Management of Aortic Stenosis

Update of TAVI results by the femoral approach

Victor Legrand

CHU Sart-Tilman

Liège (B)

Currently two devices are commercialised:

Edwards SAPIEN CoreValve ReValving

23 & 26mm 26 & 29mm

retro- & antegrade retrograde (femoral or subclavian)

•Each approach has

its advantages.

•No direct

comparative studies

for the two

approaches.

Description of outcomes according to

transfemoral (TF)( ES or CV) or

transapical (TA) (ES) approach.

TAVI offers an option to treathigh-risk patients

Study Design Patients Log. Euroscore

REVIVE/REVIVAL TF 161 31%

REVIVAL II TA 40 35%

TRAVERSE TA 169 27%

PARTNER EU TF 61 26%

PARTNER EU TA 69 34%

SOURCE registry TF 463 26%

SOURCE registry TA 575 29%

France registry TF 95 26%

France registry TA 71 27%

Corevalve registry TF 2426 22%

France registry TF 66 25%

Belgian registry TF 141 25%

4

2005 2009

Comprehensive Training Has Resulted in Improved TF THV Clinical Outcomes

34 Centres Initially

Participating in Commercial

Launch

1123 patients

Included:

32 centres

1038 patients

The SOURCE Registry has

100% procedure data

98% 1 year data

All consecutively enrolled

Excluded:

2 Centres / 85 patients• Unable to obtain Ethic Cte approval

• Unable to secure administrative support

• One missing patient due to admin. error

5

S-E SOURCE Registry Cohort I

Nov 07 to Dec 08

TF(n=463)

TA (n=575) P-Value

Age (yrs) 81.7 80.7 0.022

Female 55.1% 55.8% NS

Pulmonary Disease 24.6% 29.9% NS

Renal Dysfunction 25.5% 32.5% 0.016

Logistic EuroSCORE 25.8 29.0 0.007

Peripheral Vascular Disease 10.6% 28.0% <0.001

Carotid Artery Stenosis (>50%) 7.1% 17.2% <0.001

Incidence of CAD 47.5% 55.1% 0.020

Porcelain Aorta 4.5% 11.3% 0.001

Prior CABG 17.5% 27.0% 0.003

Mitral valve disease 15.8% 32.0% <0.001

5/03/2010Data Snapshot6

Baseline Demographics

and Risk Factors

TF (n=463) TA (n=575) Total (n=1038)

Death 6.3% 10.8% 8.8%

Stroke 2.6% 2.4% 2.5%

Renal Failure Requiring Dialysis

1.3% 7.0% 4.4%

Permanent Pacemaker

6.0% 7.7% 6.9%

5/03/10Data Snapshot7

Major Complications (≤ 30 Days)

Edwards Pooled Monitored & SOURCE: Freedom from Stroke Curve (1 Yr)

8

SOURCE: COHORT 11 Year Survival (All Approaches)

9

30 Day Survival:

TA 89.2%

TF 93.7%

ALL 91.2%

10

Early Vascular Access Complications

Relationship to 1 Year Mortality (NB 22/24F Device)

Approach

% Survival in Pts who did

not have vascular access

complications

% Survival in Pts who did

have vascular access

complications

P-Value

TF 83.9% 72.2% 0.0121

TA 73.2% 47.4% 0.0188

11

Causes of Death30 Days to 1 Year

ALL

ALL

179

Cardiac

45 (25.1%)

Heart Failure

28 (62.2%)

Myocardial Infarction

6 (13.3%)

Endocarditis

3 (6.7%)

Other*

8 (17.8%)

Non Cardiac

88 (49.2%)

Pulmonary***

21 (23.9%)

Renal Failure

11 (12.5%)

Cancer

10 (11.4%)

Stroke

9 (10.2%)

Gastrointestinal

5 (5.6%)

Other**

32 (36.4%)

Unknown

46 (25.7%)

Sudden Death

18 (39.1%)

Unknown

18 (39.1%)

Other

10 (21.7%)

Other * = Arrhythmia, cardiac arrest

Other** = Sepsis, vascular access related, major

bleeding, infection, suicide, and multiple organ failure

Pulmonary***= Respiratory Failure, Pulmonary

Embolism and Pneumonia

Multivariate Analysis – 1YR Mortality (TF)

13

*Logisitic EuroSCORE is not a predictor for 1 year mortality in patients

treated with the transfemoral approach

Analysis of Maximum Likelihood Estimates (C statistic=0.6852)

