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10/31/2017 1 Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories, Inc Vitatron/Medtronic Pfizer Velocimed, Inc Affiliation with these companies is by way of research Disclosure of Financial Interest 2 Aortic Stenosis •Involves calcification and immobilization of valve leaflets - Stiffening and narrowing - Decreased valve opening and cardiac output •Etiologies - Congenital: bicuspid - Associated with aging
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Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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Page 1: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

10/31/2017

1

Aortic Valve Disease

� Steven K. Rowe, MD, FACC� CoxHealth’s 2017 Cardiovascular

Symposium

� Boston Scientific Advisory Council� Berlax Laboratories, Inc� Vitatron/Medtronic� Pfizer� Velocimed, Inc

Affiliation with these companies is by way of research

Disclosure of Financial Interest

2

Aortic Stenosis•Involves calcification and

immobilization of valve leaflets- Stiffening and narrowing- Decreased valve opening and

cardiac output

•Etiologies- Congenital: bicuspid- Associated with aging

Page 2: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

10/31/2017

2

What Causes Aortic Stenosis in Adults?

More CommonLess Common

4

Images courtesy of John Webb, MD at St. Paul’s Hospital and Renu Virmani, MD at the CVPath Institute

Age-Related Calcific Aortic

Stenosis

Congenital Abnormality

RheumaticFever

Pathophysiology of Aortic Stenosis

•Traditionally considereddegenerative disease ofthe elderly

•New evidenceCommon features of CADLipoprotein deposition and oxidationChronic inflammation and cell infiltrateMicroscopic calcification

Aortic Stenosis U.S. Prevalence

Page 3: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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Population at Risk for Aortic Stenosis is Increasing

7

� Aortic Stenosis is estimated to be prevalent with 12.4% of the population over the age of 75. 2

� The elderly population will more than double between now and the year 2050, to 80 million.3

� 80% of adults with symptomatic aortic stenosis are male4

Approx. 2.5 Million People in the U.S. Over the Age of 75 suffer from this

disease. 1

ELDERLY AVERAGE ANNUAL GROWTH RATE: 1910 to 2030

2.6%

3.1%

2.4%2.2%

1.3%

2.8%

0.0%

1.0%

2.0%

3.0%

4.0%

1910-1930 1930-1950 1950-1970 1970-1990 1990-2010 2010-2030

1. U.S. Census Bureau, Population Division. June 2015; 2. Ruben L.J.et al. Heart. 2000;84:211-21; 3. U.S. Census Bureau Statistical Brief. May 1995;4. Ramaraj R, Sorrell VL. Br Med J 2008;336: 550–5.

� Shortness of breath

� Angina

� Fatigue

� Syncope or Presyncope

� Other� Rapid or irregular heartbeat

� Palpitations

Symptoms of Aortic Stenosis

8

The symptoms of aortic disease are commonly misundersto od by patients as ‘normal’ signs of aging. 5 Many patients initially appear asymptomatic, but on closer examination up to37% exhibit symptoms. 6

The symptoms of aortic disease are commonly misundersto od by patients as ‘normal’ signs of aging. 5 Many patients initially appear asymptomatic, but on closer examination up to37% exhibit symptoms. 6

Sandy Severe Aortic Stenosis

(Actual Patient)

5. Das P. European Heart Journal. 2005;26:1309-1313; 6 . Lester SJ et al. CHEST 1998;113(4):1109-1114.

Hemodynamic Implications

•As valve size decreases, pressure in the left ventricle must increase to overcome the resistance to ejection and maintain cardiac output

•Aortic stenosis is considered severe; -valve area is < 0.8-1 cm2

-pressure gradient > 40 mmHg-aortic velocity > 4 m/sec-valve area index <0.6

Page 4: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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Pathological Process for Aortic Stenosis

After the onset of symptoms, patients with severe aortic stenosis have a survival rate as low as 50% at2 years and 20%at 5 years without aortic valve replacement7

Severe Aortic Stenosis is Life Threateningand Treatment is Critical6

11

50% of patients died within 1 year without valve rep lacement

Per the Inoperable Cohort of the PARTNER Trial

100%

80%

60%

40%

20%

00 40 50 60 70

Age, Years

Sur

viva

l, %

Onset Severe Symptoms

Average Survival, y

Angina

Syncope

Failure

0 2 4 6

Latent Period(Increasing Obstruction, Myocardial Overload)

