Cardiac α_Vβ₃ integrin expression following acute myocardial infarction in humans.

ABSTRACT:

Objective

Maladaptive repair contributes towards the development of heart failure following myocardial infarction (MI). The α_vβ₃ integrin receptor is a key mediator and determinant of cardiac repair. We aimed to establish whether α_vβ₃ integrin expression determines myocardial recovery following MI.

Methods

¹⁸F-Fluciclatide (a novel α_vβ₃-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 (TBR_mean) 1.34±0.22 vs 0.85±0.17; p<0.001) and myocardium of healthy volunteers (TBR_mean 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 (TBR_mean 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; TBR_mean 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 (TBR_mean 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.

SUBMITTER: Jenkins WS 

PROVIDER: S-EPMC5566089 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature