The VentrAssist U.S. Pivotal Bridge to Cardiac Transplantation Trial A Boyle, N Moazami, R John, G Ewald, A Anyanwu, S Pinney, S Desai, N Burton, J Teuteberg, R Kormos, M Parides, A Gelijns, D Ascheim, U Rawiel, L Joyce, and the VentrAssist Investigators University of Minnesota, Washington University, Mt. Sinai School of Medicine, Inova Fairfax Hospital, University of Pittsburgh

Presenter Disclosure Information Andrew J. Boyle, MD The following relationships exist related to this presentation: Scientific AdvisorVentracorno financial relationship Consulting FeesThoratec Modest Level

VentrAssist: 1 st Centrifugal LVAD Small size (298 g) Single moving part - rotor No valves, diaphragms or mechanical bearing Diamond-like carbon coating on blood contacting surfaces Hydrodynamic suspension (rotor is supported by the blood within the pump) Rotor contains high-strength magnets Controller delivers power to copper coils via lead Magnetic forces from the coils spin the rotor

VentrAssist Components Implantable blood pump Powered via percutaneous lead Controller logs parameters & alarms Battery or AC power supply Laptop PC for clinician use Blood pump Outflow cannula Controller and battery receptacle Percutaneous lead Inflow cannula

US Feasibility Study Outcomes At 6 months, 86% of patients were transplanted or alive on support Boyle A et al. ISHLT, Boston, MA, 2008.

Summary Total number of patients implanted421 Longest support duration (d)1594 Mean support duration (d)219 Number of patients currently supported180 VentrAssist Support Duration > 6 months192 > 12 months67 > 24 months16 Worldwide VentrAssist Experience* * As of 3/3/09

Bridge To Transplant Pivotal Trial Design Multi-center, prospective, single-arm study Performance goal set by FDA (75% success rate) Null hypothesis: Treatment with VentrAssist LVAD is non-inferior to the Performance Goal Non-inferiority margin = 10% Pre-specified Interim Analysis after 98 outcomes (70%): Null hypothesis rejected if 74 or more successes (observed success rate of 75.5%)

Study Enrollment Target Enrollment n = 144 Pre-specified interim analysis 2/09 98 patients reached endpoint and available for outcomes analysis 138 patients enrolled and available for SAE analysis One patient received a BiVAD and not a VentrAssist device. One patient received a Thoratec LVAD and not a VentrAssist device. One patient had an esophageal perforation during initial implant procedure and did not receive a VentrAssist device.

Endpoints Primary endpoint : Success ―Survival to transplantation or ―On support for ≥180 days and listed UNOS 1A/1B Failure ―Mortality prior to outcome ―Device replacement prior to outcome Secondary endpoints: INTERMACS defined SAEs Quality of life Functional status Neurocognitive function

Inclusion Criteria Age ≥ 18 yrs BSA ≥ 1.5 m 2 Approved for transplant & listed as Status 1A or 1B Clinical indication for BTT LVAD

Exclusion Criteria Cardiotomy within 30 days Acute MI within 48 hours Hypertrophic or restrictive cardiomyopathy Prior heart transplant or LVAD Mechanical aortic or mitral valve > 1+ aortic insufficiency Platelets < 80,000 or coagulopathy Anticipated need for RVAD PVR > 8 Woods units Creatinine > 3.5 mg/dl or dialysis Liver function tests > 5 X upper limits of normal Stroke < 90 days Contraindication to anticoagulation

Clinical Sites University of Minnesota Washington University Fairfax Inova Mt. Sinai St. Vincent’s Indianapolis Mayo Clinic Northwestern University University of Alabama University of Pittsburgh Newark Beth Israel Allegheny General Sacred Heart University of Florida Columbia University Montefiore Hospital Ohio State University University of Pennsylvania University of Utah Duke University St. Luke’s Medical Center University of Maryland Methodist Hospital University of Rochester University of Washington

Baseline Characteristics N=98 Mean (±SD) N=138 Mean (±SD) Age (years) 53 (12) LVEF (%)18.0 (6.8)17.5 (6.7) BP systolic (mmHg)100.1 (15.7)100.0 (15.3) Cardiac Output (l/min)4.2 (1.3) Cardiac Index (l/min/m 2 )2.0 (0.6) PCWP (mmHg)24.3 (8.4)24.8 (8.2) PVR (Wood Units)3.1 (2.0)3.1 (1.9)

Baseline Labs N=98 Mean (±SD) N=138 Mean (±SD) Hgb (g/dl)11.6 (1.8)11.6 (2.3) PLT (10 3 /ml)235.4 (90.2)234.0 (92.2) INR1.3 (0.3)1.4 (0.4) Na (mM/L)134.1 (5.3)134.2 (5.0) BUN (mg/dl)27.1 (13.9)28.6 (14.5) Creat (mg/dl)1.3 (0.5)1.4 (0.5) Alb (g/dl)3.5 (0.7)3.5 (0.6) AST (U/l)48.2 (71.4)51.1 (77.3) ALT (U/l)59.6 (92.0)58.3 (83.9) TBili (mg/dl)1.1 (0.7)1.3 (1.1)

