Symptomatic Severe AS (LF/LG/NEF/LEF)TAVR in Patients at High, Moderate (SS) or

Low Risk (Dr Joseph Bavaria)

Samin K Sharma, MD, FACC, FSCAI

Director Clinical & Interventional Cardiology

Anandi L Sharma Professor of Medicine

President Mount Sinai Heart Network

Mount Sinai Hospital, NY

NY CV Symposium 2016

Treatment Choices for AS:

SAVR TAVR BAV

Sapien

CoreValve

MR, 94 yrs F

Presentation: Presented on March 28th 2014 with progressive

exertional dyspnea and fatigue – NYHA class III. Pt was medically

stabilized and work-up revealed severe AS

PMH: Hypertension, GIB on aspirin

Medications: None

TTE: Severe aortic stenosis; mean gradient = 44 mmHg, Doppler

valve area = 0.6 cm2, Ao peak CW velocity = 4.2 m/sec, LVEF =

65%

EKG : Normal sinus rhythm

R/L Cath 03/28/14 and course: Severe 2V+LM CAD, normal LV

systolic LV function, mild pulmonary hypertension, severe AS and

mild AI

Echo Images: Annulus Measurement

22 Aortic annular size (mm)

0.41 Aortic valve area (cm2)

0.211 Aortic valve area index (cm2/m2)

48 Mean gradient (mmHg)

4.4 Peak velocity (m/sec)

62 LVEF (%)

Echo Image

CT Angiography: Minimum diameters of 0.4 x 0.7 cm for the

Right and 0.6 x 0.6 cm for the Left common femoral arteries

STS risk mortality: 8.15%

EuroScore risk: 6.84%

Logistic Euroscore mortality: 15.81%

Course: Patient is determined to be High risk for surgical

AVR+CABG due to advanced age by Heart Team discussion

Contd….

Hence decision was made for percutaneous approach to

Treat both AS and CAD in a staged manner:

Live relay in ACC March 30, 2014

?

SET 1 – RM R3

SET 1 – RM R4

SET 1 – RM R7

SET 1 – RM R9

SET 2 – RM R3

SET 2 – RM R23

SET 3 – RM R7

SET 3 – RM R10

SET 3 – RM R12

SET 3 – RM R13

SET 3 – RM R15

Transcatheter Aortic Valves:

FDA Approved Devices

Aortic Stenosis and Surgical risk

Surgical risk is a continuum (STS risk score)

Low-risk Intermediate-risk High-risk Extreme-risk Too-sick

~30% ~20% ~20% ~20% ~10%

STS <3%

Operable AS pts

3 to 8-10% 10-15% >15% >50%

Direct-aortic (DA)(TA)(TF) Trans-apicalTrans-femoral

Others: Subclavian L or R

Trans-carotid

Trans Venacaval

Various Access Approaches for TAVR

>85-90%

159 86 70 44 31 15

163 91 71 46 31 15

Mean

Gra

die

nt

(mm

Hg

)V

alv

e A

rea (c

m²)

N =

EOA

Mean GradientError bars = ± 1 Std Dev

PARTNER Trial: Aortic Mean Gradient & Valve Area

PARTNER Trial Cohort B:

Inoperable Extreme Risk

Makkar et al., N Engl J Med 2012;366:1696

Rate of Death (N=358)

20%

CoreValve Extreme

Risk: No Randomization

1 Year Mortality (N=489)

Popma et al., J Am Coll Cardiol 2014;63:1972

5 yrs

94%

71%

PARTNER Trial Cohort A: Time-to-Event

Curves for Primary Endpoints at 3-Yrs

Kodali et al., NEJM 2012;366:1686

Death from Any Cause,

Intention-to-Treat Population

Death from Any Cause,

As-Treated Population

CoreValve High Risk Pivotal trial: Primary

Endpoint-- 1 Year All-cause Mortality

19.1%

4.5%

Surgical (N= 357)

14.2%

P = 0.04 for superiority

3.3%

TAVR (N= 390)

0 1 2 3 4 5 6 7 8 9 10 11 12 Months Post-Procedure

All-c

au

se

Mo

rta

lity

(%

)