ADULTS AVERAGE COURSE WITH VALVULAR AORTIC STENOSIS

6. Lester SJ et al. CHEST 1998;113(4):1109-1114; 7. Otto CM. Heart. 2000:84:211-218.

5-YEAR SURVIVAL(Distant Metastasis)

8

Sur

viva

l, %

12

Worse Prognosis than Many Metastatic Cancers

5 year survival of breast cancer, lung cancer, pros tate cancer, ovarian cancer and severe inoperable aortic stenosi s

23

4

12

3028

3

0

5

10

15

20

25

30

35

Breast Cancer Lung Cancer Colorectal Cancer Prostate Cancer Ovarian Cancer Severe InoperableAS*

*Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu, MD, Cleveland Clinic

8. National Institutes of Health. http://seer.cancer.gov/statfacts/. Accessed Nov. 2010.

Page 5: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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� In the absence of serious comorbid conditions, aortic valve replacement (AVR) is indicated in the majority of symptomatic patients with severe aortic stenosis

� Consultation with or referral to a Heart Valve Center of Excellence is reasonable when discussing treatment options for: � Asymptomatic patients with severe valvular heart disease

� Patients with multiple comorbidities for whom valve intervention is considered

� Because of the risk of sudden death, replacing the aortic valve should be performed promptly after the onset of sym ptoms

� Age is not a contraindication to surgery

Timely Intervention is Critical for Patientswith Symptoms9

13

2014 Valvular Disease

Guidelines

2014 Valvular Disease

Guidelines

AHA / ACCAHA / ACC

2014 Valvular Disease

Guidelines

AHA / ACC

9. Nishimura RA et al. JACC. 2014. doi: 10.1016/j.jacc.2014.02.537.

Definition Valve Hemodynamics

High-gradient severeaortic stenosis

� Aortic jet velocity ≥ 4 m/s or mean gradient ≥ 40 mmHg� Or aortic valve area index ≤ 0.6 cm 2/m2

Low-flow/low-gradient with reduced left ventricular ejection fraction

� Resting aortic jet velocity < 4m/s or mean gradient < 40 mmHg� Dobutamine stress echocardiography shows aortic valve area ≤ 1.0

cm 2 with aortic jet velocity ≥ 4m/s at any flow rate

� Left ventricular ejection fraction < 50%

Low-gradient withnormal left ventricular ejection fraction orparadoxical low-flow

� Aortic jet velocity < 4m/s or mean gradient < 40 mmHg

� Indexed aortic valve area ≤ 0.6 cm 2/m2

� Stroke volume index < 35 mL/m 2 measured when patient is normotensive (systolic blood pressure < 140 mmHg)

� Left ventricular ejection fraction ≥ 50%

Patients with severe aortic stenosis typicallyhave an aortic valve area ≤ 1.0 cm2

Symptoms: Dyspnea or decreased exercise tolerance, heart failure, angina, syncope and presyncope

Definition of Severe Aortic Stenosis9

14

2014 Valvular Disease

Guidelines

2014 Valvular Disease

Guidelines

AHA / ACCAHA / ACC

2014 Valvular Disease

Guidelines

AHA / ACC

9. Nishimura RA et al. JACC. 2014. doi: 10.1016/j.jacc.2014.02.537.

� Dobutamine stress echocardiography canbe used to differentiate between true and pseudo severe aortic stenosis� Better define the severity of the aortic stenosis

� Accurately assess contractile / pump reserve

� Some patients with severe aortic stenosis based on valve area have a lower than expected gradient (e.g. mean gradient < 30 mmHg) despite preserved LV ejection fraction (e.g. EF > 50%)� Up to 35% of patients with severe aortic

stenosis present with low flow, low gradient

� These low gradients often lead to an under estimation of the severity of the disease,so many of these patients do not undergo surgical aortic valve replacement

Paradoxical Low Flow and/or Low GradientSevere Aortic Stenosis10

15

Dobutamine stress in low gradient, low ejection fractionAS Chambers, Heart. 2006 April; 92(4): 554–558

