TAVItalk - Edwards Lifesciences

Clinical Cardiology Edition 2011-2012
GUEST EDITORS:
John B. Chambers, MD, FESC
The Edwards Transcatheter Heart Valve (THV) Newsletter
TAVItalk
Consultant cardiologist and President of the British Heart Valve Society
The Cardiovascular Centre
Guy’s & St Thomas’ Hospital, London, UK
Mauro romano, md
thomas heitzer, MD
Department of Cardiac Surgery
Hôpital Privé Jacques Cartier
Massy, France
Director, Cardiology
Klinikum Dortmund GmbH
Dortmund, Germany
Aortic stenosis
today
John B. Chambers, MD, FESC
Consultant cardiologist and
President of the British Heart Valve Society
The Cardiovascular Centre
Guy’s & St Thomas’ Hospital
A
ortic valve thickening is common. Moderate or
severe stenosis is found in about 3% of people aged
75 and over1. Symptomatic aortic stenosis is fatal if left
untreated but intervention, whether by conventional surgery or TAVI, is effective2.
However, aortic stenosis may still not be detected3 and more
than 50% are not diagnosed until after death3,4. (See
special box “Key developments required” on page 2).
There are many reasons for failing to make a
diagnosis. Patients may not present and there are
no national screening programmes anywhere
in the world. Family practitioners tend to underestimate the significance of a murmur, and
may mistakenly assume that systemic hypertension rules out severe aortic stenosis5.
Identifying aortic stenosis allows meticulous follow-up to watch for early LV decompensation or even minor symptoms including
a reduction in exercise capacity. These are easy
to miss without specialist attention. Minor symptoms may incorrectly be blamed on old-age or another cause (for
(continued on page 2)
New technology, new success
Jean-Luc lemercier
Vice President, THV Europe
Edwards Lifesciences
W
2012
elcome to this special edition of TAVItalk, the
newsletter of the Transcatheter Heart Valve Group at
Edwards Lifesciences. This edition, intended for Clinical
Cardiologists, focuses on Aortic Stenosis. Guest Editors,
Dr. John B. Chambers, Dr. Mauro Romano and Dr. Thomas
Heitzer, share their perspectives on how this new technology
has helped a large number of patients with severe aortic valve
disease.
A significant number of patients with severe
symptomatic aortic stenosis are not diagnosed or
treated in time and, through identifying appropriate
patients at the right time, physicians can play a vital role
in improving heart valve disease detection.
With more than 50 years experience in the creation and
development of heart valves, Edwards Lifesciences recognises the
importance of maintaining an open dialogue between the clinical
cardiologists who refer patients for TAVI, the Heart Teams who
have TAVI experience and the engineers who design and
manufacture the valves and delivery systems used in the TAVI
procedure. The interaction between these three important stakeholders is as vital today to Edwards as it was half a century ago.
Early referral to a Heart Team has been shown to reduce the
(continued on page 12)
THIS ISSUE
1 Aortic stenosis today john b. chambers
1 new technology, new success jean-luc lemercier
3What is tavi? a guide for clinicians
3 new treatment options
lead to increased referral, awareness and proper treatment
4 new data from the source registry olaf wendler
5 the cardiac surgeon's perspective mauro romano 
5 Quotable pieter stella
FOR USE OUTSIDE THE UNITED STATES ONLY. NOT INTENDED FOR GENERAL DISTRIBUTION.
6 tavifest: reunion in dortmund Thomas heitzer et al
8 clinical evidence for tavi continues to solidify
jodi akin
10 Engineers' corner: an inside look at the edwards sapien &
edwards sapien XT THVs laksen sirimanne
10 QUOTABLE pilar tornos mas
12 Edwards Lifesciences receives FDA approval for first
transcatheter aortic heart valve in the USA
12 quotable jean fajadet
TAVItalk
CLINICAL CARDIOLOGY EDITION
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john p. Chambers
(continued from page 1)
REFERENCES
Key developments required
Identification in the community with standard
echocardiography of those with abnormal
screening echocardiography or murmurs on
auscultation
Specialist clinics to allow meticulous follow-up
Education of clinicians about results of
intervention to encourage appropriate referral
Patient education to encourage presentation to
screening process
Trials of early prophylactic surgery in
asymptomatic aortic stenosis
“Too many patients with severe
symptomatic valve disease are
denied surgery.”11
—B. Iung, Bichat Hospital, Paris
‘‘Guidelines are not consistently
followed. In actual practice, more than one
third of patients eligible for AVR are not
referredFig.
for1: evaluation.
Additionally, the
Effect of surgery on survival in severe AS
Euro Heart Survey of 5,000 patients from
100
92 centres in 25 European countries deter80
mined that
32.3% of patients over the age
60
of 75 were denied surgery.”11
40
As illustrated
in Figure 2 below, five
20
different surveys identified 30% to 60%
1
3
5
7
9
11
13
15
of patients who were
referred for
YEARS
AVR, severe
ASYMPTOMATIC
NO AVR, ASYMPTOMATIC
surgery with
symptomatic
aortic
AVR,
SYMPTOMATIC
NO
AVR,
SYMPTOMATIC
stenosis but were not treated.
Fig. 1: Effect of surgery on survival in severe AS
% SURVIVAL
2. Brown ML et al. The benefits of early valve replacement in
asymptomatic patients with severe aortic stenosis. J Thorac
Cardiovasc Surg 2008;135: 308-315
3. Chambers, JB. Aortic stenosis is common but often
unrecognised. Brit Med J 2005;330:801-802.
4. Andersen JA, et al. Isolated valvular aortic stenosis.
Clinico-pathological findings in an autopsy material of elderly
patients. Acta Medica Scandinavica 2009;16:61-4.
5. Das P, et al The patient with a systolic murmur: severe
aortic stenosis may be missed during cardiovascular
examination. Quart J Med 2000;93:685-8.
