INTERMACS 2016 - 2020 So, with more detailed analyses from databases such as CTRD and ISHLT, there is an opportunity for identifying pts who, with their co-morbidities, might expect a nearly equivalent survival with either VAD or Tx.

Disclosure I have no financial relationships to disclose A number of issues amplify the challenges and enigma of this rather final platform of care. ..(read slide)

Goals of the Registry Facilitate the refinement of patient selection to maximize outcomes with current and new device options. Identify predictors of good outcomes as well as risk factors for adverse events after device implantation. Develop consensus “best practice” guidelines to improve clinical management by reducing short and long term complications of MCSD therapy.. Utilize Registry information to guide improvements in technology, clinical application and evolution of next generation devices. Provide hospital specific Quality Assurance Reports. (added 2010)

Goals of the Registry Facilitate the refinement of patient selection to maximize outcomes with current and new device options. Identify predictors of good outcomes as well as risk factors for adverse events after device implantation. Develop consensus “best practice” guidelines to improve clinical management by reducing short and long term complications of MCSD therapy.. Utilize Registry information to guide improvements in technology, clinical application and evolution of next generation devices. Provide hospital specific Quality Assurance Reports. (added 2010)

INTERMACS Each of these goals provides an opportunity for innovation within INTERMACS

Timing of a unique opportunity Innovation within INTERMACS is the amalgamation of NHLBI willingness to push this experiment, dedication of the stakeholders & caregivers to engage, and the vision of the leadership Timing of a unique opportunity Skill, vision, & preparation

INTERMACS has expanded and evolved during the past nine years Research registry Refined adverse event definitions Expanded data collection Quality Assurance registry Analyses that can be used for reports to The Joint Commission Research priorities that facilitate patient decisions Industry/FDA collaborations Self-sustainability, Protocol 4.0: Waiver of consent

In this rapidly evolving and changing platform of MCS, individual centers must frequently reevaluate the outcome effects of programatic refinements in surgical or medical management on such critical metrics as Survival, Adverse Events, and HRQOL? In addition to survival, pts may increasingly incorporate “life satisfaction” into the decision about therapies.

In order for hospitals to see their own trends early and allow for “midcourse corrections” , they need “real time” access to both their own information AND comparisons to national (or international) aggregate data. But, if we are going to triage medical or tx pts to device Rx, we must have data to answer the fundamental question….

Intermacs Annual Report Agenda Devin Koehl, BS Research Programming and Statistical Review   Data Quality Report Quality Assurance Report Live Data Download Site Datasets (SAS) Research Datasets Customized Cohort Reports Outcome Analytics Patient Informatics I. Accessing Your Data Examining/Validating your data ü Compliance Rates Electronic copies of your data II. Patient Management Tools Clinical timeline Clinical measures across time III. Patient Selection and Outcomes Quality Assurance Report Cohort (subset) report Benchmarking ü  IV. Quality Initiatives Joint Commission Internal Initiatives V. Using Intermacs for Your Research Within your site Across Intermacs

Quality Assurance Report Customized Cohort Reports 10th Annual Meeting: Friday, March 11th – Products for the Sites Web Based Reporting – Tools Under Development: Customized Cohort Reports and Outcome Analytics Ryan S. Cantor, MSPH Director, Statistical Reporting   Data Quality Report Quality Assurance Report Live Data Download Site Datasets (SAS) Research Datasets Customized Cohort Reports Outcome Analytics Patient Information I. Accessing Your Data Examining/Validating your data ü Compliance Rates Electronic copies of your data II. Patient Management Tools Clinical timeline Clinical measures across time III. Patient Selection and Outcomes Quality Assurance Report Cohort (subset) report Benchmarking ü  IV. Quality Initiatives Joint Commission Internal Initiatives V. Using Intermacs for Your Research Within your site Across Intermacs ADD PAGE NUMBER FOCUS ON ds

Cohort Comparison Reports Outcome Analytic Reports Phase 1. Form Download Status: Complete Phase 2. Cohort Comparison Reports Status: Testing Phase 3. Outcome Analytic Reports Status: Design

The Impact of Changes in CMS Coverage for MCSD Post Implant Survival - Primary LVADs