10. Dumesnil et al. European Heart Journal 2010; 31, 281-289.

Page 6: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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16

UNDERTREATEMENT OF AORTIC STENOSIS

Pat

ient

s, %

Studies show that patients with severe aortic stenosis are under-diagnosed and under-treated

46%57%

40% 39%26%

48%

31%

54% 43% 60% 61% 74% 52% 69%

0%

20%

40%

60%

80%

100%

Bouma 1999 Pellikka 2005 Charison 2006 Varadarajan 2006 January 2009 Bach 2009 Freed 2010

Aortic Valve Replacement (AVR) No AVR

At Least 40% of Patients Who Need Valve Replacement Do Not Get Treatment 11-17

11. Bouma BJ et al. Heart. 1999;82:143-148; 12. Pellikka PA et al. Circulation. 2005;111:3290-3295; 13. Charlson E et al. J Heart Valve Dis. 2006;15:312-321; 14. Varadarajan P et al. Ann Thorac Surg. 2006;82:2111-2115; 15. Jan F et al. Circulation. 2009;120;S753; 16. Bach DS et al. Circ Cardiovasc Qual Outcomes. 2009;2:533-539; 17. Freed BH et al. Am J Cardiol. 2010;105:1339-1342.

Aortic Valve

Normal Stenosis

Aortic Valve

Normal Stenosis

Page 7: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

10/31/2017

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ACC/AHA Guidelines for Aortic Valve Replacement in AS� Class I (“Should be performed”)

Symptomatic severe AS� Severe AS in pts undergoing CABG,

aortic or other valvular surgery� Severe AS with LVEF < 50%

� Class IIa (“It is reasonable to perform”)Moderate AS in pts undergoing other cardiac surgery

Bonow RO, J Am Coll Cardiol 2006

ACC AHA Guidelines for AVR in Patients with Aortic Stenosis

� Class IIb (“Procedure may or might be considered”)Severe AS in asymptomatic pts with abnormal ETT response

� Severe AS in asymptomatic pts with high likelihood of progression (age, degree of valvular calcium, CAD)

� Severe AS in asymptomatic pts in whom surgery might be delayed at time of symptom onset

� Mild AS in pts undergoing other cardiac surgery at risk for rapid progression

� Extremely severe AS in asymptomatic pts in whom the expected operative mortality is <1%

ACC/AHA Guidelines for Aortic Valve Replacement in AS

� Class III (“Procedure should not be performed”)For prevention of sudden cardiac death in asymptomatic patients who have none of the class IIa or IIbfindings

Page 8: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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Surgical vs. Medical Therapy in Asymptomatic Pts with Severe AS

� Relative risks of medical vs. surgical therapy� Surgical mortality variable

- If > 2-3% operative risk exceeds risk of SCD in asymptomatic pt

- AVR doesn’t abolish risk of SCD� Complications of prosthetic heart valves

- Dependent upon valve type, clinical variables-1-3% per year

Undertreated Aortic Stenosis

� Data suggests that for every patient who receives an AVR, there are up to 4 who would benefit in terms of symptoms and survival, but who do not get surgery.

Asymptomatic Severe Aortic Stenosis-Clinical Concerns

� LVH/ischemia� LV diastolic dysfunction� LV systolic dysfunction

- Afterload mismatch- Myocardial fibrosis

� Rapid Progression- (>0.3 m/sec within 1 year)

� Onset of Atrial fibrillation

Page 9: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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Exercise Testing in Asymptomatic Severe AS

� ETT to predict symptom development� Controversy in literature� 125 pts with moderate to severe AS (mean EOA 0.9 cm2)

- 26 developed symptoms during ETT

� 1 Year follow-up- 36 pts symptomatic

- 24 pts with severe AS (EOA< 0.8cm2)

- No pt with EOA >1.2cm2 became symptomatic

Das P, Eur Heart J 2005; 26: 1309.

