Title: What have we learned? What is next?
1Research Topics in INTERMACS
What have we learned? What is next? Panel B
Functional Capacity, Quality of Life and
Outcomes H. Functional Capacity
I. Neurocognitive Assessment J. Quality of
Life K. Terminal Events and Risk Factors
L. Discussion
INTERMACS Annual Meeting March 2012
2Research Topics in INTERMACS
Functional Capacity JoAnn Lindenfeld So
far we have learned little about functional
capacity
INTERMACS Annual Meeting March 2012
3June 2006 Sept 2008 Adult Prospective Implants
- Pt Seen in 6 Minute Walk
VO2 Max R at Peak - Follow-up Hospital/Clinic n
n n
- Pre-Implant 957 30 3.1 58 6.1
28 2.9 - 3 Month 426 79 18.5 14 3.3
12 2.8 - 6 Month 202 38 18.8 10 5.0 8
4.0 - 12 Month 71 16 22.5 1 1.4 0
- 18 Month 16 3 18.8 0 - 0
- - 24 Month 3 1 33.3 0 - 0
- - Total 1675
167 10.0 83 5.0 48 2.9
INTERMACS Annual Meeting March 2012
4Is Frailty Predictive of Hospital Complications,
Duration and Success of Rehabilitation, and
Ultimate Quality of Life?
INTERMACS Annual Meeting March 2012
5Frailty Increased Vulnerability to Stress
LVAD-Responsive Frailty
LVAD-Independent Frailty
Systolic and diastolic dysfunction
Inflammation Anorexia Hypoxia Polypharmacy
AGING COPD / lung disease Cancer Diabetes Osteopor
osis Peripheral vascular disease Cirrhosis Neurolo
gic disease
?PCWP and CVP ?Cardiac output
Sarcopenia Malnutrition Cognitive
deficits Injurious falls
Impaired Health Status Disability Loss of
ADLs Institutionalization
Post-Operative Complications Prolonged LOS Need
for ICU care
Reduced Survival
INTERMACS Annual Meeting March 2012
Flint et al Circ Heart Failure In Press
6LVAD-Independent Frailty
LVAD-Responsive Frailty
Patient A
Patient C
Patient B
Pre-LVAD Frailty
Post-LVAD Frailty
INTERMACS Annual Meeting March 2012
Unfavorable Outcome High risk for premature
death and complications with failure to improve
functional status
Intermediate Outcome Moderate risk for premature
death and complications with some persistent
functional limitation
Favorable Outcome Lower risk for premature death
or complications, with marked improvement in
functional status
Flint et al Circ Heart Failure In Press
7Research Topics in INTERMACS
Functional Capacity
- Can we improve collection of functional capacity
data? - How much does functional capacity improve in LVAD
recipients? - What limits improvements in functional capacity?
- Can we measure gait speed in a high percentage of
patients? - Does gait speed add to the ability to predict
mortality? - Does gait speed add to the ability to predict
post-operative complications and length of stay? - Can we measure frailty using gait speed alone or
combined with other parameters (weight loss,
albumin, anemia, etc) in the database? - Can we predict reversible frailty?
INTERMACS Annual Meeting March 2012
8Research Topics in INTERMACS
Functional Capacity
- Is gait speed predictive in those lt 60 years?
- Do any of these measures of functional capacity
predict QoL? - What are the predictors of return to good
functional capacity? - What are the best measures of frailty in
end-stage heart failure? - How do we determine if frailty is reversible?
INTERMACS Annual Meeting March 2012
9Research Topics in INTERMACS
Neurocognitive Assessment K Grady
INTERMACS Annual Meeting March 2012
10Research Topics in INTERMACS
- What have we learned?
- There are challenges to data collection for
assessing neurocognitive function via the Trail
Making Part B - e.g., patient and coordinator burden, as it is
directly administered to the patient by an
examiner - Data collection for the Trail Making Part B has
been poor - There are no INTERMACS abstracts/publications
to date - What is next?
- Consider adding an expert (i.e., champion) in
neurocognitive assessment to the INTERMACS QOL
Committee and examine next steps to enhance data
collection. -
-
INTERMACS Annual Meeting March 2012
11Research Topics in INTERMACS
- Neurocognitive Assessment
- The biggest challenges with neurocognitive
assessment in INTERMACS are - Collecting the Data
- Making neurocognitive assessment a part of MCSD
standard of care -
INTERMACS Annual Meeting March 2012
12Research Topics in INTERMACS
- Neurocognitive Assessment
- What are the Next Steps?