Baseline Medical History N=98 N (%) N=138 N (%) Ischemic Cardiomyopathy51 (52%)65 (48%) CABG27 (28%)33 (24%) AICD84 (86%)116 (85%) Biventricular PM39 (40%)59 (43%) TIA6 (6%)6 (4%) CVA8 (8%)11 (8%) Diabetes Mellitus25 (26%)36 (27%) IABP38 (39%)53 (39%) One Inotrope 70 (73%)98 (73%) > One Inotrope 13 (14%)18 (13%)

Primary Endpoint (n=98) SuccessFailure Success Rate Lower 95% Confidence Bound (Success) N%N% Total Transplantation Listed UNOS 1A/B at 180 days Device Replacement (<180 days) Death Protocol defined outcomes (only 1 per patient)

Clinical Duration of Support (n=98) All patients (N=98) Trans- planted (N=60) Died (N=19) Device Replace- ment (N=8) On Support Δ (N=19) Mean Median Range Δ Patients on support who reached outcome Clinical outcomes independent of protocol defined endpoints as of Jan 27, 2009 (patients may have multiple outcomes)

Study Outcomes: Interim Analysis Population (n=98)

Outcomes – KM Survival Curve (n=98) Patients at Risk

Cause of Death on LVAD Support Deaths (N)Deaths (%) Bleeding – Non peri-implant211 LVAD Failure15 Multi-Organ System Failure527 Neurologic Stroke–Ischemic15 Neurologic Stroke–Hemorrhagic15 Other Cardiovascular316 Acute MI with arrhythmias and ICD shocks15 Cardiogenic shock15 Congestive heart failure15 Sepsis15 Unknown Causes15 Other Immediate Cause of Death421 Methamphetamine toxicity15 Necrotic bowel15 Pulmonary edema15 Massive hemothorax / hemorrhagic bullae15 Total19100%

Serious Adverse Events Does not include SAEs after replacement to a device other than VentrAssist Total Support = Person-Days as of January 27, 2009 VentrAssistHeartMate II Rate per pt-year (N=98) Rate per pt-year (N=135) Rate per pt- year (N=133) Ischemic Stroke Hemorrhagic Stroke TIA Major Bleeding Bleeding Requiring Surgery Bleeding Requiring ≥ 2 U Hemolysis

VentrAssistHeartMate II Rate per pt-year (N=98) Rate per pt-year (N=135) Rate per pt- year (N=133) DM-Pump Failure Percutaneous lead DM-Pump Thrombus (confirmed) Infection-Driveline Exit Infection-Pump Pocket Infection-Sepsis Renal Dysfunction (acute) Right Heart Failure BTT Adjudicated SAEs (cont’d)

Device Replacements 8 device replacements in 8 patients 5 device replacements < 180 days on support primary reasons for replacement Device Failure (2) Pump Thrombus (2) Percutaneous lead failure (2) Other (2): controller failure, inflow cannula malposition Outcomes following replacement: 3 transplanted, 2 alive on support, and 3 deaths

NYHA Class Over Time (n= 138) p-value <0.001

Minnesota Living with Heart Failure Questionnaire (N=138) NYHAClassOverTime(N=138)NYHAClassOverTime(N=138) MINNESOTALIVING WITH HEARTFAILUREQUESTIONAIRE-N=138MINNESOTALIVING WITH HEARTFAILUREQUESTIONAIRE-N=138 Better (0) Worse (105) p-value <

EuroQoL (N=138) Worse (0) Better (100) p-value <

LVA3 Percutaneous lead – 6.4mm diameter Continuous lead from pump to controller LVA4 Percutaneous lead - 3mm diameter Intermediate connector and extension lead VentrAssist LVA3 & LVA4 Lead conductor fractures reported in 11/187 LVA4 patients worldwide Cause was accidental damage [n=3] or likely stress failure where a contributing factor was not wearing the lead support belt [n=8] No stress failures in patients wearing the lead support belt Patient outcomes include death [n=2], pump exchange [n=3] (1 later transplanted); emergency repair [n=6] (1 later transplanted, 1 later death), Product Advisory issued to emphasize the importance of lead support belt. Additional corrective actions are under consideration

VentrAssist Inflow Cannulas

Conclusions VentrAssist LVAD exceeded performance goal at pre-specified interim analysis 85% of patients transplanted or alive on support at 180 days Statistically & clinically significant improvement in QOL & functional status over duration of support Adverse event profile similar to other current LVADs and improved over pulsatile VADs Projects ongoing to improve percutaneous lead & inflow cannula design