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

Acute ST-elevation Myocardial Infarction Clinical Trial

— BHF MR-MI  

Official title:

Cardiac Magnetic Resonance Imaging: New Pathological Insights and Their Functional and Clinical Significance in ST Elevation Acute Myocardial Infarction.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02072850
• Other study ID #: 10/S0703/28
• Secondary ID: Research grant n
• Status: Active, not recruiting
• Start date: May 2011
• Est. completion date: May 1, 2031

Study information

• Verified date: August 2021
• Source: NHS National Waiting Times Centre Board
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Heart imaging with magnetic resonance imaging (MRI) provides detailed insights into heart function and injury. The nature and significance of heart injury after a heart attack is incompletely understood. We propose a 'natural history' study of heart attack injury using contemporary MRI methods. In a large hospital in the West of Scotland, heart attack patients will be invited to have at least two MRI scans and also continue with life-long follow-up. The results from the MRI scans will be assessed with all of the other clinical information obtained at the time of the heart attack and during follow-up. The results of our study should provide new insights into heart attack injury and these results should help improve how heart attack patients should be treated.

Description:

Magnetic resonance imaging (MRI) provides detailed insights into soft tissue characteristics and this technique has particular value for imaging patients with acute myocardial infarction (MI). Recent advances in MRI have the potential to reveal new insights into the evolution and functional significance of myocardial injury and repair.

Here, we will study at least 300 consecutive patients with acute ST elevation MI (STEMI) and focus on oedema, scar and bleeding in the heart using MRI in patients managed by emergency percutaneous coronary intervention (PCI). Cardiac MRI scans will be performed at 1.5 Tesla (MAGNETOM, Siemens Healthcare). MRI will be used to assess initial heart function and injury. Myocardial salvage and haemorrhage are prioritised outcomes. Novel MRI methods will also be used to quantify the extent of myocardial jeopardy representing the initial area-at-risk (AAR), and the nature of this injury (strain, haemorrhage). The MRI methods will include T1, T2 and T2* relaxometry (mapping). Secondly, we will assess coronary artery disease severity by angiography and coronary artery function at the time of the heart attack treatment using a pressure-sensitive coronary guidewire (St Jude Medical). This wire can be used instead of the usual coronary wire and can provide information on heart injury, which can be linked in turn to the MRI findings. All of this information will be linked with health outcomes in the longer term.

We hypothesise that myocardial salvage, oedema, haemorrhage, and strain as revealed by MRI, have functional and prognostic significance. In all patients MRI will be performed at baseline (~day 2) and again at 6 months. In a subgroup of 30 patients, MRI will be performed on days <12 hours, and days 2, 7-10 days and 6 months post-MI. A blood and urine sample and quality of life will be obtained at baseline and at 6 months post-MI. Clinical outcomes (e.g. rehospitalisation, death) will be assessed at the end of the study (minimum 1 year) and again during longer term follow-up (minimum 3 years, maximum 20 years) by electronic linkage through central National Health Service (NHS) and government health records in order to determine the long-term prognostic significance of our initial observations with angiography, MRI and the pressure wire. The main statistical analyses will be conducted by an independent trials unit statistician.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 324
• Est. completion date: May 1, 2031
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Acute STEMI

Exclusion Criteria:

• Major systemic illness (e.g. cancer limiting survival < 6 months);

• Metallic implant (e.g. cochlear implant);

• Metallic foreign body

• Pregnancy.

Related Conditions & MeSH terms

• Acute ST-elevation Myocardial Infarction
• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction

Intervention

Device:
• Coronary pressure wire
Guidewire-based coronary pressure- and temperature recordings (coronary thermodilution) with and without hyperaemia induced by intravenous administration of adenosine (140 ug/kg/min) in patients with acute ST-elevation myocardial infarction treated by emergency PCI.

Other:
• Magnetic resonance imaging of the heart
Cardiac magnetic resonance imaging (MRI) with gadolinium contrast imaging at baseline (~ day 2) and 6 months (all participants) and in 30 subjects at 4 time-points (< 12 hours, days 2, 7-10 and at 6 months).

