Saibal Kar, MD, FACC on behalf of the EVEREST II Investigators Effectiveness of Transcatheter Reduction of Significant Mitral Regurgitation in High Surgical Risk Patients with MitraClip®: Final 5 Year Results of The EVEREST II High Risk Registry Saibal Kar, MD, FACC on behalf of the EVEREST II Investigators ACC 2014 Washington, DC

Disclosure Statement of Financial Interest Saibal Kar, MD, FACC 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 Consulting Fees/Honoraria Other Financial Benefit Abbott Vascular, Atritech, AGA Medical , St Jude Medical, Circulite, Coherex Abbott Vascular, AGA Medical, Atritech, Gore Coherex Off-label use of products and investigational devices will be discussed in this presentation The EVEREST II High Risk Registry was funded by Abbott Vascular 1

MitraClip Therapy Worldwide Experience More than 13,000 patients have been treated with the MitraClip device worldwide Nearly 2,000 patients have been enrolled in prospective clinical trials worldwide A majority of patients are considered high risk for mitral valve (MV) surgery On October 24, 2013, FDA approved MitraClip for treating significant symptomatic DMR in patients who have been determined to be at prohibitive risk for MV surgery by a heart team Data as of 3/14/2014. Source: Abbott Vascular

Background EVEREST II High Risk Registry The EVEREST II High Risk Registry was a prospective, multi-center single arm clinical study designed to assess the safety and effectiveness of the MitraClip device in patients with significant MR considered to be high risk for MV surgery

Background EVEREST II High Risk Registry One-year outcomes in the EVEREST II High Risk Registry have been reported*: Procedural safety demonstrated Reduction of MR with the MitraClip device was associated with improved LV function, NYHA Class & Quality of Life, and a reduction in CHF hospitalizations MV surgery was not required for any EVEREST II High Risk Registry patient through 1 year Five-year follow-up on all patients is complete and the EVEREST II High Risk Registry is closed Totality of DMR data in the EVEREST II High Risk Registry provided foundation for approved indication 25 (78%) of the 32 DMR patients in the HRR contributed directly to the overall 127 PR DMR approval cohort, comprising 25/127 or 20% of it. *Whitlow et al. JACC 2012;59:130-9

Class IIb recommendation Level of Evidence B “Transcatheter MV repair may be considered for severely symptomatic patients (NYHA class III/IV) with chronic severe primary MR (stage D) who have a reasonable life expectancy but a prohibitive surgical risk because of severe comorbidities.”

Purpose To present final 5-year results from the EVEREST II High Risk Registry

Study Design EVEREST II High Risk Registry Symptomatic patients with significant MR (≥3+) Surgical risk based on a STS calculated risk score ≥12% or a surgeon estimated risk score ≥12% based on prespecified criteria Left ventricular function: EF>20%; LVESD<60mm Mitral valve anatomy suitable for the MitraClip Device Functional MR N=46 (59%) 78 High Surgical Risk Patients Enrolled Degenerative MR N=32 (41%)

Study Design Predicted Procedural Mortality Risk: STS-Calculated or Surgeon Estimate High Risk Eligibility = Risk Score ≥12% STS calculated score or Surgeon estimate based on the presence of at least one pre-specified co-morbidity 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: Creatinine > 2.5 mg/dL Prior chest surgery Age over 75 EF<35

Baseline Co-morbidities EVEREST II High Risk Registry EII - HRR N=78 Euro Heart Survey* Not Operated, N=193 Operated, N=203 Age (mean) 77 69 63 Gender, male (%) 47 53 NYHA Class III or IV (%) 90 70 65 History Coronary Artery disease (%) 85 60 38 Prior Cardiac Surgery (%) 59 7 3 Prior MI (%) 56 28 18 Hypertension (%) Diabetes Mellitus (%) 41 21 10 COPD / Chronic Lung Disease (%) 35 11 Moderate to Severe Renal Failure (%) 23 n/a Atrial Fibrillation (%) 62 36 32 Ejection Fraction, % (mean) 54 48 LVIDs, cm (mean) 3.9 4.1 4.0 *Mirabel et al. European Heart Journal 2007;28:1358-65

Clinical Follow-Up EVEREST II High Risk Registry 1st patient enrolled: February 14, 2007 Baseline: 78 Patients Last patient enrolled: January 30, 2008 N = 8 Withdrawals 5-Years: 70 Patients 90% Clinical Follow-Up Median follow-up 3.05 years. 229 total patient-years of follow-up.