6. Iung B, et al. A prospective survey of patients with valvular
heart disease in Europe: The Euro Heart Survey on valvular heart
disease. Europ Heart J 2003;24:1231-1243
Fig. 2: Surgery vs. no surgery in AS patients12
8. Iung B. Management of the elderly patient with aortic
stenosis. Heart 2008;94:519-24
9. Dua A, Dang P, Shaker R, Varadarajan P, Pai RG. Barriers to
surgery in severe aortic stenosis patients with class I indications
for aortic valve replacement. J Heart Valve Disease
2011;20:396-400.
10. Chan KL, Teo K, Dumesnil JG et al. Effect of lipid lowering
with rosuvastatin on progression of aortic stenosis. Circulation
2010;121:306-314.
11. Iung B, Baron G, Tornos P, et al. Valvular heart disease in
the community: a European experience. Curr Probl Cardiol
2007;32:609-61
12. van Geldorp MW, van Gameren M, Kappetein AP, et al.
Therapeutic decisions for patients with symptomatic severe
aortic stenosis: room for improvement? Eur J Cardiothorac Surg
2009;35:953-7.
13. Bouma BJ, van Den Brink RB, van Der Meulen JH, et al. To
operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999; 82:143-8.
14. Iung B, Cachier A, Baron G, et al. Decision-making in elderly
patients with severe aortic stenosis: why are so many denied
surgery? Eur Heart J 2005;26:2714-20.
15. Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of
622 adults with asymptomatic, hemodynamically significant
aortic stenosis during prolonged follow-up. Circulation 2005;
111:3290-5.
16. Charlson E, Legedza AT, Hamel MB. Decision-making and
outcomes in severe symptomatic aortic stenosis. J Heart Valve
Dis. 2006;15:312-21.
17. Bach DS, Cimino N, Deeb GM. Unoperated patients with
severe aortic stenosis. J Am Coll Cardiol 2007;50:2018-9.
Fig. 3: Who is responsible for opting not to have
intervention despite clinical indications?
Patient
36%
100
100
80
80
60
60
40
40
20
20
1
3
5
7
9
11
13
15
YEARS
AVR, ASYMPTOMATIC
NO AVR, ASYMPTOMATIC
AVR, SYMPTOMATIC
NO AVR, SYMPTOMATIC
41
33
30
60
48
50
67
70
40
52
Fig. 2: Surgery vs. no surgery in AS patients12
Other
9%
Cardiologist
33%
1999
2005
2005
2006
2007
Bouma13 Iung14 Pellikka15 Charlson16 Bach17
NO SURGERY
For use outside The United States only | Not intended for general distribution.
100
1. Nkomo VT, et al. Burden of valvular heart diseases: a
population-based study. Lancet 2006;368:1005-1011
7. Dunning J et al Aortic valve surgery – marked increases in
volume and significant decreases in mechanical valve use; an
analysis of 41,227 patients over 5 years from the Society for
Cardiothoracic Surgery of GB and Ireland National database.
Heart in press
Research on medical modulators of disease
progression
% SURVIVAL
example obesity), or patients may slow
their walking pace to avoid getting symptoms. For this reason, exercise-testing
to reveal symptoms is indicated in any
asymptomatic patient who is at low risk
for surgery. However, it is still performed
only rarely, 6% in the EuroHeart Survey6. The same survey showed that, as a
result of imperfect detection and followup, patients tend to have surgery too late,
when 47% are already in NYHA Class III
or IV.
Access to surgery is variable7. The
situation is particularly unsatisfactory
for those aged over 75, at least a third of
whom are not referred for surgery at all
despite having symptomatic severe stenosis8. (Figures 1-2) The main reasons
cited , either age per se, or an LV ejection fraction reduced to 35-50% are not
valid in the absence of significant comorbidity. Once referred, a third may refuse
conventional surgery9 (Figure 3) and
whether this is because of inadequate
preparation and information, needs to be
investigated.
We lack a medical therapy for slowing
the rate of progression of aortic stenosis.
Lipid lowering does not reduce the risk
of events unless other indications for lipid lowering also exist, notably diabetes10.
We await more research into the modulation of inflammation and calcification.
Until then, the only treatment is with invasive intervention. Our surgical and interventional cardiac skills are now good.
Although more data are needed, particularly on the durability of transcatheter
valves, the main challenge is now the
organisation of services for valve disease
to improve detection rates and follow-up
and reduce variability in access.
SURGERY
Cardiothoracic
surgeon 20%
R
TAVItalk
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Definitions
What is TAVI?
T
ranscatheter Aortic Valve Implantation (TAVI) is an alternative
approach to surgical Aortic Valve Replacement (surgical AVR). A
less-invasive procedure, it avoids cardiopulmonary bypass and cardiac arrest, takes less time and requires less anaesthesia compared to
open-heart surgery and is an alternative option for patients at high
risk for traditional open heart surgery.
TAVI is performed via a transfemoral or transapical access without cardiopulmonary bypass. Both approaches involve inserting and
deploying a crimped valve across the native aortic valve after it has
been initially widened by balloon valvuloplasty (BAV). The transcatheter heart valve or THV is mounted onto a transfemoral (TF)
or transapical (TA) balloon-expandable delivery system. Patients
may be suitable for either approach, and the Heart Team will decide
which is the best option, taking into consideration whether it would
be better to be treated by TAVI or surgical AVR. 
Fig. 1: Transfemoral
balloon expandable
delivery system
Fig. 3: Edwards SAPIEN XT
transcatheter heart valve
in position after insertion.
Fig. 2: Transapical
balloon-expandable
delivery system
“A significant population of patients
with AS are still treated medically.”
“Surgical intervention should be performed
promptly once even minor symptoms occur.”
