The development of transcatheter aortic valve replacement (TAVR) can certainly be
considered one of the most fascinating examples of successful translational research
in medicine. Thanks to an outstanding partnership between multidisciplinary clinicians
and engineers, we could move from concept to bench, bench to bedside, bedside to clinical
feasibility trials, then on to larger clinical registries and evidence based trials,
leading ultimately to a breakthrough technology with durable impact on the pattern
of medical practice.
This disruptive technology evoked scepticism and criticism in the beginning, but thanks
to innumerable clinical trials and evidence based investigations, it is now widely
accepted by the medical community and its acceptance is continuing to grow. In the
last fourteen years, TAVR has been performed in around 300,000 patients in 65 countries
and adoption is increasing by 40% year on year.
The field of TAVR is rapidly evolving, with major refinements in technology, procedural
techniques, patient selection and biomedical engineering. With the development of
better devices, new approaches and new implantation strategies, TAVI has become much
simpler and safer. The indications were initially limited to elderly aortic stenosis
patients with multiple co-morbidities. The same are now cautiously and appropriately
growing to include a broader population of patients with lower surgical risk, degenerated
surgical bioprosthesis, and even patients with other valvular diseases such as pure
aortic or even mitral insufficiency. There are few examples of clinical fields in
medicine that match the rapid and careful evolution of TAVI.
Calcific aortic stenosis (AS) is the most frequently acquired valvular heart disease
in developed countries, and its prevalence increases with an ageing population.
The natural history of symptomatic aortic stenosis carries a poor prognosis
with a survival rate of 60% and 32% at one and five years respectively.
The only effective treatment for decades was surgical aortic valve replacement (SAVR)
with remarkable results in ideal candidates, but which required invasive heart surgery
with extracorporeal circulation. Operative mortality of SAVR is low, <5%
and alleviation of symptoms and a return to normal life expectancy are observed. However,
the operative risks, including post-operative complications and mortality, significantly
increase in very old patients and/or in the presence of associated cardiac or non-cardiac
These factors are considered one of the main reason for which at least one-third of
patients with symptomatic AS are not referred for SAVR
In the 1980s, age of over 75 years was considered a contraindication of SAVR, and
this stimulated our group to develop a less invasive therapy, balloon aortic valvuloplasty
(BAV), consisting of enlarging the calcified native valve with a balloon catheter
using standard catheterization techniques.
This technology was adopted with enthusiasm by the medical community, as highlighted
by the thousands of patients included in broad European and US registries and the
1,300 indexed articles dedicated to the procedure.
However, the enthusiasm progressively declined following the recognition of important
limitations, headed by early valve restenosis. BAV appeared to provide only temporary
relief of symptoms with a modest survival benefit
, its role remaining controversial in US guidelines.
Interest in BAV resurged with the development of TAVR and its frequent integration
in the procedure. BAV is also used today as a palliative option in patients with contra-indication
to TAVR or SAVR, as a bridge to those procedures in severely depressed left ventricular
function, or when urgent non-cardiac surgery is indicated. Even though age is no longer
considered a surgical contraindication, large numbers of severe AS patients are not
offered valve replacement in Europe or the United States.
Rational for developing interventional technologies for severe AS: An Unmet Clinical
From balloon valvuloplasty to the concept of percutaneous aortic valve
For those of us who had been pioneering BAV, addressing the issue of post-BAV valvular
restenosis became an obsession in the early 1990s. Placing a balloon expandable stent
frame containing a valvular structure (stented-valve) within the calcified native
valve appeared a possible option (Fig. 2). The project had the advantage of requiring
similar approaches and techniques to those used for BAV. Among several visions of
endovascular valve implantation, with initial animal investigation performed by Davies,
H. R. Andersen’s project was the most elaborated. In 1992 he developed and patented
a hand-made “stented valve” for the treatment of various cardiovascular diseases,
but the project remained at the experimental stage. In 2000, Bonhoeffer first used
a stented-valve in a human, a bovine jugular vein in a metallic stent to treat degenerative
ventriculo-pulmonary conduits in children.
