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

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.

Conditions

• Myocardial Infarction, Acute
• Myocardial Ischemia
• Myocardial Injury

Interventions

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.

Sponsors & Collaborators

• British Heart Foundation

  collaborator OTHER

• University of Edinburgh

  lead OTHER

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-10-23

Primary Completion

2020-11-06

Completion

2021-11-06

Countries

• United Kingdom

Study Locations