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
0%
20%
40%
60%
80%
100%
AS AR MR MS
Other
Ischemic
Congenital
Inflammatory
Endocarditis
Rheumatic
Degenerative
(Iung. Eur Heart J 2003;24:1244-53)
43% 13% 32% 12%
Aortic Stenosis: Survival
NEJM 1997;337;32-41 and UK Heart Valve Registry
Years
% S
urv
ival
3 15
45% alive
97.2% alive
Onset of symptoms
Surgery
Failure
Syncope
Angina
Age
(years)
70 years
(%)
1 comorbidity
(%)
AS 69±12 56 36
AR 58±16 25 26
MS 58±13 18 22
MR 65±14 44 42
Patient Characteristics
in the Euro Heart Survey
(Iung. Eur Heart J 2003;24:1244-53)
Surgical Risk vs. Benefit
Poor value:
•Patient
•Purchaser
•Physician
Optimum
Value
Surgical Risk
Clinical Benefit
Limited
Value
Increasing age
?
22 centres, 67,764 patients, 4,743
octogenarians
0
2
4
6
8
10
12
50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-90
Age (years)
Co
mp
lic
ati
on
s (
%).
.
Mortality
Renal failure
Stroke
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
One third of patients did not undergo surgery
because of age, comorbidities or LV dysfunction
Not surprisingly….
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)
No Symptoms
N=68
Symptoms
N=216
Intervention
N=144 (67%)
No Intervention
N=72 (33%)
NYHA III :106
NYHA IV : 36
Angina : 148
Severe symptomatic AS
(Iung. Eur Heart J 2005;26:2714-20)
At least 30-40% of Cardiologists’
AS Patients Go Untreated
59
41
68
32
70
30
40
60
52
48
69
31
55
45
0
10
20
30
40
50
60
70
80
90
100
Bouma 1999 Iung* 2004 Pellikka 2005 Charlson 2006 Bach Spokane
(prelim)
Vannan (Pub.
Pending)
Severe Symptomatic Aortic StenosisPercent of Cardiology Patients Treated
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
No AVR
AVR
Under-treatment
especially
prevalent among
patients
managed by
Primary Care
physicians
Aortic Valve Implantation
The Evolving Process
Conventional midline sternotomy
Surgical through Minimal Incision
On pump, arrested heart sutureless valve replacement
Transaortic, beating heart delivery
Transapical delivery
Percutaneous - antegrade or retrograde
Inva
siveness
F.I.M. Balloon Aortic Valvuloplasty
1985
0
100
200
First attempt of treating non surgical AS patients
Thousand of cases performed worldwide
Hemodynamic / symptomatic improvement
No effect on patient’s survival
ONE MAIN LIMITATION
Early valve restenosis: 80% at one year
BAV
THE LANCET, JANUARY 11, 1986
F.I.M.: 20mm Balloon
Sept 1985
THE GOAL….
F.I.M. Balloon Aortic Valvuloplasty
1985Concept of« stented valve », to rule out post-BAV valvular restenosis
1987
1989
First animal implantation (balloon exp) in pig
Post mortem studies of intra-valvular stenting
« Percutaneous Valve Technology » (prototypes)
1999 First animal implantation(self exp)
2000Large series of animal implantation
2000-02 F.I.M. PHV implantation2002
Feasibility Studies (antegrade)2002-03
First in ManCorevalve 25 F
2004
International TF Feasibility Studies2005-07
CE markcommercialization2007
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
8 days post-implantation
F.I.M Alain Cribier 2002
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.
