1. Lev-OR, A New Guide Wire “Sheath” for Resistant Lesion Crossing and Collagenase Update
Dr. Bradley Strauss
CIHR Team in Vascular Occlusive Disease
Reichmann Chair in Cardiovascular Research
Sunnybrook Health Sciences Centre
University of Toronto
Toronto, Canada

2. Bradley H. Strauss, MD, PhD
DISCLOSURES
Bradley H. Strauss, MD, PhD
Royalty
Baylis Medical
Consulting Fees
Abbott Vascular, Interface Biologics
Ownership Interest (Stocks, Stock Options or Other Ownership Interest)
Matrizyme Pharma

3. Conflict of Interest I disclose the following financial relationships:
Receipt of Intellectual Property Rights / Patent Holder:
Collagenase for chronic total occlusions
CTO guide sheath
Angiogenic therapy for chronic total occlusions
Contracted Research: Abbot Vascular, Baylis Medical
Ownership Interest: Matrizyme Pharma
I intend to reference unlabeled/unapproved uses of a products in my
presentation: CTO guide wiresheath for Chronic Total Occlusions

4. Why I failed CTO PCI? Could not cross with a guide wire (95%)
Could not cross with a balloon catheter (5%)
But occurs very commonly (10-20% cases), prolonging procedure and increasing complexity

5. Why I failed CTO PCI?
Could not cross with a balloon catheter

6. The Spectrum of Lumen Morphology in CTO: Clinical Challenges of a Fibrotic Plaaque
Large recanalization
channels
Small recanalization
channels
Proteoglycan-rich
Fibrotic plq:
Negative
remodelling
Necrotic core
Calcification
Inflammation

7. Proximal Fibrous Cap at 12 weeks
EEL
PFC L
PFC L M
EEL
Proximal Fibrous Cap at 12 weeks

8. What are the Crossing Profiles?
Guide wire 360 μm (0.014”)
Fixed-wire balloon (ACE): 610 μm
RX balloon (1.5 mm Maestro): 900 μm
OTW balloon (Opensail): 1100 μm
Microcatheter (Excelsior): 670 μm
Non-Balloon Devices
0.9 mm high-energy excimer pulsed laser catheter (X80, Spectranetics)
Rotational atherectomy

9. Tornus- Asahi Vascular
- 8 stainless steel wires stranded into the coil
OD 700 μm
-tip profile 620 μm, stainless-platinum alloy

10. Desired Characteristics of Crossing Device
Flexible
Low-profile
Distal tip strength
Monorail design

11. Lev-ORTM Device Concept
Flexible Nitinol Sleeve
Ultra-low Distal Profile
OD 559 μm (0.022”)
ID 432 μm (0.017”)
Hydrophilic coating
Gradual Taper
“Dotter” and stretch the lesion
Option of progressively larger sleeves

12. Guidewire Sheath Device
Radiopaque Marker
Tapered Distal Tip
2. Intermediate Shaft Section
- Polymer shaft
1. Distal Section
- Flexible nickel-titanium alloy (Nitinol)
Tapered distal tip
Polymer coat (except distal taper)
3. Proximal Shaft Section
-Polymer shaft
-Stainless steel wire for pushing
- monorail port
The Lev-ORTM is not approved for sale in the USA

13. Lev-ORTM Final Design Distal Section Handle
The Lev-ORTM is not approved for sale in the USA

14. Current Status
First clinical cases planned for March 2010

15. Novel Biologic Therapies: Intralesional Treatments for Improved Guidewire Crossing

16. Therapy Target Onset of Action Current Status Contrast Collagenase
Enlarge Microchannels
Immediate
Clinical Use
Collagenase
Degrade Collagen
Hours
FIM Nov 2009
Angiogenic Factors
Induce new microchannels
Days
Pre-clinical Studies
Fefer P, Can J Cardiol 2010 In press

17. The microchannel technique
The MCT is an anterograde method of percutaneous revascularization of CTO that utilizes already existing channels within occluded vessels. 17

23. Collagenase Total Occlusion-1 (CTO-1) Clinical Trial
Study Design
Prospective, two-centre, Phase I Safety and Feasibility Study
4 dose cohorts of acute intracoronary injected collagenase (300 – 1200 µg) prior to routine percutaneous revascularization procedures.
5 subjects / dose cohort, previously failed attempt
Dose escalation only upon successful dosing of each subject in the cohort and a favorable safety review of the entire cohort

24. Milestones of CTO-1 Trial
GMP Collagenase production completed, with stability data at 6 months
Jan 2009: Canadian Institute of Health Research Approved Funding
Health Canada Approval-August 2009
1st patient enrolled November 4, 2009

25. Patient #1 52 years old labourer, inferior wall infarction in 2006
New changes in stress test Dec 2008
Angiogram now shows complete blockage of LAD (CTO)
Unsuccessful attempt in June 2009
Currently shortness of breath and some chest pains walking up hill

26. June 11, 2009: Initial Attempt

29. November 3, 2009

30. Balloon Positioned in Occlusion

31. Injection of Collagenase Into Chronic Total Occlusion

32. November 4, 2009

33. Guidewire Crossing with Whisper GW

34. Full Crossing of CTO

35. Follow Up No acute changes in echo or cardiac biomarkers
Clinically well and asymptomatic at 3 months
Unremarkable CTA at 3 months
Stents in LAD widely patent
No myocardial changes

36. Summary
Lev-ORTM is a rapid exchange device for facilitating balloon crossing after successful guidewire crossing in CTO
Intralesional therapies represent a novel approach for improving guidewire crossing in CTO
CTO-1 trial expected to be completed December 2010