— SC Malaisrie, Bluhm Cardiovascular Institute
Northwestern University Memorial Hospital, Chicago, Illinois1
— CM Otto, University of Washington School of Medicine
Seattle, Washington
New treatment options lead to increased referral, awareness,
and proper treatment
A
retrospective study determined that the introduction of TAVI was associated
with an increase in aortic
valve replacement referrals
and a decrease in the rate of
unoperated AS. This positive
impact was due to increases
in both TAVI and AVR volume. Increased volume was
not associated with worse
patient survival.1
European Society of Cardiology
Aortic Stenosis Treatment Guidelines4
According to the ESC Guidelines, severe AS is defined by these characteristics:
rating the latest recommendations for TAVI
and AVR procedures are
underway and will be
published in early 2012. 
Aortic valve area: <1 cm2 or <0.6cm2/m2 BSA
Jet velocity: >4.0 m/sec
references
1. Malaisrie SC, Tuday E, Lapin B,
et al. Transcatheter aortic valve
implantation decreases the rate of
unoperated aortic stenosis.
Eur J Cardiothorac Surg;
e-pub Jan. 11, 2011.
2. Vahanian A, Blanc JJ, Budaj A, et al.Guidelines on the management of valvular heart disease.
Eur Heart J 2007;28:230-68.
3. Bonow RO, Carabello BA, Chatterjee K, et al. ACC/AHA 2006 Guidelines for the Management
of Patients With Valvular Heart Disease. Circulation 2006;114:450-527
4. Baumgartner H, Hung J, Bermejo J, Chambers J, Evangelista A, Griffin BP, Iung B, Otto CM,
Pellikka P, Quinones M.Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Europ J Echo 2009;10:1-25.
Mean transvalvular pressure gradient: >50 mmHg (ESC), >40 mmHg (AHA)
The 2007 ESC guidelines for AS recommend valve replacement for
Class I patients, i.e., those with severe AS and symptoms.2 The 2006
ACC/AHA Guidelines recommended that AVR should be performed
in virtually all symptomatic patients with severe AS. They stress that
age is not a contraindication to surgery.3 New guidelines incorpo-
TAVItalk
CLINICAL CARDIOLOGY EDITION
4
New data from The SOURCE Registry
Olaf Wendler, MD, PhD, FRCS
Clinical Director for Cardiovascular Services
Consultant Cardiothoracic Surgeon
King’s College Hospital, Denmark Hill
London, United Kingdom
INTRODUCTION
Olaf Wendler gave a presentation at EuroPCR 2011 of the final
one-year outcomes from more than 2,300 patients enrolled in The
SOURCE Registry. These results have also been published recently1,2.
This is a summary of his presentation.
T
he SOURCE Registry began in 2007 to
monitor procedural results with the commercialised Edwards SAPIEN valve. The registry has two Cohorts: Cohort 1, consisting
of consecutive patients enrolled at 32 centres
across Europe from November 2007 to January 2009; and Cohort 2, consisting of consecutive patients at 37 European centres followed
from February 2009 to December 2009.
still have a higher incidence of comorbidities, particularly extracardiac, such as pulmonary, peripheral vascular and carotid artery
disease. This explains their 74.2% survival at 1-year compared
with 80.1% for the TF approach. One-year mortality was significantly higher in patients with vascular access complications. Not
unexpectedly, causes of death were mainly non-cardiac related.
Interestingly, there was no significant improvement in terms of
1-year mortality between Cohorts 1 and 2. It will therefore be
interesting to see what impact the new generation Edwards SAPIEN XT
valves and delivery devices will have on patient
outcomes.
"In the first year,
TAVI AND CABG
An interesting sub-analysis of The SOURCE
Registry data focused on patients who subsequently underwent TAVI after they previously
received coronary bypass surgery (CABG). Early
included and data have
reports on TAVI from North America demonstrated inferior outcomes of TAVI in patients
now been presented
with previous CABG or percutaneous coronary
All centres were required to provide comintervention. In The SOURCE Registry, howplete data sets on consecutive patients; the
for the entire cohort
ever, previous CABG was shown not to be a risk
strict criteria for inclusion in the registry. At
factor for TAVI 1-year mortality.
EuroPCR 2011, the complete 1-year data
Interestingly, there was no significant differof 2,307 patients."
from 2,307 patients in both cohorts were
ence in mortality between the TF and TA appresented. The primary aim was to generate
proach, although the incidence of comorbidities
scientifically robust and comprehensive data
in the TA group was again higher. One contribon patient results as well as to identify predictors of outcome. Early
uting factor to these outstanding results may be the elimination of
publication of 30-day data showed survival of 92.5% in patients who
apical complications in the TA group, which again demonstrates that
underwent TAVI via a transfemoral (TF) approach and 89.1% in
reliable closure techniques for the left ventricular apex after TA-TAVI
those who underwent TAVI via the transapical (TA) approach.
would potentially improve outcomes even more.
over 1,000 patients were
ADVANCES IN PATIENT SELECTION
Patients selected for either the TF or TA approach continue to
be at high-risk for conventional AVR. While the European learning curve has had some influence on the range of patients' logistic
EuroSCOREs, the overall EuroSCOREs remain high. Compared
with the TF route, patients undergoing TAVI via the TA approach
REFERENCES
1. Thomas M et al. One-Year Outcomes of Cohort 1 in the Edwards SAPIEN Aortic Bioprosthesis
European Outcome (SOURCE) Registry: The European Registry of Transcatheter Aortic Valve
Implantation Using the Edwards SAPIEN Valve. Circulation. 2011 Jul 26;124(4):425-33. Epub
2011 Jul 11.
2. Wendler O et al. The SOURCE Registry: what is the learning curve in trans-apical aortic valve
implantation? Eur J Cardiothorac Surg. 2011 Jun;39(6):853-9; discussion 859-60
KAPLAN-MEIER 1 YEAR SURVIVAL
COHORT 1 & 2
KAPLAN-MEIER 1 YEAR SURVIVAL BY THE
TRANSFEMORAL & TRANSAPICAL PROCEDURES
SURVIVAL ALL COHORT 1 COHORT 2 P
SURVIVAL ALL
30 days
1 year
90.5%
76.5%
91.2%
76.0%
100%
ns
ns
30 days
1 year
90.5%
76.5%
TF
92.5%
80.1%
100%
All (N=2307)
Cohort 1 (N=1038)
Cohort 2 (N=1269)
90
80
70
TA
89.1%
74.2%
All (N=2307)
Transfemoral (N=920)
Transapical (N=1387)
90
Survival
Survival
89.8%
77.0%
80
70
60
60
50
50
0
3
6
9
12
15
18
Time to death (months)
21
24
For use outside The United States only | Not intended for general distribution.
