Transcript Survival - Amazon Web Services

History and Future
of
Aortic Valve Implantation
OTTAVIO ALFIERI
S.Raffaele University Hospital
Milano
Aetiologies of Single Valvular
Heart Diseases in the Euro Heart
Survey
43%
13%
32%
12%
100%
80%
Other
Ischemic
Congenital
Inflammatory
Endocarditis
Rheumatic
Degenerative
60%
40%
20%
0%
AS
AR
MR
MS
(Iung. Eur Heart J 2003;24:1244-53)
Aortic Stenosis: Survival
Onset of symptoms
% Survival
97.2% alive
Surgery
45% alive
Failure
Syncope
Angina
3
15
Years
NEJM 1997;337;32-41 and UK Heart Valve Registry
Patient Characteristics
in the Euro Heart Survey
AS
Age
(years)
69±12
 70 years
(%)
56
 1 comorbidity
(%)
36
AR
58±16
25
26
MS
58±13
18
22
MR
65±14
44
42
(Iung. Eur Heart J 2003;24:1244-53)
Surgical Risk vs. Benefit
Surgical Risk
Optimum
Value
Limited
Value
Poor value:
•Patient
•Purchaser
•Physician
?
Clinical Benefit
Increasing age
22 centres, 67,764 patients, 4,743
octogenarians
12
Complications (%). .
10
8
6
Mortality
Renal failure
Stroke
4
2
0
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85-90
Age (years)
Central Cardiac Audit Database, UK
Survival after Isolated Aortic Surgery
in patients aged 80+:
Influence of pulmonary disease
No lung
disease
COPD/emphysema/asthma
Discharge
96.7%
75.7%
1 year
90.6%
69.6%
2 years
88.9%
54.9%
5 years
63.6%
20.0%
Central Cardiac Audit Database, UK
Survival after Isolated Aortic Surgery in
patients aged 80+:
Influence of peripheral vascular
disease
No PVD
PVD
Discharge
96.0%
79.6%
1 year
90.2%
68.2%
2 years
88.3%
52.3%
5 years
57.8%
28.5%
Central Cardiac Audit Database, UK
Not surprisingly….
One third of patients did not undergo surgery
because of age, comorbidities or LV dysfunction
Severe symptomatic AS
Severe AS : Valve Area ≤ 0.6 cm²/m² BSA or Mean Gradient  50 mmHg
Symptomatic AS : NYHA Class III or IV or Angina
Aortic Stenosis  75 years
N=408
No Severe AS
(n=114)
Severe AS
(n=284)
NYHA III :106
NYHA IV : 36
No Symptoms
N=68
Symptoms
N=216
No Intervention
N=72 (33%)
Angina : 148
Intervention
N=144 (67%)
(Iung. Eur Heart J 2005;26:2714-20)
At least 30-40% of Cardiologists’
AS Patients Go Untreated
Severe Symptomatic Aortic Stenosis
No AVR
Percent of Cardiology Patients Treated
AVR
100
90
80
41
32
30
31
60
70
45
48
60
50
40
68
30
70
69
59
55
52
40
20
10
0
Boum a 1999
Iung* 2004
Pellikka 2005
Charlson 2006
Bach
Spokane
(prelim )
Vannan (Pub.
Pending)
1. Bouma B J et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999;82:143-148
2. Iung B et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. European Heart Journal
2003;24:1231-1243 (*includes both Aortic Stenosis and Mitral Regurgitation patients)
3. Pellikka, Sarano et al. Outcome of 622 Adults with Asymptomatic, Hemodynamically Significant Aortic Stenosis During Prolonged Follow-Up. Circulation 2005
4. Charlson E et Decision-making and outcomes in severe symptomatic aortic stenosis al.. J Heart Valve Dis2006;15:312-321
Under-treatment
especially
prevalent among
patients
managed by
Primary Care
physicians
Aortic Valve Implantation
The Evolving Process
Conventional midline
sternotomy
Invasiveness
Surgical through Minimal
Incision
On pump, arrested heart
sutureless valve replacement
Transaortic, beating heart
delivery
Transapical delivery
Percutaneous - antegrade or
retrograde
BAV
Sept 1985
200
100
0
F.I.M.: 20mm Balloon
First attempt of treating
non surgical AS patients
THE LANCET, JANUARY 11, 1986
Thousand of cases performed worldwide
 Hemodynamic / symptomatic improvement
 No effect on patient’s survival
1985
ONE MAIN LIMITATION
Early valve restenosis: 80% at one year
F.I.M. Balloon Aortic Valvuloplasty
THE GOAL….
CE mark
commercialization
2007
International TF
Feasibility Studies
2005-07
2004
2002-03
2002
2000-02
2000
1999
1989
1987
1985
First in Man
Corevalve 25 F
Feasibility Studies (antegrade)
F.I.M. PHV implantation
Large series of animal implantation
First animal implantation(self exp)
« Percutaneous Valve Technology » (prototypes)
First animal implantation (balloon exp) in pig
Post mortem studies of intra-valvular stenting
Concept of« stented valve », to rule out post-BAV valvular restenosis
F.I.M. Balloon Aortic Valvuloplasty
The pioneers
 Henning Andersen (May 1st 1989)
 First successful pig implant
 Granted with 2 patents
 Alain Cribier (April 16, 2002)
 Parallel research and proof of concept
 Implanted first percutaneous aortic valve
on a patient via an antegrade approach
F.I.M Alain Cribier 2002
8 days post-implantation
F.I.M. and Feasibility Studies
pre CE approval
RESULTS
Procedural success about 90%
 Mortality at 30 days ranges from 5 to 18%
 Acute myocardial infarction in 2 to 11%
 Severe AR in about 5%
 Vascular complications in 10 to 15%
 Stroke in 3 to 9%
 AV bock in 4 to 20%
 Survival :70 to 80% at 2 y.

