of patients are subsequently referred to further testing by invasive coronary angiography (ICA) or non-invasive perfusion evaluation due to suspected obstructive CAD. In cases with severe calcifications, a discrepancy between CCTA and ICA often occurs, leading to the well-described, low-diagnostic specificity of CCTA. As ICA is cost consuming and involves a risk of complications, an optimized algorithm would be valuable and could decrease the number of ICAs that do not lead to revascularization.The primary objective of the Dan-NICAD study is to determine the diagnostic accuracy of cardiac magnetic resonance imaging (CMRI) and myocardial perfusion scintigraphy (MPS) as secondary tests after a primary CCTA where CAD could not be ruled out. The secondary objective includes an evaluation of the diagnostic precision of an acoustic technology that analyses the sound of coronary blood flow. It may potentially provide better stratification prior to CCTA than clinical risk stratification scores alone.Methods/designDan-NICAD is a multi-centre, randomised, cross-sectional trial, which will include approximately 2,000 patients without known CAD, who were referred to CCTA due to a history of symptoms suggestive of CAD and a low-risk to intermediate-risk profile, as evaluated by a cardiologist. Patient interview, sound recordings, and blood samples are obtained in connection with the CCTA. All patients with suspected obstructive CAD by CCTA are randomised to either stress CMRI or stress MPS, followed by ICA with fractional flow reserve (FFR) measurements. Obstructive CAD is defined as an FFR below 0.80 or as high-grade stenosis (>90 % diameter stenosis) by visual assessment.Diagnostic performance is evaluated as sensitivity, specificity, predictive values, likelihood ratios, and C statistics. Enrolment commenced in September 2014 and is expected to be complete in May 2016.DiscussionDan-NICAD is designed to assess whether a secondary perfusion examination after CCTA could safely reduce the number of ICAs where revascularization is not required. The results are expected to add knowledge about the optimal algorithm for diagnosing CAD.Trial registrationClinicaltrials.gov identifier, NCT02264717. Registered on 26 September 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1388-z) contains supplementary material, which is available to authorized users.

Comparison of quantitative flow ratio and fractional flow reserve with myocardial perfusion scintigraphy and cardiovascular magnetic resonance as reference standard. A Dan-NICAD substudy

“…This is a pre-planned substudy and the design of the main Dan-NICAD study was previously published [14]. In short, CCTA is the preferred first-line test in patients with stable chest pain in Denmark.…”

“…For CMR, an abnormal scan was defined as subendocardial or transmural changes by stress imaging or irreversible defects in ≥ 2 contiguous segments by late gadolinium enhancement imaging. Full description of MPS and CMR analysis was reported in the Dan-NICAD papers [14,15]. CMR core-lab readings were performed in an experienced core lab (William Harvey Research Institute, Queen Mary University of London, London, UK) while MPS Images were analyzed by a different independent core lab (Department of Nuclear Medicine, Aarhus University Hospital, Aarhus, Denmark).…”

“…Remaining segments were defined as distal. We refer to the Dan-NICAD papers for further details [14,15].…”

Correlations of First and Second Heart Sounds with Age, Sex, and Body Mass Index

“…The Dan-NICAD study [2] is a cross-sectional trial that included 1675 patients who were referred to coronary computed tomography angiography (CCTA) due to symptoms suggestive of coronary artery disease (CAD). These patients had no previous history of CAD, or advanced AV-block.…”

Autoregressive Whitening Filter for Detection of Coronary Artery Disease Based on Phonocardiography

“…Phonocardiography recordings were pooled from three different studies: AdoptCAD [5], BIO-CAC (NCT02913144), and Dan-NICAD [6,7] as shown in Table 1. Only one recording for each subject was included; in cases where more than one recording were available, the first recording was selected.…”