STEPHAN WINDECKER

DEPARTMENT OF CARDIOLOGY

SWISS CARDIOVASCULAR CENTER AND CLINICAL TRIALS UNIT BERN

BERN UNIVERSITY HOSPITAL, SWITZERLAND

AORTIC VALVE DISEASE

RANDOMISED TRIALS

COMPARING

TAVI WITH SAVR

RANDOMISED

EVIDENCE

INTERMEDIATE

RISK PATIENTS

TAVI VERSUS

SURGERY

TAVI LIMITATIONS

PCI VS. CABG AND TAVI VS. AVR

PCI vs.

CABG

TAVI vs. AVR

1990 1995 2000 2005 2010 2020

1970 1980 1990 2000 20202010

1977CORONARY

ANGIOPLASTY

(GRÜNTZIG)

1994STENTS

INTRODUCED

1969FIRST

DESCRIPTION

OF CABG(FAVOLARO)

1995 CABRIn=1054

CABG/PCI

1996 BARIn=1829CABG/PCI(1%BMS)

1994 EASTn=392

CABG/PCI

1998 RITAn=1011CABG/PCI

2002 AWESOMEn=454CABG/BMS(54%)

2005 ARTS I n=1205CABG/BMS (98%)

2005 ERACI IIn=450CABG/BMS

2007 MASS IIn=611

CABG/BMS (68%)

2008 LE MANSn=105CABG/DES (35%)

2011 LEIPZIGn=201 CABG/DES

2011 PreCOMBATn=600 CABG/DES

17 YEARS TO THE FIRST COMPARISON

1992FIRST DESCRIPTION OF A

TRANSCATHETER HEART VALVE

(ANDERSEN)