Birth of the idea of “stented-valve” in AS.
Left panel: A stent crimped over a high-pressure valvuloplasty balloon might keep
the valve open and prevent restenosis. A valve structure should be added within the
stent. Right panel: Validation of the concept of intra-valvular stenting and optimal
height of the frame to respect adjoining structures.
Our goal to implant a stented valve in calcific AS, on the beating heart, was very
original but posed specific, difficult and at first sight insurmountable issues. These
issues came from the calcified nature of the diseased native valve, and the immediate
proximity of essential anatomical structures: coronary ostia, mitral valve, and interventricular
septum (seat of the conduction system).
Validation of intra-aortic valve stenting and feedback of experts
To validate the concept of intravalvular stenting in aortic stenosis, an autopsy study
was conducted in Rouen in 1994 on 12 cases of calcific AS (Fig. 2). The study demonstrated
that a balloon-expandable peripheral artery stent of 23 mm in diameter (Palmaz stent)
was able to maintain a circular opening in all calcified aortic valves. The study
also made it possible to establish the optimal dimensions of the stent height, avoiding
any contact with the neighboring structures. Furthermore, the stent required a high
traction force to be dislodged from the annulus, thus lowering the potential risk
of device embolization.
This study was a fundamental milestone and validated the concept of aortic valvular
stenting in a model of human calcific AS. At that stage, the type of valve prosthesis
and its physical properties were still limited to drawings, however they were still
used to file a European patent (Fig. 3).
1994: Drawings and model prefiguring a balloon expandable transcatheter bioprosthesis.
A: specific stent frame design allowing to attach a tricuspid valvular structure.
Partial external coverage would limit the risk of aortic regurgitation through the
struts. B: Hand made model of stented-valve before and after crimping over a balloon
catheter (external diameter: 8 mm). C: Drawing of the different phases of transcatheter
aortic valve implantation.
Getting biomedical companies interested in this concept was a total failure with unanimously
unfavorable opinions from all experts with regard to the design of the prosthesis,
the potential risks of the procedure and the medical indication itself. Major clinical
issues were constantly brought up: coronary occlusion, mitral valve injury, stroke,
aortic regurgitation, prosthesis migration, permanent auriculo-ventricular block,
bleeding, endocarditis, and non-lasting results. The project was looking like the
“most stupid ever proposed”.
From concept to prototypes: pre-clinical evaluation
Creation of the start-up: Percutaneous Valve Technologies
To accomplish this venture, a start-up company, ‘Percutaneous Valve Technologies’
(PVT, NJ, USA) was finally formed in 1999 (Alain Cribier, MD, Martin Leon, MD, Stan
Rabinovich and Stanton Rowe, PhDs). A development and first investment partner was
found in Israel (ARAN, R&D, Ltd, Caesarea) a small biomedical company with great engineers
which became our long-lasting partner in this venture. This was the start of a strong,
durable and successful collaboration between engineers and clinicians. The translational
pathway to TAVR, set by PVT and ARAN, would remain unchanged in the future for all
companies working on the development of such a procedure (Fig. 4).
The translational pathway of transcatheter aortic valve replacement: driving for superior
Preclinical engineering output: From concept to finalized prototype
Indications given to the engineers for the development of a transcatheter heart valve
(THV) were particularly challenging. They had to integrate many innovative technologies:
a balloon-expandable stent, a high-pressure balloon for stent expansion, a valvular
structure and a delivery system. According to the “philosophy” of the THV, they had
to create a prosthesis made of a highly resistant frame containing a valve structure,
able to be homogeneously compressed to 7-9 mm over a high pressure balloon (trans-femoral
artery insertion) and expanded to a diameter of 23 mm by balloon inflation, without
damaging the frame and leaflets. Selection of the valve material, conceiving its attachment
to the frame, and the valve design to provide sufficient strength, low profile and
durability were other issues. The question of how to deliver the valve accurately,
within the calcified valve, on the beating heart, would come later.
