The VentrAssist U.S. The VentrAssist U.S. Pivotal Bridge to Cardiac Pivotal Bridge to Cardiac

Transplantation TrialTransplantation 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 InformationAndrew J. Boyle, MD

The following relationships exist related to this presentation:

Scientific Advisor Ventracor no financial relationship

Consulting Fees Thoratec Modest Level

VentrAssist: 1VentrAssist: 1stst Centrifugal LVAD Centrifugal LVADSmall 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 ComponentsVentrAssist 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 OutcomesUS 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 implanted 421

Longest support duration (d) 1594

Mean support duration (d) 219

Number of patients currently supported 180

VentrAssist Support Duration

> 6 months 192

> 12 months 67

> 24 months 16

Worldwide VentrAssist Experience*Worldwide VentrAssist Experience*

* As of 3/3/09

Bridge To Transplant Pivotal Trial DesignBridge 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 EnrollmentStudy EnrollmentTarget 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.

EndpointsEndpointsPrimary 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 CriteriaInclusion Criteria

Age ≥ 18 yrs

BSA ≥ 1.5 m2

Approved for transplant & listed as Status 1A or 1B

Clinical indication for BTT LVAD

Exclusion CriteriaExclusion 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 SitesClinical 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 CharacteristicsBaseline CharacteristicsN=98

Mean (±SD)

N=138

Mean (±SD)

Age (years) 53 (12) 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) 4.2 (1.3)

Cardiac Index (l/min/m2) 2.0 (0.6) 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 LabsBaseline LabsN=98

Mean (±SD)

N=138

Mean (±SD)

Hgb (g/dl) 11.6 (1.8) 11.6 (2.3)

PLT (103/ml) 235.4 (90.2) 234.0 (92.2)

INR 1.3 (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 HistoryBaseline Medical HistoryN=98

N (%)

N=138

N (%)

Ischemic Cardiomyopathy 51 (52%) 65 (48%)

CABG 27 (28%) 33 (24%)

AICD 84 (86%) 116 (85%)

Biventricular PM 39 (40%) 59 (43%)

TIA 6 (6%) 6 (4%)

CVA 8 (8%) 11 (8%)

Diabetes Mellitus 25 (26%) 36 (27%)

IABP 38 (39%) 53 (39%)

One Inotrope 70 (73%) 98 (73%)

> One Inotrope 13 (14%) 18 (13%)

Primary Endpoint (n=98)Primary Endpoint (n=98)

Success Failure

Success Rate

Lower 95% Confidence

Bound (Success)N % N %

Total 77 78.6 21 21.4 78.6 69.1

Transplantation 47 48 --- ---

Listed UNOS 1A/B at 180 days 30 31 --- ---

Device Replacement (<180 days) --- --- 5 5

Death --- --- 16 16

Protocol defined outcomes (only 1 per patient)

Clinical Duration of Support (n=98)Clinical Duration of Support (n=98)

All patients (N=98)

Trans-planted(N=60)

Died (N=19)

Device Replace-

ment (N=8)

On SupportΔ

(N=19)

Mean 155 134 95 216 279

Median 131 125 49 195 216

Range 1 - 574 16 - 497 1 - 403 64 - 447 64 - 574

ΔPatients 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)Study Outcomes: Interim Analysis Population (n=98)

Outcomes – KM Survival Curve (n=98)Outcomes – KM Survival Curve (n=98)

Patients at Risk 98 83 76 60 52 41 35

Cause of Death on LVAD SupportCause of Death on LVAD SupportDeaths (N) Deaths (%)

Bleeding – Non peri-implant 2 11LVAD Failure 1 5Multi-Organ System Failure 5 27Neurologic Stroke–Ischemic 1 5Neurologic Stroke–Hemorrhagic 1 5Other Cardiovascular 3 16 Acute MI with arrhythmias and ICD shocks 1 5 Cardiogenic shock 1 5 Congestive heart failure 1 5Sepsis 1 5Unknown Causes 1 5Other Immediate Cause of Death 4 21 Methamphetamine toxicity 1 5 Necrotic bowel 1 5 Pulmonary edema 1 5 Massive hemothorax / hemorrhagic bullae 1 5Total 19 100%

Serious Adverse EventsSerious Adverse Events

Does not include SAEs after replacement to a device other than VentrAssist

Total Support = 19435 Person-Days as of January 27, 2009

VentrAssist HeartMate II

Rate per pt-year (N=98)

Rate per pt-year (N=135)

Rate per pt-year

(N=133)Ischemic Stroke 0.10 0.11 0.13 Hemorrhagic Stroke 0.02 0.02 0.05 TIA 0.12 0.09 0.10

Major Bleeding 0.68 0.64 ---Bleeding Requiring Surgery 0.12 0.15 0.78 Bleeding Requiring ≥ 2 U --- --- 2.09 Hemolysis 0.00 0.00 0.06

VentrAssist HeartMate II

Rate per pt-year (N=98)

Rate per pt-year (N=135)

Rate per pt-year

(N=133)DM-Pump Failure 0.05 0.04 ---

Percutaneous lead 0.09 0.11 ---DM-Pump Thrombus (confirmed) 0.12 0.09 0.03

Infection-Driveline Exit 0.05 0.04 0.37

Infection-Pump Pocket 0.02 0.02 0.00

Infection-Sepsis 0.43 0.41 0.62

Renal Dysfunction (acute) 0.27 0.26 0.31Right Heart Failure 0.29 0.24 0.36

BTT Adjudicated SAEs (cont’d)BTT Adjudicated SAEs (cont’d)

Device ReplacementsDevice 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)NYHA Class Over Time (n= 138)

p-value <0.001

Minnesota Living with Heart Failure Minnesota Living with Heart Failure Questionnaire (N=138)Questionnaire (N=138)

NYHA Class Over Time (N=138)

MINNESOTA LIVING WITH HEART FAILURE QUESTIONAIRE - N=138

Better(0)

Worse (105)

p-value < 0.0001   

EuroQoL (N=138)EuroQoL (N=138)

Worse (0)

Better(100)

p-value < 0.0001

• LVA3 Percutaneous lead – 6.4mm diameter• Continuous lead from pump to controller

• LVA4 Percutaneous lead - 3mm diameter• Intermediate connector and extension lead

VentrAssist LVA3 & LVA4VentrAssist 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 CannulasVentrAssist Inflow Cannulas

ConclusionsConclusions

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