Update on Update on TranscatheterTranscatheter

Aortic Valve ReplacementAortic Valve Replacement

VinodVinod H. H. ThouraniThourani, MD, MD

Associate Professor of Cardiothoracic SurgeryAssociate Professor of Cardiothoracic Surgery

Associate Director, Structural Heart CenterAssociate Director, Structural Heart Center

Associate Director, CTS Clinical Research UnitAssociate Director, CTS Clinical Research Unit

Associate Director, CT Surgery Residency ProgramAssociate Director, CT Surgery Residency Program

Emory University School of MedicineEmory University School of Medicine

American Association for Thoracic SurgeryAmerican Association for Thoracic Surgery

April 28, 2012April 28, 2012EMORY

• During the past 12 months, I have received research grants,

advisory boards, consultation fees/honoraria, and/or travel

expenses from:

– Edwards LifeSciences: Emory Co-PI, National Steering and Publications

Committee

– St Jude Medical

EMORY

Disclosures

– St Jude Medical

– DirectFlow

– Sorin Medical

– Co-Founder and IP (via Emory University): Apica Cardiovascular

• Some of the products are investigational and/or not FDA-

approved or available for sale in the US (Corevalve, Sapien non-

TF, DirectFlow, Portico, Apica). Some products have only been

tested in non-humans

Transcatheter Aortic Devices

• Current-

– Edwards Sapien

– Medtronic Corevalve

• Future-

– St. Jude Portico

– Sadra

– Direct Flow

– Symetis

– Medtronic Engager (Ventor)

– JenaValve

EMORY

TAVR: Transfemoral (TF) and

Transapical (TA)

TransfemoralTransfemoral TransapicalTransapical

4885051400

59390 61000

50000

60000

70000

TAVI SAVR

# of procedures

Number of T-AVR and S-AVR in Europe

6093510

900012000

48850

0

10000

20000

30000

40000

50000

1 2 3 42007 2008 2009 2010

# of procedures

EMORYEMORY

Tests to Assist in Decision MakingTests to Assist in Decision Making

n TTE/TEE (3D echo beneficial in some)

n Determine accurate annulus sizing

nn Cardiac Catheterization within past 6 monthsCardiac Catheterization within past 6 months

nn Iliac vessel angiogramIliac vessel angiogram

CT SCANCT SCANnn CT SCANCT SCAN

nn Chest/Chest/abdabd/pelvis/through the mid thigh with 1.5 mm /pelvis/through the mid thigh with 1.5 mm

cuts and 3D cuts and 3D reconstructionreconstruction

nn Without contrast in those with Without contrast in those with creatininecreatinine > 1.5> 1.5

nn Evaluate the ascending aorta for calcificationEvaluate the ascending aorta for calcification

nn Evaluate femoral and iliac arteries for Evaluate femoral and iliac arteries for

calcificationcalcification

nn Pulmonary function testsPulmonary function tests

nn Carotid duplexCarotid duplex

• Annular diameter: 18-21mm

• Use 23mm Valve

EMORYEMORY

TTE/TEE MeasurementsTTE/TEE Measurements

• Annular diameter: >21-

24.5mm

•Use 26mm Valve

EMORY

CT Imaging for TAVR

EMORYEMORY

Potential Transapical PatientPotential Transapical Patient

EMORY

CT Imaging for TAVR

EMORYEMORY

Our First Patient at Emory: 2007Our First Patient at Emory: 2007

EMORYEMORY

The Patient Population with AS

74 yo primary AVR 90 yo redo AVR

• Background

• Preoperative Assessment

• Intraoperative Technical Aspects

• Postoperative Complications

EMORY

Outline

• Postoperative Complications

• Outcomes

Innovative Catheter Tip Design

Sapien XT/Novaflex

RF3New shorter

softer tip

New balloon

Processing for

Smooth transition

To valve NF - Original

RF3

NF - Original

NF - Improved

TAVI Approaches

Transfemoral

+++• Less invasive

• Percutaneous

• Local anesthesia

- - -• Delivery more difficult

than TA

• More stroke?

