Surgical Replacement and Transcatheter Aortic Valve Implantation Trial 10 Year Follow-up

Aortic valve stenosis (AS) is the most prevalent valve disorder in the adult
population in developed countries affecting approximately 2% to 4% of people
over 65 years of age. This corresponds to approximately 3 million people with
AS in Europe and approximately 1.5 million in the United States. One in five
will eventually progress to symptomatic AS representing more than 900,000
patients in these two greographies.
Patients with severe AS face a grim prognosis once they become symptomatic. The
landmark paper on symptomatic AS by Ross and Braunwald in 1968 highlighted this
premise: median survival averages only 2, 3 and 5 years after symptom onset of
angina, syncope and heart failure respectively. Furthermore mortality is
already substantial in the months following the first symptoms. The dismal
prognosis of patients with untreated severe, symptomatic aortic stenosis has
been recently corroborated in the conservative treatment arm of the PARTNER B
cohort. Both, the ESC and ACC/AHA cardiology societies have endorsed guidelines
on valvular heart disease emphasizing the need for surgical aortic valve
replacement (SAVR) once symptoms develop or in case of impaired LV function
(Level of evidence grade 1).

Physicians'preferences for lesser invasive strategies have fuelled the ongoing
interest in developing minimally invasive transcatheter therapies. Alain
Cribier pioneered the transcatheter aortic valve implantation (TAVI) technology
and reported the first in man experience of TAVI in a patient with symptomatic
AS who was deemed inoperable in 2002. Subsequent feasibility studies validated
the proof of concept. The Edwards-SAPIEN valve (Edwards Lifesciences, Irvine,
CA, USA) and the Medtronic-CoreValve system (Medtronic Corporation,
Minneapolis, MN, USA) were the first two TAVI platforms with CE mark approval,
followed by the Symetis Acurate (Semetis, Ecublens, Switzerland) and JenaValve
(JenaValve, Munich, Germany). Numerous single-center and multi-center
observational registries followed suggesting the safety and performance of the
TAVI technology. The TAVI technology comes with its own specific complications,
not necessarily overlapping with those of SAVR: vascular injury; stroke,
cardiac injury such as heart block, coronary obstruction, and cardiac
perforation; paravalvular leak; and valve misplacement. The non-uniformity in
presenting respective data makes a comparison of results from different centers
challenging. The Valvular Academic Research Consortium (VARC), a FDA-endorsed
collaboration between academic research organizations and professional
societies in the United States and Europe is an initiative to generate a
consensus statement on TAVI related definitions aiming to create order and
uniformity making data more prone to analysis and comparison.

Technical refinements and commercial entrepreneurship have made the technology
accessible to many centers worldwide. This might pose future implications since
few randomized trials with TAVI have been performed.

There are three types of medical practices. The first is the institution with
on-site interventional cardiologic and cardiothoracic surgical acivity and with
close inter-disciplinary collaboration where interventional cardiologists and
cardiothoracic surgeons reach a consensus on which patients to select for a
specific surgical or interventional treatment strategy. These centers would
reasonably respect and adhere to CE mark labelling indications. Second there
are centers where interventional cardiologists and cardiothoracic surgeons do
not often convene and usually work as two separate departments. Finally there
are practices with an interventional cardiology program but without on-site
cardiothoracic surgery, estimated to make up 37% of all PCI centers in the
European Union. Expectedly, these kinds of organizations without intimate
collaboration between cardiothoracic surgeons and interventional cardiologists
will look to broaden their interventional activities with an attractive
innovation like TAVI. A worldwide practice that is less controlled would
potentially cloud the safety and efficacy profile of the procedure. This
criticism by the medical community and health authorities could jeopardize
future reimbursement policies. The advent of randomized trial data is crucial
and this next step in establishing a new treatment strategy should not be taken
for granted as governmental authorities entitled to grant premarket approval to
cardiovascular devices are under increased scrutiny and quality control.

After nearly a decade of worldwide mounting TAVI experience, the Cohort -B arm
of the much anticipated PARTNER (Placement of AoRTic TraNscathetER Valve Trial)
trial representing the first randomized data set, reported a dramatic 20%
absolute reduction in mortality in favor of TAVI compared to medical therapy in
patients who, as determined by surgeons could not undergo conventinal surgical
valve replacement.

In the Cohort-A of the PARTNER trial, patients for whom a surgeon and
cardiologist concurred that the predicted risk of operative mortality was 15%
and/or with a minimum STS score of 10, were randomized to TAVI or SAVR. The
trial completed its randomization in early 2009 and first data were presented
at ACC in April 2011 reporting successful achievement of the primary endpoint
(TAVR was non-inferior to SAVR for all-cause mortality at 1 year).

