Download Prognosis following MCS complications: implications for transplant

Survival following VAD
complications: implications for
transplant priority.
Todd Dardas, MD, MS
May 16, 2015
Disclosures
• Funding:
– American College of Cardiology/Sankyo
Daiichi Career Development Grant
Candidate survival
Wever-Pinzon, O, et. al.; Circulation 2012
Cumulative Mortality
Status 1A: Indexed by “first status”
Ventilator
Paracorporeal
Exception
VAD Complication
IABP/Dual Inotrope
Implanted VAD
0.4
0.3
0.2
0.1
0
0
15
30
45
60
Days from initial listing
Dardas T, et al J Am Coll Cardiol 2012
75
90
Status 1A exceptions
Meyer D, et. al. American Journal of Transplantation 2015; 15: 44–54
UNOS 1A(b) justifications
4%
15% 11%
Thrombosis
Infection
Device malfunction
18%
52%
Arrhythmias
Other
Unpublished data, UNOS registry
Tier Proposals
1. MCS with arrhythmias, non-dischargeable
VAD
2. Device malfunction, IABP
3. MCS (infection, thromboembolism, other
complications), LVAD 30 days, dual
inotropes
4. Inotrope w/o HD monitor, stable VAD
5. Multi-organ transplants
6. Remaining candidates
Meyer D, et. al. American Journal of Transplantation 2015; 15: 44–54
Guidance from OPTN
1.
2.
3.
4.
5.
6.
7.
8.
Aortic insufficiency
Hemolysis
Pump thrombosis
Pump-related local or systemic infection
Bleeding
Right heart failure
Recrudescent arrhythmias
Device malfunction
Meyer D, et. al. American Journal of Transplantation 2015; 15: 44–54
OPTN infection guidance
Pump-related or systemic infection with one of:
• Symptoms along driveline with leukocytosis
AND:
+ blood culture or
+ site culture
• Surgical debridement of the driveline AND + site
culture
• + Pump pocket culture
• Bacteremia with the same organism 4 weeks
following treatment
Meyer D, et. al. American Journal of Transplantation 2015; 15: 44–54;
http://www.uab.edu/medicine/intermacs/appendices-4-0/appendix-a-4-0
Research aims
• Determine mortality for complications
following CF VAD placement and compare
to non-MCS UNOS candidates.
• Evaluate whether subgroups within
complications have distinct risks useful for
ranking in the tier system.
Methods
• INTERMACS data for all primary implants of CF
devices implanted between 4/2012 and 3/2014
• DT and BTT included unless otherwise specified
• Complications:
– Multiple complications per time point
– First and isolated complication
– First infection of any number reported
• OPTN/UNOS registry data for patients without
MCS
Sample
Complications/
interval
0
1
2
3
4
5
6
7
Strategy
Other
BTT
BTE
DT
Total
5
162
53
12
1
1
0
0
151
2,607
808
118
24
9
1
0
186
4,320
1,385
207
44
9
4
4
299
6,011
2,052
342
87
17
3
0
641
13,100
4,298
679
156
36
8
4
Outcome
• Death during VAD support
• Censoring at transplant or recovery
Sample
•
•
•
•
•
4725 primary CF VAD implants
22,524 complications
2975 1st and isolated complications
No AE report n=641
Final cohort: n= 3616
Mortality following first complication
N = 3616
Freedom from major
complication
Major Complications: INTERMACS
1
0.8
0.6
0.4
0.2
0
0
365
730
1095
Days since implant
Kirklin J et. al., J Heart Lung Transplant 2013
1460
INTERMACS AEs
Hemolysis
Other SAE
Respiratory Failure
Neurological Dysfunction
Right Heart Failure
Hepatic Dysfunction
Venous Thromboembolism
Cardiac Arrhythmias
Device Malfunction
Hypertension
Wound Dehiscence
Pericardial Fluid Collection
Major Bleeding
Myocardial Infarction
Arterial Non-CNS embolism
Psychiatric Episode
Major Infection
Renal Dysfunction
Mortality following first AE reported
Adverse Event
Cumulative hazard at 90 days
following report
Std. err.
Renal Dysfunction
0.46
Neurological Dysfunction
0.45
0.09
Status 1A
0.10
Respiratory Failure
0.21
0.04
Device Malfunction
0.21
0.10
Right Heart Failure
0.17
0.04
Bleeding
0.15
0.02
Pericardial Drainage
0.12
0.05
Infection
0.12
Other SAE
0.10
Status 1B 0.02
0.02
Venous Thromboemb.