0
3
6
9
12
15
18
Time to death (months)
21
24
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TAVItalk
The cardiac surgeon's perspective
Mauro romano, md
cardiac imaging experts, anaesthesiologists, internists, geriatric
specialists, etc.
In the real world, this harmonious team approach needs to be
seen along with adequate training of the individual specialists to
reach the technical excellence required to offer the patient the
ince its introduction and First-in-Man implantation in 2002,
maximum safety, performing the procedures in an appropriate entranscatheter aortic valve implantation (TAVI) has been increasvironment, such as the hybrid operating suites.
ingly accepted as a valid alternative to
Concerning patient selection itself, we
surgical aortic valve replacement for elknow that the risk scores are not perfect and
derly and/or high risk patients.
may be inadequate. They help in the decision making process, but should not comThe recent publication of the results
"From this amount of
pletely replace our clinical common sense.
of The PARTNER Trial corroborate this
Training is further facilitated by expert procchoice. Cohort B clearly shows the striktoring, protecting newcomers from the risks
positive information
ing superiority of TAVI over conservative
of the learning curve which today is becomtreatment, while Cohort A demonstrates
ing shorter and safer.
non-inferiority to conventional aortic
we should learn...TAVI has
Implanting devices and prostheses imvalve replacement in high-risk surgical
proves
continuously, making us more
candidates. These encouraging findings
become an essential tool
confident during these procedures that
are strengthened by the mid-term clinical
nowadays reach nearly 100% of success
and echographic results of The SOURCE
rate. There are points that are still open to
Registry evaluating more than 2,300 high
in the treatment of
debate, such as the durability of the prosrisk or inoperable patients in both transtheses, as well as the question of offering
femoral and transapical subsets. And yet
aortic valve stenosis."
these procedures to younger and/or stananother positive point comes from the
dard risk patients. While further studies
FRANCE II registry showing the costare necessary before answering these queseffectiveness of TAVI versus conventional
tions, still, to my knowledge, primary tisAVR for high-risk patients.
sue failure responsible for explant of transcatheter valves seems
From this amount of positive information we should learn some
to be rare.
lessons and draw some conclusions that over a short time, TAVI
Today, we can clearly say that after 40,000 worldwide implants,
has become an essential tool in the treatment of aortic valve steTAVI is here to stay. Furthermore, our patients’ profile is dramatinosis, providing the surgical community with a novel approach to
cally changing as we are faced with an increasingly ageing populathis disease from a multidisciplinary point-of-view.
tion with higher-risk individuals being referred for treatment. This
Patient selection must be accurate to warrant the best results, and
can only prompt the surgical community to move toward a novel
this can be obtained only through the perfect cooperative work of
approach in cardiac surgical training turned toward less invasive,
cardiac surgeons, interventional cardiologists, echocardiographers,
transcatheter procedures and ultimately, a team approach. 
Department of Cardiac Surgery
Hôpital Privé Jacques Cartier
Massy, France
S
TAVItalk
QUOTABLE
On the importance of including general cardiologists in
TAVI patient care decisions
“I believe it's essential to involve referral cardiologists in this new treatment option for their patients. Involvement meaning a better understanding of the indications, current techniques and patient outcomes of TAVI procedures. This will
also provide a better follow-up for the patients and secure continuous engagement of all involved.”
Pieter Stella, MD, PhD
Director of the Interventional Cathlab
University Medical Centre (UMC)
Utrecht, The Netherlands
TAVItalk
CLINICAL CARDIOLOGY EDITION
6
TAVIfest: Reunion in Dortmund with 74 TAVI
patients
PROF. DR. THOMAS HEITZER et al
Director, Cardiology
Klinikum Dortmund GmbH
Dortmund, Germany
A
ll together we are more than 6,000 years old looking forward to
many more years.”
Dr. Krakor, Medical Director of the Department of Cardiovascular
Surgery.
That was the slogan of a very special event that took place on
13 July 2011 at the Klinikum Dortmund when former patients
were invited to celebrate two and a half years of successful transcatheter aortic valve implantations at the clinical centre. The first
TAVI intervention in Dortmund was performed in January 2009 and since then,
the clinical centre has implanted over 200
Edwards SAPIEN valves.
There were many reasons for choosing Edwards SAPIEN valves.
Prof. Dr. Heitzer, Medical Director of the Department of Cardiology, explained that “Edwards has fifty years of experience in inventing heart valves that have been used by our surgeons, more
than ten years of expertise in constructing transcatheter aortic valve systems, as
well as a balanced and comprehensive
training program for the multidisciplinary Heart Teams.”
In the course of a get-together with
‘Kaffee und Kuchen’, the TAVI patients
had the opportunity to speak with the doctors, as well as other patients and their
families. The agenda also included lectures
about the history of TAVI, and the main issues in terms of post-procedural care.
6,000 years and more:
The first
TAVI patient meeting
Dr. Saul, Assistant Medical Director
of the Department of Cardiology, highlighted the many advantages of TAVI for
patients suffering from aortic stenosis
(AS), “No life support machine is necessary, and there is no need to stop the
heart or open the patient’s chest.” It is
like “changing the valve while the engine
is still running,” he explained.
