trans catheter aortic valve replacement · discuss future developments in tavr. 5 16.5 million...

Satish K Surabhi, MD,FACC,FSCAIMedical Director, Cardiac Cath Labs

AnMed Health Heart and Vascular Care

Trans Catheter Aortic Valve Replacement

No financial conflict of interest related to this talk

Will discuss some non –FD approved devices

Review the clinical course of severe symptomatic aortic stenosis

Identify treatment options for severe symptomatic aortic stenosis

Review clinical trial data regarding TAVR Discuss future developments in TAVR

5

16.5 Million People in US

Over the Age of 652

Percentage Diagnosed with Aortic Stenosis

Aortic stenosis is estimated to be

prevalent in up to 7% of the population over

the age of 651

It is more likely to affect men than

women; 80% of adults with symptomatic aortic stenosis are

male3

Presenter

Presentation Notes

Aortic stenosis is a common public health problem affecting millions of people in the United States. It is estimated to be prevalent in up to 7% of the population over the age of 65. It is also more likely to affect men than women; 80% of adults with symptomatic aortic stenosis are male.

Aortic stenosis in patients over the age of 65 is usually caused by calcific (calcium) deposits

associated with aging

Age-Related CalcificAortic

Stenosis

Congenital Abnormality

In some cases adults may develop aortic stenosis resulting from a congenital abnormality

More Common

Less Common

Rheumatic Fever

Adults who have had rheumatic fever may also be at risk for aortic stenosis

Presenter

Presentation Notes

There are various causes of aortic stenosis. Aortic stenosis in patients over the age of 65 is usually caused by calcific (calcium) deposits associated with aging. It can also be caused by infection, rheumatic fever, or a congenital abnormality.

3 Major Etiologies for aortic stenosis

Shortnss of breath Syncope/ pre-syncope Angina Fatigue Dyspnea on exertion CHF A-fib related

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

Surgical intervention for severe aortic stenosis should be performed promptly once even minor symptoms occur1

Presenter

Presentation Notes

Literature shows - Survival after onset of symptoms is 50% at 2 years and 20% at 5 years - Surgical intervention for severe aortic stenosis should be performed promptly once even minor symptoms occur

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

5-Year Survival8Su

rviv

al, %

BreastCancer

LungCancer

ColorectalCancer

ProstateCancer

OvarianCancer

SevereInoperable AS*

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

Presenter

Presentation Notes

Data shows a sobering perspective for inoperable patients: 5 year survival of breast cancer, lung cancer, prostate cancer, ovarian cancer and severe inoperable aortic stenosis

0102030405060708090

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Sur

viva

l, %

AVR, no Sx

AVR, Sx

No AVR, no Sx

No AVR, Sx

Study data demonstrate that early and late outcomes were similarly good in both symptomatic and asymptomatic patients

It is important to note that among asymptomatic patients with SAS, omission of surgical treatment was the most important risk factor for late mortality

Patient Survival16AVR, No Symptoms

AVR, Symptoms

No AVR, No Symptoms

No AVR, Symptoms

Years

Presenter

Presentation Notes

Study data demonstrate that early and late outcomes were similarly good in both symptomatic and asymptomatic patients It is important to note that among asymptomatic patients with SAS, omission of surgical treatment was the most important risk factor for late mortality

Studies show at least 40% of patients with severe AS are not treated with an AVR

Aortic Valve ReplacementNo Aortic Valve Replacement

Presenter

Presentation Notes

Studies show at least 40% of SAS patients are not treated with an AVR9-15

An aortic valve replacement as an alternative to traditional thoracotomy.

Less invasive than traditional thoracotomy for patients considered too high risk for traditional surgery.

16

Presenter

Presentation Notes

If a cardiac surgeon determines that you are too sick for open-heart surgery and if medicine is not helping you feel better, TAVR may be an alternative. This less invasive procedure allows your aortic valve to be replaced with a new valve while your heart is still beating.

Edwards SapienValve

Stainless Steel Frame More Aortic

Regurg, less AV block/PPM

Better for severe bulky calcification.

Medtronic CoreValve Nitinol Frame-self

expanding Less Aortic

Regurg, More heart block/PPM

Patients at Extreme Surgical Risk

Foundational trials tested new TAVR therapy in patients without the option for a surgical aortic valve replacement

CoreValve, N=489, STS 10.3% SAPIEN, N=179, STS 11.2%

US CoreValve Pivotal Trial PARTNER 1B

• PARTNER showed that by 3 years, TAVR had reduced mortality by approximately 30% compared to standard medical management.

