Jeffrey W. Moses , MDJeffrey W. Moses , MD

Columbia University Medical CenterColumbia University Medical CenterCardiovascular Research FoundationCardiovascular Research Foundation

New York CityNew York City

The State of TAVR -PARTNER: The State of TAVR -PARTNER: From Concept to Mortality BenefitFrom Concept to Mortality Benefit

Presenter Disclosure Information forPresenter Disclosure Information forU Minn Grand Rounds; U Minn Grand Rounds;

Jeffrey W. Moses , M.D.Jeffrey W. Moses , M.D.

Equity Relationship: Equity Relationship: ClaretClaret

Equity Relationship: Equity Relationship: ClaretClaret

At Least 30% of Patients with Severe At Least 30% of Patients with Severe Symptomatic AS are “Untreated”!Symptomatic AS are “Untreated”!

5968 70

4052

69

55

4132 30

6048

3145

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Bouma1999

Iung* 2004

Pellikka2005

Charlson2006

Bach 2009

Spokane(prelim)

Vannan(Pub.

Pending)

Severe Symptomatic Aortic StenosisSevere Symptomatic Aortic StenosisPercent of Cardiology Patients TreatedPercent of Cardiology Patients Treated

1.1. Bouma B J et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999;82:143-148Bouma B J et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999;82:143-148

2.2. Iung B et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. European Heart JournalIung B et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. European Heart Journal2003;24:1231-1243 (*includes both Aortic Stenosis and Mitral Regurgitation patients)2003;24:1231-1243 (*includes both Aortic Stenosis and Mitral Regurgitation patients)

3.3. Pellikka, Sarano et al. Outcome of 622 Adults with Asymptomatic, Hemodynamically Significant Aortic Stenosis During Prolonged Follow-Up. Circulation 2005Pellikka, Sarano et al. Outcome of 622 Adults with Asymptomatic, Hemodynamically Significant Aortic Stenosis During Prolonged Follow-Up. Circulation 2005

4.4. Charlson E et al. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis2006;15:312-321Charlson E et al. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis2006;15:312-321

AVRAVR

No AVRNo AVR

Under-treatment Under-treatment especially especially

prevalent among prevalent among patients patients

managed by managed by Primary Care Primary Care physiciansphysicians

SEVERE AORTIC STENOSISSEVERE AORTIC STENOSIS

AORTIC VALVE AORTIC VALVE REPLACEMENT SURGERYREPLACEMENT SURGERY

BALLOON AORTIC BALLOON AORTIC VALVULOPLASTYVALVULOPLASTY

PT. REFUSALSPT. REFUSALS

NOT REFERREDNOT REFERRED

? ASYMPTOMATIC? ASYMPTOMATIC

Potential Patients for Potential Patients for Transcatheter Aortic Valve TherapyTranscatheter Aortic Valve Therapy

HIGH-RISKHIGH-RISK PATIENTSPATIENTS

TechnologyTechnologyReviewReview

TAVR 2011TAVR 2011

Early Catheter-Based AV DesignsEarly Catheter-Based AV Designs

The Davis valve (1965)

The Andersen valve (1992)

DiastoleSystole

1 2 3

Alain Cibier Sketches (1990)Alain Cibier Sketches (1990)

First generation – polyurethaneFirst generation – polyurethane

Second generation – bovine pericardiumSecond generation – bovine pericardium

PVT-Edwards PVT-Edwards Percutaneous Heart ValvePercutaneous Heart Valve

Cribier-Edwards DeviceCribier-Edwards Device

• equine pericardial valveequine pericardial valve• stainless steel stentstainless steel stent• 23mm and 26mm diameters23mm and 26mm diameters• balloon-expandableballoon-expandable• AVA = 1.7-1.9 cmAVA = 1.7-1.9 cm22