2002FIRST IN MAN

TAVI (CRIBIER) 2010 PARTNER Bn=358

TAVI / MED

2011 PARTNER An=699TAVI / AVR

9 YEARS TO THE FIRST COMPARISON

2010 CARDian=510CABG/DES+BMS

2009 SYNTAXn=705CABG/DES

2008 SOSn=988CABG/BMS(97%)

2012PARTNER 2SurTAVI

RECRUITING

TAVI / AVR

10 YEARS OF DEVELOPMENTTHE PROCEDURE

ANTEGRADE TF ACCESSRETROGRADE ACCESS

Direct Carotid

Axillary

2012

PATIENT - ADAPTED

ACCESS SITE SELECTION

ACCORDING TO

INDIVIDUAL ANATOMICAL

CHARACTERISTICS

PROCEDURAL SUCCESS

%

COREVALVE

EDWARDS SAPIEN

72,6

91,297,2 98,2 97,6

77,8

86

94,1 95,2 97

0

20

40

60

80

100

Buellesfeld Grube 2008 Piazza Petronio Gilard Webb Webb Webb Thomas Gilard

N=126

Büllesfeld

S&E MCV

JACC 2011

N=136

Grube

Circ Interv

2008

N=646

Piazza

EIJ

2008

Gilard

NEJM

2012

N=1143N=514

Petronio

Circ Interv

2010

N=18

Webb

Circulation

2006

N=50

Webb

Circulation

2007

N=113

Webb

Circulation

2009

N=463

Thomas

Circulation

2010

Gilard

NEJM

2012

N=2107

PARTNER BLeon et al. N Engl J Med 2010 Oct 21;363(17):1597-607

INOPERABLE PATIENTSWITH SYMPTOMATIC AS

MEDICAL TREATMENT TAVI

n = 358

Randomized

n = 179n = 179

124/124 patients100% followed at 1 Yr

85/85 patients100% followed at 1 Yr

101/102 patients99.0% followed at 2 Yrs

46/46 patients100% followed at 2 Yrs

80/82 patients97.6% followed at 3 Yrs

19/19 patients100% followed at 3 Yrs

Cross over

11 pts

Cross over

9 pts

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

ALL – CAUSE DEATH CARDIAC DEATH

TAVI VS. MEDICAL TREATMENT

IN INOPERABLE PATIENTS – 3 YEAR F/ULEON MB ET AL. NEJM 2010; PRESENTED AT TCT 2012, MIAMI

PARTNER B

30.7%

50.8%

43.0%

68.0%

54.1%

80.9%

Months

HR [95% CI] = 0.53 [0.41, 0.68]p (log rank) < 0.0001

20.1%

25.0%

26.8%

NNT=5.0pts

NNT=4.0pts

NNT=3.7pts

Standard Rx

TAVI

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

20.5%

44.6%

30.7%

62.4%

41.4%

74.5%

HR [95% CI] = 0.41 [0.30, 0.56]p (log rank) < 0.0001

24.1%

31.7%

33.1%

NNT=4.1pts

NNT=3.2pts

NNT=3.0pts

PARTNER B

MORTALITY STRATIFIED BY

STS SCORE (ITT)

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

MO

RTA

LITY

(%)

Months Months Months

STS: 0 - 4.9 STS ≥ 15STANDARD RX

TAVI

∆ = 66.8%

NNT = 1.5 pts NNT = 4.5 pts NNT = 4.8 pts

∆ = 20.8%∆ = 22.3%

Numbers at Risk

Standard Rx 12 8 7 6 5 3 0 123 86 61 44 33 19 13 43 27 17 12 8 5 4

TAVR 28 26 25 24 21 19 16 113 84 79 70 65 55 44 38 28 20 16 15 14 10

100%

33.2%

86.6%

65.8%55.2%

77.5%

STS: 5.0 - 14.9

LEON MB ET AL. NEJM 2010; PRESENTED AT TCT 2012, MIAMI

Makkar et al. N Engl J Med 2012;366:1696-704

INOPERABILITY CONDITIONS BY

STS RISK SCORE

13

23

28

33

16

6

20

86

10

76

2523

24

0

5

10

15

20

25

30

35

0-4.9 5-14.9 ≥15

Frailty

Porcelain Aorta

Radiation

Chest Deformities

Respiratory Disease

%

PARTNER B

MANAGEMENT OF SEVERE AORTIC STENOSISESC GUIDELINES ON VALVULAR HEART DISEASE 2012

Severe AS

Symptoms

LVEF < 50%

No

Physically active

No

Presence of risk factors and low/intermediate individual surgical risk

No Yes

Re-evaluate in 6 months

AVR

AVR or TAVI

No Yes

Symptoms or fall in bloodpressure below baseline

No

Contraindication for AVR

No Yes

Short life expectancy

No

TAVI

Yes

Med Rx

High risk for AVR

Exercice test

No YesYes

Yes

Yes

Eur Heart J 2012 - doi:10.1093/eurheartj/ehs109 & EurJ Cardiothorac Surg 2012 - doi:10.1093/ejcts/ezs455).

