J138-0711

Contemporary Outcomes With the HeartMate II® LVAS

David J. Farrar, PhDVice President, Research and Scientific AffairsThoratec Corporation

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.)

Implantable

Pump

Controller

PercutaneousLead

Batteries

HeartMate II® LVAS

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

HeartMate II—Indications for Use

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

More than 6,000 patients, spanning over 6,000 patient years across 254 centers worldwide have now been implanted with the HeartMate II LVAD

Patients supported 2 years: 700

Over 60 patients supported 4 or more years

Longest support duration: 6 years

Smallest patient: 1.1 BSA

Largest patient: 3.2 BSA; 44 BMI

Age range: 9–91

More than 6,000 patients, spanning over 6,000 patient years across 254 centers worldwide have now been implanted with the HeartMate II LVAD

Patients supported 2 years: 700

Over 60 patients supported 4 or more years

Longest support duration: 6 years

Smallest patient: 1.1 BSA

Largest patient: 3.2 BSA; 44 BMI

Age range: 9–91As of March, 2011* Based on clinical trial and device tracking data

HeartMate II—Worldwide Clinical Experience*

Miller LW, Pagani FD, Russell SD, et al. NEJM. 2007;357:885-96.Pagani FD, Miller LW, Russell SD, et al. JACC. 2009;54:312-21.

Starling, Naka, Boyle, et al. JACC. 2011;57:19.

HeartMate II—Improvement in BTT Outcomes

Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361:2241-51.

Park SJ. AHA Scientific Sessions, November 2010.

HeartMate II—Improvement in DT Outcomes

HeartMate II—Recent Publications

Starling, Naka, Boyle, et al. JACC. 2011;57:19.

HeartMate II—Post-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. 2011;57:19.

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

1. Starling, Naka, Boyle, et al. JACC. 2011;57:19.

2. Pagani FD, Miller LW, Russell SD. extended mechanical circulatory support with a

continuous-flow rotary left ventricular assist device. J Am Coll Cardiol. 2009;54:312-21.

Demographics and Patient Characteristics

Starling, Naka, Boyle, et al. JACC. 2011;57:19.

INTERMACS Profiles

Post-Approval Study

Starling, Naka, Boyle, et al. JACC. 2011;57:19.

HeartMate II—Actuarial Survival

1. Starling, Naka, Boyle, et al. JACC. 2011;57:19.

2. Pagani FD, Miller LW, Russell SD. Extended mechanical circulatory support with a

continuous-flow rotary left ventricular assist device. J Am Coll Cardiol. 2009;54:312-21.

HeartMate II—Adverse 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.

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. 2011;30:4.

Boyle, Ascheim, Russo, et al. JHLT. 2011;30:4.

Clinical Outcomes Based on INTERMACS Profile

Length of Stay Post-VAD Actuarial Survival Post-VAD

Less acutely ill, ambulatory patients in INTERMACS profiles 4–7 had better survival and reduced length of stay compared to patients who were more accurately ill in profiles 1–3.

Group 1: INTERMACS 1Group 2: INTERMACS 2–3Group 3: INTERMACS 4–7

“… 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 50–90 mmHg) mostly inhabited by patients requiring mechanical assistance to the left ventricle.”

Salamonsen RF, Mason DG, Ayre PJ. Artif Organs. 2011.

Analysis of Response of Four Rotary Pumps

HeartMate II—Recent Presentations

HeartMate II Risk Score—Study 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. 2007;116:497-505.

HeartMate II Risk Score—Study Cohorts

Patients undergoing HeartMate II implant enrolled into the HeartMate II Bridge-to-Transplant (N=489)1,2 and Destination Therapy (N=633)3 trials were included (total N=1,122).

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. 2007;357:885-96.2. Pagani F, Miller L, et al. JACC. 2009;54:312-21.

3. Slaughter M, Milano C, Rogers J, et al. N Engl J Med. 2009;361:2241-51.

Multivariate Predictors* of Death PostLVAD

Cowger J, Sundareswaran K, Rogers J, et al. ISHLT 2011.

Risk Stratification in HeartMate II PatientsComparison of Derivation and Validation Cohorts

Cowger J, Sundareswaran K, Rogers J, et al. ISHLT 2011.

Russell SD, Boyle A, Sun B, et al. ISHLT 2011.

Risk of Bleeding and Stroke in HeartMate II Outpatients

Russell SD, Boyle A, Sun B, et al. ISHLT 2011.

Preoperative Predictors of Bleeding

Hazards Ratio

0.0 0.5 1.0 1.5 2.0 2.5

Ischemic Etiology

Female

Albumin <=3.3

Age > 65

Univariate Correlates

Multivariate Risk Factors

P = 0.003

Russell SD, Boyle A, Sun B, et al. ISHLT 2011.

Female Gender—Only 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.

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

Impact of Infection on Stroke and Thrombosis

Driveline Exit SiteComparison 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.

Ledford ID, Miller DV, Mason NO, et al. ISHLT 2011.

Velour

N=16

Silicone

N=16

Mean Age (years) 55 51

Gender (M/F) 14/2 13/3

Indication (BTT/BTC/DT) 11/1/4 13/1/2

Velour

N=16

Silicone

N=16

Mean Age (years) 55 51

Gender (M/F) 14/2 13/3

Indication (BTT/BTC/DT) 11/1/4 13/1/2

Velour Versus Silicone Skin Interface

Ledford ID, Miller DV, Mason NO, et al. ISHLT 2011.

Histology

Velour exhibits more dermal inflammation and an irregular shaped stratum corneum.

Silicone is smooth and regular, and shows less inflammation.

Contemporary Destination Therapy Results

Park SJ. AHA Scientific Sessions, November 2010.

1. Slaughter M, Milano C, Rogers J, et al. N Engl J Med. 2009;361:2241-51 .

Contemporary Destination Therapy Results

Park SJ. AHA Scientific Sessions, November 2010.

The CAP results show a decrease in major adverse events.

Contemporary Destination Therapy Results

Park SJ. AHA Scientific Sessions, November 2010.

In Summary

Over 7,000 patients implanted with HeartMate II—long-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