1. Total Artificial Heart (TAH): Survival Outcomes, Risk Factors,
Adverse Events
March 12, 2016
P = presentation, M=manuscript,
Authors: F. Arabia1, I. Gregoric2, V. Kasirajan3, J. D. Moriguchi4, D. C. Naftel5, S. L. Myers5, J. K. Kirklin5.
1Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, CA,
2University of Texas Health Science Center Houston, Houston, TX,
3Virginia Commonwealth University Medical Center, Richmond, VA, 4Cedars-Sinai Medical Center, Los Angeles, CA,
5University of Alabama at Birmingham, Birmingham, AL,
P/M

2. Purpose Outcomes: P Overall (comparison of TAH with LVAD recipients)
Implants June 2006 – March 2015: TAH – Survival Outcomes
Purpose
Outcomes:
Overall (comparison of TAH with LVAD recipients)
Patient selection across time by Era and Levels
Era
Risk factors
Implant volume P

3. TAH indications Dilated (idiopathic) CM Adult and Pediatric Congenital
Ischemic Cardiomyopathy
Valvular Cardiomyopathy
Hypertrophic (obstructive) CM
Hypertrophic (non-obstructive)
Restrictive Cardiomyopathy
Peripartum Cardiomyopathy
Ethylic Cardiomyopathy
Acute Myocardial Infarction
Post-Cardiopulmonary Bypass
Myocarditis
Acute Rejection – Donor Heart
Chronic Rejection – Donor Heart
Sarcoidosis
Amyloidosis
Malignant Arrhythmias
Adult and Pediatric Congenital
Ventricular Septal Defect
Ventricular Thrombus
LVAD/BiVAD Device Failure
Cardiac Tumors
Scleroderma
Mixed Cardiomyopathy
Chagas Disease
Non-ischemic Cardiomyopathy
Postcardiotomy Cardiogenic Shock
Endocarditis
Viral Cardiomyopathy
Familial Cardiomyopathy
Acute Type A Aortic Root Dissection

4. P/M (txt) Cohort Inclusion/Exclusion Criteria Inclusions: Exclusions:
Implants June 2006 – March 2015: TAH – Survival Outcomes
Cohort Inclusion/Exclusion Criteria
Inclusions: Exclusions:
Syncardia TAH-t devices ■ Pediatrics ( < 19 years at implant)
Adults (age ≥ 19 years at implant) ■ No Informed consent
Implant dates: June 1, 2006 – March 31, 2015
Follow-up date: March 31, 2015
Study Group
Patients: patients / 362 devices
Patient years:
Total deaths with a device in place: 111
Total heart transplants: 210
Mean Follow-up (Months): 4.98
Contributing Institutions: 44
P/M (txt)

5. Cohort All adult patients implanted From June 2006 through March 2015
Implants June 2006 – March 2015: Bi-VAD – Survival Outcomes
Cohort
All adult patients implanted
From June 2006 through March 2015
N=15194 patients
16467implants
RVAD
N=298 (2%)
341 implants
LVAD
N= (90%)
14896 implants
Bi-VAD
N= 863 (6%)
868 implants
TAH
N= 359 (2%)
3 patients have a 2nd TAH implanted
(n=362 TAH implants)
Discuss n=362 patients in manuscript.
Comparison Group
Inclusion Criteria:
Primary CFLVAD
BTT: Listed
N=3473
Compare

