1. 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 Meeting March 2012

2. Functional Capacity JoAnn Lindenfeld So far we have learned little about functional capacity Research Topics in INTERMACS INTERMACS Annual Meeting March 2012

3. 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-Implant95730 3.1% 58 6.1% 28 2.9% 3 Month4267918.5% 14 3.3% 12 2.8% 6 Month2023818.8% 105.0% 8 4.0% 12 Month 711622.5% 11.4% 0 ­ 18 Month 16 318.8% 0 - 0 - 24 Month 3 133.3% 0 - 0 - Total 1675 16710.0% 835.0%48 2.9% INTERMACS Annual Meeting March 2012

4. Is Frailty Predictive of Hospital Complications, Duration and Success of Rehabilitation, and Ultimate Quality of Life? INTERMACS Annual Meeting March 2012

5. LVAD-Responsive Frailty Systolic and diastolic dysfunction ↑PCWP and CVP ↓Cardiac output Inflammation Anorexia Hypoxia Polypharmacy Frailty Increased Vulnerability to Stress AGING COPD / lung disease Cancer Diabetes Osteoporosis Peripheral vascular disease Cirrhosis Neurologic disease Sarcopenia Malnutrition Cognitive deficits Injurious falls LVAD-Independent Frailty Post-Operative Complications Prolonged LOS Need for ICU care Reduced Survival Impaired Health Status Disability Loss of ADLs Institutionalization Flint et al Circ: Heart Failure In Press INTERMACS Annual Meeting March 2012

6. Pre-LVAD Frailty Post-LVAD Frailty LVAD-Responsive Frailty LVAD-Independent Frailty Patient APatient CPatient B 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 INTERMACS Annual Meeting March 2012

7. 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? Research Topics in INTERMACS INTERMACS Annual Meeting March 2012

8. 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? Research Topics in INTERMACS INTERMACS Annual Meeting March 2012

9. Neurocognitive Assessment K Grady Research Topics in INTERMACS INTERMACS Annual Meeting March 2012

10. 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. Research Topics in INTERMACS INTERMACS Annual Meeting March 2012

11. Neurocognitive Assessment The biggest challenges with neurocognitive assessment in INTERMACS are: Collecting the Data Making neurocognitive assessment a part of MCSD standard of care Research Topics in INTERMACS INTERMACS Annual Meeting March 2012

12. Neurocognitive Assessment What are the Next Steps? Improving Patient Outcomes Device Evaluation and Development Research Topics in INTERMACS INTERMACS Annual Meeting March 2012

13. Quality of Life K Grady Research Topics in INTERMACS INTERMACS Annual Meeting March 2012

14. Mobility I have no problems in walking about  I have some problems in walking about  I am confined to bed  Self-Care I 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 or leisure 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/Discomfort I have no pain or discomfort  I have moderate pain or discomfort  I have extreme pain or discomfort  Anxiety/Depression I am not anxious or depressed  I am moderately anxious or depressed  I am extremely anxious or depressed  EQ-5D Health Questionnaire English version for the US QOL Instrument INTERMACS Annual Meeting March 2012

15. EQ-5D VAS (N=39) Pre and Post Implant EQ-5D (primary implant, prospective, adult) Visual Analogue Scale (VAS) Across Time (mean ± SD) Pre-Implant3 month6 month12 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% INTERMACS Annual Meeting March 2012

16. 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. INTERMACS Annual Meeting March 2012

17. 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) INTERMACS Annual Meeting March 2012

18. 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 INTERMACS Annual Meeting March 2012

19. June 2006 – March 2011: HRQOL by Patient Profiles (All patients with opportunity for 1 year follow-up (n=1559) Months Post Implant Proportion of Patients Pre-implant Alive (device in place) 100% Txpl 0% Dead 0% Rec 0% Alive (device in place) 83% Alive (device in place) 69% Alive (device in place) 50% Txpl 8% Dead 9% Rec 0% Txpl 19% Dead 11% Rec 1% Txpl 34% Dead 15% Rec 1% INTERMACS Annual Meeting March 2012

