Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06070662 |
| Other study ID # |
0844 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 1, 2023 |
| Est. completion date |
September 2024 |
Study information
| Verified date |
September 2023 |
| Source |
University of Leicester |
| Contact |
Ranjit Arnold |
| Phone |
+44116 258 3038 |
| Email |
jra14[@]leicester.ac.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
- 40% of patients presenting with stable chest pain (angina) have no significant blockage
of the main heart arteries. Identifying why these patients have symptoms will mean
better treatment options can be developed.
- About 60% of these patients have evidence of coronary microvascular disease (CMD). In
this condition there is a problem with the heart's microvessels (very small blood
vessels that branch from the main heart arteries). Due to problems with these vessels
there is a mismatch between the blood supply to the heart and its oxygen consumption,
causing chest pain and this can also lead to major heart events.
- At present, to diagnose this condition, specialised techniques during an invasive test,
called a coronary angiogram, are required. As this is an invasive test, it can be lead
to complications and cause discomfort.
- Non-invasive ways of diagnosing CMD are required to improve the diagnosis and management
of this condition.
- This study aims to provide initial data on whether novel imaging techniques using CT and
MRI scans, which are much less invasive, could identify CMD.
- To do this, patients with suspected angina referred for angiography and who are already
participants in the main research study 'CMR versus CT-FFR in CAD' study will be
recruited.
- These will be patients with suspected CMD and also those with blockage of the main heart
arteries (triple vessel disease) to compare against.
- Participants in this pilot study will have additional tests used to diagnose CMD during
their invasive angiography procedure. Participants will then have an MRI scan involving
novel techniques and exercise MRI, where individuals exercise use a cycle or stepping
machine during the MRI scan. Further analysis will also be undertaken of CT images
acquired as part of the main study.
- These tests will be compared against invasive test results to see which show potential
in being able to diagnose CMD.
Description:
- Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the
United Kingdom. Approximately 40% of patients presenting with angina, however, have no
evidence of significant obstructive CAD.
- About 60% of these patients have evidence of coronary microvascular disease (CMD), where
there is dysfunction of the coronary microvessels leading to a mismatch between the
blood supply to the myocardium and oxygen consumption. This may be due to a number of
structural and functional changes including vascular remodelling, perivascular fibrosis,
endothelial dysfunction and vascular smooth muscle dysfunction. Although previously
thought of as a benign entity, recent studies suggest that CMD is associated with major
adverse events.
- Symptoms caused by CMD and obstructive CAD cannot be distinguished sufficiently to guide
diagnosis and management plans and conventional cardiac risk factors are poor
discriminators of the two conditions, therefore clinicians are reliant on further
investigations to diagnose CMD.
- Growing evidence supports invasive coronary physiological testing for this and methods
to measure coronary vascular function during angiography have been developed. Once
significant epicardial CAD has been excluded, CMD can be identified by impaired coronary
flow reserve (CFR) and the index of microvascular resistance (IMR).
- Despite the ability of invasive testing to detect CMD, these methods come with attendant
risks, as well as cost implications. Additionally, there is limited expertise and uptake
amongst interventional cardiologists in intracoronary physiological assessment, limiting
its widespread use. Hence, non-invasive surrogates are required to improve diagnosis and
management of CMD. However, currently available non-invasive tests, including exercise
ECG, stress echocardiography and nuclear imaging, lack the sensitivity and specificity
to diagnose CMD.
- Microvascular volume analysed using novel imaging methods may provide the diagnostic
accuracy required for the non-invasive identification of CMD. In CMD, patients may
exhibit reduced microvascular volume, in contrast to epicardial disease where there is
microvascular expansion and therefore these methods may be able to differentiate between
the two disease processes. A number of methods have been proposed for assessment of
microvascular volume using computed tomography (CT) and CMR. These methods include
coronary luminal volume to myocardial mass (V/M) ratio using computational CT analysis,
as well as CMR methods such as T1 mapping and Blood oxygen level-dependent CMR.
Furthermore, compared to using pharmacological stress, exercise CMR could provide
superior diagnostic ability to identify CMD, as it allows assessment during more
'physiological' stress.
- This study aims to provide pilot data on whether these novel CT and MRI and the use of
physiological stress (exercise CMR) could identify CMD in patients presenting with
angina. It aims to identify which of the proposed imaging methods could prove to be
clinically useful for non-invasive identification of CMD, providing justification for a
larger-scale diagnostic accuracy study.
- This is a prospective, single centre pilot study which will recruit individuals with
angina referred for angiography who are participants in the research study 'CMR versus
CT-FFR in CAD'.
- This pilot study will recruit both patients with suspected CMD and controls with
multi-vessel CAD to compare against.
- Participants will be consented to have additional invasive testing at angiography for
CMD. Those with confirmed CMD at angiography and all control participants will then have
an MRI scan compromising of advanced MRI techniques for assessment of microvascular
volume at rest and physiological stress (exercise). In addition, previously acquired CT
images from the main research study will be transferred to Heartflow for computation of
coronary blood volume.
- This will allow assessment of whether the novel imaging modalities proposed could be
clinically useful for non-invasive identification of CMD and distinction from epicardial
disease to inform larger future studies of these techniques.
