mitral valve disease bleeding (≥2u or surgery for rebleeding) 12.6% non-cerebral thromboembolism...

Mitral Valve Disease James Hermiller, MD, FACC, FSCAI

St Vincent Heart Center Indianapolis, IN

Disclosures

• Consulting Fees/Honoraria

• Speaker Bureau

• Abbott, BSC, Medtronic, Edwards and St Jude

• Medicines Company, Astra-Zeneca

Affiliation/Financial Relationship Company

• Introduction

• Transcatheter Repair

– MitraClip

– Annular Approaches

• TMVR

• Summary/Conclusions

Outline

Complexity Mitral Valve Aortic Valve

Complex Simple

Euro Heart Survey: Surgery for Functional Mitral Regurgitation Not an Option

Isolated MR

(n=877)

Severe MR

(n=546)

No Severe MR

(n=331)

No Symptoms

(n=144)

Symptoms

(n=396)

No Intervention

(n=193) 49%

Intervention

(n=203) 51%

Mirabel et al, European

Heart J 2007;28:1358-

1365

• Introduction


– MitraClip


• TMVR


Outline

Edge-to-Edge Technique

Maisano. JACC 2011;58:2174-82.

Ottavio Alfieri

In the Beginning: Lost

In the Beginning: Confused

Steerable Sleeve

Delivery Catheter

Guiding Catheter

MitraClip

In the Beginning: Off Target

Ahah!!!!

LAA

300

600

300

A1

A2 A3

P1

P2

P3

FOSSA

AO

LATERAL

MEDIAL

ANTERIOR

POSTERIOR

Transseptal

Essential: 3D Imaging

3D TEE

• Aligning the Clip so the DC shaft is

perpendicular to the plane of the

mitral valve

Lining up the Clip: Trajectory

Grasping Leaflets

Slow Pull-Back –

Leaflets Fall In

Systematic

Confirmation of

Grasp Success

Confirming: Leaflet Grasp

Wait Look

MitraClip Smoking Relaxing Transseptal Location Vector into Valve Grasping/Verifying Grasp Patient Selection Imaging (3D TEE)

MitraClip

• Surgical candidates- 5 year EVEREST II randomized trial

• High risk global experience

– Improved symptoms, procedural safety, short stays

– Decreased heart failure hospitalizations

– Expanded anatomic substrates

• High risk FMR US COAPT Trial

– Randomized MitraClip vs GDMT ± CRT

CONCLUSIONS

Although percutaneous repair was less effective at reducing mitral regurgitation than conventional surgery, the procedure was associated with superior safety and similar improvements in clinical outcomes.

5 year Follow-Up

Mitral Regurgitation Grade EVEREST II RCT All Treated Patients (N=258)

0

20

40

60

80

100

Baseline MitraClip 5Years

Surgery 5Years

4+

3+

2+

1+

0

Perc

ent

of

pat

ien

ts

3+ 2+ 1+

Residual MR with MitraClip…

2+ 1+ 0

Stability of Mitral Annular Dimensions Diastolic SLAD

3.7 3.6 3.7 3.8

0

1

2

3

4

5

BL 1 Year BL 5 Years

Me

an S

LAD

dia

st (

cm)

N = survivors with paired data; p-values for descriptive purposes only

N=32 N=18

MitraClip (N=48)

p=0.07 p=0.20

4.0 3.9 4.0 3.9

0

1

2

3

4

5

BL 1 Year BL 5 Years

Me

an S

LAD

dia

st (

cm)

N=92 N=72

MitraClip (N=130)

p<0.05 p=0.18

DMR FMR

Long-Term MitraClip Device Safety EVEREST II RCT

Through 1 Year # (%) of patients

1 Year to 5 Years # (%) of patients

Single Leaflet Device Attachment (SLDA)

10 (6.3%) 0 (0.0%)

MV stenosis 1 (0.6%) 0 (0.0%)

Device Embolization 0 (0.0%) 0 (0.0%)

Based on N=158 who were implanted with 1 or 2 MitraClip devices

6-Month Landmark Analysis

97.1% 98.7% 1 year 91.4%

93.7% 5 years

Kaplan-Meier Freedom From MV Surgery in MitraClip Group or Re-operation in Surgery Group

MitraClip

Surgery

EVEREST II RCT

Feldman T et al. N Engl J Med 2011;364:1395-1406

Subgroup Analyses for the Primary End Point at 12 Months

Endovascular Valve Edge-to-Edge REpair STudy

Glower, et al. J Am Coll Cardiol 2014;64:172–81

The percutaneous mitral valve device significantly reduced MR,

improved clinical symptoms, and decreased LV dimensions at

12months in this high-surgical-risk cohort.

