Contemporary Outcomes With the HeartMate II LVAS David J

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Contemporary Outcomes With the HeartMate II LVAS
David J. Farrar, PhD Vice President, Research and
Scientific Affairs Thoratec Corporation
J138-0711
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HeartMate II LVAS

• A surgically implanted, rotary continuous-flow
  device in parallel with the native left ventricle
• Left ventricle to ascending aorta
• Percutaneous driveline
• Electrically powered
• Batteries and line power
• Fixed-speed operating mode
• Home discharge with ability to return to
  activities of daily life (work, school, exercise,
  hobbies, etc.)

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HeartMate IIIndications for Use

• HeartMate II is the first and only FDA-approved
  continuous-flow device for both
  Bridge-to-Transplantation (BTT) and Destination
  Therapy (DT).

• Bridge-to-Transplantation
• Risk of imminent death from nonreversible left
  ventricular failure
• Candidate for cardiac transplantation
• Destination Therapy
• NYHA Class IIIB or IV heart failure
• Optimal medical therapy 45 of last 60 days
• Not a candidate for cardiac transplantation

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HeartMate IIWorldwide Clinical Experience

• More than 7,000 patients worldwide have now been
  implanted with the HeartMate II LVAS.
• Patients supported 1 year 2,439
• Patients supported 2 years 851
• Patients supported 3 years 269
• Patients supported 4 years 83
• Patients supported 5 years 20
• Patients supported 6 years 1
• Patients supported 7 years 1

Based on clinical trial and device tracking data
As of March, 2011
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HeartMate IIImprovement in BTT Outcomes
Miller LW, Pagani FD, Russell SD, et al. NEJM.
2007357885-96. Pagani FD, Miller LW, Russell
SD, et al. JACC. 200954312-21. Starling, Naka,
Boyle, et al. JACC. 20115719.
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HeartMate IIImprovement in DT Outcomes
Slaughter MS, Rogers JG, Milano CA, et al.
Advanced heart failure treated with
continuous-flow left ventricular assist device. N
Engl J Med. 20093612241-51. Park SJ. AHA
Scientific Sessions, November 2010.
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HeartMate IIRecent Publications
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HeartMate IIPost-Approval BTT Study

• Initiated post-BTT approval to assess outcomes in
  a broader patient care environment
• First approved study to use INTERMACS
• The first 169 consecutive HeartMate II patients
  enrolled in INTERMACS
• Listed or likely to be listed for transplant
• Enrolled across 77 centers from April to August
  2008
• Patients followed for at least 1 year

Starling, Naka, Boyle, et al. JACC. 20115719.
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Study Endpoints

• Primary endpoint
• Survival
• Secondary endpoint
• Adverse events
• Reported upon occurrence
• Quality of life
• EuroQol EQ-5D visual analog scale determined at
  baseline and 3, 6, and 12 months
  postimplant

Starling, Naka, Boyle, et al. JACC. 20115719.
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Demographics and Patient Characteristics
1. Starling, Naka, Boyle, et al. JACC.
20115719. 2. Pagani FD, Miller LW, Russell SD.
extended mechanical circulatory support with
a continuous-flow rotary left ventricular assist
device. J Am Coll Cardiol. 200954312-21.
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INTERMACS Profiles
Starling, Naka, Boyle, et al. JACC. 20115719.
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HeartMate IIActuarial Survival
Post-Approval Study
Starling, Naka, Boyle, et al. JACC. 20115719.
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HeartMate IIAdverse Events

• Patients in the post-approval study experienced a
  reduced or similar rate of adverse events in a
  broader patient care environment compared to
  clinical trial patients.
• There were zero pump replacements through the
  first 6 months of HeartMate II support in the
  post-approval study group.

1. Starling, Naka, Boyle, et al. JACC.
20115719. 2. Pagani FD, Miller LW, Russell SD.
Extended mechanical circulatory support with
a continuous-flow rotary left ventricular assist
device. J Am Coll Cardiol. 200954312-21.
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Clinical Outcomes Based on INTERMACS Profile

• 101 BTT / DT continuous-flow LVAD patients at
  three centers were preoperatively categorized by
  INTERMACS profiles and followed to determine if
  there were differences in outcomes.
• Hypothesis that patients with higher INTERMACS
  profiles (lower acuity of heart failure) would
  have reduced lengths of stay postVAD in
  comparison to patients with lower INTERMACS
  profiles (higher acuity of heart failure).
• Outcomes observed included actuarial survival,
  survival to discharge, and length of stay.