At the PCR London Valves meeting in October 2010, it was reported that over
22000 patients had been treated with TAVI worldwide. To date over 25000
Medtronic CoreValve Systems have been implanted worldwide (data on file
provided by Medtronic). Inevitably, with increased operator experience and
access to the device, physicians will shift their attention to younger patients
with a less pronounced operative risk due to the decreased invasiveness of the
TAVI procedure as compared with SAVR, coupled with the safety and performance
observed in the PARTNER trial and other literature reports in the extreme and
high risk populations. Similar to the coronary revascularization arena, the
blending of surgical and interventional expertise has created unique
interdisciplinary dynamics paving the way for a randomized trial comparing TAVI
with SAVR in a surgical intermediate risk patient population.

It is in this spirit that the SURTAVI trial (SURgical and Transcatheter Aortic
Valve Implantation) was conceived. The interdisciplinary approach and consensus
of the Heart Team (the cardiothoracic surgeon, interventional cardiologist and
other treating physicians if necessary) is crucial. This aspect of decision
making cannot be over-emphasized and is essential for the quality of current
medical practice in general and any planned randomized trial of TAVI versus
SAVR in particular. The VARC publication on TAVI definitions and the
accumulating TAVI expertise in Europe has created a unique momentum for such a
randomized initiative complementary to the US pivotal IDE randomized trial in
AS patients with high operative risk.

For a new technology to be accepted as a new asset for treating symptomatic AS
several essential questions need to be answered: is the technology effective?
Which patients are likely to benefit (patient selection)? How does this new
strategy compare with the alternatives? And what is the cost of the
intervention relative to alternatives? The proof of concept has been validated.
The innovative and less invasive transcatheter approach should be at least as
effective and safe as conventional SAVR or have proof of superiority for both
safety and efficacy compared to medical therapy.

The theoretical benefits seem evident of this transcatheter approach by
avoiding the need of musculoskeletal incisions, cardioplegic arrest, aortic
cross clamping, aortotomy, full cardiopulmonary bypass. Ultimately the
cost-effectiveness will determine whether the new treatme

The objective of this trial is to characterize annually the safety and
durability data through 10 years in a subset of subjects randomized in the
SURTAVI trial.

This is a longitudinal observational clinical trial with long-term follow up of
subjects who were randomized in the SURTAVI Trial.

General Procedural Considerations (TAVI)

Transcatheter Aortic Valve Implantation (TAVI) requires meticulous preparation
and typically a multi-disciplinary team approach involving among others,
interventional cardiologists, cardiac imaging specialists, cardio-thoracic
surgeons and anesthesiologists.
In case of significant coronary artery disease that requires revascularization,
the heart team will assess the feasibility of performing PCI simultaneously
with the TAVI procedure based on the coronary lesion characteristics. When it
is anticipated PCI can be performed in timely fashion with only a limited
amount of additional contrast medium it is encouraged to perform PCI
concomitant with the TAVI. When PCI is deemed challenging requiring relatively
more time and contrast medium, staged PCI is recommended: TAVI will then be
performed at least 7 days after PCI.
The implantation procedure itself takes place either in a catheterization
laboratory with adequate hygiene precautions or ideally in a hybrid operating
room equipped for state-of-the-art transcatheter and/or surgical procedures.
The execution of the TAVI involves an operating team typically consisting of 1
or 2 operators, an anesthesia team and at least 2 nurses/technicians.
Both the dedicated *valve team* and the operators should have the expertise to
select the appropriate access route and device size on a patient-per-patient
basis.
All patients undergoing TAVI should be treated using the ilio-femoral access
route by default (first treatment strategy). Additional non-ilio-femoral access
routes will only be used in case ilio-femoral access is not feasible.
The use of an embolic protection device during the TAVI procedure is not
permitted.

Minimum standards for surgical aortic valve replacement:
Subjects randomized to SAVR should be treated according to the surgeon and
hospital*s standard practices. The surgeon or co-surgeon performing the SAVR
must be a trial investigator for the site. The choice of surgical valve is left
to the discretion of the investigator. However, the use of a bioprosthetic
valve is required.

Surgical Considerations:
Surgical aortic valve replacement is typically performed with cardio-pulmonary
bypass (CPB) on an arrested heart with a clamped aorta. Local practice and
surgical standards should govern type of cardioplegia and the
temperature/flow/pressure perfusion strategy as well as the activated clotting
time used at either institution for safe CPB. Typically a minimum of 2
liters/m²/minute with a systemic arterial blood pressure of 60mmHg during CPB
should be maintained and possibly increased in the elderly patients.
Cannulation for isolated SAVR CPB should be ascending aorta for arterial return
unless there is ascending aortic arteriosclerosis or dilatation (>4 cm in
diameter), and right atrial for venous drainage. Embilic devices are not
routinely used in SAVR.

Echocardiography
Physical exam inclusive NYHA classification evaluation