1. Martin B. Leon, MD on behalf of the PARTNER Investigators TCT 2010; Washington, DC; September 23, 2010 Transcatheter Aortic Valve Implantation in Inoperable Patients with Severe Aortic Stenosis

2. Presenter Disclosure Information for PARTNER at TCT ; September 23, 2010 Martin B. Leon, M.D. Scientific Advisory Board Edwards Lifesciences, Medtronic, Scientific Advisory Board Edwards Lifesciences, Medtronic, and Symetis Equity Relationship and Symetis Equity Relationship Sadra Sadra Scientific Advisory Board Edwards Lifesciences, Medtronic, Scientific Advisory Board Edwards Lifesciences, Medtronic, and Symetis Equity Relationship and Symetis Equity Relationship Sadra Sadra

3. Background Background There has been explosive growth in transcatheter aortic valve implantation (TAVI) since the first procedure in 2002.There has been explosive growth in transcatheter aortic valve implantation (TAVI) since the first procedure in 2002. Although patient selection, operator skills, and technology have improved, all previous TAVI studies have been observational registries, without standardization of endpoint definitions.Although patient selection, operator skills, and technology have improved, all previous TAVI studies have been observational registries, without standardization of endpoint definitions. There is a paucity of evidence-based clinical data to substantiate incremental benefits of TAVI compared with current standard therapies.There is a paucity of evidence-based clinical data to substantiate incremental benefits of TAVI compared with current standard therapies.

4. Purpose Purpose To assess the safety and effectiveness of TAVI compared with standard therapy, in patients with severe aortic stenosis and cardiac symptoms, who cannot undergo surgery (“inoperable”), using rigorous evidence-based clinical trial methodologies. To assess the safety and effectiveness of TAVI compared with standard therapy, in patients with severe aortic stenosis and cardiac symptoms, who cannot undergo surgery (“inoperable”), using rigorous evidence-based clinical trial methodologies.

5. Symptomatic Severe Aortic Stenosis ASSESSMENT: High Risk AVR Candidate 3105 Total Patients Screened ASSESSMENT: High Risk AVR Candidate 3105 Total Patients Screened PARTNER Study Design High Risk TA ASSESSMENT: Transfemoral Access TAVITrans femoralTAVITrans Surgical AVR High Risk TF Primary Endpoint: All Cause Mortality (1 yr) (Non-inferiority) TAVITransfemoralTAVITransfemoral Surgical AVR 1:1 Randomization VS Standard Therapy (usually BAV) Standard Therapy (usually BAV) ASSESSMENT: Transfemoral Access Not In Study TAVITransfemoralTAVITransfemoral Primary Endpoint: All Cause Mortality over length of trial (Superiority) 1:1 Randomization VS Total = 1058 patients 2 Parallel Trials: Individually Powered High Risk n= 700 InoperableInoperable n=358

6. Primary and Co-Primary Endpoints PRIMARY: All-cause mortality over the duration of the studyPRIMARY: All-cause mortality over the duration of the study  Superiority test (two-sided), 85% power to detect a difference, α = 0.05, sample size = 350 total patients CO-PRIMARY: Hierarchical composite of all-cause mortality and repeat hospitalizationCO-PRIMARY: Hierarchical composite of all-cause mortality and repeat hospitalization  Non-parametric method described by Finkelstein and Schoenfeld (multiple pair-wise comparisons)  > 95% power to detect a difference, α = 0.05 Positive study if both endpoints P < 0.05, or if either endpoint is < 0.025Positive study if both endpoints P < 0.05, or if either endpoint is < 0.025

7. Other Important Endpoints Cardiovascular mortalityCardiovascular mortality Repeat hospitalization (after the index procedure)Repeat hospitalization (after the index procedure)  Due to valve or procedure-related clinical deterioration  Mortality and repeat hospitalization (KM analysis) Major strokes (modified Rankin Score ≥ 2 @ ≥ 30 days)Major strokes (modified Rankin Score ≥ 2 @ ≥ 30 days)  Mortality and major strokes (KM analysis) Major vascular complications (VARC definition)Major vascular complications (VARC definition) NYHA symptom classificationNYHA symptom classification QOL and cost-effectiveness assessmentsQOL and cost-effectiveness assessments Six-minute walk testsSix-minute walk tests Echo assessments of valve function (core lab)Echo assessments of valve function (core lab)  EOA, mean gradient, aortic regurgitation

