10/10/2015

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What Can We Treat and

What Should We Treat

Christian Spies, MD Interventional Cardiology

The Queen’s Medical Center

Associate Professor of Medicine

University of Hawaii

Percutaneous Mitral Valve Repair:

Innovative Procedures, Devices & State of

the Art Care for Arrhythmias, Heart Failure &

Structural Heart Disease October 8-10, 2015

Hilton Hawaiian Village, Honolulu, HI

Can treat (FDA approved): • Moderate to severe, degenerative mitral regurgitation in patients

who are deemed too high risk for surgery (STS score >6/8%)

Should treat (Not FDA approved): • Isolated moderate to severe, functional mitral regurgitation

irrespectively of the operability of the patient

What Can We Treat and

What Should We Treat

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3 Nkomo et al. Lancet, 2006; 368: 1005-11.

> 9.3% for ≥75 year olds (p

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Annulus

Leaflets

Cordae

Papillary

Muscles

Adjacent

Myocardium

Mitral Regurgitation Anatomy

Primary: Anatomic abnormality

the mitral valve

• Leaflets

• Subvalvular

apparatus

• Chordae and

papillary muscles

Secondary : LV dilation; often

secondary to ischemic

heart disease

• Leads to mitral

annular dilation

• Incomplete coaptation

of the mitral valve

Mitral Regurgitation Classification

Primary = Degenerative MR

Secondary = Functional MR

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Primary

“The Valve”

Secondary

“The Ventricle”

Usually myxomatous Ischemic or not

Mitral Regurgitation Classification

8

Natural History

Avierinos JF, et al. Circulation 2002;106:1355

100

90

80

70

60

50

Surv

ival %

0 2 4 6 8 10

2 RF

1 RF

95 ±2

70 ±5

55 ±9

Risk Factors

Age 50 yrs

Atrial fibrillation

LA enlargement

Flail

Mild MR

MR 3

or

EF

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9

Severity and Survival

Enriquez-Sarano M et al. NEJM 2005;352:875-83

Worse Survival

100

90

80

70

60

50

0

Surv

ival

(%)

Years

0 1 2 3 4 5

P

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6

11

100

80

60

40

20

0

Surv

ival %

Years

0 1 2 3 4 5 6 7 8 9 10

NYHA I-II

NYHA III-IV

P

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Wu AH, et al. J Am Coll Cardiol 2005;45:381-87

1.0

0.8

0.6

0.4

0.2

0.0

Event-

free S

urv

ival

Time (Days)

0 500 1000 1500 2000

Functional MR- No Mortality Benefit with Surgery

Glower. JACC 2012;60:1315-22

Functional MR- High Risk of Recurrence

0 1 2 3 4 5 6 7 8 9 10 12 14 16 18 20

Years

100

80

60

40

20

0 Fre

edom

Fro

m

Mitra

l R

egurg

itation

DMR >3+

DMR >2+

IMR > 2+

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Degenerative MR

Surgery for symptoms or

LV dysfunction

Functional MR

Asymptomatic

if repairable

and low risk

Medical

therapy first

No medical

option for valve

Consider CRT

Surgery only in highly

selected patients with HF

Surgery is Class I

Indication

Surgery is Class II b

Indication

Nishimura et al. JACC 2014;63:e57

Current General Principals

of Therapy

16 Mirabel M, et al. Eur Heart J 2007;28:1358-1365

No surgery in 49%

Predictors were

age, morbidity, non-

ischemic etiology,

MR severity

396 patients with symptomatic severe MR

53% degenerative

0

20

40

60

80

100

120

140

160Decision notto operate

Decision to

operate

P

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Percutaneous Mitral Valve Repair MitraClip® System

EVEREST II Trial

279 Patients enrolled at 37 sites

Randomized 2:1

Significant MR (3+-4+) Specific Anatomical Criteria

Device Group MitraClip System

N=184

Control Group Surgical Repair/Replacement

N=95

Feldman et al. Engl J Med 2011;364:1395-406.

Echocardiography Core Lab and Clinical Follow-Up:

Baseline, 30 days, 6 months, 1 year, 18 months, and

annually through 5 years

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EVEREST II Trial

Inclusion – Candidate for MV Surgery

– Moderate to severe (3+) or severe (4+) MR

• Symptomatic – >25% EF & LVESD

≤55mm

• Asymptomatic with one or more of the following

– LVEF 25-60%

– LVESD ≥40mm

– New onset atrial fibrillation

– Pulmonary hypertension

Exclusion – AMI within 12 weeks

– Need for other cardiac surgery

– Renal insufficiency • Creatinine >2.5mg/dl

– Endocarditis

– Rheumatic heart disease

– MV anatomical exclusions • Mitral valve area 11mm) and length (

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Feldman et al. Engl J Med 2011;364:1395-406.

EVEREST II Trial –

Conclusions

FDA approval of MitraClip for all patients with mitral

regurgitation (degenerative and functional)?

Age: 82 ±9 years

Prior MI: 24%

Prior stroke: 10%

Diabetes: 30%

COPD: 32%

Renal disease: 28%

Mean STS Risk

13.2%

Lim et al. JACC 2014;64:182-192.

