what have we learned? what is next? panel b: functional capacity,

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

Research Topics in INTERMACS

INTERMACS Annual Meetin

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March 2012

Functional Capacity

JoAnn Lindenfeld

So far we have learned little about functional capacity



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March 2012

June 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%


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March 2012

Is Frailty Predictive of Hospital Complications, Duration and

Success of Rehabilitation, and Ultimate Quality of Life?


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March 2012

LVAD-Responsive Frailty

Systolic and diastolic dysfunction

↑PCWP and CVP↓Cardiac output

InflammationAnorexiaHypoxia

Polypharmacy

FrailtyIncreased Vulnerability to Stress

AGINGCOPD / lung disease

CancerDiabetes

OsteoporosisPeripheral vascular disease

CirrhosisNeurologic diseaseSarcopenia

MalnutritionCognitive deficits

Injurious falls

LVAD-Independent Frailty

Post-OperativeComplications

Prolonged LOSNeed for ICU care

ReducedSurvival

ImpairedHealth Status

DisabilityLoss of ADLs

Institutionalization Flint et alCirc: Heart Failure

In PressINTERMACS Annual M

eeting

March 2012

Pre-LVAD Frailty

Post-LVAD Frailty

LVAD-Responsive Frailty LVAD-Independent Frailty

Patient A Patient CPatient B

Unfavorable OutcomeHigh risk for premature death and complications with failure to improve

functional status

Intermediate OutcomeModerate risk for premature death and complications with

some persistent functional limitation

Favorable OutcomeLower risk for premature death or complications, with marked

improvement in functional status

Flint et alCirc: Heart Failure

In PressINTERMACS Annual M

eeting

March 2012

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?



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March 2012

Functional Capacity

• Is gait speed predictive in those < 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?



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Neurocognitive Assessment

K Grady



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March 2012

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.



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The biggest challenges with neurocognitive assessment in INTERMACS are:

• Collecting the Data

• Making neurocognitive assessment a part of MCSD standard of care



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What are the Next Steps?

• Improving Patient Outcomes

• Device Evaluation and Development



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Quality of Life

K Grady



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March 2012

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-5DHealth Questionnaire

English version for the US

QOL Instrument


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EQ

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VA

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(N=39)

Pre and Post Implant EQ-5D (primary implant, prospective, adult)

Visual Analogue Scale (VAS) Across Time (mean ± SD)

Pre-Implant 3 month 6 month 12 month

(N=312)

(N=183) (N=96)

P (pre vs 3 mo) <0.001

Months Post Implant

Best

Worst

N=878 adult MCS patients, primary implant (pulsatile and continuous flow [LVAD, Bi-VAD, TAH]: 6/06-9/08); Profile 1 = 36%, Profile 2 = 38%


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CONCLUSIONS• 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.


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March 2012

PURPOSE

• 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)


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March 2012

Primary continuous flow LVAD, n=1559

Patient Profile Levels (Pre-Implant) Status at 1 year 1 2 3 4 5-7 Total Post implant (n= 262) (n=695) (n=330) (n=175) (n=97) (n=1559)

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

Implants: June 2006 – March 2010, Follow-up: March 2011


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0 3 6 9 12 15 18 21 24

June 2006 – March 2011: HRQOL by Patient Profiles

(All patients with opportunity for 1 year follow-up (n=1559)

Months Post Implant

Pro

po

rtio

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f P

atie

nts

Pre-implant

Alive (device in place) 100%

Txpl 0%

Dead 0%

Rec 0%




Txpl 8%Dead 9%

Rec 0%

Txpl 19%

Dead 11%

Rec 1%

Txpl 34%

Dead 15%Rec 1%


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March 2012

0102030405060708090

100

Level 1: Level 2: Level 3: Level 4: Levels 5-7

Pre-Implant

3 months post implant

1 year post implant

EQ-5D: Visual Analog Scale

INTERMACS Patient Profile Levels

BestHealth

WorstHealth

Mea

n V

AS

Primary Continuous Flow LVADs, n=2807


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100.0%


Pre-Implant


1 year post implant

EQ-5D: Mobility, Any Problems%

Pat

ient

s w

ith A

ny M

obili

ty P

robl

ems




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0.0%10.0%20.0%30.0%40.0%50.0%60.0%70.0%80.0%90.0%

