1 investigational device only in the u.s. not available for sale in the u.s.everest ii and continued...
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Comparison of EVEREST II High Surgical Risk and Continued Access High Surgical
Risk Patient Cohorts
1 Year Preliminary Results
Michael Rinaldi, Saibal Kar, Scott Lim, Ted Feldman, and the EVEREST II
InvestigatorsSCAI 2011
Baltimore, MD
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Disclosures
Consulting Fees/Honoraria• Abbott Vascular
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Percutaneous Mitral Valve Repair
MitraClip® System
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
MitraClip TherapyWorldwide Clinical Experience
Over 3,000 patients have been treated with the MitraClip device worldwide:
• 75% are considered high risk* for mitral valve surgery
• 67% have functional mitral regurgitation (MR)
1,453 patients have been enrolled in prospective clinical trials worldwide:
• 50% are considered high risk* for mitral valve surgery
• 60% have functional MREstimates of worldwide clinical experience as of March 31, 2011
* Determination of high surgical risk based on: logistic EuroSCORE ≥ 20%, or STS calculated mortality ≥ 12%, or pre-specified high surgical risk comorbidities.
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
High Surgical Risk Patients Treated with the
MitraClip Device in EVEREST II Trials
EVEREST High Surgical Risk Clinical Trials
EVEREST II – High Risk Trial 78
EVEREST II Continued Access – High Risk Trial
294
TOTAL High Surgical Risk Patients 372
As of April 12, 2011
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
BackgroundEVEREST II Outcomes Through 2 Years
Randomized Controlled Trial (RCT) comparing percutaneous device and mitral valve surgery
• Percutaneous repair provides increased safety• Surgery provides more complete MR reduction• Both percutaneous and surgical treatment
reduced MR and demonstrated significant clinical benefits
High Risk study evaluating MitraClip device• Patients experienced reduced MR and significant
clinical benefits
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
EVEREST II Continued Access InvestigatorsT Feldman, J Alexander, R Curran, E Chedrawy, S Smart, M Lampert NorthShore University HealthSystem, Evanston, ILA Wang, D Glower, J Jollis Duke University, Durham, NCM Kellett, P Weldner, R Quinn Maine Medical Center, Portland, MER Quesada, J Lamelas, N Moreno, R Machado Baptist Hospital of Miami, Miami, FLP Grayburn, B Hamman, R Hebeler, M Mack, W Ryan Baylor University Medical Center, Dallas, TXV Rajagopal, J Kauten, W Mashman Piedmont Hospital, Atlanta, GAJ Hermiller, D Heimansohn, K Allen, D Segar The Care Group, Indianapolis, INM Rinaldi, E Skipper, R Steigel, J Cook, G Rose Carolinas Medical Center, Charlotte, NCS Kar, G Fontana, A Trento, R Kass, W Cheng, R Siegel, K Tolstrup Cedars-Sinai Medical Center, Los Angeles, CAP Whitlow, T Mihaljevic, N Smidera, L Svenssen, E Roselli, L Rodriquez, W Stewart The Cleveland Clinic, Cleveland, OHW Gray, A Stewart, M Williams, M Argenziano, S Homma, R Pizzarello, L Gillam Columbia University, New York, NY; Danville, CTD Steinberg, F Crawford, J Ikonimidis, D Gregg, P Zwerner Medical University of South Carolina, Charleston, SCB Whisenant, S Clayson, B Reid, S Horton, J Orford Latter Day Saints Hospital, Salt Lake City, UTR Smalling, G Letsou, J Walkes, C Loghin Memorial Hermann Hospital, Houston, TXW Pedersen, V Kshettry, F Eales, T Flavin, T Kroshus, R Bae Minneapolis Heart Institute, Minneapolis, MNC Rammohan, C Vial, R Beygui, D Nair, A Prakash El Camino Hospital, Mountain View, CASC Wong, OW Isom, L Girardi, K Krieger, R Devereux, R Mishra New York Presbyterian Hospital, New York, NY J Slater, A Galloway, G Perk, I Kronzon NYU Medical Center, New York, NYC Ruiz, D Loulmet, V Subramanian, I Kronzon, N Marino Lenox Hill Hospital, New York, NYR Kipperman, S Lucas, RM Bodenhamer, J Randolph, J Williams Oklahoma Heart Hospital, Okalahoma City, OKZ Hijazi, R March, K Cao, J Soble Rush University Medical Center, Chicago, ILP Kramer, B Castlemain, A Schwartz, L Crouse, V Pasnoori Shawnee Mission Medical Center, Shawnee Mission,
KSA Berke, N Robinson, R Colangelo, P Damus, H Fernandez, J Taylor, N Bercow, A KatzSt. Francis Hospital, Long Island, NYT Bajwa, D O’Hair, D Kress, K Sagar St. Luke’s Medical Center, Milwaukee, WIM Sanz, S Tahta, JM Maxwell, B Berry, J Knapp St. Patrick's Hospital & Health Science Ctr, Missoula,
MTM Reisman, W Curtis, D Gartman, J Teply, D Warth, K Krabill Swedish Medical Center, Seattle, WA P Fail, K Paape, T Fudge, M Trotter, M Allam, E Feinberg, V Tedesco, D Solet Terrebonne General Medical Center, Houma, LAR Low, N Young, K Shankar, R Calhoun, W Bommer University of California at Davis, Sacramento, CAJ Carroll, J Cleveland, R Quaife University of Colorado Health Sciences Center,
Denver, COH Herrmann, M Acker, YJ Woo, F Silvestry, S Wiegers University of Pennsylvania, Philadelphia, PA S Bailey, E Sako, J Erikson University of Texas Health Sciences Ctr, San
Antonio, TXDS Lim, I Kron, J Kern, J Dent, H Gutgesell University of Virginia, Charlottesville, VAR Kipperman, J Brown, D Cohen, H Hamrah Morristown Memorial Hospital, Morristown, NJK Kent, S Boyce. P Sears-Rogan Washington Hospital Center, Washington DCJ Lasala, M Moon, R Damiano, B Lindman, A Zajarias, J Madrazo Washington University Medical Center, St. Louis, MO G Hanzel, F Shannon, M Sakwa, A Abbas, M Gallagher, P Markovitz William Beaumont Hospital, Royal Oak, MI
Interventional Cardiologist, Cardiac Surgeon, Echocardiologist
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Purpose
To present initial safety and effectiveness data of MitraClip device in Continued Access “real world” high surgical risk patients • Enrollment is ongoing
To compare initial Continued Access high surgical risk study results to EVEREST II high surgical risk study results
To assess the impact of operator learning on outcomes of high surgical risk patients
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
KEY INCLUSION CRITERIA• Predicted procedural mortality risk ≥ 12% (STS calculated or Surgeon estimated based on specific co-morbidities)• Symptomatic significant (3+ or 4+) MR• Etiology: Degenerative or Functional • Primary regurgitant jet originates from leaflet mal-coaptation at A2 / P2 region
KEY EXCLUSION CRITERIA• Evidence of an AMI in 2 weeks prior• EF ≤ 20% and/or LVESD > 60mm• Leaflet anatomy which may preclude MitraClip device implantation / proper positioning• Prior MV leaflet surgery• Echo evidence of intra-cardiac mass, thrombus, vegetation• Active endocarditis• Clip implant criteria
• Mitral valve area < 4 cm2
• Flail gap ≥ 10 mm, • Flail width ≥ 15 mm•Coaptation length < 2 mm
All high risk patients were enrolled using the same inclusion/exclusion criteria
Key Eligibility CriteriaEVEREST II and Continued Access High Surgical Risk
Patients
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
High Surgical Risk Concurrent Control Group
Control group includes 36 patients screened for EVEREST II – High Surgical Risk• All patients met clinical eligibility criteria• All patients had significant MR (3+ to 4+) and
met high surgical risk criteria
Baseline co-morbidities well matched with EVEREST II High Surgical Risk Cohort
Management of MR through 1 year• 86% medical management • 14% mitral valve surgery
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Mitral Valve Anatomic CriteriaHigh Surgical Risk Concurrent Control
(N=36)
22%
20%
19%
11%
11%
8%
6%
3%
0% 10% 20% 30% 40%
Met all MitraClip anatomic criteria
No TEE performed
Leaflet calcification
MVA<4.0cm2
Jet origin other than A2-P2
Captation length >2mm
Flail width >15mm, or flail gap >10mm
Severely retracted posterior leaflet
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
EVEREST II High Surgical Risk CohortEnrollment
* As of April 12, 2011, ^ Enrolled by February 28, 2010
1 YearN = 133
1 YearN = 78
REALISM High Surgical Risk Trial^
N = 294 Enrolled
EVEREST II High Surgical Risk CohortN = 372*
EVEREST II High Surgical Risk CohortWith 1 Year Follow-Up^
N = 211
EVEREST High Surgical Risk Trial^
N = 78 Enrolled