Adams et al., N Engl J Med 2014;370:1790

CoreValve High-risk Pivotal Trial: 1-Year

Results

%

SAVR (n=357)

TAVR (n=390)

p=0.10

p=0.59

p=<0.001

p=0.004

p=0.03

p=<0.001

Adams et al., N Engl J Med 2014;370:1790

p=<0.001

Any stroke Major stroke AKI PPM Vasc MACCE Life-threatening/

compl disabling bleeding

CoreValve: Echocardiographic Findings

TAVR for Futile AS CasesSTS Morbidity/Mortality risk of >50%

Data from PARTNER IB Trial ES Valve

Makkar et al., NEJM 2012;366:1696

Partner Trial Cohort B: TAVR for Inoperable

Severe Aortic Stenosis; Impact of Co-morbidities

Two Trials: PARTNER IIA (Presented)

SURTAVI Trial (Completed, results pending)

TAVR for Intermediate Risk AS patients

STS mortality risk of 3-4 to 8-10%

PARTNER 2A Trial: Study Design

CR Smith, ACC 2016

Primary Endpoint: All-Cause Mortality or Disabling Stroke at Two Years

Randomized Patients

n = 2032

Symptomatic Severe Aortic Stenosis

ASSESSMENT by Heart Valve Team

Operable (STS ≥ 4%)

TF TAVR

(n = 775)

Surgical AVR

(n = 775) VS.VS.

ASSESSMENT:

Transfemoral Access

Transapical (TA) / TransAortic (TAo)Transfemoral (TF)

1:1 Randomization (n = 482)1:1 Randomization (n = 1550)

TA/TAo TAVR

(n = 236)Surgical AVR

(n = 246)

Yes No

PARTNER 2A Trial: Primary Endpoint (ITT)

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%

Months from Procedure

All

-Ca

use

Mo

rtality

or

Dis

ab

lin

g S

tro

ke

(%

)All-Cause Mortality or Disabling Stroke

Leon M et al. NEJM 2016;374:1609

PARTNER 2A Trial: Primary Endpoint (ITT)All-Cause Mortality or Disabling Stroke

All

-Ca

us

e M

ort

ality

or

Dis

ab

lin

g S

tro

ke

(%

)

Months from Procedure

p (log rank) = 0.05

HR: 0.79 [95% CI: 0.62, 1.00]

16.8%

20.4%

0 3 6 9 12 15 18 21 24

0

10

20

30

40

50

15.9%

7.7%

12.3%

4.9%

TF TAVR

TF Surgery

Leon M et al. NEJM 2016;374:1609

PARTNER 2A Trial: Clinical Endpoints (ITT)

at 2 Years

0

5

10

15

20

25

30

19.3

16.7

9.5

6.2

8.6

11.8

3.8

21.1

18.0

8.9

6.45.5

10.3

6.2

Death/stroke Death All stroke Disabling Major vasc PPM AKI

stroke compl

TAVR (n=1011) SAVR (n=1021)

p=0.33

p=0.45

p=0.67

p=0.83

p=0.005

p=0.29

p=0.02%

Leon M et al. NEJM 2016;374:1609

PARTNER 2A Trial: Severity of PVR at 30 Days and

All-Cause Mortality at 2 Years A

ll-C

au

se M

ort

ality

(%)

Months from Procedure

14.1%

13.5%

34.0%

0

10

20

30

40

50

0 3 6 9 12 15 18 21 24

Overall Log-Rank p = 0.001

Mod/Sev (reference = None/Trace)

p (Log-Rank) < 0.001None/Trace

Mild

Moderate/Severe

Leon M et al. NEJM 2016;374:1609

Sapien-3 Observational Study: The PARTNER 2A and S3i TrialLancet On-line

Sapien-3 Observation Study of TAVR in

Intermediate Risk: Outcomes at 1 Year

Death Stroke Disabling All-cause Rehosp New PPM

stroke death/ stroke

%

Sapien 3 TAVR (n=1077) SAVR (n=944)

