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Transcatheter Aortic Valve Replacement (TAVR)

A less Invasive Treatment Option for Severe Aortic Stenosis.

Timinder Biring, MD FACC Interventional Cardiologist, Fairview Southdale Hospital

TAVR team UMP Heart

Disclosure

• Consultant Boston Scientific

• Speakers bureau Edwards Lifescience

• Sub PI – Reprise 3 trial

• I will discuss off label use of TAVR

Outline

• Background and Perspective

• TAVR Clinical Data

• Approved Commercial Devices

• Future of TAVR

• UMP Heart Valve team experience

Objectives

• Understand the pathophysiology of Aortic Stenosis

• Become familiar with trial data supporting the advent of TAVR.

• Become familiar with current TAVR platforms.

• Understand limitations of devices and future directions.

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Prevalence

• Prevalence is estimated to be 4% • Bicuspid AV present in 50% of the patients undergoing AVR

Otto, M. et al, Cardiology Clinics, 1998;16: 353 – 373

Age Group

( y )

Normal Aortic Valve

( %)

Aortic Sclerosis

( %)

Aortic

Stenosis

( %)

All Subjects 72 26 4

65 – 74 78 20 1.3

75 – 84 62 35 2.4

> 84 48 48 4

Stewart BF, et al. J Am Coll Cardiol 29: 630-634, 1997

At risk

Disease initiation

Progressive Disease

Valve obstruction

Aortic sclerosis AS

Genotype Valve morphology Age, gender Dyslipidemia Diabetes/MetS Hypertension Smoking Renal insufficiency Serum phospate

Shear stress Inflammation Lipid infiltration Myofibroblast diff.

Oxidative stress Angiotensin II Pro-calcific stimuli OPG/RNAKL Wnt/LRP

Hydroxyapatite nodules Cartilage and bone formation

Normal leaflets

? 10-15% ~100%

Infl

amm

atio

n

Leaf

let

calc

ific

atio

n

Age Current Imaging Window

or

2014 ACC/AHA Valve Guidelines Concept of Valve Disease Stages

Natural History of Aortic Stenosis

from Ross and Braunwald, Circulation 1968

40 50 60 70 80 0

20

40

60

80

100

Age

Years

Survival

Percent Onset severe

symptoms

6 4 2 0 Avg. survival

Years

Angina

Syncope

Failure

Latent Period

(Increasing

Obstruction,

Myocardial

Overload)

“Surgical intervention should be performed promptly once even … minor symptoms occur”

Source: Chart: Ross J Jr, Braunwald E.

Aortic stenosis. Circulation

1968;38 (Suppl 1) C.M. Otto. Valve Disease: Timing of Aortic

Valve Surgery. Heart 2000

23

4

12

30

28

30

5

10

15

20

25

30

35

Worse Prognosis than Many Metastatic Cancers

5-Year Survival (Distant Metastasis)8

Su

rviv

al, %

Breast

Cancer

Lung

Cancer

Colorectal

Cancer

Prostate

Cancer

Ovarian

Cancer

Severe

Inoperable AS* *Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu, MD, Cleveland Clinic

5 year survival of breast cancer, lung cancer, prostate cancer, ovarian cancer and severe inoperable aortic stenosis

8

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• Shortness of breath

• Angina

• Fatigue

• Syncope or presyncope

• Other

– Rapid or irregular heartbeat

– Palpitations

Symptoms of Aortic Stenosis4

The symptoms of aortic disease are commonly misunderstood by

patients as ‘normal’ signs of aging.5 Many patients initially appear

asymptomatic, but on closer examination up to 37% exhibit symptoms.6

Sandy

Actual TAVR Patient

Pre-Procedure

Inopera

9

Aortic Valve Replacement

• Current standard of care – open heart surgery.

• >200,000 Surgical AV replacements annually worldwide.

• Cardiac surgeon opens the heart, removes the diseased valve, and inserts a prosthetic valve.

• Recovery time: 1-3 months until normal activity

• Extended hospital stay (4-7 days).

Who Likes Surgery? Early Catheter-Based AV Designs

• Dr. Henning Anderson “father of TAVR.” – Cardiologist in Denmark

• Concept conceived in 1989.

• Built device from materials at local hardware store

• Performed first in animal implantation

• Company sold to Edwards Lifesciences.

