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Advances in the Percutaneous Repair of Mitral Regurgitation
Topics in Cardiovascular CareLG Health Heart & Vascular Institute
February 5, 2016
James E. Harvey, MD, MSc
Interventional Cardiologist
Medical Director, Structural Heart Intervention
The Heart Group of Lancaster General Health
Objectives:
Review the common causes of mitral regurgitation
Recognize the prevalence and impact of mitral
regurgitation on the population
Recognize the prevalence of undertreatment of
mitral regurgitation with surgery
Identify the current indications and outcomes for
percutaneous repair of mitral regurgitation with the
MitraClip
Disclosures
None: There are no financial relationships that may
bias my presentation.
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Mitral Regurgitation: Presentation Outline
What is it? Classification and Etiology
Who has it? Prevalence
Why do we care? Natural history
What can we do? Treatment options
Classification of MR
Incompetent mitral valve closure
Systolic retrograde blood flow from
the LV into the LA
Mayo Clinic (www.mayoclinic.com)
Primary:Anatomic abnormality
the mitral valve
•Leaflets
•Subvalvular apparatus
•Chordae and papillary
muscles
Secondary :LV dilation; often
secondary to ischemic
heart disease
•“Tethering” of the
chordae and mitral
leaflets
•Incomplete coaptation
of the mitral valve
Classification of MR: Pathway
Sorajja, Paul, MD; Abbott Northwestern Hospital
Primary
“The Valve”
Secondary
“The Ventricle”
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Valvular Heart Disease
12
Prevalence of Valvular Heart Disease by Age
Prevalence
increases from
0.5% for 18-44
year olds to
9.3% for ≥75
year olds
(p<.0001)
See Important Safety information Referenced Within
1. Heart Disease and Stroke Statistics 2010 Update: A Report From the American Heart Association. Circulation.2010;121:e46-e215.
2. Nkomo et al. Burden of Valvular Heart Diseases: A Population-based Study, Lancet, 2006; 368: 1005-11.
MR Progresses to Heart Failure
MR
Impaired Hemodynamics
LVRemodeling
MR initiates a cascade of events progressing to heart failure, then death, if untreated2,3
ClinicalManifestationsNYHA symptoms
Poor quality of life
HF hospitalizations
Death
1 Cioffi G, et al. Functional mitral regurgitation predicts 1-year mortality in elderly patients with systolic chronic heart failure. European Journal of Heart Failure 2005 Dec;7(7):1112-72 Grigioni F, et al. Outcomes in mitral regurgitation due to flail leaflets a multicenter European study. JACC Cardiovasc Imaging. 2008 Mar;1(2):133-413 Enriquez-Sarano M, et al. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med. 2005 Mar 3;352(9):875-83
Mitral Regurgitation: Symptoms
Shortness of breath
Fatigue
Cough
Orthopnea
“Bendopnea”
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Severity of MR Predictive of HF Survival
0%
20%
40%
60%
80%
100%
0 1 2 3 4 5
East West North
Su
rviv
al P
rob
abili
ty
N = 2057 N = 1587 N = 1252 N = 977 N = 772 N = 623
No MR
Mild MR (1+ or 2+)
Mod/sev MR (3+ or 4+)
Years:
Survival of Heart Failure Patients with MR by Degree of MRAdjusted for demographics and clinical variables at baseline
Note: Adjusted survival estimates are shown.Source: Trichon BH et al. Am J Card. 2003,91:538-43.
MR: Largely Untreated
Total MR Patients1,2
Eligible for Treatment3,4
(MR Grade ≥3+)
4,100,000
1,700,000
Annual MV Surgery5
Annual Incidence3
(MR Grade ≥3+)250,000
30,000Only 2% Treated Surgically
14% Newly Diagnosed
Each Year
1,670,000
Untreated Large
and Growing Clinical
Unmet Need
1. US Census Bureau. Statistical Abstract of the US: 2006, Table 12.2. Nkomo et al. Burden of Valvular Heart Diseases: A Population-based Study, Lancet, 2006; 368: 1005-11.3. Patel et al. Mitral Regurgitation in Patients with Advanced Systolic Heart Failure, J of Cardiac Failure, 2004.4. ACC/AHA 2008 Guidelines for the Management of Patients with Valvular Heart Disease, Circulation: 20085. Gammie, J et al, Trends in Mitral Valve Surgery in the United States: Results from STS Adult Cardiac Database, Annals of Thoracic Surgery 2010.
