Primary objective: To validate the new, non-invasive QP-CMR imaging, stress T1 mapping reactivity and OS-CMR imaging with breathing maneuvers against invasive gold standard FFR for detection of obstructive CAD.Secondary objectives: 1) To compare (…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint: Diagnostic accuracy (sensitivity, specificity, accuracy, area
under the curve [AUC], positive predictive value [PPV], negative predictive
value [NPV]) of QP-CMR (stress MBF, stress rMBF, MPR and rMPR) to detect
obstructive CAD, as defined by FFR.
Secondary outcome
Secondary endpoints: 1) Diagnostic accuracy (sensitivity, specificity,
accuracy, AUC, PPV, NPV) of stress T1 mapping reactivity to detect obstructive
CAD, as defined by FFR; 2) Diagnostic accuracy (sensitivity, specificity,
accuracy, AUC, PPV, NPV) of OS-CMR (B-MORE) to detect obstructive CAD, as
defined by FFR; 3) Head-to-head comparison of diagnostic accuracies
(sensitivity, specificity, accuracy, AUC, PPV, NPV) of QP-CMR (stress MBF,
stress rMBF, MPR, rMPR), stress T1 mapping reactivity, OS-CMR (B-MORE) and
conventional visual assessment of GBCA-based first pass perfusion imaging to
detect obstructive CAD, as defined by FFR; 4) Diagnostic accuracy (sensitivity,
specificity, accuracy, AUC, PPV, NPV) of QP-CMR (stress MBF, stress rMBF, MPR
and rMPR) to detect obstructive CAD, as defined by iFR and resting Pd/Pa; 5)
Diagnostic accuracy (sensitivity, specificity, accuracy, AUC, PPV, NPV) of
stress T1 mapping reactivity to detect obstructive CAD, as defined by iFR and
resting Pd/Pa; 6) Diagnostic accuracy (sensitivity, specificity, accuracy, AUC,
PPV, NPV) of OS-CMR (B-MORE) to detect obstructive CAD, as defined by iFR and
resting Pd/Pa; 7) Head-to-head comparison of diagnostic accuracies
(sensitivity, specificity, accuracy, AUC, PPV, NPV) of QP-CMR (stress MBF,
stress rMBF, MPR, rMPR), stress T1 mapping reactivity, OS-CMR (B-MORE) and
conventional visual assessment of GBCA-based first pass perfusion imaging to
detect obstructive CAD, as defined by iFR and resting Pd/PaRelation of stress
and rest MBF and rMBF, MPR and rMPR, stress T1 mapping and B-MORE to Seattle
Angina Questionnaire (SAQ)-7 Summary score, SAQ-7 Angina Frequency score, SAQ-7
Physical Limitation score and SAQ-7 Quality of Life score (before and after
revascularization) and score in Rose Dyspnea Scale; 8) Prognostic value of
QP-CMR (stress MBF, stress rMBF, MPR and rMPR), stress T1 mapping reactivity
and OS-CMR (B-MORE) in predicting occurrence of a A) composite of
cardiovascular death, myocardial infarction, ischemia-driven coronary
revascularization or stroke; B) composite of myocardial infarction or
ischemia-driven coronary revascularization; C) composite of cardiovascular
death, stroke or myocardial infarction; D) myocardial infarction; E)
Ischemia-driven coronary revascularization; F) Stroke; G) Death from any cause;
H) Cardiovascular death
Tertiary endpoints: 1) Diagnostic accuracies (sensitivity, specificity,
accuracy, AUC, PPV, NPV) of QP-CMR (stress MBF, stress rMBF, MPR and rMPR),
stress T1 mapping reactivity and B-MORE to detect MVD, as defined by CFR; 2)
Diagnostic accuracy (sensitivity, specificity, accuracy, AUC, PPV, NPV) of
QP-CMR (stress MBF, stress rMBF, MPR and rMPR), stress T1 mapping reactivity
and B-MORE to differentiate between MVD (as defined by CFR) and 3-vessel
obstructive CAD; 3) Change in stress and rest MBF and rMBF, MPR and rMPR,
stress T1 mapping and B-MORE before and after revascularization; 4) Costs and
procedural time of QP-CMR, stress T1 mapping reactivity and OS-CMR compared to
ICA
Background summary
Obstructive coronary artery disease (CAD) involves formation of atherosclerotic
plaques in the lumen of coronary arteries, which causes the demand-supply
mismatch of oxygen and consequently leads to recurrent, transient episodes of
chest pain (angina pectoris), reflecting myocardial ischemia. Early diagnosis
of obstructive CAD enables fast initiation of targeted treatment, improves
patient quality of life, facilitates rehabilitation, accelerates quick return
to previous socio-economic environment and reduces costs for the society.
Invasive coronary angiography (ICA) is regarded as the *golden standard* to
detect obstructive CAD and multiple trials have demonstrated that coronary
revascularizations should be ischemia-driven, as measured by fractional flow
reserve (FFR), to relieve symptoms and to improve outcome. However, in
two-thirds of women and in one-third of men, ICA does not show obstructive CAD.
