Clinical ReviewClinical Review AbioCor® Implantable Replacement HeartAbioCor® Implantable Replacement Heart

H040006H040006

Julie Swain M.D.

Cardiovascular Surgeon

Ileana Piña M.D.

Heart Failure Cardiologist

DRAFT

2

Multicenter Single-Arm Feasibility Trial

0

2

4

6

8

Louisville THI Hahn UCLA

# pts per center

3

Indication For Use

The AbioCor is designed to serve a subset of transplant-ineligible end-

stage heart failure patients with biventricular failure not treatable by drugs, pacing devices, or approved

cardiac assist devices.

4

Approved HUD Inclusion

Heart failure patients who are on optimal medical therapy and meet all of the following:

• < 75 years old • not transplant candidates • estimated 30-day survival of <30%• in biventricular failure not supportable by an

implantable left ventricular assist device (LVAD) alone

• multiple inotropes OR those not weanable from a temporary BIVAD

5

Proposed Additional Inclusions(page 69, Post Approval Study)

The Sponsor claims patients with contraindications to LVAD placement would be included in the indications for the device:

• refractory arrhythmias• aortic regurgitation• prosthetic aortic valve• “Massive MI”: patients who are “…at risk of inlet cannula

dislodgement due to fragility of the infarcted ventricular tissue.”• Mural thrombus in the ventricles• Ventricular septal rupture• Transplant rejection

** It should be noted that none of the 14 patients in the feasibility study had any of the above conditions

6

Post Hoc Proposed Controls

• REMATCH control pts– Changes in medical care – Different patients (LV failure, gatekeeper, OMM)– Subset analysis (61 pts, many withdrew from care)

• AMI-SHOCK Index– No pts had acute MI

• AbioScore– 42 prospective and retrospective records– ICD-9 codes for heart failure and CPT and NDC

codes for inadequate hemodynamics – age 20 - 79 years – 26% were female – 38% were on LVAD’s for bridge-to-transplant

7

AbioScore

• used to estimate survival for inclusion of > 70% mortality in 30 days

• 27 clinical items (renal function, NYHA class, etc.)

• components include items normally used by clinicians

• validation unproven• No known predictive system• Very ill, malnourished patients

8

Reasons for Non-transplant Candidacy

0

2

4

6

8

10

12

14

AGE* PHTN DM CRI COPD CA End-organdysf

# Pts

*4 solely because of age

9

Age at Implant

0

1

2

3

4

5

50-54 55-59 60-64 65-69 70-74 75-79

# pts

Patient Age

10

Right-sided Pressures (mmHg)

0

1

2

3

4

5

0-5 6-10 11-15 16-20 21-250

1

2

3

4

5

<20 21-26 26-30 31-36 36-40 41-46

CVP PAP

mean 9.6 mmHg mean 34.5 mmHg

CI 2.1L/min/M2

11

14 Patients

6 patients

131, 128, 290, 105, 146, 132

Death <60 d

2

Op Death

2

Discharged1

No Benefit ???? Probable Benefit

died <90 days

3

12

151

512

142

56

293

1 0

100

53

109115

86

146 164

0

600

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Days of Support

Median 112 days

13

Serious Adverse Events

0

10

20

30

40

50

1 2 3 4 5 6 7 8 9 10 11 12 13 14

Patient #

# o

f AE

's

6 pts >=20 AE’s

# SAE<60d181

512

293

10

10053

109

11586

146

164142

56

#’s above columns are days of survival

14

Cause of Death

0

1

2

3

4

5

6

7

CVA Operative Pump MOF

15

Serious Adverse Events(out of 12 pts who survived op)

0

4

8

12

Stroke TIA Bleed Infection Renal Fail

# ptswith SAE

19#

4#

50# 34#

8#

# = events

16

Bleeding

# bleedsper pt

Patient #* Survived <60 days

0

5

10

15

1 2 3 4 5 6 7 8 9 10 11 12 13 14* * **

17

Functional Measurements

• QOL– No validated measures– Occasional notes on walking or taking excursions

out of the hospital• No functional measurements (6 min walk or MVO2

postop)

• Difficult to understand functional level and to balance high mortality and SAE’s

18

Summary of Clinical Data

• Implanted in patients who, in the judgment of the investigator, appeared not to have any other options to prolong survival

• Provided physiological cardiac outputs and pressures

• Some had improvement and/or stabilization of end-organ function

• Some patients could sit, stand, walk, and take excursions outside of the hospital

19

Conclusion from Clinical Data

The risk/benefit determination for this device is difficult due to the lack of validated QOL and functional data

20

Post Market Study Inclusion (page 69, Post Approval Study)

The Sponsor claims patients with contraindications to LVAD placement would be included in the indications for the device:

• refractory arrhythmias• aortic regurgitation• prosthetic aortic valve• “Massive MI”: patients who are “…at risk of inlet cannula

dislodgement due to fragility of the infarcted ventricular tissue.”• Mural thrombus in the ventricles• Ventricular septal rupture• Transplant rejection

It should be noted that none of the 14 patients in the feasibility study had any of the above conditions

21

Post Market Study-Items for Discussion

• What should be measured?– Pre-implant status (demographics, hemodynamics,

reason not Tx candidate)– Survival– Major adverse events (bleeding, stroke, renal

failure, hepatic failure, infection)– Validated Function/QOL measurements– Rankin score

• For how long?– To death or device removal

• In how many patients?– 20 (no statistics possible)