1. MitraClip: A Therapeutic Solution for Patients with Severe MR – Not a Candidate for Surgery
Brij Maini MD, FACC
Regional Medical Director of Transcatheter Therapies
Tenet Healthcare Corporation
Florida Region

2. Disclosure Statement of Financial Interest Brijeshwar Maini 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
Abbott Vascular
Medtronic
Abiomed
SJM
Siemens
Atritech/Boston Scientific 2

3. Degenerative MR is common, affecting ~600,000 persons in the U.S.
Background
Degenerative MR is common, affecting
~600,000 persons in the U.S.
Surgery is the standard of care, and is indicated for patients with symptoms or LV dysfunction
However, there are patients in whom the risk of surgery is prohibitive

4. EVEREST
TVT
OUR EXPERIENCE

5. Methods Determination of Prohibitive Risk
141 high surgical risk DMR patients treated in the EVEREST Registries with 1-year follow-up available
Prohibitive risk definition retrospectively applied by heart team
Two cardiac surgeons experienced in MV surgery
Cardiologist experienced in MV disease
127 patients were documented to meet prohibitive risk

6. Methods Definition of Prohibitive Risk
“Prohibitive risk” is due to the presence of one or more of the following documented surgical risk factors:
30-day STS predicted operative mortality risk score of
≥8% for patients deemed likely to undergo MV replacement or
≥6% for patients deemed likely to undergo MV repair
Porcelain aorta or extensively calcified ascending aorta
Frailty (assessed by in-person cardiac surgeon consultation)
Hostile chest
Severe liver disease / cirrhosis (MELD Score > 12)
Severe pulmonary hypertension (systolic pulmonary artery pressure >2/3 systemic pressure)
Unusual extenuating circumstance, such as
Right ventricular dysfunction with severe tricuspid regurgitation
Chemotherapy for malignancy
Major bleeding diathesis
Immobility
AIDS
Severe dementia
High risk of aspiration
Internal mammary artery (IMA) at high risk of injury, etc.

7. Baseline Demographics and Comorbidities
Characteristic
Prohibitive Risk DMR N = 127
Age (mean ± SD)
82 ± 9 years
Patients over 75 years of age
84%
Male Gender
55%
Coronary Artery Disease
73%
Prior Myocardial Infarction
24%
Previous Cardiovascular Surgery
48%
Atrial Fibrillation History
71%
Prior Stroke
10%
Diabetes
30%
Moderate to Severe Renal Disease
28%
Chronic Obstructive Pulmonary Disease
32%
STS Mortality Risk (mean ± SD) [v2.73, replacement]
13.2 ± 7.3%
SF-36 QoL Physical Component Score (mean ± SD)
32.0 ± 8.7
SF-36 QoL Mental Component Score (mean ± SD)
46.1 ± 12.5 7

8. Baseline Cardiac Comorbidities
Characteristic
Prohibitive Risk DMR N = 127
Congestive Heart Failure
98%
NYHA Functional Class III or IV
87%
LV Ejection Fraction (mean ± SD)
60.6 ± 9.5 %
LV End Diastolic Volume (mean ± SD)
127.0 ± 40.5 ml
LV Internal Diameter, systole (mean ± SD)
3.4 ± 0.8 cm 8

9. Reasons For Prohibitive Surgical Risk
Prohibitive Risk Factor ╪
Prohibitive Risk DMR N = 127 n %
STS mortality risk score ≥ 8% (mean 13.2 ± 7.3%)
101
79.5%
Risk factors in patients with STS mortality risk score < 8% that are not captured in STS calculator:
Porcelain Aorta 8
6.3%
Hostile chest 5
3.9%
Severe liver disease or cirrhosis 4
3.1%
Severe pulmonary hypertension 3
2.4%
Frailty 2
1.6%
Unusual extenuating circumstance:
High risk of aspiration
IMA at high risk of injury
Major bleeding diathesis
Severe dementia
Chemotherapy for malignancy 1
0.8%
Immobility
AIDS
╪Non-hierarchical listing; 78 (61.4%) patients presented with more than 1 prohibitive risk factor 9

10. MitraClip Implant Rate
Prohibitive Risk DMR (N=127) 95.3% Implant Rate 10

11. Post-Procedural and Discharge Results
Prohibitive Risk DMR N = 127
Post-Procedural (mean ± SD)
ICU/CCU duration
1.4 ± 1.8 days
Length of hospital stay
2.9 ± 3.1 days
Discharge MR, (%)
MR ≤ 2+ at Discharge
82%
MR ≤ 1+ at Discharge
54%
Discharged home, (%)
87% 11

12. 30 Day Mortality: Predicted vs Observed
Prohibitive Risk DMR (N=127)
p < 0.001
13.2%
6.3%
Mean Predicted
Mortality Risk:
STS v2.73 Replacement Score
Observed Mortality 12

