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

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.

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

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

VPD Implant Procedure

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

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

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

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

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.

PARACHUTE Clinical Studies EU-PARACHUTE trial initiated in October, 2005 - completed in June, 2007 US-PARACHUTE trial initiated in March, 2008 - 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

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

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

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

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

Methods Device implantation under local anesthesia 14F / 16F trans-femoral sheath Follow-up: TTE @1,3,6,9,12 months and then yearly to 5 years LV-gram (EU) + CT Scan @ 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 MWT @1,3,6,9,12 mos (echo) and then yearly thereafter up to 5years. At 6 m FU, a RHC and LVgram are to be performed.

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

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

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

CT Scan before 6 months

LVEDP (OUS only), Paired Data, n= 8 20

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

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

EF (%) N = 21 P<0.001

NYHA N = 21 P<0.01

Minnesota LWHFQ Score N = 21 P<0.01

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

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

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