Cardiac catheterization Labs AngioSculpt® A New Scoring Balloon Pre-stent plaque modification in complex, calcified coronary artery lesions Ehud Grenadier M.D Cardiac catheterization Labs Haifa;Herzlia ISRAEL

Why is Lesion Preparation Essential?

POSTIT Trial : when using only the stent delivery balloon over 70% of the pts. did not achieve optimal stent deployment. Percent of Population Patients who did not achieve optimal stent deployment with SDS 40 50 60 70 80 90 100 120 130 MSD as percent of RLD MSD as a percentage of RLD following stent deployment. Optimum stent deployment : (MSD 90% RLD). Patients not achieving criteria with the stent delivery system (71%) Brodie B. et al POSTIT Trial, Cath. Card. Int. 2003: 59,184-192.

Manufacturer’s Predicted MSD (mm) Manufacturer’s Predicted Minimal Stent Diameter (MSD) is Usually Not Achieved With the Original Stent Balloon + x 2.5 3.0 3.5 4.0 4.5 1.5 2.0 2.5 3.0 3.5 4.0 4.5 Manufacturer’s Predicted MSD (mm) IVUS Measured MSD (mm) Nominal Stent Size Manufacturer A Manufacturer B Manufacturer C Manufacturer D Costa et al, Am J Cardiol 2005:96,74-78

MSA and stent under expansion are major predictors of stent thrombosis Non-uniform stent strut distribution and malapposition may result in more intimal hyperplasia after stenting MSA and stent under expansion are major predictors of stent thrombosis R E S T N O I Takebayastri Study: Hideo Takebayastri et al. “Non-uniform Strent Strut Distribution Correlates with More Neointimal Hyperplasia after Sirolimus-Elluting Stent Implantation” Circulation 2004;110:3430-3434 B.Brodie. Adjunctive balloon post dilatation after stent deployment. J Interven Cardiol 2006;19:43-50 H B IVUS guidance may result in more effective stent expansion and results in 44% reduction in TVR Only 22% of patients that experience SAT have an optimum PCI result as assessed by IVUS CRUISE study: Peter J. Fitzgerald et.al. “Final Results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE) Study” Circulation 2000 102:523-530 .Cheneau Study: Edouard Cheneau,et al. “Predictors of Subacute Thrombosis. Results of a Systematic Intravascular Ultrasound Study.” Circulation 2003; 108:43-47 T V R S A

Benefit of the AngioSculpt for Pre-dilatation of DES Group I (n=145) Group II (n=117) Group III (n=37) p value MSD/PSD 76% ± 10% 76% ± 13% 88% ± 18% <0.001 MSA/PSA 67% ± 16% 70% ± 23% 88% ± 22% Final stent CSA < 5.0mm2 26.2% 25.6% 10.8% 0.03 Group I = direct stenting Group II = pre-dilatation with POBA Group III = pre-dilatation with AngioSculpt CSA = cross sectional area, MSA = minimum stent area, MSD = minimum stent diameter, PSA = predicted stent area, PSD = predicted stent diameter Costa et al, AHA 2006

AngioSculpt Scoring Balloon Catheter Semi-compliant balloon with an external nitinol shape memory helical scoring edge

Centrally Located Within the Arterial Lumen

The AngioSculpt is Comprised of: B A - Rapid exchange or OTW semi-compliant balloon B - Laser cut nitinol scoring element

Histopathology of the AngioSculpt vs. POBA Acute histopathology specimen of a patient post conventional balloon angioplasty demonstrating extensive dissection and laceration (yellow arrows) Post-AngioSculpt scoring of porcine ISR (yellow arrows)

Herzliya & Rambam Med. Ctrs. Herzliya & Haifa, ISRAEL Use of the Angiosculpt for Pre-dilation of Challenging Coronary Lesions Prior to Stenting Personal Experience Ehud Grenadier, Arthur Kerner, Nabeel Makhoul, Luis Gruberg, Ariel Roguin Herzliya & Rambam Med. Ctrs. Herzliya & Haifa, ISRAEL