Many different valve configurations were investigated. Valve design was dependent
New testing equipment designed by PVT for the evaluation of valve structure and frame.
Frame material and design (profile, dimensions, skirt, crimping process and expansion,
Leaflets design (material, attachments, cooptation, stress distribution, leak, hemodynamics,
fatigue and durability, calcification).
Loading and delivery catheter system.
Each of these elements required specific work on design-geometry, material selection,
manufacturing and processing. Geometry optimization used the Finite Element Analysis
(FEA) method. The goal was to maintain the durability constraints while reducing the
crimping profile. For laboratory testing (Fig. 5), the company had to design its own
equipment for a new technology: crimping tools, pulse duplicators, accelerated wear
and durability testers, various frame testers, hydrodynamic testers, and a leaflet
The first “finalized” device (Fig. 6) consisted of a stainless steel stent, 23 mm
in diameter, 17 mm in height, containing a tri-leaflet valve initially made of polyurethane
(later changed to a bovine pericardium valve), which had been proven for more than
25 years in surgical bioprosthesis to have excellent properties. The device was compatible
with a 24F (8 mm) introducer sheath.
A: Various prototypes and finalized device (B) created by PVT.
C: Crimped device over a 23 mm Numed balloon catheter, and 24F introducer for implantation
in the sheep model. Angiographic evaluation post-implantation within the native aortic
valve, and transesophageal echocardiography evaluation of valvular function.
From prototypes to animal model
In the year 2000, we started animal experimentation on the sheep model (Fig. 5). Over
100 THV implantations at various cardiac sites (pulmonary artery, aorta, aortic valve)
were performed by myself and my collaborator, Helene Eltchaninoff. In spite of the
clear limitations of this animal model, the experimentation contributed to the optimization
of bioprosthesis, delivery systems, and implantation techniques, guidewires and procedural
aspects (assessment of annulus size, accuracy of valve positioning, optimal X-ray
projection, technique of valve delivery, methods of cardiac standstill, evaluation
of results by angiography and echocardiography, anticoagulant strategy).
Chronic (5-month) evaluation in the systemic circulation was obtained using an original
method of THV implantation in the descending aorta.
This was mandatory before being committed to FIM trial as post-durability testing
and as a test of biocompatibility. The persistence of an excellent valve function
and the integrity of the THV on pathological examination were thus demonstrated.
From bench to bedside
On 16th April 2002, we performed the first-in-human TAVR (Fig. 7) on a 57-year-old
patient with severe AS who presented in cardiogenic shock with major left-ventricular
dysfunction (ejection fraction 12%) with multiple comorbidities contraindicating SAVR.
After failed emergent BAV, TAVI appeared to be the last-resort option for this young
patient. The indication was particularly challenging in this patient, who also had
subacute leg ischaemia related to an aorto-femoral bypass occlusion and severe contralateral
atherosclerosis preventing the use of the planned transfemoral retrograde access.
The procedure was successfully performed using a challenging approach, the antegrade
transseptal approach via the femoral vein. The THV could be accurately deployed in
the middle of the valvular calcification. After deployment, the patient’s hemodynamic
and echocardiographic status improved remarkably.
First-in-Man implantation (Rouen, April 16th, 2002).
A—The complex antegrade transseptal route used for TAVR. B—View of the transcatheter
valve in place within the native calcified valve and hemodynamic result (no gradient).
C—The patient immediately after valve implantation and D, 8 days later.
From a single case, the feasibility of THV implantation on the beating heart using
transcatheter techniques was confirmed. There was no coronary occlusion, no mitral
dysfunction, no atrio-ventricular block and only a mild paravalvular aortic regurgitation,
thus translating well our 1994 post-mortem study. The patient unfortunately died four
months after the procedure, due to complications unrelated to TAVR (leg amputation
consecutive to his pre-hospitalization leg ischemia). This first-in-man case confirmed
the feasibility of implanting a THV in a human on the beating heart using transcatheter
techniques, with perfect subcoronary position and no interference with the surrounding
structures. In that, it can be considered an important milestone in interventional
cardiology. The international reaction to this spectacular case defied imagination.
