0. 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

1. 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

2. 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/ Source: Abbott Vascular

3. 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

4. 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

5. 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.”

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

7. 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%)

8. 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

9. 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:

10. 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 total patient-years of follow-up.

11. 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

12. 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
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13. 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
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14. 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. CirculatorySystemDevicesPanel/UCM pdf.
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15. 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:
at 471 days (STS score 16.1%)
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):
at 1024 days; Death 1,214 days (3.3 years) post-index due to metastatic esophageal adenocarcinoma
at 45 days; Death 67 days post-index due to respiratory failure and CHF

16. 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

17. 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
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18. 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
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19. 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

20. 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

21. 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

22. 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

23. COAPT Trial
COAPT is an Abbott Vascular sponsored trial

24. COAPT Trial COAPT is an Abbott Vascular sponsored trial
2013 ACCF/AHA Guideline for the Management of Heart Failure: Circulation 2013; 128:e
COAPT is an Abbott Vascular sponsored trial

25. COAPT Trial
COAPT is an Abbott Vascular sponsored trial

26. COAPT Trial
COAPT is an Abbott Vascular sponsored trial

27. Abbott Vascular
4045 Campbell Avenue, Menlo Park, CA USA, Tel:
EVEREST II and COAPT are Abbott Vascular Sponsored Clinical Trials.
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©2014 Abbott. All rights reserved. PML04248 Rev. A