Edwards SAPIENCore Valve
CE-MARKED DEVICES
(Transfemoral / Transaxillary) (Transfemoral / Transapical)
Generation 1
25FrEndovascular
Generation 2
21FrEndovascular
Generation 3
18FrPercutaneous
14 patients
65 patients
>3000 patients
*
CoreValve evolution
General anesthesiaSurgical cutdown/repairVentricular assistance
• Pre-closing with ProStar™ • Local Anesthesia• Beating heart • Valve delivery without rapid pacing• No cardiac assistance
18 French Procedural Progress
Evolution to a « real cath lab procedure »
within the first 40 Patients of 18 Fr study
Developments and Improvments
Untreated
Equine Tissue
Cribier-Edwards™ THV
23mm
Edwards SAPIEN™ THV
23mm, 26mm
Treated
Bovine Tissue
DurabilityHeamodynamic Performance
Profile – Ease of Use
Edwards SAPIEN™ THV II
23mm, 26mm
Low profile
Cobalt-chrome
Ascendra Introducer Sheath 26Fr.
RetroFlex II
Edwards SAPIEN
RETROFLEX DELIVERY SYSTEM
Stainless Steel Braid – BETTER TORQUE
Front end rotational grip – SINGLE HANDED ARTICULATION
Edwards SAPIEN evolution
Joint Task Force Positioning Paper:‟Transcatheter valve implantations for patients with Aortic Stenosis”
TAVI is reserved to pts. with
severe AS and symptoms who
are inoperable or at high risk
for surgery
INDICATION
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 and Valve Area
ECHO TT and TEE
Hemodynamics
CT
MRI
Dobutamine testing
Pouleur AC , et al, Radiology, 2007;244: 745-754
MDCT MRI TEE
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 ao-
fem.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 ofAmplatz Ultra stiff0,35 CookWire
Contraindications for TA approach
Previous surgery of the LV (Dor)
Calcified pericardium
Severe respiratory insufficiency
Dislocated LV apex
Teamwork
anesthesiologist
Surgeon
cardiologist
others
Interventionalist
40
The procedure requires the close cooperation of a team of specialists in valve disease, including clinical cardiologists, echocardiographists, interventional cardiologists, cardiac surgeons, and anaesthesiologists.
Appropriate environment
Hybrid room
Cath lab
Operating room
NO COMPROMISES
Imaging quality
Sterility
Instrumentation
Ergonomics
Device availability
POST CE MARK RESULTS
(from registries)
Edwards THV Clinical Studies
Program
Methods
34 Centres Initially Participating
in Commercial Launch
1123 patients
Included:
32 Centres
1038 Patients
The SOURCE Registry has
100% procedure data
98% 30 day data
All consecutively enrolled
Excluded:
2 Centres / 85 Patients• Unable to obtain Ethic Cte approval
• Unable to secure administrative support
• One missing patient due to admin. error
Source Registry
Baseline Demographics and Risk
FactorsTF
(n=463)
TA
(n=575) P-value
Age (yrs) 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
Logistic EuroSCORE 25.7 29.2 <0.005
Peripheral Vascular
Disease
10.9% 27.5% <0.001
Carotid Artery Stenosis
(>50%)
7.6% 17.1% <0.001
Incidence of CAD 47.4% 56.0% <0.006
Porcelain Aorta 4.6% 11.5% <0.001
Prior CABG 17.6% 26.9% <0.001
Mitral Valve Disease 16.1% 32.8% <0.001
Risk Analysis: Logistic
EuroSCORE
0
10
20
30
40
50
Pe
rce
nt
of
Pa
tie
nts
< 20 20 - 40 41 - 60 > 60
Baseline EuroSCORE - The SOURCE Registry
Transapical
Transfemoral
6% 3%
16%
12%
49%48%
30%
37%
As EuroSCORE gets higher, ratio of TA to
TF is greater
TF (n=459) TA (n=571)
