Danish Study of Non-Invasive Diagnostic Testing in Coronary Artery Disease 2

NCT03481712 | Completed

• 1 other identifier: 000-0001
• Study Type: observational
• Target: 1,732
• Locations: 1 country
• Sites: 5

Brief Summary

In a cohort of symptomatic patients referred to coronary computed tomography angiography (CCTA), the investigators aim:

1. 1.To investigate and compare the diagnostic precision of Rubidium Positron Emission Tomography (Rb PET) and 3 Tesla Cardiac Magnetic Resonance imaging (3T CMRI) in patients where CCTA does not exclude significant coronary artery disease (CAD) using invasive coronary angiography with fractional flow reserve (ICA-FFR) as reference standard.
2. 2.To evaluate the diagnostic precision of quantitative flow ratio (QFR) and ICA-FFR in patients where CCTA does not exclude significant CAD using Rb PET and 3T CMRI as reference standard.
3. 3.To show superiority for the CADScor®System compared to the Diamond-Forrester score in detection of CAD with CCTA and ICA quantitative coronary angiography (ICA-QCA) as reference standard.
4. 4.To study the diagnostic accuracy of computed tomography fractional flow reserve (CT-FFR) in patients where CCTA does not exclude significant CAD with ICA-FFR as reference standard.
5. 5.To identify and characterize genetic risk variants´ and circulating biomarkers´ importance in developing CAD.
6. 6.To evaluate the bone mineral density in the hip and spine and correlate this to the degree of vascular calcification.

Conditions

Angina Pectoris; Atherosclerosis; Coronary Artery Disease; Myocardial Ischemia

Outcome Measures

Primary Outcomes (3)

• Diagnostic accuracy of 3T CMRI vs. Rb PET.

  Head-to-head comparison using ICA-FFR as reference standard. Diagnostic accuracy is measured using specificity, sensitivity, positive and negative predictive value and likelihood ratios.

  4 weeks after inclusion.

• Diagnostic accuracy of QFR vs. ICA-FFR.

  Head-to-head comparison using myocardial perfusion examinations as reference standard. Diagnostic accuracy is measured using specificity, sensitivity, positive and negative predictive values, likelihood ratios and area under receiving operating curves (AUC-ROC).

  4 weeks after inclusion.

• Diagnostic accuracy of CADScor vs. Diamond-Foster Score.

  AUC-ROC for CAD-score and Diamond-Forrester score in detection of CAD with CCTA and ICA-QCA as reference in patients ≥40 years.

  4 weeks after inclusion.

Secondary Outcomes (14)

• Genome-wide Associations.

  4 weeks after inclusion.

• Bone mineral density.

  1 day after inclusion.

• Coronary flow measurement´s impact on diagnostic accuracy of myocardial perfusion imaging (MPI).

  4 weeks after inclusion.

• Diagnostic accuracy of quantitative CMRI analysis.

  4 weeks after inclusion.

• Absolute measurements of coronary flow with quantitative CMRI analysis.

  4 weeks after inclusion.

Interventions

Diagnostic tests DIAGNOSTIC_TEST

Head-to-head comparison between: * CADScor and Diamond-Foster score * Rb PET and 3T CMRI * QFR and ICA-FFR

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with an indication for CCTA.

You may qualify if:

• Patients with an indication for CCTA.
• Qualified patients who have signed a written informed consent form.

You may not qualify if:

• CADScor specific
• Fragile or compromised skin in the area for application of the CADScor®Patch.
• Known allergy to polyacrylate adhesives.
• Significant operation scars or abnormal body shape in left IC4 (4th Inter Costal region).
• Use of vasodilating agents at the same day and prior to CAD-score measurements.
• Demography and co-existing cardiac morbidity specific
• Age below 30 years.
• Patients having a donor heart, a mechanic heart, or mechanical heart pump.
• Suspicion acute coronary syndrome Previous revascularization.
• Scan specific
• CCTA:
• Pregnant women, including women who are potentially pregnant or lactating.
• Reduced kidney function, with an estimated glomerular filtration rate (eGFR) \< 40 mL/min.
• Allergy to X-ray contrast medium.
• CMRI and PET:

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (5)

Aarhus University Hospital

Aarhus, Central Jutland, 8200, Denmark

Location

Regional Hospital of Herning

Herning, Central Jutland, 7400, Denmark

Location

Regional Hospital of Silkeborg

Silkeborg, Central Jutland, 8600, Denmark

Location

Regional Hospital of Randers

Randers, 8900, Denmark

Location

Regional Hospital of Viborg

Viborg, 8800, Denmark

Location

Related Publications (9)

• Rasmussen LD, Sikjaer M, Soby JH, Pedersen OB, Westra J, Efthekhari A, Christiansen EH, Foldyna B, Williams MC, Dweck MR, Newby DE, Douglas PS, Bottcher M, Winther S. Dual probability approach for risk adjustment in patients with a low clinical likelihood of coronary artery disease. Eur Heart J Cardiovasc Imaging. 2025 Aug 29;26(9):1507-1517. doi: 10.1093/ehjci/jeaf193.

