Determining the Mechanism of Myocardial Injury and Role of Coronary Disease in Type 2 Myocardial Infarction (DEMAND-MI)


University of Edinburgh




Myocardial Ischemia
Myocardial Infarction, Acute
Myocardial Injury


Radiation: CT coronary angiography
Diagnostic Test: Invasive coronary angiography
Diagnostic Test: Cardiac MRI

Study type


Funder types




Details and patient eligibility


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.

Full 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.


100 patients




No Healthy Volunteers

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)

Trial design

100 participants in 1 patient group

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: Cardiac MRI
Diagnostic Test: Invasive coronary angiography
Radiation: CT coronary angiography

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