Transcatheter Valve Implantation in Patients With Dysfunctional Left and Right Sided Heart Valves

Many forms of congenital and structural heart disease require surgical placement of
prosthetic valves and conduits. These conditions include many common congenital heart
abnormalities such as Tetralogy of Fallot, Double Outlet Right Ventricle, Truncus Arteriosus
and patients who require the Ross procedure for aortic stenosis. There are a variety of
acquired conditions, including calcific aortic valve stenosis that may require surgical or
transcatheter valve treatment. Unfortunately, when valved conduits are placed surgically,
they ultimately become narrowed or regurgitant and require periodic replacement. Thus,
patients with these conditions often undergo multiple open heart surgeries during their
lifetime. Although the risk of mortality with this kind of surgery is low, surgical
intervention is associated with significantly longer recovery times and more patient
discomfort when compared to transcatheter interventions. Over the last decade, techniques
have been developed to palliate these forms of congenital and structural heart disease using
catheters inserted through blood vessels in the groin. These transcatheter techniques have
allowed patients to delay or avoid open heart surgery.

The Medtronic Melody Trancatheter Valve and the Edwards SAPIEN Transcatheter Heart Valve are
both bioprosthetic valves mounted within metal stents. Their entire structure is collapsible,
allowing it to be inserted through delivery sheaths and threaded into the heart, typically
without the need of surgical cardiopulmonary bypass. Some of these procedures may be
performed using a hybrid technique of minimal surgical access and transcatheter valve
delivery. The valves can then be expanded into place by inflating a balloon (similar to how
stents are placed elsewhere in the heart, like the coronary artery). The Melody Valve
received a humanitarian device exemption (HDE) from the FDA and the Edwards Sapien Valve has
market approval from the FDA.The investigators plan to offer these transcatheter valves as
alternatives to eligible patients who require replacement of a stenotic or regurgitant valve
in all left and right sided positions.

The intended role of the Melody Transcatheter Pulmonary Valve is to restore pulmonary valve
function in patients with a dysfunctional RVOT conduit and a clinical indication for
pulmonary valve replacement. Unlike currently available options for pulmonary valve
replacement, the TPV is intended to be placed with a transcatheter delivery system, and thus
does not require surgical incisions, open heart surgery, cardiopulmonary bypass, or the
various morbidities associated with surgical pulmonary valve replacement. The Edwards Sapien
Valve is delivered in the same manner, but was intended for use in the aortic position. The
ultimate goals and durability of the TPV may differ among patients with different
indications. At a minimum, the intention is that the TPV will improve hemodynamic function,
mitigate the adverse impact of valve regurgitation and/or obstruction, and effectively extend
the longevity of the existing conduit and defer or obviate the need for conduit replacement.
These techniques may decrease the number of open heart surgeries required over the course of
a patient's lifetime, thereby decreasing the cumulative morbidity and risk associated with
such operations.

With regards to valve replacement in any position with an adequate landing zone, the Melody
Valve and Edwards Sapien Valve are presently being utilized at multiple United States centers
for valve replacement in all positions in patients who are considered high risk candidates
for surgical valve replacement. A recent article published by Zahn et al reported an
experience in tricuspid valve implantations at three United States centers and one
Austrailian center. Procedural success was achieved in all patients. Tricuspid regurgitation
was reduced to mild or none in all patients. Noted complications were consistent with known
risks of cardiac catheterization and Melody Valve implantation, regardless of indication.
Similarly, an article published by Kenny et al demonstrated the successful implantation of
the Sapien valve in the tricuspid position. Gillespie et al, recently published a series of
Melody implants in the mitral position in sheep that had undergone annuloplasty ring
placement. Other investigators have successfully implanted the Melody valve in the aortic and
mitral positions in patients with good immediate and short/intermediate term outcomes
(Ben-Gal et al, Hasan et al, Gossl et al). The Edwards Sapien Valve has several reports of
positive outcomes when implanted within the aortic position (Thomas et al, Moat et al, Webb
et al) and two case series that report encouraging results when placed in the mitral
position. (Seiffert et al, Cheung et al)

Inclusion Criteria:

- Patients will be considered eligible for transcatheter valve implantation if the risk
of serious morbidity or mortality with surgical intervention is deemed to be greater
than 10 percent by the treating cardiologist and consulting surgeon. The Melody Valve
is intended for use in the following clinical conditions:

- Existence of a full (circumferential) RVOT conduit that was equal to or greater than
16 mm in diameter when originally implanted, AND

- Dysfunctional RVOT conduits with a clinical indication for intervention, AND EITHER

- Regurgitation ≥ moderate

- Stenosis: mean right ventricular outflow tract gradient ≥ 35 mmHg

- The Edwards Sapien Valve will be used in the aortic position for valves and conduits
larger than 23mm in diameter with a landing zone less than 26-27mm, otherwise the
melody valve will be considered

- The Edwards Sapien Vavle will also be considered in other positions that have an
adequate landing zone and a large enough circumference

- The Melody valve may be utilized outside of its approved indications for valve
replacement in high risk surgical patients

Exclusion Criteria:

- There are no known contraindications for implantation of the Melody Valve or the
Edwards Sapien Valve