Mitral Regurgitation 2009 U.S. Prevalence
High-risk MR: Not Surgical Candidates
1.U.S. Census Bureau, Statistical Abstract of the U.S.
2.Nkomo et al. Burden of Valvular Heart Diseases: A Population-based Study, Lancet, 2006; 368: 1005-11.3.Patel, et al. Mitral Regurgitation in Patients with Advanced Systolic Heart Failure, J of Cardiac Failure, 2004.
4.Rankin, et al, J of Thoracic and Cardiovascular Surgery, March 2006
5.Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP III, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P. Sundt TM III, Thomas JD, 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease, Journal of the American College of Cardiology (2014, doi; 10.1016/j.jacc.2014.02.536
49%High-Risk
Patients*,1-3
(860K)
49%Surgical
Candidates
(850K)
2%Surgical Patients (30K)Factors prohibiting
surgery include4:
• Impaired LVEF
• High operative risk
• Multiple comorbidities
• Advanced age
Nearly half of MR patients not considered appropriate for mitral valve surgery 4
“When patients with
VHD are referred for
intervention in a
timely manner, there
is an improved
outcome in
preservation of
ventricular function
as well as enhanced
survival.”5
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Mirabel M, et al. Eur Heart J 2007;28:1358-1365
No surgery in 49%
Unoperated MR in Europe
396 patients with symptomatic severe MR (53% degenerative)
0
20
40
60
80
100
120
140
160
Decision not tooperate
Decision tooperate
P<0.0001
63% 59%67% 42%
15%
<50 50-60 60-70 70-80 >80
Age
Reduced LV function
Porcelain aorta
Prior Radiation
COPD
Renal insufficiency
Dementia
Frailty
RS von Bardeleben TCT 2013 image court. H Reichenspurner UHC
data:European Heart Journal 2007 28(11):1358-1365
Too high risk for mitral surgery?
Therapy Considerations
Medical Therapy
Less Invasive
Increased MR Reduction
MV Surgery
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Bones, I need you to fix the mitral valve
without opening the
chest.
Damn it Jim I’m a doctor…
Not a miracle worker!
EVEREST I: Feasibility and Safety
Abbott MitraClip
First-in-class Percutaneous Mitral Valve Repair System
Echo-guided
Well tolerated
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Abbott MitraClip
Feldman T, Wasserman HS, Herrmann HC, et al. Percutaneous mitral valve repair using the edge-to-edge technique: six-month results of the EVEREST Phase I Clinical Trial. J Am Coll Cardiol 2005;46:2134-40.
EVEREST I EVEREST II
EVEREST I: Feasibility
EVEREST II: Randomized Clinical Trial
EVEREST II: High Risk Registry
EVEREST REALISM: Continued Access Registry
EVEREST Clinical Studies
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Patient Demographics
MitraClip Therapy (n=184)
Surgery (n=95) P-value
Age (mean) 67 years 66 years 0.32
Male 63% 66% 0.60
History of CHF 91% 78% 0.005
Degenerative MR Etiology 74% 73% 0.81
Functional MR Etiology 26% 27% 0.81
Mean Ejection Fraction 60% 61% 0.65
Previous Cardiovascular Surgery
22% 19% 0.54
NYHA Functional Class III/IV 51% 47% 0.61
Atrial Fibrillation 34% 39% 0.42
Surgery N=80
279 Patients Enrolled at 37 SitesSignificant MR (3+ or 4+)
Specific Anatomical Criteria
Echocardiography Core Laband Clinical Follow-up
Baseline, 30 days, 6 months, 1 year,
18 months, and annually through 5 years
MitraClip TherapyN=178
R 2:1
EVEREST II: RCT Study Design
Mitral Regurgitation Severity
NYHA Functional Class LV End Diastolic Volume
Major Adverse Events at 30 DaysAll Treated Patients (N=258)
P <0.05 for all changes from Baseline within groups
(N=149) (N=126) (N=119)
MitraClip (N=178)84% MR ≤2+ at 3 Years
Matched (N=66) (N=57) (N=50)
Surgery (N=80)96% MR ≤2+ at 3 Years
Matched
Description of Event
# (%) Patients experiencing event
MitraClip (N=178) Surgery (N=80)
Death 2 (1.1%) 2 (2.5%)
Myocardial Infarction 0 0
Re-operation of Mitral Valve 0 1 (1.3%)
Urgent / Emergent CV Surgery 4 (2.2%) 4 (5.0%)
Stroke 1 (0.6%) 2 (2.5%)
Renal Failure 1 (0.6%) 0
Deep Wound Infection 0 0
Ventilation > 48 hrs 0 4 (5.0%)