CE-MARKED DEVICES
Core Valve
(Transfemoral / Transaxillary)
Edwards SAPIEN
(Transfemoral / Transapical)
CoreValve evolution
Generation 1
25Fr
Endovascular
14 patients
Generation 2
21Fr
Endovascular
Generation 3
18Fr
65 patients
Percutaneous
>3000 patients
*
18 French Procedural Progress
Evolution to a
« real cath lab procedure »
within the first 40 Patients of 18 Fr study
•
•
•
•
•
General anesthesia
Surgical cutdown/repair
Ventricular assistance
Pre-closing with ProStar™
Local Anesthesia
Beating heart
Valve delivery without rapid pacing
No cardiac assistance
Edwards SAPIEN
Developments and Improvments
Untreated
Equine Tissue
Cribier-Edwards™ THV
23mm
Treated
Bovine Tissue
Edwards SAPIEN™ THV
23mm, 26mm
Heamodynamic Performance
Low profile
Cobalt-chrome
Ascendra Introducer Sheath 26Fr.
RetroFlex II
Durability
Edwards SAPIEN™ THV II
23mm, 26mm
Profile – Ease of Use
Edwards SAPIEN evolution
RETROFLEX DELIVERY SYSTEM
Stainless Steel Braid – BETTER TORQUE
Front end rotational grip – SINGLE HANDED ARTICULATION
Joint Task Force Positioning Paper:
‟Transcatheter valve implantations for patients with Aortic Stenosis”
INDICATION
TAVI is reserved to pts. with
severe AS and symptoms who
are inoperable or at high risk
for surgery
STEPS OF PTS. SELECTION
-Confirmation of severity of AS
-Evaluation of symptoms-QoL
-Analysis of surgical risk
-Evaluation of life expectancy
-Assessment of feasibility and
exlusion of contraindications
 Gradients
 ECHO
and Valve Area
TT and TEE
 Hemodynamics
 CT
 MRI
 D obutamine testing
MDCT
MRI
TEE
Pouleur AC , et al, Radiology, 2007;244: 745-754
Analysis of surgical risk
 Logistic
Euroscore > 20
 STS Score > 10 (new M & M)
 Parsonnet
 Ambler
 Mini
Nutritional Assesment
(Geriatric Version)
Contraindicatios (general)
Aortic annulus (too small or to large)
 Bicuspid valve ( ? )
 Asymmetric heavy valvular calcification
 Aortic root dilatation (for self-expandable)
 Presence of LV thrombus

TT<TEE<CT
 Risk
of embolism
 Risk of coronary
occlusion
 Prosthesis selection
Contraindications for TF approach
Iliac arteries severe calcification
tortuosity,small diameter;previous aofem.by-pass
 Aorta:severe atheroma of the
arch,coartation,aneurysm with protruding
thrombus….
 Bulky atherosclerosis of the asc. aorta
 Transverse asc.aorta

 Size
 Calcifications
 Tortuosity
 Stenosis
 Degree
 lenght
 Atheromatous
disease
Insertion of
Amplatz
Ultra stiff
0,35 Cook
Wire
Contraindications for TA approach
Previous surgery of the LV (Dor)
 Calcified pericardium
 Severe respiratory insufficiency
 Dislocated LV apex

The procedure
requires the close
cooperation of a team
of specialists in valve
disease, including
clinical cardiologists,
echocardiographists,
interventional
cardiologists, cardiac
surgeons, and
anaesthesiologists.
Interventionalist
anesthesiologist
others
Surgeon
cardiologist
Teamwork
40

