BRS Sizing and Vessel Preparation BRS Technologies: Technology & Innovation BRS for Clinical Use, Implantation Technique and Patient Selection BRS Sizing and Vessel Preparation Ricardo A. Costa, MD, PhD Institute Dante Pazzanese, Sao Paulo, Brazil Sunday, Feb. 19th 2017 – 11:08 to 11:15 am (7 minutes) Room Congressional AB – The Omni Shoreham Hotel Washington, DC, USA

Conflict of Interest Statement Ricardo A. Costa, MD, PhD   I have no relevant financial relationships to disclose

BRS Issues Associated with Vessel Sizing Thick struts (~150 microns) Limited size range Rectangular/square shape Limited overexpansion capability Impact on flow dynamics Suboptimal expansion Need to full embedment and apposition

Lipinski et al. JACC Cardiovasc Interv 2016;9(1):12-24 Increased Risk of ST with 1st Generation BVS compared to 2nd Generation EES Lipinski et al. JACC Cardiovasc Interv 2016;9(1):12-24

Increased Risk of Very Late ST in ABSORB II Serruys et al. Lancet 2016;http://dx.doi.org/10.1016/S0140-6736(16)32050-5

Meta-Analysis: 16,830 pts in 59 Studies Variable Coefficient 95% CI P value Univariate Model Dyslipidemia -0.0127 -0.0238 to -0.0016 0.03 Diabetes mellitus -0.0285 -0.0537 to -0.0033 Vessel size (RVD) -1.0520 -1.9467 to -0.1573 0.02 Residual % DS 0.0673 0.0272 to 0.1075 <0.0001 Residual stenosis (%) 0.001 Multivariate Model 0.091 -0.00009 to 0.1832 0.052 Collet et al. Minerva Cardioangiol 2016:published online

Inaccuracy of Visual Estimation of Vessel Size NC 3.5 x 12 (20 atm) 3.25 x 18 mm Scaffold (After pre-dil w/ 3.0x15 NC Balloon) Pre-PCI Angio Control Angio This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Courtesy: Daniel Chamié, MD, Brazil 7

Inaccuracy of Visual Estimation of Vessel Size Control Angio After 3.25x18 mm PLLA-based scaffold post-dilated to > 3.5 mm 3.25x18 mm scaffold This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 8

Inaccuracy of Visual Estimation of Vessel Size B 3 2 1 A A 1 2 3 B This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Lumen Area: 12.43 mm2 Max. Diam.: 4.13 mm Lumen Area: 7.42 mm2 Max. Diam.: 3.23 mm 9

Farooq V, et al. Cathet Cardiovasc Interv. 2012;79:880-888

Inaccuracy of Visual Estimation of Vessel Size Quantification by QCA of vessels treated with 3.0-mm scaffolds in ABSORB Cohort B (n=102) (visual estimation of vessel size) 56.9% 47.1% 40.2% 39.2% 16.7% This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 2.9% Inadequately sized scaffolds Adequate reference size range for a 3.0 Absorb Inadequately sized scaffolds Farooq V, et al. Cathet Cardiovasc Interv. 2012;79:880-888 11

QCA: Interpolated Diameter vs. Max. Diameter Quantification by QCA of vessels treated with 3.0-mm scaffolds in ABSORB Cohort B (visual estimation of vessel size) and in ABSORB EXTEND (QCA mandated - DMAX) P=0.001 69.4% P=0.057 56.9% 57.0% 47.1% P=0.002 40.2% 41.1% 39.2% 26.9% 16.7% This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 2.9% 3.7% 1.9% ABSORB Cohort B (n=102) ABSORB EXTEND (n=108)a (n=107)b a n=108 for Dmax assessment b n=107 for interp. diam. assessment Farooq V, et al. Cathet Cardiovasc Interv. 2012;79:880-888 12

QCA vs. IVUS vs. OCT 100 CAD patients from 5 centers were studied with Angio, IVUS and FD-OCT 5 Phantom models, with known luminal dimensions were examined with FD-OCT and IVUS Differences in MLD among Angio, IVUS and FD-OCT Differences in Lumen Area between IVUS and FD-OCT This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Kubo T, et al. JACC Cardiovasc Imaging 2013;6:1095-1104 13

Intravascular Imaging: Vessel Diameter Sizing Maximum diameter of the smaller reference. Average of the maximum diameters of the prox. and distal references. Maximum diameter of the largest reference. Mid-wall to mid-wall diameters (between lumen and media) Media-to-media diameter 2 Increasingly Aggressive 1 2 1 2 1 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Max. LD: 4.01 mm Mean Mid-wall diam.: 4.18 mm Mean EEM diam: 4.28 mm Max. LD: 3.09 mm Mean Mid-wall diam.: 3.14 mm Mean EEM diam: 3.26 mm Max. LD: 3.96 mm Mean Mid-wall diam.: 4.02 mm Mean EEM diam: 4.19 mm Max. LD: 3.00 mm Mean Mid-wall diam.: 3.09 mm Mean EEM diam: 3.19 mm 14

Integrating Concepts This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 15

