1. The role of BVS in CTO PCI : Mid-term Clinical Outcomes with Multi-imaging Techniques CTO NYC 2016 Yaron Almagor M.D. Antonio Serra M.D. Director Interventional Cardiology Shaare Zedek MC, Jerusalem Sant Pau M.C, Barcellona

2. Disclosure Statement of Financial Interest I DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation. All CTO 2016 faculty disclosures are listed on the CRF Events App.

3. Is one of the most challenging scenarios to test, due to long fibrocalcified lesions with high plaque burden 1, 2 In this setting is where “vessel reparation” might be most needed. Avoid a “full metal jacket”, precluding future CABG Rationale: BVS in CTOs 1.- Rubartelli A, et al. Eur Heart J 2010 2.- Galassi AR, et al. EuroIntervention 2011

4. Objectives CTO-ABSORB pilot study is a prospective, observational, two-center registry designed to : Assess the safety and performance of the Absorb everolimus-eluting scaffold BVS, in unselected consecutive patients undergoing PCI for CTO, under guidance of imaging techniques To provide preliminary observations and generate hypotheses for future studies with a large proportion of patients.

5. Objectives All comers registry with few exclusion criteria : - Patient or referring physician refusal - Extremely calcified lesions + tortuosity - True bifurcated lesions with SB > 2.5 mm - Reference vessel diameter < 2.5 mm or < 4.5 mm (out of the Absorb measures) - Complications treated with metallic stents

6. Methods Wire Crossing 1 st dilatation small balloon 1.25- 2.0mm NTG 400 mcgr IVUS analysis Further dil. with NC /Cutting/ Rota + cutting IVUS analysis BVS implantation OCT,IVUS analysis Further dil. with NC if needed Renal function & CK, US Troponin - Pre & 6, 12 & 24 hours post-PCI

7. Follow-up Clinical FU by Phone Call: 1 month Angio FU & OCT: 12 months Clinical Visit & MSCT: 18 months Clinical Visit & MSCT/MRI: 6-8 month Clinical FU by Phone Call: 24 months, 3, 4 and 5 years

8. 67 successful CTOs (2014-2015) 49 clinical eligible CTOs 38 Absorb CTO cases 35(44) Absorb CTO cases 7 patients excluded: Patient or referent physician refuse 6 patients excluded: Live CTO courses with other DES 5 patients excluded: Old patients with comorbilities Clinical criteria (n=18) 5 patients excluded: Angio Calcium + tortuosity 4 patients excluded: True bifurcated lesions + SB ≥ 2.5mm 2 patients excluded: Reference vessel diameter < 2.5 (n=1) or ≥ 4mm (n=1) Angiographic criteria (n=11) Bail-out stent (DES) used (n=3) (1) Coronary perforation after balloon: stent graft (1) Aorto-ostial disection after rotational atheretomy: 4mm DES (1) Distal coronary disection after BVS: 2.25mm DES 28.5% of clinical eligible CTOs were excluded due to predefined-angio criteria or PCI related complications Study Profile

9. Pre-procedure RCA CTO J- CTO Score Complexity 2 1 1 4 4 3 3 2 2 IVUS pre- BVS implantation Side branch Cutting balloon pre- dilatation After wiring & pre-dilatation 21mm

10. 3.0 x 28mm 3.5 x 28mm 2.25 x20 mm Drug- coated Balloon 3 overlapped BVS Absorb 3.0 x 28; 3.5 x 28 & 3.5 x 28 mm (84 mm length) + drug-eluting balloon 2.25 x 20 mm in LPD Post-BVS implantation

11. Final OCT 1. 2*. 3. 4*. 5. OCT post-BVS implantation After NC balloon post-dilatation

12. LAO 30º/ CRAN 12º 6-months MSCT FU12-months Angio FU * * * *

13. 1. 2. 3*. 4*. 5. OCT 12 months post-BVS

17. Results

18. Age (years) (mean±SD) 55.7  9.7 Male gender84.0 (36) Risk Factors Diabetes23.0 (10) Hypertension58.0 (25) Dyslipidemia76.3 (33) Current Smoker18.6 (8) Clinical Presentation Silent ischemia/Stable angina 85.7 (5/25) Baseline cMRI 48.6 (17) Baseline MSCT88.0 (31) LVEF (≤ 50%) 22.9 (8) 3 vessel disease25.0 (5) Unless specified otherwise, values are % and (n) of patients Clinical Characteristics (n=44) History of Myocardial Infarction23.2 (10) PCI30.2 (13)