• Similar survival results were achieved with CoreValve in the US Pivotal Trial

Patients at Extreme Surgical Risk3-Year Follow-Up

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

Months

All-

Cau

se M

orta

lity

PARTNER B All-CausePARTNER B Standard Rx50.8

68.0

80.9

26.5%

31.5%

30.6%

Presenter

Presentation Notes

30% of the deaths were due to non-cardiac causes, highlighting the severe comorbidities in these patients.

Patients at High Surgical Risk

Trials randomizing high risk patients to either TAVR or SAVR soon followed

US CoreValve Pivotal Trial PARTNER 1A

SAPIEN, N=348, STS 11.8% vs. SAVR, N=351, STS 11.7%

CoreValve, N=390, STS 7.3% vs. SAVR, N=357, STS 7.5%

1Mack, et al., presented at ACC 2015

• PARTNER showed that ~35% of patients survived to 5 years, regardless of treatment

• This study provided the first confirmation that TAVR is a reasonable alternative to surgery in high risk patients

PARTNER 1A5-Year Follow-Up Presented at ACC 2015

CoreValve US Pivotal Trial 3-Year Follow-Up Presented at ACC 2016

1Deeb, et al., J Am Coll Cardiol 2016 Mar 22; doi: 10.1016/j.jacc.2016.03.506

The CoreValve Pivotal Trial was the first to show a survival advantage with TAVR compared to SAVR, with separation of the all-cause mortality curves maintained to 3 years

Randomized trial data comparing TAVR to SAVR in lower-risk patients recently became available

SAPIEN XT and SAPIEN 3 CoreValve

Patients at Intermediate Surgical Risk

1Smith, et al., presented at ACC 2016

The PARTNER 2A Trial showed that TAVR with SAPIEN XT was non-inferior to surgery for the primary endpoint of all-cause mortality or disabling

stroke at 2 years

Intermediate RiskPARTNER 2A | SAPIEN XT

1Smith, et al., presented at ACC 2016

• This study also generated convincing

evidence that transfemoral TAVR provides an outcome

advantage to intermediate risk

patients

• In the as-treated population, TF TAVR significantly reduced all-cause mortality or disabling stroke vs. surgery (p = 0.04)

Intermediate RiskPARTNER 2A | SAPIEN XT

All cause mortality 1.1% vs 4% at 30 days 7.4% vs 13.5 % at 1 yr

Disabling Stroke 1% vs 4.4% at 30 days 2.3% vs 5.9 % at 1 year

75% reductionIn Death and in disabling stroke

Low Surgical RiskActive Trials Randomizing TAVR to SAVR

1Popma, et al., presented at TCT 2016; 2Mack, et al., presented at TCT 2016; 3Moat, et al., presented at TCT 2016; 4Sondergaard, et al., presented at TCT 2016

Medtronic Low Risk1

UK TAVI3

N = ~1200

Up to 80 centers Evolut R, all routes

Industry-sponsored10-year follow-up

N = 1228

Up to 64 centersSAPIEN

3, transfemoral

Industry-sponsored10-year follow-up

PARTNER 32

N = 808

All UK TAVI centers All valves, all routes

Publically funded5-year follow-up

NOTION-24

N = 992

All Nordic countriesAll

valves, transfemoral

Physician and industry-sponsored5-year follow-up

Currently there is significant clinical investment in applying TAVR to younger patients at low surgical risk, both in North America and in Europe

EARLY TAVR TAVR in asymptomatic severe AS

TAVR UNLOAD TAVR in moderate AS with CHF/ LV dysfunction

CoreValve SAPIEN XT SAPIEN

Foundational TAVR Devices Complications

Foundational randomized trials did provoke some concern about the safety of TAVR due to the incidence of certain

complications, including stroke, conduction disturbances, paravalvular leak, and vascular trauma

Death Stroke Vascular Complications Pacemaker implantation Paravalvular regugitation Late valve dysfunction

Transfemoral TAVR DevicesIterative Device Design

Iterative devices have been designed to mitigate complications, simplify the procedure, and improve upon current anatomic exclusions to enable the

treatment of more patients

SAPIEN 3 ACURATE neo

Evolut R Lotus Portico

Frame Nitinol Nitinol CobaltChromium Nitinol Nitinol

PVL Managment Extended Skirt Adaptive Seal PET Fabric Skirt Pericardial cuff Pericardial skirt