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Patient AccountabilityEVEREST II and Continued Access High Surgical Risk
Patients
EVEREST IIHigh Surgical Risk Patients
N = 78
211 EVEREST IIHigh Surgical Risk Patients
With 1 Year Follow-up
Enrolled by 28 Feb 2010
Continued Access High Surgical Risk Patients
N = 133
N = 1281 Year Analysis
N = 75 1 Year Analysis
N = 3 Withdrawals
N = 5 Withdrawals
96% of patient data available for analysis
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Baseline Demographics and Co-MorbiditiesEVEREST II and Continued Access High Surgical Risk
PatientsEVEREST II
High Surgical Risk Patients (N = 78)
Continued Access High Surgical Risk
Patients (N = 133)
p-value
Age, years, Mean ± SD 77 ± 10 76 ±11 0.43
Estimated Mortality Risk* (%) 18 ± 8 19 ± 8 0.73
Gender, male (%) 63 59 0.66
Coronary Artery Disease (%) 84 80 0.47
Atrial Fibrillation (%) 62 65 0.76
Moderate – Severe Renal Disease (%)
23 35 0.07
Prior CV Surgery (%) 59 58 0.89
Prior MI (%) 56 45 0.15
NYHA Class III/IV (%) 90 84 0.23
Functional MR (%) 59 78 0.008
LVEF, Mean ± SD (%) 54 ± 14 46 ± 13 < 0.001
LVID-s, Mean (cm) 3.9 ±1.1 4.5 ± 1.0 < 0.001*STS risk calculated or surgeon estimate based on prespecified co-morbidities
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Implant Rate and Procedural ResultsEVEREST II and Continued Access High Surgical Risk
PatientsEVEREST II
High Surgical Risk Patients (N = 78)
Continued Access High Surgical Risk
Patients (N = 133)
p-value
MitraClip Implant Rate (%) 96 95 0.80
0 MitraClips 4 5 n/a
1 MitraClip 59 62 n/a
2 MitraClips 37 33 n/a
MR ≤ 2+ at discharge, all patients (%) 72 88 0.009
MR ≤ 2+ at discharge for patients with MR ≥ 3+ at baseline (%)
71 81 0.20
Procedural Results (min)
Mean Procedure Time 190 153 < 0.001
Mean Device Time 145 117 0.005
Mean Fluoroscopy Duration 53 39 < 0.001
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Implant Rate and Procedural ResultsEVEREST II and Continued Access High Surgical Risk
Patients
EVEREST II High Surgical Risk
Patients (N = 78)
Continued Access High Surgical Risk
Patients (N = 133)
p-value
Post-Procedural Results
ICU Duration (hours) 52 25 0.005
Hospital Stay (days) 3.9 2.5 0.05
Discharged To, (%)
0.26
Home 80 87
Home With Home Health Care 10 8
Nursing Facility 10 3
Died Prior to Discharge 4 2
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Predicted vs Observed 30 Day Mortality EVEREST II and Continued Access High Surgical Risk
Patients
0
2
4
6
8
10
12
14
16
18
20
EVEREST II HR Continued Access HR
% M
orta
lity
PredictedObserved
7.7%
18.2%
P = 0.006
3.8%
18.2%
P < 0.0001
P = 0.34
N = 78 N = 133
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
30 Day MAEEVEREST II and Continued Access High Surgical Risk
PatientsEVEREST II
High Surgical Risk Patients (N = 78)
# (%) Patients
Continued Access High Surgical Risk
Patients (N = 133)
# (%) Patients
p-value
Death 6 (7.7%) 5 (3.8%) 0.34
Major Stroke 2 (2.6%) 4 (3.0%) > 0.99
Re-operation of Mitral-Valve 0 0 n/a
Urgent / Emergent CV Surgery 0 1 (0.8%) > 0.99
Myocardial Infarction 2 (2.6%) 1 (0.8%) 0.56
Renal Failure 3 (3.8%) 1 (0.8%) 0.14
Deep Wound Infection 0 0 n/a
Ventilation >48 hrs 2 (2.6%) 2 (1.5%) 0.63
New Onset Permanent Atrial Fib 0 0 n/a
Septicemia 0 1 (0.8%) > 0.99
GI Complication Requiring Surgery 1 (1.3%) 0 0.37
Transfusions ≥ 2 Units 14 (17.9%) 16 (12.0%) 0.31
Total 21 (26.9%) 22 (16.5%) 0.08
Total Excluding Transfusions 10 (12.8%) 10 (7.5%) 0.23
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Investigator MitraClip Procedure Experience
EVEREST II and Continued Access High Surgical Risk Patients
EVEREST II High Surgical Risk
Patients (N = 78)
Continued Access High Surgical Risk
Patients (N = 133)
p-value
Number of Operators 25 34
Operator Experience:
Rolling average number of cases performed
10 23 < 0.0001
Median (Inter-quartile range) 7 (5, 16) 17 (8, 27)
* Includes patients treated in all EVEREST studies
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Baseline Demographics and Co-Morbidities EVEREST II, Continued Access and Concurrent
ControlEVEREST II
High Risk Patients
(N = 78)
Continued Access High Risk Patients
(N = 133)
