1. INTERMACS 10th Annual Meeting March 11- 12, 2016 Quality of Life
… More than Just Survival by
Kathleen L. Grady, PhD, RN, MS, FAAN
Professor, Feinberg School of Medicine,
Northwestern University, Chicago, IL
Administrative Director, Center for Heart Failure,
Bluhm Cardiovascular Institute
at Northwestern Memorial Hospital, Chicago, IL
I will not discuss off label use and/or investigational use of drugs/devices.

2. Why Measure HRQOL? Research Clinical Inform shared decision making
Compare the effectiveness of different treatment options (e.g., medical vs surgical) regarding HRQOL
Describe change in HRQOL across time (before to after an intervention)
Determine risk factors for poor HRQOL
Demographic characteristics
Pre intervention disease severity and co-morbidities
Clinical course
Treatment-related adverse events
Determine whether HRQOL is a predictor of other outcomes (e.g., mortality)
Inform shared decision making
Inform prognosis
Monitor across time
Inform clinical care
Inform disease surveillance and population health
Rumsfeld J, et al. Circulation, 2013.

3. Why Measure HRQOL? Informed by INTERMACS analyses Research Clinical
Compare the effectiveness of different treatment options (e.g., medical vs surgical) regarding HRQOL
Describe change in HRQOL across time (before to after an intervention)
Determine risk factors for poor HRQOL
Demographic characteristics
Pre intervention disease severity and co-morbidities
Clinical course
Treatment-related adverse events
Determine whether HRQOL is a predictor of other outcomes (e.g., mortality)
Inform shared decision making
Inform prognosis
Monitor across time
Inform clinical care
Inform disease surveillance and population health

4. Change in Health-Related Quality of Life from before to 6 months after LVAD Implantation and Factors Related to Change: Findings from Intermacs
Grady KL, Wissman S, Naftel D, Myers S, Gelijns A, Moskowitz A, Pagani F, Young J, Spertus J, Kirklin JK

5. Pool: Adult primary CFLVADs implanted
Jun 2006 – Mar 2013
(follow-up thru March 2014)
N= (133 sites)
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)
6 month post implant patients, n=5931
patients with completed*
6 month EQ-5D VAS
n=3353 (57%)
Study Cohort, n=7353
*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

6. Proportion of Patients
MCS Competing Outcomes Depiction & Rates of EQ-5D Completion after implant
April 2008 – March 2013
100%
88%
77%
60%
Proportion of Patients
Alive (device
in place)
Txpl
22%
Dead
12%
17% 8%
11% 4% 0% 0% 1%
Recovery
Pre-implant
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

7. VAS Scores pre and post implant & change in VAS scores over time
Pre-implant months
VAS (n=5640**) (n=3353**)
0 – (48.1%) (12.1%)
26 – (28.2%) (10.3%)
51 – (16.1%) (29.0%)
76 – (7.6%) (48.6%)
Total (100%) (100%)
Change in VAS (n=2748*) n %
Increase
> %
11 – %
1 – %
Decrease (or no change)
0 – %
11 – %
> %
* 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.

8. Risk Factors Estimates (SE) p value
Factors Associated with Change in HRQOL Pre-implant – 6 months post implant
Risk Factors Estimates (SE) p value
Pre-implant conditions
INTERMACS Level (1.6)
BTT: Listed (1.2)
Pre COPD (1.8)
Alcohol abuse (1.7) 0.02
Pre-implant VAS Score (0.02) <
Clinical Course
BTT: Unlikely at 6 months (2.9)
BTT: Mod likely at 6 months (1.9) 0.01
NYHA 4 at 6 months (2.9) <
Events within first 6 months
Renal Dysfunction (2.5) 0.03
Respiratory Failure (1.8)
Neurological Dysfunction (1.9)
Infection (1.1) 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’

9. 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)
Events during 1st 6 months
Renal Respiratory Neuro Infection
No No No No
Yes No No Yes
Yes No Yes Yes
Yes Yes Yes Yes
Visual Analog Score (VAS)
Time Course
Level 1

10. 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)
Events during 1st 6 months
Renal Respiratory Neuro Infection
No No No No
Yes No No Yes
Yes No Yes Yes
Yes Yes Yes Yes
Visual Analog Score (VAS)
Time Course
Level 2

11. 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)
Events during 1st 6 months
Renal Respiratory Neuro Infection
No No No No
Yes No No Yes
Yes No Yes Yes
Yes Yes Yes Yes
Visual Analog Score (VAS)
Time Course
Level 3

