The challenges in transcathetermitral interventions

Alec Vahanian

University Paris VII

Primary MR

(or Organic MR)

Secondary MR

(or Functional MR)

Valve structure Abnormal Normal

Mechanism Primary valve / subvalvular

lesion

Distortion of the valvular

apparatus due to LV

remodelling

Causes Degenerative / Rheumatic /

Endocarditis / Other

Ischaemic heart disease /

Cardiomyopathy

LV dysfunction Consequence Cause

Primary / Secondary MR

« Pathophysiology Triad »Aetiology - cause of the disease

Lesions - results of the disease

Dysfunction - result of the lesions

A. Carpentier

• MitraClip

• The other repair techniques

• Combination therapies

• Valve implantation

• How can we move forward ?

Global MitraClip experience

1. Includes clinical and commercial procedures as of 30/11/2016. Source: Data on file at Abbott Vascular

> 55000 Cases

Primary MR

30% of patients in TRAMI have LVEF < 30%

MitraClip is not a palliative therapy…... when performed properly,

Correct patient selection periprocedural imaging

Procedural performance assessment of intraprocedural outcomes

• Proper performance implies:

Better technology

A « Newcomer »: PASCAL

(Praz ,Lancet ,390,August 2017)

23 high risk patients

96% technical success

………..

Advanced techniques for Degenerative MR

• Implantation of 2 or more clips

• Grasping during asystole (Adenosine infusion)

• Grasping during rapid pacing

• Volume control (ventilation manoeuvres)

• Use of two delivery systems

Zipping technique

(Courtesy H Ince)

Multimodality Imaging for Procedural GuidanceLinked Live 3DTEE and fluoroscopic images

16(Maisano Eur Heart J 2016)

Learning curve

Learning curve :registries on MitraClip

(Boekstegers et al. Clin Res Cardiol 2014;103:85–96)

Anatomic Indications for MitraClip

(Boekstegers et al. Clin Res Cardiol 2014;103:85–96)

Extended Anatomic Indications for MitraClip

“The choice between TAVR and SAVR in the futureis likely to rely less on risk stratification and more on assessment of risks and benefits to individual patients by multidisciplinary heart teams which might lead to improved therapy alternatives for wider subgroups of patients “

Bonow Lancet 2016

Risk evaluation beyond the scores It already happens for TAVI ……………

Main inclusion criteria

Main objective:Show non-inferiority for clinical efficacy of an endovascular treatment strategy with the MitraClip® as compared to a surgical treatment strategy at 12 months

Principal secondary objective:Show superiority for safety over 30 days of an endovascular treatment strategy in the MitraClip® arm in comparison with surgery.

MitraClip after Annuloplasty Failure

(Courtesy of KH Kuck)

Normal heart Secondary MR

Prevalence of Secondary MR in Chronic Heart Failure with Impaired LVEF

N= Recruitment Quant. MR Ischaemic

(%)

MR Severity

Varadarajn 370 HF clinic J.A.+

Q.Dop.

39 15% grade 3/4

14% grade 4/4

Rossi 1256 Hospit. Q.Dop. 61 24% ERO ≥0.20 cm²

or Reg.vol >30 ml

Agricola 198 Hospit. Q.Dop. 0 50% ERO ≥0.20 cm²

Bursi 469 Outpatients J.A. 36 30% grade 3/4

14% grade 4/4

Deja 121 Hospit. Site report 100 18% moderate/severe

(Benjamin MM et al. Curr Cardiol Rep 2014;16:517)

The Spectrum of Secondary MR

Functional MR and LV Remodelling

Is FMR another variable associated

with adverse outcomes

or a risk factor which may potentially be treated ?

When it is Too Late to Treat MR in HF ?

(Beaudoin. Circulation. 2013;128:S248-S252)

MitraClip treated patients

Medically treated patients

(Source: CERGAS Dr Tarricone)

Need for Rehospitalisation

Observational Studies

Survival

What is the impact of MitraClip on Survival ?

(Gianini. Am J Cardiol 2016)Velasquez. Am Heart J 2015)(Swaans. J Am Coll Cardiol Intv 2014)

But these are not RCT’s

Predictors of 1 year mortality after MitraClip

(Puls M et al. Eur Heart J 2016;37:703-12)

When is it too late?

(Schafer ACCESS EU RegistryEuroPCR 2015)

But ….

• MitraClip

• The other repair techniques

• Combination therapies

• Valve implantation

• How can we move forward ?

