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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
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

  • United Kingdom
      • Edinburgh, United Kingdom, EH16 4SB
        • Centre for Cardiovascular Science

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Diagnostic test: Invasive coronary angiography
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.
Radiation: CT coronary angiography
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.
Diagnostic test: Cardiac MRI
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Prevalence of coronary disease
Time Frame: 30 days of index presentation
Defined as obstructive (if stenosis >50% in the left main stem or >70% in a major epicardial vessel) or non obstructive disease
30 days of index presentation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Lesion severity
Time Frame: 30 days of index presentation
Assessed using the invasive (FFR) or non-invasive (CT-FFR) fractional flow reserve technique
30 days of index presentation
Presence of intraluminal plaque rupture
Time Frame: 30 days of index presentation
Determined using invasive optical coherence tomography
30 days of index presentation
Pattern of myocardial injury
Time Frame: 30 days of index presentation
Determined using the late gadolinium enhancement technique
30 days of index presentation
Cardiovascular death and future myocardial infarction
Time Frame: 1 year
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.
1 year
All cause mortality
Time Frame: 1 year
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.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Edinburgh

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
British Heart Foundation

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

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 23, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 6, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 6, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 7, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 7, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 9, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 10, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 9, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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