Post on 26-Oct-2020
transcript
4/1/2015
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Transcatheter Aortic Valve Replacement (TAVR)
A less Invasive Treatment Option for Severe Aortic Stenosis.
Timinder Biring, MD FACC Interventional Cardiologist, Fairview Southdale Hospital
TAVR team UMP Heart
Disclosure
• Consultant Boston Scientific
• Speakers bureau Edwards Lifescience
• Sub PI – Reprise 3 trial
• I will discuss off label use of TAVR
Outline
• Background and Perspective
• TAVR Clinical Data
• Approved Commercial Devices
• Future of TAVR
• UMP Heart Valve team experience
Objectives
• Understand the pathophysiology of Aortic Stenosis
• Become familiar with trial data supporting the advent of TAVR.
• Become familiar with current TAVR platforms.
• Understand limitations of devices and future directions.
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Prevalence
• Prevalence is estimated to be 4% • Bicuspid AV present in 50% of the patients undergoing AVR
Otto, M. et al, Cardiology Clinics, 1998;16: 353 – 373
Age Group
( y )
Normal Aortic Valve
( %)
Aortic Sclerosis
( %)
Aortic
Stenosis
( %)
All Subjects 72 26 4
65 – 74 78 20 1.3
75 – 84 62 35 2.4
> 84 48 48 4
Stewart BF, et al. J Am Coll Cardiol 29: 630-634, 1997
At risk
Disease initiation
Progressive Disease
Valve obstruction
Aortic sclerosis AS
Genotype Valve morphology Age, gender Dyslipidemia Diabetes/MetS Hypertension Smoking Renal insufficiency Serum phospate
Shear stress Inflammation Lipid infiltration Myofibroblast diff.
Oxidative stress Angiotensin II Pro-calcific stimuli OPG/RNAKL Wnt/LRP
Hydroxyapatite nodules Cartilage and bone formation
Normal leaflets
? 10-15% ~100%
Infl
amm
atio
n
Leaf
let
calc
ific
atio
n
Age Current Imaging Window
or
2014 ACC/AHA Valve Guidelines Concept of Valve Disease Stages
Natural History of Aortic Stenosis
from Ross and Braunwald, Circulation 1968
40 50 60 70 80 0
20
40
60
80
100
Age
Years
Survival
Percent Onset severe
symptoms
6 4 2 0 Avg. survival
Years
Angina
Syncope
Failure
Latent Period
(Increasing
Obstruction,
Myocardial
Overload)
“Surgical intervention should be performed promptly once even … minor symptoms occur”
Source: Chart: Ross J Jr, Braunwald E.
Aortic stenosis. Circulation
1968;38 (Suppl 1) C.M. Otto. Valve Disease: Timing of Aortic
Valve Surgery. Heart 2000
23
4
12
30
28
30
5
10
15
20
25
30
35
Worse Prognosis than Many Metastatic Cancers
5-Year Survival (Distant Metastasis)8
Su
rviv
al, %
Breast
Cancer
Lung
Cancer
Colorectal
Cancer
Prostate
Cancer
Ovarian
Cancer
Severe
Inoperable AS* *Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu, MD, Cleveland Clinic
5 year survival of breast cancer, lung cancer, prostate cancer, ovarian cancer and severe inoperable aortic stenosis
8
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• Shortness of breath
• Angina
• Fatigue
• Syncope or presyncope
• Other
– Rapid or irregular heartbeat
– Palpitations
Symptoms of Aortic Stenosis4
The symptoms of aortic disease are commonly misunderstood by
patients as ‘normal’ signs of aging.5 Many patients initially appear
asymptomatic, but on closer examination up to 37% exhibit symptoms.6
Sandy
Actual TAVR Patient
Pre-Procedure
Inopera
9
Aortic Valve Replacement
• Current standard of care – open heart surgery.
• >200,000 Surgical AV replacements annually worldwide.
• Cardiac surgeon opens the heart, removes the diseased valve, and inserts a prosthetic valve.
• Recovery time: 1-3 months until normal activity
• Extended hospital stay (4-7 days).