Three years ago, the medical staff came
in Dortmund, Germany
across the minimally invasive procedure
called TAVI for the first time. Initial adminThe event itself was a great success,
istrator doubts quickly disappeared as they
providing a platform, not only for dereviewed the potential consequences of
tailed information about TAVI procewhat could be achieved with this new interdures, but a celebration for individual
vention. “The complication rate remained
patients and their TAVI experiences as well.
very low, and with every recovered patient who left the hospital our decision to go ahead with a TAVI procedure was further confirmed” said
Alfred Zarnoch, 91, recovered quickly enough to walk through the hospital in 2 days.
Patient focus:
Alfred Zarnoch
91-years-old
“If you reject surgery, you won’t live longer than six
months or even less.” That was the devastating prognosis
given to Alfred Zarnoch by his doctors when he had been
diagnosed with severe AS. A heart valve replacement was
inevitable.
Nevertheless, Alfred Zarnoch hesitated. He was scared
of undergoing an open heart surgery procedure. But
when the doctors, members of the Heart Team at Klinikum
Dortmund recommended the new minimally invasive treatment option called TAVI to him, he finally accepted.
The transapical valve implantation went well and Alfred
Zarnoch recovered quickly. “I was back on my feet again
very soon,” the 91-year-old great-grandfather remembers.
Only two days after the intervention, he was able to get out
of bed and walk around in the hospital.
For use outside The United States only | Not intended for general distribution.
TAVItalk
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“I am able to climb stairs without any breathing problems....
That is just such a wonderful feeling.” 
able to climb the 88 stairs to their flat
on the fourth floor without any trouble.
“The intervention completely changed
my life!” says Horst Schmechel.
Patient focus:
Horst Schmechel
87-years-old
“Actually, I'm a very active person. I was always used to doing sports, gardening, hiking and things like that.” That’s how Horst
Schmechel describes himself. But when the
first symptoms of AS occurred, his physical
ability decreased little by little.
Patient focus :
Hildegard Brinkmeier
85-years-old
When the doctors recommended
Hildegard Brinkmeier undergo TAVI
to treat AS, she was suffering from
breathlessness and chest tightness.
Nevertheless, the 84-year-old woman
didn’t expect any remarkable benefits
from TAVI or surgery and decided to
reject heart valve replacement of any
kind. But as her symptoms and physical impairments were getting worse,
she finally agreed.
The former factory owner experienced
shortness of breath and had a burning sensation in his chest. After several months
Horst Schmechel wasn’t able to walk anymore. “Those were difficult times,” his wife
Karin Schmechel remembers, “anxiety was
always present.”
As their patient was too weak to undergo
conventional open heart surgery, doctors
decided to perform a transfemoral TAVI
procedure. Only one week after the intervention, Horst Schmechel was able to leave
the hospital.
Today he is clearing weeds in his garden
again, and even travelling to visit friends in
Berlin is no longer a problem—as he is now
The July, 2011 Klinikum Dortmund TAVI patient reunion
celebrated over 200 Edwards SAPIEN valve implantations.
Horst Schmechel, 87 (center) hails the TAVI intervention that changed his life.
To her own surprise, Hildegard
Brinkmeier recovered very quickly
and noticed some significant improvements shortly after TAVI. “I am able
to climb stairs without any breathing
problems,” she says. “That is just such
a wonderful feeling.” 
Hildegard Brinkmeier, 86, is now climbing stairs with no problem.
TAVItalk
CLINICAL CARDIOLOGY EDITION
8
Clinical evidence for TAVI continues to solidify
Jodi Akin
Vice President, Global Clinical Affairs
Edwards Lifesciences
In Cohort A, the safety and effectiveness of the Edwards SAPIEN
Transcatheter Heart Valve (THV) was
compared to surgical aortic valve replacement (AVR) in high-risk patients
with severe aortic stenosis. Patients
were evaluated for viable femoral access, and then assigned accordingly
to either the transfemoral (TF) and
transapical (TA) study groups. Within
both the TF and TA groups, patients
were randomised to TAVI or surgical
AVR procedures. The primary endpoint was death from any cause at
one year. The primary hypothesis was
that TAVI is not inferior to
surgical replacement.
The PARTNER Trial (Placement of
AoRTic TraNscathetER Valve Trial),
is the world’s first prospective, randomised, controlled trial for transcatheter heart valves (THV)1,2. Here
is a summary of each of the two cohorts involved in this trial.
INTRODUCTION
The “Nautilus” depicts the evolution and momentum of the Edwards
Lifesciences global clinical research
program for TAVI. In 2010, the results of TRAVERCE, PARTNER EU,
The SOURCE Registry, and The
PARTNER Trial were all
published in peer-reviewed
journals. Each study and
manuscript reflects upon
unique aspects of the TAVI
experience, from feasibility
through randomised controlled pivotal trials, as well
as extensive post-market
surveillance of real-world
practice.
We are also pleased that
recently, in the United
States, the FDA has approved of the use of the
THVs studied in much of
this clinical research (see
article on back page).
1
T H E PA RT N E R T R I A L P R O T O C O L4
Severe Symptomatic Aortic Stenosis
ASSESSMENT
Yes
No
The “Nautilus”
depicts the evolution
and momentum of the
Operability
Edwards Lifesciences global clinical research program for TAVI.
2 Cohorts
Cohort A
ASSESSMENT
Transfemoral Access
Yes
Cohort B
Individually Powered
(N = 1,057)
n = 699
No
n = 358
ASSESSMENT
Transfemoral Access
Yes
Not in
Study
TA
TF
(n = 207)
(n = 492)
No
The PARTNER Trial
The past year has witnessed
publications of significant
results of The PARTNER
Trial
(Placement
of
AoRTic
TraNscathetER
Valve Trial), the world’s first
prospective,
randomised,
controlled trial for transcatheter heart valves (THV)1,2.
Following is a summary of
each of the two cohorts involved in this trial.
Patients in
The PARTNER Trial were
assigned to two individually
powered patient cohorts.
STUDY DESIGN
1:1 Randomisation
TF
TAVI
1:1 Randomisation
AVR
VS (Control)
(n = 244)
TA
TAVI
(n = 248)
Because Cohort B concluded enrolment before
Cohort A, the results of
Cohort B were published
ahead of Cohort A.
