TCT AP 2013Seoul, Corea April 18, 2013

CoreValve is Enough“!CoreValve is „Enough !(Core Valve is Better?)(Core Valve is Better?)

Eberhard Grube MD, FACC, FSCAIUniversity Hospital, Dept of Medicine II, Bonn, Germany

Hospital Alemão Oswaldo Cruz, São Paulo, BrazilSt f d U i it P l Alt C lif i USAStanford University, Palo Alto, California, USA

Eberhard Grube, MD,Within the past 12 months, the presenter or their spouse/partner h h d fi i l i t t/ t ffili ti ith thhave had a financial interest/arrangement or affiliation with the organization(s) listed below.

Physician Name Company/Relationship

Eb h d G b MD M d i C V l C SB AB OFEberhard Grube, MD Medtronic, CoreValve: C, SB, AB, OFSadra Medical: E, C, SB, ABDirect Flow: C, SB, ABMitralign: AB SB EMitralign: AB, SB, EBoston Scientific: C, SB, ABBiosensors: E, SB, C, ABCordis: ABCordis: ABAbbott Vascular: ABCapella: SB, C, ABValtech: E SBValtech: E, SB, Claret: SB

KeyG Grant and or Research Support E Equity Interests S Salary AB Advisory BoardG – Grant and or Research Support E – Equity Interests S – Salary, AB – Advisory Board

C – Consulting fees, Honoraria R – Royalty Income I – Intellectual Property Rights SB – Speaker’s Bureau O – Ownership OF – Other Financial Benefits‘

TAVI ArrivesTAVI ArrivesCurrent Generation DevicesCurrent Generation DevicesCurrent Generation DevicesCurrent Generation Devices

>75,000 patients treated thru 2013in >650 interventional centers

around the globe!around the globe!

Edwards LifesciencesEdwards Lifesciences Medtronic CoreValveMedtronic CoreValve

Anatomic Anatomic ““FootprintFootprint”” of Edwards Sapien valve of Edwards Sapien valve vs MDT CoreValvevs MDT CoreValvevs. MDT CoreValve vs. MDT CoreValve

CoreValve Global GrowthNew Market Expansion

(past 24 months)Cumulative Implant Growth

40,000>40,000 Implants

20 000

30,000

10,000

20,000

0 2007 2008 2009 2010 2011 2012

Addressable Market Share

58%42%

Medtronic

Edwards

MDT CoreValve share of TF OUS Market

Advantages of BE Edwards SapienAdvantages of BE Edwards Sapien

Sh t f d iSh t f d i l i t f ith il i t f ith i l tl t•• Short frame design Short frame design –– less interference with periless interference with peri--valve anatomy valve anatomy (conduction system, CAs)(conduction system, CAs)

•• Precise positioning in the subPrecise positioning in the sub--annular zone (but requires RV pacing annular zone (but requires RV pacing for deployment)for deployment)

•• Deflectable delivery system to negotiate arch anatomy and vessel Deflectable delivery system to negotiate arch anatomy and vessel tortuositytortuosity

•• Circular frame/valve deployment in annular zone Circular frame/valve deployment in annular zone

F ll thi k b i i diF ll thi k b i i di d d bilit (?)d d bilit (?)•• Full thickness bovine pericardium Full thickness bovine pericardium –– good durability (?)good durability (?)

•• Access site versatility (TF, TA, TAo)Access site versatility (TF, TA, TAo)

Advantages of SE MDT CoreValveAdvantages of SE MDT CoreValve

•• More valve sizes to accommodate full range of annular dimensionsMore valve sizes to accommodate full range of annular dimensions•• More valve sizes to accommodate full range of annular dimensions More valve sizes to accommodate full range of annular dimensions (esp. large sizes)(esp. large sizes)

Sl t ll d l d l t ith t d f id RV iSl t ll d l d l t ith t d f id RV i•• Slow controlled valve deployment without need for rapid RV pacingSlow controlled valve deployment without need for rapid RV pacing

•• Partial repositioning features during deploymentPartial repositioning features during deployment

•• Less trauma to annulus and aorta Less trauma to annulus and aorta –– reduced risk of rupturereduced risk of rupture

•• Circular frame/valve in supraCircular frame/valve in supra--annular zone (better for small annulus annular zone (better for small annulus and small Vand small V--inin--V)V)

•• Access site versatility (TF, SC, TAo)Access site versatility (TF, SC, TAo)

•• LMA distance from annulus less importantLMA distance from annulus less important•• LMA distance from annulus less importantLMA distance from annulus less important

Areas of Consideration

• Patient Selection• Patient Selection

• ProcedureProcedure

• Post Procedure

• Future

Aortic Size Considerations

Annulus Diameter in mm

CoreValve Able to Treat > 27-29 mm; at least ~20% more patients

Edwards

Sizing Concept

SAPIEN XT

* EW 20 mm Valve not yet CE marked

MedtronicMedtronic CoreValve

Medtronic and Edwards Product IFU’s

Vessel Size ConsiderationsCoreValve is able to Treat Patients with Small and Challenging

