1. health and fitness
2. disease
3. heart disease

LVAD UPDATE
Axial Flow vs. Centrifugal Pumps
Rob Adamson, M.D.
SHARP Memorial Hospital
San Diego, CA
DISCLOSURES

Trainer and Proctor for Thoratec
Participated in REMATCH, BTT and DT trials
 94 HM I implants since 1991
 >200 HM II implants since 2005


Participant in the HeartWare trial
FEELING DIVIDED?
BLOOD FLOW PATH
 Inflow from LV
 Inlet Stator
 3 vanes “straighten” the flow
before it enters the rotor
 Rotor
 Propel blood toward the exit
and spins it radially imparting
kinetic energy
 Outlet stator
 “Straightens” flow as leaves
rotor and pressure is further
increased
HEARTMATE II -- DESIGNED FOR LOW TE & PUMP THROMBOSIS
Optimal flow
dynamics reduce
damage to blood cells,
minimizing the risk of
TE formation
A single moving part
helps to optimize the
blood flow path
Sintered titanium
encourages neointima
formation and
adherence of LV clot
and helps reduce the
need for
anticoagulation
Ruby bearings help
dissipate heat and
minimize damage to
blood cells, reducing
the risk of TE
formation
INTERNAL VIEW
Outlet Housing
Rotor Magnet
Rotor
Bearings
Inlet Stator
Outlet Stator
Rev. 12.0 (3/24/04)
Motor Capsule
Motor Winding
Inlet Housing
PUMP ROTOR AND STATORS
Flow
Outflow
Stator
Inflow
Stator
Rotor
Outflow
Bearing
Inflow
Bearings
HeartWare Update
Mike Karim, Director International
The HeartWare® Ventricular Assist System
• Miniaturized implantable HVAD® pump
•
50 cc displacement volume
•
50 mm outside diameter
•
Smaller and lighter than FDA approved
continuous flow LVAD
• 10 liters of flow/min
• Hybrid magnetic and hydrodynamic bearings
creates a unique wearless impeller
• Thin (4.2 mm) driveline with fatigue resistant
cables
• Small 10 mm outflow graft allows for expanded
anastomotic options
Implanted in Pericardial Space
Pericardial benefits
• No abdominal surgery
• No pump pocket
• Less surgical time
• Smaller BSA patients
• Fewer antibodies due to no blood
transfusions
CAUTION: Investigational device. Limited by United States law to investigational use.
CENTRIFUGAL PUMP; DESIGNED FOR LONG TERM USE
Primary flow path
Washes flow channels and
immediately enters outflow
graft
Tertiary flow path
Provides fluid “cushion”;
washes thrust bearings
Secondary flow path
Washes underside and
center post regions
CAUTION: Investigational device. Limited by United States law to investigational use.
OVERALL SURVIVAL COMPARISON TO SEATTLE HEART
FAILURE MODEL (SAME PATIENTS)
Wayne C. Levy, et al, ISHLT 2011
CAUTION: Investigational device. Limited by United States law to investigational use.
ADVANCE TRIAL
HEARTWARE OUTCOME
EXPLANTED HVAD™ PUMP FROM FIRST PATIENT
PATHOLOGY PICTURES AFTER 427 DAYS
Pump housing
Impeller
Images taken at Texas A&M University by Dr. Fred Clubb, D.V.M., Ph.D., DACLAM, Clinical Professor
HEARTWARE LVAD
THORATEC CORPORATION
Lead the use of Mechanical Circulatory Support (MCS) to dramatically improve outcomes for patients with advanced heart failure
Market leadership across the spectrum of MCS
Our Values / Our Commitments
 Continual improvement of clinical outcomes
 Transparent, rigorous clinical research
 Increasing awareness and education
Vision for and commitment to the future of MCS*
*In development. Not approved for clinical use.
 Technology innovation leadership
CentriMag®
HEARTMATE® III*
*In development. Not approved for clinical use.
HEARTMATE III*
Hemotologically Friendly, Proven Full Magnetically Levitated VAD
Features
• Fully Magnetically Levitated
• Designed to be Hemotologically compatible
• Large pump gaps leading to reduced blood trauma
• Textured blood contacting surfaces
• Artificial pulse
• Wide range of operation
• Full support (10L / min)
• Surgically Intelligent
• Advanced Implant / Explant – Engineered apical attachment • Modular Driveline
• Pocket Controller
Program Status
• Target CE Mark Clinical trials initiation mid 2013 and US trial before the end of 2013
*In development. Not approved for clinical use.
HEARTMATE III*: FULL MAGLEV TECHNOLOGY
Key Design Benefits: Optimized Geometry
– HeartMate III secondary flow paths are ~0.5 mm along the side, and ~1.0 mm pump above and below the rotor.
– Conversely, hydrodynamic bearings are typically operated with much smaller gaps, 1/20th of a millimeter or so.
– HeartMate III pump surfaces are flat and flow is undisturbed, wedging surfaces and other features required for hydrodynamic bearings are not required.
~ 0.5 mm along the side
~ 1.0 mm top and bottom
*In development. Not approved for clinical use
HEARTMATE III*: FULL MAGLEV TECHNOLOGY
Key Design Benefits: Fluid Dynamics
– The HeartMate III rotor and volute have been designed to minimize shear and avoid stasis over the entire range of operation (2 to 10 L/min).
– The relatively large secondary flow paths facilitate smooth flow transitions, generous washing, and low shear.
– Impressively low hemolysis has been demonstrated in both in vitro and in vivo (plasma‐free hemoglobin always <10 mg/dL) studies. *In development. Not approved for clinical use.
HEARTMATE III*: FULL MAGLEV TECHNOLOGY
Key Design Benefits: Wide Range of Operation
– HeartMate III rotor levitation is independent of rotor speed; levitation is maintained at any rotor speed, even zero.
– Conversely, for a hydrodynamic bearing the rotor scrapes the housing surface until it comes up to speed and entrains a thin layer of blood to produce lift; a certain critical speed must be maintained to avoid rotor/housing contact.
– Rotor speed independence permits flexibility in operating speeds, which could in the future enable use in low‐speed conditions, e.g., pulmonary circulation, weaning protocols, etc.
– These large gaps also enable the rapid speed changes used by our artificial pulse feature without rotor/housing contact.
*In development. Not approved for clinical use.
PERSONAL EXPERIENCE
It’s not whether the glass is half full or half
empty, it is who poured the water that matters.
 Our experience