Boyle, Ascheim, Russo, et al. JHLT. 2011304.
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Clinical Outcomes Based on INTERMACS Profile
Length of Stay Post-VAD
Actuarial Survival Post-VAD
Less acutely ill, ambulatory patients in
INTERMACS profiles 47 had better survival and
reduced length of stay compared to patients who
were more accurately ill in profiles 13.
Group 1 INTERMACS 1 Group 2 INTERMACS 23 Group
3 INTERMACS 47
Boyle, Ascheim, Russo, et al. JHLT. 2011304.
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Analysis of Response of Four Rotary Pumps
the characteristic of the HeartMate II can be
considered superior to the centrifugal pumps in
so far that the zone of maximum preload
sensitivity occurs at the low end of the
afterload scale (i.e., mean afterload of 5090
mmHg) mostly inhabited by patients requiring
mechanical assistance to the left ventricle.
Salamonsen RF, Mason DG, Ayre PJ. Artif Organs.
2011.
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HeartMate IIRecent Presentations
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HeartMate II Risk ScoreStudy Goals

• Derive and then validate a risk model for
  predicting short- and longer-term survival
  following continuous flow LVAD implantation.

Cowger J, Sundareswaran K, Rogers J, et al. ISHLT
2011. Lietz, et al. Circulation.
2007116497-505.
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HeartMate II Risk ScoreStudy Cohorts

• Patients undergoing HeartMate II implant enrolled
  into the HeartMate II Bridge-to-Transplant
  (N489)1,2 and Destination Therapy (N633)3
  trials were included (total N1,122).
• Patients were prospectively and randomly assigned
  to either the derivation cohort or to the
  validation cohort.
• Multivariable analyses were performed to identify
  the risk factors of death following LVAD
  implantation.

Cowger J, Sundareswaran K, Rogers J, et al. ISHLT
2011. 1. Miller L, Pagani F, et al. N Engl J
Med. 2007357885-96. 2. Pagani F, Miller L, et
al. JACC. 200954312-21. 3. Slaughter M, Milano
C, Rogers J, et al. N Engl J Med.
20093612241-51.
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Multivariate Predictors of Death PostLVAD
Cowger J, Sundareswaran K, Rogers J, et al. ISHLT
2011.
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Risk Stratification in HeartMate II
PatientsComparison of Derivation and Validation
Cohorts
Cowger J, Sundareswaran K, Rogers J, et al. ISHLT
2011.
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Risk of Bleeding and Stroke in HeartMate II
Outpatients
Russell SD, Boyle A, Sun B, et al. ISHLT 2011.
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Preoperative Predictors of Bleeding
Univariate Correlates
Multivariate Risk Factors
P 0.003
Russell SD, Boyle A, Sun B, et al. ISHLT 2011.
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Female GenderOnly Independent Risk Factor for
Stroke and Pump Thrombosis
Females were twice as likely to experience a
stroke or pump thrombosis event.
Russell SD, Boyle A, Sun B, et al. ISHLT 2011.
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Impact of Infection on Stroke and Thrombosis

• During a 14 day window around an infection event
  patients were
• 4 times more likely to experience a hemorrhagic
  stroke event
• 8 times more likely to experience an ischemic
  stroke event
• 9 times more likely to experience a pump
  thrombosis event

Russell SD, Boyle A, Sun B, et al. ISHLT 2011.
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Driveline Exit Site Comparison of Velour Versus
Silicone Skin Interface

• Hypothesized that
• Silicone interfaces will be associated with lower
  infection rates and faster incorporation times
• Surface characteristics will differ significantly
  between velour and silicone

Ledford ID, Miller DV, Mason NO, et al. ISHLT
2011.
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Velour Versus Silicone Skin Interface
Ledford ID, Miller DV, Mason NO, et al. ISHLT
2011.
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Histology

• Velour exhibits more dermal inflammation and an
  irregular shaped stratum corneum.
• Silicone is smooth and regular, and shows less
  inflammation.

Ledford ID, Miller DV, Mason NO, et al. ISHLT
2011.
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Contemporary Destination Therapy Results
Park SJ. AHA Scientific Sessions, November
2010. 1. Slaughter M, Milano C, Rogers J, et al.
N Engl J Med. 20093612241-51 .
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Contemporary Destination Therapy Results
The CAP results show a decrease in major adverse
events.
Park SJ. AHA Scientific Sessions, November 2010.
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Contemporary Destination Therapy Results
Park SJ. AHA Scientific Sessions, November 2010.
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In Summary

• Over 7,000 patients implanted with HeartMate
  IIlong-term durability
• Improvements in Bridge-to-Transplant and
  Destination Therapy survival and adverse event
  rates
• Adverse-event differences in LVAD patients may
  lead to targeted approaches for men and women
• Driveline infections can possibly be reduced by
  new tunneling techniques
• New HeartMate II risk model along with INTERMACS
  profiles may help guide future patient selection