20. EQ-5D: Visual Analog Scale INTERMACS Patient Profile Levels Best Health Worst Health Mean VAS Primary Continuous Flow LVADs, n=2807 INTERMACS Annual Meeting March 2012

21. EQ-5D: Mobility, Any Problems % Patients with Any Mobility Problems INTERMACS Patient Profile Levels Primary Continuous Flow LVADs, n=2807 INTERMACS Annual Meeting March 2012

22. EQ-5D: Self Care, Any Problems % Patients with Any Self Care Problems INTERMACS Patient Profile Levels Primary Continuous Flow LVADs, n=2807 INTERMACS Annual Meeting March 2012

23. Predictors 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, p< 0.0001), the most important factor for increased overall health status was MCS implant. INTERMACS Annual Meeting March 2012

24. Quality of Life What are the Next Steps? Improving Patient Outcomes Device Evaluation and Development Research Topics in INTERMACS INTERMACS Annual Meeting March 2012

25. 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 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.) Utility analyses, QALYs, etc. INTERMACS Annual Meeting March 2012

26. Terminal Events and Risk Factors D Naftel Research Topics in INTERMACS INTERMACS Annual Meeting March 2012

27. 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) % Survival Months after Device Implant Pulsatile Flow Intracorporeal Device, n=470, deaths=140 INTERMACS: Survival After LVAD Implant INTERMACS Annual Meeting March 2012

28. Survival % Survival Months after Device Implant Event: Death (censored at transplant or recovery) 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 Deaths / Month (Hazard) INTERMACS: Survival After LVAD Implant INTERMACS Annual Meeting March 2012

29. 65+ years, n=66, deaths=35 P (overall) <.0001 Event: Death (censored at transplant or recovery) % Survival Months after Device Implant 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) INTERMACS Annual Meeting March 2012

30. 65+ years, n=144, deaths=29 P (overall) =.002 Event: Death (censored at transplant or recovery) % Survival Months after Device Implant 30 – 65 years, n=691, deaths=81 < 30 years, n=61, deaths=2 By Age Groups INTERMACS: Survival after LVAD Implant Adult Primary Continuous Intracorporeal Flow LVAD Pumps: n= 896 INTERMACS Annual Meeting March 2012

31. Early Constant Risk Factor Hazard ratio p-value Hazard ratio p-value Female 1.71 0.04 --- --- Age (older) 1.14 1 0.006 1.13 1 0.008 Previous CABG2.71 <0.0001 --- --- Previous Valve Surgery1.99 0.01 --- --- Dialysis (current)2.45 0.01 --- --- INR (higher)1.49 2 0.003 --- --- Ascites 2.32 0.002 --- --- RVEF: Severe --- --- 2.33 0.04 RA Pressure (higher) 1.52 3 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: Survival After LVAD Implant Adult Primary Intracorporeal LVADs (n=1366) INTERMACS Annual Meeting March 2012

32. INTERMACS: Survival after LVAD Implant Adult Primary Intracorporeal LVADs: n= 1366 Months after Device Implant Predicted % Survival Pulsatile Intracorporeal Continuous Intracorporeal Risk Factor Unadjusted Adjusted Constant Phase Hazard ratio p-value Hazard ratio p-value Pulsatile pump 12.54 <0.0001 3.02 0.001 “Average” Patient INTERMACS Annual Meeting March 2012

33. 33 Early Constant Risk Factor Hazard ratio p-value Hazard ratio p-value Age (older) 2.42 1 <.0001 1.55 1.0005 Bilirubin (higher) 1.41 2.0002 --- --- RA Pressure (higher) 2.08 3.0009 --- --- Cardiogenic Shock 1.97.02 --- --- BTC or DT --- --- 1.80.02 Pulsatile pump --- --- 2.74.001 Table 9 Risk 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 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

34. Terminal Events and Risk Factors What are the Next Steps? Improving Patient Outcomes Device Evaluation and Development Research Topics in INTERMACS INTERMACS Annual Meeting March 2012

35. Panel B: G.Functional Capacity H.Neurocognitive Assessment I.Quality of Life J.Terminal Events and Risk Factors K.Panel Discussion Young Research Topics in INTERMACS INTERMACS Annual Meeting March 2012