HeartMate I vs. HeartMate II
Early Overall Sharp Experience
100
1.0
HM I
HM II
80
0.8
Percent of Patients
77%
Survival
P = 0.024
0.6
0.4
67%
67%
67%
60
40
20
0.2
0.0
0
HM I; N = 81 HM II; N = 53
500
1000
1500
Time
2000
2500
0
At Risk:
84
0
39
1
13
2
Time (Years)
7
3
5
4
OVERVIEW
The controversy
 Published points of comparison






Stroke
Thrombosis
GI bleeding
Driveline infections
Anticoagulation
Why we have done what we have done …..
 My concerns regarding new guidelines to
decrease stroke for DT patients

ADVANCE TRIAL
PRESUMED SUPERIOR DIFFERENCES



We studied a small, intrapericardially positioned, continuousflow centrifugal pump in patients requiring an implanted
ventricular assist device as a bridge to heart transplantation.
Conclusions—A small, intrapericardially positioned,
continuous-flow, centrifugal pump was noninferior to
contemporaneously implanted, commercially available
ventricular assist devices.
Functional capacity and quality of life improved markedly, and
the adverse event profile was favorable.
Circulation. 2012 Jun 26;125(25):3191-200. doi: 10.1161/CIRCULATIONAHA.111.058412. Epub 2012 May 22.
Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart
transplantation.
STRAW MAN
Small
 Intrapericardial (no pocket)

Ease of insertion and removal
 Less invasive, comfortable


Centrifugal
Bridge to Transplant
 Destination Therapy

WORLDWIDE HEARTMATE II® CLINICAL
EXPERIENCE
More than 15,000 patients worldwide have now been
implanted with the HeartMate II LVAS.
Over 6,000 patients on ongoing support

