0. LV Reduction: Update on the PARACHUTE Trials
CRT 2010
Washington, USA, Feb 21-23, 2010
LV Reduction: Update on the PARACHUTE Trials
LEFT ATRIAL CLOSURES
Moderator: Mark Reisman, MD
5:05 PM Update on the Watchman
Device
David R. Holmes, MD
5:15 PM Update on PFO Stents
Mark Reisman, MD
5:25 PM LV Reduction: Update on
the PARACHUTE Trial
Horst Sievert, MD
5:35 PM Adjourn
Horst Sievert, Nina Wunderlich
CardioVascular Center Frankfurt
Frankfurt, Germany

1. Horst Sievert, MD DISCLOSURES Consulting Fees
AccessClosure, Inc., AGA Medical Corporation, Angiomed, Ardian, Inc., Arstasis, Inc., Avinger, BridgePoint Medical, CardioKinetix, Inc., CardioMEMS Inc., Coherex Medical, Inc., CSI Medical, EndoCross, Boston Scientific Corporation, ev3, Inc., FlowCardia, Inc., W.L. Gore & Associates, Inc., Abbott Vascular, Lumen Biomedical, Kensey Nash Corporation, Kyoto Medical, NDC, NMT Medical, Inc., OAS, Occlutech, Osprey Medical, Inc., Ovalis, Inc., Pathway Medical Technologies, Inc., Pfm Medical, Inc., PendraCare, Percardia Inc., Remon Medical Technologies, ROX Medical, Sadra Medical, Sorin Group, Spectranetics, Square One Medical, Viacor, Inc., St. Jude Medical, Medinol Ltd., Lutonix, Inc.
Grants/Contracted Research
Abbott Vascular, AccessClosure, Inc., AGA Medical Corporation, Angiomed, Boston Scientific Corporation, CardioKinetix, Inc., CoAptus Medical Corporation, Cordis, a Johnson & Johnson company, CSI Medical, Edwards Lifesciences LLC, ev3, Inc., W.L. Gore & Associates, Inc., Kensey Nash Corporation , Mind Guard, NDC, Neovasc, NMT Medical, Inc., Percardia Inc., Sorin Group, St. Jude Medical, Terumo Medical Corporation, TopSpin Medical Ltd., St. Jude Medical, Lumen Biomedical
Ownership Interest (Stocks, Stock Options or Other Ownership Interest)
Cardio-Kinetics Inc., AccessClosure, Inc., CoAptus Medical Corporation, Lumen Biomedical, Cierra
I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation.
I intend to reference PFO, ASD devices, carotid stents, and EPD.

2. Dor Procedure Aneurysm Resection
Reduces the LV size and LV wall stress
Improves contractility of remote myocardium
The Parachute (or VPD implant) mimics the Dor procedure
Athanasuleas CL et al, JACC 2004 2

3. Parachute Effects On scarred LV wall On remote myocardium Overall
Excludes scarred apex
Prevents further dilatation
Restores conical apex
On remote myocardium
Reduces LV wall stress
Increases contractility
Prevents further remodeling
Promotes reverse remodeling
Overall
Reduces diastolic & systolic volume
Increases ejection fraction
Reduces LVED pressure 3

4. VPD Implant Procedure

5. Cardiokinetix System Components
Ventricular Implant:
75mm & 85mm diameter
Nitinol struts
ePTFE membrane
Radiopaque Pebax polymer foot
Investigational Device. Limited by Federal (US) law to Investigational Use Only.
This material copyrighted and confidential 5 5

6. Vascular Access and Delivery System
14 & 16 French
Guide Catheters
Delivery System
Investigational Device. Limited by Federal (US) law to Investigational Use Only.
This material copyrighted and confidential 6 6

7. Delivery Catheter Balloon inflation port Proximal injection port
Implant detachment knob
Distal balloon

8. VPD Implant: GLP Animal Study Tissue In-Growth 3 Weeks Post Implant

9. Ejection Fraction Animal Study%
n.s.
P<0.001
P<0.001
Meistens sage ich: In the final pre-clinical trial, it was shown that Ejection fraction was significantly improved immediately after VPD implantation. As there were no statistically significant changes in Ejection Fraction between early and late post-implant, we assume that the early post-implant ejection fraction ratet might be a good longterm predictor.
A total of 100 animals implantations were performed. Within the final pre-clinical trial we could show that Ejection fraction was significantly improved already immediately following the procedure. EF was re-assessed between 4-12 weeks following the procedure. As there were no statistically significant changes in Ejection Fraction, we assume that the early result might be a good longterm predictor. However, this data is of course prelimary.
Also LVED, LVS and stroke volume showed encouraging outcomes after the VPD implant.

