Transcript Quantifying the Impact of Adverse Events on Health

INTERMACS 9th Annual Meeting
May 15- 16, 2015
Quality of Life Session
Presentations:
• Quantifying the impact of adverse events
on HRQOL early after implant
• Patient selection and estimation of
prognosis using health status measures
• Predicting patients at risk for poor global
outcomes after DT MCS therapy
Improvement in Survival after LVAD Implant
Actuarial survival for primary device implant, stratified by device type. Error bars indicate ± 1 SE. Patients are censored at transplant
and recovery. CF, continuous flow; LVAD, left ventricular assist device; PF, pulsatile flow; TAH, total arti...
Kirklin JK , Naftel DC, Pagani FD, et al., Sixth INTERMACS annual report: A 10,000-patient database.
The Journal of Heart and Lung Transplantation, 2014;33(6):555 – 564.
Improvement in Survival after LVAD Implant
↓ adverse events
Actuarial survival for primary device implant, stratified by device type. Error bars indicate ± 1 SE. Patients are censored at transplant
and recovery. CF, continuous flow; LVAD, left ventricular assist device; PF, pulsatile flow; TAH, total arti...
Kirklin JK , Naftel DC, Pagani FD, et al., Sixth INTERMACS annual report: A 10,000-patient database.
The Journal of Heart and Lung Transplantation, 2014;33(6):555 – 564.
The Time is Right …
to Assess Quality of Life after LVAD Implant
Since 1948, when the World Health
Organization defined health as being not only
the absence of disease and infirmity, but also
the presence of physical, mental, and social
well-being, quality of life issues have become
steadily more important in health care practice
and research.
Testa & Simonson, NEJM, 1996
What is the Clinical Importance of Measuring QOL?
Clinical
• Inform shared decision making
•
Diagnosis or screening
•
Monitoring patients in routine clinical care
•
Evaluating benefits and risks of treatment
•
Prognosis
•
Quality assessment / improvement
Why Study QOL Outcomes?
Research
● Determine the benefits of one treatment versus
another regarding outcomes that are important to
patients (e.g., HRQOL)
● Differentiate HRQOL benefits of two therapies with
marginal differences in mortality or morbidity
● Estimate the burden of different diseases
● Compare impact of different diseases on
functioning and well-being
● Inform relationships between QOL outcomes and
clinical outcomes
INTERMACS HRQOL Abstracts and Publications
Abstracts (published):
7 abstracts
Articles (published):
Beyond survival: Recommendations from INTERMACS for Assessing Function and Quality of Life with
Mechanical Circulatory Support
Grady KL, Warner Stevenson L, Pagani FD, Teuteberg J, Pamboukian SV, Birks E, Moore S, Kirklin JK.
J Heart Lung Transplant. 2012 Nov;31(11):1158-64.
Overall Quality of Life Improves to Similar Levels after Mechanical Circulatory Support Regardless of
Severity of Heart Failure before Implantation
Grady KL, Naftel D, Stevenson L, Dew MA, Weidner G, Pagani FD, Kirklin JK, Myers S, Baldwin T, Young J.
J Heart Lung Transplant. 2014 April;33 (4): 412-21.
Change in Health-Related Quality of Life from Before to After Destination Therapy Mechanical Circulatory
Support is Similar for Older and Younger Patients: Analyses from INTERMACS
Grady KL, Naftel DC, Myers S, Dew MA, Weidner G, Spertus JA, Idrissi K, Lee HB, McGee EC, Kirklin JK.
J Heart Lung Transplant. 2015 Feb;34(2):213-21.
Articles (submitted):
Age and gender differences in HRQOL and factors related to change in HRQOL from before to 6 months
after LVAD implantation: Findings from INTERMACS
Grady KL, Wissman S, Naftel D, Myers S, Gelijns A, Moskowitz A, Pagani F, Young J, Kirklin JK. J Heart Lung
Transplant.
