Siegburg

Transcatheter Aortic Valve Replacement

Update

Eberhard Grube MDHELIOS Klinikum Siegburg, Germany

Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil Stanford University, Palo Alto, California, USA

Siegburg

Standard therapy for critical AS is/was

Surgical Aortic Valve Replacement

30day Mortality 3%

Mechanical Tissue Stentless

Options for sAVR:

70’s - Today

Outcome of AVR in High Risk Patients Outcome of AVR in High Risk Patients with severe ASwith severe AS

StudyStudy # pts# pts High risk High risk featuresfeatures

In-Hosp In-Hosp mortalitymortality

Late Late mortalitymortality

Brogan (1993)Brogan (1993) 1818 LVEF + LVEF + gradient gradient 33%33% nana

Powell (2000)Powell (2000) 5555 LVEF ≤ 30% LVEF ≤ 30% 18%18% nana

Jegaden (1986)Jegaden (1986) 7171 LVEF ≤ 40%LVEF ≤ 40% 10%10% 5yr – 28%5yr – 28%

Connolly (2000)Connolly (2000) 5252 LVEF ≤ 35% + LVEF ≤ 35% + gradient gradient 21%21% 3yr – 29%3yr – 29%

Pereira (2002)Pereira (2002) 6868 LVEF ≤ 35% + LVEF ≤ 35% + gradient gradient 8%8% 1yr – 18%1yr – 18%

Sundt (2000)Sundt (2000) 133133 ≥ ≥ 80 yo80 yo 11%11% 1yr – 20%1yr – 20%

Mortasawi (2000)Mortasawi (2000) 105105 ≥ ≥ 80 yo80 yo 9%9% 1yr – 10%1yr – 10%

Kohl (2001)Kohl (2001) 8383 ≥ ≥ 80 yo80 yo 13%13% 1yr – 14%1yr – 14%

Bloomstein (2001)Bloomstein (2001) 180180 ≥ ≥ 70 yo70 yo 17%17% nana

Bernard (1992)Bernard (1992) 2323 > 75 yo> 75 yo 9%9% 17%17%

High RiskHigh Risk AVR Patients AVR Patientswith Poor Outcomeswith Poor Outcomes

• Radiation chest wall/heart diseaseRadiation chest wall/heart disease• Octogenarians with multiple co-morbiditiesOctogenarians with multiple co-morbidities• Cirrhosis with portal hypertensionCirrhosis with portal hypertension• Porcelain aortaPorcelain aorta• COPDCOPD• Degenerative neurocognitive dysfunction Degenerative neurocognitive dysfunction • Previous Cardiac SurgeryPrevious Cardiac Surgery• ESRD (esp. on dialysis)ESRD (esp. on dialysis)

Surgery Percutaneous

Edwards~4,000 patients

CoreValve~4,000 patients

Current Generation DevicesCurrent Generation Devices

Transcatheter AVRTranscatheter AVR

Siegburg

Transcatheter AVRClinical Data Sources

PARTNER FDA*(US/OUS, TF/TA 456 pts)

PARTNER FDA*(US/OUS, TF/TA 456 pts) PIVOTAL RCTPIVOTAL RCT

* still enrolling patients* still enrolling patients

CE-APPROVALCE-APPROVAL18 Fr Transfemoral OUS Experience (1,243 pts)*

18 Fr Transfemoral OUS Experience (1,243 pts)*

PARTNER EU (OUS, TF/TA 125 pts)SOURCE (OUS, TF/TA, 598 pts)*PARTNER EU (OUS, TF/TA 125 pts)SOURCE (OUS, TF/TA, 598 pts)*

FEASIBILITYFEASIBILITY21 and 18 Fr Transfemoral OUS Experience (177 pts)21 and 18 Fr Transfemoral OUS Experience (177 pts)

REVIVE (OUS, TF, 106 pts) TRAVERCE (OUS, TA, 172 pts) REVIVAL (US, TF/TA, 95 pts)

REVIVE (OUS, TF, 106 pts) TRAVERCE (OUS, TA, 172 pts) REVIVAL (US, TF/TA, 95 pts)

Transseptal Experience (RECAST, I-REVIVE; 36 pts)

Transseptal Experience (RECAST, I-REVIVE; 36 pts) FIRST-in-MANFIRST-in-MAN 25 Fr Transfemoral

Experience (14 pts)25 Fr Transfemoral Experience (14 pts)

EdwardsEdwards CoreValveCoreValve

PARVISIn Planning with FDA

PARVISIn Planning with FDA

SiegburgF.I.M. Balloon Aortic Valvuloplasty

1985Concept of« stented valve », to rule out post-BAV valvular restenosis

1987

1994

Post-mortem studies of intra-valvular stentingSketches of stented valve

« Percutaneous Valve Technology » (prototypes)

1999 First animal implantation (sheep)2000

Large series of animal implantation

2000-02 F.I.M. PHV implantation2002

Feasibility Studies (antegrade)2002-03

Edwards LifesciencesTechnological improvements

2004

International TF and TA Feasibility Studies2005-07

CE mark commercialization2007

20 y

ears

THV developmentA long road:

