Significance of Clot Properties in Mechanical Thrombectomy

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2 Neuravi Thromboembolic Initiative Significance of Clot Properties in Mechanical Thrombectomy Mahmood Mirza, BASc, MD, Senior Clinical R&D Engineer, Neuravi Ltd. 6/16/2017 May 16, 2017 WLNC 2017 Los Angeles, California ML091

3 Disclosures Employee: Neuravi, a Johnson & Johnson company Training: Engineering (2006), Medicine (2015) 6/16/2017 ML091 3

4 Soft, cohesive clot Bifurcation occlusion 4

5 Soft, friable clot Multiple fragments, bifurcation occlusion 5

6 Firm clot Mid-MCA occlusion 6

7 Significant Outcomes Improvement Reperfusion (TICI 2b-3) Good clinical outcome (mrs 0-2) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Failed Historic Meta analyses 6/16/2017 ML091 7

8 Significant Room for Outcomes Improvement Reperfusion (TICI 2b-3) Good clinical outcome (mrs 0-2) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Failed Historic Meta analyses ~30% 6/16/2017 ML091 8

9 All original thrombectomy publications 2016 TICI 2b and TICI 3 reported separately Retrospective Author Single / Multi Patient Selection Posterior? n TICI 2b-3 TICI 2b TICI 3 Evaluation Ishikawa K Single All comers Yes % 58.37% 33.3% Self Kashka IN Single ICA, M1 only, no tandem No 34 79% 41.16% 38.2% Self Kaesmacher J Single Isolated MCA, <=6hrs, No % 43.05% 39.7% Indpenedant Matsumoto H Single All comers No % 44.08% 44.1% Self Vargas J Single All comers Yes % 49.70% 44.5% Blinded Vargas J Single Distal locations only Yes % 45.99% 45.7% Blinded Mascitelli JR Single ADAPT intent No % 43.42% 48.7% Self Kuhn AL Single Distal locations Yes % 45.67% 51.4% Self Wong JH Single RAPID software Yes % 42.29% 51.6% Self Massari F Single All comers Yes % 42.84% 54.8% Self Kabbasch C Multiple ASPECTS >=5, Sofia catheter, non-consecutive Yes 30 90% 33.33% 56.7% Re-evaluated Wiesmann M Single ICA, M1 only, APD technique No % 23.12% 65.4% Independent 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% TICI 3 6/16/2017 ML091 9

10 Development Approach: Understand the Problem! VASCULAR MODEL CLOT ANALOGS 6/16/2017 ML091 10

11 Development Approach: Understand the Problem! VASCULAR MODEL CLOT ANALOGS 6/16/2017 ML091 11

12 Gasparian et al. Imaging of occlusinve thrombi in acute ischemic stroke. Int J Stroke Apr;10(3): Chueh et al. Mechanical characterization of thromboemboli in acute ischemic stroke and laboratory embolus analogs. AJNR Am J Neuroradiol 2011;32: Variation in AIS clots retrieved via thrombectomy

13 Kumar: Robbins and Cotran, Pathologic Basis of Disease, 8 th Edition. Pisimisis. 2010, Vascular and Endovascular Surgery. Carotid Disease Clot Fibrin-rich clot Fresh erythrocyte rich clot Mature fibrin rich clot Clot Analogs Mature Left Atrial Appendage Clot Highly organised fibrin-rich clot Eleni Doufekias. 2008, Journal of American College of Cardiology. Cardiac Valve Clot Fresh Left Atrial Appendage Clot Shear & Foreign Body induced fibrinrich clot Hybrid clot with mature fibrin base and fresh erythrocyte deposition Jun Ogata, 2008, Annals of Neurology 13

14 Liebeskind et al Cline et al Boeckh-Behrens et al 100% 80% Histopathologic Composition of 100 Retrieved Clots WBC 60% 40% Fibrin 20% 0% RBC 6/16/2017 ML091 14

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16 Different Appearance - Different behaviour?? 16 16

