Objective Maladaptive repair contributes towards the development of heart failure following myocardial infarction (MI). The αvβ3 integrin receptor is a key mediator and determinant of cardiac repair. We aimed to establish whether αvβ3 integrin expression determines myocardial recovery following MI.
Methods 18F-Fluciclatide (a novel αvβ3-selective radiotracer) positron emission tomography (PET) and CT imaging and gadolinium-enhanced MRI (CMR) were performed in 21 patients 2 weeks after ST-segment elevation MI (anterior, n=16; lateral, n=4; inferior, n=1). CMR was repeated 9 months after MI. 7 stable patients with chronic total occlusion (CTO) of a major coronary vessel and nine healthy volunteers underwent a single PET/CT and CMR.
Results 18F-Fluciclatide uptake was increased at sites of acute infarction compared with remote myocardium (tissue-to-background ratio (TBRmean) 1.34±0.22 vs 0.85±0.17; p<0.001) and myocardium of healthy volunteers (TBRmean 1.34±0.22 vs 0.70±0.03; p<0.001). There was no 18F-fluciclatide uptake at sites of established prior infarction in patients with CTO, with activity similar to the myocardium of healthy volunteers (TBRmean 0.71±0.06 vs 0.70±0.03, p=0.83). 18F-Fluciclatide uptake occurred at sites of regional wall hypokinesia (wall motion index≥1 vs 0; TBRmean 0.93±0.31 vs 0.80±0.26 respectively, p<0.001) and subendocardial infarction. Importantly, although there was no correlation with infarct size (r=0.03, p=0.90) or inflammation (C reactive protein, r=−0.20, p=0.38), 18F-fluciclatide uptake was increased in segments displaying functional recovery (TBRmean 0.95±0.33 vs 0.81±0.27, p=0.002) and associated with increase in probability of regional recovery.
Conclusion 18F-Fluciclatide uptake is increased at sites of recent MI acting as a biomarker of cardiac repair and predicting regions of recovery.
Trial registration number NCT01813045; Post-results.
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MRD and DEN contributed equally.
Contributors All authors have contributed significantly to the submitted work. DEN, MRD, WSAJ, IW, AF, CL, EJRvB and JHFR undertook the conception and design of the study and the collection, analysis and interpretation of the data was undertaken by WSAJ, ATV, MC, AN, CM, AV, TP, CS and SM. The drafting of the manuscript and its revision was completed by WSAJ, ATV, MRD and DEN. All authors have read and approved the manuscript as written.
Funding 18F-Fluciclatide FASTlab materials were provided by General Electric Healthcare. The study and MRD, WSAJ and DEN are supported by the British Heart Foundation (FS/12/84, FS/10/026, CH/09/002, RM/13/2/30158, RE/13/3/30183). DEN is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). JHFR is part-funded by the National Institute for Health Research Cambridge Biomedical Research Centre. The Wellcome Trust Clinical Research Facility and Clinical Research Imaging Centre are supported by NHS Research Scotland through NHS Lothian.
Competing interests None declared.
Patient consent Obtained.
Ethics approval South East Scotland Research Ethics Committee 2.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Unpublished data are available on request in keeping with the data-sharing legislation of the University of Edinburgh.
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