U.S. patent application number 10/893127 was filed with the patent office on 2005-03-10 for devices and methods for percutaneously treating aortic valve stenosis.
Invention is credited to Helkowski, Rick, Laird, Rob.
Application Number | 20050054977 10/893127 |
Document ID | / |
Family ID | 34107771 |
Filed Date | 2005-03-10 |
United States Patent
Application |
20050054977 |
Kind Code |
A1 |
Laird, Rob ; et al. |
March 10, 2005 |
Devices and methods for percutaneously treating aortic valve
stenosis
Abstract
Devices and methods for their use in percutaneously increasing
the aortic valve flow of a stenotic aortic valve are provided. The
subject devices include an aortic valve isolation element, a shunt
element and an aortic valve flushing element. Also provided are
systems and kits that include the subject devices and can be
employed in practicing the subject methods. The subject devices,
methods, systems and kits find use in treating conditions
associated with the presence of stenotic aortic valves.
Inventors: |
Laird, Rob; (Pinole, CA)
; Helkowski, Rick; (Menlo Park, CA) |
Correspondence
Address: |
BOZICEVIC, FIELD & FRANCIS LLP
1900 UNIVERSITY AVE
SUITE 200
EAST PALO ALTO
CA
94303
US
|
Family ID: |
34107771 |
Appl. No.: |
10/893127 |
Filed: |
July 16, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60531473 |
Dec 19, 2003 |
|
|
|
60488507 |
Jul 17, 2003 |
|
|
|
Current U.S.
Class: |
604/96.01 |
Current CPC
Class: |
A61B 2017/22067
20130101; A61M 2025/109 20130101; A61B 17/12131 20130101; A61B
2017/22054 20130101; A61M 25/10 20130101; A61B 17/12045 20130101;
A61B 17/22 20130101; A61B 2017/22084 20130101; A61B 17/12136
20130101; A61M 2025/1052 20130101; A61B 2017/12127 20130101; A61M
2025/1095 20130101 |
Class at
Publication: |
604/096.01 |
International
Class: |
A61M 029/00 |
Claims
1. A device comprising: (a) a valve isolation element that
includes: (i) a ventricular side aortic valve occlusion element;
and (ii) an ascending aorta occlusion element; and (b) an aortic
valve flushing element.
2. The device according to claim 1, wherein said flushing element
includes: (a) a fluid introducing element; and (b) a fluid
aspiration element.
3. The device according to claim 2, wherein said fluid introducing
element is in fluid communication with a source of stenotic
dissolution fluid.
4. The device according to claim 4, wherein said stenotic
dissolution fluid is an acidic dissolution fluid.
5. The device according to claim 1, wherein said ventricular side
aortic valve occlusion element is a balloon.
6. The device according to claim 1, wherein said ventricular side
aortic valve occlusion element is a funnel.
7. The device according to claim 1, wherein said device further
includes shunt element that provides for blood flow through an
aortic valve isolated with said valve isolation element.
8. The device according to claim 7, wherein said shunt element
further includes a valve element.
9. The device according to claim 8, wherein said valve is
positioned distal from said isolation element.
10. The device according to claim 8, wherein said valve is
positioned proximal to said isolation element.
11. The device according to claim 1, wherein said device further
includes a fluid flow diverter element.
12. The device according to claim 1, wherein said device is
configured for percutaneous delivery to a target site.
13. The device according to claim 13, wherein said device further
comprises an integrated introducer.
14. The device according to claim 1, wherein said an ascending
aorta occlusion element has an isolation bell configuration.
15. A method of increasing the aortic valve area of a stenotic
aortic valve, said method comprising: (a) isolating said stenotic
aortic valve with a valve isolation element that includes: (i) a
ventricular side aortic valve occlusion element; and (ii) an
ascending aorta occlusion element; and (b) flushing said isolated
stenotic aortic valve with a stenosis dissolution fluid for a
period of time sufficient to increase said stenotic aortic valve's
aortic valve area.
16. The method according to claim 15, wherein said flushing
comprises contacting said isolated stenotic aortic valve with said
stenosis dissolution fluid and removing fluid from said isolated
stenotic aortic valve.
17. The method according to claim 16, wherein said dissolution
fluid is an acidic dissolution fluid.
18. The method according to claim 15, wherein said method further
comprises contacting said isolated stenotic aortic valve with a
dissolution fluid attenuating fluid.
19. The method according to claim 18, wherein said dissolution
fluid is an acidic dissolution fluid and said dissolution fluid
attenuating fluid is a pH elevating fluid.
20. The method according to claim 19, wherein said pH elevating
fluid is a buffer.
21-31. (canceled)
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority (pursuant to 35 U.S.C.
.sctn. 119 (e)) to the filing date of U.S. Provisional Patent
Application Ser. No. 60/531,473 filed on Dec. 19, 2003 and to the
filing date of U.S. Provisional Patent Application Ser. No.