Hybrid room
Cath lab
 Operating room


NO COMPROMISES
Imaging quality
 Sterility
 Instrumentation
 Ergonomics
 Device availability

Appropriate environment
POST CE MARK RESULTS
(from registries)
Edwards THV Clinical Studies
Program
Methods
34 Centres Initially Participating
in Commercial Launch
1123 patients
Excluded:
2 Centres / 85 Patients
• Unable to obtain Ethic Cte approval
• Unable to secure administrative support
• One missing patient due to admin. error
Included:
32 Centres
1038 Patients
The SOURCE Registry has
100% procedure data
98% 30 day data
All consecutively enrolled
Source Registry
Baseline Demographics and Risk
Factors
TF
(n=463)
TA
(n=575)
P-value
81.7
80.7
NS
Female
55.2%
56%
NS
Pulmonary Disease
25.4%
29.4%
NS
Renal Failure
26.3%
32.9%
0.024
25.7
29.2
<0.005
10.9%
27.5%
<0.001
7.6%
17.1%
<0.001
47.4%
56.0%
<0.006
4.6%
11.5%
<0.001
Prior CABG
17.6%
26.9%
<0.001
Mitral Valve Disease
16.1%
32.8%
<0.001
Age (yrs)
Logistic EuroSCORE
Peripheral Vascular
Disease
Carotid Artery Stenosis
(>50%)
Incidence of CAD
Porcelain Aorta
Risk Analysis: Logistic
EuroSCORE
Baseline EuroSCORE - The SOURCE Registry
49% 48%
50
Percent of Patients
37%
40
Transapical
Transfemoral
30%
30
16%
12%
20
6% 3%
10
0
< 20
20 - 40
41 - 60
> 60
As EuroSCORE gets higher, ratio of TA to
TF is greater
Survival
TF (n=459)
TA (n=571)
93.7%
89.7%
EuroSCORE <20
94.6%
(Mean 12.5)
93.4%
(Mean 12.4)
EuroSCORE >20
93.3%
(Mean 33.7)
63% of pts
88.1%
(Mean 36.3)
70% of pts
30 day
SOURCE 30 Day All Cause Mortality -- Transfemoral Approach
Stratified by Logistic EuroSCORE
SOURCE 30 Day All Cause Mortality -- Transapical Approach
Stratified by Logistic EuroSCORE
1
1
0.95
0.95
0.9
0.85
Survival
Survival
0.9
0.8
0.85
0.8
0.75
0.75
< 20
p=0.068
>= 20
0.7
0.7
0.65
0.65
< 20
>= 20
0.6
0.6
0
0.1
0.2
0.3
0.4
0.5
0.6
Fraction of Months post Procedure
0.7
0.8
0.9
1
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
Fraction of Months post Procedure
Survival of TA pts with ES< and >20 are significantly different (93.4 vs. 88.1) (p=0.067)
1
Procedure Complications (<30 Days)
TF (n=463)
TA (n=575)
Total (n=1038)
Acute procedure
success
436/95.6%
523/92.9%
959/94.1%
n=456
n=563
n=1019
Device Success
Comp
428/92.4%
522/90.8%
950/91.5%
8/1.7%
20/3.5%
28/2.7%
15 (3.2%)
34 (5.9%)
49 (4.7%)
Valve Migration
0(0.0%)
3(0.5%)
3(0.3%)
Valve Malposition
8(1.7%)
8 (1.4%)
16(1.5%)
Coronary
Obstruction
3(0.7%)
3(0.5%)
6 (0.6%)
Conversion to
sAVR
AR >+2**
Major Complications (< 30 Days)
TF (n=463)
TA (n=575)
Total (n=1038)
Death
29 (6.3%)
59(10.3%)
88(8.5%)
Stroke
11 (2.4%)
16 (2.6%)
27(2.5%)
Renal Failure
Requiring
Dialysis
23(5.0%)
69 (11.7%)
92 (8.7%)
Permanent
Pacemaker
31 (6.7%)
42 (7.3%)
73 (7.0%)
Major Vascular / Access Complications
TF : 10.6 % (not significant predictor of 30 d. survival)
TA: 2.4 % (significant predictor of 30 d. survival)
CoreValve post CE mark experience
18 F Expanded Evaluation Registry(EER)
CLINICAL INDICATIONS
 Native Aortic Valve Disease
 Severe AS: AVAI ≤0.6 cm2/m2
 27mm ≥AV annulus ≥20mm
 Sino-tubular Junction ≤43mm
Age ≥80 y (21F)
≥75 y (18F)
Logistic EuroSCORE ≥20% (21F)
Age ≥65 y
≥15% (18F)
+1 or more
Primary Endpoints:
• Procedural success
• 30-Day outcomes
• Long term outcomes









