Danish study of Non-Invasive testing in Coronary Artery Disease 2 (Dan-NICAD 2): study design for a controlled study of diagnostic accuracy

Laust Dupont Rasmussen, Simon Winther, Jelmer Westra, Christin Isaksen, June Anita Ejlersen, Lau Brix, Jane Kirk, Grazina Urbonaviciene, Hanne Maare Søndergaard, Osama Hammid, Samuel Emil Schmidt, Lars Lyhne Knudsen, Lene Helleskov Madsen, Lars Frost, Steffen E. Petersen, Lars Christian Gormsen, Evald Høj Christiansen, Ashkan Eftekhari, Niels Ramsing Holm, Mette NyegaardAmedeo Chiribiri, Hans Erik Bøtker, Morten Böttcher

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background: Coronary computed tomography angiography (CTA) is the preferred primary diagnostic modality when examining patients with low to intermediate pre-test probability of coronary artery disease (CAD). Only 20-30% of these have potentially obstructive CAD. Because of the relatively poor positive predictive value of coronary CTA, unnecessary invasive coronary angiographies (ICAs) are conducted with the costs and risks associated with the procedure. Hence, an optimized diagnostic CAD algorithm may reduce the numbers of ICAs not followed by revascularization. The Dan-NICAD 2 study has 3 equivalent main aims: (1) To examine the diagnostic precision of a sound-based diagnostic algorithm, The CADScor®System (Acarix A/S, Denmark), in patients with a low to intermediate pre-test risk of CAD referred to a primary examination by coronary CTA. We hypothesize that the CADScor®System provides better stratification prior to coronary CTA than clinical risk stratification scores alone. (2) To compare the diagnostic accuracy of 3T cardiac magnetic resonance imaging (3T CMRI), 82rubidium positron emission tomography ( 82Rb-PET), and CT-derived fractional flow reserve (FFR CT) in patients where obstructive CAD cannot be ruled out by coronary CTA using ICA fractional flow reserve (FFR) as reference standard. (3) To compare the diagnostic performance of quantitative flow ratio (QFR) and ICA-FFR in patients with low to intermediate pre-test probability of CAD using 82Rb-PET as reference standard. Methods: Dan-NICAD 2 is a prospective, multicenter, cross-sectional study including approximately 2,000 patients with low to intermediate pre-test probability of CAD and without previous history of CAD. Patients are referred to coronary CTA because of symptoms suggestive of CAD, as evaluated by a cardiologist. Patient interviews, sound recordings, and blood samples are obtained in connection with the coronary CTA. If coronary CTA does not rule out obstructive CAD, patients will be examined by 3T CMRI 82Rb-PET, FFR CT, ICA, and FFR. Reference standard is ICA-FFR. Obstructive CAD is defined as an FFR ≤0.80 or as high-grade stenosis (>90% diameter stenosis) by visual assessment. Diagnostic performance will be evaluated as sensitivity, specificity, predictive values, likelihood ratios, calibration, and discrimination. Enrolment started January 2018 and is expected to be completed by June 2020. Patients are followed for 10 years after inclusion. Discussion: The results of the Dan-NICAD 2 study are expected to contribute to the improvement of diagnostic strategies for patients suspected of CAD in 3 different steps: risk stratification prior to coronary CTA, diagnostic strategy after coronary CTA, and invasive wireless QFR analysis as an alternative to ICA-FFR.

OriginalsprogEngelsk
TidsskriftAmerican Heart Journal
Vol/bind215
Sider (fra-til)114-128
Antal sider15
ISSN0002-8703
DOI
StatusUdgivet - 1 sep. 2019

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Coronary Artery Disease
Coronary Angiography
Positron-Emission Tomography
Pathologic Constriction
Magnetic Resonance Imaging
Computed Tomography Angiography
Denmark
Calibration
Cross-Sectional Studies
Interviews
Costs and Cost Analysis