Severe AS

Symptoms

Yes

Contraindication for AVR

YesNo

Short life expectancyHigh risk for AVR

No

Yes

TAVI

TAVI

RANDOMISED

EVIDENCE

INTERMEDIATE

RISK PATIENTS

TAVI VERSUS

SURGERY

TAVI LIMITATIONS

INTENTION TO TREAT

POPULATION

AS TREATED

POPULATION

TAVI VS. SURGERYALL – CAUSE DEATH

Kodali et al. N Engl J Med 2012;366:1686-95

PARTNER A

3,7

21,3

8,2

25,2

8,7

29,1

7,6

25,3

0

5

10

15

20

25

30

35

30 Days 12 Months

AT

TF TAVI

TF SAVR

TA TAVI

TA SAVR

TAVI VS. SURGERYALL – CAUSE DEATH

Smith C et al. N Engl J Med 2011;364:2187-98

PARTNER A

AS TREATED PATIENT POPULATION

P=0.05

P=0.33

P=0.79

P=0.55

%

TAVI VS. SURGERYSUBGROUP ANALYSES OF TREATMENT EFFECT

Smith C et al. N Engl J Med 2011;364:2187-98

PARTNER A

TAVI SAVR

TAVI

SAVR

AORTIC VALVE AREA MEAN AORTIC GRADIENT

TAVI VS. SURGERYECHOCARDIOGRAPHIC FINDINGS

Kodali et al. N Engl J Med 2012;366:1686-95

PARTNER A

TAVI VS. SURGERYEFFECT OF TAVI ON QOL AT 12 MONTHS

Reynolds MR et al. J Am Coll Cardiol 2012;50:548-58

PARTNER A

NYHA FUNCTIONAL CLASS

75

128

165152

71 75

192

175

0

50

100

150

200

250

Baseline 30 Day 6 Month 1 Year

TAVI

AVR

6 –

MIN

UTE

WA

LKTE

ST(M

EDIA

ND

ISTA

NC

E(M

))

FUNCTIONAL CAPACITY

p=0.73p=0.002

p=0.33p=0.76

TAVI AVR TAVI AVR TAVI AVR TAVI AVR

P=1.00 P<0.001 P=0.05 P=0.74

NYHA

ROLE OF TAVI

IN ROUTINE CLINICAL PRACTICEWenaweser P et al. J Am Coll Cardiol 2011;58:2151-62

0

10

20

30

40

50

60

70

80

90

100

Cum

ula

tive

inci

de

nce

(%)

254 187 121 88 43 17TAVI

107 82 53 34 22 13Surgical

78 46 29 26 13 9Medical

No. at risk

0 6 12 18 24 30Follow-up, months

___ Medical- - - Surgical-.-.- TAVI

p=<.0001

All cause death

All Cause Mortality

56.4%

20.6%

20.6%

Medical Treatment, N=78 (18%)

Surgical AVR: adj. HR = 0.51 (0.30-0.87)

N=107 (24%)

TAVI: adj. HR = 0.34 (0.22-0.54)

N=257 (58%)

N=452

ESC RECOMMENDATIONS FOR THE

TREATMENT OF VALVULAR HEART DISEASE

Eur Heart J 2012 - doi:10.1093/eurheartj/ehs109 & EurJ Cardiothorac Surg 2012 - doi:10.1093/ejcts/ezs455).

RANDOMISED

EVIDENCE

INTERMEDIATE

RISK PATIENTS

TAVI VERSUS

SURGERY

TAVI LIMITATIONS

TAVI VS. SAVRCEREBROVASCULAR ACCIDENTS (ITT)

p=0.12

Primary EP: MortalityRetrospective Assessment of stroke severityAge = 85±6EuroScore = 29±16Atrial fibrillation: 43%Cerebrovascular dz: 27%

SYNTAX (CABG group)Stroke = 2.2% @ 1 year

Age = 65±10EuroScore = 4±3

TRANSCATHETER AORTIC VALVE IMPLANTATION

AND CEREBROVASCULAR EVENTSSTORTECKY S, WINDECKER S CIRCULATION 2012;126:2921-4

EMBOLIC PROTECTION DEVICES

RADIAL ACCESS FEMORAL ACCESS RADIAL ACCESS

EMBOLIC DEFLECTOR DEVICES EMBOLIC FILTER DEVICE

AORTIC STENOSIS AND ATRIAL FIBRILLATION

IN PATIENTS UNDERGOING TAVISTORTECKY S ET AL. CIRC CARDIOVASC INTERV FEB 2013; [EPUB AHEAD OF PRINT]

BERN TAVI REGISTRY N=389; AGE 83±6 YEARS; 58% FEMALE GENDER

MECHANISMS OF AORTIC REGURGITATIONBuellesfeld L et al. JACC Cardiovasc Interv 2012;5:578-81

TAVI VS. MEDICAL TREATMENTECHOCARDIOGRAPHIC OUTCOMES – TAVI COHORT

Makkar et al. N Engl J Med 2012;366:1696-704

15,3

34,3

20,1

31,3

52,1

29,9

11,84,5

0,7 0

0%

20%

40%

60%

80%

100%

30 DAYS 2 YEARS

Severe

Moderate

Mild

Trace

None

32,6 28,4

38,9 49,3

27,8 17,9

0,7 4,5

1 2

PARAVALVULAR AR TRANSVALVULAR AR

p=0.001 p=0.75

30 DAYS 2 YEARS

PARTNER B

AORTIC REGURGITATION AND

IMPACT ON OUTCOMESKodali SK et al. N Engl J Med. 2012;366:1686-95

DEA

THFR

OM

AN

YC

AU

SE(%

)