VH Thourani, ACC 2016

CoreValve US Pivotal SURTAVI Trial: Design

Severe AS Indication for AVR

Separate randomization for AS+CAD

Heart Team Discussion

• Europe: STS mortality risk score > 3% and < 8%

• US: STS mortality risk score > 4 and < 10%

Suitable for

Randomization1:1 Randomization Non-randomization

Registries

TAVI AVR Control TAVI AVR

Medical

ManagementPrimary Endpoint:

All cause Mortality

and Stroke at 2 yrs Endpoint: All-cause Mortality at 2 yrs

VS

N = 1100

Yes No

N = 220

N = 220

VS

N = 1760

Transcatheter Aortic Valves Replacement (TAVR)

Surgical risk is a continuum: Symptomatic AS

STS: <3% 3 to 8-10% 10-15% 15-50% >50%

Low-risk Intermediate-risk High-risk Extreme-risk Too-sick

~30% ~20% ~20% ~20% ~10%

SAVR vsTAVR

TAVR(PARTNER IIA, SURTAVI?)/ SAVR

TAVR TAVR FUTILE?BAV

Operable AS pts

Pt with prohibitive surgical risk are appropriate

For TAVR even with low STS risk:

- hostile mediastinum, egg-shell aorta, RT

- prior CABG with IM stuck to mediastinum

- severe COPD, extreme frailty

RCTs of low risk AS

for both Sapien-3 and

Evolut-R vs SAVR

have started: Dr Bavaria

Summary of Recommendations for AS:

Choice of Surgical or Transcatheter Intervention

Nishimura et al., J Thorac Cardiovasc Surg 2014;148:e1

TAVR

BAV may provide palliative symptomatic benefit in these pts

I

STS Risk Calculator

No Additional risk or comorbidity

STS Risk Calculator

No Additional risk or comorbidity

STS Risk Calculator

Even a small additional risk: CAD, PAD, LVEF, SCr

Emerging TAVR Devices Involving Improved

Technologies, Potentially Minimizing PVL/AR after TAVR

0.9

2.5

2.8

40.4

7.5

5.4

0.0

10.0

20.0

30.0

40.0

50.0

60.0

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Baseline 1-7 Days 30 Days

Eff

ecti

ve O

rifi

ce A

rea,

cm

2 Mean

Gra

die

nt, m

m H

g

Effective orifice area Mean gradient

N=15

Evolut-R 34 Study: Valve Performance

J Popma, TCT 2016

COREVALVE™

EVOLUT™ R 34 MM

UP TO 30MM AORTIC ANNULUS SIZE

TAVR in Evolution (2016+)

Future Clinical Indications

• Valve-in-valve for bio-prosthetic AV failure

• Predominant Aortic regurgitation (AR, AI)

• Bicuspid aortic valve stenosis

• Low flow-low gradient AS

• Asymptomatic severe AS

• Moderate AS with CHF Class III-IV (Unload TAVR)

Valve in Valve TAVI

Eggebrecht et al., JACC 2011;4:1218

Valve-in-Valve for Bio-Prosthetic AS

Valve-in-Valve for Bio-Prosthetic AS

Valve-in-Valve for Bio-Prosthetic AS

Valve-in-Valve for Bio-Prosthetic AS

Adverse Events Reported with Aortic

Valve-in-Valve Procedures for Failed

Bioprosthesis

Sedaghat et al., Ann Thorac Surg 2016;101:118

Results of Valve-in-Valve Measurements Within

the Edwards Perimount

CoreValve US Clinical Trial: TAVR for Failed Aortic

Bio-prosthesis: All-Cause Mortality or Major Stroke

N=107

GM Deeb – on Behalf of CoreValve US Investigators, TCT 2015

• Internal stent diameter (ID) of SAV

using valve in valve application

developed by Dr. Vinayak Bapat &

UBQO Technology

What is the impact of a

higher mean valve

gradient?

What is driving higher gradient at

discharge?

