Joseph Rogers, MD Professor of Medicine Duke University

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

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

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 Rogers JG et al: ROADMAP Trial Design: Am Heart J 2015;169:205-10 3

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 Rogers JG et al: ROADMAP Trial Design: Am Heart J 2015;169:205-10 4

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 6 * Median [range]

7. Baseline Data 7 * Median [IQR]

8. Reasons Provided for Choosing LVAD or OMM at Baseline 8

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

10. Primary End-Point *Significantly more LVAD than OMM patients were alive at 12 months on original therapy with increase in 6MWD by 75m Stratified by INTERMACS Profile 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 ***17% of OMM patients crossed over to LVAD 10

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