INTERMACS HRQOL Data Capture across Time
INTERMACS Pre-implant Data for June 2006 through March 2015 for Patients at Primary Implant
EQ-5D Completion by Implant Year
Implant Year
Completed
Not Completed
Total
2006
26 (27%)
70 (73%)
96
2007
100 (30%)
237 (70%)
337
2008
301 (41%)
439 (59%)
740
2009
457 (45%)
553 (55%)
1010
2010
903 (55%)
747 (45%)
1650
2011
1025 (53%)
895 (47%)
1920
2012
1356 (59%)
937 (41%)
2293
2013
1553 (57%)
1190 (43%)
2743
2014
1465 (55%)
1204 (45%)
2669
2015
343 (59%)
238 (41%)
581
Total
7529 (54%)
6510 (46%)
14039
INTERMACS HRQOL Data Capture across Time
INTERMACS Pre-implant Data for June 2006 through March 2015 for Patients at Primary Implant
EQ-5D Completion (with non-completion reasons) by Implant Year
Implant Year
Completed
Not completed reason other than
too sick
2006
26 (27%)
21 (22%)
49 (51%)
96
2007
100 (30%)
79 (23%)
158 (47%)
337
2008
301 (41%)
208 (28%)
231 (31%)
740
2009
457 (45%)
304 (30%)
249 (25%)
1010
2010
903 (55%)
449 (27%)
298 (18%)
1650
2011
1025 (53%)
531 (28%)
364 (19%)
1920
2012
1356 (59%)
613 (27%)
324 (14%)
2293
2013
1553 (57%)
807 (29%)
383 (14%)
2743
2014
1465 (55%)
726 (27%)
478 (18%)
2669
2015
343 (59%)
141 (24%)
97 (17%)
581
Total
7529 (54%)
3879 (27%)
2631 (19%)
14039
Not completed –
too sick
Total
Quantifying the Impact
of Adverse Events
on Health-Related Quality of Life
Early after Implant
Grady KL, Wissman S, Naftel D, Myers S, Gelijns A,
Moskowitz A, Pagani F, Young J, Kirklin JK
I will not discuss off label use and/or investigational use of drugs/devices.
• Background
– Risk factors for poor HRQOL after LVAD implant are
unknown
– Understanding risk factors
• May inform selection criteria for device implant
• Reinforce the ongoing need to improve device technology, in
order to reduce rates of adverse events
• Purpose
– Identify pre and post implant factors related to change
in overall HRQOL from before to 6 months after LVAD
implantation
– Rationale for 6month post implant time period
• Patients are adjusting to “life on a device” while
potentially dealing with early post implant adverse
events
METHODS
Study Cohort, n=7353
(from 133 sites)
Pool: Adult primary CFLVADs
implanted Jun 2006 – Mar 2013
(follow-up thru March 2014)
N=7353
6 month post implant patients, n=5931
patients with completed*
6 month EQ-5D VAS
n=3353 (57%)
Pre-implant patients, n=7353
Patients with completed*
pre-implant EQ-5D VAS
n=5640 (77%)
Patients with both completed*
pre-implant and 6 month post
implant EQ-5D VAS
n= 2748 (37% of total cohort)
*completed includes patients who filled out the EQ-5D and also those patients
captured as ‘too sick’. ‘Too sick’ patients were assigned 0 for the VAS and ‘extreme
problems’ for the 3 physical dimensions of Mobility, Self Care and Usual Activities
Study Cohort, n=7353
Pool: Adult primary CFLVADs implanted
Jun 2006 – Mar 2013
(follow-up thru March 2014)
N=7353 (133 sites)
6 month post implant patients, n=5931
patients with completed*
6 month EQ-5D VAS
n=3353 (57%)
Pre-implant patients, n=7353
Patients with completed*
pre-implant EQ-5D VAS
n=5640 (77%)
Patients with both completed*
pre-implant and 6 month post
implant EQ-5D VAS
n= 2748 (37% of total cohort)
*completed includes patients who filled out the EQ-5D and also those patients
captured as ‘too sick’. ‘Too sick’ patients were assigned 0 for the VAS and ‘extreme
problems’ for the 3 physical dimensions of Mobility, Self Care and Usual Activities
METHODS (cont.)