-Surgical valve size

-Modality of failure (> in stenosis)

-Patient prosthesis mismatch

All-Cause Mortality by

Discharge GradientHemodynamic Outcomes

GM Deeb – on Behalf of CoreValve US Investigators, TCT 2015

CoreValve US Clinical Trial: TAVR for Failed Aortic

Bio-prosthesis- All-Cause Mortality or Major Stroke

N=107

TAVR in Bicuspid Aortic Valve DiseaseClinical Outcomes

Mylotte et al., J Am Coll Cardiol 2014;63:2330

0

10

20

30

40

Mortality Stroke Bleeding Vascularcomplications

Newpacemaker

17.5

2.2

26.6

21.623.2

20.8

2.1

16.7

12.5

16.7

12.5

2.2

31.9

26.4 26.7

%

p=0.12

p=0.99

p=0.07p=0.08 p=0.21

All patients (n=139) Sapien (n=48) CoreValve (n=91)

PARTNER Trial: Event Curves of Death in Pts

Undergoing TAVR & Standard Therapy based on LVEF

Passeri et al., Heart 2015;0:1

Death from Any Cause Stratified

by Baseline LVEF for TAVR

Standard Therapy Stratified by

Baseline LVEF for TAVR

Baron et al., J Am Coll Cardiol 2016;67:2349

One Year Clinical Outcomes after TAVR

Stratified by AVG and LEVF

0

5

10

15

20

25

30

35

40

LVEF <30% 30% ≤ LVEF ≤ 50%

LVEF >50%

33.1

29.4

24.524.222.7

20.9

%

0

5

10

15

20

25

30

35

40

LVEF <30% 30% ≤ LVEF ≤ 50%

LVEF >50%

23.622

16.6

13.5 13.711.2

%

Mortality Heart Failure

AVG <40 mmHg AVG >40 mmHg

CoreValve US Clinical Trial: 1 Year Outcomes

Expanded Use Low

Gradient (<40 mm Hg)

N=159

US Pivotal

Trial

Outcome, % or mean ± SD

LG-NEF

(>50%)

N=113

LG-LEF

(<50%)

N=46

Pivotal Extreme

Risk Trial

N=616

All-cause mortality or stroke 26.0 26.3 27.3

All-cause mortality 21.6 26.3 25.8

All stroke 10.7 4.4 7.6

Major vascular complications 10.7 4.4 8.2

Aortic valve hospitalization 23.4 18.7 20.4

Change in KCCQ score 25.8 ± 23.6 30.5 ± 31.7 27.1 ± 26.1

Mean gradient (mmHg) 6.66 ± 3.04 7.04 ± 2.75 9.11 ± 4.83

Effective orifice area (cm2) 1.84 ± 0.52 1.82 ± 0.63 1.67 ± 0.53

NYHA III/IV (%) 9.2 7.1 10.4

SJ Chetcuti – on Behalf of CoreValve US Investigators, TCT 2015

warfarin

Transcatheter Heart Valve (THV) Thrombosis:

Detection by Multidetector Computed Tomography

Hansson et al., J Am Coll Cardiol 2016;68:2059

& VIV

Cumulative TAVR Procedures: TVT Registry

2012 to 2014 TAVR in USA

Holmes et al., J Am Coll Cardiol 2015

Procedural Performance and Outcome of TAVR since FDA Approval

65% 35%

2016 Projections: ≈3000 TAVR per month in USA

Next 5-7 yrs: >100,000 per year in USA

There is a Range of TAVR Mortality in US

Practice

Risk Adjustment:

Using variables from

the previously

developed TVT in-

hospital mortality

model.

Edwards et al., JAMA, Epub March 9, 2016

TAVR Complications: Transfemoral Population

JD Carroll, ACC 2016

In-Hospital Outcomes - Volume

Mortality Vascular complications Bleeding Complications

P Value for Association

Unadjusted = <0.0001

Adjusted = 0.1494

P Value for Association

Unadjusted = <0.0001

Adjusted = <0.0001

P Value for Association

Unadjusted = <0.0001

Adjusted = <0.0001

Unadjusted

Adjusted

Unadjusted

Adjusted

Unadjusted

Adjusted

Stroke

0

50

100

150

200

250

2010 2011 2012 2013 2014 2015

126

89104

162

201

201

Growth in TAVR Procedures at MSH

2010 to 2015

Major complication: N = 0 1 2 4 7 8

24 %

N

2016 Projection: N=280

2017 Projection: N=380

Structural Heart Webcast Serieswww.structuralheartlivecases.org

2nd Tuesday of the Month

9-10am:Next webcast December

13th 2016

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