Intended landing zones Integrating Concepts 6F guide 3.5 x 20 mm NC balloon Intended landing zones This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 16

Step back and rethink your strategy Integrating Concepts A B C C B A LA: 8.68 mm2 Max. LD: 3.56 mm Mean EEM: 4.00 LA: 7.25 mm2 Max. LD: 3.04 mm LA: 11.58 mm2 Max. LD: 4.18 mm Mean EEM: 4.46 mm This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) Step back and rethink your strategy 17

Post-dil w/ 4.5/15 NC balloon Integrating Concepts 4.0x30 mm DES Post-dil w/ 4.5/15 NC balloon This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 18

Take Advantage of the Inflated Balloon Acquire a proper angiogram after IC nitro administration; Pre-dilate the lesion with a NC balloon sized 1:1 to the target vessel size at the intended landing zones NC Balloon 3.0 x 15 mm NC Balloon 3.0 x 15 mm This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 19

Puricel et al. J Am Coll Cardiol 2016;67(8):921-31 Impact of Optimal Implantation Technique on the Reduction of the Risk of ST 1) pre-dilatation with NC balloon – same size as RVD (1:1) 2) BVS implant only if optimal result achieved 3) BVS same size as RVD implanted at 10-12 atm 4) Systematic postdilatation with NC balloon up to 0.5 mm larger with 14-16 atm Puricel et al. J Am Coll Cardiol 2016;67(8):921-31

Tanaka et al. EuroIntervention 2016;published online Milan Series: 264 pts Treated with BVS with Optimal Technique – FU @ 2 Yrs 400 complex lesions (B2/C >70%) Bifurcation 47%, Heavy calcium 23%, CTO 6%, ISR 5% Mean scaffold length: 53.2 mm 44% received scaffold sized 2.5 mm IVUS/OCT in 86% (AVIO criteria) Additional treatment in 25% due to: Underexpansion in 82 Malapposition in 11 Edge dissection in 4 Incomplete lesion coverage in 1 ST: 3 cases (1.2%) up to 2 years (no very late ST) Tanaka et al. EuroIntervention 2016;published online

Impact of OCT-Guided PCI

Baseline Lesion Characteristics Variable BVS (n=50) DES (n=50) P value LAD 68% 50% 0.11 Type C lesion (ACC/AHA) 64% 74% 0.38 Significant calcium 62% 0.28 Ostial location 14% 10% 0.76 Bifurcation 34% 46% 0.30 ISR 12% 6% 0.48 QCA Lesion length, mm 24.7 25.1 0.86 RD, mm 2.7 MLD, mm 0.8 0.7 0.16 AS, % 83.7 86.9 0.25 Mattesini et al. JACC Cardiovasc Interv 2014;7(7):741-50

Mattesini et al. JACC Cardiovasc Interv 2014;7(7):741-50 Procedure Variable BVS (n=50) DES (n=50) P value Balloon predilatation - Maximal diameter, mm 3.0 2.5 <0.01 - Maximal pressure, atm 18.7 15.1 - Balloon/artery ratio 1.1 0.9 - Balloon type: NC 100% 87% Scaffolds/Stents 63 61 - - Nominal diameter, mm 0.94 - Nominal length, mm 28.0 0.42 - Devices per lesion 1.3 1.2 0.28 Balloon postdilatation 3.5 0.60 21.3 17.1 Mattesini et al. JACC Cardiovasc Interv 2014;7(7):741-50

Mattesini et al. JACC Cardiovasc Interv 2014;7(7):741-50 OCT Findings Variable BVS (n=50) DES (n=50) P value Mean device area, mm2 7.3 7.5 0.51 Minimal stent area, mm2 5.9 5.5 0.67 Mean lumen area, mm2 7.2 7.4 0.40 Minimal lumen area, mm2 5.8 0.97 Minimal device diameter, mm 2.7 2.8 0.46 Residual area stenosis, % 20.2 21.7 0.32 - >20% 39.7 42.6 0.85 Eccentricity index 0.86 0.45 ISA (per struts), % 1.7 1.9 0.62 Prolapse area, mm2 1.5 0.8 0.08 Fracture, % 3.2 0.49 Edge dissection, % 7.9 11.5 0.55 Mattesini et al. JACC Cardiovasc Interv 2014;7(7):741-50

Chamie et al. Catheter Cardiovasc Interv. 2016;88(S1):38-53 How to Size the Vessel? Chamie et al. Catheter Cardiovasc Interv. 2016;88(S1):38-53

Proposed Algorithm

Considerations Visual estimation is the standard method of vessel sizing, but it is subject to high variability and inaccuracy. QCA (DMAX) helps standardize measurements, but it underestimates lumen diameters in comparison to intravascular imaging methods. NC compliant balloon fully expanded at 1:1 ratio to the target landing zones is extremely helpful. Intravascular imaging (IVUS/OCT) is not mandatory, but lower threshold for use is highly recommended. OCT provides more accurate lumen quantification than IVUS. Specific protocol for sizing with IVUS/OCT for BRS still needs validation. Careful lesion predilatation under the PSP guidance may significantly improve outcomes. This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 32

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