1:1 Randomisation
TF
TAVI
AVR
VS (Control)
(n = 104)
(n = 103)
VS
Standard Therapy
(n = 179)
In Cohort B, the safety
and effectiveness of the
Edwards SAPIEN THV
was compared to best
medical
management
(standard therapy) in inoperable patients with
severe aortic stenosis.
Patient selection required
at least two cardiothoracic
surgeons and an interventional cardiologist to agree
that patients were not suitable candidates for surgery.
Patients were randomised
to receive either the
Edwards SAPIEN THV or
standard therapy.
(Control)
(n = 179)
COHORT A INCLUSION C RITERIA1 - 3
COHO R T B I N C LUSI ON C R I TE R I A2
RESULTS : Cohort B
STS score
STS score
In September 2010 the
results from Cohort B
were simultaneously published in The New England Journal of Medicine
and presented at Transcatheter Cardiovascular
Therapeutics (TCT).1 Cohort B examined 358 patients with severe, symp-
≥ 10
and/or
Predicted operative mortality
≥ 15%
NYHA functional class
≥ II
AVA
< 0.8 cm2
or
Mean AVG
> 40 mm Hg
or
Peak jet velocity
> 4.0 m/s
Predicted operative mortality
NYHA functional class
AVA
or
Mean AVG
or
Peak jet velocity
11.6*
> 50%†
> II
2
< 0.8 cm
> 40 mm Hg
> 4.0 m/s
*This mean score reflects enrolled patient group; not required for inclusion.
†Patient selection required at least two cardiothoracic surgeons and an interventional cardiologist to agree that patients were
not suitable candidates for surgery.
4,5
AVA, aortic valve area; AVG, aortic valve gradient; NYHA, New York Heart Association; STS, Society of Thoracic
Surgeons; TA, transapical; TF, transfemoral.
For use outside The United States only | Not intended for general distribution.
TAVItalk
9
EUROPE
Survival with Edwards SAPIEN
THV was equivalent to AVR in
high-risk patients
PRIMARY ENDPOINT:
All-cause mortality at 1 year (ITT)1
The investigators concluded that “on the
basis of a rate of death from any cause at
1 year that was 20 percentage points lower
with TAVI than with standard therapy, balloon-expandable TAVI should be the new
standard of care for patients with aortic
stenosis who are not suitable candidates for
surgery.”
Cohort A
In April 2011, the results from Cohort A
were presented at the Annual Scientific Session of the American College of Cardiology and were subsequently published in the
New England Journal of Medicine². The investigators at 25 centres randomly assigned
699 high-risk patients with severe aortic
stenosis to undergo either TAVI (with the
26.8%
0.2
24.2%
0.1
NO. AT RISK:
EDWARDS THV
AVR
12
Months
298
252
18
260
236
24
147
139
67
65
Edwards SAPIEN THV
significantly improved survival
in inoperable patients
CO-PRIMARY ENDPOINT:
All-cause mortality 1,2
All-cause mortality, %
100%
P < .001
∆ at 1 Y = 20.0%
NNT = 5.0 pts
80
60
50.7%
40
20
30.7%
0
6
12
18
24
Months
NNT:
Number needed to treat
Edwards THV
Standard therapy
Edwards SAPIEN THV
significantly improved
symptoms and quality of life*
NYHA class over time1,2
P = .68
100
P < .001
I
80
II
60
III
40
IV
20
0
Edwards Standard
THV therapy
Baseline
Edwards Standard
THV therapy
1 year
KCCQ scores over time1
MCID = 5 pts
Edwards THV
Control
70
Edwards SAPIEN valve delivered via either
a transfemoral or a transapical approach)
or surgical replacement. The results from
Cohort A demonstrated equivalence between TAVI and surgical AVR in the high
surgical risk patient population.
The mortality rates from any cause
were 3.4% in the TAVI group and
6.5% in the surgical group at 30 days
(P = .07) and 24.2% and 26.8%, respectively, at 1 year (P = .44), The rates of
major stroke were 3.8% in the TAVI group
and 2.1% in the surgical group at 30 days
(P=.2) and 5.1% and 2.4%, respectively, at 1
year (P = .07). At 30 days, major vascular
complications were significantly more frequent with TAVI (11% vs 3.2%; P < .001);
adverse events that were more frequent
after surgical replacement included major
bleeding (9.3% vs. 19.5%; P < .001) and
new-onset atrial fibrillation (8.6% vs 16%;
P = .006). More patients undergoing TAVI
had an improvement in symptoms at 30
AVR & Edwards SAPIE
days, but by 1 year, there was
not a signifiimproved
haemodyna
cant between-group difference.
sustained valve perfor
The PARTNER Trial investigators
conECHO FINDINGS:
Aortic
valve
gradients1
cluded that in high-risk patients
with
severe
aortic stenosis, transcatheter and 80surgical
Peak G
Peak G
procedures for aortic valve replacement
60
Mean
Mean
were associated with similar rates40of survival at 1 year, although there were impor20
tant differences in periprocedural risks.
0
Major vascular complications and
neu-30 days
Baseline
rological events were more frequent with
327
n = 267
TAVI, while major bleeding Edwards
and THV
newn = onset
Standard Th’py n = 301
n = 231
atrial fibrillation were more frequent with
AVR. Functional improvement as measured by the New York Heart Association
class and 6-minute walk distance favoured
TAVI at 30 days and was similar to AVR at
1 year. 
Mean & Peak Gradiant
As-treated trial arms (mmHg)
0.3
6
Patients %
At 1 year, the rate of death from any
cause (Kaplan–Meier analysis) was 30.7%
with TAVI, as compared to 50.7% with
standard therapy (hazard ratio with TAVI,
0.55; 95% confidence interval [CI], 0.40–
0.74;P < .001). The rate of the composite
endpoint of death from any cause or repeat hospitalisation was 42.5% with TAVI
compared to 71.6% with standard therapy
(hazardratio, 0.46; 95% CI, 0.35–0.59;
P < .001). Among survivors at 1 year, the
rate of cardiac symptoms (New York Heart
Association class III or IV) was lower
among patients who had undergone TAVI
than among those who had received standard therapy (25.2% vs. 58%; P < .001).
