Dr. Jan Kovac, MUDr., FACC, FESC Cardiology Division, Glenfield Hospital University of Leicester NHS Trust, Leicester UK The Future of Percutaneous Valve.

Dr. Jan Kovac, MUDr., FACC, FESC

Cardiology Division, Glenfield Hospital

University of Leicester NHS Trust, Leicester UK

The Future of Percutaneous Valve The Future of Percutaneous Valve Therapies Therapies

Presenter Disclosure:None

Interventional Cardiology ‘Credo’Interventional Cardiology ‘Credo’

“Anything a cardiac

surgeon can do,

an interventional

cardiologist can do

as well or better

percutaneously”

AH Gershlick, 2003

1. Percutaneous aortic valve replacement (AS,AI) PVT, Corevalve, Pananigua, 3F, Corazone…

2. Percutaneous therapy of mitral regurgitation leaflet fixation coronary sinus techniques transventricular techniques

3. Pulmonary valve replacement (P.Bohnhoffer)

Percutaneous Valve Therapies in 2006Percutaneous Valve Therapies in 2006

The standard for critical AS RX is Surgical The standard for critical AS RX is Surgical AVRAVR

RossHomograft

Mechanical StentlessTissue

Ikonomidis, J. S. et al.; J Thorac Cardiovasc Surg 2003;126:2022-2031

Actuarial and "actual" freedom from valve-related Actuarial and "actual" freedom from valve-related morbidity or mortality after AVR and MVRmorbidity or mortality after AVR and MVR

Mortality in Aortic Valve ReplacementMortality in Aortic Valve Replacementn = 1.984n = 1.984

%mortality%mortality

Burr et al.: Annals of Thor Surg, 1995, 60, S264-269

Aortic valve replacementAortic valve replacement

Refused for SurgeryRefused for SurgeryEuro Heart Survey on Valvular Heart Disease (5001 Euro Heart Survey on Valvular Heart Disease (5001

Patients)Patients)

Iung B. and al, Eur. Heart Journal 2003 : 24, 1231-1243

32 % did not undergo surgery !32 % did not undergo surgery !

Diseases desperate grown, By desperate appliances are reliev’d,Or not at all”(Hamlet Act IV)

Prosthetic Aortic Valve FunctionsProsthetic Aortic Valve Functions

1. Allow normal LVOT function

2. Restore anulus flexibility

3. Conserve sinus motion and sinus flow dynamics

4. Ensure physiological orientation of trileaflet valve

5. Do better than current valves

First Clinical Percutaneous Aortic ValveFirst Clinical Percutaneous Aortic ValveAlain Cribier - 16/4/02Alain Cribier - 16/4/02

• Equine pericardial valveEquine pericardial valve sewn on 23mm BES;sewn on 23mm BES;

• PVT acquired by EdwardsPVT acquired by Edwards 1/041/04

Percutaneous Aortic Valve ReplacementPercutaneous Aortic Valve ReplacementDesigns/TrialsDesigns/Trials

1. PVT-Edwards-Cribier

2. COREVALVE

3. Panaguia

4. 3F

5. SORIN

6. CORAZONE

7. SADRA Medical

8. ValveXchange

9. Direct Flow

• Tricuspid valve, equine pericardium

• Stainless steel stent frame

• 22mm Numed ballon catheter

• Original crimper device

• Compatible with 24-Fr sheath

Cribier Edwards AV ImplantCribier Edwards AV Implant

Patients >70 years of age Aortic valve area < 0.7 cm²Aortic annulus diameter: 19-23 mmDyspnoea NYHA class IV

At extremely high risk for open heart surgery and formally declined by two cardiac surgeons for surgical valve replacement

Cribier PVT Trials Inclusion CriteriaCribier PVT Trials Inclusion Criteria

Alan Cribier-Edwards PVT Rouen Experience

Alan Cribier-Edwards PVT RECAST Experience

CoreValve’s Self-Expanding CoreValve’s Self-Expanding ProsthesisProsthesis

A pericardium porcine tissue valveA pericardium porcine tissue valve

Fixed to the frame in a surgical Fixed to the frame in a surgical manner with PTFE suturesmanner with PTFE sutures

HIGHER PARTHIGHER PART : increases : increases quality of fixation and axes the quality of fixation and axes the systemsystem

MIDDLE PART :MIDDLE PART : is is constrained to avoid coronaries constrained to avoid coronaries (no rotational positioning) and (no rotational positioning) and carries the valve carries the valve

LOWER PART:LOWER PART: High radial High radial force of the frame pushes aside force of the frame pushes aside the calcified leaflets and avoids the calcified leaflets and avoids recoil andrecoil and para-valvular leaks para-valvular leaks

CoreValve StudyCoreValve StudyResultsResults

0

10

20

30

40

50

60

70

80

90

100Clinical succesClinical succes

In hospitalIn hospital deathdeath

ConvertionConvertion to Surgeryto Surgery

Phase 1Phase 1 Phase 2Phase 2

Phase 1&2: Phase 1&2: July 2004-Dec 2005 (28 patientsJuly 2004-Dec 2005 (28 patients))