Two successive feasibility trials on a total of 38 patients
restricted to compassionate use (imminent death) were thereafter initiated in our
center. These studies confirmed the feasibility of TAVI (80% procedural success) using
the transseptal approach and the lasting haemodynamic and functional improvement after
implantation. However, a high (25%) incidence of > grade 2 paravalvular regurgitation
was noted, indicating an insufficient coverage of the annulus in a number of patients
and the need to develop larger size bioprosthesis ( >23 mm).
As expected, several of these critically ill patients died of their comorbidities
within weeks or months but, amazingly, some survived beyond 2–5 years and even as
long as 6.5 years in our most striking case, without any prosthesis dysfunction. Protocol
extension to other centers in Europe, USA and Canada was started but demonstrated
a significant degree of technical complexity and adverse outcomes associated with
the antegrade delivery. In our series, TAVR was also attempted in 7 patients using
the initially-planned, and technically simpler, transfemoral retrograde approach.
The procedure was carried out successfully in 4 patients in spite of the lack of any
specific delivery system adapted to this route. Obviously, further expansion of TAVR
required technical improvements, procedure simplification, more friendly approaches
and larger valve sizes.
Edwards Lifesciences input after acquisition of Percutaneous Valve Technologies (2004):
development of the SAPIEN valve and of new approaches for TAVR: transfemoral retrograde
and transapical antegrade.
From bedside to feasibility trials
When Edwards Lifesciences Corporation (Irvine, CA, USA) acquired PVT in 2004, TAVR
entered a new era. The prosthesis underwent several iterations and an easier delivery
system and new approaches were developed (Fig. 8).
The Edwards-SAPIEN (originally Cribier-Edwards) valve prosthesis became available
in two diameters: 23 mm and 26 mm. This model of bioprosthesis consisted of a tri-leaflet
bovine pericardium valve pretreated to decrease calcification, mounted within a stainless
steel stent externally covered by a longer pet cuff (50% versus 33% of the frame height).
A specific delivery system was conceived for facilitating the retrograde transfemoral
approach, the deflectable RetroFlex catheter, evaluated by Webb et al. in Vancouver,
Simultaneously, a new approach was developed, the minimally invasive transapical approach
using the Ascendra delivery system, evaluated by Walther et al. in Leipzig, Germany.
The onset of these two approaches made TAVR available to the vast majority of patients,
regardless of the suitability of the femoral access. Our team in Rouen was included
in the setting of several European feasibility studies (REVIVE, PARTNER Europe, TRAVERSE)
including hundreds of patients. The satisfactory results of these trials, despite
specific complications with the two approaches, led to a fast expansion and acknowledgement
(in particular by cardiac surgeons) of TAVR.
In 2004, a concurrent THV, the CoreValve (later commercialized by Medtronic, Irvine,
CA, USA), an auto-expandable nitinol frame containing a porcine pericardial valve,
was launched and evaluated in feasibility studies.
This device could be inserted via a transfemoral approach through smaller sheath sizes
(21F then 18F) than those required for Edwards devices (22F and 24F). As an alternative
to the femoral delivery, the subclavian access was proposed with the CoreValve. The
Conformité Européenne (CE) mark was obtained for both models of transcatheter valves
From feasibility trials to larger clinical registries and evidence-based trials
Thereafter, acceptance and expansion of TAVR was amazing, with an annual 40% increase
in the number of procedures. In line with the recommendations of the European Societies
of Cardiology (ESC) and Cardiothoracic Surgery (EACTS),
thousands of inoperable or high-risk elderly patients were enrolled in post-marketing
national (France, Germany, Italy, UK, Canada etc.) and international registries with
the two models of THV.
These registries included:
Single valve evaluation as in the SAPIEN Aortic Bioprosthesis European Outcome (SOURCE)
which has enrolled 1,123 patients since 2007 receiving transfemoral or transapical
The Evaluation of the Medtronic CoreValve System in a “Real-World” (ADVANCE) Registry,
presented at the EuroPCR meeting in Paris, in May 2013, including 1,015 patients enrolled
at 44 centers.
