Emerging LVAD Technology for the Use - Washington Hospital Center

Emerging LVAD Technologies for the
Use of Life Long Mechanical Support
Steven W. Boyce, MD
Surgical Director, Advanced Heart Failure Program
MedStar Heart Institute
MedStar Washington Hospital Center

Disclosures
• Stocks, Stock Options, other Ownership
Interest:
• Heartware
• Thoratec
• My discussion will include off-label
discussions.
• These devices are not yet FDA
approved

Continuous Flow LVADs
• Thoratec VADs
• HeartMate ® II LVAS
• HeartMate ® III LVAS
• HeartMate ® X
• HeartWare Ventricular Assist Systems
• HVAD ® pump
• MVAD pump
• Jarvik 2000 ® LVAD
• MicroMed CardioVascular HeartAssist 5 ®
• CircuLite ® Synergy ® MicroPump

Second Generation Axial Flow Pumps
Physiology
• Adequate end-organ perfusion (Russell et al, J Heart Lung
Transplant 2006)
• No detrimental effects on cerebral perfusion or
pulmonary function (Thalmann et al, J Heart Lung Transplant 2005)
• Attenuation of neurohormones, inflammatory
markers, cellular hypertrophy (Thohan et al, J Heart Lung
Transplant 2006)
• ↓ allosensitization and fewer post-transplant
rejections (George et al, J Heart Lung Transplant 2006)
• Fewer driveline infections (Hipkin et al, J Heart Lung Transplant
2006)
• Adequate support with exercise (Thalmann et al, J Heart Lung
Transplant 2005)
• Improved QOL (Miller et al, CHF 2004)

• Electrically powered
• Percutaneous driveline
• Flow range 3-10 l/min
• FDA Approved
HeartMate II LVAD
– Bridge to Transplantation
– Destination Therapy
• Clinical Experience
– Over 1000 patients
implanted
– Over 7000 pt-years of
support

• Continuous flow, rotary pump
• Axial design
• Small
HeartMate II LVAD
• 1/7 th size (65 cc displacement)
• 1/4 th weight (295 gm)
• Quiet operation
• No requirement for venting
• 40% smaller percutaneous lead
• Single internal moving part
• Potential for long-term durability

• FDA approved
Thoratec HeartMate II LVAS
– Bridge to transplant – 2009
– Destination Therapy – 2010
• Clinical Experience
– > 10,000 implants worldwide
– Patients supported ≥ 3 years: 455
– Patients supported ≥ 4 years: 158
– Patients supported ≥ 5 years: 43
– Patients supported ≥ 6 years: 14
0
– Patients supported ≥ 7 years: 2 Months
Percent Survival
100
90
80
70
60
50
40
30
20
10
Implant dates n 30 d 6 Mo 12 mo
a Apr ’08 - Oct ‘10 1496 95% 89% 85%
b Apr ’08 - Aug ‘08 169 96% 90% 85%
c Mar ’07 - Apr ‘08 205 95% 86% 80%
d Mar ’05 - Mar ‘07 281 92% 82% 73%
e Mar ’05 - May ’06 133 89% 75% 68%
a John et al STS 2011
b Starling et al JACC (in press)
d Pagani et al JACC 2009
e Miller et al NEJM 2007
0 6 12
Late Trial c
Post-Trial a
Post-Approval Study b
Early-mid Trial d
Early Trial e

Percent Survival
100
90
80
70
60
50
40
30
20
10
0
Improving Survival in LVAD Trials
HM II BTT Starling HFSA 2009
0 6 12 18 24
Months
HM II BTT Pagani JACC 2009
HM II BTT Miller NEJM 2007
HM II DT Slaughter NEJM 2009
VE DT LVAD REMATCH Rose NEJM 2001
XVE DT LVAD Slaughter NEJM 2009
Novacor DT LVAD INTrEPID Rogers JACC 2007
OMM REMATCH Rose NEJM 2001
OMM INTrEPID Rogers JACC 2007

Thoratec HeartMate III
• Full-magnetic levitation:
allows precise rotor
control → ability to
develop pulsatile flow
• Textured bloodcontacting
surfaces
• Intra-thoracic placement
• Modular percutaneous
lead (driveline)

Thoratec HeartMate III
Large pump gaps
View Inside the Pump
Chamber
Low Shear Stress
Rotor
Textured surfaces
inside pump
chamber