17 standard clot & prototype stentriever Organized fibrin clot & prototype stentriever 17

18 Better or Worse? Before Pass After One Pass 6/16/2017 ML091 18

19 FRICTION INDENTATION COMPRESSION FRAGMENTATION TENSILE 19

20 Hydromechanical Forces on Clot F pressure P distal Ffriction Fretrieval P carotid 6/16/2017 ML091 20

21 Friction Test Method θ o Coefficient of Friction µ = Tanθ 6/16/2017 ML091 21

22 Friction Test Method RBC Rich Fibrin Rich Tested on a variety of substrates materials, incl. artery 22

23 Friction Test Method RBC Rich Fibrin Rich Tested on a variety of substrates materials, incl. artery 23

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26 Simulate Effects of Single Pass Before Pass After One Pass 6/16/2017 ML091 26

27 Coefficient of Friction Clot Compression increases Friction 0% 20% 40% 60% Clot Compression 27

28 Coefficient of Friction Clot Compression increases Friction 0% 20% 40% 60% Clot Compression 28

29 Coefficient of Friction Better or Worse? 0% 20% 40% 60% Clot Compression 29

30 Friable RBC rich clot: Prototype stentriever device Aspiration catheter alone 30

31 Heterogenous Clot Analogues Image courtesy of Dr P. Brouwer, Karolinska University Hospital. CLOT ANALOGS Image courtesy of Dr M. Stauder, Alfried Krupp Krankenhaus, Essen 6/16/2017 ML091 31

32 Heterogenous clots Prototype stentriever Failed retrievals most interesting! Many different mechanisms possible May not be apparent on Angiogram Direct aspiration

33 Impact of Procedural Technique variants

34 Interaction with Devices 6/16/2017 ML091 34

35 Retrieval Techniques 6/16/2017 ML091 35

36 Retrieval Techniques + Flow Visualization 6/16/2017 ML091 36

37 Conclusion

38 tpa? Vessel wall adhesion? Collaterals / time? Full composition data? Imaging Identification? Permeability significance? Different clot types present different challenges. Greater understanding can lead to better solutions. In-vitro modelling can be a valuable tool, but output is only as good as the input, and clot is a key input. A lot left to learn! 38

39 Team Neuravi Thromboembolic Initiative Michael Gilvarry, VP R&D Mahmood Mirza, BASc, MD Gillian Gunning, PhD Sharon Duffy, PhD in training Maeve Holian, MSc Brian Fahy, B.Eng. Sean O Rourke, Intern 6/16/2017 ML091 39

40 Thank you! 6/16/2017 ML091

41 Backup 6/16/2017 ML091

42 Moisture loss May impact variability No trend No significant impact 80% RBC, 20% fibrin 0% RBC, 100% fibrin Moisture loss Moisture loss 42

43 Question Articles Cor? Comments Histology and etiology 9 No Conflicting RBC A-fib, large-artery Histology and angio outcomes 4 No Imaging and histology 8 Yes HAS -> RBC SVS -> RBC Imaging and angio outcomes 8 Yes/No HAS -> better outcomes - 5 positive, 1 no, 1 negative SVS -> better oucomes - 2 positive Imaging and etiology 7 No Conflicting. Meta-analysis said no. 6/16/2017 ML091 43

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45 Thrombus Migration in vitro 6/16/2017 ML091 45

46 BG vs IC 2 x Clot Types Tested Fresh RBC-Rich Firm fibrin n = 30 n = 30 4 x Intermediate Catheters CSA Sofia mm 2 Navien mm 2 5 Max Ace mm 2 Navien mm 2 3 Techniques: Balloon Guide Intermediate catheter EPIC 6/16/2017 ML091 46

47 BGC IC Full Retrieval IC EPIC Procedure with BGC 6/16/2017 ML091 47

48 % 1-Pass TICI 3 Success Overall Results 100 BGC removed under aspiration to retrieve clot 50 0 Intermediate Catheter: Standard Retrieval EPIC 6/16/2017 ML000 Balloon Guide Catheter 48

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