Elena Matteucci Global Product Manager - CID Spa The CID technological approach to the open questions in peripheral vascular intervention Elena Matteucci Global Product Manager - CID Spa

Disclosure Statement of Financial Interest I, Elena Matteucci, have the following financial interest/arrangement or affiliation: CID employee

Peripheral Procedures Outcomes Scenario setting specific Patients related issues Post-procedural implications

What do physicians need from implantable devices?

..improved clinical outcomes.. ..in Femoral Procedures ..improved clinical outcomes..

..improved technical features such as: ..in Iliac Procedures ..improved technical features such as: - Precise deployment - Radial force - Flexibility - Deliverability

..in Renal Procedures ..avoid geographic miss

..a gold standard solution to improve clinical outcomes ..in BTK Procedures ..a gold standard solution to improve clinical outcomes

The CID technological approach

The CID technological approach Dedicated platforms and delivery systems setting specific Unique fundamental features every-setting required

Dedicated platforms and delivery systems setting specific Renal Stent Iliac Stent Femoral Stent BTK Stent

Unique fundamental features every-setting required PRECISE POSITIONING RADIAL FORCE / FLEXIBILITY FAST ENDOTHELIAZATION & OPTIMIZED CLINICAL OUTCOMES

Unique fundamental features every-setting required PRECISE POSITIONING RADIAL FORCE / FLEXIBILITY FAST ENDOTHELIAZATION & OPTIMIZED CLINICAL OUTCOMES

Unique fundamental features every-setting required PRECISE POSITIONING STENT MARKERS guarantee perfect placement exceptional visibility ZERO FORESHORTENING UPON EXPANSION preserving the original stent length

Unique fundamental features every-setting required UNIQUE CELLS DESIGN PRECISE POSITIONING BX Stents SX Stents RADIAL FORCE / FLEXIBILITY FAST ENDOTHELIAZATION…

Unique fundamental features every-setting required PRECISE POSITIONING RADIAL FORCE / FLEXIBILITY FAST ENDOTHELIAZATION & OPTIMIZED CLINICAL OUTCOMES BIO INDUCER SURFACE

Heart valve: the worst setting for thrombotic events Pyrolitic Carbon (PyC) is the only material used to realize mechanical heart valve leaflets since more than 35 years thanks to its un-matched thrombo-resistant properties Sorin St. Jude Carbomedics Medtronic (ATS) ...others...

The Bio Inducer Surface (BIS) The Bio-Inducer Surface is made of pure carbon atoms Bio/haemo-compatibility Diamond Graphite % % This 2nd generation pure carbon coating (≤0.3 µm) brings the cristalline structure closer to the diamond structure with a further improvement of its bio/haemo compatibility

BIS - Foreseen clinical impact The BIS coating is the only surface in contact with vessel wall and blood stream BIS BMS Time Day 0 Thrombo-resistant surface Pro-thrombotic surface Day 3 Partially endothelialized + thrombo-resistant surface Pro-thrombotic surface Day 7 Endothelialized surface Partially endothelialized + pro-thrombotic surface Slide pictures are of a purely illustrative nature and are not intended to depict reality

The Bio Inducer Surface in coronary arteries Continuous endothelial layer @ 5d in preclinical study 3.9% of struts uncovered @ 4/7d in ACS patients # Stent implants in pig coronary arteries. University of Turin. Anal Bional Chem 2012 Oct 9. J Cardiovasc Med (hagerstown) 2012 Apr 19.

The Bio Inducer Surface in peripheral settings Benefits in endothelization Reduced restenosis in high restenosis setting due to flow turbolences – e.g. ostial lesions Seals the bulk Nitinol material (Nickel-Titanium alloy) avoiding any release of heavy metal ions Reduced risk of thrombosis especially high in long stents implantation and in distal lesion with low ABI index, because there is no metal in contact with the vessel wall and the blood flow

The CID future developments

Drug Eluting Stent - BX and SX – today available Drug Eluting Stents Drug Eluting Stent - BX and SX – today available STANDARD POLYMERIC DES Polymer drug elution towards vessel wall Polymer + drug towards lumen STANDARD NO POLYMERIC DES No guarantee controlled drug elution towards vessel wall

CID DES efficacy free from limits Abluminal Reservoir Technology - ART Amphilimus™ Formulation: Sirolimus + organic acid BIS: Bio Inducer Surface

CID DES efficacy free from limits -II Abluminal Reservoir Technology - ART CID utilizes a proprietary polymer-free drug release system (ART) constituted by reservoirs on the stent's outer surface ARTERIAL WALL Drug elution is controlled and directed exclusively towards the vessel wall BLOOD FLOW Lack of any polymer - Lack of any drug No interaction with endothelization process

CID DES efficacy free from limits - III Controlled and directed drug elution - ART The reservoir’s design directly impacts on drug amount and release kinetic FICK’S LAW Kinetic examples The amount of drug released overtime is proportional to the area of contact and to the drug concentration gradient

CID DES efficacy free from limits - IV Amphilimus™ Formulation : Sirolimus + Organic Acid Specific properties/contributions Sirolimus Amphiphilic carrier Immunosuppressant Anti-proliferative action Anti-microbial Inhibitor of inflammatory cell activities High potency Sustained drug elution timing Modulated drug bioavailability Raised homogeneous drug distribution Enhanced drug stability

Conclusions The technological contents of today available implantable devices are not meeting all physicians needs in endovascular settings CID has focused its development efforts into 3 different areas: - unique design attributes optimizing visibility, positioning and mechanical performances - Bio-inducer-surface to fast endothelization and improve clinical outcomes - Polymer –free DES technology with controlled elution to enhance device performance in complex endovascular clinical conditions

Interventions in highly calcified iliac arteries Assoc. Prof. V. Chervenkoff

Dealing with highly calcified lesions of the iliac arteries could be a very challenging task. Extremely hard plaques Higher risk of vessel rupture Difficult navigation of the devices

Clinical case 61 y.o. male Peripheral occlusive arterial disease: rest pain in the left lower extremity ABI sin – 0 Comorbidities: IHD, AH, T2DM, Dislipidemia

Preoperative CT-Angiography CTO of the left common iliac artery Highly calcified plaque

Stages of intervention Initial angiogram

Stages of intervention Intraluminal recanalisation – verifying the true lumen proximal to the lesion

Stages of intervention Implanting a balloon expandable BMS

Stages of intervention Completion angiogram

What made our choice? Low profile High radial force Precise implantation Suitable size Fracture resistancy

What did we used Isthmus, 9x59 mm, 75 cm, 6F

Outcomes Lower class Fontaine PAOD from III to IIa ABI sin from 0 to 0.55 18 months follow-up

Thank you for attention!