Locations

Country	Name	City	State
United Kingdom	Golden Jubilee National Hospital	Clydebank	Dunbartonshire

Sponsors (3)

Lead Sponsor	Collaborator
NHS National Waiting Times Centre Board	British Heart Foundation, Siemens Healthcare Diagnostics Inc

Country where clinical trial is conducted

United Kingdom, 

References & Publications (26)

Ahmed N, Carberry J, Teng V, Carrick D, Berry C. Risk assessment in patients with an acute ST-elevation myocardial infarction. J Comp Eff Res. 2016 Nov;5(6):581-593. Epub 2016 Sep 1. — View Citation

Ahmed N, Carrick D, Layland J, Oldroyd KG, Berry C. The role of cardiac magnetic resonance imaging (MRI) in acute myocardial infarction (AMI). Heart Lung Circ. 2013 Apr;22(4):243-55. doi: 10.1016/j.hlc.2012.11.016. Epub 2012 Dec 29. Review. — View Citation

Berry C, Carrick D, Haig C, Oldroyd KG. "Waves of Edema" Seem Implausible. J Am Coll Cardiol. 2016 Apr 19;67(15):1868-1869. doi: 10.1016/j.jacc.2015.11.073. — View Citation

Berry C, McEntegart M, Petrie MC, Eteiba H, Lindsay M, Hood S, Watkins S, Davie A, Carrick D, Payne AR, McGeoch RJ, Oldroyd KG. Meta-Analysis of the Index of Microvascular Resistance in Acute STEMI Using Incomplete Data. JACC Cardiovasc Interv. 2017 Feb 2 — View Citation

Carberry J, Carrick D, Haig C, Ahmed N, Mordi I, McEntegart M, Petrie MC, Eteiba H, Hood S, Watkins S, Lindsay M, Davie A, Mahrous A, Ford I, Sattar N, Welsh P, Radjenovic A, Oldroyd KG, Berry C. Persistence of Infarct Zone T2 Hyperintensity at 6 Months A — View Citation

Carberry J, Carrick D, Haig C, Ahmed N, Mordi I, McEntegart M, Petrie MC, Eteiba H, Hood S, Watkins S, Lindsay M, Davie A, Mahrous A, Ford I, Sattar N, Welsh P, Radjenovic A, Oldroyd KG, Berry C. Persistent Iron Within the Infarct Core After ST-Segment El — View Citation

Carberry J, Carrick D, Haig C, Rauhalammi SM, Ahmed N, Mordi I, McEntegart M, Petrie MC, Eteiba H, Hood S, Watkins S, Lindsay M, Davie A, Mahrous A, Ford I, Sattar N, Welsh P, Radjenovic A, Oldroyd KG, Berry C. Remote Zone Extracellular Volume and Left Ve — View Citation

Carrick D, Berry C. Prognostic importance of myocardial infarct characteristics. Eur Heart J Cardiovasc Imaging. 2013 Apr;14(4):313-5. doi: 10.1093/ehjci/jes296. Epub 2012 Dec 17. Review. — View Citation

Carrick D, Haig C, Ahmed N, Carberry J, Yue May VT, McEntegart M, Petrie MC, Eteiba H, Lindsay M, Hood S, Watkins S, Davie A, Mahrous A, Mordi I, Ford I, Radjenovic A, Oldroyd KG, Berry C. Comparative Prognostic Utility of Indexes of Microvascular Functio — View Citation

Carrick D, Haig C, Ahmed N, McEntegart M, Petrie MC, Eteiba H, Hood S, Watkins S, Lindsay MM, Davie A, Mahrous A, Mordi I, Rauhalammi S, Sattar N, Welsh P, Radjenovic A, Ford I, Oldroyd KG, Berry C. Myocardial Hemorrhage After Acute Reperfused ST-Segment- — View Citation