Percutaneous mitral repair techniques

Mitralign

Cardioband procedure: Major Steps

43

Pre-Procedure Planning

1TransseptalPuncture

2System Insertion

3Implant Deployment

4Implant Size Adjustment

Pre-procedure CT for Planning

CT Analysis provides

Sizing of the Annulus

Expected Fluoroscopy Projections

Transseptal Puncture Location

3D Preview of System Position

1

2

48

9

76

3

5

10

(Maisano. JACC Cardiovascular Interventions 2014;7:1326 -1328)

Edwards Cardioband Mitral Repair System -MR Reduction

Baseline

Final Size

Post

Adjustment

Cardioband : Early Outcomes (N=61)

Effectiveness

• MR ≤ 2+ in 6 month follow up (N=32) 87%

• MR ≤ 2+ in 12 month follow up (N=20) 92%

Procedure

• Implants successfully deployed on annulus 85%

• Average reduction of septo lateral diameter 30%

Safety

• Procedural mortality 0

• 30 Day mortality 3.3%

(Vahanian Euro PCR 2017)

Functional Improvement at 12 Months

304

376

200

225

250

275

300

325

350

375

400

41

18

0

10

20

30

40

Baseline 12 MonthsBaseline 12 Months

N = 24 N = 28

6MWTP<0.01Δ = 72

MLHFQ ScoreP<0.01Δ = -23

Me

ters

Wal

ked

MLH

FQ S

core

IV

III

III

II

II

I

0%

20%

40%

60%

80%

100%

Baseline 12 Months

N = 34

79

% N

YH

A I/II

% o

f p

op

ula

tio

n

NYHA ClassP<0.01

Unfovavorable characteristicsfor surgical annuloplasty in secondary MR

(ESC/EACTS Guidelines 2012)

Percutaneous mitral repair techniques

Mitralign

Mitral valve

Tricuspid

valve

Coronary

sinus

PercutaneousCoronary Sinus Annuloplasty

Coronary sinus annuloplasty is easy to perform but efficacy is limited (n~400)

Percutaneous Repair Techniques with Approval in Europe

Mitralign

The TACT Study

(Seeburger. J Am Coll Cardiol 2014;63:914–9)

Adequate(Type B)

Challenging(Type C)

Ideal(Type A)

Patient Stratification in Padova

Central P2 towards P1/P3 Pericommissural

Eccentric Jet +Central jet component

Good Coapt. Marginal Coapt.

No LV Dilatation LV Dilatation

No Tethering Leaflet Tethering

Freedom From Return of MR By Patient Type

At Risk: Type A 25 24 18

Type B 36 29 15

Type C 23 15 7

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 30 60 90 120 150 180

Type A

Type B

Type C

96%

81%

58%

(Courtesy Dr Gerosa)

The new repair devices

• MitraClip

• The other repair techniques

• Combination therapies

• Valve implantation

• How can we move forward ?

Combining Annuloplasty + MitraClip

(Courtesy of S Van Bardeleben and F Maisano)

Combination of Techniques

Surgical and upcoming transcatheter experienceswill tell us:

➢ Which techniques should be combined ?

➢ How ?

➢ When ?

• MitraClip

• The other repair techniques

• Combination therapies

• Valve implantation

• How can we move forward ?

(Goldstein D et al. N Engl J Med 2015)

We should read carefully surgical literature before extrapolating to THV…

251 pts with severe ischaemic MR (ERO >0.4 cm²)Randomized to valve repair or replacement ± CABGPrimary End-point: LVESVI at 1 yr: 61.1±26.2 ml/m² vs. 65.7±27.4 ml/m² (p=0.18)

• The feasibility of TMV replacement has been recently reported in a

limited number of extreme risk patients (<200) with native mitral

valve disease.

• Over 10 devices are currently in development. Four are in early

feasibility trials in the US including Neovasc Tiara™ , Tendyne Mitral

Valve System , CardiAQ™ TMVI System and Twelve Transcatheter

Mitral Valve Replacement .

• In 2015, > 2 Billion Dollars were invested in TMVR….

Transcatheter Mitral Valve Implantation

Challenges

(Courtesy of F Maisano)

(Blanke P et al. J Am Coll Cardiol Img 2015;8:1191–208)

Multimodality for procedural planningbefore valve implantation

The upcoming devices

(Barbantini ,J Am Coll Cardiol Int 2017 10 1662-75)

Valve in a « Docking Device «

Transcatheter Mitral Replacement vs Repair ?

Replacement

• Simpler

• Versatility (?)

• Reproducibility

• Predictable MR reduction

BUT

• High profile of the devices

• Durability ?

• PV leak ?

• Artifact hemodynamics

Repair

• More natural hemodynamics

• Safe

BUT

• More complex

• Works only in selected patients

• Learning curve

• MR reduction is less predictable

• Durability ?

/

annuloplasty

mitraclipreplacement

• Stand-alone Annuloplasty: earlytreatment FMR

• Stand-alone Mitraclip: FMR with asymmetric tethering (IMR)

• Combined Annuloplasty and MitraClip: DMR and Advanced FMR

• MV Replacement: advanced DMR and Advanced FMR

The complementary role of transcatheter techniques

• MitraClip

• The other repair techniques

• Combination therapies

• Valve implantation

• How can we move forward ??