12. Predictions of post implant VAS score by pre implant INTERMACS Profile
Predictions of VAS at 6 months post implant, n=2748
Levels Pre-implant (n=473)
Events during 1st 6 months
Renal Respiratory Neuro Infection
No No No No
Yes No No Yes
Yes No Yes Yes
Yes Yes Yes Yes
Visual Analog Score (VAS)
Time Course
Levels 4-7

13. Overall Quality of Life Improves to
Similar Levels after Mechanical Circulatory Support Regardless of Severity of Heart Failure Before Implantation by
Kathleen L. Grady, David C. Naftel,
Lynne W. Stevenson, Mary Amanda Dew, Gerdi Weidner, Francis D. Pagani, James K. Kirklin, Susan Myers, Timothy Baldwin, and James Young

14. Available for HRQOL assessment at 1 year post implant* (n=1559)
Patient Profile Levels (Pre-Implant)
Status at 1 year Total
Post implant (n= 262) (n=695) (n=330) (n=175) (n=97) (n=1559)
Death % 16% % % % %
Transplant % 32% % % % %
Recovery % 1% % % % %
Alive (on device)* % 51% % % % %
Total % % % % 100% %

15. EQ-5D: Visual Analog Scale INTERMACS Patient Profile Levels
Best
Health
Mean VAS
Worst
Health N=
p = < < < < <.0001
(Pre implant vs 12 mos. post implant)
INTERMACS Patient Profile Levels
Utilizes all EQ-5D available at each time period

16. EQ-5D: Mobility, Patients with any Problems
% Patients with Any Mobility Problems N=
p = < < < < <.0001
(Pre implant vs 12 mos. post implant)
INTERMACS Patient Profile Levels
Utilizes all EQ-5D available at each time period

17. INTERMACS Patient Profile Levels
EQ-5D: Usual Activities, Patients with any Problems
% Patients with Any Usual Activities Problems N=
p = < < < < <.0001
(Pre implant vs 12 mos. post implant)
INTERMACS Patient Profile Levels
Utilizes all EQ-5D available at each time period

18. EQ-5D: Self Care, Patients with any Problems
% Patients with Any Self Care Problems N=
p = < < <
(Pre implant vs 12 mos. post implant)
INTERMACS Patient Profile Levels
Utilizes all EQ-5D available at each time period

19. EQ-5D: Anxiety/Depression, Patients with any Problems
% Patients with Any Anxiety/Depression Problems N=
p= <
(Pre implant vs 12 mos. post implant)
INTERMACS Patient Profile Levels
Utilizes all EQ-5D available at each time period

20. EQ-5D: Pain, Patients with any Problems
% Patients with Any Pain Problems N= p=
(Pre implant vs 12 mos. post implant)
INTERMACS Patient Profile Levels
Utilizes all EQ-5D available at each time period

21. Change in HRQOL from Before to After DT MCS is Similar
for Older and Younger Patients:
Analyses from INTERMACS
Kathleen L. Grady, David C. Naftel, Susan Myers,
Mary Amada Dew, Gerdi Weidner, John Spertus,
Kathy Idrissi, Hochang Lee, Edwin C. McGee Jr,
and James K. Kirklin

22. INTERMACS: Jan, 2010 – March, 2012 Patient Pool All Primary Implants
January 21, 2010 – March 31, 2012
n=3960*
Patient Pool
Pediatric Patients
(< 19 yrs of age)
n=33**
Adults
n=3927
Pulsatile
n=8
Continuous Flow
n=25
Pulsatile
n=149
Continuous Flow
n=3778
TAH, n=1
BiVAD, n=4
LVAD, n=3
BiVAD, n=1
LVAD, n=24
TAH
n=39
BiVAD
n=84
LVAD
n=26
BiVAD
n=97
LVAD
n=3681
DT=0
DT=3
DT=5
BTR, n=2
BTC, n=38
BTT Listed, n=19
DT, n=33
Rescue, n=3
Other, n=2
BTR, n=24
BTC, n=1312
BTT Listed, n=847
DT, n=1470
Rescue, n=7
Other, n=21
DT n=1470
* 7 sites removed from study due to incomplete EQ5D data collection
** No pediatric patients are designated as ‘destination therapy’

23. Sample
Adult Primary Continuous Flow LVAD patients who are Destination Therapy at time of implant (with opportunity for 1 year follow-up)
N=1,470
Age Group 1
< 60 years
n=457 (31%)
Age Group 2a
60-64 years
n=199 (13%)
Age Group 2b
65-69 years
n=321 (22%)
Age Group 3
70 + years
n=493 (34%)
Age Group 2
60-69 years
N=520 (35%)

