Transcript slides

Clinical Update on the AngioSculpt Scoring Balloon
& Development of a Drug-Coated Device
Gary Gershony, MD, FACC, FSCAI
John Muir Medical Center
Walnut Creek, California
Gary Gershony, MD
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
Grant/Research Support
Consulting Fees/Salary Support
AngioScore, Inc.
Major Stock Shareholder/Equity
Royalty Income
Ownership/Founder
Intellectual Property Rights
Other Financial Benefit
AngioScore, Inc.
Angioplasty Balloon Inadequacies
• DES/BMS pre-dilatation (geographic miss,
inadequate stent expansion/wall apposition)
• Heavily calcified/hard lesions
• ISR (balloon slippage, tissue recoil)
• Diffuse/small vessel disease
• Bifurcation side branch ostial lesions
• Unpredictable results and high rate (≥30%) of
uncontrolled dissections
AngioSculpt
• 2 component system
• OTW or rapid exchange (RX or EX) semi-compliant balloon
• Laser cut nitinol spiral scoring element
AngioSculpt – Mechanical Forces
Edges lock in
~15-25x force
1x force
AngioSculpt – Mechanism of Action
Acute histopathology specimen of a
patient post-POBA demonstrating
extensive dissection and laceration
(yellow arrows)
Post-AngioSculpt scoring of
porcine ISR (yellow arrows)
Human IVUS demonstrating scoring
post-AngioSculpt (yellow arrows)
Pre-Angioplasty
IVUS of SFA
IVUS Post-POBA
IVUS Post-AngioSculpt
• Same SFA treated in
different locations
• Post-POBA deep
dissection is apparent
• Post-AngioSculpt
scoring is evident and
no dissection
OCT of RCA Lesions Post-AngioSculpt
De Novo (E) and ISR (F) Lesions
Post-AngioSculpt
OCT of De Novo Lesion
Post-AngioSculpt
demonstrating scoring
(white arrowheads)
Takano et al, Int J Cardiol 2008, doi:10.1016/j.ijcard.2008.11.154.
OCT of ISR Lesion PostAngioSculpt demonstrating
scoring (white arrowheads)
AngioSculpt Features – Coronary
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PMA approval for coronary indications (includes ISR & complex type C lesions)
CE Mark for coronary indications
Japanese Shonin coronary approval – January 2008
Low crossing profile (~2.7F)
Balloon catheter-like performance
OTW or rapid exchange design (EX in U.S., RX in rest of world)
0.014” guidewire compatible
6F guide catheter or 5F sheath compatible
3 nitinol spiral “scoring” wires (~0.005” & rectangular shape)
Nitinol enhanced active deflation
2.0 – 3.5 mm diameters
10, 15 and 20 mm lengths
AngioSculpt Features – Peripheral
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510(k) clearance for infra-inguinal disease and AV fistulae
CE Mark for peripheral indications
Japanese Shonin peripheral approval – June 2009
Low crossing profile & balloon catheter-like performance
OTW design: 0.014” guidewire for ≤ 3.5 mm diameter devices & 0.018”
guidewire for ≥ 4.0 mm diameter devices
Sheath compatibility: 5F for ≤ 3.5 mm diameter devices and 6F for ≥ 4.0
mm diameter devices (guide catheters are 1F larger)
3 or 4 nitinol spiral “scoring” wires (0.005” or 0.007” & rectangular)
Nitinol enhanced active deflation
2.0 – 6.0 mm diameters
10 – 40 mm lengths
AngioSculpt 5.0 x 40 mm
Pre-Inflation
Inflated @ 8 atm
Post-deflation
Proposed AngioSculpt Benefits
• Prepare Vessel for DES/BMS
– Non-slip (avoid “geographic miss”)
– Full stent expansion/apposition at lower balloon pressures
• Calcified & Fibrotic Lesions
– Lesion expansion at lower balloon pressures
– Less trauma/dissection leading to more predictable results
• Bifurcation Lesions
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Less elastic “recoil” in ostial side-branches or plaque-shifting
Lower rate of dissection and need for second stent in side-branch
Non-slip
Overcome “stent jail” of side-branch
• In-Stent Restenosis
– Non-slip (avoid “geographic miss”)
– Less tissue “recoil”
– More optimal re-expansion of original stent