8. Study Administration Study Administration Co-Principle InvestigatorsCo-Principle Investigators  Martin B. Leon, Craig R. Smith Columbia University Med Center Executive CommitteeExecutive 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 BoardData & Safety Monitoring Board  Chairman: Joseph P. Carrozza Tufts University School of Med Clinical Events CommitteeClinical Events Committee  Chairman: John L. Petersen Duke University Med Center Echo Core LaboratoryEcho Core Laboratory  Chairman: Pamela C. Douglas Duke University Med Center Quality of Life and Cost Effectiveness Assessments  Chairman: David J. Cohen Mid-America Heart Inst, KC Independent Biostatistical Core Laboratory  Chairman: Stuart Pocock London School of Hygiene & Tropical Medicine  William N. Anderson Publications CommitteePublications Committee  Co-Chairman: Jeffrey W. Moses, Lars G. Svensson SponsorSponsor  Edwards Lifesciences: Jodi J. Akin

9. Executive Committee Executive Committee Michael MackJohn Webb Murat TuzcuCraig Miller Marty LeonJeff Moses Craig Smith Lars Svensson

10. Total Enrollment TF TATotal High Risk Surgical Roll-in211940 Randomized493207700 Cont Access (non-rand)*251242493 Inoperable Roll-in21NA21 Randomized358NA358 Cont Access (rand)91NA91 Cont Access (non-rand)*132NA132 Overall1,3654641,835 *as of September 1, 2010

11. Intermountain Medical Center Salt Lake City Emory University Atlanta, GA Univ. of Miami Miami, FL St. Luke’s Hospital Kansas City, MO Barnes-Jewish Hospital St. Louis, MO Medical City Dallas Dallas, TX St. Paul's Hospital Vancouver, Canada Univ of Washington Seattle, WA Mayo Clinic Rochester, MN Stanford University Palo Alto, CA Hospital Laval Quebec City, Canada Ochsner Foundation New Orleans, LA Scripps Clinic La Jolla, CA Cedars-Sinai Medical Center Los Angeles, CA Cleveland Clinic Cleveland, OH Columbia University New York, NY Washington Hosp. Center Wash., DC Cornell University Univ. Penn Phila., PA Mass General Boston, MA Brigham & Women’s Boston, MA Northwestern Univ. Chicago, IL Toronto Gen. Hospital Canada Evanston Hospital Leipzig Heart Center Leipzig, Germany Total Enrollment Univ. of Virginia Charlottesville, VA n = 1058 patients 26 Investigator Sites 22 USA, 3 Canada, 1 Germany

12. Intermountain Medical Center Salt Lake City Emory University Atlanta, GA Univ. of Miami Miami, FL St. Luke’s Hospital Kansas City, MO Barnes-Jewish Hospital St. Louis, MO Medical City Dallas Dallas, TX St. Paul's Hospital Vancouver, Canada Univ of Washington Seattle, WA Mayo Clinic Rochester, MN Stanford University Palo Alto, CA Hospital Laval Quebec City, Canada Ochsner Foundation New Orleans, LA Scripps Clinic La Jolla, CA Cedars-Sinai Medical Center Los Angeles, CA Cleveland Clinic Cleveland, OH Columbia University New York, NY Washington Hosp. Center Wash., DC Cornell University Univ. Penn Phila., PA Mass General Boston, MA Brigham & Women’s Boston, MA Northwestern Univ. Chicago, IL Toronto Gen. Hospital Canada Evanston Hospital Leipzig Heart Center Leipzig, Germany Enrollment - Inoperable n = 358 patients 21 Investigator Sites 17 USA, 3 Canada, 1 Germany Univ. of Virginia Charlottesville, VA