Carrick D, Haig C, Ahmed N, Rauhalammi S, Clerfond G, Carberry J, Mordi I, McEntegart M, Petrie MC, Eteiba H, Hood S, Watkins S, Lindsay MM, Mahrous A, Welsh P, Sattar N, Ford I, Oldroyd KG, Radjenovic A, Berry C. Temporal Evolution of Myocardial Hemorrha — View Citation

Carrick D, Haig C, Carberry J, May VTY, McCartney P, Welsh P, Ahmed N, McEntegart M, Petrie MC, Eteiba H, Lindsay M, Hood S, Watkins S, Mahrous A, Rauhalammi SM, Mordi I, Ford I, Radjenovic A, Sattar N, Oldroyd KG, Berry C. Microvascular resistance of the — View Citation

Carrick D, Haig C, Maznyczka AM, Carberry J, Mangion K, Ahmed N, Yue May VT, McEntegart M, Petrie MC, Eteiba H, Lindsay M, Hood S, Watkins S, Davie A, Mahrous A, Mordi I, Ford I, Radjenovic A, Welsh P, Sattar N, Wetherall K, Oldroyd KG, Berry C. Hypertens — View Citation

Carrick D, Haig C, Rauhalammi S, Ahmed N, Mordi I, McEntegart M, Petrie MC, Eteiba H, Hood S, Watkins S, Lindsay M, Mahrous A, Ford I, Tzemos N, Sattar N, Welsh P, Radjenovic A, Oldroyd KG, Berry C. Prognostic significance of infarct core pathology reveal — View Citation

Carrick D, Haig C, Rauhalammi S, Ahmed N, Mordi I, McEntegart M, Petrie MC, Eteiba H, Lindsay M, Watkins S, Hood S, Davie A, Mahrous A, Sattar N, Welsh P, Tzemos N, Radjenovic A, Ford I, Oldroyd KG, Berry C. Pathophysiology of LV Remodeling in Survivors o — View Citation

Carrick D, Oldroyd KG, McEntegart M, Haig C, Petrie MC, Eteiba H, Hood S, Owens C, Watkins S, Layland J, Lindsay M, Peat E, Rae A, Behan M, Sood A, Hillis WS, Mordi I, Mahrous A, Ahmed N, Wilson R, Lasalle L, Généreux P, Ford I, Berry C. A randomized tria — View Citation

Gao H, Carrick D, Berry C, Griffith BE, Luo X. Dynamic finite-strain modelling of the human left ventricle in health and disease using an immersed boundary-finite element method. IMA J Appl Math. 2014 Oct;79(5):978-1010. Epub 2014 Jul 1. — View Citation

Gao H, Mangion K, Carrick D, Husmeier D, Luo X, Berry C. Estimating prognosis in patients with acute myocardial infarction using personalized computational heart models. Sci Rep. 2017 Oct 19;7(1):13527. doi: 10.1038/s41598-017-13635-2. — View Citation

Haig C, Carrick D, Carberry J, Mangion K, Maznyczka A, Wetherall K, McEntegart M, Petrie MC, Eteiba H, Lindsay M, Hood S, Watkins S, Davie A, Mahrous A, Mordi I, Ahmed N, Teng Yue May V, Ford I, Radjenovic A, Welsh P, Sattar N, Oldroyd KG, Berry C. Curren — View Citation

Layland J, Carrick D, Lee M, Oldroyd K, Berry C. Adenosine: physiology, pharmacology, and clinical applications. JACC Cardiovasc Interv. 2014 Jun;7(6):581-91. doi: 10.1016/j.jcin.2014.02.009. Epub 2014 May 14. Review. — View Citation

Mangion K, Carrick D, Carberry J, Mahrous A, McComb C, Oldroyd KG, Eteiba H, Lindsay M, McEntegart M, Hood S, Petrie MC, Watkins S, Davie A, Zhong X, Epstein FH, Haig CE, Berry C. Circumferential Strain Predicts Major Adverse Cardiovascular Events Followi — View Citation

Mangion K, Carrick D, Clerfond G, Rush C, McComb C, Oldroyd KG, Petrie MC, Eteiba H, Lindsay M, McEntegart M, Hood S, Watkins S, Davie A, Auger DA, Zhong X, Epstein FH, Haig CE, Berry C. Predictors of segmental myocardial functional recovery in patients a — View Citation