Dr. Alain CribierDr. Alain CribierFirst-in-Man PIONEERFirst-in-Man PIONEER

April 16, 2002April 16, 2002

Percutaneous Transcatheter Implantation of Percutaneous Transcatheter Implantation of an Aortic Valve Prosthesis for Calcific an Aortic Valve Prosthesis for Calcific Aortic Stenosis Aortic Stenosis First Human Case Description First Human Case Description Alain Cribier, MD; Helene Eltchaninoff, MD; Assaf Bash, PhD; Alain Cribier, MD; Helene Eltchaninoff, MD; Assaf Bash, PhD; Nicolas Borenstein, MD; Christophe Tron, MD; Fabrice Bauer, MD; Nicolas Borenstein, MD; Christophe Tron, MD; Fabrice Bauer, MD; Genevieve Derumeaux, MD; Frederic Anselme, MD; FranGenevieve Derumeaux, MD; Frederic Anselme, MD; Franççois ois Laborde, MD; Martin B. Leon, MD Laborde, MD; Martin B. Leon, MD

AHA; Nov, 2002AHA; Nov, 2002Conclusions—Conclusions— Nonsurgical implantation of a prosthetic heart Nonsurgical implantation of a prosthetic heart valve can be successfully achieved with immediate and midterm valve can be successfully achieved with immediate and midterm

hemodynamic and clinical improvement.hemodynamic and clinical improvement.

Sapien XT + NovaFlex Delivery SystemSapien XT + NovaFlex Delivery System

18 Fr profile18 Fr profile

TransfemoralTransfemoral TransapicalTransapical

Transcatheter AVRTranscatheter AVRTrans-apical Access RouteTrans-apical Access Route

The The PARTNER PARTNER

TrialTrial

TAVR 2011TAVR 2011

Published on-line September 22, 2010Published on-line September 22, 2010@ NEJM.org and print October 21, 2010@ NEJM.org and print October 21, 2010

On behalf of the Executive Committee, the Investigator Sites,On behalf of the Executive Committee, the Investigator Sites,and the courageous patients who participated in the PARTNER trial! and the courageous patients who participated in the PARTNER trial!

N = 179

N = 358InoperableInoperable

StandardTherapyStandardTherapy

ASSESSMENT: Transfemoral

Access

ASSESSMENT: Transfemoral

Access

Not In StudyNot In Study

TF TAVRTF TAVR

Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority)

Co-Primary Endpoint: Composite of All-Cause Mortalityand Repeat Hospitalization (Superiority)

Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority)

Co-Primary Endpoint: Composite of All-Cause Mortalityand Repeat Hospitalization (Superiority)

1:1 Randomization1:1 Randomization

VS

YesYes NoNo

N = 179

TF TAVRTF TAVR AVRAVR

Primary Endpoint: All-Cause Mortality at 1 yr(Non-inferiority)

Primary Endpoint: All-Cause Mortality at 1 yr(Non-inferiority)

TA TAVRTA TAVR AVRAVR VS

VS

N = 248 N = 104 N = 103N = 244

PARTNER Study DesignPARTNER Study Design

Symptomatic Severe Aortic StenosisSymptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate3,105 Total Patients Screened

ASSESSMENT: High-Risk AVR Candidate3,105 Total Patients Screened

Total = 1,057 patients

2 Parallel Trials: Individually Powered

N = 699 High RiskHigh Risk

ASSESSMENT: Transfemoral

Access

ASSESSMENT: Transfemoral

Access

Transapical (TA)Transapical (TA)Transfemoral (TF)Transfemoral (TF)

1:1 Randomization1:1 Randomization1:1 Randomization1:1 Randomization

YesYes NoNo

Executive Committee Executive Committee

Michael MackJohn Webb

Murat TuzcuCraig Miller

Marty LeonJeff Moses

Craig Smith

Lars Svensson

Transcatheter AVRTranscatheter AVRHybrid OR-Cath LabHybrid OR-Cath Lab

A unique collaborative experience!A unique collaborative experience!

Inoperable: Patient Characteristics - 1Inoperable: Patient Characteristics - 1

CharacteristicCharacteristic TAVITAVIn=179n=179

Standard RxStandard Rxn=179n=179

P valueP value

Age - yrAge - yr 83.1 ± 8.6 83.2 ± 8.3 0.95

Male sex (%) 45.8 46.9 0.92

STS ScoreSTS Score 11.2 ± 5.8 12.1 ± 6.1 0.14

Logistic EuroSCORE 26.4 ± 17.2 30.4 ± 19.1 0.04

NYHA I or II (%) III or IV (%)