Exercise Testing in Asymptomatic AS

� Stop test if: - B/P drop of > 10 mmHg- Pt develops symptoms, complex ventriculararrhythmias

� Concerning:- Reduced exercise tolerance (<80% predicted

normal level of exercise)

- Blunted BP rise (<20 mmHg)- Symptoms

ETT/BNP in Aortic Stenosis

� Higher levels in symptomatic pts

� NTProBNP<80 pml/L associated with higher symptom free survival at 6 and 12 months

� 34 asymptomatic patients with moderate or severe AS (mean valve area 0.96+/-0.3 cm(2)) and 15 age matched controls underwent echo, treadmill ETT, and BNP analysis.

� Compared to control subjects, AS patients had ↑ LV mass index, E/E' ratio, LVEF, resting BNP and ↓ exercise duration.

VanPelt Int J Cardiol 2007

Page 10: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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� There was an association between ↑ BNP and ↓ exercise capacity.

� AS patients with increase in systolic BP of </=20 mmHg during exercise (n=18) had higher plasma levels of BNP (13.8+/-6.1 vs 8.6+/-6.0 pmol/L, p=0.003).

� Presence of symptoms with exercise predicted onset of symptoms within one year, BP and ECG were not predictive- Sensitivity 72%, specificity 78%

ETT/BNP in Aortic Stenosis

Early AVR in Asymptomatic Patients

SurSurvival for AVR patients w/ or w/out symptoms was similar

....and the survival for non-AVR patients w/symptoms was a dismal 50% @ 1yr and <40% @ 2yrs

…and superior to asymptomatic group (w/ severe AS) who did not have AVR

Increased Survival ?

Page 11: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

10/31/2017

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IDENTIFYING POTENTIAL CANDIDATES FOR TAVR

Cohesive, Multi-disciplinary Approach Embodies

� Optimal patient centric care

� Dedication across medical specialties

� Collaborative treatment decision

TAVR Heart Team Concept

32

InterventionalCardiologist

CardiologistSurgeon

Valve ClinicCoordinator

CardiacCATH Lab

and O.R. Staff

Anesthe-siologist

ReferringCardiologist

Imaging Specialists TAVR

Heart Team

National Coverage Determination 18

The patient (preoperatively and postoperatively) is under

the care of a heart team

2014 Valvular Disease

Guidelines

2014 Valvular Disease

Guidelines

AHA / ACCAHA / ACC

2014 Valvular Disease

Guidelines

AHA / ACC

18. National Coverage Determination (NCD) for Transcatheter Aortic Valve Replacement (TAVR). 2012.

Pre-screening Review of RecordsPre-screening Review of Records

Clinical EvaluationClinical Evaluation

Gated CTA (Chest / Abdomen / Pelvis)Gated CTA (Chest / Abdomen / Pelvis)

RHC / LHC Coronary AngiographyRHC / LHC Coronary Angiography

Functional Status Assessment (Cognitive Function, Frailty, etc.)Functional Status Assessment (Cognitive Function, Frailty, etc.)

STS Score CalculationSTS Score Calculation

Treatment PlanTreatment Plan

TAVR Evaluation Pathway

33

Note: The above is a suggested flow for the patient screening process, however, the order in which screening tests are conducted varies depending on the patient’s profile and should be at the discretion of the Heart Team.

Page 12: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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� Prevalence of frailty increases with aging; old does not necessarilyequal frail

� Elderly patients achieve measurable benefit from cardiac surgery, particularly in terms of� Quality of life� Increased survival� Prevention of adverse

cardiovascular events

� The “Eyeball Test”

Frailty: An Important Parameter in Assessing Operative Risk

34

Source: Slide provided courtesy of Todd Dewey, MD, Medical City Dallas

Same age(90) and

predicted risk(12%)

One passesthe

“eyeball test,”one does not

PARTNER II Trial Frailty Index Assessment

Multiple Modalities for Assessing Frailty

35

15-Foot Walk Katz Activitiesof Daily LivingSerum AlbuminGrip

Strength

TAVR: HISTORY OF EVIDENCE

Page 13: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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37

Alain Cribier: First Human TranscatheterValve Replacement (2002)

History of Edwards’ Transcatheter Heart Valve Technology

38

First successful TAVR procedure in U.S.

Landmark PARTNER clinical trials begin in U.S.