24. Mean VAS scores for adult primary DT LVAD patients, by age
Best
Too sick is assigned 0 for VAS
70+ yrs (p(change) < .0001)
60-69 yrs
(p(change) < .0001)
p (equality of change) = .77
< 60 yrs (p(change) < .0001)
% Visual Analog Scale (VAS)
p = .02
p = .03
Worst
Note: error bars include standard error

25. Mean VAS scores for adult primary DT LVAD patients, by age
Sensitivity analysis: Too sick is NOT assigned 0 for VAS
Best
70+ yrs (p(change) < .0001)
p (equality of change) = .57
< 60 yrs
(p(change) < .0001)
60-69 yrs
(p(change) < .0001)
% Visual Analog Scale (VAS)
p = .59
p = .09
Worst
Note: error bars include standard error

26. Factors Associated with Change in HRQOL (VAS score), n=435
Re-hospitalization during 1 year No
Predicted value of difference in VAS at 1 year
Improvement
Decline
Yes
Factors estimate p-value
Higher VAS score, pre implant < .0001
Re-hospitalization < .0001
R2=61.3%, intercept=77.1
VAS at pre-implant

27. Global and Disease-Specific Health Status in Patients Undergoing Continuous-Flow Left Ventricular Assist Device Placement
Kelsey Flint, MD
University of Colorado School of Medicine
Division of Cardiology
General Cardiology Fellow

28. Pre-operative health status and 24-month mortality and hospitalization
VAS
KCCQ
Mortality
Q1 N=552
Q2 N=558
Q3 N=556
Q4 N=559
Q1 N=508
Q2 N=592
Q3 N=545
Q4 N=560
p=0.66
p=0.55
Quartile 1
Quartile 2
Quartile 3
Quartile 4
Similar to our findings with the Thoratec data, pre-operative KCCQ was not associated with 24-month mortality or hospitalization
Interestingly, global health status was also not associated with 24-month mortality or hospitalization
*unadjusted – this is the raw association*
Q1 N=552
Q2 N=558
Q3 N=556
Q4 N=559
Q1 N=508
Q2 N=592
Q3 N=545
Q4 N=560
Hospitalization
p=0.07
p=0.22

29. 3-month Health Status and 24-month Mortality and Hospitalization
KCCQ
VAS
Mortality
Q1 N=512
Q2 N=516
Q3 N=516
Q4 N=516
Q1 N=512
Q2 N=516
Q3 N=516
Q4 N=516
P<0.001
P=0.23
Quartile 1
Quartile 2
Quartile 3
Quartile 4
Interestingly, 3-month KCCQ was associated with 24-month mortality. Both KCCQ and VAS were associated with 24-moth hospitalization, but given the minimal separation we see between those lines this statistical relationship may have limited clinical significance (hospitalization is a much more common outcome than death)
For those ppl who survive to 3 mo, if at that time they have a low HS, they have sig decreased subsequent survival, as you can see from the the raw KM curve. Dz specific meas was better
Hosp was statistically sig, but visually less obvious
Q1 N=512
Q2 N=516
Q3 N=516
Q4 N=516
Q1 N=512
Q2 N=516
Q3 N=516
Q4 N=516
Hospitalization
P<0.001
P=0.01

30. Conclusions
Pre MCS implant HRQOL is poor for patients with all levels of advanced heart failure severity and improves significantly post implant.
While the amount of change over time varies by pre implant heart failure severity, patients improve to similar levels of HRQOL after implant.
Improvement in HRQOL varies by domain, with more improvement in physical domains than mental domains.
For patients undergoing MCS as DT, the amount of improvement in HRQOL, from before to after implant, is similar for all adult age groups.
Factors related to worse HRQOL from before to after MCS implant:
- better pre implant HRQOL
- co-morbidities
- post implant adverse events
- more frequent re-hospitalization
Post implant HRQOL is related to other post implant outcomes

31. Implications
Serial assessment of HRQOL from before to after MCS implantation and identification of factors related to HRQOL may inform:
Prognosis and goals of care discussions
Shared decision making
Pre implant, when considering MCS as a treatment option
Post implant, when considering treatment options based on “event milestones”

32. Thank you!
“And in the end, it’s not the years in your life that counts, it’s the life in your years.”
Abraham Lincoln