7.892.2

6.193.9

0.680.68

CAD (%) 67.6 74.3 0.20

Prior MI (%) 18.6 26.4 0.10

Prior CABG (%) 37.4 45.6 0.17

Prior PCI (%) 30.5 24.8 0.31

Prior BAV (%) 16.2 24.4 0.09

CVD (%) 27.4 27.5 1.00

CharacteristicCharacteristic TAVITAVIn=179

Standard RxStandard Rxn=179

P valueP value

PVD (%)PVD (%) 30.3 25.1 0.29

COPDCOPD Any (%)Any (%) O2 dependent (%)O2 dependent (%)

41.321.2

52.525.7

0.040.38

Creatinine >2mg/dL (%)Creatinine >2mg/dL (%) 5.6 9.6 0.23

Atrial fibrillation (%)Atrial fibrillation (%) 32.9 48.8 0.04

Perm pacemaker (%) Perm pacemaker (%) 22.9 19.5 0.49

Pulmonary HTN (%)Pulmonary HTN (%) 42.4 43.8 0.90

Frailty (%)Frailty (%) 18.1 28.0 0.09

Porcelain aorta (%)Porcelain aorta (%) 19.0 11.2 0.05

Chest wall radiation (%)Chest wall radiation (%) 8.9 8.4 1.00

Chest wall deformity (%)Chest wall deformity (%) 8.4 5.0 0.29

Liver disease (%)Liver disease (%) 3.4 3.4 1.00

Inoperable: Patient Characteristics - 2Inoperable: Patient Characteristics - 2

11ryry Endpt - All Cause Endpt - All Cause MortalityMortality

Numbers at RiskNumbers at Risk

TAVITAVI 179179 138138 122122 6767 2626 Standard RxStandard Rx 179179 121121 8383 4141 1212

All

-cau

se m

ort

alit

y (%

)

Months

HR [95% CI] =0.54 [0.38, 0.78]

P (log rank) < 0.0001

Standard Rx

TAVI

Numbers at RiskNumbers at Risk

TAVITAVI 179179 138138 122122 6767 2626 Standard RxStandard Rx 179179 121121 8383 4141 1212

Standard Rx

TAVI

All

-cau

se m

ort

alit

y (%

)

Months

∆ at 1 yr = 20.0%NNT = 5.0 pts

50.7%

30.7%

11ryry Endpt - All Cause Endpt - All Cause MortalityMortality

OutcomeOutcome 30 Days 30 Days n=179n=179

TAVIStandard

RxP-value

  1 Year 1 Year n=179n=179

TAVIStandard

RxP-value

Clinical Outcomes at 30 Days & 1 YearClinical Outcomes at 30 Days & 1 Year

Myocardial infarction

All (%) 0 0 . 0.6 0.6 1.00 Peri-procedural (%

0 0 . 0 0 .