20 Yearsfrom conceptto real world

June, 2009 – ~4,000

implanted worldwide

Siegburg

TAVI – CoreValveNumber of Countries & Centers

417

266

59

151

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Centers

Siegburg

TAVI – CoreValveNumber of Cases

10

763

3529

0

500

1000

1500

2000

2500

3000

3500

40002

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Siegburg

All SAPIEN® Studies, TransfemoralContinued improvement in implantation success

REVIVE REVIVALPARTNER EU

TFn=61

SOURCETF

Mean Euroscore (%) 28.8 ± 13.4 34.1 ± 18.0 25.7 ± 11.5 25.7

Procedure time (min) 158 ±-138.5 138.0 ± 63.6 140.9 ± 62 NAV

Fluoroscopy time (min) 30.56 ±7.6 NAV 28.1 ± 17 NAV

Device success composite incl AR <2+ 70.0% 88.9% 91.0 92.5

Freedom from death at 30D 85.9% 92.7% 92% 93.7

Freedom from stroke at 30D 96.7% 90.8% 97% 97.6

Freedom from  MI at 30D 90.9 83.6% 98.4% 99.8

Perforation or damage to vessels, myocardium, valvular structures

15.0% 9.1% 19.7% 17.9

Freedom from reoperation at 30D 99.0% 98.1% 98.4% NAV

Freedom from Structural valve deterioration 30D

100% 100% 100% 100%

Data Extract Jan 2009 Jan 2009 18 Mar 09 May, 2009

Edwards Transcatheter AVR Edwards Transcatheter AVR Survival at 1, 6 and 12 monthsSurvival at 1, 6 and 12 months

93.692.092.786.8

71.967.2

90.083.4

78.3

46.2

33.6

75.871.4

40.4

28.0

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

iREVIVE(n=22)

RECAST (n=24)

REVIVE(n=106)

REVIVAL(n=59)

PARTNER EU(n=54)

SOURCE(n=303)

1 month 6 months 12 months

Transfemoral ExperienceTransfemoral Experience

Siegburg

REVIVE & REVIVALVascular Complications

Vascular Complications

(n=25)

Perforations (n=12)

Aortic Dissection (n=3)

Flow Limiting Iliac Dissection

(n=4)

Avulsed Iliac Artery (n=3)

Lower Extremity Ischemia (n=4)

Covered Stent - 3

Surgical Bypass - 9

Surgical Repair - 4

Surgical Bypass - 3

Surgery - 1

Medical - 2

Surgery - 2

Medical - 2

3 Deaths

2 Deaths

2 Deaths

2 Deaths

In Hospital Mortality in Patients with a Vascular Complication – 36%

In Hospital Mortality in Patients without a Vascular Complication – 10.3%

Siegburg

P = .006P = .006

Vascular Access Vascular Access Complication Rate, Complication Rate, by patientby patient

January 2006 – January 2006 – June 2006June 2006

30%30%

Vascular Screening withVascular Screening withColumbia University Columbia University

Medical CenterMedical CenterCore LabCore Lab

INSTITUTEDINSTITUTED(in coordination with DSMB)(in coordination with DSMB)

Vascular Screening withVascular Screening withColumbia University Columbia University

Medical CenterMedical CenterCore LabCore Lab

INSTITUTEDINSTITUTED(in coordination with DSMB)(in coordination with DSMB)

Vascular Access Vascular Access Complication Rate, Complication Rate, by patientby patient

August 2006 – August 2006 – December 2007December 2007

5.8%5.8%

REVIVE improved screening to reduce vascular complications

Siegburg

TA Survival PARTNER EU & TRAVERCE

Overall Survival TRAVERCE vs. PARTNER EU (TA)

Pro

bab

ility

(ev

ent

free

)

0 1 2 3 4 5 6

0.0

0.2

0.4

0.6

0.8

1.0

PARTNER EU (TA)

TRAVERCE

6M surv: 0.70

6M surv: 0.55

Time (months)

Siegburg

Complications N=25(18.5%)

Descending Ao dissection 1

Apical bleeding/ventricular injury 8

Arrhythmias requiring intervention 4

Hemodynamic instability requiring intervention

3

Severe CHF 4

Partial coronary occlusion 3

Coronary occlusion 2

TRAVERCE Transapical Intraprocedural Complications

Siegburg

TA Survival Overall (n=159)

EuroSCORE 30%STS Score 15%

132 78 64 Pts at risk

30 D

ays

6 M

on

ths

1 Y

ear

Off-pump 94.0%Conversion 2.5%Stroke None

2 Y

ears

20

0 200 400 600 800 1,0000,0

0,2

0,4

0,6

0,8

1,090 ±3%

76 ±4% 74 ±4%

Days

Leipzig TA ExperienceSurvival

Siegburg

CoreValveCoreValveProcedural ResultsProcedural Results

21F S&E 18F S&E 18F EE

Siegburg

Global 18-Fr ExperienceGlobal 18-Fr Experience

18 Fr. CVSS&E Study – CE

Marking

European Registry (Post-

CE Mark)*

Australian New

Zealand Trial*

Single Center Experience

Munich(Lange)