These K-M depictions for a variety The Impact of Changes in CMS Coverage for MCSD Post Implant Survival - Primary LVADs These K-M depictions for a variety of individual center patient cohorts with near instantaneous simultaneous depictions of the same cohort from all of INTERMACS will be available by summer , 2016

Platform for INTERMACS investigators to compete for NIH funding INTERMACS: Developments on the Horizon for Science Platform for INTERMACS investigators to compete for NIH funding Research to target QOL and its relationship to adverse events and choice of therapies Development of a composite tool to quantify “life satisfaction” with the choice of MCS for advanced heart failure

INTERMACS: Developments on the Horizon for Patient Decisions Platform for truly informed patient decisions about therapies for advanced heart failure For INTERMACS levels 1 – 3, the survival benefit is so large that it dominates the Life Satisfaction Equation. The relative components become especially important in INTERMACS level 4 – 6 patients , where survival may be similar between therapies

Future of Tx/VAD Rx Education War Era Cardiac Surgery Hypothesis: the SEMI-QUANTIFICATION of the subjective outcomes of “Is your life better with the device?” or “Are you functional with a good quality of life?” will become a critical component of the denominator of the Cost-effectiveness calculations

Thus, the interaction between Survival and Life Satisfaction in Decisions about Medical Rx vs VAD Therapy calls for Quantification that only large databases like INTERMACS can provide Read.

So, how do we frame the patient conversation to help him/her and their family make a truly informed decision? Read.

Multivariable Risk Model Life Satisfaction Survival

Life Satisfaction HRQOL : Generic – EQ5D , VAS HRQOL: Disease specific – KCCQ Specific Domains Functional outcome: 6 minute walk Visual Analog Score

Life Satisfaction Physical Domain incorporates the physical components of EQ5D and KCCQ plus 6-minute walk (functional outcome) Mental/emotional Domain incorporates those components of EQ5D and KCCQ Adverse Events VAS

Adverse Events Rank by severity of deficit Rank by number of hospital days Modulated renewal analysis of serious adverse event impact on HRQOL and survival

MCS ( or other therapy): Life Satisfaction Time-related Depictions Separate Analysis for Each Major Domain: Emotional/Psychological (Quantified Scale) Separate Analysis for Each Major Domain: Physical (Quantified Scale) Serious Adverse Events

MCS ( or other therapy): Life Satisfaction Time-related Depictions Separate Analysis for Each Major Domain: Emotional/Psychological (Quantified Scale) Separate Analysis for Each Major Domain: Physical (Quantified Scale) Serious Adverse Events Modulated renewal after each AE VAS

Survival MCS ( or other therapy): Life Satisfaction/Survival Multi- Variable Analysis Time-related Depictions Separate Analysis for Each Major Domain: Emotional/Psychological (Quantified Scale) Separate Analysis for Each Major Domain: Physical (Quantified Scale) Serious Adverse Events Modulated renewal after each AE Survival VAS

HRQOL Physical Analytic Goals: So, we have some work to do… Multiple INTERMACS studies are needed to condense the physical domains within KCCQ and EQ5D +/- 6MW so that we can generate a single score in order to compare the patient’s pre- and postoperative state. HRQOL Physical

HRQOL Mental/Emotional Analytic Goals: So, we have some work to do… Multiple INTERMACS studies are needed to condense the mental/emotional domains within KCCQ and EQ5D so that we can generate a single score in order to compare the patient’s pre- and postoperative state. HRQOL Mental/Emotional

Research and Analytic Goals for Truly Informed Consent in Ambulatory Heart Failure Patients Expected Outcome =f ( a survival + b freedom from various key adverse events….+ c physical domain LS +d mental/emotional LS estimates)

Analytic Goals Patient weighs the importance of each Life Satisfaction Domain (physical vs mental/emotional) (60/40,50/50,etc) An expected quantified score is developed for each major domain at specified intervals. A combined event of survival with life satisfaction in the relevant domain &/or domain ratios is created

Analytic Goals The most relevant multivariate is solved with the patient’s risk profile to examine the likelihood of MCS or another therapy fulfilling their goals by including the specified components of survival and the HRQOL domains Additional models of the effect of serious adverse events on VAS and survival can also be displayed