Vasculature >/= 6mm

Low Delivery Profile: 18Fr delivery system for all l / l i

18 29Annulus Size (mm)

valve/annulus sizes

18 29Annulus Size (mm)

Maximum Sheath Size

18FR 18FR 18FR 18FR21.8FR 21.8FR 21.8FR 21.8FR

20 1FR 26 7FR* 21 6FR 26 7FR* 24 0FR 29 7FR*

18FR21.7FR

19.4FR22.5FR

16FR EX

20.1FR 26.7FR*

18FR 20FR EXEX

21.6FR 26.7FR* 24.0FR 29.7FR*

• The E-Sheath starts as small as 16F, but expands to maximum diameter of 29.7F as the valve passes through the delivery system1.

1.  Sapien XT Instructions for Use

Direct Comparisons of CoreValve and Edwards

• 3 studies have directly compared TF‐TAVI outcomes between CoreValve and Edwards valves1,2,3.  – PRAGMATIC1 performed propensity score matching due to differences in 

baseline characteristics.  Seiffert2 and Buchanan3 represent real world cohorts.

14.3%

14.0%

16.0%

%)

p=0.037

p=0.004p=0.583

8.3%

9.7%

12.0%12.5%

10.0%

12.0%

mplications (%

8.3%

4 0%

6.0%

8.0%

Vascular Co

m

2.2%

0.0%

2.0%

4.0%

Major V

CoreValve      (n=252)

Sapien/Sapien XT (n=252)

CoreValve      (n=93)

Sapien XT      (n=142)

CoreValve      (n=45)

Sapien/Sapien XT (n=104)

PRAGMATIC SAPERE SeiffertPRAGMATIC SAPERE Seiffert

1. Chieffo, abstract  TCT‐859 presented at TCT 2012                                    3.      Buchanan et al., Poster Abstract TCT-843, Presented at TCT 2012 2. Seiffert, et al., Cath Card Int 2012;  epub Nov 21, 201

Potential for Expanded IndicationsPotential for Expanded Indications

Failed Pure BicuspidBioprothesis Aortic

Insufficiency

pValve

TAVI in Failed Surgical Bioprosthetic Valve

TAVI for Pure Severe Native AR

• 43 patients from 14 centers

• TAVI with CoreValve prosthesis

• Procedural success 97.7%

• 8 patients (18.6%) second valve

• AR ≤ I in 79.1%

• Only in 2 patients AR ≥ III

• Pacemaker in 16.3%

• 30 day‐stroke rate 4.7%

• 30 day‐mortality rate 9.3%

• Prosthesis deployment– Rapid pacing

– “Two pigtail”‐techniqueTwo pigtail technique

Roy et al., JACC 2013, epub Feb 20, 2013

Implantation in Bicuspid Native Valve

CoreValve system with conformable Nitinol frame and supra-annular valve function adapts to extreme elliptical deployments

Areas of Consideration

• Patient Selection• Patient Selection

• ProcedureProcedure

• Post Procedure

• Future

Ease of ImplantEase of Implant

18Fr delivery Partial Slow controlled Conformable at18Fr delivery Partial repositioning with gradual

Slow, controlled valve

deployment

Conformable at annulus with supra-annular g

Releasep y

without need for rapid ventricular

pacing

pfunction

pacing

Frame Design Flexibility

• Valve in supra-annular zone (better for elliptical annulus, and V-in-V)

• Less trauma to annulus and aorta reduced risk of• Less trauma to annulus and aorta – reduced risk of annular rupture

CoreValve Supra Annular Valve Location May Produce Higher EOAProduce Higher EOA

CoreValve Hemodynamic Results

ADVANCE RegistryRegistry

ANZ Registry g yResults @ 2 Years

Linke et al, TCT 2012; Meredith  et al, TCT 2012 

CoreValve Results Sustained to Three Years

Ussia et al, European Heart Journal 2012 

Opportunity for Further Procedural SimplificationSimplification

• Pilot study of 60 consecutive patients undergoing CoreValve implantations at 13 international centers from 2009 to 2010.

• Procedural success was 96.7% (58 of 60 patients). 

• A new pacemaker was implanted in 11.7% (7 of 60) of the patients w/out  balloon pre‐dilation, as compared to 27.8% in a historical control group (n=126)

• The stroke rate was 5% in patients without balloon pre‐dilation as compared to 11 9% in the historical control group11.9% in the historical control group.

• Indicates that TAVI w/out balloon pre‐dilation seems to be feasible and should be investigated further in a larger Trial.be investigated further in a larger Trial.

