TAVR in Intermediate & Low Risk Patients 643 628 604TF Surgery 595 577 569 557 538 TF TAVR p (log...

TAVR in

Intermediate & Low Risk Patients

Prakash Balan, MD, JD, FACC, FSCAI

Assistant Professor

Interventional Cardiology

The University of Texas Health Science Center Houston

McGovern Medical School

Disclosures • Member PARTNER Case

Review Board

• No relevant financial

interests


TAVR High Risk

(STS > 8%)

PARTNER

+

COREVALVE US

PIVOTAL

SAVR/TA

VR

Intermediate Risk

(STS 4-8%)

PARTNER 2

+

SURTAVI

SAVR

Low Risk

(STS < 4%)

PARTNER 3

+

COREVALVE EVOLUT

LOW RISK

TAVRinPerspective

EarlyTAVRPioneers

-PhilippBonhoeffer-

2000:Firsthumanimplant(RVtoPAconduit)

-HeningRudAndersen-

1989:Firstporcineimplant

Valve

Technology

SAPIEN

SAPIEN XT

SAPIEN 3

Sheath

Compatibility

Available

Valve Sizes

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

PARTNER SAPIEN Platforms Device Evolution

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

23mm 26mm

*First Implant Oct 30, 2012

29mm*

April 16, 2002; FIM-TAVI, Transseptal

15 min Post-TAVI


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%)

The PARTNER 2A Trial Study Design

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

From Craig R. Smith on behalf of PARTNER Trial Investigators, ACC, April 2, 2016, Chicago, IL.


Purpose—PARTNER 2A

To compare the safety and effectiveness of the

second generation

SAPIEN XT TAVR system

with conventional surgery

in intermediate-risk patients using rigorous

clinical trial methodologies.

From Craig R. Smith on behalf of the PARTNER Trial Investigators, ACC, April 2, 2016, Chicago, IL.

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

Characteristic TAVR

(n = 1011)

Surgery

(n = 1021) p-value

Age - yrs 81.5 ± 6.7 81.7 ± 6.7 0.63

Male - % 54.2 54.8 0.79

STS Score - % 5.8 ± 2.1 5.8 ± 1.9 0.29

NYHA Class III or IV - % 77.3 76.1 0.53

CAD - % 69.2 66.5 0.20

Prior CABG - % 23.6 25.6 0.33

Cerebrovascular Disease - % 32.1 31.0 0.60

PVD - % 27.9 32.9 0.02

Baseline Patient Characteristics Demographics and Vascular Disease


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

alit

y o

r D

isab

ling

Stro

ke (

%)



1

775 718 709 685 663 652 644 634 612

775 643 628 604 595 577 569 557 538

TF TAVR

TF Surgery

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

TF TAVR

TF Surgery

Months from Procedure Number at risk:

All-

Cau

se M

ort

alit

y o

r D

isab

ling

Stro

ke (

%)



Intermediate Risk Operable

(PII S3i)

High Risk Operable / Inoperable

(PII S3HR)

Symptomatic Severe Aortic Stenosis

ASSESSMENT by Heart Valve Team

n = 1076 Patients

n = 583 Patients

ASSESSMENT: Optimal Valve Delivery Access

ASSESSMENT: Optimal Valve Delivery Access

SAPIEN 3

2 Single Arm Non-Randomized Historical-Controlled Studies

Transfemoral (TF)

TF TAVR SAPIEN 3

TAA TAVR SAPIEN 3

Transapical / Transaortic (TA/TAo)

TF TAVR SAPIEN 3

PI A SAPIEN

PII A SAVR

Transfemoral (TF)

TAA TAVR SAPIEN 3

Transapical / Transaortic (TA/TAo)

Susheel Kodali on behalf of PARTNER Trial Investigators. Clinical and Echocardiographic Outcomes at 30 Days with the

SAPIEN 3 TAVR System in Inoperable, High-Risk and Intermediate Risk AS Patients. ACC 2015, San Diego.