Concurrent Control(N = 36)
Age, years, Mean ± SD 77 ± 10 76 ±11 77 ± 13
Estimated Mortality Risk (%) 18 ± 8 19 ± 8 17 ± 7
Gender, male (%) 63 59 50
Coronary Artery Disease (%) 84 80 71
Atrial Fibrillation (%) 62 65 53
Moderate – Severe Renal Disease (%)
23 35 31
Prior CV Surgery (%) 59 58 53
Prior MI (%) 56 45 36
NYHA Class III/IV (%) 90 84 84
Functional MR (%) 59 78 64
LVEF, Mean ± SD (%) 54 ± 14 46 ± 13^ 55 ± 18
LVID-s, Mean (cm) 3.9 ±1.1 4.5 ±1.0^ 3.8 ±1.1^p<0.001, REALISM HR vs CC
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
EVEREST II High Risk
Continued Access High Risk
Kaplan-Meier Freedom from Death At 1 Year EVEREST II, Continued Access and Concurrent
Control
Concurrent Control
75.6%
75.2%
55.6%
1yr6m0 Days 30 Days# At RiskEVEREST II High RiskREALISM High RiskConcurrent Control
133 126 115 5378 72 64 58
36 32 28 20
p = 0.048 vs CC
p = 0.008 vs CC
At 1 Year
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Kaplan-Meier Freedom from MV Surgery At 1 Year
EVEREST II and Continued Access High Surgical Risk Patients
1yr6m0 Days 30 Days# At RiskEVEREST II High RiskREALISM High Risk 133 126 115 53
78 72 64 58
EVEREST II High Risk
Continued Access High Risk
100%
96.8%
At 1 Year
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Core Lab MR Grade at 1 Year (matched)EVEREST II and Continued Access High Surgical Risk
Patients
78%
0
20
40
60
80
100
Baseline 1 Year
Perc
ent Pa
tient
s 3+
4+3+
4+
2+
1+
2+
p < 0.0001
0
20
40
60
80
100
Baseline 1 Year
3+
4+3+
4+
2+
1+
83%
2+
0+
p < 0.0001
EVEREST IIHigh Surgical Risk Patients
(n=54 matched cases)
Continued Access High Surgical Risk Patients
(n=69 matched cases)
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
LV End Diastolic and Systolic Volumes EVEREST II and Continued Access High Surgical Risk
PatientsEVEREST IIHigh Surgical Risk Patients
(n=54 matched cases)
Continued AccessHigh Surgical Risk Patients
(n=63 matched cases)
0
40
80
120
160
200
LVEDV LVESV
Baseline 1 Year
0
40
80
120
160
200
LVEDV LVESV
Baseline 1 Year
158 143
89 80
p = 0.0003 p = 0.011
172 140
82 72
Vo
lum
e (
mL
)
p < 0.0001 p = 0.0012
Baseline 1 year Baseline 1 year Baseline 1 year Baseline 1 year
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
NYHA Functional Class at 1 Year EVEREST II and Continued Access High Surgical Risk
PatientsEVEREST II
High Surgical Risk Patients(n=54 matched cases)
Continued Access High Surgical Risk Patients
(n=89 matched cases)
0
20
40
60
80
100
Baseline 1 Year
Perc
ent
Patien
ts
II
III
IV
II
III
IV
I
0
20
40
60
80
100
Baseline 1 Year
II
III
IV
II
III
I
P < 0.0001 P < 0.0001
I
IV
74%84%
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
SF-36 Quality of Life Scores at 1 Year EVEREST II and Continued Access High Surgical Risk
PatientsBaseline 1 Year
Continued Access HRn=70 matched
EVEREST II HRn=47 matched
Physical Component
p < 0.05 p < 0.001
Mental Component
p < 0.0001p < 0.06
Baseline 1 year Baseline 1 year Baseline 1 year Baseline 1 year
Continued Access HRn=70 matched
EVEREST II HR n=47 matched
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Hospitalization for CHFEVEREST II and Continued Access High Surgical Risk
Patients
0.86
0.45
0
0.2
0.4
0.6
0.8
1p=0.0002
1 Year Prior to MitraClip 1 Year Post MitraClip
48% Reduction0.65
0.36
0
0.2
0.4
0.6
0.8
1
An
nu
al R
ate
of
CH
F R
eh
op
*
p=0.02
45% Reduction
*CHF hospitalizations per patient-year
EVEREST II High Surgical Risk Patients
Continued Access High Surgical Risk Patients
1 Year PriorN=78
1 Year PostN=75
1 Year PriorN=133
1 Year PostN=128
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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Summary
Results consistent with previously demonstrated data in high surgical risk patients• MitraClip procedure safe• MitraClip device provides significant MR reduction and clinical benefits
– LV function, NYHA Function Class and Quality of Life (SF-36)
Procedural safety improved with increased experience• Significantly decreased procedure time with comparable effectiveness• Significantly decreased post-procedure ICU time and hospital stay• Decreased 30-day mortality