The SynCardia CardioWestTM Total Artificial Heart Marvin J. Slepian, M.D. Sarver Heart Center University of Arizona Tucson, Arizona 2010

SynCardia CardioWest TAH: Indication for Use As an in-hospital bridge to transplantation in cardiac transplant candidates at imminent risk of death due to irreversible biventricular failure

CardioWestTM TAH: Advantages over LVAD Complete biventricular replacement/performance TAH obviates the following native heart issues that could affect a patient on a LVAD 1) Arrhythmias 2) Right ventricle function Prosthetic Aortic Valve Thrombus in ventricle 5) Septal defects

TAH Advantages 3 2 Decreased CVP Overcome PA Cardiac output 4) Organ Recovery 1 4

SynCardia CardioWestTM Total Artificial Heart System Implantable Full Cardiac Replacement Full Normalization of Hemodynamics CE Approved - Europe FDA approved - USA The CardioWest

SynCardia CardioWestTM Total Artificial Heart System Implantable TAH External Console Drivelines

CardioWestTm Total Artificial Heart Stroke volume 70 milliliters Inflow valve 27 mm., Medtronic Hall Outflow valve 25 mm., Medtronic-Hall Seamless blood diaphragm Four flexible polyurethane membranes Maximum output > 9 liter per minute Weight 180 grams

CardioWest TAH: Characteristics Implantable components - chest only Shortest blood path and exposure to artificial surfaces Full circulatory support No dependence on native heart Highest level of cardiac output Normalizes hemodynamics Effective on the sickest of patients Implantable components simple and reliable

CardioWestTm Total Artificial Heart System Fill phase Eject phase

Hypothesis Patients with irreversible biventricular failure, could be saved utilizing the CardioWest TAH as a bridge to transplantation Copeland….Slepian NEJM 361:859, 2004

Study Design Failing Bi-ventricular CHF Cardiectomy TAH removal TAH implantation Transplantation 1 mo 2o EPV 1oEPV 5 Centers, 12 Surgeons N=130, 95 TAH, 35 “Control” Copeland….Slepian NEJM 361:859, 2004

Study End Point Variables Primary Efficacy Endpoint Treatment Success (at 30 days post-transplant) Alive, NYHA Class I or II, Ambulatory Not on ventilator or dialysis Secondary Efficacy Endpoints Survival Hemodynamics End-Organ Function and Ambulation Safety Parameters Adverse Events Copeland….Slepian NEJM 361:859, 2004

Primary End Point: Treatment Success Alive 30 days post TX NYHA Class I or II Ambulatory Not on a ventilator Not on dialysis Copeland….Slepian NEJM 361:859, 2004

Compares favorably with published survival data Clinical Utility TAH 95% CI Survival to transplant 79.1% 68.5%-87.3% Survival to 30d post-transplant 71.6% 60.5%-81.1% 1 year survival from study entry 70.4% 63.3%-77.4% 1 year survival from transplant 85.9% 79.9%-92.0% Compares favorably with published survival data Copeland….Slepian NEJM 361:859, 2004

Survival to Transplantation 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 10 20 30 40 50 60 70 Time (weeks) Proportion Alive Control Core TAH Copeland….Slepian NEJM 361:859, 2004

Time to Transplant (Mean) Median = 47 days (longest 414 days) Total Study Days 6,411 Cores 299 Controls Median = 6 days Copeland….Slepian NEJM 361:859, 2004

Survival from Transplantation 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 2 4 6 8 10 12 Control Core TAH UNOS Proportion Alive Time (years) Copeland….Slepian NEJM 361:859, 2004

Able to Get-out-of-Bed Ambulation (Core TAH) Able to Get-out-of-Bed (% of Patients) Able to Walk >100 Ft (% of Patients) From Kaplan Meier Estimates Copeland….Slepian NEJM 361:859, 2004

LVAD Mortality Risk Factor Profile vs TAH Cohort Baseline Odds Ratio {Death} TAH Cohort Urine output < 30 ml/h (3.9) {67%} BUN > 40 {54%} 36 + 19 CVP > 16 mmHg (3.1) {40%} 20 + 7 Mechanical Vent (3.0) {35%} 42 % PT > 16 s (2.4) {50%} 16 + 4 Reoperation (1.8) {33%} 38 % Oz, MC, et al Circulation 1995;92:II 169-73. Farrar, DJ. J Heart Lung Transplant 1994;13:93-101

52 risk factors 5 centers Ann Thoracic Surg 85:1639, 2008

TAH vs BiVAD in BTT: Penn + Arizona Experience n = 151 pts Class IV CHF with Biventricular CHF 61 pts Arizona (TAH) , 90 pts Penn (BiVAD) BiVAD TAH BTT 46% 77% Discharge 38% 68% Reoperation 70% 21% RF/ Dialysis 34% 20% MOF Death 11% Stroke 29% 5%

BIVAD/TAH: Flow vs BSA BSA CardioWest TAH Thoratec BIVAD Flow L/M

Active Centers: TAH Implants North American Centers Arizona 110 Barnes 1 Cleveland 15 Loyola 39 Maryland 3 Mayo-Phx 13 MCV 24 Michigan 5 Milwaukee 12 Montreal 10 Ohio St 4 Ottawa 32 Penn State 1 Sharp 7 Salt Lake City 8 U Penn 6 European Centers Bad Oyenhausen 132 Berlin 48 Cologne 1 Erlagen 1 Frieburg 4 Hannover 1 La Pitie 193 Leipzig 2 Muenster 1 Nantes 48 Padua 1 Bern Goteborg 2 Innsbruck 1 Naples Rome 1 Sydney N = 16 N = 17 > 830 implants Total = 33 9/09

Official as of May 1, 2008 Friday February 1, 2008 MEDICARE PROPOSES COVERAGE WITH EVIDENCE DEVELOPMENT FOR ARTIFICIAL HEART DEVICES The Centers for Medicare & Medicaid Services (CMS) today proposed coverage with evidence development of artificial heart devices. CMS proposes to cover artificial heart devices in Medicare beneficiaries who are enrolled in Food and Drug Administration (FDA)-approved studies. “Our proposal relaxes a long-standing non-coverage policy, gives access to our beneficiaries and promotes evidence development through FDA approved studies of this advanced technology,” said CMS Acting Administrator Kerry Weems. Official as of May 1, 2008

2008

TAH Discharge Experience Largely Germany, > 35 pts 78 yrs of outpatient experience 56% of Total TAH experience At home de facto DT Have more data at home than in hospital ! Inpt TAH 44% Outpt TAH 56%

Evolution of SynCardia “Mobility” Drivers The Future “ 400 - 40 - 4 “

SynCardia New Replacement TAH-t Driver “Companion System”

Companion DriverTM

SynCardia Freedom Driver

Blurring Short term support Bridge to Transplant Destination Tx Changing Landscape Bridge to Recovery Bridge to Decision Bridge to Bridge Short term support Bridge to Transplant Destination Tx Long term support Blurring Time vs Dictated Outcome

The CardioWestTM TAH substantially increases the quality of care Summary TAH-t: Immediate Hemodynamic Recovery for irreversible bi-ventricular failure Lower mobidity/mortality than BiVADs End-Organ Recovery Saves lives Higher BTT rate than any VAD/BiVAD QOL/ Patients Out of Bed, Walking New driver technology - enhanced mobility/discharge The CardioWestTM TAH substantially increases the quality of care