The PARTNER II S3 Trial Study Design


Baseline Patient Characteristics S3i Patients

Average STS =

5.3% (Median 5.2%)

TF, 89%

TA, 7%

TAo, 4%

N = 1076

4.1%

32.2% 43.7%

20.0%

20 mm 23 mm 26 mm 29 mm

Average Age =

81.9yrs

Male 62%

Female 38%

Susheel Kodali on behalf of PARTNER Trial Investigators. Clinical and Echocardiographic Outcomes at 30 Days with the SAPIEN 3 TAVR System in Inoperable, High-Risk and Intermediate Risk AS Patients. ACC 2015, San Diego.


1.6 1.1 1.0 0.9 0

20

40

60

80

100

S3HR S3i

All-Cause Cardiovascular

5.4 1.6 3.3 0.8

S3HR S3i

All-Cause Cardiovascular

Transfemoral Transapical / Transaortic

%

Mortality: S3HR & S3i At 30 Days (As Treated Patients)

491 947 92 125

Susheel Kodali on behalf of PARTNER Trial Investigators. Clinical and Echocardiographic Outcomes at 30 Days with the SAPIEN 3 TAVR System in Inoperable, High-Risk and Intermediate Risk AS Patients. ACC 2015, San

Diego.


Pre-sp

ecified

non-inf

eriority

margin

= 7.5%

-10 -8

-6 -4

-2 0

2 4

6 8

10

Primary

Non-In

feriorit

y Endpo

int Met

Weight

ed Differ

ence

-9.2%

Upper 1

-sided 9

5% CI

-6.0%

Non-Inf

eriority

p-value

< 0.001

Favors

TAVR

Favors

Surgery

Primary

Endpo

int - No

n-inferi

ority

Death, Stroke, or AR ≥ Mod at 1 Year (VI)

From Vinod H. Thourani on behalf of the PARTNER Trial Investigators, ACC, April 3, 2016, Chicago, IL.


From Vinod H. Thourani on behalf of the PARTNER Trial Investigators, ACC, April 3, 2016, Chicago, IL.


PatientFlow

9

ContinuedAccessStudy(CAS)290patients

15notattempted:-1died- 2withdrewconsent- 11physicianwithdrew- 1pendingprocedure

TAVRattemptedimplant:N=275

TAVRimplantedgroup:N=274

1notimplanted

TAVRITTgroup:N=879

TAVRimplantedgroup:N=863 SAVRimplantedgroup:N=794

*Themodifiedintention-to-treat(mITT)populationincludesallsubjectswithanattemptedprocedure

SAVRITTgroup:N=867

2notimplanted1wenttoSAVR

2surgicalpatientsreceivedTAVR

TAVRmITT*group:N=864

15notattempted:-4died- 6withdrewconsent- 5physicianwithdrew

71notattempted:-4died- 43withdrewconsent- 23physicianwithdrew- 1losttofollow-up

SAVRmITT*group:N=796

1notimplanted2wenttoTAVR

1TAVRpatientreceivedSAVR

RandomizedControlledTrial(RCT)1746patients

Age,years 79.7± 6.1 79.9± 6.2 79.0± 6.1

STSPROM,% 4.5± 1.6 4.4± 1.5 4.1± 1.5

n(%)ormean±SD RCT* CAS

SAVR(N=796) TAVR(N=864) TAVR(N=275)

Malesex 438(55.0) 498(57.6) 127(46.2)

Bodysurfacearea,m2 1.9± 0.2 1.9± 0.2 1.9± 0.2

LogisticEuroSCORE,% 11.6± 8.0 11.9± 7.6 9.1± 6.5

Diabetesmellitus 227(34.8) 295(34.1) 100(36.4)

Serumcreatinine>2mg/dl 17(2.1) 14(1.6) 2(0.7)

Priorstroke 57(7.2) 57(6.6) 16(5.8)

PriorTIA 46(5.8) 58(6.7) 8(2.9)

Peripheralvasculardisease 238(29.9) 266(30.8) 71(25.8)

Pre-existingIPG/ICD 72(9.9) 87(10.1) 19(6.9)

BaselineCharacteristics

10*mITTpopulation;nosignificantdifferenceinanybaselinecharacteristics

From VanMeighem VM. Transcathether Aortic Valve Replacement with a Self-Expanding Prosthesis or Surgical Aortic Valve Replacement in

Intermediate Risk Patient. TCT 2017.