13. Cedars-Sinai Medical Ctr Los Angeles, CA G. Fontana, R. Makkar 169 Columbia University New York City, NY M. Leon, C. Smith 133 Medical City Dallas Dallas, TX D. Brown, M. Mack 120 Emory University Atlanta, GA P. Block, R. Guyton 118 Washington Hospital Ctr District of Columbia P. Corso, A. Pichard 99 Cleveland Clinic Found Cleveland, OH L. Svensson, M. Tuzcu 97 University of Pennsylvania Philadelphia, PA J. Bavaria, H. Herrmann 95 University of Miami Miami, FL W. O’Neill, D. Williams 44 Barnes-Jewish Hospital St. Louis, MO R. Damiano, J, Lasala 41 St. Paul's Hospital Vancouver, BC, Canada A. Cheung, J. Webb 41 Stanford University Palo Alto, CA C. Miller, A. Yeung 39 Northwestern University Chicago, IL C. Davidson, P. McCarthy 30 Overall Enrollment by Site

14. St. Luke’s Hospital Kansas City, MO K. Allen, D. Cohen 24 Mass General Hospital Boston, MA I. Palacios, G. Vlahakis 24 Mayo Clinic Rochester, MN C. Rihal, T. Sundt 20 Scripps Clinic La Jolla, CA S. Brewster, P. Teirstein 20 Univ of Washington Seattle, WA M. Reisman, E. Verrier 19 Northshore Univ Health Sys Evanston, IL J. Alexander, T. Feldman 17 Universitaire de Quebec Laval, Quebec, CA D. Doyle, J. Rodes-Cabau 12 Herzzentrum Leipzig Leipzig, Germany F. Mohr, G. Schuler 11 University of Virginia Charlottesville, VA I. Kron, S. Lim 7 Brigham & Women’s Hosp Boston, MA M. Davidson, A. Eisenhauer 6 Cornell University New York City, NY K. Krieger, C. Wong 5 Ochsner Foundation New Orleans, LA E. Parrino, S. Ramee 5 Intermountain Med Center Salt Lake City, UT K. Jones, B. Whisenant 4 Toronto General Hospital Toronto, Ontario, CA C. Feindel, E. Horlick 2

15. Enrollment by Site - Inoperable Cedars-Sinai Medical Ctr Los Angeles, CA G. Fontana, R. Makkar 36 Columbia University New York City, NY M. Leon, C. Smith 33 Medical City Dallas Dallas, TX D. Brown, M. Mack 21 Emory University Atlanta, GA P. Block, R. Guyton 43 Washington Hospital Ctr District of Columbia P. Corso, A. Pichard 50 Cleveland Clinic Found Cleveland, OH L. Svensson, M. Tuzcu 45 University of Pennsylvania Philadelphia, PA J. Bavaria, H. Herrmann 21 University of Miami Miami, FL W. O’Neill, D. Williams 15 Barnes-Jewish Hospital St. Louis, MO R. Damiano, J, Lasala 12 St. Paul's Hospital Vancouver, BC, Canada A. Cheung, J. Webb 22 Stanford University Palo Alto, CA C. Miller, A. Yeung 6 Northwestern University Chicago, IL C. Davidson, P. McCarthy 6

16. St. Luke’s Hospital Kansas City, MO K. Allen, D. Cohen 5 Mass General Hospital Boston, MA I. Palacios, G. Vlahakis 2 Mayo Clinic Rochester, MN C. Rihal, T. Sundt 7 Scripps Clinic La Jolla, CA S. Brewster, P. Teirstein 8 Univ of Washington Seattle, WA M. Reisman, E. Verrier 8 Northshore Univ Health Sys Evanston, IL J. Alexander, T. Feldman 10 Universitaire de Quebec Laval, Quebec, CA D. Doyle, J. Rodes-Cabau 4 Herzzentrum Leipzig Leipzig, Germany F. Mohr, G. Schuler 2 University of Virginia Charlottesville, VA I. Kron, S. Lim 0 Brigham & Women’s Hosp Boston, MA M. Davidson, A. Eisenhauer 0 Cornell University New York City, NY K. Krieger, C. Wong 0 Ochsner Foundation New Orleans, LA E. Parrino, S. Ramee 0 Intermountain Med Center Salt Lake City, UT K. Jones, B. Whisenant 0 Toronto General Hospital Toronto, Ontario, CA C. Feindel, E. Horlick 2 Enrollment by Site - Inoperable

