Stent Thrombosis After Drug-Eluting Stenting Insights from the European- Wide PRESTIGE Registry

Transcription

1 Stent Thrombosis After Drug-Eluting Stenting Insights from the European- Wide PRESTIGE Registry Robert A. Byrne MB BCh PhD FESC Deutsches Herzzentrum, Technische Universität, Munich CRT, Washington DC, 24 th February

2 Late Stent Thrombosis Technische Universität München LAD Thr Thr * * NC * * LAD * * * * * * Sudden death 7 years after stenting

3 The European Approach Project Number: Duration: EC Contribution: 5,979, Coordinator: DHM, GERMANY Participating clinical centres DHM Munich, DE BER Bergamo, IT LEU Leuven, BE KRAK Kracow, PL UKEIC Leicester, UK NIE Nieuwegein, NL KRO Bad Kroz., DE SC Madrid, ES

4 The European Approach 4

5 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

6 PRESTIGE Work Overview 6

7 Technische Universität München Project Number: Duration: EC Contribution: 5,979, 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

8 Work Package 1: ST Mechanisms Mouse model of stent thrombosis

9 Work Package 2: Novel Coatings Task 1 - Coating of discs with α v β 3 -active RGD peptidomimetic: Coronary Artery Endothelial Cell (CAEC) adhesion DAPI for CAEC + PBS + Plain polymer coating chitosan + α v β 3 active RGDpeptidomimetic + without coating chitosan + α v β 3 active RGDpeptidomimetic + polymer coating chitosan 300 CAEC cell count Treatment stent surface Endothelial cell specific integrin ligand isothiocyanate anchor group aminofunctionalized polymer

10 Work Package 3: Intravascular Imaging 10

11 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

12 OCT Tissue Characterization Technische Universität München mature immature autopsy 1,0 Animal model 1,0 Autopsy Clinical 0,9 0,8 0,9 0,8 mature Sensitivity 0,7 0,6 0,5 0,4 0,3 AUC: 0.95 Sensitivity 0,7 0,6 0,5 0,4 0,3 AUC: ,2 0,1 0,0 0,00 0,20 0,40 0,60 0,80 1-Specificity 0,2 0,1 0,0 0,00 0,20 0,40 0,60 0, Specificity Immature Malle et al. ATVB 2013

13 Work Package 3: Intravascular Imaging 13

14 Animal Model of Neoatherosclerosis Technische Universität München Accelerated Atherosclerosis Healing after Stent Implantation Pre-established plaque

15 OCT Signal Attenuation Analysis 330 ± 10 0 ± ± ± ± ± ± ± ± ± ± ± 10

16 WP4: Human studies of stent thrombosis Multiplate Analyzer In patients with DES thrombosis: 1. Assessment of platelet function (Multiplate, Verify Now) 2. Collection of blood samples for DNA 3. Thrombus aspiration for histology 4. OCT and/or IVUS imaging 5. 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)

17 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

18 VLST: ruptured plaque in lipid laden neointima SES 3.0/18mm SES 3.5/18mm D1

19 Mixed thrombus Stent Underexpansion Stent Malapposition

20 DES Stent Thrombosis: Principal Causative Factors (interim n=80, Feb 2013) PRESTIGE OCT Explorative Data Analysis

21 Work Package 4 Stent Thrombosis Cases (Target n = 500) Enrolled Outstanding 4% 96%

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23 Acknowledgements

24 Thank you for your attention Robert A. Byrne MB BCh PhD FESC Deutsches Herzzentrum, Technische Universität, Munich

25 De novo In-stent Atherosclerosis PRESTIGE FP7 Preventing Stent Thrombosis 2012

26 The missing link between DES restenosis and late stent thrombosis? In-stent neoatherosclerosis 26

27 Experimental setup: optic fibre NIRF scan for CF660C First set of arteries Two images of the Set 1. Different dynamic range. Fluorescent channel (bias correction) Fluorescent channel (bias correction) scanning direction Normal Artery Denuded Artery Normal Artery Denuded Artery Normal Artery Denuded Artery Native Positive CD31 Position (mm) Control for Background Position (mm) catheter Angle (degrees) Angle (degrees) 0.95