Edwards SAPIEN valve approved in the U.S. for inoperable patients

Edwards SAPIEN valve approved in U.S. forhigh-risk patients

EdwardsSAPIEN XT valve approved in U.S. for high or greaterrisk patients

2005 2011 2012 20142007

Edwards SAPIEN XT

Valve

Edwards SAPIEN

Valve

Edwards SAPIEN 3 valve approved in U.S. for high or greater risk patients

Edwards SAPIEN 3

Valve

2015

Over 100,000 Patients Treated Worldwide

Over 30,000 Patients Treated in the United States

Treating Patients in Over 60 Countries

Backed by Unprecedented Outcomes andReal World Results

*As of February 2015

Edwards SAPIEN transcatheter heart valves are the most widely used transcatheter heart valves worldwide and consistently demonstrate clinical

excellence in both trials and real-world experience*:

39

Page 14: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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Edwards SAPIENis superior to medical management in inoperable patients

TAVR is Better than Medical Managementfor Inoperable Patients

40

TAVR with Edwards SAPIEN valves is a reasonable alternative to surgery

Edwards SAPIEN 3 valve: Transformational design

TAVR is superior to medical management for Inoperable Patients

Edwards SAPIEN Valves

Significantly Improve Survival

Without treatment 94% of patientsin the standard therapy groupdied within

5 years

21.8% absolute reduction in mortality at

5 years

Standard Therapy is an Ineffective Treatmentfor Severe Aortic Stenosis Patients

71.8%

Months

HR [95% CI] = 0.50 [0.39, 0.65]p (log rank) < 0.0001

93.6%

Standard therapy includes medical management and BAV

41

All-

Cau

se M

orta

lity

(%)

0 12 24 36 48 60

100%

80%

60%

40%

20%

0%

Standard Rx (n = 179)

TAVR (n = 179)

50.7%

30.7%

A L L - C A U S E M O R T A L I T Y I n o p e r a b l e C o h o r t

87.3% of patients with standard therapy were rehospitalized

for cardiac issues

39.7% absolute reduction of

rehospitilizationat 5 years

Standard Therapy Patients Were RehospitalizedTwice as Often as TAVR Patients

Standard therapy includes medical management and BAV

42

Months

100%

80%

60%

40%

20%

0%

87.3%

47.6%

Standard Rx (n = 179)

HR [95% CI] = 0.40 [0.29, 0.55]p (log rank) < 0.0001

0 12 24 36 48 60

TAVR (n = 179)

Hos

pita

lity

(%)

R E H O S P I T A L I Z A T I O N I n o p e r a b l e C o h o r t

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At 5 YearsPatients that

had TAVR with the Edwards

SAPIEN valve showed survival

equivalent to SAVR

TAVR is Equivalent to Surgery in High-Risk Patients

43

Per ACC / AHA Guidelines, TAVR is a reasonable alternative to surgery in patientswho meet an indication for AVR and who have high surgical risk for surgical AVR9

Error Bars Represent95% Confidence Limits

All-

Cau

se M

orta

lity

(%)

Months Post Randomization0 12 24 36 48 60

100%

80%

60%

40%

20%

0%

SAVR

TAVR

HR [95% CI] = 1.04 [0.86, 1.24]p (log rank) = 0.76

67.8%

62.4%

No. at Risk

TAVR 348 262 228 191 154 61

SAVR 351 236 210 174 131 64

A L L C A U S E M O R T A L I T YA t 5 Y e a r s

9. Nishimura RA et al. JACC. 2014. doi: 10.1016/j.jacc.2014.02.537.

At both 1 year and 5 year follow up, 85% of Patients treated with the Edwards SAPIEN valve were in NYHA Class I or II compared to only 6% at baseline.

