BRS Summit – Scaffold Fractures Stephen G. Ellis, MD Section Head of Invasive/Interventional Cardiology Professor of Medicine, Cleveland Clinic Lerner College of Medicine

Potential Conflicts of Interest Research Support Abbott Vascular Consultant Abbott Vascular Boston Scientific Medtronic Stock Options/Royalties Keystone

BVS Strut Fracture When is it normal to see a “strut fracture” after BVS implantation? Proposed nomenclature How often are we seeing abnormal strut fracture? What are the clinical consequences? How to avoid strut fracture

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Classification of Stent Fractures I II III IV V I = single strut, II = 2 or more struts fracture without deformation, III = 2 or more struts fracture with deformation, IV = multiple fractures with acquired transection without gap, V = multiple fractures with acquired transections with gap Nakazawa, JACC 2009 SGE; 1109-2, 29

Impact of DES Fracture Associated with fracture 0 0 0 0 6 (67)* NA Grade I N = 10 Grade II N = 14 Grade III N = 12 Grade IV N = 6 Grade V N = 9 Adverse Pathologic Findings Fracture (-) N = 121 Associated with fracture 0 0 0 0 6 (67)* NA Event rate, % 4 (40) 3 (21) 3 (25) 1(17) 7 (78)** 46 (37) Restenosis 0 0 0 0 1 (11) 5 (4) Thrombosis 4 (40) 3 (21) 3 (25) 1(17) 6 (67) 42 (33) *p<0.0001 vs Grade I to IV, ** p = 0.03 vs fracture (-) group Nakazawa, JACC 2009 SGE; 1109-2, 33

Chakravarty et al., Am J Cardiol 2010;106:1075-80 SGE; 0714-6, 38

Bioresorbable Vascular Scaffolds Loss of Continuity Basic design concept is rings joined by links Ring Link Design decouples radial support and axial flexibility Rings provide resistance to radial loads Links provide flexibility to navigate tortuous paths and conformability to match vessel curvature It is acceptable for links become discontinuous prior to rings, because they are not necessary for support Images are on file at Abbott Vascular. SGE; 0714-6, 9

Strut Disruption or Discontinuity Metallic DES BRS Detectable best by high resolution cine OCT Repeated flexing, stent overlap Overexpansion Maintenance of strut continuity over time is a design requirement Unintended event Result of fatigue over time Loss of strut continuity over time is a design requirement Programmed and expected event Result of fatigue and polymer degradation (≥3M) SGE; 0714-6, 4

OCT Findings and Definitions Overlaid struts: – two struts that overlay each other in the same angular sector of the lumen perimeter Overhung struts –overlaid struts without close contact Stacked struts– overlaid struts with direct contact in at least 1 frame Incomplete apposition (isolated, intraluminal) – struts with visible separation from the arterial wall

Cumulative Risk of 3.0 mm Scaffold Fracture Comparison of Cohort B to Absorb (final design) SGE; 0714-6, 14

ABSORB Cohort B Experience SGE; 0714-6, 13

QCAVessel Sizing of the Target Lesion ABSORB Cohort B Group 1 (L=52, N=45) Dmax >3.3 mm: 9 lesions Dmax: 2.5-3.3 mm: 30 lesions Dmax <2.5 mm: 13 lesions Message: with limited scaffold sizes available, 20-25% of scaffolds were oversized, and 10% would have had to be overstretched to match reference diameter Gomez-Lara J, et al, Eurointervention 2012; 8:214-224 SGE; 0714-6, 15 18

Case #1 78y male with recent onset angina, culprit lesion in the OM Predilated with a 2.5 mm balloon Implanted with 3.0 x 18 mm Absorb at 16 atm Post-dilated with 3.25 mm NC balloon at 24 atm Malapposition in proximal half of scaffold by OCT Post-dilated with 3.5 mm compliant balloon at 16 atm IVUS and OCT showed persistent strut malapposition At 1 month, patient reported with confirmed ischemia and treated with 3.0 x 18 mm XIENCE V stent Event free since Ormiston J A et al. Circ Cardiovasc Interv. 2011;4:535-538