PARAVALVULAR AR OVERALL AR

PARTNER A

2-Y

ea

r D

ea

th (

%)

0

10

20

30

40

50

60

Time in Days

0 60 120 180 240 300 360 420 480 540 600 660 720

388 373 339 300 238 127 119 112 76400 388 350 303 247 125 114 106 74120 113 97 81 66 37 34 32 23

Number At RiskNone or Trace PVLMild PVLMod or Sev PVL

Log Rank P= <.001

20.2%21.7%

37.8%

NRCA-TF - None or Trace PVL at 30DNRCA-TF - Mild PVL at 30DNRCA-TF - Mod or Sev PVL at 30D

* Events adjudicated to one year

PARTNER 1 NRCA ONLYMORTALITY & PARAVALVULAR LEAK

NEW GENERATION TAVI DEVICES

EFFECT ON PARAVALVULAR AR?

EDWARDS SAPIEN 3 MEDTRONIC ENGAGER

SEALING CUFF

TECHNOLOGY

NATIVE VALVE CLIPPINGMECHANISM

RELATIONSHIP OF THE

AORTIC VALVE AND THE

CONDUCTION SYSTEMEPSTEIN A ET AL. N ENGL J MED 2007;357:2706

PIAZZA N ET AL. CIRC CARDIOVASC INTERV 2008;1:74-81

PERMANENT PACEMAKER IMPLANTATION

%COREVALVE

EDWARDS SAPIEN

26,2

33,3

16,3

35,2

24,2

4 4,46 6,7

11,5

0

5

10

15

20

25

30

35

40

S&E Sgb Ital Spai Fran2 Web7 Web9 Him Thom Fran2

N=126

Büllesfeld

S&E MCV

JACC 2011

N=136

Grube

Circ Intv

2008

Avanzas

Rev Esp

Card 2010

N=108 N=50

Webb

Circulation

2007

N=113

Webb

Circulation

2009

N=51

Himbert

JACC

2009

N=514

Petronio

Circ Intv

2010

Gilard

NEJM

2012

N=1043 N=463

Thomas

Circulation

2010

Gilard

NEJM

2012

N=2107

PARTNER B: 3.4%PARTNER A: 3.8%

IMPACT OF PERMANENT PACEMAKER IMPLANTATION

ON CLINICAL OUTCOMES AFTER TAVI

BUELLESFELD L ET AL. J AM COLL CARDIOL 2012;60:493-501COREVALVE ADVANCE

PRESENTED BY BAUERNSCHMITT R. AT EUROPCR 2012

RANDOMISED

EVIDENCE

INTERMEDIATE

RISK PATIENTS

TAVI VERSUS

SURGERY

TAVI LIMITATIONS

HEART TEAM DECISION

STS - SCORE

ALL – CAUSE MORTALITY

@ 30 DAYS

7,1

6,25,8

4,8

0

1

2

3

4

5

6

7

8

Q1 Q2 Q3 Q4

% 11,4 11,4 11,4

3,8

0

2

4

6

8

10

12

Q1 Q2 Q3 Q4

Assessed for eligibility (n= 3666)

TAVI= 782 (21.3%)SAVR= 2884 (87.7%)

Unmatched: n= 2856TAVI= 377

SAVR= 2479

PS matched patients with TAVI (n= 405)

Lost to follow-up (n=4)

PS matched patients with SAVR (n= 405)

Lost to follow-up (n=10), Patient declined (n=2)

PS matched patients with TAVI eligible for SURTAVI (n= 255)

Lost to follow-up (n=3)

PS matched patients with SAVR eligible for SURTAVI (n= 255)

Lost to follow-up (n=8)

Not eligible for SURTAVI (n= 150)