- Improving Patient Outcomes
- Device Evaluation and Development
-
INTERMACS Annual Meeting March 2012
13Research Topics in INTERMACS
Quality of Life K Grady
INTERMACS Annual Meeting March 2012
14 QOL Instrument
EQ-5D Health Questionnaire English version for
the US
Mobility I have no problems in walking about q I
have some problems in walking about q I am
confined to bed q Self-Care I have no problems
with self-care q I have some problems washing or
dressing myself q I am unable to wash or dress
myself q Usual Activities (e.g. work, study,
housework, family or leisure activities) I have
no problems with performing my usual activities
q I have some problems with performing my usual
activities q I am unable to perform my usual
activities q Pain/Discomfort I have no pain or
discomfort q I have moderate pain or discomfort
q I have extreme pain or discomfort
q Anxiety/Depression I am not anxious or
depressed q I am moderately anxious or depressed
q I am extremely anxious or depressed q
INTERMACS Annual Meeting March 2012
15N878 adult MCS patients, primary implant
(pulsatile and continuous flow LVAD, Bi-VAD,
TAH 6/06-9/08) Profile 1 36, Profile 2
38
Pre and Post Implant EQ-5D (primary implant,
prospective, adult) Visual Analogue Scale (VAS)
Across Time (mean SD)
Best
(N39)
(N96)
(N183)
EQ-5D VAS
(N312)
P (pre vs 3 mo) lt0.001
Worst
INTERMACS Annual Meeting March 2012
Pre-Implant
3 month
6 month
12 month
Months Post Implant
16CONCLUSIONS
- Quality of life was poor before MCS implant and
improved significantly from before to after MCS
implant. - The frequency of problems in the areas of
mobility, self-care, usual activities, and
anxiety / depression decreased from before to
after MCSD implantation. - The frequency of pain / discomfort was similar
before and after MCSD implantation. - Some problems were reported more frequently
than extreme problems in all QOL domains after
MCSD implant. - Differences in QOL before and after MCSD
implantation were identified by gender and age. -
INTERMACS Annual Meeting March 2012
17PURPOSE
- To examine differences in HRQOL scores, among
INTERMACS profiles, both before and at 3, 6, and
12 months after implant - To examine patterns of HRQOL scores from before
MCS implant through 1 year after implant, by
INTERMACS patient profiles - Definition Health-related Quality of Life
- The functional effect of an illness and its
consequent therapy upon a patient as perceived by
the patient. - HRQOL Domains mobility, self-care, usual
activities, anxiety / depression, pain /
discomfort, perception of overall health
status - Schipper H, in Spilker B (ed) Quality of Life
Assessment in Clinical Trials (1990)
INTERMACS Annual Meeting March 2012
18Implants June 2006 March 2010, Follow-up
March 2011
Primary continuous flow LVAD, n1559
Patient Profile Levels (Pre-Implant)
Status at 1 year 1 2
3 4 5-7 Total
Post implant (n 262) (n695)
(n330) (n175) (n97) (n1559) Death
21 16 9 14
12 15 Transplant 36 32
37 33 29
34 Recovery 2 1 0
0 1 1 Alive (on
device) 41 51 54
53 58 50 Total 100
100 100 100 100
100 Available for quality of life assessment
at 1 year post implant
INTERMACS Annual Meeting March 2012
19 June 2006 March 2011 HRQOL by Patient
Profiles (All patients with opportunity for 1
year follow-up (n1559)
Alive (device in place) 100
Alive (device in place) 83
Alive (device in place) 69
Alive (device in place) 50
Proportion of Patients
Txpl 34
Txpl 19
Dead 9
Dead 11
Txpl 8
Dead 15
Rec 1
Rec 1
Rec 0
Txpl 0
INTERMACS Annual Meeting March 2012
Dead 0
Rec 0
Pre-implant
Months Post Implant
20EQ-5D Visual Analog Scale
Primary Continuous Flow LVADs, n2807
Best Health
Mean VAS
Worst Health
INTERMACS Annual Meeting March 2012
INTERMACS Patient Profile Levels
21EQ-5D Mobility, Any Problems
Primary Continuous Flow LVADs, n2807
Patients with Any Mobility Problems
INTERMACS Annual Meeting March 2012
INTERMACS Patient Profile Levels
22EQ-5D Self Care, Any Problems
Primary Continuous Flow LVADs, n2807
Patients with Any Self Care Problems
INTERMACS Annual Meeting March 2012
INTERMACS Patient Profile Levels
23Predictors of better QOL at 6 months after
continuous flow MCS
- Since the mean VAS score improved dramatically
from pre-implant to 6 months post implant (42 vs
74, plt 0.0001), the most important factor for
increased overall health status was MCS implant.
INTERMACS Annual Meeting March 2012
24Research Topics in INTERMACS
- Quality of Life
- What are the Next Steps?
- Improving Patient Outcomes
- Device Evaluation and Development
-
INTERMACS Annual Meeting March 2012
25What is next?
- Identify preoperative psychosocial stress
factors (e.g., poor QOL, social isolation,
education) as predictors of outcomes in women and
men after primary continuous flow LVAD implant. - Longitudinal change in HRQOL (EQ-5D re 5
dimensions VAS and KCCQ) from before to 12, 24,
and 36 months after MCS - - Overall
- - By demographic characteristics (i.e., age,
gender) - - By pre implant INTERMACS profile
- - By implant strategy (i.e., DT, BTT, BTR)
- Risk factors for poor HRQOL outcomes at 12, 24
and 36 months after continuous flow LVAD implant - DVs EQ-5D VAS and 5 dimensions, EQ-5D index
- KCCQ (including domains and summary scores)
- IVs Demographic factors (e.g., age, gender,
education) - Clinical factors
- pre (e.g., INTERMACS profiles,
co-morbidities) - post (e.g., adverse events)
- Other risk factors (e.g., stress, coping,
self-efficacy) - Analyses of specific domains of interest (e.g.,
social support, self-efficacy, symptom frequency
/ burden, etc.)