Procedures
•
•
•
•
Approval from all INTERMACS site IRBs
Written consent from patients
Patients completed a self-report HRQOL survey preimplant and post-implant at 3 and 6 months
Medical records data collected per INTERMACS protocols
HRQOL instrument
•
EQ – 5D – 3L Survey
–
–
–
–
Generic, self-report health profile
HRQOL items: 1 VAS scale (health status) and 5 questions
If incomplete EQ-5D reason is “too sick”, VAS is assigned 0
Reliable and valid & norms in multiple populations
Statistics
•
Pearson correlations and multiple regression analyses
HRQOL Instrument
Mobility
EQ-5D-3L
I have no problems in walking about q
Health Questionnaire
I have some problems in walking about q
English version for the U.S.
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
RESULTS
Characteristics of CF LVAD Patients
Pre-implant LVAD with
EQ-5D data (n=5640)
Pre-implant LVAD w/out
EQ-5D data (n=1713)
p-value
56.7+12.86
57.1+13.01
0.22
Male (%)
78.6
80.8
0.05
Race (% white)
70.5
67.7
0.02
Married at implant (%)
66.9
65.3
0.22
>HS education (%)
53.4
48.6
0.004
1
15.3
10.8
< 0.0001
2
40.8
35.8
0.0002
3
27.2
26.4
0.55
4
12.4
18.9
<0.0001
5
2.3
4.8
<0.0001
6
1.3
2.0
0.04
7
1.2
0.7
0.04
Pre-implant
Age at implant (mean yr+ SD)
INTERMACS profile at implant (%)
MCS Competing Outcomes Depiction & Rates of EQ-5D Completion after implant
April 2008 – March 2013
100%
7.0%
6.0%
88%
Proportion of Patients
10.0%
77%
4.0%
22.0%
60%
20.0%
7.0%
12.0%
Alive (device
5.0%
in place)
22%
54.0%
8%
4%
0%
Pre-implant
52.0% 12%
11%
0%
Txpl
Dead
17%
1%
Recovery
Months Post Implant
**completed forms includes patients who filled out the EQ-5D and also those patients captured as ‘too sick’ to complete the EQ-5D. ‘Too sick’
patients were assigned a value of 0 for the VAS and ‘extreme problems’ for the 3 physical dimensions of Mobility, Self Care and Usual Activities
VAS Scores pre and post implant & change in VAS scores over time
VAS
0 – 25
26 – 50
51 – 75
76 – 100
Total
Pre-implant
(n=5640**)
2714 (48.1%)
1589 (28.2%)
908 (16.1%)
429 (7.6%)
5640 (100%)
Change in VAS (n=2748*)
Increase
>20
11 – 20
1 – 10
Decrease (or no change)
0 – 10
11 – 20
> 20
6 months
(n=3353**)
404 (12.1%)
347 (10.3%)
974 (29.0%)
1628 (48.6%)
3353 (100%)
n
%
1637
254
274
59.6%
9.2%
10.0%
396
62
125
14.4%
2.3%
4.6%
* Only includes paired data (patients with both pre and post 6
months completed EQ-5D)
**completed forms includes patients who filled out the EQ-5D and also those patients captured as ‘too
sick’ to complete the EQ-5D. ‘Too sick’ patients were assigned a value of 0 for the VAS.