17. Study Devices Retroflex 1 Edwards-SAPIEN THV 23mm and 26mm valve sizes 22F and 24F sheath sizes

18. Inclusion Criteria Severe calcific aortic stenosis defined as echo derived valve area of 40 mmHg or jet velocity > 4.0 m/s NYHA functional class II or greater Risk of death or serious irreversible morbidity as assessed by cardiologist and two surgeons must exceed 50% Risk of death or serious irreversible morbidity as assessed by cardiologist and two surgeons must exceed 50%

19. Key Exclusion Criteria - 1 Aortic valve is bicuspid or non-calcifiedAortic valve is bicuspid or non-calcified Aortic annulus diameter (echo measurement) 25 mmAortic annulus diameter (echo measurement) 25 mm Aortic dissection or iliac-femoral dimensions or disease which precludes safe sheath insertionAortic dissection or iliac-femoral dimensions or disease which precludes safe sheath insertion Severe LV dysfunction (LVEF < 20%)Severe LV dysfunction (LVEF < 20%) Untreated CAD requiring revascularizationUntreated CAD requiring revascularization Severe AR or MR (> 3+) or prosthetic valve (any location)Severe AR or MR (> 3+) or prosthetic valve (any location)

20. Key Exclusion Criteria - 2 Serum Cr > 3.0 mg/dL or dialysis dependentSerum Cr > 3.0 mg/dL or dialysis dependent Acute MI within 1 monthAcute MI within 1 month Upper GI bleed within 3 monthsUpper GI bleed within 3 months CVA or TIA within 6 monthsCVA or TIA within 6 months Any cardiac procedure, other than BAV, within 1 month or within 6 months for DESAny cardiac procedure, other than BAV, within 1 month or within 6 months for DES Hemodynamic instability (e.g. requiring inotrope support)Hemodynamic instability (e.g. requiring inotrope support) Life expectancy < 12 months (or little hope for meaningful lifestyle recovery)Life expectancy < 12 months (or little hope for meaningful lifestyle recovery)

21. Patient Characteristics - 1 CharacteristicTAVIn=179 Standard Rx n=179 P value Age - yr 83.1 ± 8.683.2 ± 8.30.95 Male sex (%)45.846.90.92 STS Score 11.2 ± 5.812.1 ± 6.10.14 Logistic EuroSCORE26.4 ± 17.230.4 ± 19.10.04 NYHA I or II (%) III or IV (%) 7.8 92.2 6.1 93.9 0.68 CAD (%)67.674.30.20 Prior MI (%)18.626.40.10 Prior CABG (%)37.445.60.17 Prior PCI (%)30.524.80.31 Prior BAV (%)16.224.40.09 CVD (%)27.427.51.00

22. Patient Characteristics - 2 Characteristic TAVI TAVI n= 179 Standard Rx Standard Rx n=179 P value PVD (%) 30.325.10.29 COPD Any (%) Any (%) O2 dependent (%) O2 dependent (%) 41.3 21.2 52.5 25.7 0.04 0.38 Creatinine >2mg/dL (%) 5.69.60.23 Atrial fibrillation (%) 32.948.80.04 Perm pacemaker (%) 22.919.50.49 Pulmonary HTN (%) 42.443.80.90 Frailty (%) 18.128.00.09 Porcelain aorta (%) 19.011.20.05 Chest wall radiation (%) 8.98.41.00 Chest wall deformity (%) 8.45.00.29 Liver disease (%) 3.4 1.00

23. Baseline Echocardiography (core lab) Characteristic TAVI n=179 Standard Rx n=179 P value Aortic valve area (cm 2 )0.6 ± 0.2 0.96 Mean AV gradient (mm Hg)44.5 ± 15.743.0 ± 15.30.39 Mean LVEF (%)53.9 ± 13.151.1 ± 14.30.06 Mod-Severe MR (%) (≥ 3+) 22.223.00.90

24. Procedural Outcomes TAVI (179 patients) 6 (3.4%) pts did not receive TAVI 6 (3.4%) pts did not receive TAVI  2 died before scheduled implant  2 unsuccessful transfemoral access  2 intra-procedural annulus measurement too large and procedure aborted After randomization, median time to TAVI was 6 days (inter-quartile range 3 - 11 days) After randomization, median time to TAVI was 6 days (inter-quartile range 3 - 11 days) During TAVI (first 24 hours) During TAVI (first 24 hours)  2 (1.1%) deaths  3 (1.7%) major strokes  1 (0.6%) valve embolization  2 (1.1%) pts with multiple (≥ 2) valve implants In the first 30 days, 11 (6.4%) pts receiving TAVI died In the first 30 days, 11 (6.4%) pts receiving TAVI died

25. Procedural Outcomes Standard Rx (179 patients) BAV performed in 114 (63.7%) pts ≤ 30 days and an additional 36 (20.1%) pts > 30 days after randomization (total BAV = 83.8% pts) BAV performed in 114 (63.7%) pts ≤ 30 days and an additional 36 (20.1%) pts > 30 days after randomization (total BAV = 83.8% pts) Despite inoperable status: Despite inoperable status:  12 (6.7%) pts received AVR  5 (2.8%) received LV - desc Ao conduit + AVR  4 (2.2%) received TAVI outside US 1-year mortality of pts receiving AVR, AVR-conduit, or TAVI (outside US): 1-year mortality of pts receiving AVR, AVR-conduit, or TAVI (outside US):  AVR - 33%  AVR + conduit - 80%  TAVI (outside US) - 0%

26. All Cause Mortality Numbers at Risk Numbers at Risk TAVI TAVI1791381226726 Standard Rx Standard Rx179121 83 834112 All-cause mortality (%) Months HR [95% CI] = 0.54 [0.38, 0.78] P (log rank) < 0.0001 Standard Rx TAVI

27. All Cause Mortality Numbers at Risk Numbers at Risk TAVI TAVI1791381226726 Standard Rx Standard Rx179121 83 834112 Standard Rx TAVI All-cause mortality (%) Months ∆ at 1 yr = 20.0% NNT = 5.0 pts 50.7% 30.7%

28. Compare, at random, every TAVI patient with every Standard Rx patient; 179 x 179 (32,041) patient pairs, which did better?Compare, at random, every TAVI patient with every Standard Rx patient; 179 x 179 (32,041) patient pairs, which did better? #1, compare “time to death”#1, compare “time to death”  72% chance that we know who died first  If so, 63% chance that Standard Rx patient died first and 37% chance that TAVI patient died first #2, if necessary, compare “time to repeat hospitalization”#2, if necessary, compare “time to repeat hospitalization”  17% chance that we know who had repeat hosp first  If so, 75% chance that Standard Rx patient had repeat hosp first and 25% chance that TAVI patient had repeat hosp first Finklestein & Schoenfeld Analysis (hierarchical multiple pair-wise comparison) FS Method Produces a P-value < 0.0001

29. 124/124 or 100% followed at 1 Yr 124/124 or 100% followed at 1 Yr 85/90 or 94.4% followed at 1 Yr 85/90 or 94.4% followed at 1 Yr 5 = Withdrawal = 0 89 = Death = 55 Study Flow - Inoperable n=358 Randomized Inoperable n=358 167/167 or 100% followed at 30 days 167/167 or 100% followed at 30 days 173/174 or 99.4% followed at 30 days 173/174 or 99.4% followed at 30 days 1 = Withdrawal = 0 5 = Death = 12 n=179 TAVI n=179 TAVI n=179 Standard therapy n=179

30. Cardiovascular Mortality Numbers at Risk Numbers at Risk TAVI TAVI1791381226726 Standard Rx Standard Rx179121 83 834112 Standard Rx TAVI Cardiovascualr mortality (%) Months 0 20 40 60 80 100 HR [95% CI] = 0.39 [0.27, 0.56] P (log rank) < 0.0001

31. Cardiovascular Mortality Numbers at Risk Numbers at Risk TAVI TAVI1791381226726 Standard Rx Standard Rx179121 83 834112 Standard Rx TAVI Cardiovascualr mortality (%) Months 0 20 40 60 80 100 ∆ at 1 yr = 24.1% NNT = 4.1 pts 44.6% 20.5%

32. Mortality or Repeat Hosp Standard Rx TAVI All-cause mortality or Repeat Hospitalization (%) Months 0 20 40 60 80 100 Numbers at Risk Numbers at Risk TAVI TAVI1791171025622 Standard Rx Standard Rx179121 49 4923 4 HR [95% CI] = 0.46 [0.35, 0.59] P (log rank) < 0.0001

33. Standard Rx TAVI All-cause mortality or Repeat Hospitalization (%) Months 0 20 40 60 80 100 Numbers at Risk Numbers at Risk TAVI TAVI1791171025622 Standard Rx Standard Rx179121 49 4923 4 ∆ at 1 yr = 29.1% NNT = 3.4 pts 71.6% 42.5% Mortality or Repeat Hosp

34. Mortality or Major Stroke Standard Rx TAVI All-cause mortality or Major Stroke (%) Months 0 20 40 60 80 100 Numbers at Risk Numbers at Risk TAVI TAVI1791321185625 Standard Rx Standard Rx179118 83 834112 HR [95% CI] = 0.58 [0.43, 0.78] P (log rank) = 0.0003

35. Mortality or Major Stroke Standard Rx TAVI All-cause mortality or Major Stroke (%) Months 0 20 40 60 80 100 Numbers at Risk Numbers at Risk TAVI TAVI1791321185625 Standard Rx Standard Rx179118 83 834112 ∆ at 1 yr = 18.3% NNT = 5.5 pts 51.3% 33.0%

36. Outcome 30 Days n=179 TAVI Standard Rx P-value 1 Year 1 Yearn=179 TAVI Standard Rx P-value Clinical Outcomes at 30 Days & 1 Year Myocardial infarction All (%)00.0.6 1.00 Peri-procedural (%00.00. Stroke or TIA All (%)6.71.70.0310.64.50.04 TIA (%)00.0.601.00 Minor stroke (%)1.70.60.622.20.60.37 Major stroke (%)5.01.10.067.83.90.18 Death (all) or major stroke (%)8.43.90.1233.050.30.001 Repeat hospitalization (%)5.610.10.1722.344.1<.0001 Death (all) or repeat hosp (%)10.612.30.7442.570.4<.0001 Death All (%)5.02.80.4130.749.70.0004 Cardiovascular (%)4.51.70.2219.641.9<.0001

37. Outcome 30 Days n=179 TAVI Standard Rx P-value 1 Year 1 Yearn=179 TAVI Standard Rx P-value Clinical Outcomes at 30 Days & 1 Year Acute kidney injury Creatinine >3 mg/dL (%)011.001.12.80.45 RRT (%)1.11.71.001.73.40.50 Cardiac re-intervention BAV (%)0.61.11.00.636.9<.0001 Re-TAVI (%)1.7na1.7na AVR (%)01.70.251.19.5<.0001 Endocarditis (%)00.1.10.60.31 Vascular complications All (%)30.75.0<.000132.47.3<.0001 Major (%)16.21.1<.000116.82.2<.0001 Bleeding - major (%)16.83.9<.000122.311.20.007 Arrhythmias New atrial fibrillation (%)0.61.11.000.61.70.62 New pacemaker (%)3.45.00.604.57.80.27

38. P (log rank) = 0.069 Major Vascular Complication (n=31) No Major Vascular Complication (n=148) Mortality (%) Months Mortality vs. Major Vasc Complics TAVI patients 27.7% 47.2%

39. P (log rank) = 0.0046 Major Bleed (n=46) No Major Bleed (n=133) Mortality (%) Months Mortality vs. Major Bleeding TAVI patients 26.3% 43.5%

40. Major Stroke (n=15) No Major Stroke (n=164) Mortality (%) Months P (log rank) <0.0001 Mortality vs. Major Stroke TAVI patients 27.7% 66.7%

41. Subgroup Analyses of Primary Endpoint (All-Cause Mortality) TAVI betterStandard Rx betterSubgroup TAVI (%) n=179 Standard Rx (%) n=179 RR (95% CI) NNT P interaction Overall30.7 49.70.62 (0.47, 0.81)5 Age <85 >85 29.2 32.5 51.1 48.3 0.57 (0.39, 0.83) 0.67 (0.46, 0.98) 56560.54 Sex Female Male 30.9 30.5 48.4 51.2 0.64 (0.44, 0.92) 0.60 (0.40, 0.88) 65650.80 Body-mass Index <25 >25 38.6 24.0 52.9 46.7 0.73 (0.52, 1.02) 0.51 (0.34, 0.78) 7474 0.20 STS score <11 >11 23.7 38.4 42.1 54.9 0.56 (0.36, 0.88) 0.70 (0.51, 0.96) 5656 0.44 LV ejection fraction <55 >55 36.6 26.4 61.1 36.4 0.60 (0.43, 0.83) 0.73 (0.46, 1.14) 4 10 0.50