U.S. Multi-Center Coronary Study – PMA
Overall Study PI: Martin B. Leon, MD, Columbia University
SITE PRINCIPAL INVESTIGATOR
CLINICAL SITE
Michael R. Mooney, MD
Abbott Northwestern Hospital
Paul S. Teirstein, MD
Scripps Clinic
Martin B. Leon, MD
Columbia University Medical Center
Mark Turco, MD
Washington Adventist Hospital
Mark Reisman, MD
Swedish Medical Center
Ron Waksman, MD
Washington Hospital Center
Jorge F. Saucedo, MD
University of Oklahoma HSC
Laura Mauri, MD
Brigham and Women’s Hospital
David Lee, MD
Stanford University Medical Center
Am J Cardiol, October 2006;98:8 Supplement:121M
Baseline Angiographic Characteristics
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200 patients with 219 lesions treated
ISR: 16%
ACC B2/C lesions: 76%
Moderate/severe calcification: 35%
Bifurcation: 29%
Ostial: 13%
Lesion length: 17.79±8.94 mm (6.2-55.2)
RVD: 2.72±0.39 mm
MLD: 0.78±0.31 mm
Diameter stenosis: 71.6±10.2%
Post-Treatment QCA
Post-AngioSculpt
Final
MLD (mm)
1.55 ± 0.45
2.34 ± 0.42
Diameter Stenosis (%)
43.5 ± 14.7
17.7 ± 7.2
13.6*
0.5
Perforation (%)
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Acute Gain (mm)
0.77 ± 0.43
1.57 ± 0.41
Dissection (%)
*most minor (A-C)
No slippage during AngioSculpt deployment (core lab)
AngioSculpt used primarily for pre-dilatation prior to stenting
AngioSculpt (2.5 mm)
Tortuous Fibro-Calcific LCx “Pre-Dilatation”
Pre-PCI
Post-AngioSculpt
AngioSculpt
Post-Stent
ISR of LCx-OM Bifurcation
Severe ISR of
LCx-OM Bifurcation
“Kissing” AngioSculpt
Balloons
Prior Stents in
LCx-OM
Post-AngioSculpt
“Stand Alone”
Am J Cardiol 2007;100:812-817
Study Results
 On average DES achieved only 77%+13% of the predicted stent
diameter and 70%+22% of the predicted final area
 No difference between patients pre-treated with POBA and those
with direct stent deployment (76%+13% vs. 76%+10%, p=0.8)
 Patients pre-treated with AngioSculpt had significantly better
stent expansion, irrespective of plaque morphology, reaching
88%+18% of the predicted final stent area (p<0.001)
Effect of AngioSculpt on Stent “Re-Expansion” in ISR
Volumetric IVUS
More optimal stent re-expansion in ISR lesions treated with the AngioSculpt
was a major contributor to the improvement in final lumen dimensions
Fonseca et al, J Invasive Cardiol 2008;20:21-27
Optimizing Plaque Modification in Complex Lesions
Utilizing the AngioSculpt Device: Acute and Long
Term Results From a Large Two-Center Registry
Ehud Grenadier, Arthur Kerner, Gary Gershony,
Nabeel Makhoul, Ariel Rougin
Am J Cardiol 2008;102, Supplement 8A:53i
Follow-up at 33.7±16.3 Months
483/521 patients (92.7%)
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Cumulative MACE: 7.1%
Cardiac death: 0.4%
Myocardial infarction (Q and non-Q wave): 3.8%
Stent thrombosis: 0.9%
Ischemia-driven TLR: 5.9%
International Infra-Popliteal Registry
Stefan Kiesz, Dierk Scheinert, Patrick Peeters, Marc Bosiers, Gerard O'Sullivan,
Sherif Sultan, Mark Turco, William Gray, John Laird, Amir Malik, Mark Mewissen,
Rajesh Dave, Tony Das, Thomas Piemonte, Puneet Khanna, Gary Gershony
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93 pts, 131 lesions, 16 clinical sites
Age 71.1±11.4 yrs, 62.4% males
CLI present in 74 pts (79.6%)
Chronic total occlusions in 14.5%, moderate/severe calcification in 54.2%,
lesion length – 28.6±34.1 mm
Successfully deployed in 130/131 (99.2%) lesions
Dissections in 13/131 (9.9%) lesions – minor or resolved with stenting
Adjunctive stenting in only 15/131 (11.5%) lesions
No significant device slippage
No perforations
17 pts referred for amputation – AngioSculpt resulted in limb salvage
J Am Coll Cardiol 2008;51 (Suppl B):75
Angiographic Results
85.8±11.6
% 90
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DS
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12.2±16.8