Siegburg

(Grube)

Patients (n) 112 14 1,424 37 137 102

30D Mortality – All Cause 15.2% 7.1%✚ 10.4% 8.1% 12.4% 10.8%

Technical Success 86.5% n.a. 97.3% 98.3% 98.5% 98.2%

* Site reported ✚Un-adjudicated

Siegburg

≤ ≤ 30-Day Adverse Events* 30-Day Adverse Events*

* Multiple events in same patients = data not cumulative* Multiple events in same patients = data not cumulative†† Includes 4 deaths where cause is not known Includes 4 deaths where cause is not known

21F S&E Study

(N = 52)

18F S&E Study

(N = 124)

18F EE Registry

(N = 1243)

30-Day All Mortality 15.4% 14.5% 6.7%

Cardiac Deaths 7.7% 11.2% 3.9%†

Myocardial Infarction 3.8% 3.4% 0.7%

Major Arrhythmias 25.0% 18.5% 4.9%

Pacemaker 17.3% 25.8% 12.2%

Renal Failure 5.8% 4.8% 1.2%

Stroke 17.3% 6.5% 1.4%

TIA 0.0% 5.6% 0.3%

Structural Valve Dysfunction 0.0% 0.0% 0.0%

Valve Migration 0.0% 0.0% 0.0%

Siegburg

Siegburg CoreValve Experience

Total number of patients*: 387

Gen 1 (2005) 10 Gen 2 (2005-2006) 26 Gen 3 (since 2006) 257 in 2008 217 in 2009 6-10/week

30 Day Mortality:

Gen 1 40.0% Gen 2 20.8% Gen 3 8.6% in 2008 4.8%

*Status of Nov 2008

Siegburg

• Native Aortic Valve Disease• Severe AS: AVAI ≤0.6 cm2/m2

• 27mm ≥AV annulus ≥20mm• Sino-tubular Junction ≤43mm

Age ≥80 y (21F) ≥75 y (18F)

Logistic EuroSCORE ≥20% (21F) ≥15% (18F)

Age ≥65 y plus 1+ of the following: • Liver cirrhosis (Child A or B)• Pulmonary insufficiency: FEV1<1L• Previous cardiac surgery• PHT (PAP>60mmHg)• Recurrent P.E’s• RV failure• Hostile thorax (radiation, burns,etc)• Severe connective tissue disease• Cachexia

TAVI Candidate Today: Who is Eligible?

Morphological Criteria:

(Mandatory)

Clinical Criteria:

?

Siegburg

0

20

40

60

80

100

0 50 100 150

Age Distribution of CoreValve Patients 2006-2008HELIOS Heart Center Siegburg

N=280

Younger Population will be approached with increasing evidence on safety and feasibility…

Siegburg

Morphological Quantification

Morphologic Criteria must be met

Siegburg

Which is the preferred access?

Transfemoral

Complexity / Invasiveness

Surgical

Interventional

Transapical

Subclavian

Siegburg

Future Challenges

Indication

Controversies:Which Technique?Which Access Site?

Which performing Discipline?

Design Features (e.g.Profile)

Siegburg

‘Percutaneous Devicesfor Aortic Valve Replacement’

Potential problems of current devices– Paravalvular leackage

– Inaccuracies in Positioning

– Embolization (Edwards prosthesis)

– ‘One shot’ procedure

Siegburg

CoreValveAortic Regurgitation post-interventional

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Pre Post

4+

3+

2+

1+

0

34.6

34.6

30.9

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Pre-Post

Worsened

Unchanged

Improved

A B

24.3 28.9

54.4 51.2

19.1 18.2

0.7

01.5

1.7

The Sadra LotusThe Sadra LotusTMTM Valve - Valve - Device Features and RationaleDevice Features and Rationale

AdaptiveTM Seal

Lockingmechanism

Siegburg

At this point the device can be fully retracted, back to step 1, and repositioned

Lotus Valve

Investigational device currently in European clinical trial Not available for sale

Multilumen

Slightly Tapered, ConformablePolyester Fabric Cuff

Tri-leaflet Valve constructed of Bovine Pericardium

Position Fill Lumens (PFLs)-Used to position/reposition valve-Complete Inflation Media Exchange

Ventricular and Aortic Rings -Inflate independently so device can be repositioned -deflatable so that device can be fully retrieved

The Direct Flow Medical (DFM) Aortic Valve Prosthesis

Direct Flow Aortic ValveDirect Flow Aortic Valve

Valve loaded in Delivery Catheter

(22F)

Introducing Tip advanced

Delivery sheath pulled back; Valve

inflated

Siegburg

PCICABG

1980’s, 1990’s

My Prediction: Repetition of an Old Story

TAVIsAVR

2000’s, 2010’s

With the same result…

Siegburg

Transcatheter AVRMy Rosey Prophecy

Surgery – The PAST

TAVR – The Future

In the next 5-10 years, most patients with In the next 5-10 years, most patients with severe AS requiring AVR will be treated severe AS requiring AVR will be treated

using transcatheter lesser-invasiveusing transcatheter lesser-invasivemodalities!modalities!

Siegburg

Vielen Dank