42. Subgroup Analyses of Primary Endpoint (All-Cause Mortality) TAVI betterStandard Rx betterSubgroup TAVI (%) n=179 Standard Rx (%) n=179 RR (95% CI) NNT P interaction Pulmonary hypertension No Yes 26.1 35.4 45.5 49.4 0.57 (0.36, 0.92) 0.72 (0.50, 1.03) 5757 0.47 Mitral regurgitation ≥3+ No Yes 32.3 23.7 46.5 60.5 0.70 (0.51, 0.95) 0.39 (0.21, 0.73) 7373 0.09 COPD (02 dependent) No Yes 29.1 36.8 48.1 54.3 0.60 (0.44, 0.83) 0.68 (0.41, 1.11) 5656 0.70 Prior CABG or PCI No Yes 27.8 27.4 47.1 54.3 0.59 (0.38, 0.93) 0.50 (0.34, 0.75) 5454 0.60 Peripheral vascular disease No Yes 28.2 37.0 52.2 42.2 0.54 (0.39, 0.75) 0.88 (0.54, 1.43) 4 19 0.10

43. Walking Distance P = 0.002 Walking distance (meters) Baseline 30 Days Six-Minute Walk Tests P = 0.004 1 Year P = 0.67 P = 0.55

44. NYHA Class Over Time Survivors P = 0.68P < 0.0001 IIIIIIIV TAVI Standard RxTAVIStandard RxTAVIStandard RxTAVIStandard Rx Percent TreatmentVisit Baseline 30 Day 6 Month 1 Year

45. Baseline N=163 30 Day N=143 6 Months N=100 1 Year N=89 Mean Gradient (mm Hg) 50 40 30 20 60 70 10 0 Error bars = ± 1 Std Dev Mean Gradients Over Time P < 0.0001 33.0 39.544.443.2 12.1 11.3 10.8 44.6 Standard Rx TAVI

46. Paravalvular Regurgitation: TAVI No changes over time None/Trace Mild Moderate Severe 30 Day 6 Month 1 Year

47. Conclusions - 1 In patients with severe AS and symptoms, who are not suitable candidates for surgery… Standard therapy (including BAV in 83.8% of pts) did not alter the dismal natural history of AS; all-cause and cardiovascular mortality at 1 year was 50.7% and 44.6% respectively Transfemoral balloon-expandable TAVI, despite limited operator experience and an early version of the system, was associated with acceptable 30-day survival (5% after randomization in the intention-to-treat population)

48. Conclusions - 2 TAVI was superior to standard therapy, markedly reducing the rate of…  all-cause mortality by 46%, P < 0.0001, NNT = 5.0 pts  cardiovascular mortality by 61%, P < 0.0001, NNT = 4.1 pts  all-cause mortality and repeat hospitalization  hierarchical (FS method), P < 0.0001  non-hierarchical (KM analysis) by 54%, P < 0.0001, NNT = 3.4 pts

49. Conclusions - 3 TAVI improved cardiac symptoms (NYHA class, P < 0.0001) and six minute walking distance (P = 0.002), after 1-year follow-up TAVI resulted in more frequent complications at 30 days, including…  major vascular complications, 16.2% vs. 1.1%, P < 0.0001  major bleeding episodes, 16.8% vs. 3.9%, P < 0.0001  major strokes, 5.0% vs. 1.1%, P = 0.06

50. Conclusions - 4 Serial echocardiograms in TAVI patients indicated…  reduced mean gradients (P < 0.0001) which were unchanged during 1-year FU  frequent paravalvular AR, which was usually trace or mild (~90%), remained stable during 1-year FU, and rarely required further Rx.

51. Clinical Implications Balloon-expandable TAVI should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery! Next generation devices (e.g. SAPIEN XT) may help to reduce the frequency of procedure-related complications in the future. The ultimate value of TAVI will depend on careful assessment of bioprosthetic valve durability, which will mandate obligatory long-term clinical and echocardiography FU of all TAVI patients.

52. September 22, 2010 on NEJM.org

53. Dedication