Annular Range 18-30 mm 20-27 mm 16-28 mm 19-27 mm 21-27 mm

Positioning Recapturable Recapturable -- Recapturable --

Caliber 14 Fr/ 16 Fr equiv. 18 Fr 14 Fr / 16 Fr 18 Fr / 19 Fr 18 Fr

Embrella Embolic Deflector (Edwards Lifesciences)

Triguard(Keystone Heart, Herzliya

Pituach, Israel)

Claret Montage (Claret Medical, CA)

Trans-thoracic

Echo (TTE)

Chest X-ray

Electro-cardiogram

Cardiac Cath.

Auscultation

Presenter

Presentation Notes

Multiple modalities may be used to diagnose severe aortic stenosis including review of a patient’s electrocardiogram, chest x-ray, cardiac catheterization, auscultation and transthoracic echocardiography (TTE).

Confirm the patient is diagnosed with severe

symptomatic native aortic stenosis

Confirm the patient has been

independently evaluated by two

cardiac surgeons and meets the indication

for TAVR

Evaluate the aortic valvular complex using

echocardiography

Evaluate the peripheral

vasculature and aortic valvular complex

using MDCT

Evaluate the peripheral vasculature and aortic valvular complex using

catheterization

Note: Evaluation using CT is typically not done unless the Heart Team confirms that patient is a candidate for TAVR

4 531 2

20 cases in the last 6 months Ages 59 to 85 High STS scores/ high risk for SAVR No Death/CVA/PPM implantation No major vascular complications ( one

pseudoaneurysm ) One expected ICD to remove life-vest

TAVR is the only option for extreme risk patients

TAVR is an equal or better for high risk patients

TAVR is an equal or better option for intermediate risk patients

TAVR for low risk patients being studied

SAPIEN SAPIEN XT SAPIEN 3

CoreValve SAPIEN XT SAPIEN

Foundational TAVR Devices Complications

Foundational randomized trials did provoke some concern about the safety of TAVR due to the incidence of certain complications, including stroke, conduction disturbances, paravalvular

leak, and vascular trauma

1Leon, et al., N Engl J Med 2010;363:1597-1607; 2Webb, et al., J Am Coll Cardiol Intv 2015;8:1797-806; 3Smith, et al., N Engl J Med 2011;364:2187-98; 4Leon, et al., N Engl J Med 2016;374:1609-20; 5Popma, et al., J Am Coll Cardiol 2014;63:1972-81; 6Adams, et al., N Engl J Med 2014;370:1790-8;;

6.7%

4.1% 4.6% 4.3%5.5%

4.0%4.9%

0%

2%

4%

6%

8%

10%

Extreme Risk P 1B

N=179

Extreme Risk P 2B

N=276

High Risk P 1A

N=348

Extreme Risk P 2B

N=284

Intermediate Risk P 2A

N=1,011

Extreme Risk US Pivotal

N=489

High Risk US Pivotal

N=390

30-D

ay A

ll St

roke

Weighted average (n=8,987)4.2%

Foundational TAVR Devices Stroke


3.4%5.9%

3.8%6.8%

8.5%

21.6%19.8%

0%

10%

20%

30%

Extreme Risk P 1B

N=179

Extreme Risk P 2B

N=276

High Risk P 1A

N=348

Extreme Risk P 2B

N=284


N=1,011


N=489


N=390

30-D

ay P

erm

anen

t Pac

emak

er


Foundational TAVR Devices New Permanent Pacemaker Implantation


16.2% 15.2%

11.0%9.5%

7.9% 8.2%5.9%

0%

5%

10%

15%

20%

Extreme Risk P 1B

N=179

Extreme Risk P 2B

N=276

High Risk P 1A

N=348

Extreme Risk P 2B

N=284


N=1,011


N=489


N=390

30-D

ay M

ajor

Vas

cula

r C

ompl

icat

ions

Minimum Vessel

Diameter (mm)

8.0/7.0 7.0 8.0/7.0 7.0 6.0/6.5 6.0

*Definitions vary across studies

Weighted average (n=8987)7.7%

Foundational TAVR Devices Vascular Complications


68.0%

43.0% 41.0% 37.9%22.5%

41.5% 35.7%

12.0%

17.1%12.0% 24.2%

3.7%

11.4%9.0%

0%

20%

40%

60%

80%

100%

Extreme Risk P 1B

N=153

Extreme Risk P 2B

N=225

High Risk P 1A

N=287

Extreme Risk P 2B

N=236


N=872


N=418


N=356

SAPIEN SAPIEN XT CoreValve

30-D

ay P

arav

alvu

lar L

eak

Weighted average (n=5,127)Mild 34% / Moderate-Severe 10%

Foundational TAVR Devices Paravalvular Leak

Transfemoral TAVR DevicesIterative Device Design

Iterative devices have been designed to mitigate complications, simplify the procedure, and improve upon current anatomic exclusions to enable the

treatment of more patients

SAPIEN 3 ACURATE neo

Evolut R Lotus Portico

Frame Nitinol Nitinol CobaltChromium Nitinol Nitinol

PVL Managment Extended Skirt Adaptive Seal PET Fabric Skirt Pericardial cuff Pericardial skirt

Annular Range 18-30 mm 20-27 mm 16-28 mm 19-27 mm 21-27 mm

Positioning Recapturable Recapturable -- Recapturable --

Caliber 14 Fr/ 16 Fr equiv. 18 Fr 14 Fr / 16 Fr 18 Fr / 19 Fr 18 Fr

Real-World Evidence BaseNew Transfemoral Valves

• A literature search was conducted to identify studies reporting procedural and 30-day outcomes for groups of patients treated

with new valves in real-world practice

• The rates of paravalvular leak, new pacemaker implantation, stroke, and major vascular complications were tabulated and the weighted average was calculated for each

valve type

389

1273

1960

5232

6300

0 1000 2000 3000 4000 5000 6000

Portico

ACURATE Neo

Lotus

Evolut R

SAPIEN 3

Patients With Data Reported

Real-World Evidence BaseNew Transfemoral Valves

45 unique cohorts were identified through the literature search, representing over 15,000 patients treated with new valves in real-world practice

0.0%

3.0%4.0%

1.9%

5.5%

2.7%1.4%

4.0%2.7%

6.8%

3.0%

0%

2%

4%

6%

8%

10%

CE

Stud

y

N=6

0

FORW

ARD

In

teri

m A

naly

sis

N=3

00

US

IFU

N=1

51

SAV

I Reg

istr

y

N=1

,000

CE

Stud

y

N=2

20

P2 S

3 IR

N

=1,0

78

P2 S

3 H

R/ER

N

=583

S3 C

E IR

N

=101

S3 C

E

N=1

50

REPR

ISE

II

N=2

50

RESP

ON

D

N=1

,014

30-D

ay A

ll St

roke

1Manoharan, et al., J Am Coll Cardiol Intv 2015; 8: 1359-67; 2Moellman, et al., presented at PCR London Valves 2015; 3Linke, et al., presented at PCR London Valves 2015; 4Kodali, et al., Eur Heart J 2016; doi:10.1093/eurheartj/ehw112; 5Vahanian, et al., presented at EuroPCR 2015; 6Webb, et. al. J Am Coll Cardiol Intv 2015; 8: 1797-806;

7DeMarco, et al, presented at TCT 2015; 8Meredith, et al., presented at PCR London Valves 2015; 10Falk, et al., presented at EuroPCR 2016

Weighted average (n=5,547)~3.5%

• In contemporary practice, the overall stroke rate remains around 3.5%

TAVR Stroke Rates with Contemporary Devices

Presenter

Presentation Notes

I added the FORWARD and US IFU data in the Medtronic section and updated the weighted average to~3%

New Permanent PacemakersReal-World Evidence

• The rate of new permanent pacemaker implantation is sensitive to device type

• The rates are typically around 15% with Evolut R and SAPIEN 3, and approximately 2x higher with the Lotus valve

30.2%

18.2%

13.4%

8.0% 6.4%

0%

5%

10%

15%

20%

25%

30%

35%

Lotus … Evolut R … SAPIEN 3 …ACURATE Neo …Portico …

New

Per

man

ent P

acem

aker

(Wei

ghte

d A

vera

ges)

Moderate / Severe Paravalvular LeakReal-World Evidence

• The Lotus valve virtually eliminates moderate or severe PVL

• Other valves have brought the rates to ~5% or less

6.1%

3.8% 3.5%

2.3%

0.5%

0%

1%

2%

3%

4%

5%

6%

7%

Evolut R …ACURATE Neo …Portico … SAPIEN 3 … Lotus …

Mod

erat

e /

Seve

re P

VL

Wei

ghte

d A

vera

ges

Major Vascular ComplicationsReal-World Evidence

4.8%

3.8%

2.4% 2.4%

0.7%

0%

1%

2%

3%

4%

5%

6%

SAPIEN 3 (N=6,300)