Two valve evaluations: the French Aortic National CoreValve and Edwards (FRANCE) registry,
followed by the FRANCE 2 registry,
reporting the French experience on a series of 3,500 patients, making it the largest
exhaustive overview of TAVR in the real life.
These registries contributed to a better appraisal of patient screening, technical
modalities, prevention, and management of complications. The procedural success rate
increased to over 95%, and with advanced technologies, immediate and long-term results
kept improving. The hemodynamic results were shown to compare favorably with surgical
valve replacement in similarly ill patients. The results of TAVR became more predictable
and the mortality rate decreased to 10% at 1 month and 20% at 1 year, as in the SOURCE
after transfemoral implantation. A dramatic and long lasting improvement in the quality
was observed in all registries, and was further confirmed in the pivotal PARTNER trial.
The first evidence-based evaluation of TAVR was obtained with the Edwards SAPIEN valve
in the multicenter pivotal randomized trial “Placement of Aortic Transcatheter Valves”
(PARTNER) in the USA. From 2007, 1,056 high surgical risk patients were enrolled in
26 centers in USA. Patients were divided into two cohorts, a non-surgical arm (Cohort
B) in which TAVR was compared with medical therapy (including BAV); and a surgical
arm (Cohort A) in which transfemoral or transapical TAVR was compared to traditional
Briefly, the results confirmed the high superiority of TAVR over medical treatment
in non-operable patients with an absolute increase in survival of 20% at 1 year, and
the non-inferiority of TAVR versus SAVR in high-risk operable patients in terms of
all-cause mortality and repeat hospitalization at 1 year, with equal improvement of
quality of life
Similar results were observed at 2, 3 and 5 years.
In view of these results, TAVR was approved by the Food and Drug Administration (FDA)
in these indications in 2011 and 2012 respectively. The pivotal CoreValve high-risk
trial also randomized TAVR vs SAVR in symptomatic high-risk patients with severe AS,
with a primary end point of all-cause mortality at 1 year. This trial was the first
and so far the only randomized trial to ever show superiority for TAVR vs SAVR (14.2
vs 19.1% respectively), results confirmed at 2 years.
In these trials, the similarity or superiority of transcatheter over surgical valves
on hemodynamic flow parameters, but the superiority of surgical valve on paravalvular
leak and the need for a permanent pacemaker were observed.
Advanced valve and delivery systems have changed the world of TAVI overtime.
Several generations of Edwards and Medtronic CoreValve led to decreased crimped sizes
and launch additional valve sizes for a better coverage of the aortic annulus.
New models of bioprosthesis approved in Europe.
Solving the problems: the essential role of translational research
After several years of experience, the task of the engineers was to improve both the
technological aspects of TAVR, while reducing the complications. Severe vascular complications
(3–16%), stroke (2–7%), paravalvular aortic regurgitation (AR: 5% > grade 2), and
complete heart block requiring pacemaker (PM: Edwards 3–12%, CoreValve 16–35%) were
the leading complications.
Improvements were achieved by creating new models of bioprosthesis and delivery systems
(Figs. 9 and 10), decreasing sheath sizes, offering a better coverage of the annulus
(additional valve sizes), and facilitating sealing and positioning of the bioprosthesis.
Technical advances are demonstrated on the successive generations of the balloon expandable
and self-expandable transcatheter valves (Fig. 9).
The SAPIEN XT featured a lower profile delivery system, compatible with the new 18-20F
e-Sheath designed to treat a broader population of patients and to reduce vascular
complications. The valve consisted of an enhanced designed trileaflet bovine pericardial
valve with a polyethylene terephlalate (PET) fabric cuff, sutured into a cobalt-chromium
balloon-expandable stent with a modified geometry. Valves sizes were 23 mm, 26 mm
and 29 mm. A 20 mm size was later available. Enhanced delivery systems were conceived
for both transfemoral and mini-surgical approaches.