Phase 2 Clinical StudyPhase 2 Clinical Study

7 European Investigative CentersPatient type: High-risk/non-surgical candidates Euroscore higher than 20Trial initiated: December 2005Primary endpoints:Acute safety and efficacyLong-term outcomesLeicester 2006

3F Transapical Antegrade Aortic Valve 3F Transapical Antegrade Aortic Valve ImplantImplant

Thin Film Nanotechnology Thin Film Nanotechnology eeNitinol Nitinol MembranePercValve™MembranePercValve™

Aortic Valve CalcificationAortic Valve Calcification

CORAZON percutaneous aortic valve system

flexible multilumen central catheter (navigable)

soft tip for placement into left ventricle and a balloon for occluding the LV outflow tractbelow the aortic valve

expandable central lumen with temporary aortic valve enabling beating heart aortic valve treatment

aortic isolation of treatment area using a compliant bell designed to conform to the shape of aortic valve cusps

balanced solution inflow and aspiration

CORAZON percutaneous aortic valve system

Percutaneous Mitral Valve Therapies

Percutaneous Transvenous Mitral Reshaping/Annuloplasty through the Coronary Sinus Straightening, Stent basedReshaping/Annuloplasty through the VentriclePercutaneous/Transatrial edge to edge(E2E or Alfieri) repairPlicating Left Atrial/Ventricular Tissue anchors

Percutaneous Mitral Repair Technologies

Percutaneous Mitral E2E RepairPercutaneous Mitral E2E Repair

EVEREST IEndovascular Valve Edge to edge REpair pair STudy

Freedom from surgery to date 35/47 = 74%•No clip deployed (n=5) for insufficient MR reduction•Operations: 4 repairs, 1 intended replacement after clip deployment (n=7)•Reasons:•1 device malfunction•4 partial detachments•Timing (days): 1, 3, 36, 40, 50, 110, 133•Surgery:•5 repairs, 2 replacement (1 intended; 1 failed repair)•Concomitant ASD repair (6), MAZE (1), CABG (1)•2 progressive MR

EVEREST IEndovascular Valve Edge to edge REpair pair STudy

EVEREST II Study DesignEVEREST II Study DesignProspective, randomized, multicenter studyControl: surgical mitral valve repair/ replacementPatients randomized 2:137 centers in US and Canada

Primary Effectiveness EndpointFreedom from surgery, death, and moderate to severe (3+) or severe (4+) mitral regurgitation at 12 months.

Primary Safety EndpointFreedom from MAE at one month

Placement of a percutaneous stitch inthe free edge(s) of the mitral leaflets,

Edwards LilfeSciences

Step 1

Step 3

Step 2

Mitral Annuloplasty TherapiesMitral Annuloplasty Therapies

Edwards PTMA Viking

Stent based anchors connected by a tetherAnchors at the CS ostium and AIVTime delay contracting tetherCinches the mitral annulus, increases mitral leaflet coaptation

CarillonTM, Cardiac Dimensions

ViacorViacor

Straightens the coronarysinus Anteriorly displaces P2 Begins with a “diagnostic”OTW procedure Implant placed OTWwithin a 7 Fr sheath Implant tethered to a hubin the infraclavicularfossa

Quantum Cor RFQuantum Cor RF

Tip of probe is smaller to conform Tip of probe is smaller to conform to to annulus shapeannulus shape8 electrodes (~1.5x2mm)8 electrodes (~1.5x2mm)Delivery of RF energy to Delivery of RF energy to electrodes is computer-electrodes is computer-controlled by maximum controlled by maximum temperatures sensed by adjacent temperatures sensed by adjacent thermocouplesthermocouples

Combined percutaneous MV Treatment

… a bow tie always need a collar

Is Percutaneous Mitral Replacement Is Percutaneous Mitral Replacement Possible?Possible?

For Cardiac Surgeons..

"In times of change, the learners inherit the Earth, while the learned find themselves beautifully equipped to deal with a world that no longer exists."

Eric Hoffer

Not quite….for a while

UK/ Leicester PerspectiveUK/ Leicester Perspective

1. Aortic valve COREVALVE 18 F Trial (2006)

2. EVEREST III Trial (pending EVEREST II, end 2006)

3. Compassionate Use ??

Very early daysVery early days

120-130 aortic and mitral implants worldwide

Does not stand up to surgical therapy at the moment

New skills needed for interventionist-TOE/ICE

Old skills refreshed (transseptal, PTMV, CS)

Teamwork (blurring boundaries interventionist/ surgeon)

Will it ultimately work?

S.Oesterle….the Beauty of Stardom

No R+D but r+D

no Venture Capitalist able to fund >1000 $/patient clinical Trial, quality assurance, manufacturing, regulatory issues, distribution

“Make a better mousetrap and world will beat path to your door ”Waldo Emerson

I don’t skate where the puck is.

I skate, to where the puck is going.

Wayne GretzkyNHL All Star 81-99