1. Cardiovacular Research Technologies
When to Repair Functional MR The Interventional Cardiologist’s Perspective
Ted Feldman, M.D., FSCAI FACC FESC
Evanston Hospital
CRT
Cardiovacular Research Technologies
Washington, D.C.
February 23 – 26, 2013

2. Ted E. Feldman, MD Consulting: Abbott Laboratories
Boston Scientific Corporation
Edwards Lifesciences, LLC

3. INDICATIONS FOR MITRAL VALVE OPERATION
ACC/AHA VHD Guidelines: 2008 Focused Update JACC Vol. 52, No. 13, 2008 September 23, 2008:e1–142

5. Mitral valve surgery in heart failure Acorn Clinical Trial
Serious adverse events by treatment group
Mean age 53.4±12.6 yrs
bjective: The study objective was to evaluate in a prospective, randomized, multicenter trial the safety and efficacy of mitral valve surgery with and without the CorCap cardiac support device (Acorn Cardiovascular, St Paul, Minn) in patients with New York Heart Association Class II to IV heart failure.
Background: Although mitral valve surgery has been performed successfully in patients with heart failure, the safety and long-term efficacy have not been estab- lished in a multicenter prospective trial. Cardiac support devices that reduce ven- tricular wall stress and promote beneficial reverse remodeling have been proposed as a new treatment option as a stand-alone procedure and as an adjunct to mitral valve surgery.
Methods: A subgroup of 193 patients were enrolled in the mitral valve repair or replacement stratum of the Acorn Clinical Trial; 102 patients were randomized to the mitral valve surgery alone group (control) and 91 patients were randomized to mitral valve surgery with implantation of the CorCap cardiac support device. Patients were followed for a median duration of 22.9 months.
Results: For the entire mitral valve surgery group, the 30-day operative mortality rate was only 1.6% at 30 days. Mitral surgery was associated with progressive reductions in left ventricle end-diastolic volume, left ventricle end-systolic volume, and left ventricular mass, and increases in left ventricle ejection fraction and sphericity index, all consistent with reverse remodeling. Recurrence of clinically significant mitral regurgitation was uncommon. Quality of life, exercise perfor- mance, and New York Heart Association functional class were all improved. Finally, the addition of the CorCap cardiac support device led to greater decreases in left ventricular end-diastolic volume and left ventricular end-systolic volume, a more elliptical shape, and a trend for a reduction in major cardiac procedures and improvement in quality of life compared with mitral surgery alone.
Conclusions: These findings suggest that there is clear benefit to the surgical elimination of mitral regurgitation and that there is additional benefit with the CorCap cardiac support device. Given the improvement in left ventricle structure and function, along with a low mortality rate, physicians should strongly consider offering mitral valve surgery in combination with the CorCap cardiac support device to patients with heart failure who are on an optimal medical regimen.
any in SAE 82%
J Thorac Cardiovasc Surg 2006;132:568-77

6. Guidelines on the management of valvular heart disease 2012
With CABG
European Heart Journal (2012) 33, 2474

7. Patient Selection for MR Therapies
Trial inclusion and exclusion criteria determine patient population
Resultant patient profile variable

8. EVEREST II Key Eligibility Criteria
Age 18 years or older
Moderate to severe (3+) or severe (4+) MR
Symptomatic
Asymptomatic with LVEF <60% or LVESD >45mm
ACC/AHA Task Force Guidelines JACC 1998;32:1486
MR originates from A2-P2 mal-coaptation
Core lab echo assessment
ASE Guideline - JASE 2003;16:
Candidate for mitral valve surgery including CPB
Transseptal deemed feasible
Key Exclusions
EF < 25% or LVESD > 55 mm
Renal insufficiency
Endocarditis, rheumatic heart disease

9. EVEREST II Randomized Clinical Trial Baseline Demographics & Co-morbidities
Device (%)
n=184
Control (%)
n=95 P
Age (mean)
67.3 years
65.7 years
0.32
Male
62.5
66.3
0.60
Congestive heart failure
90.8
77.9
<0.01
Coronary artery disease
47.0
46.3
>0.99
Myocardial infarction
21.9
21.3
Atrial fibrillation
33.7
39.3
0.42
Cerebrovascular disease
7.6
5.3
0.62
Cardiomyopathy
17.9
14.7
0.61
Diabetes
10.5
0.50
Previous cardiovascular surgery
22.3
18.9
0.54
MR Severity: 3+ to 4+
95.7
92.6
0.48
MR Etiology: Degenerative / Functional
73 / 27
0.81

10. EVEREST II Randomized Clinical Trial Demographic Comparison
EVEREST II RCT
n=279
2008 STS Database
Isolated 1st Elective
Operation for MR*
Repair
Replace
High Volume Hospitals (>140/Yr)
Age yrs (mean) 68 60 61 59
≥65 yrs
58%
37%
45%
n/a
≥75 yrs
32% 0%
NYHA Class III or IV
50%
26%
CHF
86%
41%
Hypertension
75%
60%
67%
43%
Diabetes Mellitus 9%
13%
23%
6.5%
COPD / Chronic Lung Disease
15%
17%
29%
EF (mean)
53%
55%
56%
*Partial year; **61% elective; ***81% elective
+Preliminary; STS 1.8
Font on top row
*Gammie JS et al Influence of Hospital Procedural Volume on Care Process and Mortality for Patients Undergoing Elective Surgery for Mitral Regurgitation. Circ 2007;115: 10

