Stent Thrombosis After Drug-Eluting Stenting – Insights from the EuropeanWide PRESTIGE Registry Robert A. Byrne MB BCh PhD FESC Deutsches Herzzentrum, Technische Universität, Munich CRT, Washington DC, 24th February 2014 1 Late Stent Thrombosis Thr LAD * * * * Technische Universität München Thr * * NC LAD * * * * Sudden death 7 years after stenting The European Approach Project Number: 260309 Duration: 2011 - 2014 EC Contribution: €5,979,641.50 Coordinator: DHM, GERMANY Participating clinical centres DHM BER LEU KRAK UKEIC NIE KRO SC Munich, DE Bergamo, IT Leuven, BE Kracow, PL Leicester, UK Nieuwegein, NL Bad Kroz., DE Madrid, ES www.prestige-fp7.eu The European Approach 4 PRESTIGE: Objectives • The principal scientific objective is to dissect mechanisms contributing to the occurrence of stent thrombosis • The principal technological objective is to develop novel prohealing stent platforms and imaging technologies allowing for earlier diagnosis and better risk prediction of ST • The principal medical objective is to develop new strategies to prevent late stent thrombosis at a minimum of bleeding cost 5 PRESTIGE Work Overview 6 Technische Universität München Project Number: 260309 Duration: 2011 - 2014 EC Contribution: €5,979,641.50 Coordinator: DHM, GERMANY WP1: Assessment of basic mechanisms leading to stent thrombosis WP2: Bio-engineering approaches to reduce the risk of stent thrombosis WP3: Imaging of vascular healing and thrombosis WP4:Human studies of stent thrombosis www.prestige-fp7.eu Work Package 1: ST Mechanisms Mouse model of stent thrombosis Work Package 2: Novel Coatings DAPI for CAEC Task 1 - Coating of discs with αvβ3-active RGD peptidomimetic: Coronary Artery Endothelial Cell (CAEC) adhesion + PBS + Plain polymer coating chitosan + αvβ3 active RGDpeptidomimetic + αvβ3 active RGDpeptidomimetic + without coating chitosan + polymer coating chitosan 300 Endothelial cell specific integrin ligand 250 CAEC cell count 215 200 159 150 isothiocyanate anchor group 125 100 50 stent surface 0 1 Treatment aminofunctionalized polymer Work Package 3: Intravascular Imaging 10 OCT Tissue Characterization Technische Universität München Grey-scale signal intensity analysis Atheroscle r animal model Human autopsy data Translation to clinical practice Malle et al ATVB 2013 OCT Tissue Characterization Technische Universität München mature immature Autopsy 1,0 1,0 0,9 0,9 0,8 0,8 0,7 0,7 Sensitivity Sensitivity Animal model AUC: 0.95 0,6 0,5 0,4 0,3 0,6 Clinical mature AUC: 0.90 0,5 0,4 0,3 0,2 0,2 0,1 0,1 0,0 0,00 autopsy 0,20 0,40 0,60 1-Specificity 0,80 0,0 0,00 Immature 0,20 0,40 0,60 1-Specificity 0,80 1 Malle et al. ATVB 2013 Work Package 3: Intravascular Imaging 13 Animal Model of Neoatherosclerosis Technische Universität München Accelerated Atherosclerosis Healing after Stent Implantation Pre-established plaque OCT Signal Attenuation Analysis 330° ± 10 300° ± 10 270° ± 10 240° ± 10 0° ± 10 30° ± 10 60° ± 10 90° ± 10 120° ± 10 210° ± 10180° ± 10150° ± 10 WP4: Human studies of stent thrombosis Multiplate Analyzer 1. 2. 3. 4. 5. In patients with DES thrombosis: Assessment of platelet function (Multiplate, Verify Now) Collection of blood samples for DNA Thrombus aspiration for histology OCT and/or IVUS imaging Data collection on eCRF 2 control groups: 1. Patients with spontaneous MI 2. Patients with DES but no stent thrombosis (matched for timing of ST) Work Package 4 Suspicion of Stent thrombosis Angiographic confirmation of the stent thrombosis Blood sampling Thrombus Aspiration (when indicated) Fix aspirated thrombus for analyses IVUS and/or OCT of the target vessel (if possible/when available) PCI Angiography + IVUS and/or OCT post-emergent PCI 17 VLST: ruptured plaque in lipid laden neointima SES 3.0/18mm SES 3.5/18mm D1 Mixed thrombus Stent Underexpansion Stent Malapposition DES Stent Thrombosis: Principal Causative Factors (interim n=80, Feb 2013) PRESTIGE OCT Explorative Data Analysis Work Package 4 Stent Thrombosis Cases (Target n = 500) Enrolled Outstanding 4% 96% www.prestige-fp7.eu Acknowledgements www.prestige-fp7.eu Thank you for your attention Robert A. Byrne MB BCh PhD FESC Deutsches Herzzentrum, Technische Universität, Munich De novo In-stent Atherosclerosis PRESTIGE FP7 Preventing Stent Thrombosis 2012 The missing link between DES restenosis and late stent thrombosis? In-stent neoatherosclerosis 26 NIRF scan for CF660C – First set of arteries Experimental setup: Two images of the Set 1. Different dynamic range. Fluorescent channel (bias correction) optic fibre Fluorescent channel (bias correction) 10 10 1.4 20 1.35 30 1.3 40 1.25 1.2 1 Normal Artery 20 2 Denuded Artery 30 1.15 3 Normal Artery 4 Denuded Artery Positive CD31 50 1.1 60 Position (mm) 40 Position (mm) scanning direction Native 50 1.2 60 1.15 1.05 70 70 1.1 5 6 Normal Artery Denuded Artery Control for Background 80 80 1.05 1 90 90 1 100 100 0.95 0.95 catheter 100 200 300 Angle (degrees) 100 200 300 Angle (degrees)