Isolated MR

(n=887)

No Severe MR

(n=347)

Severe MR

(n=540)

No Symptoms

(n=144)

Symptoms

(n=396)

Intervention

(n=203) 51%

No Intervention(n=193) 49%

Management of Severe MR in real life

(Mirabel et al. Eur Heart J 2007;28:1358-1365)

Background and Purpose

Real-Life Management of Mitral Regurgitations. Lesson from a European Survey.

•

• The Education Committee of the ESC and AXDEV Group performed a

mixed-methods needs assessment including case-based evaluation of the

management of MR in a wide panel of practitioners in Europe.

Conclusions

• Medical therapy is over-used in primary MR and under-used

in secondary MR.

• Indications for interventions are appropriate in most asymptomatic or symptomatic patients with primary MR.

• Indications for interventions are unexpectedly high in

patients with secondary MR and suboptimal medical therapy.

• The use of MitraClip is frequently proposed in high-risk

patients with primary and secondary MR.

• These findings highlight the need for education programs to

improve guideline implementation.

B. Iung 1, V. Delgado 2, S. Murray 3, S. Hayes 3, M. De Bonis 4, R. Rosenhek 5, M. Haude 6, G. Hindricks 7, P. Lazure 3, J. Bax 2, A. Vahanian 1.1 Bichat Hospital AP-HP, Paris, France; 2 Leiden University Medical Center, The Netherlands; 3 AXDEV Group Inc., Brossard, Quebec, Canada; 4 IRCCS San Raffaele Hospital, Milan, Italy;

5 Medical University of Vienna, Austria; 6 Städtische Kliniken Neuss, Germany; 7 Heart Center, Leipzig, Germany.

Methods

Interviews were conducted online from March to May 2016 in 7 countries:

France, Germany, Italy, Spain, Poland, Sweden and United Kingdom

503 practitioners participated to the quantitative phase using case

scenarios:

- 108 Primary care Physicians (PCPs)

- 203 General Cardiologists

- 192 Subspeciality Cardiologists or Cardiac Surgeons

(%)

PMVR

Surgery

(Repair, Replacement,

LVAD,

Transplantation)

Patient Selection for Intervention on the Mitral Valve

Medical Rx

« Futility > Utility »Because of cardiac and extra-

cardiac factors

Need for a team discussion with

HF and EP specialists and transplant

team to evaluate respective

indications of transcatheter therapy

or surgery or LV assist as a

destination therapy or transplant

Variation in THV Utilization/Health Policy and Reimbursement

MitraClip Utilization

• Survey in 301 TAVI centres (Nov 2015-Jan 2016)

• 30% do not perform TMVR

• 1/3 of the centres who do not perform TMVR do not plan to start (because of economic reasons in 69%)

• 74% of TMVR centres perform < 40 procedures /yr and 58% < 10 procedures /year.

• 82% of centres performing > 40 procedures /yr are fromGermany

(Capodanno. EuroIntervention 2017)

Ongoing trials on mitral valve repair

“Valvular Heart Disease II Survey”

• Primary objectives: to analyse existing practices in the management of patients

with severe native heart valve disease or any previous valvular intervention

to compare these practices with existing ESC guidelines

• Secondary objectives: In-hospital and 6-month mortality & morbidity after

enrolment in the study according to the chosen management strategy

• Other Objectives: Use of diagnostic proceduresUse and results of valve interventionsManagement of patients after a valve interventionAssessment of specific subgroups of patients of

interest because of their increasing incidence (Elderly; Interventions in asymptomatic; Heart Failure patients; ...)

➢ 7000 patients included Q1/Q2 2017➢ Final presentation: ESC 2018

Transcatheter mitral and tricuspid valve repair

(Courtesy of F Nielspatch)

Transcatheter tricuspid intervention

Combined Mitral and tricuspid procedures usingMitraclip

• 22 patients (Nickenig )+ 12 patients (Braun)

• The combination is feasible :success rate :100%

• Duration of the procedures is « acceptable » :115mn

• Safety is good :no procedural death

• Moderate improvement in the degree of TR : 55% moderate ,9 % severe

• Moderate improvement in functional condition at 1 month : 30 to 75% are in NYHA Class III

Challenges in mitral regurgitation

• Role of interventions in the treatment of secondary mitral regurgitation

• Efficacy and durability of MitraClip for treatment of high-risk patients and intermediate risk patients with primary mitral regurgitation

• Feasibility and effectiveness of transcatheter mitral annuloplasty/ chordal replacement techniques

• Feasibility and effectiveness of combination of repair techniques

• Feasibility and effectiveness of transcatheter mitral valve replacement

• Respective indications of repair and replacement

• Combination with Tricuspid repair

(Nishimura ,Lancet 2016)

Mitral valve interventions in Germany

(Courtesy of S Van Bardeleben)

A larger number of patients with MR

will be treated

by less invasive surgery or interventional cardiology

Thank You