As evaluated in the SOURCE-XT registry (2688 patients in 99 European centers), the
results confirmed important clinical benefits with a marked decrease of vascular complications
and bleeding, and a decrease of all causes of mortality and cardiovascular mortality
to 19.8% and 10.8% respectively at one year.
The most important data came from the results of the randomized PARTNER 2 trial reported
early this year.
The trial enrolled 2,032 intermediate-risk patients at 57 centers, to undergo either
TAVR or SAVR. At 2 years, non-inferiority of TAVR versus SAVR on rate of death or
disabling stroke was demonstrated. Furthermore, in the transfemoral-access cohort,
TAVR resulted in a significantly lower rate of death or disabling stroke than surgery.
TAVR resulted in larger aortic-valve areas and lower rates of acute kidney injury,
severe bleeding, and new-onset atrial fibrillation - whereas surgery resulted in fewer
major vascular complications and less paravalvular aortic regurgitation. This led
the FDA to extend approval of TAVR to intermediate risk patients.
Further progress came with the launch of the SAPIEN 3, the newest member of the SAPIEN
family. The main improved features were a lower profile (compatible with 14-16F e-Sheath)
allowing us to perform TAVR in about 90% of cases, an improved delivery system for
more accurate positioning, and an external skirt to reduce paravalvular regurgitation.
The SAPIEN 3 was approved in Europe in 2014 and in the US in 2015 for the treatment
of high-risk and inoperable patients. Outcomes for high- and intermediate-risk patients
treated with the SAPIEN 3 have been evaluated in the PARTNER II S3 trial,
a nested registry of the PARTNER II Trial.
It reported 1-year follow-up in 1,077 intermediate risk patients implanted with SAPIEN
3 and compared outcomes using propensity score analysis, to the 747 patients treated
with SAVR in the PARTNER 2A trial. For the primary endpoint of mortality, stroke,
and moderate to severe aortic regurgitation, TAVR was superior to SAVR at one year
(p < 0.001). The study showed the lowest rate of mortality, stroke and aortic regurgitation
at 1 year of all SAPIEN trials and a superiority of TAVR over SAVR for these composite
endpoints (p < 0.001). The conclusions suggested that TAVR might become the preferred
treatment alternative in intermediate risk patients.
The Medtronic Evolut R is the new generation of the CoreValve self-expanding THV.
The valve has been re-engineered to improve anatomic fit and sealing, to provide a
more consistent radial force, to facilitate repositioning and retrieval, and reduce
paravalvular leak. On a limited series of patients, the 30-day data showed a low rate
of moderate to severe PVL and pacemaker implantation in comparison to previous Medtronic
CoreValve series (3.4% and 12.4% respectively).
This valve is currently approved in the United States for high- and extreme-risk patients
with symptomatic severe AS.
The field of TAVR is constantly evolving. A number of next-generation devices, markedly
different to existing devices, are in clinical evaluation and already CE accredited
(Fig. 10). They incorporate features to reduce delivery catheter profile, facilitate
positioning (repositionability), retrieval, and reduce paravalvular AR. However, it
is too early to say whether these new bioprosthesis will represent the future of TAVR,
but these advances create an active and stimulating competition. As examples, the
LOTUS (Boston Scientific Marlbourough, MA, USA), comprises a nitinol frame with bovine
pericardium valve released by an original mechanism offering optimal recapture, the
DIRECT FLOW MEDICAL (Direct Flow medical, Lake Forest, CA, USA), comprises a rigid
scaffold with a bovine pericardium valve and two inflatable aortic and ventricular
rings, which almost eliminate paravalvular regurgitation.
From trials to day-to-day practice: the growing place of TAVR as a breakthrough technology
In parallel to the advances in technologies, additional tools were developed regarding
patient screening and procedures (new multimodality imaging technologies leaded by
Multislice Computed Tomography), vascular complications (improved vascular closure
devices), and stroke (embolic protection devices). Even the procedural “milieu” was
modified with the development of a hybrid environment allowing integration, in the
same setting, of interventional and surgical therapies. This testifies to the considerable
impact of TAVR on the world of industry.
