TAVR vs SAVR:

Is There Really Any Debate?

Jeffrey A Southard, MD, FACC

Aortic Stenosis

– Etiology Calcific degenerative

• Degenerative process with proliferative & inflammatory changes, lipid accumulation, up regulation ACE, infiltration with macrophages & T lymphocytes . Bone formation (vascular calcification)

Congenital - Bicuspid • Turbulent flow - traumatizes leaflet

fibrosis, rigidity, calcification & narrowed orifice Rheumatic

• Adhesion & fusion of commissures & cusps retraction & stiffening cusps borders.

• Calcific nodules both surfaces - small round or triangular opening

*

According to the 2008 ACC/AHA guidelines, severe aortic stenosis is defined as: Aortic valve area (AVA) less than 1.0 cm2

Mean gradient greater than 40 mmHg or jet velocity greater than 4.0 m/s

Echocardiographic Guidelines are the Gold Standard

*Doppler-Echocardiographic measurements

PresenterPresentation NotesEchocardiographic guidelines are the gold standard in diagnosing a patient with severe aortic stenosis. According to the 2008 ACC/AHA guidelines, severe aortic stenosis is defined as aortic valve area (AVA) less than 1.0 cm2, mean gradient greater than 40 mmHg or jet velocity greater than 4.0 m/s.

Natural History-Severe Aortic Stenosis

Ross and Braunwald. Circulation 1968;38(Suppl. V):61.

PresenterPresentation NotesLiterature shows (Otto CM. Timing of aortic valve surgery. Heart. 2000;84:211-21.)

- Survival after onset of symptoms is 50% at 2 years and 20% at 5 years- Surgical intervention for severe aortic stenosis should be performed promptly once even minor symptoms occur

5 year survival of breast cancer, lung cancer, prostate cancer, ovarian cancer and severe inoperable aortic stenosis

5

Sobering Perspective

5-Year Survival S

urvi

val,

%

Breast Cancer

Lung Cancer

Colorectal Cancer

Prostate Cancer

Ovarian Cancer

Severe Inoperable AS*

PresenterPresentation NotesData shows a sobering perspective for inoperable patients: 5 year survival of breast cancer, lung cancer, prostate cancer, ovarian cancer and severe inoperable aortic stenosis

Aortic Stenosis

• Symptomatic Aortic Stenosis - Surgical Aortic Valve Replacement is the standard of care

• Surgical Aortic Valve Replacement - Mortality Risk

Isolated AVR - 3.3 to 5.7%

AVR with CABG - 6.8 to 7.3%

• Percutaneous Aortic Valve Implantation in high risk aortic stenosis patients - feasible and safe

Operative Risk

Adapted from - Ambler G. et al. Circulation 2005;112(2):224-231

• Highest Risk Factors Shock Emergency surgery Age - especially > 80 years Renal dysfunction - worse

with dialysis Left Ventricular dysfunction

- LVEF < 30-35% Previous Cardiac Surgery CHF Diabetes

(%) AS

≥ 1 Cause (%) 68

Age 35

Renal failure 10

COPD 21

Other EC 26

Short life expectancy 26

Many Patients Do Not Receive Surgery Due to Co-Morbidities

Reasons for Absence of Intervention in Symptomatic Patients (NYHA Class III / IV) Extra Cardiac Causes

SEVERE AORTIC STENOSIS NON-SURGICAL

REFUSALS

MEDICAL THERAPY

ASYMPTOMATIC AORTIC VALVE REPLACEMENT SURGERY

BALLOON AORTIC VALVULOPLASTY

-This is why we need another option for patients

PresenterPresentation NotesPER EURO SCORE

• Studies show at least 40% of SAS patients are not treated with an AVR9-15

Addressing a Serious Unmet Need

PresenterPresentation NotesStudies show at least 40% of SAS patients are not treated with an AVR9-15

PresenterPresentation NotesDaniel Hale Williams in 1893- first open heart surgery in a patient with a stab woundOperating room in 1952

PresenterPresentation NotesThey don’t change. There is no innovation. They are stuck, there was no competition to speak of.

