David J. Cohen, M.D., M.Sc. On Behalf of the PARTNER Investigators Saint Luke’s Mid America Heart and Vascular Institute

1. Health Related Quality of Life after Transcatheter Aortic Valve Implantation vs. Non-Surgical Therapy among Inoperable Patients with Severe Aortic Stenosis:Results from the PARTNER Trial (Cohort B) David J. Cohen, M.D., M.Sc. On Behalf of the PARTNER Investigators Saint Luke’s Mid America Heart and Vascular Institute University of Missouri-Kansas City Kansas City, Missouri

2. Disclosures The PARTNER trial was funded by a research grant from Edwards Lifesciences, Inc.

3. Background • Over the past decade, transcatheter aortic valve implantation (TAVI) has been developed as a less-invasive alternative to surgical valve replacement for high-risk patients with severe aortic stenosis • Recently, the PARTNER trial demonstrated that for patients who are not suitable candidates for surgery, TAVI led to a significant reduction in all-cause mortality (20% ARR at 1-year, p<0.001) but also an but also an increase in the incidence of major strokes and vascular complications • Given the advanced age and multiple comorbid conditions in these inoperable patients, improvements in quality of life may be an equally important therapeutic goal as improved survival

4. Study Objectives • To compare health-related quality of life outcomes among inoperable patients with severe aortic stenosis, treated with either TAVI or standard therapy • To examine whether the HRQOL benefits of TAVI are influenced by pre-specified patient characteristics • To provide key “input” data for ongoing economic evaluation of TAVI for the inoperable patient population

6. Patient Population • Inclusion Criteria • Severe, symptomatic AS (AVA <0.8 cm2, mean gradient > 40 mmHg, or peak aortic jet velocity >4.0 m/sec) • “Inoperable”  Predicted risk of mortality or irreversible morbidity >50% as determined by 2 independent surgeons • Exclusion Criteria (Selected) • LVEF < 20% • Severe (>3+) MR or AR • Untreated CAD requiring revascularization • Serum creatinine > 3.0 mg/dl or hemodialysis • Recent MI (1 month), stroke or TIA (6 months) • Life expectancy < 12 months

7. Methods: Quality of Life Assessments performed by self-administered questionnaires at baseline, 1, 6, & 12 months

8. KCCQ: Development and Validation • 23 items that measure 5 clinically relevant domains of health status from the patient’s perspective • Symptoms Physical Limitation • Quality of Life Social Limitation • Self-Efficacy • Individual scales combined into an global summary scale (KCCQ Overall Summary) • Independently predictive of mortality and cost among patients with HF Green CP et al. JACC 2000; 35:1245-55 Soto G, et al. Circulation 2004;110:546-51

10. Statistical Analysis • Primary QOL Endpoint = KCCQ Overall Summary Score • All other QOL scales considered secondary endpoints • Scores at each follow-up time point compared between groups by ANCOVA, adjusting for baseline • Longitudinal analyses performed using random effect growth curve models, adjusting for treatment group (TAVI vs. control), time (linear, quadratic, cubic effects), and all potential 2-way and 3-way interactions

11. Baseline Characteristics P=NS for all comparisons

13. Baseline QOL P=NS for all comparisons

18. KCCQ-Summary: Significant Improvement * P <0.001 for all time points * Improvement ≥ 10 points vs. baseline among patients with available QOL data

19. KCCQ-Summary: Favorable Outcome * P <0.001 for all time points *Favorable Outcome = Alive and KCCQ-Summary Score improved ≥ 10 points vs. baseline

20. KCCQ-Summary: Excellent Outcome * P <0.001 for all time points * Excellent Outcome = Alive and KCCQ-Summary Score improved ≥ 20 points vs. baseline

22. Summary • Among patients with severe, inoperable aortic stenosis, TAVI– as compared with non-operative therapy (including BAV in ~80%)-- led to substantial and sustained improvement across a broad range of health status and quality of life domains • The extent of benefit was large for both disease-specific and general QOL and was consistent across all pre-specified subgroups • KCCQ Summary Score 20-25 points (~2-level NHYA Class improvement on average) • SF-12 Physical Component 5 points (~10 year reduction in effective age)

23. Summary- 2 • When QOL was considered along with survival, the number needed to treat to obtain an excellent outcome (i.e., 1-year survival with at least a 20 point improvement in the KCCQ ) was ~3 Clinical Implications: These findings add further support to the concept that TAVI should be considered an emerging standard of care for patients with severe aortic stenosis who are not candidates for surgical AVR

24. Study Administration Co-Principal Investigators Martin B. Leon, Craig R. SmithColumbia University Med Center Executive Committee Martin B. Leon, Michael Mack, D. Craig Miller, Jeffrey W. Moses, Craig R. Smith, Lars G. Svensson, E. Murat Tuzcu, John G. Webb Data & Safety Monitoring Board Chairman: Joseph P. CarrozzaTufts University School of Med Clinical Events Committee Chairman: John L. PetersenDuke University Med Center Echo Core Laboratory Chairman: Pamela C. Douglas Duke University Med Center • Quality of Life and Cost Effectiveness Assessments • Chairman: David J. CohenMid-America Heart Inst, KC • Independent Biostatistical Core Laboratory • Chairman: Stuart PocockLondon School of Hygiene &Tropical Medicine • William N. Anderson • Publications Committee • Co-Chairman: Jeffrey W. Moses, Lars G. Svensson • Sponsor • Edwards Lifesciences: Jodi J. Akin

25. Enrollment by Site - Inoperable

26. Enrollment by Site - Inoperable