Day 33 Ischemia Confirmed RVD=3.26 mm Dmax Deployment with malapposition Post-dil up to 3.96 mm. Overhung struts, malapposed Figure 4. Coronary angiography and OCT of a patient with scaffold pattern irregularity at post-implantation. Patient affected of a moderate lesion in the obtuse marginal. The interpolated-RVD was 3.26 mm (A) and the proximal and distal Dmax of the scaffolded segment (prior to the implantation) were 4.09 and 3.34 mm respectively (B). After the BVS implantation the OCT imaging showed severe malapposition of the scaffold (C); and the operator decided to post-dilate with a compliance balloon up to 3.96 mm of predicted diameter. A second OCT pullback showed scaffold pattern irregularities highly suggestive of fracture (D) that were untreated. At day 33, the patient presented with ischaemia and was re-catheterised (E). A new OCT (F) showed scaffold pattern irregularities with attached thrombi (arrow). Day 33, patient with angina and dx ischemia. OCT shows overhung and stacked struts Gomez-Lara J, et al, Eurointervention 2012; 8:214-224 SGE; 0714-6, 17 20

ABSORB Cohort B-1 Experience TLR No Clinical Event Signs of scaffold resorption Ormiston J, et al., CCI 2012; 5:620-632 SGE; 0714-6, 20

Acute Disruption, Case #2 2.5 mm BVS implanted in 2.4 mm ramus branch (A,B) Followed by 3.0 NC post-dil at 24 ATM Overhung struts are seen by OCT but not IVUS Onuma et al. JACC2014;7:1406 SGE; 0115-18, 7

Acute Disruption, Case #2 At 6 months w/o symptoms cath and IVUS Look fine But operator had difficulty crossing lesion With OCT device After rewiring, disrupted struts are seen (J) Onuma et al. JACC2014;7:1406 SGE; 0115-18, 8

Acute Disruption, Case #2 At 2 yrs patient remains asymptomatic. Angiogram looks good. OCT shows struts Covered by neointima Onuma et al. JACC2014;7:1406 SGE; 0115-18, 9

Recommendations for Implantation 5 Ps for Optimal Implantation of Absorb Prepare the Lesion Properly Size the Vessel Pay Attention to Expansion Limits Post-Dilate with a Non-Compliant Balloon Prescribing and maintaining DAPT therapy SGE; 0714-6, 21

#2 Properly Size the Vessel Vessel Sizing Technique Limitations Angiography (Visual Estimate) Actual Vessel Size OCT IVUS QCA 3.0 mm 3.0 mm 3.1 mm 2.8 mm 2.7 – 3.3 mm Most Accurate Over-Estimates Under-Estimates Inter/Intra-Observer Variability Margin of Error*  Recognize the risk of under-estimating vessel size by visual estimation *Margin of error estimates based on resolution for each imaging modality: Resolution of OCT and IVUS: Bezerra, H.G., J Am Coll Cardiol.: Cardiovasc Interv. 2009; 2: 1035. Resolution of QCA: Dahm, J. and van Buuren, F. Int J Vasc Med. 2012. Offset and variability of visual estimate: data on file at Abbott Vascular. SGE; 0714-6, 27

#3 Pay Attention to Expansion Limits Scaffold expansion limits are nominal scaffold diameter + 0.5 mm It is important to stay within the expansion limits of the device Nominal Scaffold Diameter Maximum Scaffold Expansion Limit 2.50 mm + 0.5 mm 3.00 mm 3.00 mm + 0.5 mm 3.50 mm 3.50 mm + 0.5 mm 4.00 mm SGE; 0714-6, 29 29

#3 Pay Attention to Expansion Limits Delivery Balloon Inflation The delivery balloon can be safely inflated up to 16 atm – rated burst pressure (RBP) – without damaging the scaffold Deploy the scaffold slowly by pressurizing the delivery system in 2 atm increments every 5 seconds, until the scaffold is completely expanded Maintain target deployment pressure for 30 seconds 2.5 mm 3.0 mm 3.5 mm Clinical Trial Average Deployment Pressure* *Average Absorb scaffold deployment balloon pressures from pooled ABSORB II and ABSORB EXTEND clinical trial data. Data on file at Abbott Vascular: 2.5 mm diameter Absorb scaffolds (n = 125) = 13.46 atm 3.0 mm diameter Absorb scaffolds (n = 798) = 13.32 atm 3.5 mm diameter Absorb scaffolds (n = 89) = 12.80 atm SGE; 0714-6, 30

Conclusions Timing of the fracture/discontinuity is important: Metallic – fracture unintended, not allowed BRS – at deployment no fracture allowed, <3M link allowed, >6M both ring and link allowed by design Nature of fracture are likely different Clinical experience from Cohort B is insufficient to answer the question “Are the clinical consequences of a fracture in DES vs BRS the same?”