13. CEC-Adjudicated Safety Events
Event (Non-Hierarchical)
Prohibitive Risk DMR (N=127)
30 Days
1 Year n %
Death* 8
6.3% 30
23.6%
Myocardial Infarction 1
0.8%
Non-elective CV Surgery for AEs
Stroke 3
2.4%
New onset of permanent AF
Renal Failure 2
1.6% 5
3.9%
Ventilation > 48 hours 4
3.1% 6
4.7%
GI complication requiring surgery
* No intra-procedural or cath lab deaths 13

14. Secondary Safety Events
Event (Non-Hierarchical)
Prohibitive Risk DMR (N=127)
30 Days
1 Year n %
Major Vascular Complications 7
5.5% 9
7.1%
Major Bleeding Complications 16
12.6% 20
15.7%
Non-Cerebral Thromboembolism 2
1.6%
Heart Block/Other Arrhythmia Requiring PPM
Atrial Septal Defect 3
2.4%
Mitral Valve Stenosis 14

15. Kaplan-Meier Freedom From Mortality Through 1 Year
75.2%
Prohibitive Risk DMR (N=127)
Survival
Baseline
30 Days
1 Year
# At Risk
127
117 85
% Event Free
100%
93.6%
75.2%
95% CI -
[87.6%, 96.8%]
[66.1%, 82.1%]
Prohibitive Risk DMR Cohort (N=127)

16. Kaplan-Meier Freedom From Mortality Through 1 Year By Discharge MR Severity
83.3%
n=48
Discharge MR = 2+
80.0%
n=27
Discharge MR = 3+/4+
52.4%
n=10
Survival
Baseline
30 Days
12 Months
MR ≤ 1+
# At Risk 66 64 48
% Event Free
100%
97.0%
83.3%
95% CI -
[88.4%, 99.2%]
[70.9%, 90.8%]
MR = 2+ 35 27
80.0%
[62.2%, 90.1%]
MR = 3+/4+ 22 16 10
76.2%
52.4%
[51.9%, 89.3%]
[28.6%, 71.6%]
p=0.61
p=0.001
p=0.02
Note: p-values unadjusted for baseline differences

17. Mitral Regurgitation Grade Through 1 Year
Patients With Data Available at Follow-Up (Completers Analysis) 2+ 1+ 1+ 3+
MR ≤ 2+ in 83%
of surviving patients at 1 year 2+ 2+ 3+ 4+ 3+ 4+
Baseline N=124 M=3 D=0
Discharge
N=123 M=3 D=1
1 Year
N=84 M=13 D=30
M=missing, D=died

18. Left Ventricular Volumes At 1 Year
Left Ventricular End Diastolic Volume
Left Ventricular End Systolic Volume
∆ = -16 mL p <
∆ = -3 mL p = 0.07
Baseline N=69
1 Year N=69
Baseline N=69
1 Year N=69
N Denotes Paired Survivors

19. NYHA Functional Class Through 1 Year
Patients With Data Available at Follow-Up (Completers Analysis) II 2+ I I
NYHA Class I/II in 87% of surviving patients at 1 year
III 3+ II II IV
III
III 4+
Baseline N=127 M=0 D=0
Discharge
N=113 M=5 D=9
1 Year
N=84 M=13 D=30
M=missing, D=died

20. SF-36 Quality of Life At 30 Days
Physical Component Score
Mental Component Score
∆ = 6.2
p <
∆ = 3.4
p < 0.01
Age-adjusted US norm (50.2)
MCID
Score
Age-adjusted US norm (39.9)
MCID ≈ ≈
N = 99
N = 99
N Denotes Paired Survivors
MCID = Minimal Clinically Important Difference (2-3 points)
Ware et al. User's manual for the SF-36v2 Health Survey. 2nd ed. Lincoln, RI: QualityMetric Incorporated, 2007

21. SF-36 Quality of Life At 1 Year
Physical Component Score
Mental Component Score
∆ = 6.0
p <
∆ = 5.6
p < 0.001
Age-adjusted US norm (50.2)
MCID
Score
Age-adjusted US norm (39.9)
MCID ≈ ≈
N = 73
N = 73
N Denotes Paired Survivors
MCID = Minimal Clinically Important Difference (2-3 points)
Ware et al. User's manual for the SF-36v2 Health Survey. 2nd ed. Lincoln, RI: QualityMetric Incorporated, 2007

22. Hospitalizations For Heart Failure
73% Reduction p <
HF Hospitalization Rates per Patient Year (1 year Pre-MitraClip to 1 Year Post Discharge)
1 Year Prior to MitraClip N = 127
1 Year Post Discharge N = 120

23. Summary
MitraClip therapy safely reduces DMR in patients at prohibitive risk for MV surgery
In this group of prohibitive risk DMR patients, MitraClip therapy provides meaningful clinical improvements
Reduction of LV volumes
Improvements in NYHA Functional Class
Improvements in Quality of Life
Reduction in Hospitalizations for Heart Failure

