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

INTERMACS 9INTERMACS 9thth Annual Meeting Annual Meeting May 15- 16, 2015May 15- 16, 2015

Quality of Life SessionQuality of Life Session

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

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

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 SupportGrady 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 ImplantationGrady 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 INTERMACSGrady 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 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 CompletedNot completed -

reason other than too sick

Not completed – too sick Total

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

INTERMACS HRQOL Data Capture across Time

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.

Quantifying the Impact Quantifying the Impact of Adverse Events of Adverse Events

on Health-Related Quality of Life on Health-Related Quality of Life Early after ImplantEarly after Implant

• 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

Study Cohort, n=7353(from 133 sites)

METHODS METHODS

*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

*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.)METHODS (cont.)

Procedures• Approval from all INTERMACS site IRBs• Written consent from patients• Patients completed a self-report HRQOL survey pre-

implant 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

MobilityI have no problems in walking about I have some problems in walking about I am confined to bed Self-CareI have no problems with self-care I have some problems washing or dressing myself I am unable to wash or dress myself Usual Activities (e.g. work, study, housework, family orleisure activities)I have no problems with performing my usual activities I have some problems with performing my usual activities I am unable to perform my usual activities Pain/DiscomfortI have no pain or discomfort I have moderate pain or discomfort I have extreme pain or discomfort Anxiety/DepressionI am not anxious or depressed I am moderately anxious or depressed I am extremely anxious or depressed

EQ-5D-3LHealth QuestionnaireEnglish version for the U.S.

HRQOL Instrument

RESULTS RESULTS Characteristics of CF LVAD Patients

Pre-implantPre-implant LVAD with

EQ-5D data (n=5640)Pre-implant LVAD w/out

EQ-5D data (n=1713) p-value

Age at implant (mean yr+ SD) 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

INTERMACS profile at implant (%)

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

52.0%

5.0%

12.0%

7.0%

20.0%

4.0%

Months Post Implant

Prop

ortio

n of

Pati

ents

Pre-implant

88%

77%

60%

4%0%

8%11%12%

0%

22%

17%

1%

MCS Competing Outcomes Depiction & Rates of EQ-5D Completion after implant

Alive (device in place)

Txpl Dead

Recovery

April 2008 – March 2013

**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

54.0%

22.0%

10.0%6.0%7.0%

100%

VAS Scores pre and post implant & change in VAS scores over time

Pre-implant 6 monthsVAS (n=5640**) (n=3353**) 0 – 25 2714 (48.1%) 404 (12.1%)26 – 50 1589 (28.2%) 347 (10.3%)51 – 75 908 (16.1%) 974 (29.0%)76 – 100 429 (7.6%) 1628 (48.6%)Total 5640 (100%) 3353 (100%)

Change in VAS (n=2748*) n %Increase

>20 1637 59.6%11 – 20 254 9.2% 1 – 10 274 10.0%

Decrease (or no change) 0 – 10 396 14.4%11 – 20 62 2.3% > 20 125 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 Estimates (SE) p valuePre-implant conditions

INTERMACS Level 1 5.0 (1.6) 0.002BTT: Listed -3.7 (1.2) 0.002Pre COPD -5.1 (1.8) 0.005Alcohol abuse -4.1 (1.7) 0.02Pre-implant VAS Score -0.76 (0.02) < 0.0001

Clinical CourseBTT: Unlikely at 6 months -9.6 (2.9) 0.0009BTT: Mod likely at 6 months -4.8 (1.9) 0.01NYHA 4 at 6 months -15.2 (2.9) < 0.0001

Events within first 6 months Renal Dysfunction -5.3 (2.5) 0.03Respiratory Failure -4.8 (1.8) 0.007Neurological Dysfunction -5.5 (1.9) 0.004Infection -2.8 (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’

12.8

70.8

62.757.1

12.8

52.3

0

10

20

30

40

50

60

70

80

90

100

Pre implant 6 months post implant

Prediction of VAS at 6 months post implant, n=2748Level 1 Pre-implant: Critical Cardiogenic Shock (n=337)

Vis

ual A

nalo

g S

core

(V

AS

)

Time Course

Level 1

Events during 1st 6 monthsRenal Respiratory Neuro Infection

No No No No Yes No No Yes Yes No Yes Yes Yes Yes Yes Yes

Predictions of post implant VAS score by pre implant INTERMACS Profile

Prediction of VAS at 6 months post implant, n=2748Level 2 Pre-implant: Progressive Decline (n=1119)

Predictions of post implant VAS score by pre implant INTERMACS Profile

31.35

70.06

61.8956.35

31.35

51.51

0

10

20

30

40

50

60

70

80

90

100

Pre implant 6 months post implant

Vis

ual A

nalo

g S

core

(V

AS

)

Time Course

Level 2

Events during 1st 6 monthsRenal Respiratory Neuro Infection

No No No No Yes No No Yes Yes No Yes Yes Yes Yes Yes Yes

Prediction of VAS at 6 months post implant, n=2748Level 3 Pre-implant: Stable but Inotrope Dependent (n=819)

Predictions of post implant VAS score by pre implant INTERMACS Profile

39.32

72.09

63.9258.38

39.32

53.54

0

10

20

30

40

50

60

70

80

90

100

Pre implant 6 months post implant

Vis

ual A

nalo

g S

core

(V

AS

)

Time Course

Level 3

Events during 1st 6 monthsRenal Respiratory Neuro Infection

No No No No Yes No No Yes Yes No Yes Yes Yes Yes Yes Yes

Predictions of VAS at 6 months post implant, n=2748Levels 4 - 7 Pre-implant (n=473)

Predictions of post implant VAS score by pre implant INTERMACS Profile

43.51

73.41

65.2359.69

43.51

54.85

0

10

20

30

40

50

60

70

80

90

100

Pre implant 6 months post implant

Vis

ual A

nalo

g S

core

(V

AS

)

Time Course

Levels 4-7

Events during 1st 6 monthsRenal Respiratory Neuro Infection

No No No No Yes No No Yes Yes No Yes Yes Yes Yes Yes Yes

CONCLUSIONSCONCLUSIONS

• 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

IMPLICATIONSIMPLICATIONS

• These findings support the ongoing need to– evaluate co-morbid risks before implant– continue to improve device technology

to enhance post implant HRQOL