GI Complication Requiring Surgery 2 (1.1%) 0
New Onset Permanent AFib 2 (1.1%) 0
Septicemia 0 0
MAE Major Bleeding Complication 9 (5.1%) 37 (46.3%)
TOTAL % of Patients with MAE 7.9% 50.0%
P <0.05 for all changes from Baseline within groups
(N=151) (N=130) (N=119)
MitraClip (N=178)97% NYHA I/II at 3 Years
Matched (N=66) (N=60) (N=50)
Surgery (N=80)98% NYHA I/II at 3 Years
Matched
P <0.05 for all changes from Baseline within groups
Mean LVEDV (mL), MitraClip (N=178)∆LVEDV = -30 mL at 3 Years
Mean LVEDV (mL), MitraClip (N=80)∆LVEDV = -44 mL at 3 Years
(N=144) (N=124) (N=116)Matched
BL 1Y BL 2Y BL 3Y
(N=65) (N=56) (N=47)Matched
BL 1Y BL 2Y BL 3Y
Stable Reduction of Mitral Regurgitation
Stable Improvement in NYHA Functional Class
Stable Reverse LV Remodeling
Positive Safety Profile
EVEREST II: RCT Outcomes
Long term event free survival comparable to surgery
Difference is initial efficacy
Kaplan-Meier Freedom from Death
EVEREST II: 4 year outcomes
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EVEREST II RCT
Reduction in MR is durable through 4 years
Surgery more effective in MR reduction
MitraClip has significantly less major adverse events
MitraClip results favorable LV remodeling
Difference in long term event free survival is initial efficacy
No difference in survival to 4 years
Sustained clinical benefits are comparable to surgery
4 (to 5) Year Data
Demographics and Co-morbidities
EVEREST II High Surgical Risk Cohort
(N=351)
Age (mean ± SD), years 76 ± 11
Patients over 75 years of age, (%) 58
Male Gender, (%) 61
Predicted Surgical Mortality Risk, (%) (mean ± SD)
18.2±8.4
NYHA Functional Class III or IV, (%) 85
Congestive Heart Failure, (%) 98
Coronary Artery Disease, (%) 82
Myocardial Infarction, (%) 51
Previous Cardiovascular Surgery, (%) 60
Atrial Fibrillation, (%) 69
Chronic Obstructive Pulmonary Disease, (%) 29
Diabetes, (%) 39
Moderate to Severe Renal Disease, (%) 31
Prior Stroke, (%) 13
†Based on STS ≥ 12% or an assigned mortality 12% for pre-specified co-morbidities
Follow-up to 2 years is ongoing
EVEREST II
High Surgical Risk CohortN=351
REALISM Continued Access High Risk Arm
N=273
EVEREST IIHigh Risk Registry
N=78
Withdrawals = 5Missing visit = 4
30-Day VisitN=342
99% Follow-Up Compliance
Withdrawals = 11Missing visit = 8
1-Year VisitN=327
98% Follow-Up Compliance
2-Year VisitN=211
*As of April 12, 2013
EVEREST Prohibitive Surgical Risk Cohort
EVEREST Prohibitive Surgical Risk Cohort
Mitral Regurgitation Grade
NYHA Functional Class Left Ventricular Volumes
Hospitalizations for Heart Failure
P <0.05 for all changes from Baseline within groups
Left Ventricular End Diastolic Volume Left Ventricular End SystolicVolume
(N=203)Paired
Data
Baseline 1Y
(N=202)
(N=325) (N=221) (N=109)
p<0.0001
Paired Data
p<0.0001 p<0.0001
1+2+
3+
4+
0+
1+
2+
4+3+
1+2+
3+
4+
1+2+
3+
4+
1+
2+
3+
0+
1+
2+
4+3+
4+
86% 83% 87%
(N=351) (N=338)
48% reduction p<0.0001
(N=233)Paired Data
p<0.0001 p<0.0001
III
III
IV
II
III
IV
I
II
IIIIV
18%
86% 83%
I
Baseline 1Y
Mean = -17.9 ml97.5% UCB = -13.5 mlp<0.0001
Mean = -8.1 ml97.5% UCB = -4.8 mlp<0.0001
Clinically Significant Reverse LV Remodeling
Clinically Significant Reduction in the Rate of Hospitalization for Heart Failure
Clinically Significant Improvement in NYHA Functional Class
Clinically Significant Reduction of Mitral Regurgitation
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MitraClip: FDA Approval
Indication for Use:
“The MitraClip Clip Delivery System is indicated for the percutaneous reduction of significant symptomatic mitral regurgitation (MR ≥ 3+) due to primary abnormality of the mitral apparatus [degenerative MR] in patients who have been determined to be at prohibitive risk for mitral valve surgery by a heart team, which includes a cardiac surgeonexperienced in mitral valve surgery and a cardiologistexperienced in mitral valve disease, and in whom existing comorbidities would not preclude the expected benefit from reduction of the mitral regurgitation.”