The EVEREST II High Surgical Risk Cohort

n=351

Age 76 ± 11

Predicted Surgical Mortality Risk, (%) 18.2±8.4

NYHA Functional Class III or IV 85%

Atrial Fibrillation 69%

Mitral Regurgitation Grade ≥ 3+ 86%

Left Ventricular Ejection Fraction (%) 47.5 ± 14.2

Functional MR 70%

30 day Mortality 6.8%

Home ± home health care 91.7 %

MR Grade I-II at 2 years 87%

Decrease LV EDV/ESV at 1 year 17.9 / 8.1 ml

Event Free Survival 1 year 77.1%

Left Ventricular Volumes

160.5

142.6

60

80

100

120

140

160

180

Me

an V

olu

me

(m

l)

87.0

78.9

60

65

70

75

80

85

90

Baseline 1 Year Baseline 1 Year

Paired data (N=203) Paired data (N=202)

Left Ventricular End Diastolic Volume

Left Ventricular End Systolic Volume

Mean = -17.9 ml

97.5% UCB = -13.5 ml

p<0.0001

Mean = -8.1 ml

97.5% UCB = -4.8 ml

p<0.0001

Hospitalizations for Heart Failure

0.79

0.41

0.0

0.2

0.4

0.6

0.8

1.0

1 Year Priorto MitraClip

1 Year PostDischarge

HF

Ho

spit

aliz

atio

n R

ate

Pe

r P

atie

nt

Year

48% reduction p<0.0001

N=351 N=338

All treated

Lim SD et al. J Am Coll Cardiol 2014;64:182–92

TMVR in prohibitive surgical risk patients is associated with safety and good clinical outcomes, including decreases in rehospitalization, functional improvements, and favorable ventricular remodeling, at 1 year.

Baseline Demographics and Comorbidities

Characteristic Prohibitive Risk DMR

N = 127

Age (mean ± SD) 82 ± 9 years

Patients over 75 years of age 84%

Male Gender 55%

Coronary Artery Disease 73%

Prior Myocardial Infarction 24%

Previous Cardiovascular Surgery 48%

Atrial Fibrillation History 71%

Prior Stroke 10%

Diabetes 30%

Moderate to Severe Renal Disease 28%

Chronic Obstructive Pulmonary Disease 32%

STS Mortality Risk (mean ± SD) [v2.73, replacement] 13.2 ± 7.3%

SF-36 QoL Physical Component Score (mean ± SD) 32.0 ± 8.7

SF-36 QoL Mental Component Score (mean ± SD) 46.1 ± 12.5

Post-Procedural and Discharge Results

Post-Procedural and Discharge Results Prohibitive Risk

DMR N = 127

Post-Procedural (mean ± SD)

ICU/CCU duration 1.4 ± 1.8 days

Length of hospital stay 2.9 ± 3.1 days

Discharge MR, (%)

MR ≤ 2+ at Discharge 82%

MR ≤ 1+ at Discharge 54%

Discharged home, (%) 87%

MitraClip implant success 95.3%;

Death* 6.3%

Myocardial infarction* 0.8%

Non-elective CV surgery for adverse events* 0.8%

Stroke* 2.4%

New onset of permanent AF* 0%

Renal failure 1.6%

Ventilation >48 hours* 3.1%

GI complication requiring surgery* 0.8

Major vascular complications 5.5%

Major bleeding (≥2U or surgery for rebleeding) 12.6%

Non-cerebral thromboembolism 1.6%

Heart block/arrhythmia requiring perm pacemaker 0%

Atrial septal defect 1.6%

Mitral stenosis 0%

MitraClip in Prohibitive-risk DMR Pts 141 pts from EVEREST studies. Mean age 82 years, 87% NYHA III/IV,

mean STS score 13.2%. MitraClip implant success 95.3%; hospital stay 2.9 ± 3.1 days. 30-Day Adverse Events:

*CEC adjudicated.