Patients supported ≥ 1 year: 3,838

Patients supported ≥ 2 years: 2,141

Patients supported ≥ 3 years: 1,117

Patients supported ≥ 4 years: 536

Patients supported ≥ 5 years: 294

Patients supported ≥ 6 years: 116

Patients supported ≥ 7 years: 22
We have 88 people on HM II device, 13 people more than
5 years and 1 patient on continuous HM >11 years.
As of July 2013
*Based on clinical trial and device tracking data
HeartMate II—Peer-Reviewed Publications
HeartMate II has an unparalleled number of peerreviewed published studies in highly regarded
publications including NEJM and JACC.
Data featuring HeartMate II has been published in
more than 350* peer-reviewed articles including:

3 in New England Journal of Medicine

17 in Journal of American College of Cardiology

14 in Circulation / Circulation Heart Failure

59 in Journal of Heart and Lung Transplantation

31 in Annals of Thoracic Surgery

20 in Journal of Thoracic Cardiovascular Surgery
CONTINUED POST-MARKET EVALUATION
ROADMAP
TRACE
 Studying Class IIIb / IV patients not
 Studying reduced anti-coagulation and
 HeartMate II compared to medical
 Enrolling in both North America and
 Enrollment: 200 / 200
 Enrollment: 200 / 200
SEE-HF
 SSI
 Evaluating new techniques to reduce
dependent on inotropic support
(INTERMACS profiles 4-6)
management
 EU study designed to involve
cardiologists and implant centers in
evaluating and implanting HeartMate
II in a slightly less sick patient
population
 Initiated enrollment in 1H’13
anti-platelet therapy in
HeartMate II patients
Europe
driveline infection in multi-center
registry
 Single-center experiences utilizing
these techniques have been highly
effective
 Enrollment: 400 / 400
Enrollment statistics as of July 2013.
LOWEST PUBLISHED STROKE RATES*
HEARTMATE II: MINIMIZING COMPLICATIONS
BTT
BTT
DT
HeartMate II1
HeartMate II2
HeartMate II3
2011
n=169
142 pt years
2011
n=1,496
1,082 pt years
2012
n=281
498 pt years
Ischemic
0.06
0.06
0.05
Hemorrhagic
0.01
0.02
0.03
Unknown Type
0.01
0.02
-
Total
0.08
0.10
0.08
Stroke Rates
1.
2.
3.
*
*
Starling, Naka, Boyle , et al. J. Am. Coll. Cardiol. 2011;57;1890-1898
John, Naka, Smedira, et al. Ann Thorac Surg 2011;92:1406 –13
Park, Milano, Tatooles, et al. Circulation Heart Failure. 2012; 5:241-248.
Boyle AJ, Russell SD, Teuteberg JJ, et al. J Heart Lung Transplant. 2009;28:881-7.
Based on published data from multi-center experience and separate studies, which may involve
different patient populations and other variables. Please refer to the HeartMate II Instructions for Use
about indications, contraindications, adverse events, warnings, and precautions (http://
www.thoratec.com/medical-professionals/resource-library/ifusmanuals/heartmate-lllvad.aspx#levelFour).
PUMP THROMBOSIS
PUBLISHED EVIDENCE
Study
Cohort
Device
Replacement for
Pump Thrombosis
Pump Thrombosis Event
Rate
Miller, Pagani, Russell, et al.
NEJM 2007; 357:885-96.
BTT
0.032 (2 events, 61.7 ptyears, 133 patients)
–
Pagani, Miller, Russell et al.
JACC 2009; 54:312-21.
BTT
0.022 (4 events, 181.8
Pt.Years, 281 pts)
–
Boyle, Russell, Teuteberg et al.
JHLT 2009; 28:881-87.
BTT
–
0.014 (3 events, 220
Pt.Years, 331 pts)
Post Discharge Events
Slaughter, Naka, John et al.
JHLT 2010; 29:616-24.
BTT
–
0.027 (9 events, 335.1
Pt.Years, 418 pts)
Slaughter, Rogers, Milano et
al. NEJM 2009;361:2241-51.
DT
–
0.024 (5 events, 211
Pt.Years, 133 pts)
–
0.025 (26 events, 1027
Pt.Years, 701 pts) – Post
Discharge Events
Russell, Boyle, Sun et al. ISHLT
2011.
BTT + DT
SHARP’S PUMP THROMBOSIS
HEMOLYSIS EXPERIENCE
Total number of HMII implants : 207
Total duration of support: 331.5 Pt.Years
Incidence
Number
Exchanges
For thrombus
Suspected
Thrombus
hemolysis
2
0.006/pt- yr
19
0.06/pt- yr
Confirmed
Thrombus
12
0.04/pt-yr
Thoratec records: Updated May 31, 2013
HM II DT 2-YEAR POST-APPROVAL OUTCOMES

