Jeffrey W. Moses , MDColumbia University Medical Center

Cardiovascular Research FoundationNew York City

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

Presenter Disclosure Information forU Minn Grand Rounds;

Jeffrey W. Moses , M.D.

Equity Relationship: Claret

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

5968 70

4052

6955

41 32 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 StenosisPercent of Cardiology Patients Treated

1. Bouma B J et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999;82:143-1482. 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 Journal

2003;24:1231-1243 (*includes both Aortic Stenosis and Mitral Regurgitation patients)3. Pellikka, Sarano et al. Outcome of 622 Adults with Asymptomatic, Hemodynamically Significant Aortic Stenosis During Prolonged Follow-Up. Circulation 20054. Charlson E et al. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis2006;15:312-321

AVRNo AVR

Under-treatment especially

prevalent among patients

managed by Primary Care physicians

SEVERE AORTIC STENOSIS

AORTIC VALVE REPLACEMENT SURGERY

BALLOON AORTIC VALVULOPLASTY

PT. REFUSALSNOT REFERRED? ASYMPTOMATIC

Potential Patients for Transcatheter Aortic Valve Therapy

HIGH-RISK PATIENTS

TechnologyReview

TAVR 2011

Early Catheter-Based AV Designs

The Davis valve (1965)

The Andersen valve (1992)

DiastoleSystole

1 2 3

Alain Cibier Sketches (1990)

First generation – polyurethane

Second generation – bovine pericardium

PVT-Edwards Percutaneous Heart Valve

Cribier-Edwards Device

• equine pericardial valve• stainless steel stent• 23mm and 26mm diameters• balloon-expandable• AVA = 1.7-1.9 cm2

Dr. Alain CribierFirst-in-Man PIONEER

April 16, 2002

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

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

hemodynamic and clinical improvement.

Sapien XT + NovaFlex Delivery System

18 Fr profile

Transfemoral Transapical

Transcatheter AVRTrans-apical Access Route

The PARTNER

Trial

TAVR 2011

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

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

N = 179

N = 358Inoperable

StandardTherapy

ASSESSMENT: Transfemoral

Access

Not In Study

TF TAVR

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

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

1:1 Randomization

VS

Yes No

N = 179

TF TAVR AVR

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

TA TAVR AVR VS

VS

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

PARTNER Study Design

Symptomatic Severe Aortic Stenosis

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

Total = 1,057 patients2 Parallel Trials:

Individually Powered

N = 699 High Risk

ASSESSMENT: Transfemoral

Access

Transapical (TA)Transfemoral (TF)

1:1 Randomization1:1 Randomization

Yes No

Executive Committee

Michael MackJohn Webb

Murat TuzcuCraig Miller

Marty LeonJeff Moses

Craig Smith

Lars Svensson

Transcatheter AVRHybrid OR-Cath Lab

A unique collaborative experience!

Inoperable: Patient Characteristics - 1

Characteristic TAVIn=179

Standard Rxn=179 P value

Age - yr 83.1 ± 8.6 83.2 ± 8.3 0.95Male sex (%) 45.8 46.9 0.92STS Score 11.2 ± 5.8 12.1 ± 6.1 0.14Logistic EuroSCORE 26.4 ± 17.2 30.4 ± 19.1 0.04NYHA I or II (%) III or IV (%)

7.892.2

6.193.9

0.680.68

CAD (%) 67.6 74.3 0.20Prior MI (%) 18.6 26.4 0.10Prior CABG (%) 37.4 45.6 0.17Prior PCI (%) 30.5 24.8 0.31Prior BAV (%) 16.2 24.4 0.09CVD (%) 27.4 27.5 1.00

Characteristic TAVIn=179

Standard Rxn=179 P value

PVD (%) 30.3 25.1 0.29COPD Any (%) O2 dependent (%)

41.321.2

52.525.7

0.040.38

Creatinine >2mg/dL (%) 5.6 9.6 0.23Atrial fibrillation (%) 32.9 48.8 0.04Perm pacemaker (%) 22.9 19.5 0.49Pulmonary HTN (%) 42.4 43.8 0.90Frailty (%) 18.1 28.0 0.09Porcelain aorta (%) 19.0 11.2 0.05Chest wall radiation (%) 8.9 8.4 1.00Chest wall deformity (%) 8.4 5.0 0.29Liver disease (%) 3.4 3.4 1.00

Inoperable: Patient Characteristics - 2

1ry Endpt - All Cause Mortality

Numbers at Risk TAVI 179 138 122 67 26 Standard Rx 179 121 83 41 12

All-

caus

e m

orta

lity

(%)

Months

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

P (log rank) < 0.0001

Standard Rx TAVI

Numbers at Risk TAVI 179 138 122 67 26 Standard Rx 179 121 83 41 12

Standard Rx TAVI

All-

caus

e m

orta

lity

(%)

Months

∆ at 1 yr = 20.0%NNT = 5.0 pts

50.7%

30.7%

1ry Endpt - All Cause Mortality

Outcome 30 Days n=179

TAVI Standard Rx P-value

 1 Year n=179

TAVI Standard Rx P-value

Clinical 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

Outcome 30 Days n=179

TAVI Standard Rx P-value

 1 Year n=179

TAVI Standard Rx P-value

Clinical 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 TimeSurvivors

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

Perc

ent

TreatmentVisit

Baseline 30 Day 6 Month 1 Year

PARTNER QOL Analyses

TAVI not only adds years to life,

but also, adds life to years!

$50,000 per LY

D Cost = $79,837 D LE = 1.59

yearsICER = $50,212/LYG

$100,000 per LY

Cost-Effectiveness of TAVR vs. Control Lifetime Results

Main Outcomes:High Risk

TAVR 2011

0

0.1

0.2

0.3

0.4

0.5

0 6 12 18 24

TAVRAVR

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 MortalityTransfemoral (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 MortalityTransapical (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 AVRDeath

8.2

AVRTFMajor Stroke

2.51.4

P=0.09

TF AVRDeath Stroke

5.4

9.5 8.7

TA AVRDeath

7.6

AVRTAMajor Stroke

7.0

4.4

TA AVRDeath Stroke

15.4

10.9

02468

1012141618

NYHA Functional Class

Baseline 1 Year6 Months30 Days

Patie

nts

Surv

ivin

g, %

I II III IV

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

Mean Gradient - AVRMean Gradient - TAVR

Peak Gradient - AVRPeak Gradient - TAVR

Mea

n an

d Pe

ak G

radi

ent

As-

Trea

ted

Tria

l 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 FindingsAortic Valve Gradients

Paravalvular Aortic Regurgitation

P < 0.001 P < 0.001 P < 0.001

1 Year6 Months30 Days

Patie

nts,

%

None Trace Mild Moderate Severe

TAVR - The FutureMy Rosey Prophecy

Surgery – The “PAST”

TAVR – The “Future”

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

will be treated using TAVR!