Therefore, up to 60% of the current diagnostic ICA procedures are unnecessary,
while patients do get exposed to the possible risk of an ICA. Therefore, a
reliable non-invasive screening tool to discriminate patients with obstructive
CAD from patients without obstructive CAD will prevent unnecessary ICA and
thereby will significantly reduce costs, increase the capacity of
catheterization laboratories, and promote efficient use of its infrastructure
for more targeted procedures. Stress perfusion cardiovascular magnetic
resonance (CMR) imaging is the guidelines-recommended non-invasive test for
detection of obstructive CAD. In daily clinical practice, stress perfusion CMR
is generally evaluated by visual assessment of first-pass perfusion images,
where the hypo-perfused myocardial segments show delayed gadolinium-based
contrast agent (GBCA) wash-in kinetics during first pass. Novel technical
advances allow absolute quantification of myocardial blood flow (quantitative
perfusion CMR; QP-CMR) and more recently, a new, fully-automated, pixel-wise
dual-bolus QP framework has been established for this purpose. Moreover, the
latest developments established several methods of assessment of CAD without
the need for a GBCA, including stress T1 mapping reactivity and
oxygen-sensitive CMR (OS-CMR) with breathing maneuvers. These methods may
overcome the need for exogenous administration of a GBCA in clinical routine,
making the evaluation of patients with suspected obstructive CAD more simple,
less invasive, time efficient and cost-effective. In addition, OS-CMR with
breathing maneuvers does not require exogenous administration of vasodilator
drug (i.e. adenosine). Such a needle- and GBCA-free approach will increase
patients comfort and safety during the CMR examination for ischemia detection.
Although these technical advancements use standard, regulatory-approved CMR
sequences for image acquisition, they require proper clinical validation
against currently recommended invasive gold standard. The studies aim to
validate the fully automated QP-CMR, stress T1 mapping reactivity and OS-CMR
with breathing maneuvers against fractional flow reserve (FFR) as a gold
standard, to detect obstructive coronary artery disease (CAD) in a real-world
population of symptomatic patients with angina pectoris with suspected or known
CAD (ADVOCATE-CMR and ADVOCATE-CMR 2, respectively). Moreover, we will
head-to-head compare the diagnostic performance of gadolinium-based contrast
agent (GBCA)-based (fully automated QP-CMR) and non-GBCA-based (stress T1
mapping reactivity and OS-CMR imaging with breathing maneuvers) methods for
non-invasive ischemia detection in patients with suspected obstructive CAD.
Furthermore, we will validate these CMR parameters against invasively measured
coronary flow reserve (CFR) to detect microvascular dysfunction (MVD) and
assess its performance to differentiate between 3-vessel obstructive CAD and
MVD, what is challenging using standard CMR imaging in current clinical
practice. We will also correlate QP-CMR, stress T1 mapping reactivity and
OS-CMR measures to short- and long-term clinical outcomes and will
comprehensively assess the impact of revascularization on CMR-derived MBF,
myocardial perfusion reserve (MPR), stress T1 mapping reactivity and myocardial
oxygenation. This will give an important pathophysiological insight into the
currently recommended treatment strategies in patients with obstructive CAD and
therefore trigger initiation of new studies aiming to optimize patient
management to improve the clinical outcomes. Based on our results, we expect to
establish a well-validated, time-efficient and cost-effective diagnostic
workflow available to a wide range of general CMR services performing CMR.
Finally, these improvements may enable CMR to become an effective, potentially
needle-free, non-invasive gatekeeper (providing functional measures) for ICA in
patients with suspected obstructive CAD and may become an alternative for
conventional invasive, radiation-based strategies.
Study objective
Primary objective: To validate the new, non-invasive QP-CMR imaging, stress T1
mapping reactivity and OS-CMR imaging with breathing maneuvers against invasive
gold standard FFR for detection of obstructive CAD.
