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.

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.

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

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

Pool: Adult primary CFLVADs implanted Jun 2006 – Mar 2013 (follow-up thru March 2014) N=7353 (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

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

VAS Scores pre and post implant & change in VAS scores over time Pre-implant 6 months VAS (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.

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 5.0 (1.6) 0.002 BTT: Listed -3.7 (1.2) 0.002 Pre COPD -5.1 (1.8) 0.005 Alcohol abuse -4.1 (1.7) 0.02 Pre-implant VAS Score -0.76 (0.02) < 0.0001 Clinical Course BTT: Unlikely at 6 months -9.6 (2.9) 0.0009 BTT: Mod likely at 6 months -4.8 (1.9) 0.01 NYHA 4 at 6 months -15.2 (2.9) < 0.0001 Events within first 6 months Renal Dysfunction -5.3 (2.5) 0.03 Respiratory Failure -4.8 (1.8) 0.007 Neurological Dysfunction -5.5 (1.9) 0.004 Infection -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’

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

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

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

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) 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

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

Available for HRQOL assessment at 1 year post implant* (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%

EQ-5D: Visual Analog Scale INTERMACS Patient Profile Levels Best Health Mean VAS Worst Health N= 51 93 68 45 389 298 239 166 202 141 127 91 111 70 63 51 55 43 43 29 p = < .0001 <.0001 <.0001 <.0001 <.0001 (Pre implant vs 12 mos. post implant) INTERMACS Patient Profile Levels Utilizes all EQ-5D available at each time period

EQ-5D: Mobility, Patients with any Problems % Patients with Any Mobility Problems N= 51 96 69 46 389 300 243 169 206 142 127 91 113 71 64 51 57 43 43 29 p = <.0001 <.0001 <.0001 <.0001 <.0001 (Pre implant vs 12 mos. post implant) INTERMACS Patient Profile Levels Utilizes all EQ-5D available at each time period

INTERMACS Patient Profile Levels EQ-5D: Usual Activities, Patients with any Problems % Patients with Any Usual Activities Problems N= 51 96 69 46 390 300 242 169 207 143 127 91 112 71 64 51 57 43 43 29 p = <.0001 <.0001 <.0001 <.0001 <.0001 (Pre implant vs 12 mos. post implant) INTERMACS Patient Profile Levels Utilizes all EQ-5D available at each time period

EQ-5D: Self Care, Patients with any Problems % Patients with Any Self Care Problems N= 51 96 68 46 390 300 242 169 207 143 127 91 113 71 64 51 57 43 43 29 p = <.0001 <.0001 <.0001 .02 .05 (Pre implant vs 12 mos. post implant) INTERMACS Patient Profile Levels Utilizes all EQ-5D available at each time period

EQ-5D: Anxiety/Depression, Patients with any Problems % Patients with Any Anxiety/Depression Problems N= 51 95 69 46 391 297 241 169 206 142 127 91 113 71 64 51 55 44 43 29 p= .0004 <.0001 .06 .05 .01 (Pre implant vs 12 mos. post implant) INTERMACS Patient Profile Levels Utilizes all EQ-5D available at each time period

EQ-5D: Pain, Patients with any Problems % Patients with Any Pain Problems N= 51 95 69 46 392 299 243 169 207 143 127 91 113 71 64 51 56 43 43 29 p= .20 .003 .04 .10 .008 (Pre implant vs 12 mos. post implant) INTERMACS Patient Profile Levels Utilizes all EQ-5D available at each time period

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

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’

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%)

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

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

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 - 0.89 < .0001 Re-hospitalization -10.90 < .0001 R2=61.3%, intercept=77.1 VAS at pre-implant

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

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

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

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

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”

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