PresenterPresentation NotesPrimitive Device- like the early cell phone and TV

Definitive Results Through Rigorous Design

14 THE PARTNER TRIAL COHORT B

PresenterPresentation NotesThe PARTNER Trial included two individually stratified and powered cohorts of patients with severe aortic stenosis who were assessed to be at high risk of operative mortality.

Cohort A includes 700 high risk patients (STS > 10) Patients in Cohort A were first assessed for transfemoral access to determine the appropriate approach (transfemoral or transapical) then randomized against surgical AVR Primary endpoint is all-cause mortality at one year (non-inferior)

Cohort B includes 358 inoperable patientsInoperability was assessed by two independent CT surgeons and a cardiologist based on the probability that The patient’s operative mortality risk was > 50% orThe probability of irreversible morbidity was > 50% Patients were then assessed for transfemoral access and randomized to TAVR or standard therapy Co-primary endpoints for Cohort B are:All-cause mortality for the duration of the trial (superiority)Composite of all-cause mortality and recurrent hospitalization (superiority)

Absolute Reduction in Mortality Continues to Diverge at 2 Years

15

PresenterPresentation NotesThe 1-year mortality rate for Edwards SAPIEN THV patients in the inoperable cohort was impressive, but the 2-year mortality rate was even more impressive. It is evident that the Edwards SAPIEN THV and standard therapy curves continue to diverge.Patients treated with the Edwards SAPIEN THV had an absolute reduction in mortality at 2 years of 24.7% (P < .0001), with a NNT of 4.0. That means only 4 patients needed to be treated in order to save a life.

> 30% Absolute Reduction in Cardiovascular Mortality

16

PresenterPresentation NotesIn addition, inoperable patients treated with the Edwards SAPIEN THV showed an absolute reduction in cardiovascular mortality of more than 30% at 2 years, with a highly significant P value. A NNT of 3.2 means that approximately only 3 patients needed to be treated in order to save a life.

Mea

n G

radi

ent,

mm

Hg

Reduced Mean Gradient

17 Error bars = ± 1 Std Dev

PresenterPresentation NotesSerial echocardiograms revealed that patients treated with the Edwards SAPIEN THV experienced a dramatic reduction in mean gradient, which remained unchanged at 1 year and 2 years.The mean gradient worsened over time for the patients in the standard therapy group, with no sustained hemodynamic benefit from BAV.

Increased Valve Area

18 Error bars = ± 1 Std Dev

PresenterPresentation NotesSimilarly, there was an impressive increase in aortic valve area for patients treated with the Edwards SAPIEN THV and this was sustained through 2 years.

0

0.1

0.2

0.3

0.4

0.5

0 6 12 18 24

TAVR Surgical AVR

Months

348 298 260 147 67

351 252 236 139 65

No. at Risk

TAVR

AVR

26.8

24.2

All-Cause Mortality High Risk Patients

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

P (log rank) = 0.62

Next Generation Transfemoral TAVR Devices

• Direct Flow Medical -Percutaneous Aortic Valve

• Boston Scientific - Sadra LotusTM Valve

• Symetis Acurate TF

• St. Jude Medical - Portico TAVI System

• Edwards - Sapien 3

• Edwards - Centera

Final Thoughts

• The greatest new technology since stents- without question

• We have as good of results with TAVR as surgery has with over 100 years of experience

• It will only get better- that I assure you!

Thanks

TAVR vs SAVR:��Is There Really Any Debate?Aortic StenosisEchocardiographic Guidelines are the Gold Standard Natural History-Severe Aortic StenosisSobering PerspectiveAortic StenosisOperative RiskMany Patients Do Not Receive Surgery �Due to Co-MorbiditiesAddressing a Serious Unmet NeedSlide Number 10Slide Number 11Slide Number 12Slide Number 13Definitive Results Through Rigorous Design Absolute Reduction in Mortality Continues �to Diverge at 2 Years> 30% Absolute Reduction in Cardiovascular MortalityReduced Mean GradientIncreased Valve AreaAll-Cause Mortality�High Risk PatientsSlide Number 20Next Generation Transfemoral� TAVR DevicesFinal ThoughtsSlide Number 23