TAVR SAVR TAVR SAVR TAVR SAVR TAVR SAVR348 349 250 226 165 145 100 97

Baseline 1 Year 3 Years 5 Years

p = 0.64 p = 0.91 p = 0.35 p = 0.9313%15% 14%100%

80%

60%

40%

20%

0%

19%15%

94%94%

20%

Per

cen

t of

Eva

luab

le E

choe

s

I II III IV

Patients Continued to Show Improved Symptom Relief 5 Years After TAVR

44

NYHA CL AS S OV E R T I M E

Longest Follow-Up in Any TAVR Randomized Study

45

5 YEARS of PROVEN VALVE DURABILITY

� Sustained hemodynamic performance

� No incidence of structural valve deterioration requiring surgical valve replacement20

� Significant and sustained improvement in functional heart class

The PARTNER Trial 5-Year Results

TAVR vs. Standard Therapy in Inoperable Patients

� Significant mortality benefit

� Statistically significant reduction in hospitalization

� NNT is 5 patients to save a life

TAVR vs. Surgical AVR in High-Risk Patients

� Equivalent mortality benefit

� Persistent symptom relief

20. Lancet. 2015 Jun 20;385(9986):2477-84. doi: 10.1016/S0140-6736(15)60308-7. Epub 2015 Mar 15.

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TAVR is superior to medical management for inoperable patients

TAVR is a reasonable alternative to surgery for high-risk patients

Transformational advance in valve design: Edwards SAPIEN 3 Valve

Now Approved: The Edwards SAPIEN 3 Valve

Edwards SAPIEN 3 valve: Transformational design

46

Unprecedented Clinical

Outcomes

All-Cause Mortality of the 491 patients in the PARTNER II Trial was 1.6% at 30 days

Cardiovascular Mortality was 1.0%

Low Mortality at 30 DaysThe PARTNER II Trial: SAPIEN 3 Valve High-Risk

1.6% 1%0%

20%

40%

60%

80%

100%

High-Risk (TF)

All-Cause Cardiovascular

47

MORTALITY(As Treated Patients)

6.3%5.2%

3.7%4.4%

3.5%

1.6%

0%

5%

10%

15%

20%

PARTNER I B (TF) PARTNER I A (All) PARTNER I A (TF) PARTNER II B (TF) PARTNER II B (TF) PARTNER II HR (TF)

AL L -CAUS E M ORT AL I T Y a t 3 0 DAYSPART NE R I T r i a l a n d PART NE R I I T r i a l

All-Cause Mortality Has Decreased Overall

175 344 240 271 282 491

SAPIEN Valve SAPIEN XT Valve

SAPIEN 3 Valve

48

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Low Stroke at 30 DaysThe PARTNER II Trial: SAPIEN 3 Valve HR

0.8%0%

20%

40%

60%

80%

100%

High-Risk (TF)

Disabling

49

DI S ABL I NG S T ROKE(As T r e a te d Pa t i e n ts )

Of the 491 Patients in the PARTNER II Trial: Disabling Strokewas 0.8% at 30 days

Other Clinical Events at 30 Days (as Treated Patients)*

SAPIEN 3 Valve HR TF

Events (%) (n = 491)

Major Vascular Comps. 5.3

Bleeding – Life Threatening 5.5

*PARTNER II Trial high-risk TF SAPIEN 3 valve cohort 30-day results.

Edwards TranscatheterHeart Valve

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Transfemoral Procedural Animation

52

Valve Deployment

Balloon-expandable valve

Resulting Orifice

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Balloon-Expandable TAVR in Inoperable Patients With Severe Symptomatic Native Aortic Valve Stenosis: The PARTNER Trial Cohort B 2-Year Results

Rigorous Study Design

56TA, transapical; TF, transfemoral.

Rigorous Study Protocols and Management

57

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Cohort B Outcomes

Key Insights for Cohort B

� Standard therapy is failing these patients with severe symptomatic native aortic valve stenosis

� TAVR with Edwards SAPIEN THV delivers:� Superior survival rate� Reduction in symptoms and restoration of

quality of life� Improvement in hemodynamics

� Sustained valve performance

59

Improvement in Hemodynamicsand Sustained Valve Performance

Serial echocardiograms in TAVR patients revealed: � Reduced mean gradients and improved

aortic valve area (AVA), which were unchanged during 1-year and 2-year follow-up

� Frequent paravalvular aortic regurgitation (AR), which was usually mild (~90%), remained stable during 1-year follow-up, slightly improved at 2 years, and rarely required further treatment 60

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Mea

n G

radi

ent,

mm

Hg

Reduced Mean Gradient

61Error bars = ± 1 Std Dev

Increased Valve Area

62Error bars = ± 1 Std Dev

Paravalvular Regurgitation Slightly Improved Over Time

63

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Reduction in Symptoms and Restoration ofQuality of LifeAt 1 year, patients that underwent TAVR with the Edwards SAPIEN THV showed significant improvements in: � NYHA functional class � Kansas City Cardiomyopathy

Questionnaire (KCCQ) � SF-12 � 6-minute walk test

64

Some surgical valves fail early

Failed Trifecta surgical valve

at 2 yearsSapien XT transcatheter valve implanted

In the surgical valve

When do surgical valves present for VIV TAVI?