At 30 days, TAVI, as compared to standard therapy, was associated with a higher
incidence of major strokes (5% vs 1.1%;
P = .06) and major vascular complications
(16.2% vs 1.1%; P < .001). In the year after
TAVI, there was no deterioration in the functioning of the bioprosthetic valve as assessed
by echocardiography.
Edwards THV
AVR
0.4
0
KCCQ Score
tomatic aortic stenosis deemed inoperable
by traditional open heart surgery. The results
demonstrated the superiority of TAVI over
best medical therapy. The study found that
in patients with severe aortic stenosis who
were not suitable candidates for surgery,
TAVI, as compared with standard therapy,
significantly reduced the rates of death from
any cause.
All-cause mortality, %
0.5
50
30
10
0
∆ = 13.9
P < .001
2
∆ = 20.7
P < .001
4
6
8
∆ = 24.5
P < .001
10
12
Months
MCID: minimum clinically important difference
*NYHA and KCCQ scores of
surviving patients only
REFERENCES
1. Smith, CR. Transcatheter vs surgical aortic valve replacement
in high risk patients with severe aortic stenosis: results from
The PARTNER Trial. Presented at: 2011 American College
of Cardiology Annual Scientific Session; April 2, 2011; New
Orleans, LA.
2. Leon MB, Smith CR, Mack M, et al.Transcatheter aorticvalve implantation for aortic stenosis in patients who cannot
undergo surgery. N Engl J Med. 2010;363;1597-1607.
3. Data on file, Edwards Lifesciences.
TAVItalk
ENGINEERS’ CORNER
Edwards SAPIEN THV
Edwards SAPIEN XT THV
An inside look at the Edwards SAPIEN
and Edwards SAPIEN XT
Transcatheter Heart Valves (THVs)
Laksen Sirimanne
Vice-President, Research & Development, THV, Edwards Lifesciences
T
he results of The PARTNER Trial Cohorts A and B support the balloon-expandable Edwards SAPIEN transcatheter heart valve (THV)
released in Europe in late 2007. Based on feedback from clinicians,
the Edwards SAPIEN XT THV was released in early 2010. Both the
Edwards SAPIEN and Edwards SAPIEN XT THVs are based upon the
same four key design elements: proven leaflet design, optimal frame
height, high radial strength and predictable valve deployment.
Proven leaflet design
T
he Edwards line of THVs share
many features that are core to
Edwards’ long history of tissue
valve design. The leaflets are made
of bovine pericardial tissue, which
has clinically proven long-term durability. The leaflets undergo the
Carpentier-Edwards ThermaFix treatment process to minimise the risk of
calcification. All leaflets are matched
for thickness and elasticity to promote consistent leaflet function and
coaptation.
The Edwards SAPIEN XT transcatheter heart valve features a new
leaflet design based on the proprietary surgical leaflet shape used in
Edwards’ surgical valves which has been enhanced for stress distribution to support valve durability.
TAVItalk
CLINICAL CARDIOLOGY EDITION
10
Expanded treatment options:
valve diameters
The Edwards SAPIEN XT THV treats an
annulus size range of 18 to 27 mm
Optimal frame height
T
he Edwards THVs
have frame heights
designed for proper
placement and noninterference with the
surrounding anatomy.
They are designed to
fit within the native
annulus, minimising
the risk of atrioventricular (AV) block and disruption of
mitral leaflet function, as well as for placement below coronary arteries, allowing clear access for future percutaneous
coronary interventions. The frames are respectively 14 mm
(23 mm valve),17 mm (26 mm valve) and 19 mm (29 mm
valve) tall.
Managing patient expectations is key
QUOTABLE
“When evaluating patients with severe aortic stenosis, it is extremely important to review the various options available and to refer them to a hospital where a multidisciplinary Heart Team will review all the information. Managing patients and family expectations is key, as many patients
will be better suited to surgical valve replacement—still the gold standard for patients with lower risk profiles. It is difficult for all concerned
when a patient arrives with his/her heart set on TAVI and is not a suitable candidate.”
Pilar Tornos Mas, MD, FESC
Hospital General Universitari Vall d’Hebron, Barcelona, Spain
Former Head of ESC Task Force of the European Society of Cardiology
for the management of valvular heart disease
For use outside The United States only | Not intended for general distribution.
TAVItalk
11
EUROPE
23 mm
26 mm
29 mm
Further
resources
23 mm valve
annulus
size (mm)
18–20
29 mm valve
21–22
23
24–25
26–27
26 mm valve
High radial strength
Predictable valve deployment
E
T
dwards THVs have established a new
paradigm for valve delivery, encompassing a strong supportive frame with high radial
strength, resulting in a large effective orifice area,
even in heavily calcified annuli. They are designed for reliable deployment with the nominal
diameter necessary for proper leaflet coaptation,
as well as proper haemodynamics and valve
durability. The Edwards SAPIEN XT THV
frame offers comparable radial strength to the
original Edwards SAPIEN THV frame while
allowing for lower profile crimping. The frame
geometry features fewer rows and is made from
cobalt chromium rather than stainless steel.
TAVItalk
he Edwards SAPIEN XT THVs are
delivered transfemorally and transapically. The balloon-expandable delivery systems were designed for their
means of access and engineered for predictably accurate valve placement. 
