PowerPoint Presentation€¦ · 2/2/2016 3 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

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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

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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%


(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


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


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


Anterior

Bi-LeafletFlail

Posterior

Primary MR


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



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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!

[email protected]

Documents

PowerPoint Presentation€¦ · 2/2/2016 3 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