History and Future of Transcatheter Mitral Valve Repair

Francesco MaisanoSan Raffaele Hospital

MilanoItaly

TAVI is moving rapidly into a clinical procedure widely available

• Replacement of the aortic valve is less demanding than MVR or repair

• Aortic stenosis is more prevalent in the elderly

• There is evidence of undertreatment of patients with aortic stenosis

Euro Heart Surveysurgery is often denied in the older patients

Isolated MRIsolated MR

(n=877)(n=877)

Severe MRSevere MR

(n=546)(n=546)

No Severe MRNo Severe MR

(n=331)(n=331)

No SymptomsNo Symptoms

(n=144)(n=144)

SymptomsSymptoms

(n=396)(n=396)

No InterventionNo Intervention

(n=193) 49%(n=193) 49%

InterventionIntervention

(n=203) 51%(n=203) 51%

Mirabel et al, European Heart J 2007;28:1358-1365

2/3 of symptomatic MR patients >70 are

denied surgery

Prevalence of valve disease in the population: MR is epidemic in the elderly

Nkomo et al , Lancet 2006

Transcatheter mitral interventionsTranscatheter mitral interventions• Balloon commissurotomyBalloon commissurotomy

• Annular repairAnnular repair– Sinoplasty (Monarc, Carillon, Sinoplasty (Monarc, Carillon,

PTMA)PTMA)– Direct reshaping (Mitralign, Direct reshaping (Mitralign,

GDS)GDS)

• Leaflet repairLeaflet repair– Edge-to-edge repair Edge-to-edge repair

(Mitraclip)(Mitraclip)– Others (plicating clips, chordal Others (plicating clips, chordal

repair)repair)

Cinching devicesCinching devices Internal (PS3)Internal (PS3) External (Coapsys)External (Coapsys)

OtherOther Hybrid devices (Mitral Hybrid devices (Mitral

Solutions, Micardia)Solutions, Micardia) Occluder (Cardiac Occluder (Cardiac

Solutions)Solutions) Transcatheter MVR Transcatheter MVR

(Endovalve)(Endovalve) Perivalvular leak closure Perivalvular leak closure

AJC 3:653,1959

1959

JAMA 1966

1984

1998-2001, Edwards suction and suture device (MILANO 1)

2002-2006 Edwards suction and suture device (MOBIUS / MILANO 2)

Clip repair in porcine heart (6 mos post repair)

Fann JI; St. Goar FG; Komtebedde J; Oz MC; Block PC; Foster E; Feldman T; Burdon TA Circulation 2003, 108:(Supp IV) 493.

2002-2003 Off-pump Edge-to-Edge Mitral Valve Technique Using a Mechanical Clip in a Chronic

Model – Initial clinical experience

FIM (2003)

Worldwide experience about 750 patients treated

Transcatheter mitral valve procedures

• Most devices are evolution of surgical devices

• Image-guided delivery vs surgical direct vision

• Therapy guided by function vs lesion

• On line effect or therapy

MONARC (Edwards Lifesciences LLC)

Two-anchor design with chronic reshaping (6weeks) by a foreshortening bridge

EVOLUTION trial (69 pts enrolled)

CARILLON (Cardiac Dimensions Inc)

Acute reshaping device acting in P2P3, repositionable, retrievable

AMADEUS trial(43 pts enrolled )

PTMA (Viacor Inc)

Tri-lumen catheter, reshapable, possibility of multiple long term adjustment

PTOLEMY(24 pts enrolled)

Devices in clinical trial

Device Positioning and Deployment

Device Positioning

Anchor Deployment

Final Confirmation

Percutaneous Mitral Valve RepairProsthetic Ring Coronary Sinus Annuloplasty

Monarch Carillon Viacor

n 69 43 26

Success implantation %

80 70 42

Death % 3 2 0

MI % 3 4 0

Tamponade % 3 4 4

Dissection CS % 0 2 8

Safety at 30 Days

Monarc Carillon Viacor

Pre 6 Mos Pre Post

(TEE no core lab)

n 21

Reduction MR>/=1+

57% 63% NA

ERO Cm² 0.31 0.20 0.33

0.19 NA

Rvol ml 42 27 40 24 NA

Efficacy

Percutaneous Mitral Valve RepairProsthetic Ring Coronary Sinus Annuloplasty

Ptolemy Trial - VIACOR implant is modifying annular geometry

• 3D ECHO annulus tracing end-diastole• Composite SL diameter reduction for 7 implants= 5.6±2.5mm

Improved quality of life / symptoms

Quality of life assessment 6-min-walking test

Coronary Sinus Devices: potential anatomical issues associated with efficacy / safety

• Anatomical relations with the mitral annulus• only posterior• atrialization

• Relation with the Cx artery– Potential risk of AMI

• Risk of lesions

• PREDICTABILITY OF RESULT

Predicting responders in EVOLUTION I and AMADEUS trials

• No differences in CS/GCV location relative to the annulus between patients with or without efficacy

• Neither MR reduction or lack of MR reduction is explained by relative position of vein to annulus

