- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03338504
Determining the Mechanism of Myocardial Injury and Role of Coronary Disease in Type 2 Myocardial Infarction (DEMAND-MI)
June 9, 2022 updated by: University of Edinburgh
Myocardial injury is common in patients without acute coronary syndrome, and therefore international guidelines propose a classification of patients with myocardial infarction by aetiology.
This differentiates between myocardial infarction due to plaque rupture (type 1) and myocardial oxygen supply-demand imbalance (type 2) in other acute illnesses.
However, these guidelines have not been widely adopted as the diagnostic criteria for type 2 myocardial infarction are not clearly defined.
Patients with type 2 myocardial infarction have poor long term outcomes, with at least twice the mortality at five years compared to those with an index type 1 myocardial infarction.
Despite the majority of deaths being attributable to non-cardiovascular events, the rate of future type 1 myocardial infarction or cardiovascular death is similar regardless of index classification.
If this future risk is related to the presence of underlying coronary artery disease, then there may be the potential to improve outcomes through targeted investigation and secondary prevention.
The investigators will undertake a systematic evaluation of the mechanism of myocardial injury and the role of coronary artery disease in 100 patients with elevated cardiac troponin concentrations where the diagnosis is likely to be type 2 myocardial infarction.
These studies will help improve the assessment of patients with myocardial injury, refine the diagnostic criteria for type 2 myocardial infarction, and aid the design of future therapeutic trials.
Study Overview
Status
Completed
Intervention / Treatment
Detailed Description
The investigators will systematically evaluate the mechanisms of acute myocardial injury in unselected patients who present to hospital with an alternative primary illness likely to cause myocardial oxygen supply or demand imbalance.
All patients will be assessed by a member of the study team during their index admission and will undergo a detailed assessment of their coronary anatomy with either computed tomography coronary angiography (CTCA), CT calcium scoring and non-invasive fractional flow reserve assessment (CT-FFR) or invasive coronary angiography with optical coherence tomography (OCT) and invasive fractional flow reserve (FFR).
The pattern of myocardial injury and its functional consequence will be evaluated by cardiac magnetic resonance (CMR) imaging.
The investigators will determine the kinetics of cardiac troponin release using serial testing at multiple time points throughout admission, and quantify other proteins and the expression of long non-coding RNA and associated mRNA to identify differences related to the presence of coronary artery disease, which may help to identify new biomarkers.
Study Type
Observational
Enrollment (Actual)
100
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Edinburgh, United Kingdom, EH16 4SB
- Centre for Cardiovascular Science
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
Hospitalized patients with acute myocardial injury (defined as a rise and or fall in cardiac troponin concentration on serial testing, with at least one value >99th centile) where the likely mechanism of injury is thought to be myocardial oxygen supply and demand imbalance (e.g secondary to hypoxia, hypotension, tachycardia or anaemia).
Description
Inclusion Criteria:
- Unscheduled hospital admission with acute myocardial injury (defined as a rise and or fall in high-sensitivity cardiac troponin I concentrations on blood testing)
- A suspected aetiology of myocardial oxygen supply and demand imbalance with symptoms or signs of myocardial ischaemia
Exclusion Criteria:
- Unable or unwilling to give informed consent
- Women who are pregnant, breastfeeding or of child-bearing potential (women who have experienced menarche, are pre-menopausal and have not been sterilised) will not be enrolled into the trial.
- Probable type 1 myocardial infarction
- Renal impairment (estimated glomerular filtration rate ≤30ml/min/1.73m2)
- Severe hepatic impairment
- Frailty with inability to self-transfer (determined using Katz Index)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Suspected type 2 myocardial infarction
The investigators will identify consecutive patients with acute myocardial injury (defined as a rise and or fall in cardiac troponin concentration on serial testing, with at least one value >99th centile) where the likely mechanism of injury is thought to be myocardial oxygen supply and demand imbalance (e.g secondary to hypoxia, hypotension, tachycardia or anaemia).
Patients will be identified through screening of cardiac troponin measurements.
Patients who meet both the inclusion and exclusion criteria, will be approached and those who provide consent will comprise the study population.
All patients will have a Cardiac MRI scan, with invasive coronary angiography or CT coronary angiography dependent on baseline fitness.
The investigators will record demographic and clinical information from the electronic patient record for patients who meet inclusion criteria but have one or more exclusion criteria.
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Where patients are fit, coronary angiography will be performed via the femoral or radial artery with 6F arterial catheters.
In patients with one or more stenoses in a major epicardial vessel, a coronary pressure guidewire (PressureWire™ Aeris™, St. Jude Medical, St. Paul, Minnesota) will be used to determine distal coronary pressure and the fractional flow reserve (FFR) calculated at maximal adenosine-induced (intravenous 140 μg/kg/min) hyperaemia.
