1. Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients Assessment of Patient Characteristics and Impact on Patient Decision-Making Joseph Rogers, MD Professor of Medicine Duke University Disclosures: None Decision-Making Challenges: The ROADMAP for Medical Patients INTERMACS 9 th Annual Meeting MCSD: Evolution, Expansion, and Evaluation May 15-16, 2015

2. ROADMAP Patient Populations 1 1 2 2 3 3 4 4 5 5 6 6 7 7 INTERMACS Profiles CMS Coverage: Class IV FDA Approval: Class IIIB/IV Currently Not Approved Limited Adoption Acceptance NYHA Class III NYHA Class III Class IIIB Class IV (Ambulatory) Class IV (On Inotropes) 1.0% 1.4% 3.0% 14.6% 29.9% 36.4% 14.3% Percent of current implants in INTERMACS

3. Objectives and Study Design Primary Objectives –Evaluate and compare the effectiveness of HM II LVAD support vs. optimal medical management (OMM) in –ambulatory NYHA Class IIIB/IV patients –not dependent on intravenous inotropic support (INTERMACS ≥ 4), and –meet the FDA approved indications for HM II LVAD destination therapy Trial Design –Prospective, multi-center, non-randomized, controlled, observational study –Permits characterization of real-world advanced HF treatments strategies in varied health care delivery systems –Includes collaborating cardiologists not directly involved in LVAD care –Includes patients who do not desire LVAD treatment –LVAD indication is already FDA approved – additional data needed to improve patient selection 3 Rogers JG et al: ROADMAP Trial Design: Am Heart J 2015;169:205-10

4. Key Inclusion and Exclusion Criteria Inclusion Criteria NYHA Class IIIB or IV ; Age 18 to 85 Left ventricular ejection fraction (LVEF) ≤ 25% Not listed (or planned) for heart transplantation On optimal medical management (OMM) 6MWT < 300 meters At least 1 hospitalization for HF in last 12 months, or 2 unscheduled ED or infusion clinic visits for HF in last 12 months Exclusion Criteria Any inotrope use within 30 days Inability to perform 6MWT Any ongoing MCS (including IABP & temporary devices) at enrollment CRT or coronary revascularization within 3 months 4 Rogers JG et al: ROADMAP Trial Design: Am Heart J 2015;169:205-10

5. Endpoints Primary Endpoint –Composite of survival with improvement in 6-MWT distance from baseline of ≥75 meters at 12 months Secondary Endpoints –Actuarial survival –Health-related Quality of Life (HRQoL) using the EQ-5D-5L Visual Analog Scale (VAS) –Depression using Patient Health Questionnaire-9 (PHQ-9) –Questionnaire on patient decisions related to LVAD therapy versus OMM –Functional status using 6-MWT distance and NYHA Classification –Adverse events, rehospitalizations 5

6. Baseline Data * Median [range] 6

7. Baseline Data * Median [IQR] 7

8. Reasons Provided for Choosing LVAD or OMM at Baseline 8 Physician Reason for selecting OMMN (%) Physician believes patient isn’t good surgical candidate14 (14%) Physician believes patient isn’t sick enough11 (11%) Other (Drug and alcohol abuse, financial, compliance concerns, etc.)9 (9%) Patient Reason for Selecting OMMN (%) Patient doesn’t like the idea of major device implantation surgery40 (39%) Patient doesn’t want to depend on a machine26 (25%) Patient doesn’t feel sick enough25 (24%) Patient is worried about too many complications with a LVAD21 (20%) Patient doesn’t think a LVAD will improve quality of life13 (13%) Patient Reason for selecting LVADN (%) Patient thinks it will improve chances to live longer81 (84%) Patient thinks it will improve QoL79 (81%) Patient thinks it will improve heart failure symptoms72 (74%) Patient thinks it will help them return to activities they enjoy72 (74%)

9. Patient Questionnaire at Baseline Impact of Baseline QoL Satisfaction 9 Not or slightly satisfied (n=123)Moderately to extremely satisfied (n=123)

10. Primary End-Point * Significantly more LVAD than OMM patients were alive at 12 months on original therapy with increase in 6MWD by 75m 10 O.R. = 2.4 [1.2-4.8] P=0.017 O.R. = 3.7 [1.1-12.2] P=0.026 O.R. = 1.7 [0.6-4.6] P=0.423 N= 85 81 57 26 26 54 Stratified by INTERMACS Profile ***17% of OMM patients crossed over to LVAD

11. Secondary Endpoints VAD Treated Patients Experienced –Better improvements in NYHA Class –Better improvements in 6 MWD –Better improvement in health-related QoL –Better improvement in depression scores

12. Summary and Conclusions ROADMAP demonstrated that patients with advanced heart failure not treated with inotropes have a better improvement in survival associated with an increase in 6MWD > 75m treated with VAD vs. OMM Patients selecting VAD in ROADMAP: –Reported worse symptoms –Had lower submaximal exercise performance –Had lower heath-related QoL and were dissatisfied with QoL –Had more depression –Thought VAD would improve survival, QoL and functionality