Prohibitive Surgical Risk

DMR Cohort (n=127)

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Primary Safety Endpoint Primary Safety Endpoint 30-day Observed Mortality Lower than Predicted

18.2% 4.8%0%

5%

10%

15%

20%

MeanMortality

Rate

N = 351

Observed Predicted

Mortality

HR Cohort (N=351):

Observed Mortality 95% UCB

4.8% 7.6%

Mean Predicted Mortality 95% LCB 95% UCB

Mean Predicted Mortality 95% LCB 95% UCB18.2% 17.3%

19.1%

p < 0.0001

As presented by Scott Lim MD, ACC 2013

ACC 2013, presented by Scott Lim, MD

Left Ventricular Volumes

Hospitalizations for Heart Failure

Left Ventricular End Diastolic Volume Left Ventricular End Systolic Volume

(N = 69) Paired

Data (N=69)

0.67

0.18

0.0

0.2

0.4

0.6

0.8

1.0

1 Year Prior… 1 Year Post…

HF

Ho

spit

aliz

atio

n R

ate

pe

r P

atie

nt Y

ear

73% Reduction

125

109

60

70

80

90

100

110

120

130

140

Baseline 1 Year

Vo

lum

em

L

-16 mL

0

49

46

30

35

40

45

50

55

60

Baseline 1 Year

0

-3 mL

4+

4+

3+

3+

2+

2+

1+

1+

0%

20%

40%

60%

80%

100%

Baseline 12 Months

Patie

nts

(%

)

Mitral Regurgitation Grade

0

1+

3+

4+

2+ Clinically Important Reduction

of Mitral Regurgitation

IV

IV IV

III

III III

II

II II

I

I I

0%

20%

40%

60%

80%

100%

Baseline 30 Days 12 Months

Patie

nts

(%

)

NYHA Functional Class

I

II

IV

III Clinically Important Improvement

in NYHA Functional Class

Clinically Important Reduction

in the Rate of Hospitalization

for Heart Failure

Clinically Important Reverse

LV Remodeling

Prohibitive Surgical Risk

DMR Cohort (n=127)

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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

FDA Approval

MitraClip Delivery System Approved by FDA on October 24, 2013.

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 surgeon experienced in

mitral valve surgery and a cardiologist experienced in mitral valve

diseased, and in whom existing comorbities would not preclude

the expected benefit from reduction of the mitral regurgitation.

Definition of Prohibitive Risk: STS score of surgical MV repair

>6% or mitral valve replacement >8%

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Medical Therapy

Less Invasive

Increased MR Reduction

MV Surgery

MitraClip®

Options for Degenerative MR

STS score > 6/8%

• Limited treatment options

(medications, CRT)

• Surgery with no mortality

benefit

• High recurrence rate after

surgical MV repair

• Class IIb indication in recent

guidelines to consider

surgery

Functional Mitral Regurgitation

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• Treating Centers: 491

• Patients: 20,018

• Implant Rate: 96%

• Etiology

• Functional MR 65%

• Degenerative MR 22%

• Mixed 13%

Data as of 03/31/2015. Source: Abbott Vascular.

FMR 65%

DMR 22%

Mixed 13%

Etiology

Realism: 70% FMR

Access-EU: 69% FMR

TRAMI: 71% FMR

Worldwide Mitraclip Experience

Functional Mitral Regurgitation

Beigel et al. JACC 2014;64:2688-2700

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Transcatheter Valve Treatment

Sentinel Pilot Registry (TCVT)

• TCVT: Transcatheter Valve Treatment Sentinel Pilot Registry

• Part of European Society of Cardiology

• Prospective, independent registry of consecutive patients

• 628 Patients at 25 centers in 8 countries

Nickenig G. Et al. J Am Coll Cardiol 2014;64:875–84

TCVT – Baseline Characteristics

Nickenig G. Et al. J Am Coll Cardiol 2014;64:875–84

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TCVT – Procedural Characteristics

TCVT – NYHA Class

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TCVT – Degree of MR

TCVT – Echo Characteristics

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Cardiovascular Outcomes Assessment of the MitraClip

Percutaneous Therapy for Heart Failure Patients with

Functional Mitral Regurgitation

Purpose

• COAPT is a landmark trial to further study the MitraClip device in symptomatic FMR patients with

heart failure

• COAPT is the first randomized controlled clinical trial to compare non-surgical (medical) standard of care

treatment to a percutaneous intervention to reduce

MR

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To evaluate the safety and effectiveness of

the MitraClip System for treatment of

functional mitral regurgitation (FMR ≥3+) in

symptomatic heart failure subjects who are

treated per standard of care and who have

been determined by the site’s local heart team

as not appropriate for mitral valve surgery

STS score is no inclusion or exclusion criterion!

Objective

41

Randomize 1:1

Clinical and TTE follow-up:

Baseline, Treatment, 1-week (phone)

1, 6, 12, 18, 24, 36, 48, 60 months

Control group

Standard of care

N=215

Symptomatic heart failure subjects who are treated per standard of care

Determined by the site’s local heart team as not appropriate for mitral valve surgery

Specific valve anatomic criteria

MitraClip

N=215

Significant FMR (≥3+ by core lab)

Goals: 430 patients at up to 79 US sites

Trial Design

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Nu

mb

er

of

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bje

cts

Months

Randomization Projection

Projected

Actual

Accelerated

Current Enrollment

Can treat (FDA approved): • Moderate to severe, degenerative mitral regurgitation in patients

who are deemed too high risk for surgery (STS score >6/8%)

Should treat (Not FDA approved): • Isolated moderate to severe, functional mitral regurgitation

irrespectively of the operability of the patient

Percutaneous Mitral Valve Repair: What Can We Treat and What Should We Treat

10/10/2015

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spies.cvm@gmail.com

(808) 225-5050