Optical coherence tomography (OCT) will be performed in all three coronary vessels using a Dragonfly® coronary imaging catheter (Abbott Diagnostics, Abbott Park, Illinois) with pullback at 20 mm/s to identify features consistent with vulnerable plaque or recent plaque rupture.(16)
If there is evidence of inducible myocardial ischaemia due to coronary artery stenosis, revascularisation with percutaneous coronary intervention may be considered if in the patients best interests.
CT coronary angiography will be performed using a 128 multidetector row CT.
Patients with a heart rate exceeding 65 beats/min will receive oral beta-blockade 1 hour before computed tomography.
Additional intravenous beta blockers will be given depending on heart rate at the time of imaging.
All patients will receive sublingual glyceryl trinitrate (300 μg) immediately prior to dual cardiac and respiratory-gated computed tomography imaging of the coronary arteries.
The investigators will quantify total plaque burden using CT calcium scoring.
A bolus of 80-100 mL of contrast will be injected intravenously at 5 mL/s.
An assessment of the functional consequences of coronary artery stenosis will be made using the computed tomography fractional flow reserve (CT-FFR) technique, using the HeartFlow platform.
Cardiovascular magnetic resonance (CMR) will be performed using a 3T scanner.
The MRI scan will consist of localisers, axial and coronal HASTE images, standard breath-held and ECG-gated cine sequences.
Short-axis cine images will be obtained for the assessment of left ventricle function and volumes.
Left ventricle volumes, mass and ejection fraction will be assessed using dedicated software and values indexed to body surface area.
Breath-held, ECG-gated T2 mapping sequences of the myocardium will be performed in the short-axis as a marker of myocardial inflammation.
T1-weighted imaging of the coronary arteries will be performed to look for evidence of recent intraplaque thrombus or haemorrhage.
The late gadolinium enhancement and T2 mapping techniques will identify regions of new or old myocardial infarction as well as other patterns of injury.
Where there are no contraindications, stress MRI will be performed using intravenous Regadenoson.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Prevalence of coronary disease
Time Frame: 30 days of index presentation
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Defined as obstructive (if stenosis >50% in the left main stem or >70% in a major epicardial vessel) or non obstructive disease
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30 days of index presentation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Lesion severity
Time Frame: 30 days of index presentation
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Assessed using the invasive (FFR) or non-invasive (CT-FFR) fractional flow reserve technique
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30 days of index presentation
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Presence of intraluminal plaque rupture
Time Frame: 30 days of index presentation
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Determined using invasive optical coherence tomography
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30 days of index presentation
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Pattern of myocardial injury
Time Frame: 30 days of index presentation
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Determined using the late gadolinium enhancement technique
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30 days of index presentation
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Cardiovascular death and future myocardial infarction
Time Frame: 1 year
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We will determine prevalence of major adverse cardiovascular events at one year in the study population, and those screened but not eligible for recruitment, to ensure a representative cohort.
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1 year
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All cause mortality
Time Frame: 1 year
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We will determine prevalence of major adverse cardiovascular events at one year in the study population, and those screened but not eligible for recruitment, to ensure a representative cohort.
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1 year
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Meah MN, Bularga A, Tzolos E, Chapman AR, Daghem M, Hung JD, Chiong J, Taggart C, Wereski R, Gray A, Dweck MR, Roobottom C, Curzen N, Kardos A, Felmeden D, Mills NL, Slomka PJ, Newby DE, Dey D, Williams MC. Distinguishing Type 1 from Type 2 Myocardial Infarction by Using CT Coronary Angiography. Radiol Cardiothorac Imaging. 2022 Oct 27;4(5):e220081. doi: 10.1148/ryct.220081. eCollection 2022 Oct.
- Chapman AR, Adamson PD, Mills NL. Assessment and classification of patients with myocardial injury and infarction in clinical practice. Heart. 2017 Jan 1;103(1):10-18. doi: 10.1136/heartjnl-2016-309530. Epub 2016 Nov 2.
- Bularga A, Hung J, Daghem M, Stewart S, Taggart C, Wereski R, Singh T, Meah MN, Fujisawa T, Ferry AV, Chiong J, Jenkins WS, Strachan FE, Semple S, van Beek EJR, Williams M, Dey D, Tuck C, Baker AH, Newby DE, Dweck MR, Mills NL, Chapman AR. Coronary Artery and Cardiac Disease in Patients With Type 2 Myocardial Infarction: A Prospective Cohort Study. Circulation. 2022 Apr 19;145(16):1188-1200. doi: 10.1161/CIRCULATIONAHA.121.058542. Epub 2022 Mar 28. Erratum In: Circulation. 2022 Apr 19;145(16):e841.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 23, 2017
Primary Completion (Actual)
November 6, 2020
Study Completion (Actual)
November 6, 2021
Study Registration Dates
First Submitted
November 7, 2017
First Submitted That Met QC Criteria
November 7, 2017
First Posted (Actual)
November 9, 2017
Study Record Updates
Last Update Posted (Actual)
June 10, 2022
Last Update Submitted That Met QC Criteria
June 9, 2022
Last Verified
June 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- FS/16/75/32533
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
IPD Plan Description
Requests for IPD will be considered on an individual basis.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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