“ Development of an Axial Flow Left Ventricular Assist Device (LVAD) from Inception to Clinical Application” George P. Noon, MD Professor of Surgery Chief, Division of Transplant & Assist Devices Meyer-DeBakey Chair of Investigative Surgery Pumps & Pipes

Heart Failure Hospitalizations The number of heart failure hospitalizations is increasing in both men and women CDC/NCHS: Hospital discharges include patients both living and dead. AHA Heart and Stroke Statistical Update 2001

CIRCULATORY ASSIST DEVICES The Methodist Hospital/Baylor College of Medicine IABP (1971-2001) 2880 Roller Pump (1971-1988) 94 DeBakey VAD (1963-1966) 6 Liotta, Hall, Crawford (1963) 1 Symbion/Jarvik (1987-1989) 4 Novacor ® LVAS (1987-2005) 53 BioMedicus ® (1986-2005) 274 MicroMed DeBakey-Noon VAD ® (2000-2005) 36 Thoratec ® LVAD (1998-2005) 31 HeartMate ® VAD (2001-2005) 17 Abiomed ® BVS 5000 (2002-2004) 7 Abiomed ® AB 5000 (2003-2004) 1

Biomedical Engineering Role in Development of Total Artificial Heart and Assist Pumps

Biomedical Engineering Pump Design Blood Contact Surface Controller Power Source

Pump Design

Blood Contact Surface

Controller

Power Source

Biomedical Engineering Blood trauma and clotting Blood contacting surface Duration of contact Stasis Cavitation Heat Shear

Blood trauma and clotting

Blood contacting surface

Duration of contact

Stasis

Cavitation

Heat

Shear

Biomedical Engineering Pump Testing Mock Loop Animal Human

Pump Testing

Mock Loop

Animal

Human

First NASA Axial Flow Prototype Two rotating components

NASA - Ames Research Center Flow Field inside impeller Minimize hemolysis Increase efficiency Provide effective washout Geometry from Johnson Space Center

Flow Field inside impeller

Minimize hemolysis

Increase efficiency

Provide effective washout

Licensed NASA Blood Pump (1996)

Hemolysis Test Setup

Red Cells

Hemolyzed Red Cells

2½ year bench study demonstrated no significant bearing wear 35 clinical pumps returned for evaluation - no evidence of bearing wear Bearing Wear Studies performed by Marconi

2½ year bench study demonstrated no significant bearing wear

35 clinical pumps returned for evaluation - no evidence of bearing wear

Titanium construction: 95 Grams Speed: 7,500 - 12,500 RPM Continuous, axial flow pump Flow rates: 10+ liters/minute Technology licensed from NASA The DeBakey-Noon VAD

Titanium construction: 95 Grams

Speed: 7,500 - 12,500 RPM

Continuous, axial flow pump

Flow rates: 10+ liters/minute

Technology licensed from

NASA

Schematic Illustration of the DeBakey VAD

Bovine tests at Baylor College of Medicine, Texas A&M Ex-Vivo In-Vivo

Novacor  HeartMate  DeBakey-Noon VAD  Device Comparison

DeBakey VAD ® and DeBakey VAD Child

Controller Pump Patient Home Support System Data Acquisition System Result: MicroMed DeBakey VAD ® System

DeBakey-Noon VAD ® Patient Ergonomics

Comparative VAD Space Requirements HeartMate ® XVE LVAD Adult Male DeBakey VAD ® 6 year old girl

DeBakey VAD ® Implantations More than 110 years of cumulative patient experience Total Patients – 437 Average support duration – 106 days 61 patients > 180 days Longest support duration – 841+ days International 286 Patients implanted As of October 2007 United States 151 Patients implanted

Average support duration – 106 days

61 patients > 180 days

Longest support duration – 841+ days

286 Patients implanted

151 Patients implanted

Physiologic Blood Flow Systemic Pulmonary Textbook of Medical Physiology, Arthur C. Guyton

Speed, Flow and Delta Pressure

Hypoperfusion Operating Range Potential for Suction Flow Characteristics

Arterial Pressure - Green VAD Flow - Yellow Pump speed VAD flow (kRPM) (L/min) OFF -2.0 7600 2.3 8900 4.5 10,800 5.6 10 0 -4 0 140 10 0 -4 0 140 10 0 -4 0 140 10 0 -4 0 140

Milan Smaller Patients Possible Miniaturization benefits large and small patients. Milan Zurich Muenster

Continuous Flow Provides Adequate Circulatory Support Resuscitation Rehabilitation Maintenance

Resuscitation

Rehabilitation

Maintenance

Results - CFD Baseline Rear Hub Washout Final Rear Hub Washout Increase gap shows an improved circulation pattern in the rear hub

Results - CFD Baseline Diffuser Inlet Angle Final Diffuser Inlet Angle Flow is entering the diffuser correctly on the pressure side of the blade indicating a small “angle of attack.”

EU Pediatric Device Required CFD of the inflow cannula Results demonstrated pediatric inflow cannula with 2 L/min washed at least as good as adult cannula with 4 L/min

Required CFD of the inflow cannula

Results demonstrated pediatric inflow cannula with 2 L/min washed at least as good as adult cannula with 4 L/min

Results – Flow Visualization Results from increased gap: Less turbulence in the diffuser Baseline Design 2.0x Gap

Results – Hemolysis at 4 L/min INCREASING THE GAP WITHOUT MODIFYING THE DIFFUSER INLET ANGLE DEMONSTRATES A TREND TO SLIGHLY HIGHER HEMOLYSIS 2.0X gap Baseline Baseline 2.0X gap, 32 ° TUNING THE DIFFUSER INLET ANGLE WITH THE LARGER GAP DEMONSTRATES A TREND OF HEMOLYSIS LOWER THAN THE BASELINE VALUE; HOWEVER, THERE IS NO STATISTICAL DIFFERENCE IN HEMOLYSIS BETWEEN THE BASELINE AND FINAL DESIGN N.I.H. = 0.006 N.I.H. = 0.014 N.I.H. = 0.009 N.I.H. = 0.006

X2 Pump Design ½ cm shorter intra-ventricular and 1cm shorter extra-ventricular length for improved anatomical fitting Smoother inlet flare for improved blood flow into the pump Seamless connection to pump housing for improved blood flow Smaller flow probe cover Titanium ring integral to gelatin sealed graft for easy, leak-free assembly

On the horizon…

Clinical Benefits of the MicroMed DeBakey-Noon VAD Size Surgeon Patient Implant Less Awareness Explant Drive Line Smaller Patients Noiseless Device Infection  5% Adequate Circulatory Support Less Expensive

Conclusion Increasing incidence of heart failure Transplantation limited by donor supply Cardiac assist devices increasingly used as Bridge to Transplant Bridge to Recovery Destination Therapy

Increasing incidence of heart failure

Transplantation limited by donor supply

Cardiac assist devices increasingly used as

Bridge to Transplant

Bridge to Recovery

Destination Therapy