Citer dette

Rasmussen, Laust Dupont ; Winther, Simon ; Westra, Jelmer ; Isaksen, Christin ; Ejlersen, June Anita ; Brix, Lau ; Kirk, Jane ; Urbonaviciene, Grazina ; Søndergaard, Hanne Maare ; Hammid, Osama ; Schmidt, Samuel Emil ; Knudsen, Lars Lyhne ; Madsen, Lene Helleskov ; Frost, Lars ; Petersen, Steffen E. ; Gormsen, Lars Christian ; Christiansen, Evald Høj ; Eftekhari, Ashkan ; Holm, Niels Ramsing ; Nyegaard, Mette ; Chiribiri, Amedeo ; Bøtker, Hans Erik ; Böttcher, Morten. / Danish study of Non-Invasive testing in Coronary Artery Disease 2 (Dan-NICAD 2) : study design for a controlled study of diagnostic accuracy. I: American Heart Journal. 2019 ; Bind 215. s. 114-128.
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title = "Danish study of Non-Invasive testing in Coronary Artery Disease 2 (Dan-NICAD 2): study design for a controlled study of diagnostic accuracy",
abstract = "Background: Coronary computed tomography angiography (CTA) is the preferred primary diagnostic modality when examining patients with low to intermediate pre-test probability of coronary artery disease (CAD). Only 20-30{\%} of these have potentially obstructive CAD. Because of the relatively poor positive predictive value of coronary CTA, unnecessary invasive coronary angiographies (ICAs) are conducted with the costs and risks associated with the procedure. Hence, an optimized diagnostic CAD algorithm may reduce the numbers of ICAs not followed by revascularization. The Dan-NICAD 2 study has 3 equivalent main aims: (1) To examine the diagnostic precision of a sound-based diagnostic algorithm, The CADScor{\circledR}System (Acarix A/S, Denmark), in patients with a low to intermediate pre-test risk of CAD referred to a primary examination by coronary CTA. We hypothesize that the CADScor{\circledR}System provides better stratification prior to coronary CTA than clinical risk stratification scores alone. (2) To compare the diagnostic accuracy of 3T cardiac magnetic resonance imaging (3T CMRI), 82rubidium positron emission tomography ( 82Rb-PET), and CT-derived fractional flow reserve (FFR CT) in patients where obstructive CAD cannot be ruled out by coronary CTA using ICA fractional flow reserve (FFR) as reference standard. (3) To compare the diagnostic performance of quantitative flow ratio (QFR) and ICA-FFR in patients with low to intermediate pre-test probability of CAD using 82Rb-PET as reference standard. Methods: Dan-NICAD 2 is a prospective, multicenter, cross-sectional study including approximately 2,000 patients with low to intermediate pre-test probability of CAD and without previous history of CAD. Patients are referred to coronary CTA because of symptoms suggestive of CAD, as evaluated by a cardiologist. Patient interviews, sound recordings, and blood samples are obtained in connection with the coronary CTA. If coronary CTA does not rule out obstructive CAD, patients will be examined by 3T CMRI 82Rb-PET, FFR CT, ICA, and FFR. Reference standard is ICA-FFR. Obstructive CAD is defined as an FFR ≤0.80 or as high-grade stenosis (>90{\%} diameter stenosis) by visual assessment. Diagnostic performance will be evaluated as sensitivity, specificity, predictive values, likelihood ratios, calibration, and discrimination. Enrolment started January 2018 and is expected to be completed by June 2020. Patients are followed for 10 years after inclusion. Discussion: The results of the Dan-NICAD 2 study are expected to contribute to the improvement of diagnostic strategies for patients suspected of CAD in 3 different steps: risk stratification prior to coronary CTA, diagnostic strategy after coronary CTA, and invasive wireless QFR analysis as an alternative to ICA-FFR.",
author = "Rasmussen, {Laust Dupont} and Simon Winther and Jelmer Westra and Christin Isaksen and Ejlersen, {June Anita} and Lau Brix and Jane Kirk and Grazina Urbonaviciene and S{\o}ndergaard, {Hanne Maare} and Osama Hammid and Schmidt, {Samuel Emil} and Knudsen, {Lars Lyhne} and Madsen, {Lene Helleskov} and Lars Frost and Petersen, {Steffen E.} and Gormsen, {Lars Christian} and Christiansen, {Evald H{\o}j} and Ashkan Eftekhari and Holm, {Niels Ramsing} and Mette Nyegaard and Amedeo Chiribiri and B{\o}tker, {Hans Erik} and Morten B{\"o}ttcher",
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month = "9",
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doi = "10.1016/j.ahj.2019.03.016",
language = "English",
volume = "215",
pages = "114--128",
journal = "American Heart Journal",
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Rasmussen, LD, Winther, S, Westra, J, Isaksen, C, Ejlersen, JA, Brix, L, Kirk, J, Urbonaviciene, G, Søndergaard, 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, Bøtker, HE & Böttcher, M 2019, 'Danish study of Non-Invasive testing in Coronary Artery Disease 2 (Dan-NICAD 2): study design for a controlled study of diagnostic accuracy', American Heart Journal, bind 215, s. 114-128. https://doi.org/10.1016/j.ahj.2019.03.016