Grube et al., JACC CV Interv 2011;4:751‐7

Direct TAVI: Bonn-Heidelberg Cohort

N = 310 patientsP = 0.05

P = 0 16

30

3530.4

27 0Direct TAVI

p P = 0.16

25

30

21.0

27.0Direct TAVI

%)

20

21.019.7

quen

cy (%

15

tive Freq

P = 0.97

P = 0.067

5

10 6.2 6.14.8Re

lat

0

5 1.3

Comb. Endpoint 30-day Mortality Stroke Pacemaker

Sinning et al, DGK 2013

Areas of Consideration

• Patient Selection• Patient Selection

• ProcedureProcedure

• Post Procedure

• Future

Post Procedure Considerations

• Positive Survival Results Across Trials for Both Devices

• ParaValvular Leak Remains a Concern for Both Devices

• Longer Term Performance of the Valves and Associated Complications Needs Further Assessmentp

Paravalvular Leak is Associated with MortalityMortality

PARTNER ADVANCE

Moderate/severe paravalvular AR25

p

20 19.0

15 217.2

21.0

1515.2

13.1 13.615.1

16.516.4

5

10

0

5

Grube, Circ, 2006 Leon, NEJM, 

2010 Abdel‐Wahab, Heart, 2011 Tamburino, 

Circ, 2011 Smith, NEJM, 2011 Moat, JACC, 

2011 Sinning, JACC,2011 Sinning, JACC, 2012 Gilard, NEJM, 

2012 Vasa‐Nicotera, JACC INT, 2012

Medtronic CoreValveEd d SAPIENEdwards‐SAPIEN

AR Similar in Matched Patient PopulationsPopulations

• Difficult to compare AR rates across studies due to differences in relevant patient

CV SAPIEN p

30-Day Outcomesdifferences in relevant patient characteristics

• In a propensity matched patient

30 Day OutcomesAll-Cause Mortality

8.8 6.4 NS

In a propensity matched patient data set (PRAGMATIC) comparing CoreValve and

CV Mortality 6.9 6.4 NS

1-Year OutcomesSAPIEN XT:• No differences in combined

safety and efficacy endpoints

Mod/Severe AR 6.2 2.8 NS

All-Cause Mortality

16.2 12.3 NSsafety and efficacy endpoints

• No differences in AR

N diff i 30 d 1

MortalityCV Mortality 8.3 7.4 NS

S ff C• No differences in 30-day or 1-year mortality

San Raffaele, Milan; Clinique Pasteur,, Toulouse; ErasmusMed Center, Rotterdam; Hôpital Rangueil, Toulouse

Chieffo, A.  JACC 2013; epub ahead of print. 

Paravalvular Aortic Regurgitation(Valve Implant)(Valve Implant)

None Trace Mild Moderate Severe

100%p = 0.12 p = 0.20

os

80%29.2%

20.9%24.2%16.9%

uabl

eec

ho

60% 40.9% 30.8%37.7%44.4%

ento

feva

lu

40%

Perc

e

20% 38.2% 40.0%38.2%38.6%

0%SAPIEN SAPIEN XT SAPIEN SAPIEN XT

30 Days 1 Year

225 236 110 120

30 Days 1 YearNo. of Echos

Late embolization

Total Number of Reported Late  Number of Required  Number of Resulting 

Embolized Valves Open Heart Surgeries Patient Deaths

Sapien or Sapien XT

11 11 3Sapien XT

CoreValve 0 0 0

• Late embolizations occurred anytime from 4 hours to 6 weeks after implant.after implant.  

• Potential reasons for late embolizations:• Impingement by a mitral prosthesis1

• Bileaflet native valve2

• Root calcification causing inadequate anchoring3, 4

• Stent malposition4• Stent malposition4

• Undersized valve4

• Possible recoil given frame material

1. Baumbach et. al., Ann Thorac Surg 2011; 92:  728‐9     2.  Schroeter et. al., Thorac Cardiovasc Surg 2011; 59(8):  503‐63.    Maroto et. al., Eur J Cardiothorac Surg 2009; 36(5):  935‐7 4.  Lida et. al., JACC Cardiovasc Imag 2012; 5(11):  1181‐6

Reasons for Increased AR, Late Migrations?

?

Recoil in Cobalt Chrome used in Coronary Stents is Well UnderstoodWell Understood

Boston Scientific, Presentation by K Dawkins Jan 2011

Areas of Consideration

• Patient Selection• Patient Selection

• ProcedureProcedure

• Post Procedure

• Future

Platform Matters

Time

Dirigible1894

The End1930s1894 1930s

Fighter Jet

1950s

PropellerPlane1936

Wright Brothers

1903

Turbo Jet1939

UnmannedAriel

Vehicle1936903 Vehicle1959

Future PlatformsFuture Platforms