Transcatheter Aortic Valve Therapies

Mark RussoAssistant Professor of Surgery

Co-Director, Center for Aortic Diseases

SUMMARY POINTS

• This is NOT experimental therapy– 45,000 implants worldwide– In Germany, 20-25% of isolated AVRs are TAVI

• Indications– Symptomatic, severe AS deemed inoperable

• Shown to be clinically effective in a well-selected patients– RCT demonstrated an absolute 20% survival benefit– 40%+ of OMM pts are dead at 6 months

ADVANCES IN THE RX OF STRUCTURAL HEART DISEASE

1951 - Cardiopulmonary Bypass

1977- Percutaneous Coronary Intervention

2011 - Transcatheter Valves

CHANGING TREATMENT PARADIGM

• Treatment options: Significant unmet need

• Delivery of care: “Heart team” concept

• Tools available: Catalyze other percutaneous technologies for treatment of structure heart disease

The Problem of Aortic Stenosis

Aortic stenosis is life threatening and progresses rapidly

– Survival after onset of symptoms is 50% at 2 years and 20% at 5 years1

– “Surgical intervention [for severe AS] should be performed promptly once even…minor symptoms occur”1

1 Lester SJ, Heilbron B, Gin K, Dodek A, Jue J. The natural history and rate of progression of aortic stenosis. Chest. 1998;113:1109-1114.

Helping to Solve a Grave Problem

Latent Period(Increasing Obstruction,Myocardial Overload)

Surv

ival

, %

100

80

60

40

20

0 40 50 60 70 80Age, y

Onset Severe Symptoms

AnginaSyncope

Average Survival, y

Failure

0 2 4 6

THE BURDEN OF AORTIC STENOSIS

• In the US:– AS: 1,500,000– Severe AS: 500,000– Severe, symptomatic AS: 250,000– AVRs performed annually: 85,000

>150,000 untreated AS patients

At least 43-74% of patients with severe aortic stenosis (AS) do not have an AVR

Addressing a Serious Unmet Need

1999 2006 2006 20092005 2010

Pat

ient

s, %

Aortic Valve Replacement (AVR) No AVR

2009

Dismal Outcomes with Severe Inoperable AS

5-Year Survival

Surv

ival

, %

* National Institutes of Health. National Cancer Institute. Surveillance Epidemiology and End Results. Cancer Stat Fact Sheets. http://seer.cancer.gov/statfacts/. Accessed November 16, 2010.

† Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu.

†**

* * *

Dismal Outcomes with Severe Inoperable AS

5-Year Survival

Surv

ival

, %

* National Institutes of Health. National Cancer Institute. Surveillance Epidemiology and End Results. Cancer Stat Fact Sheets. http://seer.cancer.gov/statfacts/. Accessed November 16, 2010.

† Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu.

†**

* * *

The predicted survival of inoperable patients with severe AS who are treated with standard non-surgical therapy is lower than with certain metastatic cancers.

– Survival after onset of symptoms is 50% at 2 years and 20% at 5 years1

1 Lester SJ, Heilbron B, Gin K, Dodek A, Jue J. The natural history and rate of progression of aortic stenosis. Chest. 1998;113:1109-1114.

Latent Period(Increasing Obstruction,Myocardial Overload)

Surv

ival

, %

100

80

60

40

20

0 40 50 60 70 80

Age, y

Onset Severe Symptoms

Angina

Syncope

Average Survival, y

Failure

0 2 4 6

TAVI for Who?

What is the Data to Support Use?