Danish study of Non-Invasive testing in Coronary Artery Disease 2 (Dan-NICAD 2) : study design for a controlled study of diagnostic accuracy. / Rasmussen, Laust Dupont; Winther, Simon; Westra, Jelmer; Isaksen, Christin; Ejlersen, June Anita; Brix, Lau; Kirk, Jane; Urbonaviciene, Grazina; Søndergaard, Hanne Maare; Hammid, Osama; Schmidt, Samuel Emil; Knudsen, Lars Lyhne; Madsen, Lene Helleskov; Frost, Lars; Petersen, Steffen E.; Gormsen, Lars Christian; Christiansen, Evald Høj; Eftekhari, Ashkan; Holm, Niels Ramsing; Nyegaard, Mette; Chiribiri, Amedeo; Bøtker, Hans Erik; Böttcher, Morten.

I: American Heart Journal, Bind 215, 01.09.2019, s. 114-128.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Danish study of Non-Invasive testing in Coronary Artery Disease 2 (Dan-NICAD 2)

T2 - study design for a controlled study of diagnostic accuracy

AU - Rasmussen, Laust Dupont

AU - Winther, Simon

AU - Westra, Jelmer

AU - Isaksen, Christin

AU - Ejlersen, June Anita

AU - Brix, Lau

AU - Kirk, Jane

AU - Urbonaviciene, Grazina

AU - Søndergaard, Hanne Maare

AU - Hammid, Osama

AU - Schmidt, Samuel Emil

AU - Knudsen, Lars Lyhne

AU - Madsen, Lene Helleskov

AU - Frost, Lars

AU - Petersen, Steffen E.

AU - Gormsen, Lars Christian

AU - Christiansen, Evald Høj

AU - Eftekhari, Ashkan

AU - Holm, Niels Ramsing

AU - Nyegaard, Mette

AU - Chiribiri, Amedeo

AU - Bøtker, Hans Erik

AU - Böttcher, Morten

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Background: Coronary computed tomography angiography (CTA) is the preferred primary diagnostic modality when examining patients with low to intermediate pre-test probability of coronary artery disease (CAD). Only 20-30% of these have potentially obstructive CAD. Because of the relatively poor positive predictive value of coronary CTA, unnecessary invasive coronary angiographies (ICAs) are conducted with the costs and risks associated with the procedure. Hence, an optimized diagnostic CAD algorithm may reduce the numbers of ICAs not followed by revascularization. The Dan-NICAD 2 study has 3 equivalent main aims: (1) To examine the diagnostic precision of a sound-based diagnostic algorithm, The CADScor®System (Acarix A/S, Denmark), in patients with a low to intermediate pre-test risk of CAD referred to a primary examination by coronary CTA. We hypothesize that the CADScor®System provides better stratification prior to coronary CTA than clinical risk stratification scores alone. (2) To compare the diagnostic accuracy of 3T cardiac magnetic resonance imaging (3T CMRI), 82rubidium positron emission tomography ( 82Rb-PET), and CT-derived fractional flow reserve (FFR CT) in patients where obstructive CAD cannot be ruled out by coronary CTA using ICA fractional flow reserve (FFR) as reference standard. (3) To compare the diagnostic performance of quantitative flow ratio (QFR) and ICA-FFR in patients with low to intermediate pre-test probability of CAD using 82Rb-PET as reference standard. Methods: Dan-NICAD 2 is a prospective, multicenter, cross-sectional study including approximately 2,000 patients with low to intermediate pre-test probability of CAD and without previous history of CAD. Patients are referred to coronary CTA because of symptoms suggestive of CAD, as evaluated by a cardiologist. Patient interviews, sound recordings, and blood samples are obtained in connection with the coronary CTA. If coronary CTA does not rule out obstructive CAD, patients will be examined by 3T CMRI 82Rb-PET, FFR CT, ICA, and FFR. Reference standard is ICA-FFR. Obstructive CAD is defined as an FFR ≤0.80 or as high-grade stenosis (>90% diameter stenosis) by visual assessment. Diagnostic performance will be evaluated as sensitivity, specificity, predictive values, likelihood ratios, calibration, and discrimination. Enrolment started January 2018 and is expected to be completed by June 2020. Patients are followed for 10 years after inclusion. Discussion: The results of the Dan-NICAD 2 study are expected to contribute to the improvement of diagnostic strategies for patients suspected of CAD in 3 different steps: risk stratification prior to coronary CTA, diagnostic strategy after coronary CTA, and invasive wireless QFR analysis as an alternative to ICA-FFR.