100.0%


Pre-Implant


1 year post implant

EQ-5D: Self Care, Any Problems%

Pat

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elf

Car

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March 2012

Predictors of better QOL at 6 months after continuous flow MCS

FACTOR Parameter estimate

SE Partial R-square

Model R-square

Better NYHA at 6 months after implant

-3.2629 0.9161 0.017 0.017

No HX of COPD

-6.5129 2.0949 0.008 0.026

Worse pre implant NYHA

3.9715 1.5153 0.009 0.035

Older age 0.0020 0.0005 0.008 0.042 No HX of CABG

-4.0862 1.8274 0.006 0.048

Being likely to be listed for HT 6 mos. after implant

3.4798 1.7100 0.005 0.054

Not being rehospitalized

-2.8237 1.3954 0.005 0.059

Total R-square = 6%, F=6.97, p<0.0001

•Since the mean VAS score improved dramatically from pre-implant to 6 months post implant (42 vs 74, p< 0.0001), the most important factor for increased overall health status was MCS implant.


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Quality of Life






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March 2012

What 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 indexKCCQ (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.)

• Utility analyses, QALYs, etc.INTERMACS Annual M

eeting

March 2012

Terminal Events and Risk Factors

D Naftel



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0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Continuous Flow Intracorporeal Device n=896, deaths=112

Pulsatile Flow Paracorporeal Device,

n=74, deaths=28

p (overall) < 0.0001

Event: Death (censored at transplant or recovery)

% S

urv

iva

l

Months after Device Implant

Pulsatile Flow Intracorporeal Device, n=470, deaths=140

INTERMACS: Survival After LVAD Implant


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Survival

% S

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Months % Survival 1 mo 94% 3 mo 89% 6 mo 84%12 mo 76%24 mo 63%

Survival after Primary LVAD(Pulsatile and Continuous Flow Devices)

Hazard

Death

s / Mo

nth

(Hazard

)INTERMACS: Survival After LVAD Implant


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65+ years, n=66, deaths=35

P (overall) <.0001


% S

urv

iva

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30 – 65 years, n=377, deaths=100

< 30 years, n=27, deaths=5

By Age Groups

INTERMACS: Survival after LVAD Implant

Adult Primary Pulsatile Intracorporeal Flow LVAD Pumps (n= 470)


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65+ years, n=144, deaths=29

P (overall) = .002


% S

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30 – 65 years, n=691, deaths=81

< 30 years, n=61, deaths=2By Age Groups


Adult Primary Continuous Intracorporeal Flow LVAD Pumps: n= 896


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March 2012

Early Constant

Risk Factor Hazard ratio p-value Hazard ratio p-valueFemale 1.71 0.04 --- ---

Age (older) 1.141 0.006 1.131 0.008Previous CABG 2.71 <0.0001 --- ---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 0.04RA 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 age2 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: Survival After LVAD Implant

Adult Primary Intracorporeal LVADs (n=1366)


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Adult Primary Intracorporeal LVADs: n= 1366


Pre

dic

ted

% S

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ival

Pulsatile Intracorporeal

Continuous Intracorporeal

Risk Factor Unadjusted Adjusted

Constant Phase Hazard ratio p-value Hazard ratio p-valuePulsatile pump 12.54 <0.0001 3.02 0.001

“Average” Patient


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33

Early Constant

Risk Factor Hazard ratio p-value Hazard ratio p-value

Age (older) 2.421 <.0001 1.551 .0005Bilirubin (higher) 1.412 .0002 --- --- RA Pressure (higher) 2.083 .0009 --- --- Cardiogenic Shock 1.97 .02 --- --- BTC or DT --- --- 1.80 .02Pulsatile pump --- --- 2.74 .001

Table 9Risk Factors for Death after Implant: June 2006 – March 2009 Primary LVAD: n=1092

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 bilirubin3 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


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Terminal Events and Risk Factors






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March 2012

Panel B: G. Functional CapacityH. Neurocognitive AssessmentI. Quality of LifeJ. Terminal Events and Risk FactorsK. Panel Discussion Young



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March 2012

what have we learned? what is next? panel b: functional capacity,

Documents

good functional capacity

functional capacitycan

reversible frailty

premature death

discussionresearch topics

best measures of frailty

lvad recipients

risk factors