30 day 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
Survival
0.6
0.65
0.7
0.75
0.8
0.85
0.9
0.95
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
Fraction of Months post Procedure
Su
rviv
al
< 20 >= 20
SOURCE 30 Day All Cause Mortality -- Transfemoral Approach
Stratified by Logistic EuroSCORE SOURCE 30 Day All Cause Mortality -- Transapical Approach
Stratified by Logistic EuroSCORE
0.6
0.65
0.7
0.75
0.8
0.85
0.9
0.95
1
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1
Fraction of Months post Procedure
Su
rviv
al
< 20 >= 20
p=0.068
Survival of TA pts with ES< and >20 are significantly different (93.4 vs. 88.1) (p=0.067)
Procedure Complications (<30 Days)
TF (n=463) TA (n=575) Total (n=1038)
Acute procedure
success
436/95.6%n=456
523/92.9%n=563
959/94.1%n=1019
Device Success
Comp
428/92.4% 522/90.8% 950/91.5%
Conversion to
sAVR
8/1.7% 20/3.5% 28/2.7%
AR >+2** 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%)
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)
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)
≥15% (18F)
Age ≥65 y
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
+1 or more
Primary Endpoints:
• Procedural success
• 30-Day outcomes
• Long term outcomes
CoreValve post CE mark experience
CLINICAL INDICATIONS
18 F Expanded Evaluation Registry(EER)
Patient Demographics
52
In-Training Solo Total EER
Mean ± SD or % N = 918 N = 565 N = 1483
Age (years) 80.8 6.7 81.7 5.9 81.2 6.4
Logistic EuroSCORE (%) 22.2 13.6 23.2 13.7 22.6 13.7
Female 55.8% 54.7% 55.4%
NYHAI-II: 17.2%
III-IV: 82.8%
I-II: 14.4%
III-IV: 85.6%
I-II: 16.1%
III-IV: 83.9%
Aortic Valve Area (cm2) 0.65 0.18 0.61 0.17 0.64 0.18
Peak gradient (mm Hg) 78.3 26.1 81.3 25.8 79.5 26.1
Mean gradient (mm Hg) 48.4 16.4 50.4 16.0 49.2 16.3
LVEF(%) 52.9 13.8 51.4 13.7 52.3 13.8
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
Age (years)
Logistic Euro SCORE
Female
NYHA I-II
NYHA III-IV
Aortic Valve Area (cm2)
Peak Gradient (mmHg)
Mean Gradient (mmHg)
LVEF (%)
Procedural Results
In-Training
(N = 867)
Solo
(N = 511)
Total EER
(N = 1378)
97.7% 98.4% 98.0%
0%
20%
40%
60%
80%
100%
Procedural Success
131.2120.5
127.2
0
20
40
60
80
100
120
140
160
180
200
Procedure Mean Time SD (minutes)
Mortality Rate
2.6%1.9%
2.4%
0%
2%
4%
6%
8%
10%
12%
In-Training
(N = 918)
Solo
(N = 565)
Total EER
(N = 1483)
24-Hour
10.7%9.7%
10.3%
0%
2%
4%
6%
8%
10%
12%
In-Training (N = 918)
Solo (N = 565)
Total EER (N = 1483)
30-Day
24 - Hour
30- Day
In Training Solo Total EER In Training Solo Total EER
0%
6%
12%
0%
6%
12%
≤ 30-Day Adverse Events*
In-Training Certified Both
CARDIAC Deaths†5.4% 3.9% 4.9%
Aortic Dissection 0.7% 0.2% 0.6%Cardiac Tamponade 3.5% 2.2% 3.0%Cardiac Perforation 2.3% 1.8% 2.1%
Access Site Complication 2.5% 0.7% 1.8%Major Bleeding 5.1% 3.3% 4.4%
Conversion to Surgery 0.6% 0.9% 0.7%Myocardial Infarction 0.9% 0.4% 0.7%
Major Arrhythmia 9.1% 4.6% 7.5%Pacemaker 18.8% 17.8% 18.4%
Renal Failure 1.9% 1.5% 1.7%Stroke 2.2% 2.2% 2.2%
TIA 0.2% 0.4% 0.3%Structural Valve Dysfunction 0.0% 0.0% 0.0%
Valve Migration 0.0% 0.0% 0.0%
* Multiple events in same patients = data not cumulative† Includes deaths where cause is not known
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 30-day 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