60/488,507 filed on Jul. 17, 2003; the disclosures of which are
herein incorporated by reference.
INTRODUCTION
[0002] 1. Background of the Invention
[0003] Aortic valve stenosis refers to a disease condition
characterized by a narrowing of the aortic valve. While aortic
valve stenosis can results from the presence of a bicuspid valve or
rheumatic fever, wear and tear of the aortic valve in the elderly
is the most common cause of this condition. This latter condition
is known as "senile calcific aortic stenosis." With aging, protein
collagen of the valve leaflets is destroyed, and calcium is
deposited on the leaflets. Once valve leaflet mobility is reduced
by calcification, turbulence across the valve increases, causing
scarring, thickening, and stenosis of the valve.
[0004] Symptoms and heart problems in aortic stenosis are related
to the degree of narrowing of the aortic valve area. Patients with
mild aortic valve narrowing may experience no symptoms. When the
narrowing becomes significant (usually greater that 50% reduction
in valve area), the pressure in the left ventricle increases and a
pressure difference can be measured between the left ventricle and
the aorta. To compensate for the increasing resistance at the
aortic valve, the muscles of the left ventricle thicken to maintain
pump function and cardiac output. This muscle thickening causes a
stiffer heart muscle which requires higher pressures in the left
atrium and the blood vessels of the lungs to fill the left
ventricle. Even though these patients may be able to maintain
adequate and normal cardiac output at rest, the ability of the
heart to increase output with exercise is limited by these high
pressures. As the disease progresses, the increasing pressure
eventually causes the left ventricle to dilate, leading to a
decrease in cardiac output and heart failure. Without treatment,
the average life expectancy after the onset of heart failure due to
aortic stenosis is between 18 to 24 months.
[0005] When symptoms of chest pain, syncope, or shortness of breath
appear, the prognosis for patients with aortic stenosis without
valve replacement surgery is poor. Medical therapy, such as the use
of diuretics to reduce high lung pressures and remove lung fluid,
can provide only temporary relief of symptoms. Patients with
symptoms usually undergo cardiac catheterization. If severe aortic
stenosis is confirmed, aortic valve replacement is usually
recommended. The overall mortality risk for aortic valve
replacement surgery is about 5%.
[0006] While effective, aortic valve replacement is not without
disadvantages, where such disadvantages include the requirement of
chronic anticoagulation therapy, risk of failure and requirement
for replacement, and the like.
[0007] As such, there is a continued interest in the development of
new protocols for treating aortic valve stenosis. Of particular
interest would be the development of a percutaneous protocol that
could be practiced in a `beating-heart` setting.
[0008] 2. Relevant Literature
[0009] See e.g., WO 01/15767; WO 01/13985; WO 00/03651; and WO
01/39783.
SUMMARY OF THE INVENTION
[0010] Devices and methods for their use in percutaneously
increasing the aortic valve flow of a stenotic aortic valve are
provided. The subject devices include an aortic valve isolation
element, a shunt element and an aortic valve flushing element. The
aortic valve isolation element is made up of a ventricular side
aortic valve occlusion element and a proximal side aortic valve
isolation element. The shunt element is made up of a shunt lumen
that includes one or more ventricular side blood inflow ports and
one or more proximal side valves that provide for one-way exit of
blood from the shunt lumen into the aorta. The aortic valve
flushing element is made up of a fluid introducing element and a
fluid removal element. In practicing the subject methods, a
stenotic aortic valve is first isolated. Next, the isolated valve
is flushed with a dissolution fluid, e.g., an acidic dissolution
fluid, for a period of time sufficient for the aortic valve flow of
the treated valve to be increased. In certain embodiments, the
valve is also contacted with a dissolution fluid attenuating fluid,
e.g., a buffer, during or after the flushing step in order to limit
the contact of non-valve tissue with the dissolution fluid. Also
provided are systems and kits that include the subject devices and
can be employed in practicing the subject methods. The subject
devices, methods, systems and kits find use in treating conditions
associated with the presence of stenotic aortic valves.
BRIEF DESCRIPTIONS OF THE DRAWINGS
[0011] FIG. 1 provides an illustration of a representative
embodiment of a device according to the subject invention.
[0012] FIG. 2 provides an illustration of an alternative
representative device configuration according to the subject
invention.
[0013] FIG. 3 provides an illustration of yet another alternative
representative device configuration according to the subject
invention.
[0014] FIGS. 4 and 5 provide two different views of yet another
alternative representative device configuration according to the
subject invention.
[0015] FIGS. 6A & 6B provide views of different points in the
delivery of a device embodiment as depicted in FIGS. 4 and 5 that
includes an integrated introducer element.