  PMID: 40590244 DERIVED

• Brix GS, Rasmussen LD, Rohde PD, Nissen L, Nyegaard M, O'Donoghue ML, Bottcher M, Winther S. Elevated lipoprotein(a) levels are independently associated with the presence of significant coronary stenosis in de-novo patients with stable chest pain. Am Heart J. 2025 Apr;282:103-113. doi: 10.1016/j.ahj.2025.01.001. Epub 2025 Jan 7.

  PMID: 39788470 DERIVED

• Karim SR, Westra JS, Rasmussen LD, Eftekhari A, Sejr-Hansen M, Winther S, Bottcher M, Christiansen EH. Effect of Guiding Catheter Extubation During Physiological Assesment of Stenosis. Catheter Cardiovasc Interv. 2025 Mar;105(4):735-744. doi: 10.1002/ccd.31370. Epub 2024 Dec 30.

  PMID: 39736151 DERIVED

• Rasmussen LD, Westra J, Karim SR, Dahl JN, Soby JH, Ejlersen JA, Gormsen LC, Eftekhari A, Christiansen EH, Bottcher M, Winther S. Microvascular resistance reserve: impact on health status and myocardial perfusion after revascularization in chronic coronary syndrome. Eur Heart J. 2025 Feb 3;46(5):424-435. doi: 10.1093/eurheartj/ehae604.

  PMID: 39217607 DERIVED

• Rasmussen LD, Murphy T, Milidonis X, Eftekhari A, Karim SR, Westra J, Dahl JN, Isaksen C, Brix L, Ejlersen JA, Nyegaard M, Johansen JK, Sondergaard HM, Mortensen J, Gormsen LC, Christiansen EH, Chiribiri A, Petersen SE, Bottcher M, Winther S. Myocardial Blood Flow by Magnetic Resonance in Patients With Suspected Coronary Stenosis: Comparison to PET and Invasive Physiology. Circ Cardiovasc Imaging. 2024 Jun;17(6):e016635. doi: 10.1161/CIRCIMAGING.124.016635. Epub 2024 Jun 18.

  PMID: 38889213 DERIVED

• Rasmussen LD, Gormsen LC, Ejlersen JA, Karim SR, Westra J, Knudsen LL, Kirk J, Sondergaard HM, Mortensen J, Knuuti J, Christiansen EH, Eftekhari A, Bottcher M, Winther S. Impact of Absolute Myocardial Blood Flow Quantification on the Diagnostic Performance of PET-Based Perfusion Scans Using 82Rubidium. Circ Cardiovasc Imaging. 2024 Jan;17(1):e016138. doi: 10.1161/CIRCIMAGING.123.016138. Epub 2024 Jan 16.

  PMID: 38227687 DERIVED

• Rasmussen LD, Winther S, Eftekhari A, Karim SR, Westra J, Isaksen C, Brix L, Ejlersen JA, Murphy T, Milidonis X, Nyegaard M, Benovoy M, Johansen JK, Sondergaard HM, Hammid O, Mortensen J, Knudsen LL, Gormsen LC, Christiansen EH, Chiribiri A, Petersen SE, Bottcher M. Second-Line Myocardial Perfusion Imaging to Detect Obstructive Stenosis: Head-to-Head Comparison of CMR and PET. JACC Cardiovasc Imaging. 2023 May;16(5):642-655. doi: 10.1016/j.jcmg.2022.11.015. Epub 2023 Feb 8.

  PMID: 36881421 DERIVED

• Rasmussen LD, Winther S, Karim SR, Westra J, Kirk Johansen J, Sondergaard HM, Hammid O, Sevestre E, Onuma Y, Nyegaard M, Ejlersen JA, Hoj Christiansen E, Eftekhari A, Holm NR, Schmidt SE, Bottcher M. Likelihood reclassification by an acoustic-based score in suspected coronary artery disease. Heart. 2023 Jul 27;109(16):1223-1230. doi: 10.1136/heartjnl-2023-322357.

  PMID: 36878672 DERIVED

• Rasmussen LD, Winther S, Westra J, Isaksen C, Ejlersen JA, Brix L, Kirk J, Urbonaviciene G, Sondergaard HM, Hammid O, Schmidt SE, Knudsen LL, Madsen LH, Frost L, Petersen SE, Gormsen LC, Christiansen EH, Eftekhari A, Holm NR, Nyegaard M, Chiribiri A, Botker HE, Bottcher M. Danish study of Non-Invasive testing in Coronary Artery Disease 2 (Dan-NICAD 2): Study design for a controlled study of diagnostic accuracy. Am Heart J. 2019 Sep;215:114-128. doi: 10.1016/j.ahj.2019.03.016. Epub 2019 May 1.

  PMID: 31323454 DERIVED

MeSH Terms

Conditions

Angina Pectoris; Atherosclerosis; Coronary Artery Disease; Myocardial Ischemia

Interventions

Diagnostic Tests, Routine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease

Intervention Hierarchy (Ancestors)

Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Morten Böttcher, MD, Ph.D

  Regional Hospital of Herning, department of cardiology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2018
• First Posted: March 29, 2018
• Study Start: January 24, 2018
• Primary Completion: December 3, 2020
• Study Completion: December 3, 2020
• Last Updated: January 20, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (5)