Thanks to these technological advancements, greater clinical experience, and the excellent
results of post-market registries and evidence-based trials, TAVR has been brought
to the fore as a treatment for AS and now appears in US and European guidelines. TAVR
is indicated in patients with severe symptomatic AS who are not suitable for surgery,
as assessed by a multidisciplinary heart team (Heart Valve Team) comprising cardiologists,
cardiac surgeons, imaging specialists, anesthetists and other specialists including
TAVR should also be considered in high-risk patients who may still be candidates for
surgery, but in whom a less invasive approach is favored, based on individual risk
profile, including frailty. New guidelines in 2017 are expected to approve TAVI in
intermediate risk patients. Another approved indication of TAVI is the treatment of
failing surgical bioprosthetic heart valves (valve-in-valve). In this indication,
TAVR is particularly appealing to achieve adequate valvular function for symptom relief
without prolonged recovery. This indication is being evaluated in an ongoing global
multicentre registry - Transcatheter Aortic Valve Implantation in Failed Bioprosthetic
This new, less invasive therapeutic option for degenerated cardiac valve is pushing
surgeons to increasingly select bioprosthetic instead of mechanical valves for primary
Subsequent to FDA approval, many centers were certified to apply TAVR in USA, currently
nearly 500 centers, with around 26,000 patients included in the Society of Thoracic
Surgery / American College of Cardiology Transcatheter Valve Therapy (TVT) registry.
An equivalent number of centers are certified in Europe, with Germany being leader
with 160 TAVR/million of inhabitants, followed by Switzerland, Austria and France.
The cost-effective “minimalist strategy” (Fig. 11) for transfemoral TAVR that we pioneered,
plays an important role in the worldwide expansion of TAVR. It includes percutaneous
transfemoral access, no general anaesthesia, no periprocedural transesophageal echocardiography,
reduced operators in the room, and early discharge programs. This strategy can be
applied in 90% of all TAVR patients, shows equivalent clinical outcomes compared to
the standard transfemoral approaches, and is cost-effective.
The different phases of transfemoral TAVI using the “minimalist” approach (SAPIEN
Development of the balloon expandable valve: an ongoing odyssey.
In the near future, TAVR will be extended to younger, lower-risk patients as reflected
by the results of the PARTNER 2 and PARTNER 2 S3 studies. Using TAVR in “all comers”
is already being evaluated. The Nordic Aortic Valve Intervention Trial (NOTION) first
randomized almost 300 patients older than 70 years with severe aortic-valve stenosis
but deemed low risk for surgery at three European centers. One-year results showed
no significant differences in the composite rate of death from any cause, stroke,
or MI (the primary outcome) between those undergoing TAVR and those undergoing SAVR.
The ongoing PARTNER 3 trial started in 2016, with the goal of comparing TAVR and SAVR
in all comers older than 65 years. A similar trial is ongoing with the Medtronic CoreValve.
The results of these studies should have enormous consequences on the indications
of TAVR in the future.
For the time being, the durability of THV compared to surgical heart valves remains
unknown and has to be confirmed over the long-term. Our knowledge on long-term clinical
follow-up is currently limited, but results are very encouraging. Normal valve function
has been reported more than five years after TAVR
and very few cases of failed THVs have been reported so far. As an anecdote, two of
our patients have reached 10 years follow-up without any change in hemodynamics and
no device deterioration.
The development of TAVR has been a 20-year long inspiring and successful journey from
concept to real world (Fig. 12). TAVR appears today a breakthrough technology, challenging
the foundations of medical practice, enabling thousands of patients with severe AS
to receive a life-saving effective alternative treatment to SAVR. This would not have
been possible without the excellent and unequalled collaborative spirit between clinicians
and engineers who have provided their expertise with the unique goal of making this
procedure not just possible, but also safe and successful. We are not reaching the
end of the story. The continuous translational work promises further technological
innovations that will soon make TAVR simpler and safer. Within 10 years, it is likely
that TAVR will become the default strategy for patients with symptomatic AS.