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Determining the Mechanism of Myocardial Injury and Role of Coronary Disease in Type 2 Myocardial Infarction

Completed
Conditions
Myocardial Ischemia
Myocardial Infarction, Acute
Myocardial Injury
Interventions
Diagnostic Test: Invasive coronary angiography
Radiation: CT coronary angiography
Diagnostic Test: Cardiac MRI
Registration Number
NCT03338504
Lead Sponsor
University of Edinburgh
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Suspected type 2 myocardial infarctionCardiac MRIThe 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.
Suspected type 2 myocardial infarctionInvasive coronary angiographyThe 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.
Suspected type 2 myocardial infarctionCT coronary angiographyThe 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.
Primary Outcome Measures
NameTimeMethod
Prevalence of coronary disease30 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

Secondary Outcome Measures
NameTimeMethod
Presence of intraluminal plaque rupture30 days of index presentation

Determined using invasive optical coherence tomography

All cause mortality1 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.

Lesion severity30 days of index presentation

Assessed using the invasive (FFR) or non-invasive (CT-FFR) fractional flow reserve technique

Pattern of myocardial injury30 days of index presentation

Determined using the late gadolinium enhancement technique

Cardiovascular death and future myocardial infarction1 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.

Trial Locations

Locations (1)

Centre for Cardiovascular Science

🇬🇧

Edinburgh, United Kingdom

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