*In development and not available for clinical use
Thoratec HeartMate X*
• Leverages HMII bearing
technology – projected 17
year lifespan
• Capable of full or partial
support
• Versatile cannulation –
RVAD/BVAD
• Lower power consumption –
potential for smaller external
batteries and components

Implanted
Controller/Battery/
Advanced Energy
Transmission (TETS)
Module
Thoratec Fully-Implantable LVAS
*In development and not available for clinical use
• Advanced wireless energy
transfer
– Eliminates the
percutaneous lead
− WiTricity’s distance
enhancing, wireless
electricity transmission
technology (no TET coils)
• Advanced battery technology
– ~3 hours initially and ~ 2
hours at 3 year mark
• Implanted components with
highly reliable electronics

HeartWare Ventricular Assist System
• Centrifugal design: hybrid magnetic/hydrodynamic impeller
suspension
• Intrapericardial placement – no abdominal surgery or pump
pocket
• Accurate flow estimation
• 4.2 mm flexible driveline with fatigue resistant cables

Pericardial Placement Advances Therapy
HeartMate XVE
HVAD Pump
HeartMate II
Thoratec
HeartMate XVE
Thoratec
HeartMate II
HeartWare
HVAD Pump

HeartWare Ventricular Assist System
International Trial
• Enrolled: 50 patients at 5 Centers
• Completed: June 2008
• CE Mark and TGA approval
ADVANCE FDA Bridge to Transplant Trial
• Enrolled: 140 patients at 30 centers
• PMA: filed December 2010
• CAP (Continued Access Protocol): enrolled 202 additional patients
ENDURANCE FDA Destination Therapy Trial
• Enrolled: 430+ patients (target 450)
• Target Enrollment Completion: 2Q12
REVIVE-IT Trial
• NHLBI sponsored trial of HVAD Pump in Class III patients
• Enrollment target: 100 patients in ten centers
• Anticipate enrollment beginning 2012

HeartWare Ventricular Assist System
Results from Pivotal ADVANCE BTT Trial
• Enrollment of 140 patients, completed February 28, 2010
• Study cohort “Success” was 92%
• Non-inferiority to INTERMACS control group (p < 0.0001)
• Overall survival was 94% at 180 days and 91% at 360 days
• 30-day mortality was 1.4%
• Favorable adverse event profile
• Results filed with the FDA December 27, 2010

Sintered HVAD Inlet

HeartWare Ventricular Assist System
Potential Future Indications for the HVAD ® pump
Potential for right or bi-ventricular
support
E. McGee, Northwestern
NOTE: The HVAD Pump is not-indicated for right ventricle or pediatric use
Potential pediatric and uni-ventricular
support
M. Hubler, German Heart Institute, Berlin

HeartWare MVAD
• Wide blade impeller
with hybrid suspension
• Significant
miniaturization - ⅓
size of HVAD
• Partial and full flow support
• Potential for right and left
ventricular support (RVAD/LVAD)

Heartware MVAD

HeartWare MVAD
Trans-Mitral “MVAD”: Right Thoracotomy
• Inflow cannula through upper right
pulmonary vein or LA then across
mitral valve to access LV
• Outflow graft to ascending aorta
• Benefits: no myocardium
incisions, no bypass, mitral
valve always opens
• Questions: procedure
acceptance, mitral valve
integrity

HeartWare MVAD
Trans-Apical “MVAD”: Left Thoracotomy
• Device in LV with inflow
pointing toward apex
• Outflow in ascending aorta
• Benefits: very quick
implantation, no outflow
graft, no bypass
• Questions: device in LV,
aortic valve integrity

• Intraventricular axial flow pump
• CE Mark 5/05
• US BTT IDE Pivotal Study
Jarvik 2000 ® VAS
• 150 patient enrollment completed
in 2011
– Study enrollment will continue up
to maximum of 160 subjects
– Pilot and Pivotal cohorts total 213 subjects
– Continuing Access Protocol (CAP) application in Q1
2012
– PMA application to be submitted in 2012

Jarvik 2000 ® VAS
Destination Therapy Study:
• IDE Study Protocol: in discussions with
the FDA
• Target initiation in 2012
• Study design: prospective,
randomized against an
approved DT LVAD
• Study implant technique will include the
Post-Auricular version of the Jarvik 2000 ®
VAS