INDICATIONS

• Severe Symptomatic AS– Aortic Velocity > 40 m/sec– Mean Gradient > 4 mmHg– Valve Area < 1.0 cm2

• Inoperable – determined by a surgeon– Mortality > 15%– Death or serious, irreversible morbidity > 50%– STS score > 8-10

The PARTNER Trial Protocol

Not in Study

AssessmentTransfemoral Access

Yes No

Primary Endpoint: All-Cause Mortality OverLength of Trial (Superiority)

Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority)

TFTAVR

(n = 179)

Standard Therapy(Control)(n = 179)

vs

1:1 Randomization

AssessmentTransfemoral Access

TF(n = 492)

TA(n = 207)

Yes No

Primary Endpoint: All-Cause Mortality (1 yr)(Non-inferiority)

TFTAVR

(n = 244)

AVR(Control)(n = 248)

vs

1:1 Randomization

TATAVR

(n = 104)

AVR(Control)(n = 103)

vs

1:1 Randomization

Cohort ACohort A(n = 699)

Cohort B(n = 358)

2 CohortsIndividually Powered

(N = 1,057)

TA, transapical; TF, transfemoral.

AssessmentOperability

NoYes

Severe Symptomatic Native Aortic Valve Stenosis

PARTNER COHORT B

Source: NEJM, 2001

• Mean Age: early 80s• Mean STS Score: 11• Mean EuroScore: 12• NYSA III/IV - 90%• s/p CABG - 40%• COPD - 45%

– O2 - 20%

• PHTN - 40%• Radiation - 10%

• Porcelain Aorta

PARTNER COHORT B

Source: NEJM, 2001

PARTNER TRIAL – COHORT B20% Reduction in Mortality

0 6 12 18 24

∆ at 1 yr = 20.0%NNT = 5.0 pts

All-C

ause

Mor

talit

y, %

50.7%

30.7%HR [95% CI] =

0.51 [0.38, 0.68]P (log rank) < .0001

Numbers at Risk

Edwards SAPIEN THV 179 138 124 103 60

Standard Therapy 179 121 85 56 24

Months

0

20

40

60

80

100 Edwards SAPIEN THV

Standard Therapy

Source: NEJM, 2001

PARTNER TRIAL – COHORT B20% Reduction in Mortality

0 6 12 18 24

∆ at 1 yr = 20.0%NNT = 5.0 pts

All-C

ause

Mor

talit

y, %

50.7%

30.7%HR [95% CI] =

0.51 [0.38, 0.68]P (log rank) < .0001

Numbers at Risk

Edwards SAPIEN THV 179 138 124 103 60

Standard Therapy 179 121 85 56 24

Months

0

20

40

60

80

100 Edwards SAPIEN THV

Standard Therapy

20% absolute reduction in mortality at

1 year

Source: NEJM, 2001

Paravalvular Leaks Over Time

PARTNER TRIAL – COHORT B

NEJM, 2011Source: NEJM, 2001

PARTNER TRIAL– COHORT BQuality of Life Benefits

60

40

20

0

80

100

0 4 6 8 10 122

Standard Therapy

Edwards SAPIEN THV

∆ = 13.9P < .001

∆ = 24.5P < .001

KCCQ

Sco

re (M

ean)

MCID, minimum clinically important difference.

MCID = 5 points

Months

Improvement in quality of life

CONCLUSIONS – PARTNER B

• 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)

Inoperability

• Operative mortality > 15% • Operative severe morbidity or death > 50%• STS score > 8• Previous cardiac surgery – multiple, s/p CABG• Home O2• PHTN• Radiation• Porcelain Aorta• Frailty

Fried Frailty IndexFried Phenotype of Frailty

Weight Loss (unintentional) > 10 lb in previous year

Grip strength Lowest 20% by sex/BMI

Exhaustion Self-report (CES-D depression scale)

Walk time, 15 feet Lowest 20% by sex/height

Low activity Males < 383 kcal/weekFemales < 270 kcal/week

Frailty: ≥ 3 criteriaIntermediate/prefrail: 1 or 2 criteria

Fried LP, et al. J Gerontol A Biol Sci Med Sci. 2001;56:M146-M156.

Approaches

Approaches

• Transfemoral• Illiac Conduit• Transapical• Subclavian• Transaortic

TAVI - Transfemoral

TAVI - Transapical

Anterior Thoracotomy

TAVI - Transapical

Source: theheart.org

TAVI – LEFT SUBCLAVIAN APPROACH

TAVI-Transaortic