796 723 678

864 813 772

All-CauseMortalityorDisablingStroke

15%

10%

5%

20%

25%

30%

All-CauseM

ortalityor

DisablingStroke TAVR

SAVR

0%

0 2 4 6

MonthsPost-Procedure

8 10 12

No.atRiskSAVR

TAVR13

P-value(log-rank)=0.55

8.5%7.8%

From VanMeighem VM. Transcathether Aortic Valve Replacement with a Self-Expanding Prosthesis or Surgical Aortic Valve Replacement in

Intermediate Risk Patient. TCT 2017.


The PARTNER 3 TrialStudy 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=200)

CT Imaging Sub-Study (n=200)

Actigraphy/QoL Sub-Study (n=200)


Trial Flow

All randomized n=280

ITT SAVR n=135

ITT TAVR n=145

Died prior to procedure n=1

IMPLANTED TAVR n=139

IMPLANTED SAVR n=135

AT TAVR n=142

AT SAVR n=134

Crossover

SAVR to

TAVR

n=1

Crossover

TAVR to

SAVR

n=1

Crossover

TAVR to

SAVR

n=3

Not implanted n=2

Died prior to procedure n=3

Thyregod HGH. An All Comers Randomized Clinical Trial Comparing Transcatheter with Surgical Aortic Valve Replacement in Patient

with Aortic Valve Stenosis. ACC 2015.

Nordic Aortic Valve Intervention (NOTION) Trial

Objective: Compare TAVR vs. SAVR in patients > 70 years eligible for

surgery (all-comers population)

Primary outcome: Composite rate of death from any cause, stroke or myocardial

infarction at 1 year (VARC II-defined)

Secondary outcomes: Safety and efficacy (NYHA), echocardiographic outcomes

(VARC II-defined)

Design: Prospective, multicenter, non-blinded, randomized trial

Enrollment period: December 2009 - April 2013

Baseline Characteristics

Characteristic, % or mean ± SD

TAVR n=145

SAVR n=135

p-value

Age (yrs) 79.2 ± 4.9 79.0 ± 4.7 0.71

Male 53.8 52.6 0.84

Society of Thoracic Surgeons (STS) Score 2.9 ± 1.6 3.1 ± 1.7 0.30

STS Score < 4% 83.4 80.0 0.46

Logistic EuroSCORE I 8.4 ± 4.0 8.9 ± 5.5 0.38

NYHA class III or IV 48.6 45.5 0.61


Death from Any Cause, Stroke or Myocardial Infarction

at 1 Year in As-Treated Population

Thyregod HGH. An All Comers Randomized Clinical Trial Comparing Transcatheter with Surgical Aortic Valve Replacement in Patient

with Aortic Valve Stenosis. ACC 2015.


Garg A et al. Transcatheter Aortic Valve Replacement versus Surgical Valve

Replacement in Low-Intermediate Surgical Risk Patients. J Invasive Cardiol

2017; 29 (6): 209-216.

Witberg G et al. Transcatheter versus Surgical Aortic

Valve Replacement in Patients at Low Surgical Risk: A

Meta-Analysis of Randomized Trials and Propensity

Score Matched Observational Studies. Cardiac Cath &

Interven. Published online 2/8/18.


CONCLUSION

• Await RCT data among low risk

• TAVR appropriate in intermediate risk patients

• Each with advantages and disadvantages:

• SAVR: AFib, AKI

• TAVR: PPM, PVL

• Heart Team


“The management of patients with complex severe VHD is best

achieved by a Heart Valve Team composed primarily of…”

• Cardiologists

• Surgeons

• Structural valve interventionalists

• Cardiovascular imaging specialists

• Cardiovascular surgeons

• Anesthesiologists

• Nurses

Old Paradigm Emerging Paradigm

Interventionalist

Patient

Cardiologist Surgeon

Patient

Interventionalist

Cardiologist Surgeon

NishmuraRA,etal.Circulation.2014;129.

Multidisciplinary Heart Valve Team AHA/ACC 2014

Guidelines

TAVR in Intermediate & Low Risk Patients 643 628 604TF Surgery 595 577 569 557 538 TF TAVR p (log...

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