11. EVEREST II High Risk Registry
Subject screened for EVEREST II
Evalve Mitraclip
Surgery
Good
Surgical
Candidate?
Yes No
High Risk Registry
Predicted operative mortality ≥12%
Primary Endpoint: Mortality at 30 days
Randomized
THIS IS THE CURRENT EFFICACY ENDPOINT:
The major effectiveness endpoint is descriptive statistics comparing the following measures: MR severity grade, need for surgery, NYHA, QOL, re-hospitalization and LV function compared to published reports for similar patients treated medically or surgically. The endpoint will be analyzed per the surviving intent to treat population at 12 months.
or in the judgment of the surgeon investigator the patient is considered a high risk surgical candidate

12. High Risk Registry Inclusion Criteria
STS surgical risk calculator ≥ 12%
or judgment of surgeon investigator the patient is considered high risk due to one of the following:
Porcelain aorta or mobile ascending aortic atheoroma
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

13. EVEREST II High Surgical Risk and Concurrent Control Baseline Demographics and Co-morbidities
High Risk Cohort
N=211
Concurrent Control
N=36
Euro Heart Survey^
Not Operated, N=193
Operated, N=203
Age (years)
76 ±10
77 ±13
69 ±13
63 ±12
≥ 75 years, (%)
57%
64%
65%
35%
Predicted Mortality*, (%)
15.0%
16.4%
n/a
Prior Cardiac Surgery, (%)
58%
50% 7% 3%
History Myocardial Infarction, (%)
49%
36%
28%
18%
Prior Stroke, (%)
14%
COPD / Chronic Lung Disease, (%)
30%
31%
21%
11%
Moderate to Severe Renal Failure, (%)
History Atrial Fibrillation, (%)
53%
32%
Diabetes Mellitus, (%)
40%
42%
10%
Mean Ejection Fraction, (%) 49 55 48 56
LV ESD (mm)
4.2
3.8 41 40
NYHA Class III or IV, (%)
86%
84%
70%
Etiology – Functional MR, (%)
71%
12%
26%
* Based on STS ≥ 12% or an assigned mortality 12% for pre-specified comorbidities
Mirabel et al. European Heart Journal, 2007
EVEREST II High Surgical Risk Cohort – EuroPCR 2011

15. Key exclusion criteria
Inclusion criteria
dilated ischaemic or non-ischaemic cardiomyopathy
≥moderate (2+) FMR
LV EF <40%
NYHA class II–IV
6 min walk distance (6MWD) 150–450m
stable heart failure medication for 3 months
Key exclusion criteria
IV inotrope infusion ≤30 days
severe tricuspid regurgitation
serum Cr.2.2 mg/dL
organic mitral valve pathology
pacing lead already in the CS

17. Randomize 1:1 ~420 patients enrolled at up to 75 US sites
Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk
~420 patients enrolled at up to 75 US sites
Significant FMR ≥3+ core lab
High risk for mitral valve surgery
Specific valve anatomic criteria
Randomize 1:1
Control group
Standard of care
MitraClip
Safety: Composite death, stroke, worsening renal function, LVAD implant, heart transplant at 12 months
Effectiveness: Recurrent heart failure hospitalizations
Protocol conditionally approved by FDA July 26, 2012

18. Key Inclusion Criteria
Functional MR ≥3+
ischemic or non-ischemic cardiomyopathy
Symptomatic
NYHA class II, III or ambulatory IV
STS mortality risk is ≥ 8% or Local Site Heart Team concludes that co-morbidities result in a prohibitive predicted operative risk of stroke or death
≥1 HF hospitalization during prior year
and/or BNP ≥400 pg/ml
or nT-proBNP ≥1600 pg/ml ≤90 days
treated per standards for CAD, LV dysfunction, MR or HF including CRT, revascularization, OMT
primary MR jet originates from malcoaptation of A2-P2 scallops
Remove lvef 18

19. Key Exclusion Criteria
severe LV dysfunction is defined as LVESD >55mm or LVEF<20%
MV area <4 cm2
MI ≤90 days
Untreated clinically significant CAD requiring revascularization
CVA or TIA within 6 months or severe carotid stenosis
Any percutaneous coronary, carotid or endovascular intervention or carotid surgery within 30 days, or any coronary or endovascular surgery within 6 months
CRT and/or ICD implant or revision within 90 days
Leaflet anatomy which may preclude MitraClip implantation, proper MitraClip positioning on the leaflets or sufficient reduction in MR
Severe right ventricular failure or severe tricuspid regurgitation

20. Grossi EA, Patel N, Woo, YJ, Goldberg JD, Schwartz CF, Subramanian V, Feldman T,
Bourge R, Baumgartner N, Genco C, Goldman S, Zenati M, Wolfe JA, Mishra YK, Trehan N, Mittal S, Shang S, Mortier TJ, Schweich CJ J Am Coll Cardiol 2010; 56:
Mean age 35yrs, LVEF35-39%
?? Greater need for trials in conjunction with Revasc??
… improved survival and a significant decrease in major adverse outcomes… validates the concept of ventricular reshaping…
Grossi EA, Patel N, Woo, YJ, Goldberg JD, Schwartz CF, Subramanian V, Feldman T, Bourge R, Baumgartner N, Genco C, Goldman S, Zenati M, Wolfe JA, Mishra YK, Trehan N, Mittal S, Shang S, Mortier TJ, Schweich CJ
J Am Coll Cardiol 2010; 56: