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The TAVI Journey: Update on Evidence

And Future trials

Philippe Généreux, MD

TCT Argentina 2016

Thursday October 13th

Interventional Cardiologist, Hôpital du Sacré-Coeur de Montréal, Canada

Director, Angiographic Core Laboratory, Cardiovascular Research

Foundation, New York, NY

Co-Director, Structural Heart Program, Morristown Medical Center

Columbia University Medical Center, New York, NY

Disclosure Statement of Financial Interest

Within the past 12 months, I or my spouse/partner have had a

financial interest/arrangement or affiliation with the

organization(s) listed below

• Edwards LifeSciences

Consultant, Speaker Fees, Proctor, Research grant

• Boston Scientific

Research grant

• Abbott Vascular

Consultant, Speaker Fees

• Cardiovascular System Inc.

Consultant, Speaker Fees, Research Grant

• Soundbite Medical Inc.

Consultant

Agenda

• The Current Evidence

• The Future Evidence!

Current Guidelines for TAVR?

Severe Aortic Stenosis

• Class I

TAVR is recommended in patients who meet

an indication for AVR who have a prohibitive

risk for surgical AVR and a predicted post-

TAVR survival greater than 12 months

• Class IIA

TAVR is a reasonable alternative to surgical

AVR in patients who meet an indication for

AVR and who have high surgical risk for

surgical AVR

Nishimura et al. J Am Coll Cardiol. 2014; 63(22):e57-185

TAVR is Available in More Than 65 Countries Around the World

>250,000 total implants to date

Estimated Global TAVR Procedure Growth

SOURCE: Credit Suisse TAVI Comment –January 8, 2015. ASP assumption for 2024 and 2025 based on analyst model. Revenue split assumption in 2025 is 45% U.S., 35% EU, 10% Japan, 10% ROW

In the next 10 years, TAVR growth will increase X4!

NO ONE Likes Surgery

(of any kind)!

SAVR Tissue SAVR Mech TF TAVR TA TAVR

TAVR now accounts for 32% of all AV

replacements

SOURCE: FY2015 MedPAR, all cases on file regardless of IPPS status

Medicare AV Cases in 2015

TAVR “Underutilization” is Largely Driven by Variation in Health Policy and Reimbursement

9

SOURCE: Eurostat, U.S. Census Bureau, Industry estimates

2015 Country TAVR Penetration Total TAVR Units / Millions of Inhabitants

Total index hospitalization cost* (TF TAVR)

Length of stay (TF TAVR)

1 2

*Index hospitalization cost adjusted to reflect commercial device price Reynolds et al.,Cost Effectiveness of Transcatheter Aortic Valve Replacement Compared with Standard Care. Circulation. 2012;125:1102-1109 Babaliaros et al., Comparison of a Minimalist Approach Transfemoral TAVR with Standard Approach Transfemoral TAVR. J Am Coll Cardiol. 2014;63(12_S)

Procedural efficiencies are reducing TAVR costs in the US

$76.063 $71.118 $64.772 $62.587 $59.893

$45.485

PARTNER Cohort B2

2012 MedPAR

2013 MedPAR

2014 MedPAR

2015 MedPAR

Emory optimized approach

10.1 days 8.1 days 7.9 days 7.1 days 6.4 days 3.0 days

TAVR in 2016…for Who?

Who are we currently treating?

The severe AS/TAVR Population

• Old…very old…

• Frail…

• Lot of comorbidities…

Prior CABG

CKD

Severe COPD

PVD

Remission of cancer

But still alive and enjoying life !

TAVR Categories (risk is a continuum)

Operable AS patients

TAVR in 2016

TAVR

preferred

Extr

Risk*

* Extreme risk = “inoperable”

Low

Risk

Surgery (AVR)

Not Yet

~65%

Intermed

Risk ¿

“equipoise”

~25%

High

Risk

TAVR or

AVR

OK

~10%

Fu

tile

No

Too

Sick

Current TAVR

Clinical Use

Potential TAVR Population My Favorite Drink = Double-shot Mocha Latte

79.9%

13.9%

6.2%

Intermediate risk

(STS 4-8%)

Low risk

(STS <4%)

High risk

(STS > 8%)

STS database 2002-2010 (141,905 pts)

Potential TAVR Population


79.9%

13.9%

6.2%

Intermediate risk

(STS 4-8%)

Low risk

(STS <4%)

High risk

(STS > 8%)

STS database 2002-2010 (141,905 pts)

PARTNER 1A, 1B CoreValve Extreme/High-Risk

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

Numbers at Risk

Standard Rx 179 121 85 62 46 27 17

TAVR 179 138 124 110 101 88 70

All Cause Mortality (ITT) Inoperable or Extreme risk: PARTNER 1B

30.7%

50.8%

43.0%

68.0%

54.1%

80.9%

All

Cause M

ort

alit

y (

%)

Months

HR [95% CI] = 0.53 [0.41, 0.68]

p (log rank) < 0.0001

20.1%

25.0%

26.8%

NNT = 5.0 pts

NNT = 4.0 pts

NNT = 3.7 pts

Standard Rx

TAVR

All-Cause Mortality (ITT) All Patients High Risk: PARTNER 1A

No. at Risk

HR [95% CI] =

1.04 [0.86, 1.24]

p (log rank) = 0.76

TAVR 348 262 228 191 154 61

SAVR 351 236 210 174 131 64

62.4%

67.8%

Error Bars Represent 95%

Confidence Limits


79.9%

13.9%

6.2%

Intermediate risk

(STS 4-8%)

Low risk

(STS <4%)

High risk

(STS > 8%)

STS database 2002-2010 (141,905 pts)

PARTNER 2A, S3i SURTAVI, UK TAVI

1

1011 918 901 870 842 825 811 801 774

1021 838 812 783 770 747 735 717 695

Number at risk:

TAVR

Surgery

p (log rank) = 0.253

HR [95% CI] = 0.89 [0.73, 1.09]

TAVR

Surgery

0

10

20

30

40

50

19.3%

21.1%

14.5%

16.4%

0 3 6 9 12 15 18 21 24

6.1%

8.0%

Primary Endpoint (ITT) All-Cause Mortality or Disabling Stroke

Months from Procedure

All

-Cau

se M

ort

ality

or

Dis

ab

lin

g S

tro

ke (

%)

1

762 717 708 685 663 652 644 634 612

722 636 624 600 591 573 565 555 537

p (log rank) = 0.04

HR: 0.78 [95% CI: 0.61, 0.99]

16.3%

20.0%

0 0 3 6 9 12 15 18 21 24

0

10

20

30

40

50

15.8%

7.5%

11.7%

4.5%

TF Primary Endpoint (AT) All-Cause Mortality or Disabling Stroke

All

-Cau

se M

ort

ality

or

Dis

ab

lin

g S

tro

ke (

%)

TF TAVR

TF Surgery

Months from Procedure Number at risk:

TF TAVR

TF Surgery

Sapien 3 THV

Intermediate Risk

Valve

Technology

SAPIEN

SAPIEN XT

SAPIEN 3

Sheath

Compatibility

Available

Valve Sizes

23 mm 26 mm 20 mm 23 mm 26 mm 29 mm

SAPIEN Platforms in PARTNER Device Evolution

22-24F 16-20F 14-16F

23 mm 26 mm 29 mm

Bovine pericardial tissue • Scalloped leaflet shape

• CE ThermaFix* process is

intended to minimize the

risk of calcification

Outer skirt • PET outer skirt designed to

reduce paravalvular leak

Low frame height • Respects the

cardiac anatomy

Frame design • Enhanced frame geometry

for low delivery profile

• High radial strength for

circularity

Inner Skirt • Polyethylene

terephthalate (PET)

SAPIEN 3 THV

Unadjusted Time-to-Event Analysis All-Cause Mortality (AT)

1077 1043 1017 991 963

944 859 836 808 795

All

-Ca

us

e M

ort

ality

(%

)

0

10

20

30

40

7.4%

13.0%

1.1%

4.0%

Number at risk:

S3 TAVR

P2A Surgery


SAPIEN 3 TAVR

P2A Surgery

0 3 6 9 12

Mo

rtality

an

d S

tro

ke (

%) Surgery (TF)

SAPIEN XT TF

SAPIEN 3 TF

0

9.9%

18.3%

14.3%

0

10

20

30

40

3 6 9 12

951 896 877 855 829

722 619 607 582 573

762 701 690 666 643

Number at risk:

SAPIEN 3 TF

SAVR TF

SAPIEN XT TF


PARTNER 2A/S3i Mortality and Stroke - TF (AT)

Other Unadjusted Clinical Outcomes At 30 Days and 1 Year (AT)

Events (%)

30 Days 1 Year

TAVR

(n = 1077)

Surgery

(n = 944)

TAVR

(n = 1077)

Surgery

(n = 944)

Re-hospitalization 4.6 6.8 11.4 15.1

MI 0.3 1.9 1.8 3.1

Major Vascular Complication 6.1 5.4 --- ---

AKI (Stage III) 0.5 3.3 --- ---

Life-Threatening/Disabling

Bleeding 4.6 46.7 --- ---

New Atrial Fibrillation 5.0 28.3 5.9 29.2

New Permanent Pacemaker 10.2 7.3 12.4 9.4

Re-intervention 0.1 0.0 0.6 0.5

Endocarditis 0.2 0.0 0.8 0.7

0%

20%

40%

60%

80%

100%

TAVR Surgery TAVR Surgery

Severe

Moderate

Mild

None/Trace

Paravalvular Regurgitation 3-Class Grading Scheme (VI)

P < 0.001 P < 0.001

No. of echos 30 Days 1 Year

P2A Surgery 755 610

S3i TAVR 992 875

Mild

39.8%

≥ Moderate

1.5%

• The conclusions from the PARTNER 2A

randomized trial and this propensity score analysis

provide strong evidence that in intermediate-risk

patients with severe aortic stenosis, SAPIEN 3

TAVR compared with surgery improves clinical

outcomes and is the preferred therapy.

The PARTNER 2A and S3i Trial Clinical Implications


79.9%

13.9%

6.2%

Intermediate risk

(STS 4-8%)

Low risk

(STS <4%)

High risk

(STS > 8%)

STS database 2002-2010 (141,905 pts)

NOTION All Comers, PARTNER 3 LR, CoreValve LR

All-

cau

se M

ort

alit

y M

I, o

r St

roke

(%

) P value (log rank) = 0.26

Months Post-procedure

SAVR

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

TAVR

15.7%

11.3%

6.3%

11.9%

No. at risk: TAVR SAVR

143 134

133 118

129 115

118 105

15%

20%

10%

5%

0%

NOTION: Death (all-cause), Stroke or MI at 1 Year (as-treated)

Low Risk PARTNER Trial Balloon Expandable THV

The PARTNER 3 Trial Study Design

1:1 Randomization

(n=1228)

TF - TAVR

(SAPIEN 3)

Surgery

(Bioprosthetic Valve)

Follow-up: 30 days, 6 mos, 1 year and annually through 10 years

CT Imaging Sub-Study (n=200)

Low Risk ASSESSMENT by Heart Team (STS < 4%, TF only)

Symptomatic Severe Calcific Aortic Stenosis

PRIMARY ENDPOINT:

Composite of all-cause mortality, all strokes,

or re-hospitalization at 1 year post-procedure

Bicuspid Valves

(n=100)

ViV (AV and MV)

(n=100)

PARTNER 3

Registries

Alternative Access

(n=100)

(TA/TAo/Subclavian)

Actigraphy/QoL Sub-Study (n=100)

CT Imaging Sub-Study (n=200)

Actigraphy/QoL Sub-Study (n=100)


79.9%

13.9%

6.2%

Intermediate risk

(STS 4-8%)

Low risk

(STS <4%)

High risk

(STS > 8%)

After PARTNER 3 Completion… You will need a 2nd Coffee!

• 1st Final Thoughts…

TAVR Journey - 2016

The ultimate role of TAVR is yet to be

determined. But we can foresee a future

time when the use of TAVR (vs. surgery)

will be a risk-benefit assessment based

upon clinical and anatomic factors, and

not an imprecise risk stratification model!

Are We There Yet?

TAVR New Indications?

New Indications for TAVR?

• Where SAVR already succeeded

Symptomatic Severe AS for intermediate-risk

Symptomatic Severe AS for low-risk

Bicuspid

Pure Aortic Regurgitation

Concomitant AS and CAD

Concomitant AS and other valvular/heart disease

• Where SAVR makes sense but is struggling…

Asymptomatic Severe AS

Symptomatic Moderate AS

Severe AS in shock

Why TAVR could go where SAVR did not?

How TAVR different than SAVR?

• Less invasive

• Less peri-procedural mortality and co-

morbidity

• Better tolerability in case of instability

• Immediate recovery

• Larger effective orifice area (EOA)

with TAVR vs. SAVR

Aortic Stenosis Spectrum:

Future TAVR Indications

Mild

AS

Moderate AS

Symptoms -

Moderate AS

Symptoms +

Severe AS

Symptoms -

Severe AS

Symptoms +

PARTNER

Trials

2016 ~2020

Strategy Trials

• EARLY TAVR:

Severe Asymptomatic AS

• TAVR-UNLOAD:

Moderate AS with Heart Failure

Severe Asymptomatic Aortic Stenosis

Recommendations and Levels of Evidence for Diagnosis, Follow-up, and Timing of

Aortic Valve Replacement in Patients With Asymptomatic Severe Aortic Stenosis ACC/AHA ESC/EACTS

Indications for aortic valve replacement

Left ventricular ejection fraction 50% I, B I, C

Undergoing other cardiac surgery I, B I, C

Symptoms on exercise test clearly related to aortic stenosis I, B I, C

Decreased exercise tolerance IIa, B IIa, C

Exercise fall in systolic blood pressure IIa, B IIa, C

Very severe AS (PV5.0 m/s [ACC]; >5.5m/s [ESC] and low surgical risk IIa, B IIa, C

Rate of PV progression ≥0.3 m/s per year and low surgical risk IIb, C IIa, C

Repeatedly markedly elevated natriuretic peptide and low surgical risk - IIb, C

Increase of MG with exercise by >20 mmHg and low surgical risk - IIb, C

Excessive LVH in the absence of hypertension and low surgical risk - IIb, C

Diagnostic

Transthoracic echocardiography as the initial diagnostic modality I, B -

Exercise testing IIa, B -

Exercise echocardiography IIa, B -

Follow-up

Echocardiography every 6-12 months 1, C - ACC = American College of Cardiology; AHA = American Heart Association; EACTS = European Association for Cardio-Thoracic Surgery;

European ESC = European Society of Cardiology


Vahanian et al. Eur Heart J. 2012; 33(19):2451-96

3 Class I indications…3 Class IIa indications…

Level of evidence B or C

No Randomized trial

ACC/AHA and ESC/EACTS Guidelines

Asymptomatic Severe AS

MG≥40mmhg, AVA≤ 1.0 cm2 and EF >50%

Exercise Testing (ACC/AHA Class IIa)

Limiting Symptoms

Angina

Syncope

Dyspnea

ACC/AHA Class I

ESC Class I

Abnormal SBP

response (drop or

<20mmhg rise)

Increase in MG with exercise by >20 mm Hg

Exercise Imaging (ACC/AHA class IIa) Decrease exercise

tolerance

ACC/AHA Class IIa

ESC Class IIa

PV ≥5m/s (ACC/AHA) or ≥5.5m/s

(ESC): Class IIa

PV progression≥0.3m/s/year:

ACC/AHA IIb and ESC Class IIa

Severe LVH: ESC Class IIb

Repeatedly markedly elevated BNP:

ESC Class IIb

ESC Class IIb

+ + -

If Stress test and Stress Echo normal:

Clinical and Echo follow-up 6-12 months ACC/AHA Class I


Vahanian et al. Eur Heart J. 2012; 33(19):2451-96

Lung et al. Eur Heart J 2003; 24, 1231–1243

“In severe AS, an exercise test was performed in only 5.7%

of patients with no symptoms…”

“This under-use may be explained by an insufficient

implementation of the current guidelines and fear of

complications or inexperience in exercise testing…”

Sudden Death


~1-2%/year

Peri-operative Mortality

SAVR

~1-5%

Why Early SAVR In Asymptomatic

Severe AS is Rarely Performed?

TAVR may be a better option for Asymptomatic patients

Généreux et al. J Am Coll Cardiol 2016;67:2263–88; Thourani et al. Lancet 2016; 387: 2218–25; Thyregod et al. J Am Coll Cardiol 2015;65:2184–94

30-day Mortality

PARTNER trial 2A Intermediate PM

Sapien 3 TAVR SAVR

1.1% 4.0%

30-day Mortality

Notion Trial all-comers

Core Valve TAVR SAVR

2.1% 3.7%

Asymptomatic Severe AS:

Rationale for Early AVR

Pros • Reduce irreversible

myocardial damage and subsequent consequences

• Decreased operative risk for asymptomatic patients

• AS progression highly variable; potential for a very rapid deterioration

• Risk of late (or too late) symptoms reporting

• Sudden death without preceding symptoms

Cons • Mortality potentially low among

a specific subset of low-risk and truly asymptomatic patients with normal stress test and stress echo

• Frequent follow-up could potentially identified patients ready for AVR in a timely fashion

• Inherent mortality and morbidity of AVR

• Long-term complication of AVR (anticoagulation, need for re-op, endocarditis, thrombosis, etc.)

Practical Issues with

“Watchful Waiting” Strategy

• Clinicians still have a fear of stress test with Severe AS patients; low penetration and underused

• Stress Imaging requires expertise and specific set-up that most community hospitals don’t have

• Sub-optimal follow-up and lost of follow-up are frequent

• Many sudden deaths occurred in Asx patients with no Class I indication of AVR and no preceding symptoms

• “Wishful Thinking” Strategy…

What is the Prevalence of

Asymptomatic Severe AS?

• ~40-50% of all Severe AS from major echo databases 1,2,3

~10-20% are bicuspid

~20-25% have multiple valve disease, clinically significant CAD, prior AVR

• Isolated Asymptomatic Severe AS represents ~25-30% of all Severe AS referred to Echo lab

• ~500,000 patients >65 years old in US4

3Kitai et al. Heart 2011;97:2029e2032. 1Pellikka et al. Circulation. 2005;111:3290-3295

2Pai et al. Ann Thorac Surg 2006;82:2116 –22 4Source U.S. Census Bureau, 2014 National Projections.

What is the Prognosis of Asx Severe AS Patients?

Généreux et al. J Am Coll Cardiol 2016;67:2263–88

Studies Comparing AVR vs. Observation in

Asymptomatic Severe AS Patients; N=2,486

Authors AS definition N Age Female Follow-up

(median)

Pellikka et

al.1990

Severe AS;

Doppler PV 4m/s

143

30 AVR

113 Medical

72 (mean)

40 to 94 38%

AVR 21 m

Medical 20 m

Pai et al.

2006

Severe AS

AVA <0.8cm2

338

99 AVR

239 Medical

71±15 49% 3.5 y

Kang et al.

2010

Very severe AS

AVA 0.75 cm2 AND PV

4.5 m/s or a

MG 50 mmHg

197:

102 AVR

95 Medical

63±12 50% AVR 1265 d

Medical 1769 d

Taniguchi et

al. 2015

Severe AS

AVA: <1cm2

MG: >40mmhg

PV: >4m/s

1808:

291 AVR

1517

Medical

AVR

71.68.7

Medical

77.89.4

60% 1361 d


All-Cause Mortality

AVR vs. Medical Therapy in

Asymptomatic Severe AS; N=2,486

Unadjusted: ~3.5 fold increase in all-cause Mortality


Stress Test

Severe Asymptomatic AS?

Studies Moderate-Severe AS Severe AS only

% Abnormal

Stress Test n N

% Abnormal

Stress Test n N

Takeda et al. 2001 27% 13 49

Amato et al. 2001 67% 44 66

Alborino et al. 2002 60% 18 30

Das et al. 2003 29% 19 65

Das et al. 2005 37% 46 125

Lancellotti et al. 2005 38% 26 69

Peidro et al. 2007 66% 67 102

Marechaux et al. 2007 48% 24 50

Lancellotti et al. 2008 47% 60 128

Lafitte et al. 2009 65% 39 60

Marechaux et al. 2010 27% 51 186

Rajani et al. 2010 15% 3 20 39% 7 18

Donal et al. 2011 33% 69 207

Levy et al. 2014 28% 12 43

Total 286 784 212 434

% Abnormal Stress test Range: 15-66% Pooled: 36.5% Range: 28-67% Pooled: 48.8%

Abnormal Stress Test in Asx Severe AS:

Range: 26-67%

~50% Abnormal Stress Test

Abnormal Stress Test in Asx AS


Abnormal stress test associated with

~6 fold increase in Cardiac Death

Rafique et al. Am J Cardiol 2009;104:972–977

Should and could we recommend

an early intervention strategy for

“truly” Asymptomatic Severe

Aortic Stenosis patients?

‘‘Low hospital mortality tends to justify a policy of

accepting patients for operation earlier in the natural

progression of their disability, because it is recognized

that there is a definite risk of rapid deterioration or

sudden death in the earlier policy of deferring

operation patients until their disability had become

definite and progressive and until their cardiac reserve

was nearly depleted.”

McGoon DC, Pestana C, Moffitt EA. Arch Surg.1965;Nov,91:779-86.

1925-1999

Evaluation of Transcatheter Aortic Valve Replacement Compared to SurveilLance for Patients with Severe Aortic Stenosis With or

Without SYmptoms: EARLY-TAVR trial

EARLY-TAVR trial

Philippe Généreux, MD, Patrick T. O’Gara, MD; Michael Mack, MD; Robert O. Bonow, MD; Philippe Pibarot, DVM, PhD, Linda D. Gillam, MD; Jeroen J. Bax, MD, PHD; Brian Lindman, MD; Raj Makar, MD, David J. Cohen, MD; Martin

B. Leon, MD

Principal Investigators:

Philippe Généreux, MD, Patrick T. O’Gara, MD

Primary endpoint (superiority):

2-year composite of death, all stroke, and cardiovascular repeat hospitalization

Treadmill Stress Test

Randomization1:1 Stratified by PV (<5m/s vs. >5m/s)

Stratified by STS (<3 vs. >3)

Stress Test Abnormal

High risk EARLY-TAVR Randomized Trial

Follow-up: Clinical and 2D-TTE: 30 days, 1 year, 2 years, and yearly up to 5 years

2D-TTE before TAVR and 1 year post TAVR

TF-TAVR Medical Observation

Asymptomatic Severe AS per questionnaire and 2D-TTE (PV ≥4m/s and AVA ≤1 cm2) Exclusion if patients clinically symptomatic, EF<50%, concomitant surgical indications, bicuspid, or STS >10%

Stress Test Normal

Intermediate risk Low risk

P3 trial TAVR as indicated

EARLY-TAVR Registry

CT Scan and Coronarography TF-TAVR eligibility

Clinical and 2D-TTE trial eligibility

Moderate AS With heart Failure


Future Indication

Low flow

Low gradient

low EF no CR

Low flow

Low gradient

Low EF with CR

Low flow

low gradient

normal EF

Mild

AS

Moderate AS

Symptoms -

Moderate AS

Symptoms +

Severe AS

Symptoms -

Severe AS

Symptoms +

EARLY-TAVR PARTNERs

Treatment of Low Flow AS

Guidelines Recommendations

ESC/EACTS

2012

ACC/AHA

2014

Classic LF AS with CR

Classic LF AS w/o CR

Paradoxical LF

II a, C

II b, C

II a, C*

* “only after careful confirmation of severe AS”

II a, B

II a, B

II a, C#

# “if clinical, hemodynamic, or anatomic data support valve obstruction as

the most likely cause for symptoms”

Nishimura et al. J Am Coll Cardiol. 2014; 63(22):e57-185 Vahanian et al. Eur Heart J. 2012; 33(19):2451-96

But what if you “only” have moderate AS and still

have recurrent symptoms of heart failure despite

optimal medical therapy?

International Multicenter Randomized

TAVR UNLOAD Trial

Heart Failure LVEF < 50% but

>20% NYHA ≥ 2

Optimal HF therapy (OHFT)

Moderate AS

R

TAVR + OHFT

OHFT alone

Follow-up: 1 month 6 months

1 & 2 years

Clinical endpoints Symptoms

Echo QoL

TAVR UNLOAD trial Concept

PIs: Nicolas Van Mieghem, Martin B. Leon

Sponsor: Edwards Lifesciences

http://www.google.nl/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://imgkid.com/netherlands-football-2014-flag.shtml&ei=B99MVYnUMeaO7AaF8YDACA&psig=AFQjCNF9bVNN5DTQs4AHK7Ytp_QsDW_1ew&ust=1431187564599156

Primary endpoint

• Hierarchical occurrence of

All-cause death

Disabling stroke

Hospitalizations related to heart failure, aortic

valve disease or non-disabling stroke

Change in KCCQ

*To be analyzed with the Finkelstein-Schoenfeld method, 99% Power

If FS endpoint is statistically significant, proceed with MACCE endpoint, with sufficient (2-sided α = 0.05)

power if 40% endpoints are reached


Functional Classification

Severe AS

Symptoms +

PARTNERs

Low Int. High

-Ext.