Liver cirrhosis (Child A or B)
Pulmonary insufficiency: FEV1<1L
Previous cardiac surgery
PHT (PAP>60mmHg)
Recurrent P.E’s
RV failure
Hostile thorax (radiation, burns,etc)
Severe connective tissue disease
Cachexia
Patient Demographics
In-Training
Solo
Total EER
N = 918
80.8 ±6.7
N = 565
81.7 ±5.9
N = 1483
81.2 ±6.4
22.2 ±13.6
23.2 ±13.7
22.6 ±13.7
55.8%
54.7%
55.4%
I-II: 17.2%
III-IV: 82.8%
I-II: 14.4%
III-IV: 85.6%
I-II: 16.1%
III-IV: 83.9%
AorticValve
ValveArea
Area
(cm2)
2)
Aortic
(cm
0.65 ±0.18
0.61 ±0.17
0.64 ±0.18
Peakgradient
Gradient
(mmHg)
Peak
(mm
Hg)
78.3 ±26.1
81.3 ±25.8
79.5 ±26.1
Mean
Gradient
(mmHg)
Mean
gradient
(mm
Hg)
48.4 ±16.4
50.4 ±16.0
49.2 ±16.3
52.9 ±13.8
51.4 ±13.7
52.3 ±13.8
Mean ± SD or %
Age (years)
Age (years)
Logistic
Euro SCORE
Logistic
EuroSCORE
(%)
Female
Female
NYHA I-II
NYHA III-IV
NYHA
LVEF LVEF(%)
(%)
52
Procedural Results
Procedure Mean Time
(minutes)
Procedural Success
100%
97.7%
98.4%
98.0%
SD
200
180
80%
160
140
60%
120
131.2
120.5
100
40%
80
60
20%
40
20
0%
0
In-Training
(N = 867)
Solo
(N = 511)
Total EER
(N = 1378)
127.2
Mortality Rate
30- Day
30-Day
24-Hour
24 - Hour
12%
12%
12%
12%
10%
10%
8%
8%
6%
6%
6%
6%
4%
4%
2.6%
2%
1.9%
10.7%
9.7%
10.3%
2.4%
2%
0%
0%
0%
0%
In Training
Solo
In-Training
Solo
(N = 918) (N = 565)
Total
EER
Total EER
In
Training
In-Training
Solo
Solo
Total
TotalEER
EER
(N = 1483)
(N = 918)
(N = 565)
(N = 1483)
≤ 30-Day Adverse Events*
In-Training
CARDIAC Deaths†
Aortic Dissection
Cardiac Tamponade
Cardiac Perforation
Access Site Complication
Major Bleeding
Conversion to Surgery
Myocardial Infarction
Major Arrhythmia
Pacemaker
Renal Failure
Stroke
TIA
Structural Valve Dysfunction
Valve Migration
* Multiple events in same patients = data not cumulative
† Includes deaths where cause is not known
5.4%
0.7%
3.5%
2.3%
2.5%
5.1%
0.6%
0.9%
9.1%
18.8%
1.9%
2.2%
0.2%
0.0%
0.0%
Certified
3.9%
0.2%
2.2%
1.8%
0.7%
3.3%
0.9%
0.4%
4.6%
17.8%
1.5%
2.2%
0.4%
0.0%
0.0%
Both
4.9%
0.6%
3.0%
2.1%
1.8%
4.4%
0.7%
0.7%
7.5%
18.4%
1.7%
2.2%
0.3%
0.0%
0.0%
CONSIDERATIONS








Multidisciplinary approach and team work essential
Both systems and different access routes should be
available to increase the spectrum of treatable pts.
The “real world” post commercialization experience
shows a high procedure success with a relatively low 30day mortality
A relatively low rate of complications is documented
Experience in managing complications improves the
outcome
Expanded indications are expected
Pts. selection remains critical
Advances and refinements in technology are ongoing
and will facilitate the procedure and improve outcome
My Wish List (P.Block,June 2009)













True percutaneous insertion
No need of general anesthesia
Multiple valve sizes
Smallest size possible < 16 Fr
Smooth outer surface to pass through aorta
Easy transition over arch
Easy transit through valve
“Self seating”
Adequate radial strength
Repositionable and retrivable if needed
No valve gradient
Conforms to annulus without AR
Long term durability
PERSPECTIVES
Progress in delivery systems and valve
manufacturing will lead to lower
profile,repositionable,retrievable and more
durable devices, as well as a wider range
of prosthetic dimensions
 Improved imaging, such as on-line 3-D
reconstruction and stereotaxis could
facilitate valve implantation
 Indications will be expanded, but
randomized trials are highy desirable