Adverse Event Rates (%) Per Patient-Year of Follow-up Site-Reported Adverse Events Through 5 Years EVEREST II High Risk Registry AE Categories Cardiac Vascular Adverse Event Rates (%) Per Patient-Year of Follow-up Neurologic Renal Index Through 30 Days 30 Days Through 1 Year 1 Year Through 2 Years 2 Years Through 3 Years 3 Years Through 4 Years 4 Years Through 5 Years

Long-Term MitraClip Device Safety EVEREST II High Risk Registry Through 1 Year # (%) of patients 1 Year to 5 Years Single Leaflet Device Attachment (SLDA) 1 (1.3%) 0 (0.0%) MV stenosis 2 (2.7%) Device Embolization MV stenosis = as confirmed by the protocol definition (Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the Echocardiographic Core Laboratory.)—pg 52 EII protocol rev G. Based on N=75 who were implanted with 1 or 2 MitraClip devices PML04248 Rev. A

Kaplan-Meier Freedom From Mortality EVEREST II High Risk Registry 75.6% 1 year Proportion of Patients Surviving 58.8% 3 years 42.5% 5 years   Baseline 6 Months 12 Months 2 Years 3 Years 4 Years 5 Years MitraClip # At Risk 78 64 58 46 40 37 14 PML04248 Rev. A

Kaplan-Meier Freedom From Mortality EVEREST II High Risk Registry and Duke High Risk Cohort 75.6% 73.8% 1 year Proportion of Patients Surviving 953 patients who were managed non-surgically were identified as high surgical risk in the Duke Database (Duke Cohort). In the overall Duke Cohort of 953 patients, mortality at 1 year was 26.2%.   There were some important differences between the Duke Cohort (N = 953) and the EVEREST II HRR patients. HRR patients were older on average by 8 years than patients in the Duke Cohort. HRR patients were also nearly twice as likely to be classified as NYHA Functional Class III/IV at baseline than their counterparts in the Duke Cohort. Comparison of mortality between the Duke Cohort and the HRR patients is therefore conservatively biased against the MitraClip. At 1 year, mortality in the HRR patients was 24.4%, comparable to the 26.2% observed in Duke Cohort patients. Thus, in a conservative descriptive analysis without patient matching, mortality at 1 year in the HRR patients was not worse than that observed in a historical cohort of younger and less sick high surgical risk patients from Duke University Medical Center who were managed non-surgically. EVEREST II High Risk Registry (N=78) Duke High Risk Cohort (N=953) Duke cohort data from Abbott Vascular Executive Summary. Presented March 20, 2013; Gaithersburg, MD. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ CirculatorySystemDevicesPanel/UCM343684.pdf. PML04248 Rev. A

Re-Interventions Through 5 Years EVEREST II High Risk Registry # (%) of patients Time to Re-Intervention Post-Index Procedure Conversion to MV Surgery 2 (2.6%) 1.3 years 3.2 years Second Intervention to Place an Additional MitraClip 45 days 2.8 years Surgeries: 25-201 at 471 days (STS score 16.1%) 21-201 at 1186 days (STS score 6.7%, baseline charac: FMR with EF <40%, HTN, hyperchol, renal dz, cerebrovasc dz) Both were FMR and both were replacements Both patients were alive at 5 years: One with 1+ MR at 5-year visit and One with 1+ MR at 4-year visit (last readable echo) Second Clip cases (both FMR): 12-204 at 1024 days; Death 1,214 days (3.3 years) post-index due to metastatic esophageal adenocarcinoma 35-205 at 45 days; Death 67 days post-index due to respiratory failure and CHF