von Bardeleben RS; TCT 2013. Court: P Grayburn and FDA document
Sorajja, Paul, MD; Abbott Northwestern Hospital
Anterior
Bi-LeafletFlail
Posterior
Primary MR
Sorajja, Paul, MD; Abbott Northwestern Hospital
Current Therapy Considerations
Medical Therapy
Less Invasive
Increased MR Reduction
MV SurgeryMitraClip®
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A bottle of wine a day has never been scientifically proven to keep the doctor away. It may, however, keep the doctor happy.
A bottle of wine a day…
“A glass of wine a day has never been scientifically proven to keep the doctor away. It
may, however, keep the doctor happy.”
MitraClip Procedure
Abbott MitraClip
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Abbott MitraClip: Non-surgical mitral valve repair
Abbott MitraClip: Non-surgical mitral valve repair
Abbott MitraClip: Non-surgical mitral valve repair
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Abbott MitraClip: Non-surgical mitral valve repair
Abbott MitraClip: Non-surgical mitral valve repair
COAPT: Ongoing FMR Trial
COAPT: Landmark trial to study the MitraClip device
in symptomatic FMR patients.
Objective: Evaluate the safety and efficacy of the
MitraClip System for treatment of symptomatic ≥3+
FMR deemed not appropriate for mitral valve surgery.
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MitraClip Utilization: Changing Experience
29%
71%
23%
77%
EVEREST II(Randomized Controlled Trial*)
EVEREST II/REALISM (High Risk Cohort^)
ACCESS EU(Europe**)
• 258 patients
• Device time – 146 minutes
• Implant rate – 89%
• 211 patients
• Device time – 128 minutes
• Implant rate – 95%
= DMR = FMR
• 567 patients
• Device time – 117 minutesꜝ
• Implant rate – 99.6%
74%
26%
Multidisciplinary Cardiovascular Team
HospitalAdministrator
Heart Failure Specialist
Cardiac SurgeonInterventional
CardiologistEchocardiographer Anesthesiologist Nursing Staff
PatientReferral
Optimal PatientSelection
Echo Guidance &Communication
Plan Therapy& Resources
Post-procedureCare
Collaboration required for:
Resulting in:
OptimalPatient Care
Multidisciplinary Team
A multidisciplinary approach and collaboration across specialties is critical to MitraClip Therapy success
55 49 51 48 51 56 56 54 52
63 90 99 113 95
135164 157 174
3075
89
0
50
100
150
200
250
300
350
2002 2003 2004 2005 2006 2007 2008 2009 2010
Pati
en
ts
MitraClip Therapy
Surgical Repair
Surgical Replacement
What’s the effect on surgery?
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Hendrik Treede e al; A Heart Team’s Perspective on Interventional Mitral Valve Repair: Percutaneous clip implantation as an important adjunct to a surgical mitral valve program for treatment of high-risk patients; The Journal of Thoracic and Cardiovascular Surgery, 2011
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Conclusions:
Mitral regurgitation:
Common and prevalence increases with age.
Considerable morbidity and mortality.
Medical therapy is ineffective.
Surgical correction is effective.
Many candidates are not identified for surgery
Many are not candidates for surgery
Conclusions:
Percutaneous repair with MitraClip:
Safe and effective
Significantly decreases MR
Significantly improve symptoms
Results in favorable LV remodeling
Durable to at least 5 years
Indicated in prohibitive risk patients with symptomatic
primary (degenerative) 3-4+ MR
Current secondary (functional) MR trials ongoing
QUESTIONS?
Thank you!