on behalf of the EVEREST Investigators Percutaneous Edge-to-Edge Evalve Mitral Valve Repair in the US “High-Risk” MR Registry on behalf of the EVEREST Investigators Ramon Quesada, MD, FACP,FACC, FSCAI Medical Director, Interventional Cardiology Baptist Cardiac & Vascular Institute Miami, Florida

Ramon Quesada, MD DISCLOSURES I have no real or apparent conflicts of interest to report.

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company Grant/Research Support None Consulting Fees/Honoraria Abbott, Cordis, St. Jude, W.L. Gore, NMT Medical, Terumo & Boston Scientific Corporation Major Stock Shareholder/Equity None Royalty Income None Ownership/Founder None Intellectual Property Rights None Other Financial Benefit None

Percutaneous mitral repair with the MitraClip® System based on the Alfieri Technique Repositionable Real time assessment of reduction of MR Received CE Mark Approval

Worldwide MitraClip Experience Enrollment Population n EVEREST I (100% enrolled) Registry patients 55 EVEREST II Roll-in Randomized Clip Randomized Surgery High Risk Registry 60 184 95 78 EVEREST II: REALISM Continued Access Registry Registry Patients (non HRR and HRR) 135 European Experience 219 TOTAL MitraClip Therapy Patients 731 * Data as of September 15, 2009 5

EVEREST I & II Enrollment Population n EVEREST I Feasibility (completed) Registry patients 55 EVEREST II Randomized n=279 (100% enrolled) Roll-in Randomized Clip Randomized Surgery 60 184 95 High Risk Registry 78 Total enrolled 472 EVEREST II High Risk Registry 78 Enrollment and one year follow up complete 38 sites

Perspective Therapeutic options for patients with FMR Current surgical options are limited Repair Undersized annuloplasty Double orifice repair New surgical approaches without substantive data Replacement Medical management is largely ineffective The MitraClip Therapy may be a reasonable alternative therapeutic option

EVEREST High Risk Registry (HRR) Endpoints Primary Safety Endpoint : 30 Day Mortality Observed vs. Predicted Mortality Risk based on STS Calculator or Surgeon Estimate Major Effectiveness Endpoint: 12 Months Reduction in hospitalizations for CHF Improvement in NYHA Class Improvement in LV Function Reduction in MR

EVEREST II High Risk Registry KEY INCLUSION CRITERIA Predicted procedural mortality risk ≥ 12% (STS calculated or Surgeon estimated) Symptomatic 3+ or 4+ MR, Degenerative or Functional 78 Enrolled FMR N=46 (59%) DMR N=32 (41%) KEY EXCLUSION CRITERIA EF ≤ 20% and/or LVESD >60mm MVA <4cm2 Leaflet anatomy unsuitable for MitraClip device FMR Patients 12 month matched MR data N=34

Predicted procedural mortality based on STS Risk Calculator or Surgeon Estimate STS Surgical Risk Calculator High Risk Eligibility met if STS calculated score ≥12% or based on surgeon judgment if one or more of following co-morbidities Porcelain aorta or mobile ascending aortic atheroma Post-radiation mediastinum Previous mediastinitis Functional MR with EF<40 Over 75 years old with EF<40 Re-operation with patent grafts Two or more prior chest surgeries Hepatic cirrhosis Three or more of the following STS high risk factors: Creatinine > 2.5 mg/dL Prior chest surgery Age over 75 EF<35

FMR Cohort: Baseline Co-morbidities Significant co-morbidities Baseline Co-Morbidities FMR N=46 Age (mean) 73 NYHA Class III or IV 91% History CAD 87% History CHF 100% Hypertension Diabetes Mellitus 52% COPD / Chronic Lung Disease 35% Moderate to Severe Renal Failure 26% Prior Cardiac Surgery 63% Predicted Surgical Mortality (STS risk Calculator or Surgeon Estimate) 17%

FMR Cohort: MitraClip Implant Rate 98% Implant Success Rate 2 Clips (n=13) 1 Clip (n=32) 0 Clip (n=1)

HRR 30 Day Mortality Safety Endpoint (ITT) Actual Mortality Predicted Risk of Surgical Mortality P Value Primary Endpoint HRR All * (N=78) 7.7% (n=6) 18.2% 0.006 Concurrent Control (n=36) 8.3% (n=4) 16.4% HRR FMR (n=46) 8.7% 17.0% Acute mortality is similar to patients managed to standard of care for High Risk Patients * TCT 2008

HRR FMR (n=46): Major Adverse Events - 30 days Freedom from MAE: 74% (34/46) 21 MAE Events occurred in 12 patients Deaths (4) MI* (1) Stroke* (1) Renal Failure (2) Ventilation >48 hours** (2) Transfusion ≥ 2 units of blood** (11) Majority of transfusions related to chronic anemia * Occurred in patient who died ** 1 event occurred in patient who died

HRR FMR (n=46): Partial Clip Detachment (ITT) Clip Embolization Partial Clip Detachment 2 (4.3%*) 1 procedural 1 > 30 days * Incidence in preliminary cohort (N=107): 9.7%

