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
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
10/31/2017
3
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
10/31/2017
4
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.
10/31/2017
5
� 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.
10/31/2017
6
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
10/31/2017
7
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
10/31/2017
8
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
10/31/2017
9
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
10/31/2017
10
� 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 ?
10/31/2017
11
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.
10/31/2017
12
� 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
10/31/2017
13
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
10/31/2017
14
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
10/31/2017
15
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.
10/31/2017
16
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
10/31/2017
17
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
10/31/2017
18
Transfemoral Procedural Animation
52
Valve Deployment
Balloon-expandable valve
Resulting Orifice
10/31/2017
19
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
10/31/2017
20
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
10/31/2017
21
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
10/31/2017
22
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
10/31/2017
23
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
10/31/2017
24
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
10/31/2017
25
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
10/31/2017
26
Absolute Reduction in Mortality Continues to Diverge at 2 Years
> 30% Absolute Reduction in Cardiovascular Mortality
77
78
25% Absolute Reduction in Mortality
10/31/2017
27
> 30% Absolute Reduction in Cardiovascular Mortality
TAVR Was Superior to Standard Therapy in All Measurements of Survival at 2 Years
80
Complications
10/31/2017
28
Higher Incidence of Stroke
82
Mortality or Stroke
83
Higher Incidence of Major Vascular Complications
84
10/31/2017
29
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
10/31/2017
30
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
10/31/2017
31
ACC AHA Guidelines, JACC 2006
TAVI