VIVID Registry

Predictors of early tissue valve

failure

• Low age

• Renal failure

• Valve type

A mean of 9 years

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BC: valve-in-valve implants to 2015

Aortic (n= 102)

STS 9.8% PROM

Mortality at 30 days

TF 1.3%

TA 7.4%

PARTNER 2 valve-in-valve

J Webb, JACC 2017, in press

PARTNER 2 Valve-in-Valve

Webb JG. JACC, 2017, in press

Page 24: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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Aortic ViV Mitral ViV

STS Approach STS Approach

Commercial

Approval≥8 All ≥8 All

PARTNER 3

Clinical Trial<8

TF/TA/T

Ao3-8 TA/TS

ViV Recent Commercial Indication

A Cheung, J Webb, D Wong, J YeAnnals of Thoracic Surgery (2009)

First-in-human successful MVIV 2008 …

Transseptal mitral valve-in-valve implant

Page 25: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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TEE post

LVOT view LA view

N=116

Need for a 2nd valve 14.7%

LVOT obstruction 11.2%

Valve embolization 4.3%

Mortality 30-day 25%

Mortality 1-year 54.7%

M Guerrero, Evanston

Tricuspid valve in valve with Sapien 3

Page 26: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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Absolute Reduction in Mortality Continues to Diverge at 2 Years

> 30% Absolute Reduction in Cardiovascular Mortality

77

78

25% Absolute Reduction in Mortality

Page 27: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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> 30% Absolute Reduction in Cardiovascular Mortality

TAVR Was Superior to Standard Therapy in All Measurements of Survival at 2 Years

80

Complications

Page 28: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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Higher Incidence of Stroke

82

Mortality or Stroke

83

Higher Incidence of Major Vascular Complications

84

Page 29: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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Higher Incidence of Major Bleeding

85* Major bleeding is defined as an event that causes death; causes a hospitalization or prolongs hospitalization; requires pericardiocentesis or an open

and/or endovascular procedure for repair or hemostasis; causes permanent disability (eg, blindness, paralysis, hearing loss); or requires transfusion of > 3 units of blood within a 24-hour period.

Conclusions

Page 30: Aortic Valve Disease · 2020. 5. 12. · Aortic Valve Disease Steven K. Rowe, MD, FACC CoxHealth’s 2017 Cardiovascular Symposium Boston Scientific Advisory Council Berlax Laboratories,

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Conclusions

At 2 years, in patients with severe symptomatic native aortic valve stenosis who were not suitable candidates for surgery:� Treatment with the Edwards SAPIEN THV

remained superior to standard therapy with incremental benefit from 1 to 2 years, reducing the rates of mortality and repeat hospitalization

� Treatment with Edwards SAPIEN THV improved NYHA functional status and decreased class III/IV symptoms compared to standard therapy

88

Conclusions

� There were significantly more strokes in patients treated with the Edwards SAPIEN THV than in patients who received standard therapy � After 30 days, differences in stroke frequency were

largely due to increased hemorrhagic strokes in patients treated with Edwards SAPIEN THV

� Patients treated with the Edwards SAPIEN THV also had a higher incidence of major vascular complications and major bleeding than standard therapy patients

89

Conclusions

� Edwards SAPIEN THV hemodynamic performance by echocardiography showed sustainable improvements in mean gradients and aortic valve areas up to 2 years after implantation

� Moderate or severe paravalvular aortic regurgitation in patients treated with the Edwards SAPIEN THV did not influence 2-year survival, and there was a trend towards reduced paravalvular aortic regurgitation between 1 and 2 years

90

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ACC AHA Guidelines, JACC 2006

TAVI