FMR Cohort: Quantification of MR Marked reduction in MR, RV, and RF at 12 months Time point Overall MR Grade (mean ± SD) n=34 Regurgitant Volume (ml) (mean ± SD) n=26 Regurgitant Fraction (%) (mean ± SD) Baseline 3.2±0.5 42±18 44±13 12 month 1.8±0.9 20±16 25±17 p value <0.0001

FMR Cohort: Mitral Regurgitation Grade Sustained MR Reduction 21% 41% MR 1 97% 79% 59% MR 2 Grade 1+/ 2+ Grade 1+ = Mild MR Grade 2+ = Moderate MR Grade 3+ = Moderate - Severe MR Grade 4+ = Severe MR Grade 3+/ 4+ 12 month Matched data, n=34

HRR FMR: NYHA Class (ITT) MitraClip therapy results in sustained symptomatic improvement 80% Improved at 12 months with 74% Class I/II at 12 months 100% Improved or remained unchanged at 12 months 12 13 8 1 18 19 3 74% n=34, Matched Data

FMR Cohort: Re-hospitalization for CHF Significant reduction in rate of re-hospitalization for CHF 36% Reduction Re-Hospitalizations Patients Re-Hospitalization Rate 12 Months Prior to MitraClip 12 Months Prior to MitraClip 12 Months Following MitraClip 12 Months Following MitraClip

The effect of valve repair without annuloplasty on septo-lateral mitral annular diameter and left ventricular (LV) function in patients with functional mitral regurgitation (FMR) is unknown

HRR FMR: LV Function (ITT) MitraClip therapy results in reverse LV remodeling P=0.001 P=0.0002 LVEDV Baseline LVEDV 12 Months LVESV Baseline LVESV 12 Months 192 153 103 87 Systolic Diastolic n=34, Matched Data

FMR Cohort: Left Ventricular Remodeling MitraClip therapy results in reverse LV remodeling P<0.0001 P<0.0001 P=ns P=0.0002 192 153 6.0 5.6 4.3 4.5 103 87 Diastolic Systolic Diastolic Systolic Baseline, Diastolic Baseline, Systolic 12 Months, Diastolic 12 Months, Systolic 12 month Matched data, n=34

FMR Cohort Ejection Fraction / Forward Stroke Volume Improved LV Efficiency P=0.06 51 55 47 44 EF(%) n=34 FSV (ml/beat) n=33 EF Baseline FSV Baseline EF 12 Months FSV 12 Months

FMR Cohort: Septal-Lateral Annular Dimension Annular Dimensions Unchanged at Discharge 3.8 3.7 3.2 3.2 Diastolic Systolic Baseline, Diastolic Baseline, Systolic Discharge, Diastolic Discharge, Systolic Matched data, n=33

FMR Cohort: Septal-Lateral Annular Dimension Annular Dimensions Reduced at 12 Months P< 0.0001 P= 0.008 3.8 3.6 3.2 3.0 Baseline, Diastolic Baseline, Systolic 12 Months, Diastolic 12 Months, Systolic Matched data, n=33

FMR Cohort: Septal-Lateral Annular Dimension Annular Dimensions Stabilized at 12 Months 3.8 3.6 3.2 3.0 Baseline, Diastolic Baseline, Systolic 12 Months, Diastolic 12 Months, Systolic 12 month Matched data, n=18

79 y/o ischemic cardiomyopathy Continued elevated Left atrial pressure Medications valsartan 320 mg carvedilol 50 mg isosorbide 120 mg furosemide 160 mg (avg dose) BP 90 sys Creatinine 2.5 Hgb 8.8 LVEF 30% Coronary angio: all vessels patent

Intermittent severe functional MR and atrial standstill 2DE when LAP = 34 mm Hg BP 100/70 mm Hg

NYHA I, BP 110 sys, furosemide 40 mg, LVEF 40%, Creatinine 1.2, Hgb 11 Asymptomatic LAP controlled 22 months NYHA I, BP 110 sys, furosemide 40 mg, LVEF 40%, Creatinine 1.2, Hgb 11

Sustained MR reduction at 18 months

Echo at Baseline and 18 months

Reduction of SL diameter at 18 months

Summary Baseline 12 Months P-value MR Grade 3.2±0.5 1.8±0.9 <0.0001 LVEDV (ml) 192±46 153±44 LVESV (ml) 103±37 87±35 0.0002 SL Annular diameter (diastole) (cm) 3.8±0.3 3.6±0.3 < 0.0001 SL Annular diameter (systole) (cm) 3.2±0.4 3.0±0.3 0.008 NYHA Class I/II (%) 9 74 CHF Hospitalization Rate 0.76 0.49 36% decrease

HRR FMR Summary The MitraClip device was successfully implanted in 98% of High Risk FMR patients Clinical benefit was delivered and sustained to 12 months Improvement in NYHA Class Decreased rate of hospitalization for CHF LV Function was improved through 12 months Decrease in LV End Diastolic and Systolic Volumes Increase in Forward Stroke Volume Decrease in Septo-lateral Annular Dimensions

International Symposium on Endovascular Therapy I S E T Save the Date January, 2011 Thank You