Coronary Microvascular Angina Cardiac Magnetic Resonance Imaging (CorCMR) Trial

  • End date
    Feb 27, 2024
  • participants needed
  • sponsor
    NHS National Waiting Times Centre Board
Updated on 27 March 2021


Anginal symptoms due to ischaemia with no obstructive coronary arteries (INOCA) is a common clinical problem, however, diagnosis and onward management is heterogeneous, and prognosis is affected. Recent advances in quantifying myocardial blood flow using stress perfusion cardiac magnetic resonance imaging (CMR) has potential for accurate detection coronary microvascular dysfunction.

The CorCMR diagnostic study involves stress perfusion CMR in patients with suspected INOCA to clarify the prevalence of subgroups of patients with underlying problems, such as microvascular disease or undisclosed obstructive coronary artery disease, that might explain their anginal symptoms.

A nested, prospective, randomised, controlled, double-blind trial will determine whether stratified medical therapy guided by the results of the stress perfusion CMR improves symptoms, well-being, cardiovascular risk and health and economic outcomes.



There are approximately 2 million men and women living with angina in the UK. In 2014, there were ~247,000 coronary angiograms performed, mostly for the investigation of known or suspected angina. However, obstructive CAD is detected in only 1 in 2 patients. The explanation for the cause(s) of the chest pain are often unclear. Microvascular or vasospastic angina may be one explanation.

Adjunctive tests of coronary artery function to diagnose these problems are rarely used during coronary angiography in the NHS, meaning that patient management may be empirical and heterogeneous. The lack of adoption of these novel tests in the NHS reflects key gaps in the clinical evidence. It is these gaps, coupled with the increasing adoption of anatomical coronary artery imaging with CT coronary angiography (CTCA), which stimulate this research. In recent large clinical trials, CT coronary angiography has been shown not to reduce the rate of invasive angiography. In fact, compared to standard care based on stress testing, CTCA is associated with less improvement in anginal symptoms and in quality of life (PUBMED ID: 28246175). Anatomical tests, such as CTCA and invasive angiography, do not provide information on myocardial blood flow. New evidence that addresses these gaps might inform therapy development and future trials.

Current gaps in evidence and guidelines point to a problem of unmet need in the NHS care pathway. Stress perfusion CMR has potential diagnostic value for microvascular disease, but whether it might discriminate clinical endotypes in a relatively unselected population of patients in daily practice, is uncertain. Further, access to stress perfusion CMR varies widely not least because evidence from randomised trials supporting clinical and economic benefits from a CMR-guided approach is lacking. CorCMR is a clinical strategy trial that is designed to address this evidence gap.


In patients with angina in whom obstructive disease in the epicardial coronary arteries has been ruled out by coronary angiography FFR, stress perfusion CMR will reclassify the diagnosis leading to changes in treatment (start or stop therapy), improvements in health and economic outcomes, as compared to decisions based standard care (CMR not disclosed).


We propose that an observational, diagnostic study involving stress CMR will provide information on the prevalence of microvascular disease in a population with anginal symptoms potentially attributable to myocardial ischaemia with no obstructive coronary arteries (INOCA). Each diagnosis is linked to a guideline-directed treatment plan.The potential value of this strategy can only be confirmed if it is associated with patient benefits, which is why we propose a nested, randomised, controlled, double-blind trial of routine disclosure of stress perfusion CMR vs. angiography-guided management


Patients undergoing invasive coronary angiography for the investigation of known or suspected angina and who do not have either structural heart disease or a systemic health problem that would explain those symptoms will be invited to participate. Written informed consent is required for participation. Eligibility is further confirmed at the time of the coronary angiogram by exclusion of obstructive (stenosis >70% in a single segment or 50 - 70% in 2 adjacent segments in an artery >2.5 mm, or FFR 0.80) coronary artery disease (CAD). Angina symptoms will be confirmed by the completion of validated questionnaires and patients will be invited to attend for a stress perfusion CMR within 3 months of the original coronary angiogram.

On arrival for the CMR, patients will be randomised (1:1) to either the intervention (CMR guided, results disclosed) or blinded control group (CMR undertaken but results not disclosed, standard of care) group.

Trial participants will be blinded to treatment group. The clinicians responsible for on-going care will also be blinded. The design is therefore 'double-blind'. Following the CMR, patients and clinicians will be advised of the diagnosis (endotype) but not the randomised group. The endotype will be informed by the CMR in the intervention group but not in the control group (CMR results not disclosed, angiography-guided). Medical therapy and lifestyle measures are linked to the endotype and informed by contemporary practice guidelines. Therefore, optimal guideline-directed medical care according to the endotype is intended to be the same, regardless of the group allocation.

The sample size is 280 randomised participants. The minimum follow-up duration is 12 months from the last participant recruitment. Follow-up will continued in the longer term including, where feasible, electronic case record linkage.

The primary outcome of the diagnostic study is the reclassification of the initial diagnosis based on findings from the cardiac MRI scan. The primary outcome of the nested randomised trial is the within-subject change at 6 months from baseline for the domains of the Seattle Angina Questionnaire.

Secondary outcomes include other Patient Reported Outcome Measures (PROMS) to describe other aspects of health and wellbeing. These include EQ-5D-5L, Illness perception (Brief IPQ), Treatment satisfaction (TSQM), Duke Activity Status Index (DASI), the International Physical Activity Questionnaire (IPAQ-SF) short-form and a pain questionnaire.

There is preliminary evidence that small vessel disease can be a systemic problem affecting different organs. Whether small vessel disease in the heart might associate with small vessel disease in the brain or retina is unknown. In the CorMicA pilot study, studies of small vessels isolated from biopsies found evidence of endothelial dysfunction and increased responsiveness of the blood vessels to naturally-occurring, constriction-inducing peptides such as endothelin and thromboxane. For these reasons, we plan heart-brain-retina and peripheral vascular substudies.

Condition Chest Pain, Chest Pain, Coronary Artery Disease, Coronary Artery Disease, Coronary heart disease, Angina Pectoris, Angina, Ischemic Heart Disease, Cardiac Ischemia, Myocardial Ischemia, Cardiac syndrome X, Stable Angina, Stable Angina Pectoris, Cerebral Small Vessel Disease, Small Vessel Cerebrovascular Disease, Non Obstructive Coronary Atherosclerosis, Angina, Cardiac Ischemia, Myocardial Ischemia
Treatment CMR results disclosed, CMR performed but results not disclosed
Clinical Study IdentifierNCT04805814
SponsorNHS National Waiting Times Centre Board
Last Modified on27 March 2021


Yes No Not Sure

Inclusion Criteria

Age 18 years
Symptoms of angina or angina-equivalent informed by the Rose Angina questionnaire
Coronary angiography 3 months with a plan for medical management

Exclusion Criteria

Obstructive coronary artery disease i.e. a stenosis >70% in a single segment or 50 - 70% in 2 adjacent segments in an artery >2.5 mm, or FFR 0.80
Coronary revascularization by percutaneous coronary intervention or coronary artery bypass graft surgery following the index angiogram
Prior coronary artery bypass surgery
A diagnosis that would explain the angina e.g. anaemia, aortic stenosis, hypertrophic cardiomyopathy
Contra-indication to contrast-enhanced CMR e.g. eGFR < 30mL/min/1.73m2
Contra-indication to intravenous adenosine, i.e. severe asthma; long QT syndrome; second- or third-degree AV block and sick sinus syndrome
Lack of informed consent
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