Appropriate BVS Utilization in the Cath Lab Ron Waksman, MD, FACC, FSCAI Professor of Medicine, (Cardiology) Georgetown University Director, Cardiovascular Research Advanced Education, MedStar Heart & Vascular Institute, Washington DC

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company Boston Scientific Biotronik Biosensors Astra Zeneca Medtronic Vascular Abbott Vascular Symetis Med Alliance LifeTech Amgen Grant/Research Support Consulting Fees/Honoraria

Interventional Cardiology Treatment: An Historical Unmet Need “From the very early days, interventional cardiologists have been dreaming of a transient scaffold that would disappear after the job has been done.” European Heart Journal, 2011, doi:10.1093/eurheartj/ehr384

SCAFFOLD IS FULLY RESORBED WITHIN 3-4 YEARS All scaffold polymer is resorbed within 2-3 years Chemical analysis of preclinical specimens shows that resorption sites contain no polymer Polymer resorbs at the same rate in animals and humans¹ Degrading polymer is replaced by provisional matrix Pre Clinical Images 6 months 12 months 18 months 24 months 30 months 36 months Scaffold Strut Resorption Site 48 months Representative photomicrographs of porcine coronary arteries implanted with Absorb BVS. Images on file with Abbott Vascular.

SCAFFOLD IS FULLY RESORBED Baseline 6 Months 2 Years 5 Years De Bruyne, B. TCT 2014 Cohort B OCT images - courtesy of RJ van Geuns, Erasmus Medical Center, Netherlands

Why implant a resorbable scaffold? Possible advantages of transient BRS vs. permanent DES Vessel angulation and curvature are anticipated to be restored by the time the scaffold loses its integrity. Restoration of vessel anatomy Liberation from the permanent metal cage will facilitate restoration of vessel pulsatility and vasomotion. Compensatory expansive remodeling and/or lumen enlargement will not be restricted. Restoration of vessel functionality The risk of late or very late scaffold thrombosis will be eliminated as the foreign material (platform & coating) will be resorbed. Restoration of low thrombogenic milieu Complete scaffold resorption, intact endothelium with restored vasomotion will potentially eliminate the risk of in-scaffold neoatherosclerosis. Potential elimination of neoatherosclerosis Vascular Restoration Therapy

Which patients?

Recomedations from the expert panel 7 experts Publication of a consensus paper on optimal patient selection Jean Fajadet: co-founder and course director of the EuroPCR congress – BRS expert Michael Haude: President of the EAPCI board – Magmaris expert Michael Joner: Expert in the pre-clinical aspect of Magmaris Jacques Koolen: Co-founder of EuroCTO – BRS expert Michael Lee: co-PI of BIOSOLVE-IV – BRS expert Ralph Tölg: Part of BIOSOLVE-II – BRS expert Ron Waksman: Associate Director, Division of Cardiology at the Washington Hospital Center – Magmaris expert

Patient and lesion characteristics Patient Characteristics Recommendation Lesion Characteristics Patients with long life expectancy *** De novo lesions  Diabetic patients ** Tortuous Vessels - STEMI Severe calcification Cardiogenic Shock In-stent restenosis Stable angina Reference vessel diameter less or larger than the available device sizes NSTEMI / Unstable angina Diffuse long lesions Contraindications for DAPT Chronic Total Occlusions Target lesion located in a SVG Ostial lesions Patients with poor medical compliance Bifurcations No adequate lesion preparation Presence of thrombus   Left main lesions - =not recommended, **=evaluation pending, ***=recommended J. Fajadet, M. Haude, M. Joner, J. Koolen, M. Lee, R. Tölg, R. Waksman, Magmaris preliminary recommendation upon commercial launch, a consensus from the expert panel on the 14th of April, EuroIntervention 2016 ;12:828-833

Limitations of BVS Mechanistic Reasons Unfavorable Lesion sub-sets High profile – difficult to deliver, issue in small vessel or already stented vessel - require careful vessel preparation Issues of overlap – stent positioning and limitation of vessel lumen in overlap. Difficult to visualize – require IVUS/OCT for proper evaluation of result Plastic stent – high chance of mal-apposition (Chance of Stent Thrombosis or BVS Recoil) – Require high pressure post dilatation Calcific or fibrotic lesions Tortuous lesions Small vessels Bifurcations ISR

Technical, procedural and DAPT recommendations Careful technique for vessel preparation and device deployment is essential, this recommendation includes: Meticulous vessel preparation with balloon predilatation for all lesions Precise lesion size and length assessed Image guided implantation with OCT or IVUS at the beginning of the learning curve Balloon postdilatation with a non-compliant balloon DAPT duration is at the physician discretion, in stable patients it is recommended for at least 12 months post deployment with ABSORB but preferably now up to 3 years if the patient does not bleed. J. Fajadet, M. Haude, M. Joner, J. Koolen, M. Lee, R. Tölg, R. Waksman, Magmaris preliminary recommendation upon commercial launch, a consensus from the expert panel on the 14th of April, EuroIntervention 2016 ;12:828-833

