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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10/31/2017
1
Aortic Valve Disease
� Steven K. Rowe, MD, FACC� CoxHealth’s 2017 Cardiovascular
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
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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
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50% of patients died within 1 year without valve rep lacement
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.
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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
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
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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
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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
� 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
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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 ?
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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
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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
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
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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.
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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
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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
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15-Foot Walk Katz Activitiesof Daily LivingSerum AlbuminGrip
Strength
TAVR: HISTORY OF EVIDENCE
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Alain Cribier: First Human TranscatheterValve Replacement (2002)
History of Edwards’ Transcatheter Heart Valve Technology
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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*:
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Edwards SAPIENis superior to medical management in inoperable patients
TAVR is Better than Medical Managementfor Inoperable Patients
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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
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
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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
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
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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
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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
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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
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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
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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
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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
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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
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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
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Higher Incidence of Stroke
82
Mortality or Stroke
83
Higher Incidence of Major Vascular Complications
84
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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
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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