• Delivery profile matters

• Not for all patients

Access/Closure

Preclosure with 2-3 Proglides

EMORY

Retroperitoneal Iliac Exposure

EMORY

Transapical AVR

EMORY

Transapical AVR

EMORY

Transapical AVR

CoreValve ReValving®

System

• Self Expandable•

Available in Europe: > 3000 cases

Medtronic CoreValve

• Self Expandable• Nitinol Frame• Porcine Pericardium• Size: 26 and 29 mm• CE Mark in Europe• 18F sheath• NOT retrievable• Porcine

CoreValve Bioprosthesis: Two Sizes

“Small” “Large”

40 mm 43 mmOutflow

55 mm 53 mmHeight

26 mm 29 mmInflow

24 mm22 mmConstrained

20 mm to

23 mm

23 mm to 27

mm

Accomodates

Annulus of:

CoreValve Delivery Step 1

CoreValve Delivery Step 2

CoreValve Delivery Step 3

CoreValve Delivery Completed

Procedural Success. Corevalve.Percent of Patients (%)

83.1%

96.8% 98.1% 97.0% 98.0% 98.7% 99.0% 98.1%

40%

60%

80%

100%

*

Procedure Success is not defined consistently across all studies.* Technical Success is reported here.

1. Medtronic Data on File. COR 2006-02: 18 Fr Safety & Efficacy Study Re-Analysis, August 14, 2009. 2. Meredith IT. A Snapshot from the Ongoing Australia-New Zealand Medtronic CoreValve® Registry. Transcatheter Cardiovascular Therapeutics 2009,

September 21-25, 2009. San Francisco, CA.3. Avanzas P, Munoz-Garcia AJ, Segura J, et al. Percutaneous implantation of the CoreValve® self-expanding aortic valve prosthesis in patients with severe

aortic stenosis: early experience in Spain. Rev Esp Cardiol. 2010;63:141-148.4. Eltchaninoff. French Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France.5. Bosmans. Belgian Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France.6. Zahn. German Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France.7. Ludman. UK Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France.

8. Petronio. Italian Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France.

N = 126 N = 62 N = 108 N = 78 N = 141 N = 588 N = 460 N = 772

Percent of Patients (%)

0%

20%

18 Fr S&E1 ANZ2 Spain3 French4 Belgian5 Germany6 UK7 Italian8

CoreValve Pacemaker Rates

(high, but vary by center)

35.2%

26.9%

42.5%

26%

31.3%

40%

30%

40%

50%

60%

Percent of Patients (%)

Weighted Average 28.5%

35.2%

26.9%

42.5%

26%

31.3%

40%

30%

40%

50%

60%

Percent of Patients (%)

Weighted Average 28.5%

35.2%

26.9%

42.5%

26%

31.3%

40%

30%

40%

50%

60%

Percent of Patients (%)

Weighted Average 28.5%

26.9%23%

26%

18.5%

0%

10%

20%

30%

18 Fr S&E1

N = 125 ANZ2

N = 118 Spain3

N = 108French4

N = 66Belgian5

N = 119German6

N = 588UK7

N = 460Italian8

N = 772

Percent of Patients (%)

26.9%23%

26%

18.5%

0%

10%

20%

30%

18 Fr S&E1

N = 125 ANZ2

N = 118 Spain3

N = 108French4

N = 66Belgian5

N = 119German6

N = 588UK7

N = 460Italian8

N = 772

Percent of Patients (%)

26.9%23%

26%

18.5%

0%

10%

20%

30%

18 Fr S&E1

N = 125 ANZ2

N = 118 Spain3

N = 108French4

N = 66Belgian5

N = 119German6

N = 588UK7

N = 460Italian8

N = 772

Percent of Patients (%)

CoreValve US Pivotal Trial Design

Medtronic CoreValve Medtronic CoreValve U.S. Pivotal TrialU.S. Pivotal Trial

“Extreme Risk”“Extreme Risk”Patient GroupPatient Group

“High Risk”“High Risk”Patient GroupPatient Group

40 Sites in the US40 Sites in the US

National CoNational Co--PIs:PIs:

Jeff Jeff PopmaPopma, MD, MD

David Adams, MDDavid Adams, MD

Patient GroupPatient Group

IliofemoralIliofemoral access?access?

CoreValveCoreValveObservationalObservational

CoreValveCoreValveSingle ArmSingle Arm

Up to 100Up to 100

Patient GroupPatient Group

Randomization 1:1Randomization 1:1

CoreValveCoreValve SAVRSAVR

395*395* 395395

790790

Yes 487Yes 487

NoNo

*Includes iliofemoral and alternative access patientsNote: 3 roll-in patients per study site equates to a maximum of 1,497 patients enrolled