BRS: Tips and Tricks for a successful procedure Correct target vessel sizing at the lesion site is crucial If uncertain about the size, use QCA, IVUS and/or OCT for quantitative lesion evaluation QCA underestimates and IVUS overestimates vessel dimensions by about 0.25mm Since the diameters available are 3.0mm and 3.5mm, do not implant into vessels <2.7mm or >3.7mm 1- Size the vessel properly Non-compliant balloon, 1:1 balloon-to-artery ratio, full expansion of the balloon should be achieved. Residual stenosis should be < 20%, accept lesion dissection, if necessary use scoring balloon If the lesion is very calcified, use rotablator followed by non-compliant balloon dilatation NB: Heavily calcified lesions are currently off-label 2- Prepare the lesion thoroughly Inflate the implantation balloon until full and homogenous expansion, but respect the maximum rated burst pressure Angiography of implant result (QCA) OCT for documentation of implant result (helpful during the learning phase) Always post-dilate with a NC balloon at high pressure (>16 atm) if OCT shows suboptimal results keeping in mind the Magmaris expansion limit of 0.6mm beyond nominal scaffold size 3- Always post-dilate with NC balloon Optimal BRS implantation

Median based on pooled Absorb and Xience Avoid Small Vessels Outcomes by QCA RVD 2.25 mm RVD <2.25 mm (median 2.09 mm) RVD ≥2.25 mm (median 2.74 mm) TLF: Pint diff = 0.31 ST: Pint diff = 0.12 1-Year Events (%) # Events: 31 11 2 71 30 9 3 # Risk: 241 133 238 1067 542 1058 540 Median based on pooled Absorb and Xience

Optimal Implantation Technique Is Imperative for Good Clinical Outcomes Implantation Guidance Has Evolved During Enrollment in ABSORB Trials Full PSP Was Not Used in Many Patients 2009 2010 2011 2012 2013 2014 2015 2016 ABSORB Cohort B ABSORB EXTEND ABSORB II ABSORB JAPAN ABSORB III ABSORB CHINA ABSORB FIRST ABSORB IV Study enrollment period Guidance on technique in commercial practice Cohort B: March 9, 2009 and November 6, 2009 EXTEND: January 11, 2010 and October 2, 2013 AII: Nov 28th, 2011, and June 4th, 2013 A-Japan: April 27th, 2013 and December 27th, 2013 A-China: July 31, 2013 and March 13, 2014 A-FIRST: January 21st 2013 and August 30th 2014 AIII: March 22, 2013 and April 3, 2014 High Pressure Post Dil RVD  2.5mm (US: FDA IFUs) Implantation technique advised against high pressure Post-Dil Ellis, S., Technique in ABSORB Trials, TCT 2016.

Learning Curve a bvs-specific implantation strategy can improve outcomes PREPARE THE LESION S SIZE APPROPRIATELY P POST-DILATE P S P Adapted from Gori, T., EuroPCR 2015

Optimal Implantation technique is imperative for good clinical outcomes Improvement over time due to patient/lesion selection and improved technique 1Hamm, C. GABI-R, EuroPCR 2016. / 2Cortese, B. RAI, EuroPCR 2016. / 3Puricell, S., et al. Bioresorbable Coronary Scaffold Thrombosis, J Am Coll Cardiol. 2016;67:921–31. / 4Gori, T. 4 Cities Registry, EuroPCR 2015.

WORLDWIDE ABSORB VOLUNTARY REPORTING OF THROMBOSIS BY IMPLANT DATE Size the vessel (3Ps) Postdil (OUS: 4Ps) High Pressure Post Dil 2.5mm  RVD (US: FDA IFUs) 2012 2013 2014 2015 2016 Implant Date 1 Data represents exponentially weighted moving average Data dated from Aug 31, 2016

Current limitations of BRS technology Mainly performance aspects: Pushability Trackability Difficult to pass complex tortuous calcified vessel segments and lesions (including bifurcation lesions) Poor visibility if at all Need excessive lesion preparation and post-dilatation Poor vessel size and shape conformability Slow scaffold expansion

Next Generation BRS Thinner struts (overlap/2 scaffolds) More overexpansion? (Tapering at side branch!) Reduce scaffold thrombosis Easier lesion crossing

Bioresorbable Scaffolds in Development REVA ReZolve ART18Z Abbott Absorb BVS 1.1 Amaranth Fortitude1 ELIXIR DESolve Biotronik Magmaris REVA Fantom Boston Scientific RENUVIA Amaranth Aptitude1 ELIXIR DESolve Cx3 ABSORB 2nd Gen PolyCarb PDLLA PLLA Mg, PLLA SES None EES MES NES 1st Generation BRS 2nd Generation BRS Scaffold Drug

New Generation BRS: Will They Overcome Current Limitations of BRS Technology? New generation BRS should overcome current limitations of first generation BRS It is imperative to adhere to appropiate patients and lesionS selection to avoid BRS complications. Once BRS overcome these limitations we should consider expanded indications The future depends on demonstrating superiority over best in class DES in a head to head comparison in prospective randomized trials

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