Parameter P-Value

Hazard

Ratio 95% Hazard Ratio Confidence Limits

NYHA Class IV 0.0067 1.948 1.203 3.153

Renal insufficiency / Failure <.0001 2.382 1.553 3.656

Hyperlipidemia / Hypercholesterolemia 0.0293 0.602 0.382 0.950

Systemic Hypertension 0.0317 0.622 0.403 0.959

Smoking 0.0009 2.268 1.399 3.677

Mitral valvuloplasty 0.0040 8.237 1.956 34.690

Coagulopathy 0.0073 5.178 1.558 17.208

Canada SAP: 2 Year F-U Survival Curves

18

Corevalve Investigators 2006-2008 / n=126

Medtronic CoreValve System

Kaplan-Meier Estimates of Survival Probability

Surv

ival

Dis

trib

uti

on F

unct

ion

0.00

0.25

0.50

0.75

1.00

Post_op_Days

0 100 200 300 400 500 600 700 800

One-year survival:

71.9%Two-year survival:

59.7%

Post Op Days

Surv

ival D

istr

ibution F

unction

Kaplan-Meier Estimates of Survival Probability

P>0.2

Overall survival

85.1±1.3

At risk 590 407

Italian Corevalve TAVI Registry

2007-2009

Overall survival

Baseline clinical characteristicsN=772

Age (years) 82±6 (IQR 79-86)Female 432 (56.0%)Log EUROSCORE (%) 22.9±13.5 (IQR 13-29)NYHA class III-IV 545 (70.6%)Hypertension 591 (76.6%)Diabetes 212 (27.5%)PAD 160 (20.7%)CAD 372 (48.2%)Prior MI 160 (20.7%)Prior PCI 225 (29.1%)Prior CABG 117 (15.2%)Prior Aortic Bioprosthesis 14 (1.8%)Prior CVA 58 (7.5%)

Italian CorevalveTAVI Registry

2007-2009

Implantation Success with Corevalve

1 Year Survival with Corevalve

New PCMK implantation with Corevalve

18,5%

81,5%

Yes No

Total population (n=772)Prior LBBB (n=85)

Prior RBBB (n=62) Low implantation (n=61)

Need for new PM

Italian Corevalve TAVI Registry

2007-2009

Additional information

• TAVI demonstrates excellent hemodynamic performance:

mean gradient: 50mmHg(pre) to <10 mmHg (post)

• Aortic Regurgitation: >/= 2+ in 15 to 45% after implant, down to 10 to 25% at 1yr

• Stroke rate are similar to high-risk surgical AoVR cohorts (1.7 to 4.5%)

• TAVI improves patient quality of life: >80% improved at least 1NYHA Class after TAVI

Summary

• TAVI is entering more and more in routine practice for patients with several co-morbidities wich make surgery challenging or at increased operative risk.

• The initial success rate has gradually improved up to 95%.

• The 30 day survival with the TF approach is of 90-95% ( 85 -90% for TA).

• One year mortality ranged from 20 to 30% and is driven largely by not cardiac causes.

• Results achieved by ES and CV retrograde systems are similar, except the higher need for PCMK implantation with the CV approach.

The Belgian TAVI Registrypatient characteristics

The Belgian TAVI Registryprocedural success

The Belgian TAVI Registryone month MACE and survival

The Belgian TAVI Registryone year survival

The Belgian TAVI RegistryEdwards TF vs TA

The Belgian TAVI Registrycauses of death

Primary EndpointNon inferiority in: Freedom from death at 1 year

Primary Endpoints Superiority in: Freedom from death over duration of trial

Superiority in: Composite of death and recurrent hospitalization

PARTNER IDE Pivotal Trial Overview

SPRING 2011 TCT 2010RELEASE TIMING

PARTNER cohort BAll Cause Mortality

Numbers at Risk

TAVI 179 138 122 67 26

Standard Rx 179 121 83 41 12

Standard Rx

TAVI

All-

cause

mort

alit

y(%

)

Months

∆ at 1 yr = 20.0%

NNT = 5.0 pts

50.7%

30.7%

Conclusions - 1

In patients with severe AS and symptoms,

who are not suitable candidates for surgery…

• Standard therapy (including BAV in 83.8% of pts) did

not alter the dismal natural history of AS;

all-cause and cardiovascular mortality at 1 year was

50.7% and 44.6% respectively

• Transfemoral balloon-expandable TAVI, despite

limited operator experience and an early version of

the system, was associated with acceptable 30-day

survival (5% after randomization in the intention-to-

treat population)

Conclusions - 2

• TAVI was superior to standard therapy, markedly

reducing the rate of…

all-cause mortality by 46%, P < 0.0001,

NNT = 5.0 pts

cardiovascular mortality by 61%, P < 0.0001,

NNT = 4.1 pts

all-cause mortality and repeat hospitalization

hierarchical (FS method), P < 0.0001

non-hierarchical (KM analysis) by 54%,

P < 0.0001, NNT = 3.4 pts