7.0±10.5
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Pre-AS
n=131
Post-AS
n=130
Post-Stent
n=15
Tibio-Peroneal Disease
Pre-AngioSculpt
AngioSculpt Deployment
Post-AngioSculpt
CLI – Severe Stenosis of Anterior Tibial
AngioSculpt 2.0 x 10 mm
Severe >95% Stenosis
of Distal AT
Occluded PT &
Peroneal Arteries
Post-AngioSculpt <10%
Residual Stenosis
Belgian Infra-Popliteal/CLI Study
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Two clinical sites
Enrolled 31 CLI (Rutherford 4-5) pts with 36 lesions
RVD 2.0 – 4.0 mm
Single vessel run-off
Age 76 (54-91) yrs, males 54.8%
Diameter stenosis: 90.4% (70-100)
Lesion length: 32.4 mm (6-100)
Lesion calcification: 54.8%
Location: popliteal 2.7%, tibio-peroneal 22.2%, anterior
tibial 47.2%, posterior tibial 13.9%, peroneal 13.9%
Bosiers et al, Vascular 2009 Jan-Feb;17(1):29-35
Results at 12 Months
Comparison of Limb Salvage Rates
(CLI Patients)
Limb Salvage @ 6 mos
Limb Salvage @ 12 mos
AngioSculpt
POBA
(Belgian Registry)
n=31
(Basil Trial)
n=224
86%
86%
79%
71%
FeMoropopliteal AngioSculpt SCoring BallOon CaTheter Study
(MASCOT - ClinicalTrials.gov: NCT 00619788)
Prospective Multicenter Non-Randomized Trial Investigating
the Safety & Efficacy of the AngioSculpt Scoring Balloon
for the Treatment of Femoro-Popliteal Stenotic Disease
Participating
centers:
MASCOT Study Design
• Femoro-popliteal lesions
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Rutherford Class 2 & 3 (intermittent claudication)
Rest pain (Rutherford Class 4)
Non-healing wounds (Rutherford Class 5)
Length: < 80mm
ref. Ø: 4.5 – 6.0 mm
• Enrollment period: March 2008 – July 2008
• Safety endpoint:
complication-free survival at 1 month
post-procedure (= absence of major
amputation, any cause of death and target limb
revascularization)
• Efficacy endpoint:
primary patency (by duplex scan) at 12 months
Acute Procedural Outcome
(N=50)
Successful scoring
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100%
Stand-alone treatment
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58%
Additional stents used
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42%
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2%
Distal embolization
(successfully treated by immediate
PTA with 3.0 x 60 mm balloon)
Most patients were treated with the AngioSculpt balloon alone
Coronary Bifurcation Study – “AGILITY”
(ClinicalTrials.gov: NCT 00686647)
• Single stent strategy (“provisional” side-branch stenting)
• Prospective multi-center trial, 9 prominent U.S. sites
• AngioSculpt stand alone for SB, DES for MB
• Single arm (OPC for SB: POBA, OPC for MB: DES)
• “Superiority” design
• Sample size: 100 patients
• Inclusion Criteria: Medina Class (x,x,1) with DS ≥50%
AGILITY Trial – Endpoints
• Primary endpoint: acute procedural success of MB and SB
• Secondary endpoints: freedom from MACE and stent
thombosis at 30 days and 9 months, 9 month clinical restenosis
(TLR), rate of SB “crossover” stenting and FKB, dissection
rate/grade, slippage rate, resource utilization
• Independent data management & core labs (QCA, ECG)
AGILITY Trial Clinical Sites
Site Name
Site PI
Columbia University Medical Center
Dr. Jeffrey Moses (Overall PI)
Harrisburg Hospital
Dr. Rajesh Dave
Johns Hopkins Hospital
Dr. Jon Resar
Holston Valley Medical Center
Dr. Christopher Metzger
Elyria Memorial Hospital
Dr. Charles O’Shaughnessy
Washington Adventist Hospital
Dr. Mark Turco
Emory Crawford Long Hospital
Dr. Henry Liberman
Emory University Hospital
Dr. John Douglas
Baptist Cardiac & Vascular Institute
Dr. Ramon Quesada
Interim Results
(un-adjudicated)
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Enrollment as of 11/23/09: 74 patients
Top enrollers: Dr. Metzger (23), Dr. Moses (21)
30-day follow-up available in 65/67 (97%) eligible pts