10. PARACHUTE Clinical Studies
EU-PARACHUTE trial
initiated in October, completed in June, 2007
US-PARACHUTE trial
initiated in March, completed in June, 2009
Current status: 39 patients enrolled world-wide
6-month data are available from all EU- and from 7 US patients
Before reviewing the human clinical results, I want to share with you our pre-clinical studies. These studies helped us prove the original concept of ventricular partitioning and gave us the confidence that we would see strong human clinical results.
The original concept was that by partitioning the ventricle and lowering ventricular volumes, the ventricular pressures responsible for initiating remodeling would lower and the ventricular function would improve as evidenced by improvements in ejection fraction. The pre-clinical studies also established other important device attributes. First, the procedure proved to be easy, fast and easily taught to interventionalists as it is very similar to what they do on a daily basis. Also, the device proved to be stable and we were able to discover and establish many of the margins of safe attachment to the ventricular wall. Last, as we had hoped, the ePTFE produced an very good tissue response with tissue matrix growing on top of and around the device, essentially creating a new tissue apex in the ventricle.
This material copyrighted and confidential 10

11. EU and US PARACHUTE Clinical Studies
Safety and feasibility trials
prospective, single-arm, multicenter
patients with heart failure due to ischemic heart disease
clinical and echo follow-up at 1, 3, 6, 9, 12 months and then yearly to 5 yrs
LV gram after 6 months (optional, EU only)
CT/MR imaging (brain, kidney and heart) follow-up at 6 months

12. Key Inclusion Criteria
Heart Failure
Apical akinesia/hypokinesia due to prior MI
NYHA Class II-IV
Optimal medical therapy
Ejection fraction < 40%
Appropriate LV anatomy to accommodate PARACHUTE
Before reviewing the human clinical results, I want to share with you our pre-clinical studies. These studies helped us prove the original concept of ventricular partitioning and gave us the confidence that we would see strong human clinical results.
The original concept was that by partitioning the ventricle and lowering ventricular volumes, the ventricular pressures responsible for initiating remodeling would lower and the ventricular function would improve as evidenced by improvements in ejection fraction. The pre-clinical studies also established other important device attributes. First, the procedure proved to be easy, fast and easily taught to interventionalists as it is very similar to what they do on a daily basis. Also, the device proved to be stable and we were able to discover and establish many of the margins of safe attachment to the ventricular wall. Last, as we had hoped, the ePTFE produced an very good tissue response with tissue matrix growing on top of and around the device, essentially creating a new tissue apex in the ventricle.
This material copyrighted and confidential 12

13. Key Exclusion Criteria
PCI, CABG, ICD, CRT > 60 days prior to enrollment
Acute MI < 60 days prior to enrollment
Thrombus in LV or LA
History of bleeding or blood disorder
At risk of contrast-induced renal failure
Allergy to anticoagulation medicine
Life expectancy < 12 month
Before reviewing the human clinical results, I want to share with you our pre-clinical studies. These studies helped us prove the original concept of ventricular partitioning and gave us the confidence that we would see strong human clinical results.
The original concept was that by partitioning the ventricle and lowering ventricular volumes, the ventricular pressures responsible for initiating remodeling would lower and the ventricular function would improve as evidenced by improvements in ejection fraction. The pre-clinical studies also established other important device attributes. First, the procedure proved to be easy, fast and easily taught to interventionalists as it is very similar to what they do on a daily basis. Also, the device proved to be stable and we were able to discover and establish many of the margins of safe attachment to the ventricular wall. Last, as we had hoped, the ePTFE produced an very good tissue response with tissue matrix growing on top of and around the device, essentially creating a new tissue apex in the ventricle.
This material copyrighted and confidential 13