MitraClip in Prohibitive-risk DMR Pts MR Grade Through 1 Year

0

20

40

60

80

100

Patients

(%

) 2+

4+

Baseline N=124

Discharge N=123

1 Year N=84

3+

4+

3+ 3+

2+ 2+

1+ 1+

Patients With Data Available at Follow-Up (Completers Analysis)

MR ≤2+ in 83% of surviving pts at 1 year


MitraClip in Prohibitive-risk DMR Pts

141 pts from EVEREST studies. Mean age 82 years, 87% NYHA III/IV, mean STS score 13.2%. LV Remodeling, Functional Class and Rehospitilization for CHF

MitraClip Systematic Review

MitraClip vs Surgery 30 Day Outcomes High Risk Patients

3.3 1.1

4.2 1.7 3

7

16.2

4.5

59

36.3

15

26

0

10

20

30

40

50

60

70

Death Stroke Bleeding ProlongedVent

ICU Days HospitalDays

MitraClip

Surgery

21 studies PhilipF et al, Cathet Cardiovasc Intervent 84:581, 2014

n=3198

n=3265

FDA MitraClip Approval October 24th, 2013

The MitraClip is approved for treatment of patients with

3+-4+ primary (degenerative) MR who are at “prohibitive risk” for mitral valve surgery and are likely to benefit

from MR reduction

History

• 87 year old man with a history of moderate MR and MVP

• Stable when he developed flash pulmonary edema 3 months prior to presentation

• Echo revealed 4+ MR with a flail leaflet; EF 60%; Flow reversal in Pas

• Refractory CHF – Turned down for OHS

• Offered Hospice – He declined

Pre-TEE

Pre TEE

Pre TEE Intercommisural

Pre-Imaging – 3D

Clip To Valve • Trajectory • Orientation • Location

2nd Clip

Confirm Grasp, R/O MS, and Release 2nd Clip

Follow Up

• Home following day

• Uneventful hospital course

6 months

• Echo – 1+ mild MR

• Functional class 1

• Back golfing

• Walking 3 miles

Therapy for MR

Degenerative Functional

Low Surgical Risk

Surgical Mitral Repair

?

High Surgical Risk

Commercial MitraClip

COAPT

Safety: Composite death, stroke, worsening renal function, LVAD implant, heart transplant at 12 months

Effectiveness: Recurrent heart failure hospitalizations

~430 patients enrolled at up to 75 US sites

Randomize 1:1

Control group

Standard of care

High risk for mitral valve surgery- Local Heart Team

Specific valve anatomic criteria

MitraClip

Significant FMR ≥3+ core lab; EF<50%; CHF hospitalization or BNP>300

Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for High Surgical Risk

Protocol conditionally approved by FDA July 26, 2012

COAPT Inclusion

• Symptomatic functional MR (≥3+) – Cardiomyopathy ischemic or non-ischemic

• LVEF ≥20% and ≤50%

• HF hospitalization ≤12 months and/or a corrected BNP ≥300 pg/ml or NT-proBNP ≥1500 pg/ml ≤90 days

• TTE on optimal therapy ≥30 days after: – any change in GDMT

– revascularization and/or implant of CRT

Version 5.1 November 11, 2013

Case History

• 79 year old man s/p prior CABG with a 6 month

history of refractory CHF and severe MR, despite maximum medical therapy. No LBBB.

