Clinical Review AbioCor® Implantable Replacement Heart H Julie Swain M.D. Cardiovascular Surgeon Ileana Piña M.D. Heart Failure Cardiologist DRAFT

2 Multicenter Single-Arm Feasibility Trial # 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 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 # Pts *4 solely because of age

9 Age at Implant # pts Patient Age

10 Right-sided Pressures (mmHg) CVP PAP mean 9.6 mmHg mean 34.5 mmHg CI 2.1 L/min/M 2

11 14 Patients 6 patients 131, 128, 290, 105, 146, 132 Death <60 d 2 Op Death 2 Discharged 1 No Benefit ???? Probable Benefit died <90 days 3

12 Days of Support Median 112 days

13 Serious Adverse Events 6 pts >=20 AE’s # SAE<60d #’s above columns are days of survival

14 Cause of Death

15 Serious Adverse Events (out of 12 pts who survived op) # pts with SAE 19 # 4#4# 50 # 34 # 8#8# # = events

16 Bleeding # bleeds per pt Patient # * Survived <60 days *** *

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)