Who Likes Surgery? Early Catheter-Based AV Designs
• Dr. Henning Anderson “father of TAVR.” – Cardiologist in Denmark
• Concept conceived in 1989.
• Built device from materials at local hardware store
• Performed first in animal implantation
• Company sold to Edwards Lifesciences.
The Andersen valve (1992)
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First-in-Man
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, 2002
Adopted from TCT presentation: Dr. Leon
Transcatheter AVR
Edwards CoreValve
“First” Generation Devices
TAVR Clinical Data
Publications in NEJM 1-Year outcomes published on-lin1-Year June 9, 2011
2-Year outcomes published on-line March 26, 2012
@ NEJM.org and print May 3, 2012
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N = 179
N = 358 Inoperable
Standard Therapy
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 Mortality and 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 = 103 N = 244
PARTNER Study Design
Symptomatic Severe Aortic Stenosis
ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened
Total = 1,057 patients
2 Parallel Trials:
Individually Powered
N = 699 High Risk
ASSESSMENT:
Transfemoral Access
Transapical (TA) Transfemoral (TF)
1:1 Randomization 1:1 Randomization
Yes No
0%
20%
40%
60%
80%
100%
0 6 12 18 24
Primary Endpoint: All Cause Mortality - Inoperable
All cause
mortality
HR [95% CI] = 0.51 [0.38, 0.68]
p (log rank) < 0.001
∆ at 1 yr = 20.0%
NNT = 5.0 pts
50.7%
30.7%
179
179
TAVR
Std Tx
Numbers at Risk
138
121
124
85
103
56
60
24
Months
TAVR
Std Tx
TAVR 348 298 261 239 222 187 149
AVR 351 252 236 223 202 174 142
All-Cause Mortality (ITT) High risk
0%
10%
20%
30%
40%
50%
60%
70%
0 6 12 18 24 30 36
All-C
au
se M
ort
ality
Months post Randomization
TAVR
AVR
No. at Risk
HR [95% CI] =
0.93 [0.74, 1.15]
p (log rank) = 0.483
26.8%
24.3%
34.6%
33.7%
44.8%
44.2%
348 287 250 228 211 176 139
351 246 230 217 197 169 139
TAVR
AVR
0%
10%
20%
30%
40%
50%
60%
70%
0 6 12 18 24 30 36
Str
okes
TAVR
AVR
Strokes (ITT)
No. at Risk
3.2%
6.0% 9.3%
8.2%
HR [95% CI] =
1.09 [0.62, 1.91]
p (log rank) = 0.763
4.9%
7.7%
Months Post Randomization
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Echocardiographic Findings (AT) Aortic Valve Area
TAVR
AVR
0
0.5
1
1.5
2
2.5
Baseline 30 Days 6 Months 1 Year 2 Years 3 Years
Val
ve A
rea
(cm
2)
TAVR
AVR
Error bars at 1 standard deviation
p = NS
No. of Echos
p = 0.0017 p = 0.0019 p = NS p = 0.0005 p = NS
p = NS
p = NS
304 271 223 211 150 88
294 226 163 154 121 70
Echocardiographic Findings (AT) Mean & Peak Gradients
TAVR
AVR
0
10
20
30
40
50
60
70
80
Baseline 30 Days 6 Months 1 Year 2 Years 3 Years
Gra
die
nt
(mm
Hg)
Peak Gradient - AVR
Peak Gradient - TAVR
Mean Gradient - AVR
Mean Gradient - TAVR
No. of Echos 310 277 233 219 155 88
299 230 169 158 123 72
Edwards Lifesciences SAPIEN/SAPIEN XT THV
] Edwards-SAPIEN THV
New
Skirt Height
Bovine Tissue
ThermaFix Treatment
Pericardial Mapping
Leaflet Deflection
Proprietary Processing
Cobalt Alloy Frame
New Leaflet Geometry
SAPIEN XT THV
New Sizes
(23, 26, 29mm)
NovoFlex Delivery System
• Unidirectional tip-deflecting flex catheter facilitates negotiating the arch
• Balloon catheter tapered distal end for crossing calcified native valve
Flex Catheter
Nose cone – 4.5 cm