Portico (N=389)

Lotus (N=1,960)

Evolut R (N=5,232)

ACURATE Neo (N=1,273)

Maj

or V

ascu

lar C

ompl

icat

ions

(W

eigh

ted

Ave

rage

)

Major vascular complications have come down under 5% across all valve types

Access TrendsUnited States 2012-2016

1Carroll, et al., presented at TCT 2016

• The preferred access site has been dynamic in the US as the regulatory landscape has changed

• With the introduction of Evolut R and SAPIEN 3, more than 90% of TAVRs are performed through the TF approach

93%

0

20

40

60

80

100

% o

f TA

VR

Proc

edur

es

femoral transapical transaortic other

FDA Approval (High Risk):

CoreValve Sapien XT

FDA Approval (High Risk):

Evolut R SAPIEN 3

• Increased use of the transfemoral approach has facilitated a simpler procedure, shown by the decreased use of general anesthesia in favor of

conscious sedation

• Wide variation in anesthesia mode likely reflects geographical differences and individual physician preferences

AnesthesiaNew Valves

Multicenter cohorts with >200 patients

37.0%60.2% 72.1%

17.8%32.9%

84.5%

40.1%

0%20%40%60%80%

100%

FORW

ARD

(N=3

00)

IMPL

AN

TERS

Re

gist

ry

(N

=264

)

STS

/ TV

T Re

gist

ry

(N

=3,8

10)

RELE

VA

NT

Regi

stry

(N=2

25)

RESP

ON

D

(N=9

96)

UK

Reg

istr

y

(2

28)

PART

NER

2 S

3

(N=1

,661

)

SOU

RCE

3

(N=1

,947

)

Evolut R Lotus SAPIEN 3

% G

ener

al A

nest

hesi

a

NR


6.7%

4.1% 4.6% 4.3%5.5%

4.0%4.9%

0%

2%

4%

6%

8%

10%

Extreme Risk P 1B

N=179

Extreme Risk P 2B

N=276

High Risk P 1A

N=348

Extreme Risk P 2B

N=284


N=1,011


N=489


N=390

30-D

ay A

ll St

roke


Foundational TAVR Devices Stroke


3.4%5.9%

3.8%6.8%

8.5%

21.6%19.8%

0%

10%

20%

30%

Extreme Risk P 1B

N=179

Extreme Risk P 2B

N=276

High Risk P 1A

N=348

Extreme Risk P 2B

N=284


N=1,011


N=489


N=390

30-D

ay P

erm

anen

t Pac

emak

er


Foundational TAVR Devices New Permanent Pacemaker Implantation


16.2% 15.2%

11.0%9.5%

7.9% 8.2%5.9%

0%

5%

10%

15%

20%

Extreme Risk P 1B

N=179

Extreme Risk P 2B

N=276

High Risk P 1A

N=348

Extreme Risk P 2B

N=284


N=1,011


N=489


N=390

30-D

ay M

ajor

Vas

cula

r C

ompl

icat

ions

Minimum Vessel

Diameter (mm)

8.0/7.0 7.0 8.0/7.0 7.0 6.0/6.5 6.0

*Definitions vary across studies

Weighted average (n=8987)7.7%

Foundational TAVR Devices Vascular Complications


68.0%

43.0% 41.0% 37.9%22.5%

41.5% 35.7%

12.0%

17.1%12.0% 24.2%

3.7%

11.4%9.0%

0%

20%

40%

60%

80%

100%

Extr

eme

Risk

P 1B

N=1

53Ex

trem

e Ri

sk

P

2B

N

=225

Hig

h Ri

sk

P 1A

N=2

87

Extr

eme

Risk

P

2B

N

=236

Inte

rmed

iat

e Ri

sk

P 2A

N=8

72Ex

trem

e Ri

sk

U

S Pi

vota

l

N=4

18

Hig

h Ri

sk

U

S Pi

vota

l

N=3

56

30-D

ay P

arav

alvu

lar L

eak

Weighted average (n=5,127)Mild 34% / Moderate-Severe 10%

Foundational TAVR Devices Paravalvular Leak

trans catheter aortic valve replacement · discuss future developments in tavr. 5 16.5 million...

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