0.08
0.06
Hemolysis
0.07
0.05
Cardiac Arrhythmia
0.07
0.01
Psychiatric Episode
0.05
0.03
st
1
Infection AE
N= 4632
Adjusting for initial device strategy
Variables
Hazard ratio
P-value
AE infection
3.1
<0.0001
DT
Ref
BTT
0.58
<0.0001
BTE
0.67
<0.0001
Other strategy
0.97
0.92
Comparison to OPTN Status
Status 1A
Status 1B
Infection Definition
OPTN
One of:
• Symptoms along driveline
with leukocytosis AND:
• + blood culture
• + site culture
• Surgical debridement
AND + site culture
• + pump pocket culture
• Bacteremia 4 wks s/p
treatment
INTERMACS
• Localized non-device
• Driveline or pump pocket
• Sepsis
• Internal pump component
Meyer D, et. al. American Journal of Transplantation 2015; 15: 44–54;
http://www.uab.edu/medicine/intermacs/appendices-4-0/appendix-a-4-0
INTERMACS subgroups
All p-values <0.01 vs. No infection AE
Adjusted for initial device strategy
Variable
Hazard ratio
P-value
Infection AE
No Inf. AE reported
Ref
Localized, non-VAD
3.2
<0.0001
Perc. lead/pocket
1.9
<0.0001
Device component
8.5
0.003
Sepsis
3.8
<0.0001
DT
Ref
BTT
0.58
<0.0001
BTE
0.68
<0.0001
Other
0.95
0.86
Strategy
INTERMACS AEs & OPTN status
Driveline vs. No inf. AE p=0.13
All other p-values <0.01
Status 1A
Status 1B
Tier Proposals
1. MCS with arrhythmias, non-dischargeable
VAD
2. MCS sepsis OR pump pocket/internal device
infection OR localized infection, IABP
3. MCS driveline infection, thromboembolism,
LVAD 30 days, dual inotropes
4. Inotrope w/o HD monitor, stable VAD
Meyer D, et. al. American Journal of Transplantation 2015; 15: 44–54
Considerations
• How should continued eligibility be
weighted in priority decisions?
Changing device strategy
Teuteberg J, et. al. J Am Coll Cardiol HF 2013
BTT vs DT: 90-day mortality
AE type
BTT
DT
DT - BTT
Bleeding
0.12
0.18
0.06
Cardiac Arrhythmia
0.01
0.12
0.11
Infection
0.14
0.12
-0.02
Neurological Dysfunction
0.22
0.59
0.37
Other SAE
0.02
0.16
0.13
Psychiatric Episode
0.07
0.00
-0.07
Renal Dysfunction
0.24
0.55
0.30
Respiratory Failure
0.23
0.28
0.05
Right Heart Failure
0.08
0.23
0.15
Considerations
• How many subgroups should be identified
and analyzed?
Stratified complications?
Yes
• Infections
• Right heart
failure
• Bleeding
• Hemolysis
Maybe
• Device
malfunction
No
• Ventricular
arrhythmias
• Thrombosis
• Aortic regurg.
Conclusions
Subgroups of patients within broad
complication types may warrant further
characterization and stratification by
INTERMACS definitions
• Susan Meyer
• Frank Pagani
• Kent Shively
Mortality following first AE reported
Cumulative hazard at 90
days following report
Std. err.
At risk
Deaths
Renal Dysfunction
0.46
0.09
53
30
Neurological Dysfunction
0.45
0.10
56
24
Respiratory Failure
0.21
0.04
95
22
Device Malfunction
0.21
0.10
38
5
Right Heart Failure
0.17
0.04
170
29
Bleeding
0.15
0.02
367
55
Pericardial Drainage
0.12
0.05
46
6
Infection
0.12
0.02
238
25
Other SAE
0.10
0.02
224
22
Venous Thromboemb.
0.08
0.06
23
2
Hemolysis
0.07
0.05
33
2
Cardiac Arrhythmia
0.07
0.01
291
22
Psychiatric Episode
0.05
0.03
41
2
Adverse Event
Risk of first AE relative to
Status 1A/B
Status 1A
Status 1B