INTERMACS Annual Meeting March 2012
26Research Topics in INTERMACS
Terminal Events and Risk Factors D Naftel
INTERMACS Annual Meeting March 2012
27INTERMACS Survival After LVAD Implant
Continuous Flow Intracorporeal Device n896,
deaths112
Pulsatile Flow Intracorporeal Device, n470,
deaths140
Pulsatile Flow Paracorporeal Device, n74,
deaths28
Survival
p (overall) lt 0.0001
Event Death (censored at transplant or recovery)
INTERMACS Annual Meeting March 2012
Months after Device Implant
28INTERMACS Survival After LVAD Implant
Survival after Primary LVAD (Pulsatile and
Continuous Flow Devices)
Survival
Months Survival 1 mo 94
3 mo 89 6 mo 84 12
mo 76 24 mo 63
Survival
Deaths / Month (Hazard)
Hazard
Event Death (censored at transplant or recovery)
INTERMACS Annual Meeting March 2012
Months after Device Implant
29 INTERMACS Survival after LVAD Implant Adult
Primary Pulsatile Intracorporeal Flow LVAD Pumps
(n 470)
By Age Groups
lt 30 years, n27, deaths5
30 65 years, n377, deaths100
Survival
65 years, n66, deaths35
P (overall) lt.0001
Event Death (censored at transplant or recovery)
INTERMACS Annual Meeting March 2012
Months after Device Implant
30 INTERMACS Survival after LVAD Implant Adult
Primary Continuous Intracorporeal Flow LVAD
Pumps n 896
By Age Groups
lt 30 years, n61, deaths2
30 65 years, n691, deaths81
65 years, n144, deaths29
Survival
P (overall) .002
Event Death (censored at transplant or recovery)
INTERMACS Annual Meeting March 2012
Months after Device Implant
31INTERMACS Survival After LVAD Implant
Adult Primary Intracorporeal LVADs (n1366)
Early Constant Risk
Factor Hazard ratio p-value
Hazard ratio p-value Female 1.71
0.04 --- --- Age (older)
1.141 0.006 1.131
0.008 Previous CABG 2.71 lt0.0001 ---
--- Previous Valve Surgery 1.99 0.01
--- --- Dialysis (current) 2.45
0.01 --- --- INR (higher) 1.492
0.003 --- --- Ascites 2.32
0.002 --- --- RVEF Severe ---
--- 2.33 0.04 RA Pressure
(higher) 1.523 0.02
--- --- Cardiogenic Shock
1.98 0.003 ---
--- BTC or DT --- ---
3.00 0.01 Pulsatile
pump --- ---
3.02 0.001
1 Hazard ratio denotes the increased risk with a
20 year increase in age 2 Hazard ratio denotes
the increased risk with a 1.0 increase in INR 3
Hazard ratio denotes the increased risk of a
10-unit increase in RA pressure
INTERMACS Annual Meeting March 2012
32 INTERMACS Survival after LVAD Implant Adult
Primary Intracorporeal LVADs n 1366
Continuous Intracorporeal
Pulsatile Intracorporeal
Average Patient
Predicted Survival
Risk Factor
Unadjusted
Adjusted Constant Phase Hazard ratio
p-value Hazard ratio
p-value Pulsatile pump 12.54
lt0.0001 3.02 0.001
INTERMACS Annual Meeting March 2012
Months after Device Implant
33Risk Factors for Death after Implant
Table 9
June 2006 March 2009 Primary LVAD n1092
Early
Constant Risk Factor
Hazard ratio p-value Hazard ratio
p-value Age (older) 2.421 lt.0001
1.551 .0005 Bilirubin (higher)
1.412 .0002 --- --- RA
Pressure (higher) 2.083 .0009
--- --- Cardiogenic Shock
1.97 .02 --- --- BTC or
DT --- --- 1.80
.02 Pulsatile pump
--- --- 2.74 .001
1 Hazard ratio denotes the increased risk from
age 60 to 70 years 2 Hazard ratio denotes the
increased risk of a 2-unit increase in
bilirubin 3 Hazard ratio denotes the increased
risk of a 10-unit increase in RA pressure LVAD,
left ventricular assist device BTT, bridge to
transplant BTC, bridge to candidacy DT,
destination therapy RA, right arterial
INTERMACS Annual Meeting March 2012
34Research Topics in INTERMACS
- Terminal Events and Risk Factors
- What are the Next Steps?
- Improving Patient Outcomes
- Device Evaluation and Development
-
INTERMACS Annual Meeting March 2012
35Research Topics in INTERMACS
- Panel B
- Functional Capacity
- Neurocognitive Assessment
- Quality of Life
- Terminal Events and Risk Factors
- Panel Discussion Young
INTERMACS Annual Meeting March 2012