Future applications
• Total Ventricular Assist
(TVA or BVAD)
applications
RV & LV support in
children
RV support in adults
Jarvik 2000 ® VAS

MicroMed HeartAssist 5 ® VAD
• Axial flow device (92 grams)-
implant above the
diaphragm.
• Implantable Flow Probe
• HeartAssistRemote
Monitoring System
• 2 VAD Sizes – allows
different size patient
anatomies.
– US IDE BTT Trial
• In discussion with the FDA
• Target multi-center study in
2012

MicroMed HeartAssist 5 ® VAD
HeartAssistRemote Monitoring
• Allows for monitoring of speed, flow and power over the
internet, which facilitates earlier intervention
• Partnership w/ Global Network of 900 Carriers

CircuLite ® Synergy ® Micro-Pump
• Miniaturized, implantable axial flow
blood pump
• Minimally invasive: off-pump,
subcutaneous (extrathoracic)
pacemaker-like “pocket” placement
• NYHA Class IIIb and early IV patients
• Provides 1.50-4.25 L/min blood flow
• Designed for long-term support
– Bench-top testing >3.5+ years
• Clinical experience in 44 patients

CircuLite ® Synergy ® Micro-Pump
• Initial issues: pump thrombosis and graft
weeping resolved → reduction in anticoagulation
therapy
• Synergy ® EU Clinical Study ongoing
• 44 patients implanted
• Demonstrated sustained improvements in
hemodynamics, functional status and
quality of life
• Longest patient supported > 2.5+ years
• Six patients supported for >1 year
• CE Mark approval anticipated in 2012
• US IDE pilot trial anticipated 2012

“May I be
excused? My
brain is full.”

Potential VAD Patient Opportunity
US Population [1] 301,000,000
Target Population – 35-74 Age Cohort [1] 139,100,000
Diagnosed CHF Population [2]
All ages 5,520,000
35 to 74 years 3,744,000
NYHA Class IIIB and IV [3] in 35 – 74 Age Cohort 374,400
(75%)
Co-morbidities estimated in this Cohort (280,800)
Target VAD Patient Population – 35 to 74 years 93,600
Estimated VAD patient per 100,000 30
[1] US Census Bureau Statistics (2008)
[2] Heart and Stroke Statistics, American Heart Association (2008)
[3] Cardiovascular Roundtable research and analysis, The Advisory Board Company (2008)

VAD Implants in the 20 Largest Metro Areas (US Only)
Implants per 100,000
2.50
2.00
1.50
1.00
0.50
0.00

Are We Ready?

Intracorporeal BVADs for DT
• Size less invasive implant
• Right sided support: RVAD
• Integrated BVAD—one controller
– In future may allow pts with RVF/sicker pts
Heartware MVAD
HeartMate X

HeartWare Ventricular Assist System
• HVAD miniaturized implantable blood pump
– Pericardial placement – no pump
pocket
– Provides up to 10 L/min of flow
– Centrifugal design, continuous flow
– Hybrid magnetic / hydrodynamic
impeller suspension
– Optimizes flow, pump surface washing,
and hemocompatibility
• Thin (4.2 mm), flexible driveline with
fatigue resistant cables

A Permanent, Partial Support LVAD: Potential for
Minimally Invasive Implantation
Pump to the
Subclavian
Artery
Subcutaneous
pump,
implanted like
a pacemaker
CircuLite
Take Blood
From LA

Fully-Implantable System: Energy Transmission
Technology
• Efficient energy transfer system under development
• Technology being optimized to minimize coil alignment
sensitivity and maintain high efficiency
• The proprietary approach is being developed for the VAD
application under an technology agreement with WiTricity
Corporation

HeartWare Ventricular Assist System
Clinical Update at EACTS 2011
• 241 patients followed in ADVANCE and CAP with at least 6 months of follow
up for 207 patient-years of support
• Average duration of support: 313 days
• Survival remains high at 92.7% at 180 days despite lower transplant rate than
in prior BTT trials
• Reoperations for bleeding as well as sepsis and driveline infections were
infrequent
• Focus on anti-platelet reduced thrombus events without increasing bleeding
• Overall, adverse event rates remain low despite prolonged exposure to device
support with improving survival and lower transplant rates

• GLP animal studies completed
HeartWare MVAD
• MVAD CE Mark study planned for
1H12, with 50 patients at 6-8 clinical
sites
• US IDE to commence after initial CE
Mark patients are implanted