The Andersen valve (1992)

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First-in-Man

April 16, 2002

Percutaneous Transcatheter Implantation of an

Aortic Valve Prosthesis for Calcific Aortic

Stenosis First Human Case Description Alain Cribier, MD; Helene Eltchaninoff, MD; Assaf Bash, PhD;

Nicolas Borenstein, MD; Christophe Tron, MD; Fabrice Bauer, MD;

Genevieve Derumeaux, MD; Frederic Anselme, MD; François

Laborde, MD; Martin B. Leon, MD

AHA; Nov, 2002

Adopted from TCT presentation: Dr. Leon

Transcatheter AVR

Edwards CoreValve

“First” Generation Devices

TAVR Clinical Data

Publications in NEJM 1-Year outcomes published on-lin1-Year June 9, 2011

2-Year outcomes published on-line March 26, 2012

@ NEJM.org and print May 3, 2012

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N = 179

N = 358 Inoperable

Standard Therapy

ASSESSMENT:

Transfemoral Access

Not In Study

TF TAVR

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

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

1:1 Randomization

VS

Yes No

N = 179

TF TAVR AVR

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

TA TAVR AVR VS

VS

N = 248 N = 104 N = 103 N = 244

PARTNER Study Design

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened

Total = 1,057 patients

2 Parallel Trials:

Individually Powered

N = 699 High Risk

ASSESSMENT:

Transfemoral Access

Transapical (TA) Transfemoral (TF)

1:1 Randomization 1:1 Randomization

Yes No

0%

20%

40%

60%

80%

100%

0 6 12 18 24

Primary Endpoint: All Cause Mortality - Inoperable

All cause

mortality

HR [95% CI] = 0.51 [0.38, 0.68]

p (log rank) < 0.001

∆ at 1 yr = 20.0%

NNT = 5.0 pts

50.7%

30.7%

179

179

TAVR

Std Tx

Numbers at Risk

138

121

124

85

103

56

60

24

Months

TAVR

Std Tx

TAVR 348 298 261 239 222 187 149

AVR 351 252 236 223 202 174 142

All-Cause Mortality (ITT) High risk

0%

10%

20%

30%

40%

50%

60%

70%

0 6 12 18 24 30 36

All-C

au

se M

ort

ality

Months post Randomization

TAVR

AVR

No. at Risk

HR [95% CI] =

0.93 [0.74, 1.15]

p (log rank) = 0.483

26.8%

24.3%

34.6%

33.7%

44.8%

44.2%

348 287 250 228 211 176 139

351 246 230 217 197 169 139

TAVR

AVR

0%

10%

20%

30%

40%

50%

60%

70%

0 6 12 18 24 30 36

Str

okes

TAVR

AVR

Strokes (ITT)

No. at Risk

3.2%

6.0% 9.3%

8.2%

HR [95% CI] =

1.09 [0.62, 1.91]

p (log rank) = 0.763

4.9%

7.7%

Months Post Randomization

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Echocardiographic Findings (AT) Aortic Valve Area

TAVR

AVR

0

0.5

1

1.5

2

2.5

Baseline 30 Days 6 Months 1 Year 2 Years 3 Years

Val

ve A

rea

(cm

2)

TAVR

AVR

Error bars at 1 standard deviation

p = NS

No. of Echos

p = 0.0017 p = 0.0019 p = NS p = 0.0005 p = NS

p = NS

p = NS

304 271 223 211 150 88

294 226 163 154 121 70

Echocardiographic Findings (AT) Mean & Peak Gradients

TAVR

AVR

0

10

20

30

40

50

60

70

80

Baseline 30 Days 6 Months 1 Year 2 Years 3 Years

Gra

die

nt

(mm

Hg)

Peak Gradient - AVR

Peak Gradient - TAVR

Mean Gradient - AVR

Mean Gradient - TAVR

No. of Echos 310 277 233 219 155 88

299 230 169 158 123 72

Edwards Lifesciences SAPIEN/SAPIEN XT THV

] Edwards-SAPIEN THV

New

Skirt Height

Bovine Tissue

ThermaFix Treatment

Pericardial Mapping

Leaflet Deflection

Proprietary Processing

Cobalt Alloy Frame

New Leaflet Geometry

SAPIEN XT THV

New Sizes

(23, 26, 29mm)

NovoFlex Delivery System

• Unidirectional tip-deflecting flex catheter facilitates negotiating the arch

• Balloon catheter tapered distal end for crossing calcified native valve

Flex Catheter

Nose cone – 4.5 cm