Courtesy of J Harnek, MD

Devices to reduce SL dimension

Ample- PS3 Myocor (Edwards) i-Coapsys

Rogers et al, Circulation 2006;113:2329

Direct annular remodeling

• Mitralign• GDS

• The closest devices to conventional suture annuloplasty

• Initial clinical trials

Other devices• Quantumcor• Percupro –

Cardiacsolutions

Transcatheter MVR

• Larger device• Anchoring• Asymmetric anatomy• Interaction with the aortic

valve• LVOT obstruction• PVL more problematic• At least 10 companies are

working on t-MVR

Evalve MitraClip® Device

Mitraclip

Description of Valve Repair System

Guide

Steerable sleeve

Clip delivery handle

Stabilizer

Atrial Septum

versatility

Functional MR Degenerative MR

Anatomic EligibilityLeaflet mal-coaptation resulting in MR

• Sufficient leaflet tissue for mechanical coaptation

• Non-rheumatic/endocarditic valve morphology

• Protocol anatomic exclusions– Flail gap >10mm – Flail width >15mm– LVIDs > 55mm– Coaptation depth >11mm – Coaptation length < 2mm

EVEREST Preliminary CohortEnrollment with 30 day Core Lab Follow-Up

• Preliminary Cohort analysis per EVEREST II definitions • 30 North American sites• 70% are 1st, 2nd, or 3rd procedure at a site

EVEREST Preliminary CohortPatients with 30 Day Major Adverse Events (N = 107)

Acute Procedural Success*MR < 2+

n=81/96 (84%)

Clip Implantedn=96 (90%)

No APSMR > 2+

n=15/96 (16%)

No ClipImplanted

n=11 (10%)

Clip Procedure AttemptedN = 107 (100%)

MR = 2+n=21/81(26%)

MR = 1-2+n=10/81(12%)

MR = 1+n=50/81(62%)

EVEREST Preliminary CohortEfficacy Results through Discharge

N = 107

* Acute Procedural Success (APS): Defined as placement of one or more Clips resulting in discharge MR severity of 2+ or less, as determined by Core Lab.

70% of proceduresare 1st, 2nd or 3rd at Site

CASE EXAMPLE, Functional MR HSR; October 23rd 2008

• 66 yo, male, 64 Kg, 164 cm, BSA 1.7 m2, BMI 24

• Post-ischemic Cardiomyopathy, CCS II, NYHA III

• Comorbidities

– Infrarenal abdominal aneurysm

– 2006 stenting of right common carotid artery and right internal carotid artery

– 2005 Bone Marrow Tx for AML

• 1994 anterior AMI; 2001 PCI followed by CABG (LIMA—LAD), followed by

multiple PTCA with DES

• 1/2008: AMI for intrastent thrombosis -> POBA on LAD

• 4/2008 Acute Pulmonary Edema CRT with Biventricular Pacing and ICD

Final result (2 hrs after, skin to skin)• Before treatment • After mitraclip

• The patient was transferred from ICU to the general ward in day 1 and discharged home 4 days after the procedure

• At 3 months the MR reduction is stable with mild residual MR, reduction of LV volumes, and the patient is in NYHA class II

HRR FMR:Mitral Regurgitation (ITT)

0%10%20%

30%40%50%60%70%

80%90%

100%

Baseline 30 day 12 month

MitraClip therapy results in sustained MR reduction

Mild-Moderate MR (Grade 1+/2+)

Moderate-Severe or Severe MR (Grade 3+/4+)

n=34, Matched Data

97%

3%

26%18%

82% 74%

52% of patients had MR grade 0 or 1+ at 12 months

HRR FMR: LV Function (ITT)

LV End Diastolic & Systolic Volumes

0

25

50

75

100

125

150

175

200

Volu

me

(ml)

MitraClip therapy results in reverse LV remodeling

n=34, Matched Data

P=0.001

P=0.0002

LVEDV Baseline

LVEDV 12 Months

LVESV Baseline

LVESV 12 Months

192

153103

87

SystolicDiastolic

European adoption of Mitraclip

• Mitraclip obtained CE mark late 2008

• 100 cases performed• Most patients treated are elderly

and high risk prolapse patients and patients with CHF

Mitraclip vs Surgery a preliminary comparison

• Safety is probably superior compared to surgery• Efficacy is probably inferior compared to surgery

– High rate of pts with residual MR– clinical benefit yet to be demonstrated

• Results will be influenced by improvements in:– Learning curve– Indications– imaging– Addition of annuloplasty

The future of endovascular mitral repair

Early treatment

Anatomical reconstruction

Neochordae Implantation

Edwards Mobius

49 di 22

TC orientation and capture

50

Chordal implant dynamic adjustment and post-mortem

51

The future of mitral valve surgery• Minimally invasive and

transcatheter approach• Image guidance and computer aided

decision making• Devices will be

– ethiology-specific– Adjustableoff pump– Implantable with no or minimal

conventional suturing

• Early treatment• Stepwise and combined strategies

Surgeons should prepare for the FUTURE

• Because transcatheter procedures are the natural evolution of surgery

• Because patients deserve an unbiased choice of the best approach

• Because surgeons own most of the core skills needed to run the procedures

Treating valve disease in the future

Tailored approach – the best option for the patient

today