Alternative AccessAlternative Access

EMORY

Complications

• Severe transvalvular or paravalvular AR

• Major bleeding

• Aortic rupture or dissection

• Coronary artery obstruction• Coronary artery obstruction

• Severe MR

• Arrhythmias/Bradycardia

• Pericardial effusion

• VSD

• Valve misdeployment

• Successful CoreValveimplantation

• Collapsed on ICU on 1st POP day

H.S., 83 y, male

EMORY

Aortic Dissection

POP day

• Resuscitationunsuccessful

• Autopsy performed

• Aortic wall perforation

Courtesy of R. Langer, et al, Munich

EMORYEMORY

Ventricular DeploymentVentricular Deployment

EMORYEMORY

Valve Positioning SoftwareValve Positioning Software

EMORYEMORY

Left Main OcclusionLeft Main Occlusion

EMORYEMORY

LV BleedingLV Bleeding

Transapical Closure Devices

“In Development”

• Apica

• Entourage CardioClose• Entourage CardioClose

• MID Permaseal

• Novogate

• SpirX Closure

• Cardiapex

EMORYEMORY

Iliac RuptureIliac Rupture

EMORYEMORY

All Cause All Cause Mortality: Mortality:

TF TF vsvs Med Med TxTx (PARTNER 1B)(PARTNER 1B)Freedom from Death (%) Standard Rx

TAVI

69.3%

Months

Freedom from Death (%)

∆ at 1 yr = 20.0%

NNT = 5.0 pts

Numbers at RiskNumbers at Risk

TAVITAVI 179179 138138 122122 6767 2626

Standard RxStandard Rx 179179 121121 8383 4141 1212

49.3%

EMORYEMORYNeuro events at 30D & 1Y: PARTNER 1B

Major Stroke All Stroke or TIA

P = 0.06P = 0.18

6.7

10.6

1.74.5

30 Days 1 Year

P = 0.03P = 0.04

TAVR (n=179) Standard Rx (n=179)

per cent

EMORYEMORYMajor Vascular Complications: PARTNER 1B

16.8%17.4%

30 Daysp < 0.001

1 YearP<0.001

1.1%2.2%

TAVR

n=30

Std Tx

n=2

TAVR

n=31

Std Tx

n=4

EMORYEMORY

PARTNER 1A: 2 YEARPARTNER 1A: 2 YEAR

Kodali, NEJM, 2012

EMORYEMORY

PARTNER 1A: 2 YEARPARTNER 1A: 2 YEAR

Kodali, NEJM, 2012

EMORYEMORY

PARTNER 1A: 2 YEARPARTNER 1A: 2 YEAR

Kodali, NEJM, 2012

DW-MRI after TAVI

Valve New

lesions

Strokes

lesions

Ghanem CoreValve 73% 10%

Knipp SAPIEN 58% 4%

Kahlert Both 84% 0%

Astarci Both 91% 0%

Rodes, Webb SAPIEN 68% 3.3%

Embrella• Deflector• Radial access• Canadian/German feasibility study

SHEF• Deflector• Femoral access• Femoral access• German feasibility

study

Claret• Dual carotid filter• German feasibility study

EMORYEMORY

PV Aortic Regurgitation: PARTNER 1APV Aortic Regurgitation: PARTNER 1A

P < 0.001 P < 0.001 P < 0.001

Patients %

60

80

100

1 Year6 Months30 Days

Patients %

None Trace Mild Moderate Severe

0

20

40

60

TAVR AVR TAVR AVR TAVR AVR

EMORYEMORY

PARTNER 1A: 2 YEARPARTNER 1A: 2 YEAR

Kodali, NEJM, 2012

EMORYEMORY

Additional Experience ThroughAdditional Experience Through

NonNon--Randomized Continued AccessRandomized Continued Access

600

700

800

900

1000Continued Access PeriodRandomized Clinical Trial

PMA-TA = 104

AVR = 103NRCA-TA = 843

0

100

200

300

400

500

600

May

2007

Sep

2009

PMA

# of

Patients

Enrolled

Sep 21, 2011

PMA Data Lock

April 2008

Dewey, STS, 2012

30 Days 1 Year

OutcomeOutcomePMAPMA--TATA

(n (n = = 104)104)

AVRAVR

(n (n = = 92)92)

NRCANRCA--TATA

(n (n = = 822)822)

PMAPMA--TATA

(n (n = = 104)104)

AVRAVR

(n (n = = 92)92)

NRCANRCA--TATA

(n = 822)(n = 822)

Clinical OutcomesClinical Outcomes

at 30 Days and 1 Year (AT)at 30 Days and 1 Year (AT)

All percents are KM

estimates.

AllAll--Cause Mortality Cause Mortality –– pts. (%)pts. (%) 9 (8.7%) 7 (7.6%) 66 (8.2%) 30 (29.1%) 23 (25.3%) 148 (23.6%)

Stroke – pts. (%) 7 (7.0%) 5 (5.5%) 16 (2.0%) 10 (10.8%) 6 (7.0%) 22 (3.7%)

Death or Stroke – pts. (%) 16 (15.4%) 11 (12.0%) 80 (9.9%) 36 (34.8%) 27 (29.7%) 163 (25.7%)

Note: p-values between NRCA-TA vs PMA-TA and NRCA-TA vs AVR are all not significant.