Stroke or TIA

All (%) 6.7 1.7 0.03 10.6 4.5 0.04 TIA (%) 0 0 . 0.6 0 1.00

Minor stroke (%) 1.7 0.6 0.62 2.2 0.6 0.37

Major stroke (%) 5.0 1.1 0.06 7.8 3.9 0.18

Death (all) or major stroke (%) 8.4 3.9 0.12 33.0 50.3 0.001

Repeat hospitalization (%) 5.6 10.1 0.17 22.3 44.1 <.0001

Death (all) or repeat hosp (%) 10.6 12.3 0.74 42.5 70.4 <.0001

Death

All (%) 5.0 2.8 0.41 30.7 49.7 0.0004

Cardiovascular (%) 4.5 1.7 0.22 19.6 41.9 <.0001

OutcomeOutcome 30 Days 30 Days n=179n=179

TAVIStandard

RxP-value

  1 Year 1 Year n=179n=179

TAVIStandard

RxP-value

Clinical Outcomes at 30 Days & 1 YearClinical Outcomes at 30 Days & 1 Year

Acute kidney injury

Creatinine >3 mg/dL (%) 0 1 1.00 1.1 2.8 0.45 RRT (%) 1.1 1.7 1.00 1.7 3.4 0.50

Cardiac re-intervention

BAV (%) 0.6 1.1 1.0 0.6 36.9 <.0001

Re-TAVI (%) 1.7 na 1.7 na

AVR (%) 0 1.7 0.25 1.1 9.5 <.0001

Endocarditis (%) 0 0 . 1.1 0.6 0.31

Vascular complications

All (%) 30.7 5.0 <.0001 32.4 7.3 <.0001

Major (%) 16.2 1.1 <.0001 16.8 2.2 <.0001

Bleeding - major (%) 16.8 3.9 <.0001 22.3 11.2 0.007

Arrhythmias

New atrial fibrillation (%) 0.6 1.1 1.00 0.6 1.7 0.62

New pacemaker (%) 3.4 5.0 0.60 4.5 7.8 0.27

NYHA Class Over TimeNYHA Class Over TimeSurvivorsSurvivors

P = 0.68 P < 0.0001 P < 0.0001 P < 0.0001

I II III IV

TAVI Standard Rx TAVI Standard Rx TAVI Standard Rx TAVI Standard Rx

Per

cen

t

TreatmentTreatmentVisitVisit

Baseline 30 Day 6 Month 1 Year

PARTNER QOL AnalysesPARTNER QOL Analyses

TAVI not only TAVI not only adds years to life, adds years to life,

but also,but also, adds life to years! adds life to years!

TAVI not only TAVI not only adds years to life, adds years to life,

but also,but also, adds life to years! adds life to years!

$50,000 per LY$50,000 per LY

Cost = $79,837 LE = 1.59 years

ICER = $50,212/LYG

Cost = $79,837 LE = 1.59 years

ICER = $50,212/LYG

$100,000 per LY$100,000 per LY

Cost-Effectiveness of TAVR vs. Control Lifetime Results

Main Main Outcomes:Outcomes:High RiskHigh Risk

TAVR 2011TAVR 2011

0

0.1

0.2

0.3

0.4

0.5

0 6 12 18 24

TAVR

AVR

Months

348 298 260 147 67

351 252 236 139 65

No. at Risk

TAVR

AVR

26.8

24.2

Primary Endpoint:All-Cause Mortality at 1 Year

HR [95% CI] =0.93 [0.71, 1.22]

P (log rank) = 0.62

All-Cause MortalityAll-Cause MortalityTransfemoral (N=492)Transfemoral (N=492)

Months

244 215 188 119 59

248 180 168 109 56

No. at Risk

TAVR

AVR

26.4

22.2

HR [95% CI] =0.83 [0.60, 1.15]

P (log rank) = 0.25

104 83 72 28 8

103 72 68 30 9

29.0

27.9

TAVR

AVR

MonthsNo. at Risk

All-Cause MortalityAll-Cause MortalityTransapical (N=207)Transapical (N=207)

HR [95% CI] =1.22 [0.75, 1.98]

P (log rank) = 0.41

PARTNER 1A :30 Day Outcomes (AT)

Transfemoral Transapical

3.7

P=0.045

TF AVR

Death

8.2

AVRTF

Major Stroke

2.51.4

P=0.09

TF AVR

Death Stroke

5.4

9.5 8.7

TA AVR

Death

7.6

AVRTA

Major Stroke

7.0

4.4

TA AVR

Death Stroke

15.4

10.9

0

2

4

6

8

10

12

14

16

18

NYHA Functional Class

Baseline 1 Year6 Months30 Days

Pat

ien

ts S

urv

ivin

g,

%

I II III IV

P = 1.00 P < 0.001 P = 0.05 P = 0.75

Mean Gradient - AVR

Mean Gradient - TAVR

Peak Gradient - AVR

Peak Gradient - TAVR

Mea

n a

nd

Pea

k G

rad

ien

tA

s-T

reat

ed T

rial

Arm

s (m

mH

g)

50

40

30

20

60

70

10

0

80

Baseline 30 Days 6 Months 1 YearTAVR

n = 327AVR

n = 301TAVR

n = 287AVR

n = 231TAVR

n = 246AVR

n = 170TAVR

n = 227AVR

n = 159

Echo FindingsEcho FindingsAortic Valve GradientsAortic Valve Gradients

Paravalvular Aortic Regurgitation

P < 0.001 P < 0.001 P < 0.001

1 Year6 Months30 Days

Pat

ien

ts,

%

None Trace Mild Moderate Severe

TAVR - The FutureTAVR - The FutureMy Rosey ProphecyMy Rosey Prophecy

Surgery – The “PAST”

TAVR – The “Future”

In 5-10 years, most patients In 5-10 years, most patients with severe AS requiring AVRwith severe AS requiring AVR

will be treated using TAVR!will be treated using TAVR!