Secondary objectives: 1) To compare (head-to-head) the diagnostic accuracy of
the new, non-invasive QP-CMR imaging, stress T1 mapping reactivity, OS-CMR
imaging with breathing maneuvers and the conventional visual assessment of
GBCA-based first pass perfusion imaging to detect obstructive CAD (defined by
invasive FFR); 2) To validate the new, non-invasive QP-CMR imaging, stress T1
mapping reactivity and OS-CMR imaging with breathing maneuvers against invasive
iFR and resting Pd/Pa for detection of obstructive CAD; 3) To compare
(head-to-head) the diagnostic accuracy of the new, non-invasive QP-CMR imaging,
stress T1 mapping reactivity, OS-CMR imaging with breathing maneuvers and the
conventional visual assessment of GBCA-based first pass perfusion imaging to
detect obstructive CAD (defined by invasive iFR and resting Pd/Pa); 4) To
correlate QP-CMR, stress T1 mapping reactivity and OS-CMR measures to short-
and long-term clinical outcomes (angina-related symptoms, function, and quality
of life, all cause death, cardiovascular death, stroke, myocardial infarction
and ischemia-driven coronary revascularization)
Tertiary objectives: 1) To validate the QP-CMR imaging, stress T1 mapping
reactivity and OS-CMR imaging with breathing maneuvers against invasively
measured coronary flow reserve (CFR) for detection of microvascular dysfunction
(MVD); 2) To assess the performance of QP-CMR imaging, stress T1 mapping
reactivity and OS-CMR imaging with breathing maneuvers to differentiate between
3-vessel obstructive CAD and MVD; 3) To study the change in stress and rest MBF
and rMBF, MPR and rMPR (assessed by QP-CMR), stress T1 mapping reactivity and
B-MORE (assessed by OS-CMR with breathing maneuvers) after coronary
revascularization; 4) To determine the procedural time and analyze costs of
QP-CMR, stress T1 mapping reactivity and OS-CMR (in comparison to ICA).
Study design
Single-center observational prospective cross-sectional cohort study performed
at the Amsterdam University Medical Centers - Location VUmc.
Study burden and risks
Patients will not benefit from study participation in any form. CMR results
will not impact any clinical decisions related to diagnosis, treatment, or any
aspect of patient management. Therefore, the CMR will be a non-invasive
examination that will be additional and completely separate from the standard
clinical diagnostic and therapeutic procedures. Risks related to participation
are minimal. Nevertheless there is a small chance for (serious) adverse events
during intra-venous or intra-coronary infusion of adenosine and or GBCA.
Disadvantages to participation are also minimal, but include time (i.e. CMR
examinations prior to and after ICA, FFR and other invasive measurements, and
phone calls for clinical follow-up) and potentially an uncomfortable feeling
due to adenosine and/or GBCA administration. All study procedures, except for
OS-CMR, are routinely performed in the Amsterdam UMC, location VUmc for
clinical and/or research purposes.
De Boelelaan 1117
Amsterdam 1091HV
NL
De Boelelaan 1117
Amsterdam 1091HV
NL
Listed location countries
Age
Inclusion criteria
ADVOCATE-CMR:
- Suspected obstructive CAD
- No documented prior history of CAD
- Clinical referral for ICA according to the referring clinician*s decision
- Age >=18 years
- Signed informed consent
ADVOCATE-CMR 2:
- Suspected obstructive CAD
- Previous myocardial infarction and/or percutaneous coronary intervention, at
least 3 months earlier
- Clinical referral for ICA according to the referring clinician*s decision
- Age >=18 years
- Signed informed consent
Exclusion criteria
ADVOCATE-CMR:
- Acute coronary syndrome
- History of coronary revascularization (percutaneous coronary intervention or
coronary artery bypass grafting surgery)
- History of CAD or acute coronary syndrome (myocardial infarction, unstable
angina)
- Use of sildenafil or dipyridamole that cannot be terminated
- Pregnancy or lactation
- Allergic reaction to iodized contrast
- Concurrent or prior (within last 30 days) participation in other research
studies using interventional drugs
- Extensive comorbidities (i.e. cancer, other severe chronic diseases)
- Contraindication for CMR with GBCA (including severe claustrophobia, MR
unsafe implants/devices or MR conditional devices not suitable for 3T scanner,
severe renal failure with eGFR<30 mL/min/1,73 m2, known hypersensitivity for
GBCA)
- Contraindications for adenosine usage (including hypersensitivity to
adenosine/dipyridamole/regadenoson, second or third degree atrio-ventricular
block, sick sinus syndrome, sinus bradycardia (heart rate <40 bpm), long QT
syndrome, severe hypertension (> 220/120 mmHg), systolic blood pressure
<90mmHg, concomitant use of dipyridamole,severe asthma or severe chronic
obstructive pulmonary disease)
ADVOCATE-CMR 2:
- Acute coronary syndrome
- History of coronary artery bypass grafting surgery
- Use of sildenafil or dipyridamole that cannot be terminated
- Pregnancy or lactation
- Allergic reaction to iodized contrast
- Concurrent or prior (within last 30 days) participation in other research
studies using interventional drugs
- Extensive comorbidities (i.e. cancer, other severe chronic diseases)
- Contraindication for CMR with GBCA (including severe claustrophobia, MR
unsafe implants/devices or MR conditional devices not suitable for 3T scanner,
severe renal failure with eGFR<30 mL/min/1,73 m2, known hypersensitivity for
GBCA)
- Contraindications for adenosine usage (including hypersensitivity to
adenosine/dipyridamole/regadenoson, second or third degree atrio-ventricular
block, sick sinus syndrome, sinus bradycardia (heart rate <40 bpm), long QT
syndrome, severe hypertension (> 220/120 mmHg), systolic blood pressure
<90mmHg, concomitant use of dipyridamole, severe asthma or severe chronic
obstructive pulmonary disease)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL84828.015.23 |