Multicenter, prospective, 2 year F/U

Compared 247 INTERMAC DT patients at 61 centers
to 133 patients at 34 centers in the pivotal trial
EVENT
Trial
Post-Approval
Length of stay
27 days
21 days
Bleeding (surgery)
30%
11%
Total Strokes
0.13 EPPY
008 EPPY
Ischemic
0.06
0.03
Hemorragic
0.07
0.05
Device Infection
0.48
0.22
1 year survival
68%
76%
2 year survival
58%
62%
Two-Year Outcomes in the Destination Therapy Post-FDA-Approval Study with a Continuous Flow Left Ventricular
Assist Device: A Prospective Study Using the INTERMACS Registry. U.P. Jorde, S.S. Khushwaha, A.J. Tatooles, et al.
Presented at the ISHLT annual meeting, April 25, 2013.
CLINICAL STRATEGIES AND OUTCOMES IN ADVANCED HEART FAILURE
PATIENTS OVER 70 YEARS OF AGE RECEIVING THE HEARTMATE II
LEFT VENTRICULAR ASSIST DEVICE:
A COMMUNITY HOSPITAL EXPERIENCE
Robert M. Adamson, MD, Marcia Stahovich, RN, Suzanne Chillcott, BSN, Sam
Baradarian, MD, Joseph Chammas, MD, Brian Jaski, MD, Peter Hoagland, MD,
Walter Dembitksy, MD
Presented at the 29th annual meeting and scientific sessions of the International Society for Heart and Lung Transplantation,
April 2009, Paris, France.
Event Rate
MAJOR ADVERSE EVENTS
Adamson et al. JACC 2011
SHARP DT EXPERIENCE

JACC elderly population
Low stroke rate
 Minimal anticoagulation
 Need to maintain BP to avoid syncope in elderly