Factors Associated with Change in HRQOL Pre-implant – 6 months post implant
Risk Factors
Pre-implant conditions
INTERMACS Level 1
BTT: Listed
Pre COPD
Alcohol abuse
Pre-implant VAS Score
Clinical Course
BTT: Unlikely at 6 months
BTT: Mod likely at 6 months
NYHA 4 at 6 months
Events within first 6 months
Renal Dysfunction
Respiratory Failure
Neurological Dysfunction
Infection
Estimates (SE)
5.0 (1.6)
-3.7 (1.2)
-5.1 (1.8)
-4.1 (1.7)
-0.76 (0.02)
p value
0.002
0.002
0.005
0.02
< 0.0001
-9.6 (2.9)
-4.8 (1.9)
-15.2 (2.9)
0.0009
0.01
< 0.0001
-5.3 (2.5)
-4.8 (1.8)
-5.5 (1.9)
-2.8 (1.1)
0.03
0.007
0.004
0.01
Intercept = 64.2, R2 = 41.3%, n=2748
HRQOL=health-related quality of life; INTERMACS=interagency Registry for Mechanically Assisted Circulatory Support;
BTT=bridge to transplant; COPD=chronic obstructive pulmonary disease; VAS=visual analog scale
Negative coefficients indicate the decrement in change
The Intercept indicates the amount of change (improvement) for a patient with no ‘risk factors’
Predictions of post implant VAS score by pre implant INTERMACS Profile
Prediction of VAS at 6 months post implant, n=2748
Level 1 Pre-implant: Critical Cardiogenic Shock (n=337)
Visual Analog Score (VAS)
100
90
Events during 1st 6 months
80
Renal
70.8
70
62.7
57.1
52.3
60
50
No
Yes
Yes
Yes
40
30
20
10
12.8
Time Course
0
Pre implant
Level 1
6 months post implant
Respiratory Neuro
No
No
No
Yes
No
No
Yes
Yes
Infection
No
Yes
Yes
Yes
Predictions of post implant VAS score by pre implant INTERMACS Profile
Prediction of VAS at 6 months post implant, n=2748
Level 2 Pre-implant: Progressive Decline (n=1119)
Visual Analog Score (VAS)
100
90
Events during 1st 6 months
80
Renal
70
70.06
60
61.89
56.35
51.51
50
No
Yes
Yes
Yes
40
30
31.35
20
Time Course
10
0
Pre implant
Level 2
6 months post implant
Respiratory Neuro
No
No
No
Yes
No
No
Yes
Yes
Infection
No
Yes
Yes
Yes
Predictions of post implant VAS score by pre implant INTERMACS Profile
Prediction of VAS at 6 months post implant, n=2748
Level 3 Pre-implant: Stable but Inotrope Dependent (n=819)
Visual Analog Score (VAS)
100
90
Events during 1st 6 months
80
Renal
70
72.09
60
63.92
58.38
53.54
50
40
No
Yes
Yes
Yes
39.32
30
20
Time Course
10
0
Pre implant
Level 3
6 months post implant
Respiratory Neuro
No
No
No
Yes
No
No
Yes
Yes
Infection
No
Yes
Yes
Yes
Predictions of post implant VAS score by pre implant INTERMACS Profile
Predictions of VAS at 6 months post implant, n=2748
Levels 4 - 7 Pre-implant (n=473)
Visual Analog Score (VAS)
100
90
Events during 1st 6 months
Renal
80
73.41
70
65.23
59.69
54.85
60
No
Yes
Yes
Yes
50
40
43.51
30
20
Time Course
10
0
Pre implant
Levels 4-7
6 months post implant
Respiratory Neuro
No
No
No
Yes
No
No
Yes
Yes
Infection
No
Yes
Yes
Yes
CONCLUSIONS
• Patients who are the sickest have the
greatest opportunity for major
improvement in HRQOL after implant
• Patients with co-morbidities that prevent
listing for HT may have limited HRQOL
improvement
• Adverse events have a detrimental impact
on HRQOL at 6 months after implant
IMPLICATIONS
• These findings support the ongoing
need to
– evaluate co-morbid risks before implant
– continue to improve device technology
to enhance post implant HRQOL