Example: Pt/family interview generates the following proportions for Survival/Life Satisfaction: Survival 60%, Physical 20%, Mental/Emotional 20% …….or Survival 40%, Physical 20%, Mental/Emotional 40%

Survival MCS ( or other therapy): Life Satisfaction/Survival Multi- Variable Analysis Time-related Depictions Separate Analysis for Each Major Domain: Emotional/Psychological (Quantified Scale) Separate Analysis for Each Major Domain: Physical (Quantified Scale) Serious Adverse Events Modulated renewal after each AE Survival VAS

The Future of VAD RX % Survival Time LVAD offers a survival benefit LVAD: Survival Medical Survival % Survival So, when we have sufficient data to generate comparative survival curves for med and VAD rx for ambulatory hrt failure, we see here an example. LVAD offers a survival benefit 6 mo 12 mo 30 mo 24 mo 18 mo 36 mo 42 mo 48 mo Time

The Future of VAD RX % Survival Time LVAD offers a survival benefit LVAD: Survival Medical Survival % Survival In which LVAD Rx provides superior survival LVAD offers a survival benefit 6 mo 12 mo 30 mo 24 mo 18 mo 36 mo 42 mo 48 mo Time

Survival – Life Satisfaction Composite The Future of VAD RX LVAD: Survival Medical Survival Survival – Life Satisfaction Composite Medical: Survival – life satisfaction composite LVAD: Survival – life satisfaction composite For the stable INTERMACS Level 4 - 7 patient, LVAD could offer a survival benefit, but if expected life satisfaction is inferior, medical therapy might offer a better overall benefit But if the adverse event burden is high with LVAD Rx, 6 mo 12 mo 30 mo 24 mo 18 mo 36 mo 42 mo 48 mo Time

Survival – Life Satisfaction Composite The Future of VAD RX LVAD: Survival Medical Survival Survival – Life Satisfaction Composite Medical: Survival – life satisfaction composite LVAD: Survival – life satisfaction composite For the stable INTERMACS Level 4 - 7 patient, LVAD could offer a survival benefit, but if expected life satisfaction is inferior, medical therapy might offer a better overall benefit But if the adverse event burden is high with LVAD Rx, 6 mo 12 mo 30 mo 24 mo 18 mo 36 mo 42 mo 48 mo Time

Survival – Life Satisfaction Composite The Future of VAD Rx LVAD: Survival Medical Survival Survival – Life Satisfaction Composite LVAD: Survival – Life Satisfaction composite Medical: Survival – Life Satisfaction composite For the stable INTERMACS Level 4 - 7 patient, LVAD could offer an overall benefit if the expected life satisfaction is sufficient to preserve an advantage over medical therapy. However, if the AE burden is sufficiently low with VADs, 6 mo 12 mo 30 mo 24 mo 18 mo 36 mo 42 mo 48 mo Time

Survival – Life Satisfaction Composite The Future of VAD Rx LVAD: Survival Medical Survival Survival – Life Satisfaction Composite LVAD: Survival – Life Satisfaction composite Medical: Survival – Life Satisfaction composite For the stable INTERMACS Level 4 - 7 patient, LVAD could offer an overall benefit if the expected life satisfaction is sufficient to preserve an advantage over medical therapy. However, if the AE burden is sufficiently low with VADs, 6 mo 12 mo 30 mo 24 mo 18 mo 36 mo 42 mo 48 mo Time

Summary Points Although controversial, the NHLBI, FDA, and the advanced heart failure community agree that major challenges confound the analyses of MCS versus alternative therapies in patient subsets with ambulatory advanced heart failure. For VADs to ultimately have a place in the therapy of this population, survival must be at least equivalent to medical therapy, adverse event burden must be favorable, and life satisfaction must be superior with device therapy. Patients and providers will demand increasing quantification of “life satisfaction”, which will complement the calculation of survival with each therapy. Patients and providers will demand increasing quantification of “life satisfaction”, which will complement the

Summary Points The adverse event profile of individual MCS devices will dramatically affect the calculus of both the “Life Satisfaction/Survival Score” (LSSS) and the “Cost-effective Care” equation. Final recommendations will weigh heavily on time-related depictions (curves) of mathematical solutions to these LSSS equations. easing quantification of “life satisfaction”, which will complement the