HEARTMATE II VS. TRANSPLANT
SURVIVAL COMPARISON
39
RESULTS
Factor
Transplant
HeartMate II
(N=59)
(N=102)
52
63
P<.01
Gender, (%)
Male
64%
(38/59)
86%
(88/102)
P<.05
LOS (days)
18
22
N.S.
Survival n (%)
At time of Discharge (n=161)
1 Year
3 Years
97%
95%
88%
95%
82%
69%
N.S.
P<.01
Cost Changes
+17%
-41%
P<.05
Age (year)
p-value
40
DOES SIZE MATTER?
IT DEPENDS ON WHO YOU ASK ……..
BSA IN THE GENERAL UNITED STATES POPULATION1
Percentile
Mean
5th
10th
15th
25th
50th
75th
85th
90th
95th
Men
2.06 1.73 1.8 1.84 1.93 2.07 2.23 2.34 2.41 2.52
Women 1.85 1.49 1.55 1.59 1.66 1.82 1.99 2.12 2.21 2.33
<2.5% of the adult US population is BSA
<1.5m2
1. U.S. Environmental Protection Agency (EPA). (2011) Exposure Factors Handbook: 2011 Edition. National Center for
Environmental Assessment, Washington, DC; EPA/600/R-09/052F. Available from the National Technical Information Service,
Springfield, VA, and online at http://www.epa.gov/ncea/efh.
UNITED STATES INTERMACS DATA
SMALL PATIENTS (<1.5M2)
INTERMACS Devices
74
1%
>1.5m2
6,048
99%
Small BSA patients
n
%
Bridge to Transplant (BTT)
44
59%
Destination Therapy (DT)
34
41%
74
100%
Total
Note: All INTERMACS small patient data as of Dec 31, 2012 are HeartMate
II.
*INTERMACS Data on File.
File as of Dec 2012.
.
SURVIVAL
Months of
Survival
BTT
DT
% Survival +/-SE
% Survival +/-SE
6
87.8 +/- 5.1
86.4 +/- 6.3
12
84.1 +/- 6.1
86.4 +/- 6.3
24
78.9 +/- 7.6
78.6 +/- 9.4
79% survival at 2 Years
*INTERMACS Data on File.
File as of Dec 2012.
.
ADVERSE EVENTS
BTT patients (n=44)
# Patients % Patients
Arterial Non-CNS Thromboembolism
2
5%
Bleeding
18
41%
Bleeding, requiring Surgery
6
14%
Cardiac Arrythmias
13
30%
Hemolysis
4
9%
Hepatic Dysfunction
5
11%
Hypertension
1
2%
Any Infection
16
36%
Drive Line Infection
5
11%
Pump Pocket Infection
1
2%
Positive Blood Culture
2
5%
Myocardial Infarction
0
0%
Stroke
4
9%
Hemorrhagic Stroke
1
2%
Ischemic Stroke
3
7%
Pericardial Drainage
2
5%
Psychiatric Episode
4
9%
Renal Dysfunction
7
16%
Respiratory Failure
10
23%
Right Heart Failure
7
16%
Venous Thromboembolism
1
2%
Suspected Device Malfunction
5
11%
Thrombus
0
0%
Wound Dehiscence
0
0%
# Events
2
59
9
18
5
7
1
46
13
1
3
0
4
1
3
2
5
8
13
10
1
10
0
0
DT patients (n=30)
Events / pt
yr
# Patients % Patients
0.04
0
0%
1.23
14
47%
0.19
0
0%
0.38
7
23%
0.10
5
17%
0.15
2
7%
0.02
2
7%
0.96
11
37%
0.27
5
17%
0.02
0
0%
0.06
2
7%
0.00
0
0%
0.08
2
7%
0.02
0
0%
0.06
2
7%
0.04
0
0%
0.10
2
7%
0.17
2
7%
0.27
8
27%
0.21
3
10%
0.02
2
7%
0.21
3
10%
0.00
0
0%
0.00
0
0%
Note: BTT patients (n=44) have 47.92 patient-years of LVAD support; DT patients (n=30) have 34.17 patient-years.
*INTERMACS Data on File.
File as of Dec 2012.
.
# Events
0
36
0
8
5
3
2
25
8
0
2
0
2
0
2
0
2
2
8
3
2
3
0
0
Events / pt
yr
0.00
1.05
0.00
0.23
0.15
0.09
0.06
0.73
0.23
0.00
0.06
0.00
0.06
0.00
0.06
0.00
0.06
0.06
0.23
0.09
0.06
0.09
0.00
0.00
QUALITY OF LIFE
6-MINUTE WALK TEST
350
294
300
Walk Distance (m)
269
250
215
208
200
Baseline
150
1 Year
100
n=1
9
n=1
6
n=1
5
50
0
BTT
*INTERMACS Data on File.
File as of Dec 2012.
.
DTT
n=1
1
HEARTMATE II SMALL PATIENT EXPERIENCE
BSA <1.5M2
United States Experience
 Patients







n=74 patients (BSA <1.5m2)
44 BTT
30 DT
Smallest patient = 1.29 m2
89% females
1/3 of the DT patients were 70+ years old
Outcomes


~79% 2-year survival (for both BTT and DT)
Low adverse event rates



Total Stroke Rate = 0.08 and 0.06 EPPY (BTT and DT respectively)
No thrombus
Significant improvement in QOL (6-minute walk test)
Outside the United States Experience**
 Smallest Patient in Europe = BSA 1.1m2
 As of June, ~50% of Japanese HeartMate II patients, post-trial, have been
≤1.5m2
*INTERMACS Data on File as of Dec 2012.
**Data on File as of June 2013
ADVANTAGES OF POCKETS
SURPRISING WHAT WILL FIT INTO A POCKET
SURPRISING WHAT WILL FIT INTO A POCKET
ADVANTAGES OF A POCKET
Broadly applicable independent of patient size
 Allows proper pump positioning

inflow cannula placement
 no RV compression
 easy exchange / replace


Room left in the mediastinum
>50% previous heart surgery
 Radiation


Infection is isolated from the mediastinum
ISHLT ABSTRACT ON HMII POSITIONING
No HM II components within the pericardium
except the inflow cannula and outflow graft
 No right ventricular compression
 No instances of malposition
 Minimal migration at 2 years