6. “HOLD on to this Slide”
Excerpt from INTERMACS Quarterly Report

7. Implants June 2006 – March 2015: TAH – Survival Outcomes
Device Strategy at time of implant n ERA ERA ERA 3
Bridge to Transplant (patient currently listed for transplant) (62.4%) (73.5%) (72.6%) (49.1%)
Possible Bridge to Transplant - Likely to be eligible (30.9%) (21.7%) (24.8%) (40.2%)
Possible Bridge to Transplant - Moderate likelihood of becoming eligible (3.1%) (2.4%) (0.9%) (5.0%)
Possible Bridge to Transplant - Unlikely to become eligible (1.7%) (2.4%) (0.9%) (1.9%)
Destination Therapy (patient definitely not eligible for transplant) (0.8%) (0%) (0%) (1.9%)
Rescue Therapy (0.8%) (0%) (0.9%) (1.3%)
Other, specify (0.3%) (0%) (0%) (0.6%)
Total (100%) (100%) 117 (100%) (100%)
Mar 2015
Intermacs Patient Profile Level at time of implant n Era 1 Era 2 Era 3
1 Critical Cardiogenic Shock (39.0%) (45.8%) (31.6%) (40.9%)
2 Progressive Decline (37.6%) (42.2%) (43.6%) (30.8%)
3 Stable but Inotrope Dependent (10.3%) (3.6%) (12.0%) (12.6%)
4 Resting Symptoms (5.9%) (3.6%) (6.8%) (6.3%)
5 Exertion Intolerant (1.4%) (1.2%) (0%) (2.5%)
7 Advanced NYHA Class (0.8%) (1.2%) (1.7%) (0%)
Unspecified (5.0%) (2.4%) (4.3%) (6.9%)
Total (100%) (100%) (100%) (100%)

8. Implants June 2006 – March 2015: TAH – Survival Outcomes
Comparison Group
Inclusion Criteria:
Primary CFLVAD
BTT: Listed
N=3473
Mar 2015
Device Strategy at time of implant n ERA ERA ERA 3
Bridge to Transplant (patient currently listed for transplant) (100%) (19.4%) (36.3) (44.3%)
Mar 2015
Intermacs Patient Profile Level at time of implant n Era Era 2 Era 3
1 Critical Cardiogenic Shock (12.5%) (15.2%) (13.3%) (10.6%)
2 Progressive Decline (42.3%) (48.1%) (45.5%) (37.1%)
3 Stable but Inotrope Dependent (28.5%) (22.2%) (24.6%) (34.4%)
4 Resting Symptoms (11.5%) (10.0%) (12.3%) (11.4%)
5 Exertion Intolerant (2.3%) (1.8%) (2.2%) (2.7%)
6 Exertion Limited (0.8%) (1.2%) (1.0%) (0.3%)
7 Advanced NYHA Class (0.8%) (1.6%) (0.8%) (0.5%)
Unspecified (1.4%) (0%) (0.2%) (3.0%)
Total (100%) (100%) (100%) (100%)

9. Implants June 2006 – March 2015: TAH – Survival Outcomes
Comparison of TAH, n=359 and CFLVAD BTT: Listed, n=3473
% Patient Profile Levels

10. Implants June 2006 – March 2015: TAH – Survival Outcomes
Comparison of TAH, n=359 and CFLVAD BTT: Listed, n=3473
Factors Associated with Right Heart Failure at time of implant

11. Implants June 2006 – March 2015: TAH – Survival Outcomes
Comparison of TAH, n=359 and CFLVAD BTT: Listed, n=3473
Patient Illness characteristics at time of implant
TAH CFLVAD/BTT Listed
n= n=3473
Pre-implant Characteristics Mean±SD Mean±SD p-value
Hemoglobin (mg/dL) ± ± 2.1 < .0001
LVEDD (cm) ± ± 1.1 < .0001
Platelet (K/uL) ± ± < .0001
Pre-albumin (mg/dL) ± ± 7.6 < .0001
Right Atrial Pressure (mmHg) ± ± 7.9 < .0001

12. Implants June 2006 – March 2015: TAH – Survival Outcomes
Comparison of TAH, n=359 and CFLVAD BTT: Listed, n=3473
Primary Diagnoses
TAH CFLVAD/BTT Listed
Primary Diagnosis n= n=3473
Cancer (0.5%) (0.1%)
Ischemic Cardiomyopathy/Coronary Artery Disease (30.1%) (38.3%)
Dilated Myopathy: Post partum (0.8%) (1.7%)
Dilated Myopathy: Viral (2.8%) (3.0%)
Dilated Myopathy: All others (48.2%) (52.6%)
Hypertrophic Myopathy (3.1%) (1.3%)
Restrictive Myopathy (6.1%) (0.9%)
Valvular Heart Disease (3.9%) (0.9%)
Congenital Heart Disease (2.8%) (0.8%)
Not specified (1.7%) (0.4%)
Totals (100%) (100%)