Dewey, STS, 2012

20%

30%

40%

Cause M

ortality

AVR

PMA-TA

NRCA-TA

AllAll--Cause Mortality (AT)Cause Mortality (AT)

23.6%25.3%

29.1%

0%

10%

0 3 6 9 12

All-Cause M

ortality

Months Post Procedure

AVRAVR 9292 7676 7171 7070 6767

PMAPMA--TATA 104104 8787 8282 7676 7373

NRCANRCA--TATA 822822 571571 370370 297297 126126

No. at Risk

∆ at 1 yr:

AVR - PMA-TA = –3.8%

AVR - NRCA-TA = +1.7%

PMA-TA - NRCA-TA = +5.5%

20%

30%

40%

Stroke

AVR

PMA-TA

NRCA-TA

Stroke (AT)Stroke (AT)

∆ at 1 yr:

AVR - PMA-TA = –3.8%

AVR - NRCA-TA = +3.3%

PMA-TA - NRCA-TA = +7.1%

0%

10%

0 3 6 9 12

Stroke

Months Post Procedure

AVRAVR 9292 7272 6767 6666 6363

PMAPMA--TATA 104104 8181 7777 7070 6767

NRCANRCA--TATA 822822 563563 365365 291291 123123

No. at Risk

3.7.%

7.0%

10.8.%

ConclusionsConclusions

• Additional experience in The PARTNER Trial NRCA-TA (n=843)

further supports transapical as a safe and effective treatment option

for high risk patients not eligible for transfemoral access:

– Mortality: – Mortality:

• PMA-TA 29.1%,

• AVR 25.3%

• NRCA-TA 23.6%

– Stroke:

• PMA-TA 10.8%

• AVR 7.0%

• NRCA-TA 3.7%

• Self expanding stent designed to be:

– Fully re-sheathable

– Repositionable* (antegrade and

retrograde) at the implant site

– Retrieveable

– TF and TA

St. Jude Medical Portico™

Transcatheter Valve Program

– TF and TA

• Bovine and porcine pericardial valve

with Linx™ anti-calcification technology

• Cuff tissue and stent geometry designed

to minimize PV leak

• Leaflet/cuff position within the frame, and

stent length, designed for minimal

protrusion into LVOT, potentially

minimizing conduction system and mitral

valve apparatus interference

Portico First-in-Human

Deployment: Vancouver

First-in-Human

Deployment

Positioning

Wires

Direct Flow Medical: Valve Concept

Aortic Ring

Check ValvesVentricular Ring

Investigational device not for sale in or outside the United States

FIM 18F DFM Valve: Final angiogram FIM 18F DFM Valve: Final angiogram (after (after

polymer exchange)polymer exchange)

Investigational device not for sale in or outside the United States

Access For TAVI

Subclavian– Minimally Diseased Vessel

– Less Invasive Than TA

– Local Anesthesia Possible

– Crosses Arch But Less – Crosses Arch But Less

Traumatic ?

– Direct Access To Valve

Direct Aortic– Most Direct Access

– Less Invasive Than TA

– Surgeons More Comfortable

With Access

EMORYEMORY

The Future: ValveThe Future: Valve--inin--Valve Valve

DeploymentDeployment

EMORYEMORY

The Future: The Future: TAoTAo

DeploymentDeployment

Two T-AVRs in One Patient..

TransTrans--apicalapical

AVRAVR

Courtesy of Dr. John WebbCourtesy of Dr. John Webb

TransTrans--apicalapical

MVRMVR

(valve(valve--inin--valve)valve)

SapienSapien

25th percentile

=STS 3.8

10th percentile

EMORYEMORY

The Creep for TAVRThe Creep for TAVR

• PARTNER II

• SUR TAVI10th percentile

= STS 8%• SUR TAVI

Symptomatic Severe Aortic Symptomatic Severe Aortic StenosisStenosisSymptomatic Severe Aortic Symptomatic Severe Aortic StenosisStenosis

ASSESSMENT: OperabilityASSESSMENT: Operability

ASSESSMENT:

Transfemoral Access

ASSESSMENT:

Transfemoral Access

ASSESSMENT:

Transfemoral Access

ASSESSMENT:

Transfemoral Access

Total = 2000 patientsTotal = 2000 patients

2 Parallel Trials:

Individually Powered

2 Parallel Trials:

Individually PoweredOperableOperableOperableOperablen= 2000n= 2000 InoperableInoperableInoperableInoperable n=500n=500