Aims of the Study To evaluate the Deliverability, Efficacy, and Safety of the AngioSculpt Scoring Balloon Catheter in patients with challenging and calcific CAD

Study Design Two-center, prospective, consecutive, non-randomized single operator registry Inclusion criteria: pts with single or multi-vessel coronary artery disease scheduled to undergo PCI Population: 221 consecutive pts enrolled at 2 sites Follow-up: outpatient visits, telephone interviews and re-catheterization if clinically indicated

I.V.U.S - Virtual Histology Performed in 111/221 [ 49.7 % ] pts. 154/279 [ 55.2 % ] lesions Evaluated in 60/221 [ 27.1 %] pts. 76/279 [ 27.2 %] lesions “Volcano Therapeutics” IVG - 3 / S-5 Eagle Eye Gold IVUS catheter

AngioSculpt Relative Contraindications Unprotected left main disease Non-calcified SVG lesion Thrombotic lesion

Primary Performance Endpoint Procedural Success Final diameter stenosis ≤10% in all AngioSculpt treated lesions following completion of the interventional procedure (including adjunctive stenting when used) without in-hospital major adverse cardiac events (MACE)

Primary Safety Endpoint Clinical Success Successful PCI and freedom from MACE at 30 day follow-up MACE is defined as death, Q wave or non-Q wave MI, CABG or TLR of the index lesion

Secondary Endpoints Flow limiting dissection Vessel perforation

Patient Demographics 221 pts, 279 lesions Age: 63.8±19.4 yrs (range 34 – 88) Males: 72% Severe Angina (CCS class 3-4): 56% Prior PCI: 43% Prior MI: 34% Prior CABG: 6%

Risk Factors 5.7% NIDDM 58.7% 35.8% 41.2% % IDDM

Vessel Distribution %

Lesion Characteristics ISR: 51/279 [18%], De-Novo: 228/279 [82%] Bifurcation: 69/279 [25%] Eccentric: 117/279 [42%] Ulcerated: 31/279 [11%] >30° angulation: 154/279[55%] Mean lesion angulation: 34.3±17˚

Lesions Classification (AHA/ACC)

Calcification Severity

Pre-Procedure QCA

Pre-Procedure Lesion Measurements (QCA) Length (mm) MLD RVD [d] 17.1+11.4 0.26±0.29 2.69±0.35

Primary Endpoint Results Procedural Success: 96.0% [268/279] Clinical Success: 94.6% [209/221]

AngioSculpt “Only” Procedural Success Diameter stenosis <50%: 224/279 [80%] Diameter stenosis ≤20%: 158/279 [57%] Final failure to cross with the AngioSculpt occurred in 8/279 lesions [2 .9%], all occurred in severe, calcified lesions with pronounced vessel/lesion angulation

QCA Results Diameter Stenosis (%) Pre-ASC Post-ASC Post-Stent 82.9+11.2 23.5+13.6 5.9+4.4

QCA Results (cont’d) Minimum Luminal Diameter (mm) Pre-ASC Post-ASC Post-Stent 0.26+0.29 2.07+0.68 2.43+0.72

IVUS Results MLD (mm) and CSA (mm2) MLD, CSA Ref. Vessel (d) Pre-dilatation Post-ASC P-Value* Post-stent 2.99±0.58 7.1±2.9 1.7±0.14 2.57±0.45 2.1±0.35 3.86±1.08 p<0.0001 2.82±1.1 5.5±2.03 p<0.002 *Paired t-Test

IVUS Results Lesion Characteristics Mod-Severe Ca++ Eccentric Post-ASC “Controlled” Dissections 72.4 % 39.1% 82.7 %

AngioSculpt Dimensions & Inflation Pressures ASC Diameter (mm) ASC Length Inflation Pressure (atm) 2.51+0.34 16.4+3.3 15.1+2.4 range: 10-18