13. Implants June 2006 – March 2015: TAH – Survival Outcomes
Comparison of TAH, n=359 and CFLVAD BTT: Listed, n=3473
Primary Cause of Death
CFLVAD/BTT Listed, n= TAH (n=359)
Primary Cause of Death Deaths = 515, % Deaths=111, %
Nervous System: Neurological Dysfunction
Multisystem Organ Failure (MSOF)
Withdrawal of Support, specify
Major Infection
Circulatory: Other, Specify
Other, specify
Circulatory: Sudden Unexplained Death
Circulatory: Right Heart Failure
Circulatory: Cardiac Arrhythmia
Circulatory: CHF
Respiratory: Respiratory Failure
Device Malfunction
Circulatory: Major Bleeding
Circulatory: End Stage Cardiomyopathy
Digestive: Hepatic Dysfunction
Digestive: Renal Dysfunction
Other: Cancer
Circulatory: Ischemic Cardiomyopathy
Circulatory: Arterial Non-CNS Thromboembolism
Respiratory: Pulmonary: Other, specify
Other: Trauma/accident, specify
Circulatory: Myocardial Infarction
Not specified
Digestive: GI Disorder
Digestive: Fluid/Electrolyte Disorder
Circulatory: Hemolysis
Circulatory: Heart Disease
Hemotalogical
Cardiovascular, Other
Totals

14. % Survival Months post Implant
Implants June 2006 – March 2015: TAH – Survival Outcomes
TAH Implants: June 2006 – March 2015, n=359
N=359, deaths=111
% Survival at:
3 months 76%
6 months 65%
12 months 56%
24 months 41%
% Survival
Event: Death (censored at transplant or device exchange)
Months post Implant

15. % Survival Months post Implant
Implants June 2006 – March 2015: TAH – Survival Outcomes
Primary CFLVAD-BTT:Listed implants: June 2006 – March 2015, n=3473
N=3473, deaths=515
% Survival at:
3 months 94%
6 months 92%
12 months 87%
24 months 80%
% Survival
Event: Death (censored at transplant or device exchange)
Months post Implant

16. TAH Implants: June 2006 – March 2015, n=359
Implants June 2006 – March 2015: TAH – Survival Outcomes
TAH Implants: June 2006 – March 2015, n=359
BY implant Era
% Survival post implant at:
Era n deaths mths mths 12 mths
% 65% 54%
% 70% 56%
% 62% 56%
P(overall) = .27
Era 1 vs Era 2: p=.80
Era 1 vs Era 3: p=.25
Era 2 vs Era 3: p=.13
% Survival
Event: Death (censored at transplant or device exchange)
Months post Implant

17. P?/M? % Survival Months post Implant
Implants June 2006 – March 2015: TAH – Survival Outcomes
TAH Implants: June 2006 – March 2015, n=359
BY implant volume by Year*
% Survival post implant at:
Volume/Yr n deaths 3 mths mths mths
1-10 implants % % %
≥ % % 80%
P = .0001
% Survival
P?/M?
Review this depiction with JKK/FP/DCN
Event: Death (censored at transplant or device exchange)
Months post Implant
* Volume is calculated by year (average implants per hospital per year from enrollment)

18. Proportion of Patients
Implants June 2006 – March 2015: TAH – Survival Outcomes
N=3473, Primary CFLVAD BTT: listed for transplant
Outcome % at: 6 months
Alive (device in place) %
Transplanted %
Dead %
Recovery 1%
Transplanted
Proportion of Patients
Alive (on a device)
Dead
Recovery
Months after Implant