Mild

AS

Moderate AS

Symptoms -

Moderate AS

Symptoms +

Severe AS

Symptoms -

TAVR-UNLOAD EARLY-TAVR

2016 ~2020

TAVR Active

Surveillance TAVR

P. Généreux TVT 2016

Conclusions: TAVR Future Indications

• TAVR will go where SAVR went if

anatomically suitable…

• TAVR may go where SAVR struggled,

failled, or never been before!


Moderate Symptomatic AS

Unstable severe AS patients

With which TAVR devices?

TAVR Systems

Global Inventory (#25)

• Sapien 3

• Evolut R

• Symetis

• Direct Flow

• Lotus

• Portico

• Engager

• Jena Valve

• Centera

• Venus A Valve

• Shanghai Valve

• Trinity

• Colibri

• Inovare

• Thubrikar

• Valve Medical

• Syntheon Verso

• Triskele

• BioValve

• MyVal

• HLT

• NVT (Nautilus)

• J - Valve

• Xeltis

• Zurich TEHV

Current

Leaders!

Future

Contenders?

TAVR at TCT 2016?

Tuesday, November 1st

• 5 years Echo follow-up TAVR vs. SAVR

Pamela S Douglas, MD

• Quality of Life PARTNER Trial 2A

David Cohen, MD

• SENTINEL Trial

Susheel Kodali, MD

TCT | Washington, DC | November 1, 2016

Mid Term Hemodynamic Trends and Between Echo Changes in Transcatheter Aortic Valves in the PARTNER 1 Trial:

Pamela S. Douglas, MD

on behalf of The PARTNER Trial Investigators

and The PARTNER Publications Office

Five Year Results

Background and Aims

• TAVR is a safe and effective treatment for severe aortic stenosis

• THV long term durability, potential for deterioration, and any

implications for patient outcomes, are incompletely understood

• The PARTNER 1 trial provides a rich, existing data resource to

address the following two aims:

– Determine the longitudinal hemodynamic profile of THVs and

factors associated with early and mid-term trends

– Assess the incidence and clinical correlates of large interval

changes in valve parameters

TCT | Washington, DC | November 1, 2016

Health Status Benefits of Transcatheter vs. Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis at Intermediate Surgical Risk

Results From The PARTNER 2 Trial

David J. Cohen, MD on behalf of The PARTNER Trial Investigators

and The PARTNER Publications Office

Study Objectives

1. To compare health-related quality of life outcomes

among patients with severe AS and intermediate

surgical risk treated with either TAVR or SAVR

2. To determine whether the QOL benefits of TAVR

vs. SAVR vary over time

3. To examine whether the QOL benefits of TAVR

vs. SAVR in the intermediate risk population differ

according to access site or other patient

characteristics

SENTINEL Study Design (TAVR RCT)

Population: Subjects with severe AS with

clinical indications for TAVR with the

Edwards Sapien THV/XT/S3 or Medtronic

CoreValve/Evolut-R

N=296 subjects randomized 1:1:1

at sites in the U.S and Germany.

SAFETY ARM

TAVR with Sentinel

TEST ARM

TAVR with Sentinel

CONTROL ARM

TAVR only

Safety Follow-up

Histopathology

Safety Follow-up MRI Assessments Neurological and

Neurocognitive Tests

Primary (superiority) Efficacy Endpoint: Reduction in median total new lesion

volume assessed by 3T DW-MR by baseline subtraction (3-7 days)

Primary (non-inferiority) Safety Endpoint: Occurrence of all MACCE at 30 days

US Co-PIs:

Samir Kapadia

Susheel Kodali

German Co-PI:

Axel Linke

RCT

Thanks!

Low risk Intermediate risk High risk

Documents

The TAVI Journey: Update on Evidence And Future trialscaci.org.ar › assets › uploads › tavi_perspectiva_dr_generaux.pdf · The TAVI Journey: Update on Evidence And Future trials