Edwards Lifesciences offers
additional resources on the web to
help inform and educate patients
and their physicians. Please visit:
• Aortic Stenosis Patient
Information:
http://www.yourheartvalve.com/eu
• Edwards Find-a-TAVI-Center
interactive web application:
http://www.edwards.com/eu/products/transcathetervalves/pages/
tavifinder.aspx
• Edwards THV Product Page:
http://www.edwards.com/eu/products/transcathetervalves
The transcatheter heart valve's progress over 2 decades
VIEW
Progress continues to be made in transcatheter heart valve design. Left to right: Andersen hand-made transcatheter aortic
valve (1989, porcine tissue, FIA); Cribier-Edwards™ THV 23 mm (2002, equine pericardial tissue, FIM); Edwards SAPIEN
THV available in 23 mm, 26 mm (late 2007, bovine pericardial tissue, ThermaFixTM anti-calcification treatment); and the
current Edwards SAPIEN XT available in 23 mm, 26 mm & 29 mm (first released in early 2010). 
TAVItalk
12
The integral and continuing importance of the Heart Team
TAVItalk
QUOTABLE
CLINICAL CARDIOLOGY EDITION | EUROPE
“...As TAVI evolves and expands, patient selection is more critical than ever and the Heart Team needs to be collectively involved in
determining best patient options. Just as awareness needs to be created regarding the under-treatment of severe Aortic Stenosis, it is
equally important to ensure that only appropriate patients are selected. The team needs to be able to decide when a surgical AVR
is more appropriate and, equally, when extenuating patient circumstances and comorbidities make TAVI an inappropriate therapeutic choice…patients and their families should not be given false hopes when the reality of the situation dictates otherwise…”
Jean Fajadet, MD, PhD, FESC
President, EAPCI
Clinique Pasteur, Toulouse, France
Edwards Lifesciences receives FDA approval for first transcatheter aortic
heart valve in the USA
O
n November 2, 2011 Edwards Lifesciences received approval
from the United States Food and Drug Administration (FDA)
for the transfemoral delivery of the Edwards SAPIEN transcatheter
aortic heart valve (THV) for the treatment of inoperable patients with
severe symptomatic aortic stenosis. This is the first U.S. commercial
approval for a transcatheter device enabling aortic valve replacement
without the need for open-heart surgery.
“This day marks an important milestone for inoperable American patients who have long been awaiting a therapeutic option for
the often debilitating symptoms associated with severe aortic stenosis,” said Michael A. Mussallem, Edwards’ chairman and CEO. “We
are extremely proud of the dedication of the Heart Teams and the
patients involved in the clinical trial for this therapy, who have paved
the way for this therapy to help even more people around the world.”
The Edwards SAPIEN valve is indicated for transfemoral delivery
in patients with severe symptomatic native aortic valve stenosis who
have been determined by a cardiac surgeon to be inoperable for open
aortic valve replacement and in whom existing comorbidities would
JEAN-LUC LEMERCIER
(continued from page 1)
number of patients who go untreated and to ensure that all appropriate treatment options are carefully assessed. Against this backdrop of
progress, clinical education continues to be of paramount importance
in the steady expansion of this procedure. Managing patient expectations also continues to be key and plays a pivotal role in our research
protocols, product development and professional education programs.
Clinical research is another major area of focus for
Edwards Lifesciences, and one which has continued to gain mo-
not preclude the expected benefit from correction of the aortic
stenosis.
The safety and effectiveness of the Edwards SAPIEN THV were
evaluated in a randomised, controlled pivotal study called The
PARTNER Trial. The name of the trial signifies the important partnership between cardiac surgeons and interventional cardiologists
who were brought together to collaborate in patient evaluation, treatment and follow-up. Additional analyses of data from The PARTNER
Trial demonstrated that patients receiving the Edwards SAPIEN valve
experienced substantially better quality of life as compared to the
control group patients; and also that TAVI was cost-effective.
As part of this approval, Edwards Lifesciences will implement
two substantial post-approval studies. One study will follow patients
already enrolled in The PARTNER Trial, and the second study will
track new US patients. Edwards Lifesciences anticipates the second study will be incorporated into a new national (USA) patient
registry. Post-market approval studies have been underway since
commercialisation in Europe in 2007. 
mentum in the last two years, with the manuscripts of TRAVERCE,
PARTNER EU, The SOURCE Registry and The PARTNER Trial all
being published in peer review journals in 2010. This year, our exciting clinical program has continued to evolve with a steady stream of
publications and enrolment commenced in four new clinical trials.
Today, many thousands of elderly patients enjoy a quality of life
many of them could only have dreamed of prior to the introduction
of the TAVI procedure. Evolution of valve technology, refinement of
operator techniques, and comprehensive Heart Team training have
all been key factors in the growing adoption of TAVI.   
Company and Product Information
Opinions, advice and all other information expressed in TAVItalk represent contributors' views
and not necessarily those of Edwards Lifesciences.
Not intended for US distribution.
The Edwards SAPIEN and SAPIEN XT transcatheter heart valve and delivery systems bearing the CE
conformity marking comply with the requirements of the European Medical Device Directive 93/42/EEC.
For professional use. For additional information, indications, contraindications, warnings, precautions
and adverse events, please refer to the Instructions For Use provided with the products.
Edwards, Edwards Lifesciences, the stylized E logo, Edwards SAPIEN, Edwards SAPIEN XT, SAPIEN,
TRAVERCE, PARTNER, PARTNER II, SOURCE, PREMIER, Ascendra2, NovaFlex+, RetroFlex 3 and
eSheath are trademarks of Edwards Lifesciences.
© 2011 Edwards Lifesciences Corporation. All rights reserved. E2402/10-11/THV
Edwards Lifesciences, S.A.
Route de l’Etraz 70, 1260 Nyon, Switzerland
Tel: +41 22 787 4362.
Additional company information can be found at http://www.edwards.com
tavitalk
PUBLISHER: Edwards Lifesciences, S.A., Europe
EDITORIAL AND DESIGN SERVICES: SAVIpartners, Paris and New York
Contact Information: For general information on the Edwards
TAVI Programme, please contact [email protected]
Edwards Lifesciences
Irvine, USA I Nyon, Switzerland I Tokyo, Japan I Singapore, Singapore I São Paulo, Brazil
edwards.com