AB - Background: Coronary computed tomography angiography (CTA) is the preferred primary diagnostic modality when examining patients with low to intermediate pre-test probability of coronary artery disease (CAD). Only 20-30% of these have potentially obstructive CAD. Because of the relatively poor positive predictive value of coronary CTA, unnecessary invasive coronary angiographies (ICAs) are conducted with the costs and risks associated with the procedure. Hence, an optimized diagnostic CAD algorithm may reduce the numbers of ICAs not followed by revascularization. The Dan-NICAD 2 study has 3 equivalent main aims: (1) To examine the diagnostic precision of a sound-based diagnostic algorithm, The CADScor®System (Acarix A/S, Denmark), in patients with a low to intermediate pre-test risk of CAD referred to a primary examination by coronary CTA. We hypothesize that the CADScor®System provides better stratification prior to coronary CTA than clinical risk stratification scores alone. (2) To compare the diagnostic accuracy of 3T cardiac magnetic resonance imaging (3T CMRI), 82rubidium positron emission tomography ( 82Rb-PET), and CT-derived fractional flow reserve (FFR CT) in patients where obstructive CAD cannot be ruled out by coronary CTA using ICA fractional flow reserve (FFR) as reference standard. (3) To compare the diagnostic performance of quantitative flow ratio (QFR) and ICA-FFR in patients with low to intermediate pre-test probability of CAD using 82Rb-PET as reference standard. Methods: Dan-NICAD 2 is a prospective, multicenter, cross-sectional study including approximately 2,000 patients with low to intermediate pre-test probability of CAD and without previous history of CAD. Patients are referred to coronary CTA because of symptoms suggestive of CAD, as evaluated by a cardiologist. Patient interviews, sound recordings, and blood samples are obtained in connection with the coronary CTA. If coronary CTA does not rule out obstructive CAD, patients will be examined by 3T CMRI 82Rb-PET, FFR CT, ICA, and FFR. Reference standard is ICA-FFR. Obstructive CAD is defined as an FFR ≤0.80 or as high-grade stenosis (>90% diameter stenosis) by visual assessment. Diagnostic performance will be evaluated as sensitivity, specificity, predictive values, likelihood ratios, calibration, and discrimination. Enrolment started January 2018 and is expected to be completed by June 2020. Patients are followed for 10 years after inclusion. Discussion: The results of the Dan-NICAD 2 study are expected to contribute to the improvement of diagnostic strategies for patients suspected of CAD in 3 different steps: risk stratification prior to coronary CTA, diagnostic strategy after coronary CTA, and invasive wireless QFR analysis as an alternative to ICA-FFR.

UR - http://www.scopus.com/inward/record.url?scp=85068842739&partnerID=8YFLogxK

U2 - 10.1016/j.ahj.2019.03.016

DO - 10.1016/j.ahj.2019.03.016

M3 - Journal article

VL - 215

SP - 114

EP - 128

JO - American Heart Journal

JF - American Heart Journal

SN - 0002-8703

ER -