Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction.

The myocardial salvage index was defined as infarct size at 6 months indexed to the initial area-at-risk revealed by T2-weighted MRI.

Final infarct size imaged on the MRI scan 6 months after initial hospitalisation for STEMI. Late gadolinium enhancement is revealed by MRI scanning 10 - 15 minutes after intravenous gadolinium contrast administration. The myocardial mass of late gadolinium (grams) will be quantified by a semi-automatic detection method using a signal intensity threshold of >5 standard deviations above a remote reference region.

Myocardial haemorrhage (a prioritised secondary outcome) is revealed by T2 weighted imaging and is defined as a confluent dark zone with a mean signal intensity <2 standard deviations of the mean signal intensity of the surrounding affected brighter area in the area of injury. Haemorrhage is specifically identified by T2* mapping, and will also be imaged with T2-weighted MRI (e.g. T2 mapping).

MVO is classified as present (central dark zone with a subendocardial or intra-mural distribution (binary)) and non-relevant (dots or nil) and quantified as a % of total left ventricular mass, after adjustment for the initial area-at-risk revealed by T2-weighted MRI. Late MVO is imaged by MRI 10 - 15 minutes after contrast administration. Late MVO should be preceded by abnormal first pass and early MVO on 1, 3, and 5 minute scans.

First pass MVO is revealed by MRI scanning during the 'first pass' of gadolinium contrast in the ventricular myocardium. The extent of the first pass perfusion deficit at rest (i.e. first pass 'wash-in' MVO) will be assessed.

Early MVO is acquired with MRI scanning 1 minute after gadolinium administration and forms part of the diagnostic criteria to confirm LATE MVO.

The jeopardised area-at-risk on each axial image is defined as the percentage of left ventricular area delineated by the hyperintense zone on T2-weighted MRI with parametric maps. The initial area-at-risk will be assessed retrospectively with MRI ~2 days after initial hospitalisation for STEMI. Area-at-risk will be assessed with T2 and T1 mapping. The area-at-risk will be quantified by a semi-automatic detection method using a signal intensity threshold of >2 standard deviations above a remote reference region.

The myocardial T1 relaxation time (ms) pre- and post-contrast will be estimated using a Modified Look-Locker Inversion recovery method (MOLLI, Siemens Healthcare). Post-contrast MOLLI scans will be obtained approximately 15 minutes after intravenous injection of gadolinium. Haematocrit will be measured from a full blood count blood test obtained at the time of the scan.

The myocardial T2 relaxation time (ms) will be estimated using a balanced steady state free precession method (Siemens Healthcare).

Left ventricular ejection fraction (LVEF) is measured by subtraction of left ventricular end-systolic volume from left ventricular end-diastolic volume. LVEF is measure of systolic function and is a prognostically validated surrogate of health outcome.

Left ventricular end-diastolic volume (millilitres)

Left ventricular end-systolic volume (millilitres)

The index of microvascular resistance (IMR) is a guidewire-derived measurement of coronary microvascular function. IMR = mean distal coronary pressure x mean transit time, measured during systemic hyperaemia induced by intravenous adenosine (140 ug/kg/min). Resting physiological parameters will also be measured.

Patient-reported quality of life and health status will be assessed at baseline and during follow-up at 6 months. The Euroquol EQ-5D questionnaire will be used. Health-related quality of life will be related to other clinical information, including the MRI findings, and for estimation of quality-adjusted life years which is relevant for health economic assessments.

The clinical characteristics that might predict recurrent cardiac events in survivors of STEMI are uncertain. The risk of recurrent MI is clinically relevant since this risk is potentially modifiable by additional PCI, as observed in the Preventative Angioplasty in Acute Myocardial Infarction (PRAMI) trial (N Engl J Med 2013 DOI: 10.1056/NEJMoa1305520).

The clinical predictors of recurrent MI, as revealed by contrast MRI at 6 months and recurrent adverse cardiac events during the longer term will be assessed. Recurrent MI may be fatal or non-fatal. The characteristics to be assessed at baseline will include clinical characteristics (e.g. age, diabetes), coronary artery disease characteristics (as revealed by quantitative coronary analysis and plaque characterisation), guidewire-derived parameters of coronary artery function, and MI characteristics as revealed by contrast-enhanced MRI.

The response to intravenous adenosine as reflected by patient-reported symptoms and changes in heart rate and blood pressure will be prospectively assessed. Adverse events, such as abnormalities in heart rate and rhythm and bronchospasm, that might be associated with the adenosine infusion will also be recorded.

Major Adverse Cardiac Events are defined as cardiac death, non-fatal myocardial infarction (MI) or hospitalisation for heart failure. The event definitions will follow the FDA guidelines (Hicks K et al 2010, 2012) and the Third Universal Definition of Myocardial Infarction (Thygesen et al Eur Heart J 2012). Events will be reviewed by a cardiologist who is independent of the research team and who is blinded to the MRI results. MACE will be related to the clinical and MRI findings at baseline. The survival analysis will be performed at the end of the study and again after a minimum of 3 years follow-up in all participants. The longer term follow-up will be performed by electronic case record linkage to hospital, NHS and government records.

Major Adverse Cardiovascular Events (MACCE) is the composite of cardiovascular death, non-fatal MI, hospitalisation for TIA or stroke. The event definitions will follow the FDA guidelines (Hicks K et al 2010, 2012) and the Third Universal Definition of Myocardial Infarction (Thygesen et al Eur Heart J 2012). THE MACCE events will be reviewed by a cardiologist who is independent of the research team and who is blinded to the MRI results. MACCE will be related to the clinical and MRI findings at baseline. The survival analysis will be performed at the end of the study and again after a minimum of 3 years follow-up in all participants. The longer term follow-up will be performed by electronic case record linkage to hospital, NHS and government records.

All serious adverse cardiovascular events including cardiovascular death, non-fatal MI, hospitalisation for unstable angina, hospitalisation for heart failure, implantable defibrillator implantation, hospitalisation for TIA or stroke, PCI, or CABG will be evaluated. Event definitions will follow the FDA guideline (Hicks K et al 2010, 2012) and the Third Universal Definition of Myocardial Infarction (Thygesen et al Eur Heart J 2012). In order to understand the prognostic significance of the clinical and MRI findings, these baseline findings will be associated with the cardiovascular events. The events will be reviewed by a cardiologist who is independent of the research team and who is blinded to the MRI results. The follow-up analysis will be performed at the end of the study and again after a min 3 years follow-up. The longer term follow-up will be performed by electronic case record linkage to hospital, NHS and government records.

All-cause death and hospitalisation for heart failure is taken to be prognostically important and mechanistically linked to impaired heart function and injury after STEM. Event definitions will follow the FDA guideline (Hicks K et al 2010, 2012). In order to understand the prognostic significance of the clinical and MRI findings, these baseline findings will be associated with the occurrence of death or heart failure. Implantation of a cardiac defibrillator for primary or secondary prevention in a post-MI patient will also be considered. The events will be reviewed by a cardiologist who is independent of the research team and who is blinded to the MRI results. The follow-up analysis will be performed at the end of the study and again after a minimum of 3 years follow-up in all participants. The longer term follow-up will be performed by electronic case record linkage to hospital, NHS and government records.