Reduction in Usage of NC Balloons Pre-ASC Usage of NC Balloons in ASC Study Reduction in Usage of NC Balloons 89% 43% 46%

AngioSculpt Crossability Planned POBA Pre-ASC Successful Primary ASC POBA Pre-dilatation After Primary ASC Failure to Cross Failure to Cross with ASC After POBA Pre-dilatation Predicted Failure to Cross (ASC not attempted) 113/279 [40.5%] 104/279 [37.3%] 31/279 [11.1%] 8/279 [2.9%] 1/279 [0.4%]

Device slippage was observed in 4/271 [1.5 %] of ASC treated lesions

Double Wire Techniques In 11/279 [3.9 %] lesions the additional use of a buddy wire resulted in successful crossing of 6/11 lesions The anchor wire [LCA] was used in 5/279 [1.8%] lesions resulting in successful crossing in 3/5 lesions

Stent Types Used in the Study Stents were implanted in 264/279 [94.6%] lesions

Distal Left Main and Proximal LCx Lesions

ANGIOSCULPT 2.0 x 15 mm

POST-DES INSERTION

IVUS Demonstrates Optimal Stent Apposition

Angiogram and IVUS Pre-Intervention MLD = 1.2mm MLA = 1.5mm² Plaque area = 5.72mm² Plaque burden = 83%

Angiogram and IVUS Post-AngioSculpt Yellow arrows indicate “scoring marks” MLD = 1.4 mm MLA = 3.1 mm² Plaque area = 4.8 mm² Plaque burden = 63%

Angiogram and IVUS Post-Stent MLD = 2.6 mm MSA = 5.2 mm²

Severe calcified Lcx Lesion

Angiosculpt Dilation

Final Angiographic Result [ Post Taxus Stent Insertion ]

Distal long RCA lesion

Pre dilated RCA lesion - Q.C.A Analysis

3.0/20 mm and 3.5/15 mm Angiosculpt Predilation

3.5 mm Endeavor Stent Insertion

FINAL Angiographic RESULT

Cumulative MACE @ 30 day F/U 215/221 [97.2%] pts Complication Rate Total MACE 6/221 [2.7 %] Death at day 10 [ non cardiac ] Sepsis ? P.E ? 0.4% (1/221) M.I (Q or Non-Q wave) 0.9% (2/221) Procedural complications (VF) 0.4% (1/221) Chest pain, Re-cath, TIMI-2 , Patent Re-Hospitalization 2.3 % (5/221) Re-Catheterization TLR TLR- PCI 0.9% (2/221) Vessel and Aortic Root - Dissection

Procedural Complications (per lesion) 0/279 Perforation 5/279 [1.8%] Distal embolism 10/279 [3.6%] Moderate side branch occlusion 1/279 [0.36%] Thrombus formation 6/271 [2.2%] Dissections (> type C), no flow limiting dissection.

Cumulative MACE @ 19.2±11.2 mon. 187/221 [84.6%] pts. Complication Rate Total MACE 4.9 % (11/221) Death at day 10. non cardiac. 0.4% (1/221) MI (Q or Non-Q wave) 0.9% (2/221) Re-Hospitalization 18.6% (41/221) Re-Catheterization 15.4% (36/221) CABG [>6 months] 0.9% (2/221) [5.6%] Re-TLR/TVR - PCI 2.7% (5/221) [13.8%] Vessel and aortic dissection

Conclusions I The ‘AngioSculpt’ is highly effective for the treatment of a broad spectrum of challenging coronary artery lesions It is very useful to avoid “geographic miss” due to device slippage A surprisingly low rate of TVR, no CARDIAC related DEATH and no Late Stent THROMBOSIS was observed during long term F/U in this study

Conclusions II NC balloon usage was reduced by 46% in the lesions in which the AngioSculpt was successfully deployed Difficulty in device deliverability may be anticipated in severe, calcified lesions associated with pronounced vessel/lesion angulation (or when the IVUS catheter was unable to cross the lesion) Deliverability enhancements including an improved crossing profile and lubricious coating are in development