Severe Aortic Valve Disease:TAVR in Four Ages and Four Etiologies

Age 25 y/o Congenital, 50 y/o Bicuspid, 75 y/o Rheumatic, 100 y/o Degenerative

Samin K. Sharma, MD, FACC, FSCAIDirector Clinical & Interventional Cardiology

President Mount Sinai Heart NetworkDean, International Clinical Affliliations

Anandi Lal Sharma Professor of Medicine (Cardiology)

Cardiovascular InstituteMount Sinai Hospital, New York

COI: No relationship to disclose for this presentation

Aortic Stenosis

Normal 3-4 cm2

AS: - mild >1.5 cm2

- moderate 1.0-1.5 cm2

- severe <1.0 cm2

- critical <0.7 cm2

Etiology:Congenital: unicuspid (25 y/o)

bicuspid (50 y/o)tricuspid

Acquired: rheumatic (75 y/o)calcific deg (100y/o)↑cholesterolemiarheumatoid

Aortic valve area:

5% at 70 yrs10% at 80 yrs18% at 90 yrs

Ross J, Braunwald E. Circulation 1968; 38: 61-67.

Treatment Choices for AS:SAVR TAVR BAV

Sapien

CoreValve

Transcatheter Aortic Valves Intervention: TAVR vs SAVRSurgical risk is a continuum (STS risk score)

Low-risk Intermediate-risk High-risk Extreme-risk Too-sick~30% ~20% ~20% ~20% ~10%

STS <3-4%

Operable AS pts

3-4 to 8-10% 10-15% >15% >50%

159 86 70 44 31 15163 91 71 46 31 15

Mea

n G

radi

ent (

mm

Hg) Valve Area (cm²)

N =

EOAMean Gradient

Error bars = ± 1 Std Dev

PARTNER Trial: Aortic Mean Gradient & Valve Area

PARTNER Trial Cohort B:Inoperable Extreme Risk

Makkar et al., NEJM 2012;366:1696

Rate of Death (N=358)

20%

CoreValve Extreme Risk:No Randomization

1 Year Mortality (N=487)

Popma et al, JACC 2014;63:1972

PARTNER Trial Cohort A:Primary Endpoints at 3-Yr

Kodali et al., NEJM 2012;366:1686

Death from Any Cause

Major drawback:ES TAVR had 2x the Stroke rates vs. SAVR

TAVR SAVR

Death from Any Cause

CoreValve Trial High Risk:Primary Endpoints at 3-Yr

Deeb et al., JACC 2016;67:2565

PARTNER 2A Trial: Clinical Endpoints (ITT) at 2 Years

0

5

10

15

20

25

30

19.316.7

9.5

6.28.6

11.8

3.8

21.1

18.0

8.96.4 5.5

10.3

6.2

Death/stroke Death All stroke Disabling Major vasc PPM AKIstroke compl

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

p=0.33

p=0.45

p=0.67

p=0.83

p=0.005p=0.29

p=0.02%

Leon et al., N Engl J Med 2016;374:1609

SURTAVI Trial: Clinical Outcomes

TAVR (n=864) Surgery (n=796)

%

0

5

10

15

20

25

Primary endpoint Death Stroke Disabling stroke MACCE

12.611.4

6.2

2.6

18.6

14.0

11.6

8.4

4.5

18.6

24 Months

Reardon et al., N Engl J Med 2017;376:1321

One Trial OUS: Notion Trial (Completed)- CoreValve

TAVR for Low Risk AS patientsSTS mortality risk of <3%

Two Trials in US have started: PARTNER-3 of Sapien-3 vs SAVR (n=1228)

Evolut-R CoreValve vs SAVR (n=1200)Trials

NOTION Trial: Clinical Outcomes at 4-5 Years

Sondergaard, ePCR, ESC 2017

0

20

40

60

PrimaryEndpoint

Death Stroke MI PPMImplantation

ValveEndocarditis

29.1

20.0

6.8 7.7

43.7

4.3

30.2

23.0

7.3 7.8 9.05.9

p=0.56

p=0.47

p=<0.001

p=0.87p=0.85

TAVR (n=145)SAVR (n=135)

%

280 patients with severe AS at low surgical risk for SAVR or TAVR with self-expanding CoreValve

p=0.47

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 < 3%, TF only)

Symptomatic Severe Calcific Aortic StenosisAge <65yrs

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)

Medtronic TAVR in Low Risk PatientsTrial Design & leaflet Sub-study

Patient Population: Low Risk Cohort Determined by Heart Team to be low surgical risk

Primary Endpoint: Safety: Death, all stroke, life-threatening bleed,

major vascular complications or AKI at 30 days

Efficacy: Death or major stroke at 2 yrs

Sample Size: ~1200 Subjects

Follow-up Evaluations: 30-days, 6-month , 18-month, and 1 through for 5 years

Number of Sites: Up to 80 sites

Transcatheter Aortic Valves Replacement (TAVR)Current Indications: Symptomatic AS

STS: <3% 3-4 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)

TAVR/SAVR

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

FDA approved two RCT of low risk AS for both Sapien-3 and Evolut-R vs SAVR are ongoing

Recommendations for Choice of Interventions in AS

Nishimura et al., J Am Coll Cardiol 2017;70:252

I

SURTAVI

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=0.07 p=0.08 p=0.21

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

TAVR in Evolution (2017+)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 (Early TAVR)

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