Mitral Regurgitation Grade EVEREST II High Risk Registry p < 0.005 p < 0.005 78% 82% 2+ 1+ % MR ≤ 2+ at 1 and 5 Years 3+ 1+ 3+ 2+ 2+ 4+ 4+ 3+ 3+ 4+ Baseline 1 Year Baseline 5 Years N=54 N=24 N = survivors with paired data; p-values for descriptive purposes only

Reduction in LV Volumes at 1 and 5 Years EVEREST II High Risk Registry LVEDV (ml) at 1 Year LVEDV (ml) at 5 Years N=54 p<0.0001 N=24 p<0.0001 -32.1 -38.2 LVESV (ml) at 1 Year LVESV (ml) at 5 Years N=54 p<0.005 N=24 p<0.05 -14.6 -10.0 Mean +/-SD (ml) Mean +/-SD (ml) N = survivors with paired data; p-values baseline vs 1 & 5 years, for descriptive purposes only PML04248 Rev. A

Reduction in LV Dimensions at 1 and 5 Years EVEREST II High Risk Registry LVIDd (cm) at 1 Year LVIDd (cm) at 5 Years N=54 p<0.0001 N=24 p=ns -0.3 -0.2 LVIDs (cm) at 1 Year LVIDs (cm) at 5 Years N=54 p=ns N=24 p<0.05 -0.1 0.2 Mean +/-SD (cm) Mean +/- SD (cm) N = survivors with paired data; p-values baseline vs 1 & 5 years, for descriptive purposes only PML04248 Rev. A

NYHA Functional Class EVEREST II High Risk Registry p < 0.005 p < 0.005 74% 83% % NYHA I/II at 1 and 5 Years II II I I III III II II IV IV III III Baseline 1 Year Baseline 5 Years N=54 N=24 N = survivors with paired data; p-values for descriptive purposes only

Septal Lateral Annular Dimensions EVEREST II High Risk Registry Systolic SLAD Diastolic SLAD p < 0.001 p = ns p < 0.001 p = ns Mean SLADdiast (cm) Mean SLADsyst (cm) Baseline 1 Year Baseline 5 Years Baseline 1 Year Baseline 5 Years N=51 N=21 N=51 N=21 N = survivors with paired data; p-values for descriptive purposes only

EVEREST II High Risk Registry – 5 Year Results Summary The EVEREST II High Risk Registry is the longest prospective follow-up of a high surgical risk cohort treated for severe MR Clinical benefits provided by MitraClip are durable in high risk patients surviving through 5 years Reduction in MR Severity Improvement in LV Volumes and Dimensions Improvement in NYHA Functional Class No new or ongoing safety concerns through 5 years in this high risk population

EVEREST II High Risk Registry – 5 Year Results Conclusion The MitraClip procedure is a safe and durable therapeutic option for select patients with significant MR who are at high surgical risk Durability of outcomes demonstrated in this limited FMR population provides foundation for COAPT trial

COAPT Trial COAPT is an Abbott Vascular sponsored trial

COAPT Trial COAPT is an Abbott Vascular sponsored trial 2013 ACCF/AHA Guideline for the Management of Heart Failure: Circulation 2013; 128:e240-327 COAPT is an Abbott Vascular sponsored trial

COAPT Trial COAPT is an Abbott Vascular sponsored trial

COAPT Trial COAPT is an Abbott Vascular sponsored trial

Abbott Vascular 4045 Campbell Avenue, Menlo Park, CA 94025 USA, Tel: 1.650.833.1600 EVEREST II and COAPT are Abbott Vascular Sponsored Clinical Trials. Caution: This product is intended for use by or under the direction of a physician. Prior to use, reference the Instructions for Use at http://www.abbottvascular.com/ifu/ for more detailed information on Indications, Contraindications, Warnings, Precautions and Adverse Events. All drawings are artist's representations only and should not be considered as an engineering drawing or photograph. MitraClip is a trademark of the Abbott Group of Companies. www.AbbottVascular.com ©2014 Abbott. All rights reserved. PML04248 Rev. A