REVOLVE HVAD REGISTRY

Post-CE mark approval study
Multicenter, prospective, single arm registry
 Largest real world reported experience
 9 centers – Europe and Australia, 50% (Leipzig)
 n=254, 252 patient years

Low CVA rate .008 EPPY
 Criticisms

Voluntary registry, non-adjudicated or peer reviewed
 Short-term follow up
 9/10 centers submitted data, no other German
centers participated

Results of the Registry To Evaluate the HeartWare Left Ventricular Assist System (The ReVOLVE Registry). M.
Strueber, R. Larbalestier, P. Jansz, et al. Presented at the ISHLT annual meeting, April 25, 2013.
CANADIAN MULTICENTER HVAD STUDY

5 Canadian centers
75 patients, mean 219 days on device
 33 female/ 42 male
 INTERMACS profiles 1-31%, 2-43%, 3-20%, 4-7%


Results of entire cohort
Sintered pumps higher stroke rate
 Total EPPY 0.57, Ischemic 0.43, hemorrhagic 0.14

Event
% pts EPPY
GI bleed
9.6
0.16
Total strokes
21.3
.035
ischemic
6.7
.024
hemorrhagic
14.7
0.11
Pump
2.6
0.04
Thrombosis
Multicenter Canadian Experience with the HeartWare HVAD. V. Rao, J.F. Legare, R. MacArthur, et al.
Presented at the ISHLT annual meeting, April 25, 2013
BAD OEYNHAUSEN HVAD VS. HM II

160 HMII compared to 146 HVAD

HVAD patients more ECMO and INTERMACS 1
Results relatively good for HVAD and poor
compared to other HM II trials
 Non-randomized

Event
HVAD
HM II
Thrombus
0.07
0.06
Total strokes
0.15
0.13
Ischemic
0.09
0.06
Hemorrhagic
0.06
0.07
A Comparison between HeartMate II and HeartWare LVAD, a Single Center Experience. M.J. Morshuis, C. Oezpeker,
J. Gummert. Presented at the ISHLT annual meeting, April 25, 2013.
ENDURANCE TRIAL STROKE RATES
450 patient, multicenter trial (50 sites)
comparing HVAD to HM II in the DT setting
with primary endpoint of stroke free survival
 360 patient supplemental cohort (2:1 HVAD:HM
II) follow-up 12 months
 FDA reviewed 2012 BTT data and prompted
ongoing delay of DT approval

EVENT
HVAD
HM II
Ischemic
6.7%
4.3%
Hemorhagic
5.1%
0%
11.8%
4.3%
Stroke
Total Stroke
HeartWare. HeartWare receives conditional approval from FDA to enroll supplemental patient cohort in destination
therapy trial [press release]. June 17, 2013
FDA WARNING

Increased neurologic events in the ENDURANCE
BTT trial
Ischemic CVA

Hemorrhagic CVA
HVAD
6.7
5.1
HM II
4.3
0
Prompted FDA review and a warning
PUBLISHED DATA CONCLUSIONS

Much more data available for HM II vs. HVAD;

patients, centers, time on device
Short-term survival equivalent
 Stroke may be increased with HVAD in the BTT
population

FDA published warning
 HeartWare changed management protocols


Little data on DT patients for HVAD

No CMS approval for DT for the HVAD
PERSONAL CONCERNS ABOUT EFFECTS IN DT

Recent HeartWare recommendations are
↑ ASA
 ↑ Coumadin (INR)
 ↓ BP


The primary group for destination therapy are
the elderly
Intolerant to anticoagulation
 BP generally higher due to ↑ near syncope and
↑ fall risk

NON-INFERIORITY
NON INFERIORITY….
DOES NOT MEAN THE SAME
CONCLUSION
HM II remains our device of choice in our older
patients
 Hoping that HVAD measures improve outcome
 Believe that 2 or more available devices good for
the field of MCS
 Awaiting real data on the HMIII