STS <3: n= 99STS >8: n= 51

Not eligible for SURTAVI (n= 150)

STS <3: n= 99STS >8: n= 51

BERMUDA – PATIENT FLOWPIAZZA N ET AL. JACC CARDIOVASC INTERV. 2013; AHEAD OF PRINT

BERMUDA TRIANGLE

TAVI IN INTERMEDIATE RISK PATIENTSPIAZZA N ET AL. JACC CARDIOVASC INTERV. 2013; AHEAD OF PRINT

0

5

10

15

20

255 237 223 216 211 205 200 199 194 191 189 188 183

255 233 215 206 203 199 186 171 161 157 153 149 143

0 1 2 3 4 5 6 7 8 9 10 11 12

Months after TAVI

HR (95% CI): 0.90 (0.57-1.42); p=0.64

0

5

10

15

20

All

–C

ause

Mo

rtal

ity

(%)

255 250 248 244 243 241 237SAVR

255 248 246 242 239 237 233TAVI

NO. AT RISK

0 5 10 15 20 25 30

Days after TAVI

TAVI SAVR

HR (95% CI): 1.12 (0.58-2.15); p=0.74

All – Cause Death@ 30 Days

All – Cause Death@ 12 Months

PROPENSITY SCORE MATCHED PATIENT POPULATION

TAVI (N=255) VS. SAVR (N=255)

SURTAVI – STUDY DESIGN

STS mortality risk ≥4% and ≤10%

Heart Team EvaluationConfirm Inclusion/Exclusion & Intermediate

Risk Classification

RandomizationStratified by need for

revascularization

SAVRMedtronic CoreValve®

TAVI

N = ~2,000 patients

• Randomized 1:1, non-inferiority study

• Up to 75 worldwide centers

Europe

Canada

United States

• Approx 2,000 total number of trial subjects

• Long-term follow-up through 5 years

PARTNER II TRIAL UPDATELEON MB, PRESENTED AT TCT 2012

NEW GENERATION TAVI DEVICES

TAVI IN INTERMEDIATE RISK PATIENTS

PRIORITY SURTAVI & PARTNER II

HEART TEAM

APPROACHCardiologist

MULTIDSCIPLINARY CONSULTATION

Imaging

Specialist

Surgeon

Technician

Anesthesiologist

“Surgeons and cardiologists must

work as a team to select

appropriate candidates, perform

the procedure, and, finally,

evaluate the results.”

Vahanian A et al. Eur Heart J. 2008;29:1463-70

10 YEARS TAVIWHAT DID WE LEARN FROM CLINICAL TRIALS

• TAVI IMPROVES PROGNOSIS TAVI is superior compared to medical treatment and non-inferior compared

to surgical aortic valve replacement.

• STROKE AFTER TAVI IS AN ISSUE• Cerebrovascular events are frequent early after TAVI

• and have a substantial impact on outcomes

• VALVE DURABILITY• is maintained beyond 2 years of follow-up• Aortic regurgitation impacts on outcomes and needs to be improved

• HEALTH RELATED QUALITY OF LIFE• TAVI effectively alleviates symptoms • and improves health-related quality of life

10 YEARS TAVIWHAT DID WE LEARN FROM CLINICAL TRIALS

• TAVI IS SAFE TAVI is superior compared to medical treatment and non-inferior compared

to surgical aortic valve replacement.

• STROKE AFTER TAVI IS AN ISSUE• Cerebrovascular events are frequent early after TAVI

• VALVE DURABILITY• is maintained beyond 2 years of follow-up• Aortic regurgitation impacts on outcomes and needs to be improved

• HEALTH RELATED QUALITY OF LIFE• TAVI effectively alleviates symptoms • and improves health-related quality of life

PATIENT

WITH COMPLEX

AORTIC VALVE DISEASE

HEART TEAM APPROACH

RANDOMISED

EVIDENCE

INTERMEDIATE

RISK PATIENTS

10 YEARS OF

TAVI

TAVI VERSUS

SURGERY

TAVI LIMITATIONS

COST

EFFECTIVENESS