24. Sites Participating in the STS/ACC TVT Registry
111 sites performing MitraClip Procedures

25. Study Population 1583 Patients
Median age (% men)…………………..
NYHA III/IV………………………………….
HF hospitalization prior yr……………....
Atrial fibrillation…………………………...
Prior CVA……………………………………
Diabetes…………………………………….
Prior CABG…………………………………
Prior MI……………………………………...
Creatinine ≥2 g/dl………………………….
O2-dependency……………………………
Peripheral Arterial Disease……………...
82 yrs (56%)
85.0%
52.9%
64.4%
10.7%
24.5%
31.7%
26.5%
15.0%
14.4%
18.1%
6 min walk – 175 m (375, 984)

26. Descriptors of Prohibitive Risk
Frailty……………
Hostile chest……………………
Porcelain aorta………………….……………..
RV dysfunction with severe TR….…....…..…
Immobility………………………………....……
Severe liver disease (MELD >12)……
IMA at high risk of injury…………………..….
Unusual extenuating circumstance……….…
Chemotherapy ………………………………..
50.0%
7.4%
2.2%
7.8%
8.7%
1.4%
4.6%
28.7%
6 min walk – 175 m (375, 984)

27. Surgical Risk for Mitral Repair By Site Median STS Score = 6. 2 [3

28. Surgical Risk for Mitral Replacement By Site
Median STS Score = 9.5 [6, 14.5]

29. Echocardiographic data
LV ejection fraction..………..…..….55% [43, 60%]
MR severity grade 3 or 4……….….94.7%
LV EDD………………………………..5.2 cm [4.6, 5.8 cm]
LV ESD………………………………..3.6 cm [3, 4.4 cm]
Degenerative MR………… %
Functional MR……………… %
Mitral annular calcification…….…. 37.5%
Leaflet calcification…….………… %
Mitral gradient ≥5 mmHg………… %
MVA <4 cm2………………………… %
Severe TR……………………………..17.0%

30. MitraClip Procedure Status

31. Procedural Adverse Events
Single leaflet device attachment……...
Device embolization……………………..
Other……………………………………….
Major bleeding....………………………...
Cardiac perforation……..……………….
Stroke……………….……………………..
Cardiac surgery………………...………..
ASD Closure………………………………
1.3%
0.2%
0.6%
3.7%
0.9%
0.06%
1.6%

32. Site Reported MR Reduction 1 Clip= 54%, 2 Clips= 40%, ≥ 3 Clips= 5%
Clip implanted = 97.7%
Grade 4
Grade 3
Grade 2
Grade 1
Mitral Regurgitation
92.9% MR ≤2
62.0% MR ≤1

33. Outcomes at Discharge MR moderate (2+) or less 92.9%
MR mild (1+) or less
62.0%
MV mean Gradient (mm Hg)
4.00 mmHg (IQR: 3-6)
Median LOS
3 days (IQR: 1-6)
Discharge location=home
84%

34. Mortality In-hospital Mortality .................. 2.6%
MR>2 / Need for Surgery (7.5%). 8.4%
MR≤ 2 / No Surgery ………………… 2.1%
30 day mortality ………………………. 5.5%
MR>2 / Need for Surgery…………. 14.6%
MR≤ 2 / No Surgery………………….. 4.9%

35. U.S. vs. Other Registries In-hospital death Age (yrs) DMR MR ≤2
STS/ACC TVT (US)...…….
SENTINEL (EU)….………..
ACCESS (EU)….……...….
TRAMI (DE)………..………
MitraSwiss (CH)
France (FR)……
GRASP (IT)……..….…….…
Netherlands (NL)…………
MARS (Asia)……………… 82 74 75 77 73 72 71
85%
28%
23%
29%
38%
24%
18%
46%
93%
95%
91%
85%
88%
100%
94%
2.6%
2.9%
4.0%
3.3%
4.2%
For EVEREST RCT, there 2 deaths within 30 days (1%)
EVEREST I………………..
EVEREST II RCT…...….…
EVEREST II HRS……...... 71 67 76
74%
77%
85%
0.9%
1.1%
2.6%
79%
51%
30%

36. OUR EXPERIENCE
SYMPTOMATIC IMPROVEMENT WITH MITRACLIP THERAPY FOR PROHIBITIVELY HIGH-RISK DMR PATIENTS. J Am Coll Cardiol. 2015;65(10_S). MAINI B ET AL.
IMPROVEMENT IN QUALITY OF LIFE IN PATIENTS WITH DEGENERATIVE MITRAL REGURGITATION ST PROHIBITIVE SURGICAL RISK FOLLOWING TRANSCATHETER MITRAL VALVE REPAIR WITH THE MITRACLIP SYSTEM. J Am Coll Cardiol. 2015;65(10_S). MAINI B ET AL.

37. Kansas City Cardiomyopathy Questionnaire P<0.001

39. PRE
POST

43. P=0.4
P<0.01

44. Conclusions
MitraClip is safe and effective for the treatment of prohibitive risk patients with symptomatic MR
The commercial outcomes in the U.S. compare favorably to pre-approval studies and other national registries
Mitraclip is a therapeutic solution for patients with severe MR– who are not a candidate for surgery