19. Proportion of Patients
Implants June 2006 – March 2015: TAH – Survival Outcomes
N=359 TAH
Outcome % at: 6 months
Alive (device in place) %
Transplanted %
Dead %
Transplanted
Proportion of Patients
Dead
Alive (on a device)
Months after Implant

20. Proportion of Patients
Implants June 2006 – March 2015: TAH – Survival Outcomes
N=3473, Primary CFLVAD BTT: listed for transplant
N=359, TAH
Outcome % at: months
Outcome % at: months
Alive (device in place) %
Transplanted %
Dead %
Recovery %
Alive (device in place) %
Transplanted %
Dead %
Months after Implant
Proportion of Patients
Transplanted
Dead
Alive (on a device)
Recovery

21. Proportion of Patients
Implants June 2006 – March 2015: TAH – Survival Outcomes
Months after Implant
Proportion of Patients
Transplanted
Dead
Alive (on a device)
TAH: Center Volume (1-10 ), n= 245
N=43 centers
Outcome % at: 6 months
Alive (device in place) %
Transplanted %
Dead %

22. Proportion of Patients
Implants June 2006 – March 2015: TAH – Survival Outcomes
Months after Implant
Transplanted
Dead
Alive (on a device)
TAH: Center Volume (11+ ), n= 114
N=4 centers
Outcome % at: 6 months
Alive (device in place) %
Transplanted %
Dead %
Proportion of Patients

23. Proportion of Patients
Implants June 2006 – March 2015: TAH – Survival Outcomes
Center Volume (1-10 ), n= 245
N=43 centers
Center Volume (11+), n= 114
N=4 centers
Outcome % at: 6 months
Outcome % at: 6 months
Alive (device in place) %
Transplanted %
Dead %
Alive (device in place) %
Transplanted %
Dead %
Months after Implant
Proportion of Patients
Transplanted
Dead
Alive (on a device)
Months after Implant
Transplanted
Dead
Alive (on a device)

24. TO BE UPDATED Implants June 2006 – March 2015: TAH – Survival Outcomes
TAH, n=362
BTT Listed (Not TAH), n= 4596
Events Patients
Adverse Events n % n %
Arterial Non-CNS Thromboembolism
Bleeding
Cardiac Arrhythmia
Device Malfunction
Hemolysis (as of 6/1/2014)
Hepatic Dysfunction
Hypertension (as of 6/1/2014)
Infection
Myocardial Infarction
Neurological Dysfunction
Other SAE
Pericardial Drainage
Psychiatric Episode
Renal Dysfunction
Respiratory Failure
Right Heart Failure (as of 6/1/2014)
Venous Thromboembolism
Wound Dehiscence
Totals
Events Patients
Adverse Events n % n %
Arterial Non-CNS Thromboembolism
Bleeding
Cardiac Arrhythmia
Device Malfunction
Hemolysis (as of 6/1/2014)
Hepatic Dysfunction
Hypertension (as of 6/1/2014)
Infection
Myocardial Infarction
Neurological Dysfunction
Other SAE
Pericardial Drainage
Psychiatric Episode
Renal Dysfunction
Respiratory Failure
Right Heart Failure (as of 6/1/2014)
Venous Thromboembolism
Wound Dehiscence
Totals
Note: This table does not consider patient exposure time.

25. TO BE UPDATED Implants June 2006 – March 2015: TAH – Survival Outcomes
Early hazard
Risk Factors for Death
Hazard Ratio
p-value
Age (older)
1.34**
.006
Pre-implant Albumin (lower)
1.62*
.001
Pre-implant Bilirubin (higher)
1.07*
.0002
Pre-implant Right Atrial Pressure (higher)
1.05*
.002
Concomitant Surgery
1.61
.03
History of Cancer
7.19
.01
History of Valve Surgery
2.77
< .0001
** 50-60yrs of age was used
* For 1 unit increase

26. TAH Trials TAH 70 cc is FDA approved as BTT
In a trial for DT
TAH 50 cc in a Pediatric and Adult trials
for BTT

27. Conclusion More details at ISHLT
Centers familiar with the technology have good outcomes with the sickest patients.