9-month follow-up available in 41/42 (98%) eligible pts
MACE (death, MI, TLR) in-hospital: 4.1%
MACE at 30-day follow-up unchanged
One reported stent thrombosis (sub-acute)
One TLR at ~ 5 months (side branch)
No reported deaths
No reported perforations
Side-branch stent: 8.7% (6/69) vs. OPC 27%
Final KB: 20.3% (14/69) vs. OPC 50%
AGILITY – Ramus Bifurcation (JHMI)
Severe >90% Ramus Bifurcation
Lesion (0,1,1) Presenting with ACS
Post-AngioSculpt 2.5 mm for SB
and 2.75 mm DES for MB
Conclusions – AngioSculpt
• Effective in a broad range of complex coronary and peripheral lesion
morphologies (“stent-like” angiographic results)
• Associated with a high procedural success rate
• Improves stent expansion compared to direct stenting or POBA
• Avoids “geographic miss” due to device slippage
• Excellent long term results (TLR and MACE) when used for plaquemodification prior to DES
• Preliminary data suggest a favorable limb salvage rate in patients with CLI
and a favorable long term patency rate in femoro-popliteal disease compared
to historical data with POBA
• Very useful in peripheral lesions where stenting should be avoided
(popliteal, CFA, ISR)
• Safe with a very low complication rate (low dissection rate, very rare
perforations or device malfunctions)
Future Developments
• Larger/Longer peripheral catheters
- larger diameter balloons (≥ 6.0 mm)
- longer balloons (≥ 100 mm)
• “Next Generation” AngioSculpt
- device deliverability in “extreme” lesions
- lubricious/hydrophilic coating
- improved distal shaft pushability/trackability
- crossing profile and lesion entry tip enhancements
• Valvuloplasty scoring device
• Anti-restenotic “drug coatings”
Longer/Larger Peripheral Devices
3.5 x 20 mm
6.0 x 100 mm
SFA Disease:
• Diffuse fibro-calcific lesions
• Optimize lesion preparation prior to long self-expanding nitinol & covered stents
• Diffuse in-stent restenosis
• Laser cut nitinol scoring element (5 rectangular wires)
“Next Generation” AngioSculpt
New Tip Design
• 5F guide catheter and .014” guide wire compatible
• More flexible scoring element with thinner end rings
• 75% more flexible inner member
• Longer tip for improved crossing
• Reduced tip entry profile by 15%
• Reduced balloon distal profile by .006”
• More pushable hypotube and distal shaft
• Lubricious/hydrophilic coating
AngioSculpt Valvuloplasty Prototypes
• 20-25 mm diameter x 3.0 cm length balloons
• Laser cut nitinol scoring element (12 rectangular wires)
Why Consider a Drug-Coated AngioSculpt?
• Results with drug-coated POBA (PaccoCath) are very promising
• May be able to deliver drug more effectively with a scoring element
• Better acute luminal results with AngioSculpt compared to POBA
• Lower rate of dissection with AngioSculpt compared to POBA
• No slippage or “geographic miss” with AngioSculpt
• May be able to avoid adjunctive stenting
All of the above may allow a drug-coated AngioSculpt to provide “stand
alone” therapy for a wide range of coronary and peripheral arterial lesions
with a significantly lower restenosis rate than POBA or allow the use of
BMS rather than DES
Drug Coating Project
• In collaboration with Elazer Edelman at MIT &
Renu Virmani at CV Path
• Initial animal feasibility testing completed
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18 Drug only - Single Expansion
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21 Drug only - Two Expansions
23 Drug only - Three Expansions
70
Taxol released into PBS (ug)
25 Drug only - Two Expansions
60
27 Drug only - Single Expansion
29 Drug only - Three Expansions
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Drug-Coated AngioSculpt (SEM)
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Time (Minutes)
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Drug-Coated AngioSculpt