The PARTNER II Study DesignThe PARTNER II Study Design

TransapicalTransapicalTransapicalTransapical

Transfemoral AccessTransfemoral Access

tAVRtAVR

TransTrans

femoral

tAVRtAVR

TransTrans

femoral

Surgical Surgical

AVRAVR

Surgical Surgical

AVRAVR

TransfemoralTransfemoralTransfemoralTransfemoral

Primary Endpoint: All Cause Mortality, Major Primary Endpoint: All Cause Mortality, Major

StrokeStroke

Primary Endpoint: All Cause Mortality, Major Primary Endpoint: All Cause Mortality, Major

StrokeStroke

tAVRtAVR

TransTrans

apicalapical

tAVRtAVR

TransTrans

apicalapical

Surgical Surgical

AVRAVR

Surgical Surgical

AVRAVR

1:1 Randomization1:1 Randomization1:1 Randomization1:1 Randomization

VSVStAVR tAVR

SAPIEN XTSAPIEN XT

tAVR tAVR

SAPIEN XTSAPIEN XT

Transfemoral AccessTransfemoral Access

Nested Registry

Transapical

Nested Registry

Transapical

tAVR tAVR

SAPIENSAPIEN

tAVR tAVR

SAPIENSAPIEN

Primary Endpoint: All Cause Primary Endpoint: All Cause Mortality, Major Mortality, Major

Stroke and Stroke and RehospitalizationRehospitalization

Primary Endpoint: All Cause Primary Endpoint: All Cause Mortality, Major Mortality, Major

Stroke and Stroke and RehospitalizationRehospitalization

1:1 Randomization1:1 Randomization

VS

• Qualified multi-disciplinary team

– Surgeon

• Open surgical AVR experience (especially in high risk AVR patients)

• Catheter-based experience

– Interventional cardiologist (skilled in structural heart disease)

– Experienced surgical OR team

EMORY

Integral Components

– Experienced surgical OR team

– Experienced transcatheter OR team

– Vascular surgeon accessible for aorto-iliac disease complications

– Perfusionist and CPB circuitry present in the OR

• Fixed-imagining fluoroscopic capability

• Minimum requirements for sterile OR environment

• Discuss and prepare for all catastrophic events with specific roles

for each member of the team.

EMORYConclusionsConclusions

nn TAVR is here!!! ARE WE READY????TAVR is here!!! ARE WE READY????

nn Results are superior to medical Results are superior to medical txtx and comparable to and comparable to

open surgeryopen surgery

nn The patient population who does not benefit from The patient population who does not benefit from nn The patient population who does not benefit from The patient population who does not benefit from

TAVR needs to be further refinedTAVR needs to be further refined

nn Techniques to prevent embolization (via imaging), Techniques to prevent embolization (via imaging),

vascular complications (via sizing), vascular complications (via sizing), paravalvularparavalvular

leaks (via imaging), and stroke (via catching of leaks (via imaging), and stroke (via catching of

emboli) need to be further refinedemboli) need to be further refined

nn Success Success can only be achieved with a collaborative and can only be achieved with a collaborative and

dedicated teamdedicated team

EMORYEMORY

The Team: Cardiologist and Cardiac The Team: Cardiologist and Cardiac

SurgeonSurgeon

Thanks

Vinod H. Thourani, MD

vthoura@emory.eduvthoura@emory.edu

EMORY

CoreValve US Pivotal Trial Design

Medtronic CoreValve Medtronic CoreValve U.S. Pivotal TrialU.S. Pivotal Trial

“Extreme Risk”“Extreme Risk”Patient GroupPatient Group

“High Risk”“High Risk”Patient GroupPatient Group

40 Sites in the US40 Sites in the US

National CoNational Co--PIs:PIs:

Jeff Jeff PopmaPopma, MD, MD

David Adams, MDDavid Adams, MD

Patient GroupPatient Group

IliofemoralIliofemoral access?access?

CoreValveCoreValveObservationalObservational

CoreValveCoreValveSingle ArmSingle Arm

Up to 100Up to 100

Patient GroupPatient Group

Randomization 1:1Randomization 1:1

CoreValveCoreValve SAVRSAVR

395*395* 395395

790790

Yes 487Yes 487

NoNo

*Includes iliofemoral and alternative access patientsNote: 3 roll-in patients per study site equates to a maximum of 1,497 patients enrolled

Alternative AccessAlternative Access

EMORY

Impact of TAVR at Emory

AVR

TAVR

AVR