19. Unless specified otherwise, values are % and (n) of patients Target Vessel: -RCA44.1% (19) -LAD46.5% (21) -LCx/Marginal Branch 9.3% (4) CTO location: -Ostial/proximal 41.8% (18) -Mid 53.4% (23) CTO involving bifurcated lesion 16.2% (7) In-stent restenosis (Class IV) 4.6% (2) Lesion Characteristics (n=44)

20. CTO angiographic characteristics Blunt stump type* 40.0 (14) Severe Tortuosity (Bending)* 11.4 (4) Significant Calcification* 34.3 (12) Previously Failed Lesion* 8.6 (3) Occlusion length ≥ 20mm* 31.4 (11) CTO complexity (J-CTO Score) Easy (score of 0) 25.6 (9) Intermediate (score of 1) 48.6 (17) Difficult (score of 2) 8.6 (3) Very difficult (score of ≥3) 17.2 (6) Occlusion length (mm) 18.6  12.5 Target Lesion length (mm) 35.9  15.8 Unless specified otherwise, values are % and (n) of patients CTO complexity (n=44)

21. Radial or bi-radial/femoral approach60.0 (21) 6- Sheath Size51.4 (18) Antegrade Strategy85.7 (30) Number of GW used per lesion 1.8  1.1 Number of pre-dilatation balloons used per lesion 2.6  0.97 Plaque modification: Cutting balloon pre-dilatation 71.4 (25)) Rotational Aterecthomy 8.6 (3) Number of scaffolds used per lesion 2.2  0.89 Total scaffold lenght implanted per lesion, mm 52.5  22.9 Post-dilatation (0.5mm bigger NC balloon / scaffold) 62.9 (22) Unless specified otherwise, values are % and (n) of patients Procedural Characteristics (n=44)

22. Immediate Results (n=44) Total number of visible analyzed SBs covered by BVS(n)109 Mean number/lesion 3.2  1.4 SB < 0.5mm41.3 (45) SB ≥ 0.5mm58.7 (64) Post-BVS SBO6.4 (7) SB < 0.5mm3.7 (4) SB ≥ 0.5mm2.7 (3) All scaffolds were successfully delivery and deployed Side Branch Occlusion (SBO) 6 : as a reduction in TIMI flow to grade 0 or 1. Accordingly, side branches with pre-BVS implantation TIMI flow grade 0 or 1, were excluded 6.- Muramatsu T, et al. JACC Cardiovasc Interv. 2013 Dissection before BVS was observed in (4/7) 57% of all SBO cases (100% of SBO with bigger SB ≥ 0.5mm)

23. Contrast-induced nephropathy0 (0) Peri-PCI Myocardial damage (only markers)7.5 (3/40) Peri-PCI Myocardial infarction0 (0) Vascular access site complication2.8 (1) 7.- Kristian Thygesen K, et al. Eur Heart J 2012 In-Hospital Results (n=44) Peri-PCI myocardial damage: CPK ≥3 times the upper limit of normal (ULN) & US troponin ≥5 times ULN. In case of symptoms and/or electrocardiogram changes suggesting MI, was defined as Myocardial infarction 7 A procedure-related contrast-induced nephropathy (CIN) was defined as an increase of 25% or 0.5 mg/dl in serum creatinine at 24-48 hours after PCI comparing baseline values 8 8.- Mehran R, et al. J Am Coll Cardiol 2004 Blood test was performed pre and 6, 12, 24h post-PCI

24. 1-month FU (n=43)6-months FU (n=35) Overall Death00 Cardiac00 MI00 TLR00 MACE00 BVS Thrombosis*00 In-scaffold re-occlusion**(2) 5.7% ARC definition* Results (44) MSCT** (100% FU completed)

25. Conclusions We reported excellent mid-term patency and safety by 6-8 months clinical and MSCT follow-up The ABSORB-CTO pilot study demonstrated the feasibility of PCI of CTO lesions with the fully bioresorbable Absorb ® BVS, in the current era under imaging guidance techniques. Further clinical and imaging follow-up at future time points is required to extend the significance of the current findings.