14. Parachute Studies Sites
Investigational Site
Subjects Enrolled*
US-IDE-PARACHUTE
Geisinger Clinic, Danville, PA 1
The Ohio State University, Columbus, OH 6
Texas Heart Institute, Houston, TX 4
Washington, DC
Northwestern University Hospital, Chicago, IL 2
Cardiology Associates, Asheville, NC
Gagnon Cardiovascular Institute, Morristown, NJ
Dedinje Cardiovascular Institute, Belgrade, Serbia
Total 18
OUS-PARACHUTE 12
Kerkhoff Klinik Bad Nauheim, Germany
Sankt Katharinen Hospital, Frankfurt, Germany 5 19
Grand Total, combined studies 37
* As of 05/19/2009. Only 7 US patients with 6-month follow-up data

15. Methods Device implantation under local anesthesia
14F / 16F trans-femoral sheath
Follow-up:
months and then yearly to 5 years
LV-gram (EU) + CT 6 months
EU: Aspirin and Clopidogrel for 6 months
US: Anticoagulation (Coumadin) for 6 months
to access the LV with the delivery system a 14 sheath is used
All patients were treated with Aspirin and Clopidogrel pre-procedural and this was continued for at least 6 months following the procedure.
FU includes:
Echo, 6 mos (echo) and then yearly thereafter up to 5years. At 6 m FU, a RHC and LVgram are to be performed.

16. Device Implantation 70 y.o. male Left ventricular aneurysm, EF 38%
AMI in 1998, CABG in 1999
Left ventricular aneurysm, EF 38%
On Aspirin, Carvedilol, Ramipril, Nitro, Lasix
NYHA III
Here you can see the VPD device in apical position.
DEVICE IN APICAL POSITION 16

17. BALLOON INFLATION TO EXPAND DEVICE
Device Implantation
To fully expand the device a 25mm Balloon was used (for device anchoring with ist expansile foot against the endocardium). Finally, the device can easily released by a distal screw mechanism.
BALLOON INFLATION TO EXPAND DEVICE
FULL DEPLOYMENT 17

18. Device Implantation FINAL ANGIO
The final angio showed only a trace leak at the side of the ventricular region where it was implanted. Leaks around the device are not part of EF calculation. Contrast injection makes this look much bigger than it actually is. On echo Doppler the jet representing leaks is ~10% of mitral regurgitation 1.
FINAL ANGIO 18

19. CT Scan
before
6 months

20. LVEDP (OUS only), Paired Data, n= 820

21. LVEDV-Index (ml/m2) N = 21
P<0.001

22. LVESV-Index (ml/m2) N = 21
P<0.001

23. EF (%) N = 21
P<0.001

24. NYHA N = 21
P<0.01

25. Minnesota LWHFQ Score N = 21
P<0.01

26. 6-minute Walk Test (m) N = 21
P<0.02

27. Serious Adverse Events up to 24 mo
1 Early death
Sepsis from undiagnosed peri-anal abscess
Device removed - culture negative for infection
Myocardial infarction, non-device related
2 late deaths, 5 months post-implant
1 ventricular dysrhythmia
1 pump failure
Minor stroke, 14 months post-implant
Bilateral carotid artery disease, full recovery
2 TIA
9 months post-implant (due to paroxysmal AF?)
24-hour post-implant (patient with severe poly-vascular disease)
Device misplacement / dislodgement
1 surgical removal, 1 catheter retrieval
Groin complications
1 femoral artery pseudo-aneurysm surgically repaired
1 bleeding requiring re-hospitalization
1 Deep vein thrombosis
Worsening heart failure during FU
11 episodes in 6 patients (1 Heart transplantation after 6-months)
Hospitalization for syncope, after 2 years
II degree heart block, Ventricular Dyssynchrony and Intermittent AF 27

29. The VPD Implant
Is the first catheter-based system to treat LV wall motion abnormalities
Implant procedure seems to be safe up to 24 months
6 month data show improved functional and hemodynamic outcome
A randomized trial is planned
This is very preliminary data but the assumed combined effect of regional and global unloading may have important consequences for myocardial energetics. Regional unloading may decrease the left ventricle´s myocardial oxygen demand ratio. Future studies will be needed to better answer these questions. 29