Cardiac αVβ3 integrin expression following acute myocardial infarction in humans

Will Jenkins; Alex Vesey; Colin Stirrat; Martin Connell; Christophe Lucatelli; Anoushka Neale; Catriona Moles; Anna Vickers; Alison Fletcher; Tania Pawade; Ian Wilson; James H F Rudd; Edwin J R van Beek; Saeed Mirsadraee; Marc R Dweck; David E Newby

doi:10.1136/heartjnl-2016-310115

Cardiac αVβ3 integrin expression following acute myocardial infarction in humans

Will Jenkins, Alex Vesey, Colin Stirrat, Martin Connell, Christophe Lucatelli, Anoushka Neale, Catriona Moles, Anna Vickers, Alison Fletcher, Tania Pawade, Ian Wilson, James H F Rudd, Edwin J R van Beek, Saeed Mirsadraee, Marc R Dweck, David E Newby

Research output: Contribution to journal › Article › peer-review

Abstract

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: (18)F-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: (18)F-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 (18)F-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). (18)F-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), (18)F-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: (18)F-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.

Original language	English
Journal	Heart
Early online date	7 Dec 2016
DOIs	https://doi.org/10.1136/heartjnl-2016-310115
Publication status	E-pub ahead of print - 7 Dec 2016

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10.1136/heartjnl-2016-310115

Newby D Cardiac avb3 integrin...
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BHF Research Excellence Award (2) (renewal) Grant 1
Mullins, J., Bailey, M., Beqqali, A., Caporali, A., Crisan, M., Mansley, M., Meloni, M., Reynolds, R. & Wu, J.
UK-based charities
1/04/14 → 30/06/19
Project: Research
BHF UK Cardiovascular Regenerative Medicine Centre
Newby, D., Brittan, M., Meloni, M., Mills, N. & Peault, B.
UK-based charities
1/10/13 → 30/09/17
Project: Research
Fellowship for W Jenkins: Identification of In Vivo Angiogenesis and Fibrosis in Cardiovascular Disease using Positron Emission Tomography
Newby, D.
UK-based charities
1/11/12 → 31/10/15
Project: Research

Christophe Lucatelli
- Deanery of Clinical Sciences - Senior Research Fellow in Radiochemistry
- Edinburgh Imaging
Person: Academic: Research Active (Research Assistant)

Cite this

Jenkins, W., Vesey, A., Stirrat, C., Connell, M., Lucatelli, C., Neale, A., Moles, C., Vickers, A., Fletcher, A., Pawade, T., Wilson, I., Rudd, J. H. F., van Beek, E. J. R., Mirsadraee, S., Dweck, M. R., & Newby, D. E. (2016). Cardiac αVβ3 integrin expression following acute myocardial infarction in humans. Heart. Advance online publication. https://doi.org/10.1136/heartjnl-2016-310115

@article{954b135844dd4982b4767dd41d74e04d,

title = "Cardiac αVβ3 integrin expression following acute myocardial infarction in humans",

abstract = "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: (18)F-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: (18)F-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 (18)F-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). (18)F-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), (18)F-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: (18)F-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.",

author = "Will Jenkins and Alex Vesey and Colin Stirrat and Martin Connell and Christophe Lucatelli and Anoushka Neale and Catriona Moles and Anna Vickers and Alison Fletcher and Tania Pawade and Ian Wilson and Rudd, {James H F} and {van Beek}, {Edwin J R} and Saeed Mirsadraee and Dweck, {Marc R} and Newby, {David E}",

note = "Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.",

year = "2016",

month = dec,

day = "7",

doi = "10.1136/heartjnl-2016-310115",

language = "English",

journal = "Heart",

issn = "1355-6037",

publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - Cardiac αVβ3 integrin expression following acute myocardial infarction in humans

AU - Jenkins, Will

AU - Vesey, Alex

AU - Stirrat, Colin

AU - Connell, Martin

AU - Lucatelli, Christophe

AU - Neale, Anoushka

AU - Moles, Catriona

AU - Vickers, Anna

AU - Fletcher, Alison

AU - Pawade, Tania

AU - Wilson, Ian

AU - Rudd, James H F

AU - van Beek, Edwin J R

AU - Mirsadraee, Saeed

AU - Dweck, Marc R

AU - Newby, David E

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

PY - 2016/12/7

Y1 - 2016/12/7

N2 - 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: (18)F-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: (18)F-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 (18)F-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). (18)F-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), (18)F-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: (18)F-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.

AB - 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: (18)F-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: (18)F-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 (18)F-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). (18)F-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), (18)F-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: (18)F-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.

U2 - 10.1136/heartjnl-2016-310115

DO - 10.1136/heartjnl-2016-310115

M3 - Article

C2 - 27927700

SN - 1355-6037

JO - Heart

JF - Heart

ER -

Cardiac αVβ3 integrin expression following acute myocardial infarction in humans

Abstract

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Projects

BHF Research Excellence Award (2) (renewal) Grant 1

BHF UK Cardiovascular Regenerative Medicine Centre

Fellowship for W Jenkins: Identification of In Vivo Angiogenesis and Fibrosis in Cardiovascular Disease using Positron Emission Tomography

Profiles

Christophe Lucatelli

Cite this