Alternative Access Approaches for Transcatheter Aortic Valve Replace (TAVR) in Inoperable Patients With Aortic Stenosis
Alternative Access Approaches for Transcatheter Aortic Valve Replace (TAVR) in Inoperable Patients With Aortic Stenosis
Investigational study of Edwards Lifesciences, LLC's "Edwards SAPIEN Transcatheter Heart
 Valve" for non-femoral delivery, (or alternative access deliver) 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 co-morbidities would not
 preclude the expected benefit from correction of the aortic stenosis. Will outcomes observed
 in a high-risk operable transapical native valve TAVR cohort receiving an Edwards SAPIEN
 device compare to inoperable patients undergoing alternative access TAVR with the Edwards
 SAPIEN device experience a reasonably similar incidence of 30 day adverse events?
Transcatheter aortic valve replacement (TAVR) using the Edwards SAPIEN valve and Retroflex 3
 delivery system provides both a mortality and quality of life benefit for inoperable
 patients. Only the transfemoral (TF) access has been approved in the US. A substantial number
 of patients cannot have a TF approach due to inadequate vessel size, vessel disease, or other
 anatomical considerations. The pivotal study did not include an assessment of safety and
 effectiveness of alternative access approaches in this inoperable patient group.

 Early approaches to TAVR included a femoral transvenous approach with transseptal access to
 the left side for delivery of the valve. This approach avoided large bore arterial
 catheterization, but it had unacceptable rates of complications and lacked reproducibility.
 Alternative access approaches have been developed because of the risks associated with
 inserting large caliber catheters into small, diseased femoral arteries often associated with
 diffuse vasculopathy. To avoid the vascular complications from femoral access, other
 transcatheter approaches have been developed to include open surgical access to the left
 ventricular apex (TA), ascending aorta, (TAO), subclavian and axillary arteries (TS), and
 retroperitoneal access to the iliac artery (TI) as well as distal aorta. In addition to
 providing TAVR to patients who cannot have TF access, additional advantages include better
 catheter control and safer closure of the access site. Commonly cited disadvantages include
 the need for surgical expertise and additional equipment, along with the potential for longer
 recovery, more incisional pain, greater radiation exposure for operators, unsuitable delivery
 catheters for alternative access sites, and a host of unique alternative access site
 complications.

 We propose to collectively analyze 30-day safety endpoints as a lumped data group for these
 alternative access approaches. These data are gathered from clinical practice in real-world
 settings and submitted to the TVT Registry. It is expected that centers will choose among the
 various choices for alternative access based the causative factors underlying the need for
 alternative access, as well as local skill sets and experience. For this lumped data group of
 alternative access approaches we will compare 30-day safety results to the TA outcomes
 reported from Cohort A of the PARTNERS 1 trial. We recognize that these TA patients were high
 risk operable patients rather than inoperable patients, but no other direct comparator group
 is available. We reason that the TA data from this published clinical trial are high quality,
 represent an alternative access approach rather than TF, and will provide a frequency of
 safety endpoints that have been found to be acceptable both clinically and from a regulatory
 perspective.
Inclusion Criteria:

 -  18 years or older

 -  Primary indication is symptomatic primary severe aortic stenosis predicted to benefit
 from relief of valvular stenosis

 -  Aortic valve area less than 0.8 centimeters squared

 -  Mean aortic valve gradient greater than or equal to 40 mmHG

 -  Peak aortic jet velocity greater than or equal to 4.0 m per second

 -  Valve sheath access site is femoral, axillary, transapical, transaortic, subclavian or
 subaxillary

 -  Patient is judged by the local heart team to be inoperable for Aortic Valve
 Replacement due to severe chest wall deformities or radiation effects, severe
 peripheral or aortic vascular disease, or severe systemic disease prohibiting the safe
 conduct of Cardiopulmonary Bypass (CPB)

 Exclusion Criteria:

 -  Aortic valve annulus size is less than 18 mm or greater than 25 mm

 -  Active infectious endocarditis

 -  Valve in prosthetic valve procedure

 -  Patients considered by the heart team to be unlikely to receive meaningful or durable
 clinical benefit from the procedure