Mangion K, Corcoran D, Carrick D, Berry C. New perspectives on the role of cardiac magnetic resonance imaging to evaluate myocardial salvage and myocardial hemorrhage after acute reperfused ST-elevation myocardial infarction. Expert Rev Cardiovasc Ther. 2016 Jul;14(7):843-54. doi: 10.1586/14779072.2016.1173544. Epub 2016 Apr 26. Review. — View Citation

Maznyczka AM, Carrick D, Carberry J, Mangion K, McEntegart M, Petrie MC, Eteiba H, Lindsay M, Hood S, Watkins S, Davie A, Mahrous A, Ford I, Welsh P, Sattar N, Oldroyd KG, Berry C. Sex-based associations with microvascular injury and outcomes after ST-seg — View Citation

Maznyczka AM, Carrick D, Oldroyd KG, James-Rae G, McCartney P, Greenwood JP, Good R, McEntegart M, Eteiba H, Lindsay MM, Cotton JM, Petrie MC, Berry C. Thermodilution-derived temperature recovery time: a novel predictor of microvascular reperfusion and pr — View Citation

Yew SN, Carrick D, Corcoran D, Ahmed N, Carberry J, Teng Yue May V, McEntegart M, Petrie MC, Eteiba H, Lindsay M, Hood S, Watkins S, Davie A, Mahrous A, Mordi I, Ford I, Oldroyd KG, Berry C. Coronary Thermodilution Waveforms After Acute Reperfused ST-Segm — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial salvage	Myocardial salvage (% left ventricular volume) was defined as the difference between the initial jeopardised area-at-risk revealed by T2-weighted MRI (1.5 Tesla, Siemens Healthcare) at baseline and final infarct size revealed by contrast-enhanced MRI at 6 months on the same MRI scanner.	Baseline and 6 months after date of index hospitalisation for STEMI
Secondary	Myocardial salvage index	The myocardial salvage index was defined as infarct size at 6 months indexed to the initial area-at-risk revealed by T2-weighted MRI.	Baseline and 6 months
Secondary	Final infarct size	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.	MRI scan at 6 months after index hospitalisation
Secondary	Myocardial haemorrhage	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).	Baseline MRI scan
Secondary	Microvascular obstruction	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.	Baseline MRI scan
Secondary	First pass MVO	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.	Baseline MRI
Secondary	Early MVO	Early MVO is acquired with MRI scanning 1 minute after gadolinium administration and forms part of the diagnostic criteria to confirm LATE MVO.	Baseline MRI
Secondary	Area-at-risk	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.	Baseline MRI scan
Secondary	Myocardial T1 time	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.	Baseline and follow-up MRI at 6 months
Secondary	Myocardial T2 time	The myocardial T2 relaxation time (ms) will be estimated using a balanced steady state free precession method (Siemens Healthcare).	Baseline and follow-up MRI at 6 months
Secondary	Left ventricular ejection fraction	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.	Baseline and follow-up MRI at 6 months
Secondary	Left ventricular end-diastolic volume	Left ventricular end-diastolic volume (millilitres)	Baseline and follow-up MRI at 6 months
Secondary	Left ventricular end-systolic volume	Left ventricular end-systolic volume (millilitres)	Baseline and follow-up MRI at 6 months
Secondary	Index of microvascular resistance	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.	Day 0 at initial hospital admission
Secondary	Quality of life	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.	Baseline and 6 months
Secondary	Recurrent myocardial infarction	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.	6 months
Secondary	Adenosine response	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.	Baseline
Secondary	MACE	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.	Minimum 12 months
Secondary	MACCE	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.	Minimum 12 months
Secondary	Serious adverse cardiovascular events.	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.	Minimum 12 months
Secondary	All-cause death or heart failure	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.	Minimum 12 months from baseline

External Links

•   British Heart Foundation
•   Chief Scientist Office, NHS Scotland and Healthscience Scotland