• Several comorbidities including Creatinine or 2.0

mg/dl, atrial fibrillation, DM, prior CVA (complete recovery)

• Echo revealed 4+ MR caused by functional valve disease and EF of 25%; turned down by two surgeons

Baseline Echo: FMR

MitraClip Placement

Follow Up

Single Clip

Follow Up

• Trace MR after one clip – Device time 43 min

• Home the following day

• No rehospitalizations

• 2 Year follow up – EF 30-35% with

mild

• 1+ MR; Functional Class II

Follow Up Echo

• Introduction


– MitraClip


• TMVR


Outline

Percutaneous Mitral Repair Devices

• PTMA

• Monarc

• Mobuis leaflet repair

• Recor RF annular remodeling

• Coapsys

• Leaflet repair

• CS annuloplasty

• Direct annuloplasty

• Cerclage

• Mitral spacer

• Midle Peak

• Chordal replacement

• Valve replacement

Already gone Still developing

CARILLON Mitral Contour System

Coronary Sinus- Indirect Annuloplasty

TITAN Trial CARILLON Mitral ystem for FunContour Sctional MR

Non-Implanted Implanted

n=36 n=17

40% reduction in MR Reverse remodeling Functional improvement

Eur J Heart Fail. 2012 Aug;14(8):931-8

24/33 Patients with MR ≤Mild at 6 Months FU

Update from European CARDIOBAND Trial 35 patients results 2/3/2015

Septo Lateral Dimension

Mean Age 72 (56-81) STS Repair 7 (1-34)

DIRECT ANNULOPLASTY Mitralign Procedure Steps

Wire Delivery Pledget Delivery Plication & Lock

Direct Annuloplasty - Transventricular Approach Mitralign System

Wire Placement Pledget Delivery

CE Mark Study 30-Day Performance: Core Lab Adjudicated

Baseline (n) 30 Day (n) 30 Day Change Paired (n)

30 Day Change P-Value

LVIDd (cm) 6.35 (44) 6.10 (38) -0.21 (36) 0.004

LVIDs (cm) 5.37 (44) 5.15 (38) -0.21 (35) 0.079

LVEDv (ml) 186.4 (44) 169.0 (38) -20.1 (31) < 0.001

LVESv (ml) 122.8 (44) 110.5 (38) -13.1 (31) 0.008

Ventricular Changes

Baseline (n) 30 Day (n) 30 Day Paired Change (n)

P-Value

A-P Dia. (cm) 3.58 (44) 3.27 (38) -0.39 (31) < 0.001

S-L Dia. (cm) 3.55 (44) 3.34 (38) -0.26 (33) < 0.001

Annular Changes

Investigational Device Only: Not Available in the EU or US

N=64

.J Am Coll Cardiol. 2015;65:1190–5

Suture bicuspidization is performed by placement of a 2-0 pledget-supported mattress suture from the

antero-posterior to the posteroseptal commissures along the posterior annulus.

Suture bicuspidization of the tricuspid valve vs ring annuloplasty for functional tricuspid regurgitation

Midterm results of 237 consecutive patients

J Thorac Cardiovasc Surg 2007;133:117-126

Kay bicuspidization procedure

Schofer et al. J Am Coll Cardiol. 2015;65:1190–5

First Human Report on Percutaneous Repair for

Functional Tricuspid Regurgitation with the

Mitralign System

JAmCollCardiol2015;65:1190–5

Schofer et al. J Am Coll Cardiol. 2015;65:1190–5

• Introduction


– MitraClip


• TMVR


Outline

Mitral Replacement Technologies

• CardiaAQ

• Neovasc TIARA

• Tendyne

• Edwards FORTIS

• Endovalve

• M-Valve

• Medtronic

• Valtech

• Lutter

• MitrAssist

• Caisson

• MitraSeal

• Twelve

• HighLife

• Others….

Mitral Replacement FIRSTS IN HUMAN

• CardiaAQ 2012

• Tendyne Temp implants 2013

• Neovasc Tiara January 2014

• Edwards FORTIS February 2014

Transcatheter mitral valve implantation (TMVI) using the Edwards FORTIS device

Bapat V: EuroIntervention 2014;10:U120-U128

• Introduction


– MitraClip


• TMVR


Outline

• Unmet need in high risk patients with MR

• MitraClip safe and effective

– Less MR reduction than surgical repair

– Approved in US for high surgical-risk patients with degenerative MR

– >80% have <2+ MR, short hospital duration, fewer repeat hospitalizations, favorable LV remodeling and functional/QOL outcomes

– Functional MR – enroll in COAPT

• Annular approaches –Early

• TMVR – even earlier - Infancy

Conclusion

Thanks for your attention!

mitral valve disease bleeding (≥2u or surgery for rebleeding) 12.6% non-cerebral thromboembolism...

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