The stented vessel wall Dr Miles Dalby Consultant Cardiologist Royal Brompton Hospital Harefield Hospital Senior Lecturer Imperial College

Conflicts of interest Dr Dalby has received travel expences speaking honoraria and research grants from Eli Lilly, Translumina, Sankyo.

DRUG ELUTING STENT IN STENT RESTENOSIS STENT THROMBOSIS HEALING ENDOTHELIALISATION COVERAGE Paradigms in stent evaluation VESSEL WALL VESSEL LUMEN MLD BARE METAL STENT ACUTE VESSEL CLOSURE IN STENT RESTENOSIS ANGIOGRAPHIC RESTENOSIS LATE LUMEN LOSS CLINICAL RESTENOSIS MINIMUM LUMEN DIAMETER

Lady diana fountain Particle residence and shear

Terminology in stent coverage ESC Congress Munich 2008

Optical Coherence Tomography

OCT and stent imaging

A Randomised optical coherence tomography study to determine 90 day stent coverage in polymer coated vs bare metal rapamicin eluting stents P Moore, P Barlis, J Spiro, G Ghimire, M Roughton, C DiMario, C Ilsley, M Mason, R Kharbanda, M Dalby Yukon using rapamicin without polymer enhances stent coverage : ‘You’re Covered’ ISRCTN no Royal Brompton & Harefield University Hospitals Imperial College London UK Dr Dalby has received an unrestricted educational grant, honoraria and travel expenses from Translumina ESC Congress Munich 2008

Rapamicin Eluting Stents YUKON ® Etched surface Drug sprayed on No Polymer CYPHER ® Polymer coated PEVA PBMA

Study Hypothesis The Yukon rapamicin eluting non- polymer coated stent has improved strut coverage compared to the Cypher durable polymer coated rapamicin eluting stent as judged by OCT at 90 days ESC Congress Munich 2008

Study Design N=24 DES eligible PCI Cypher n=12 Yukon n=12 OCT at 90 days Primary Randomisation guided by UK NICE criteria for DES/BMS Primary End point: Neointimal thickness at 90 days (um) Binary strut coverage at 90 days (%) Stent Strut Luminal Protrusion (%) ESC Congress Munich 2008

VariablePolymer-coated rapamycin stentnon-polymer rapamycin stent Number12 Age (years)61.6 (55.0, 66.2)62.3 (53.7, 63.8) Male11 (92)10 (83) Follow-up (mean days)91 (85, 92)91 (86, 96) Hypertension8 (67) Diabetes mellitus4 (42)3 (25) Hypercholesterolaemia10 (83)11 (92) Current or Ex-smoker6 (50)7 (58) Acute coronary syndrome 4 (33)3 (25) Chronic stable angina6 (67)9 (75) Patient Characteristics ESC Congress Munich 2008

Variable Polymer coater rapamicin stent Non-Polymer rapamicin stent p value Vessel treatedLAD 9 Cx 1 RCA 1LAD 6 Cx 4 RCA 2 Stent diameter(mm)2.88 (0.20)2.88 (0.38)1 Stent length(mm)18.0 (3.0)20.2 (2.9)0.089 Postdilatation, n (%)5 (41.7)1 (8.3)0.059 Max inflation pressure(atm)17.0 (3.1)16.7 (2.8)0.785 Inflation duration(s)18.9 (6.2)15.4 (7.2) stent, n (%)8 (66.7)6 (50.0) stents, n (%)3 (25.0)6 (50.0) 3 stents, n (%)1 (8.3)0 (0) Stent:Artery ratio1.14 (0.09)1.06 (0.09)0.034 Procedural Characteristics ESC Congress Munich 2008

Variable Polymer coater rapamicin stent Non-Polymer rapamicin stent p value 90 day binary restenosis, n (%) 0 (0) 1 Late loss (mm)0.06 (0.29)0.16 (0.33)0.417 Angiographic 90 day Outcome There were no clinical adverse events at 90 days and no OCT related complications

Results: LAD PCI 90 Day ESC Congress Munich 2008

Results: LAD PCI 90 Day OCT pullback from mid-proximal LAD ESC Congress Munich 2008

Results: RCA PCI 90 Day ESC Congress Munich 2008

Results: RCA PCI 90 Day OCT pullback from mid-proximal RCA ESC Congress Munich 2008

CypherYukon Results: Neointimal Thickness P<0.001 Group Mean Patient Strut sections/Group Cypher n=2465 Yukon n=2865Strut sections/Patient: Cypher n=193 Yukon n=167 ESC Congress Munich 2008

CypherYukon Results: Strut Coverage Group Mean Patient Strut sections/Group Cypher n=2465 Yukon n=2865Strut sections/Patient: Cypher n=193 Yukon n=167 P=0.03 ESC Congress Munich 2008

CypherYukon Results: Luminal Protrusion P=0.001 Group Mean Patient Strut sections/Group Cypher n=2465 Yukon n=2865Strut sections/Patient: Cypher n=193 Yukon n=167 ESC Congress Munich 2008

Conclusion Mean NIT was significantly less with the polymer coated rapamicin stent than the non-polymer stent As a result, coverage was non-homogenous with >10% of struts being uncovered by OCT criteria with the polymer coated rapamicin stent compared with <3% with the non-polymer stent Luminal protrusion of struts into the vessel lumen occurred in >25% of sections with the polymer coated rapamicin stent compared with <5% with the non-polymer stent In Press JACC-Intervention 2009

Computer modelling But how much does strut protrusion matter, and if so how much protrusion matters? What objective parameters can be calculated?

If bareness of struts and strut protrusion are the key determinants of stent thrombosis then there ought to be an inverse relationship between late loss and stent thrombosis-especially with very low late loss BUT Meta-regression analysis from 26 randomised clinical DES studies & 8971 patients The risk of stent thrombosis is not necessarily directly inversely related to in stent late lumen loss Riviero et al Eurointevention 2008 Stent Thrombosis & lumen loss In Stent Late Loss Stent Thrombosis ?

Virchow’s Triad & Stent thrombosis Virchow’s triad: Thrombosis occurs with adverse Blood coagulability Blood flow Vessel wall conditions