DETAILED DESCRIPTION OF THE INVENTION
[0016] Devices and methods for their use in percutaneously
increasing the aortic valve flow of a stenotic aortic valve are
provided. The subject devices include an aortic valve isolation
element, a shunt element and an aortic valve flushing element. The
aortic valve isolation element is made up of a ventricular side
aortic valve occlusion element and a proximal side aortic valve
isolation element. The shunt element is made up of a shunt lumen
that includes one or more ventricular side blood inflow ports and
one or more proximal side valves that provide for one-way exit of
blood from the shunt lumen into the aorta. The aortic valve
flushing element is made up of a fluid introducing element and a
fluid removal element. In practicing the subject methods, a
stenotic aortic valve is first isolated. Next, the isolated valve
is flushed with a dissolution fluid, e.g., an acidic dissolution
fluid, for a period of time sufficient for the aortic valve flow of
the treated valve to be increased. In certain embodiments, the
valve is also contacted with a dissolution fluid attenuating fluid,
e.g., a buffer, during or after the flushing step in order to limit
the contact of non-valve tissue with the dissolution fluid. Also
provided are systems and kits that include the subject devices and
can be employed in practicing the subject methods. The subject
devices, methods, systems and kits find use in treating conditions
associated with the presence of stenotic aortic valves.
[0017] Before the present invention is described further, it is to
be understood that this invention is not limited to particular
embodiments described, as such may, of course, vary. It is also to
be understood that the terminology used herein is for the purpose
of describing particular embodiments only, and is not intended to
be limiting, since the scope of the present invention will be
limited only by the appended claims.
[0018] Where a range of values is provided, it is understood that
each intervening value, to the tenth of the unit of the lower limit
unless the context clearly dictates otherwise, between the upper
and lower limit of that range and any other stated or intervening
value in that stated range is encompassed within the invention. The
upper and lower limits of these smaller ranges may independently be
included in the smaller ranges is also encompassed within the
invention, subject to any specifically excluded limit in the stated
range. Where the stated range includes one or both of the limits,
ranges excluding either or both of those included limits are also
included in the invention.
[0019] Unless defined otherwise, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention belongs. Although
any methods and materials similar or equivalent to those described
herein can also be used in the practice or testing of the present
invention, the preferred methods and materials are now described.
All publications mentioned herein are incorporated herein by
reference to disclose and describe the methods and/or materials in
connection with which the publications are cited.
[0020] It must be noted that as used herein and in the appended
claims, the singular forms "a", "and", and "the" include plural
referents unless the context clearly dictates otherwise.
Conversely, it is contemplated that the claims may be so-drafted to
exclude any optional element. This statement is intended to serve
as antecedent basis for use of such exclusive terminology as
"solely," "only" and the like in connection with the recitation of
claim elements or by use of a "negative" limitation
[0021] The publications discussed herein are provided solely for
their disclosure prior to the filing date of the present
application. Nothing herein is to be construed as an admission that
the present invention is not entitled to antedate such publication
by virtue of prior invention. Further, the dates of publication
provided may be different from the actual publication dates which
may need to be independently confirmed.
[0022] As summarized above, the subject invention provides devices
and methods for increasing the aortic valve flow of a stenotic
aortic valve, as well as systems and kits for use in practicing the
subject methods. In further describing the invention, the subject
devices are described first in greater detail, followed by a review
of the subject methods, systems and kits.
Devices
[0023] The subject invention provides devices that are capable of
locally flushing an aortic valve in situ with a dissolution fluid.
As such, the subject devices are capable of locally flushing an
aortic valve when present in a heart, where the heart is generally
present in a subject or patient (host). By "locally flushing" is
meant that the aortic valve and, at most, the immediately adjacent
tissue structures are flushed with the fluid, but not the remainder
of the heart or host in which the subject aortic valve is present.
As such, the subject devices do not systemically administer the
dissolution fluid, such that it contacts the vasculature of the
heart/host beyond the aortic valve.
[0024] The subject devices are also characterized in that they are
dimensioned to be sufficiently small for introduction into the
vascular system (i.e., vasculature) from a remote location, e.g.,
femoral approach, so that they can be percutaneously introduced to
the aortic valve.
[0025] The devices and methods of the present invention are
designed to be employed in beating heart applications, by which is
meant that the subject methods may be performed while the heart is
still beating, i.e., where the heart has not been stopped.
[0026] As summarized above, the subject devices include an aortic
valve isolation element, a shunt element and a valve flushing
element. Each of these elements is now described separately in
greater detail.
[0027] Valve Isolation Element
[0028] The valve isolation element of the subject devices is made
up of three different sub-elements that work in concert to isolate
the target aortic valve to be treated from the remainder of the
heart/vasculature of the host. By "isolate" is meant that the fluid
flow between the target aortic valve and the remainder of the
vascular system is substantially, if not completely, inhibited. As
such, the valve isolation system effectively partitions the target
aortic valve from the remainder of the vasculature. The
sub-elements that make up the valve isolation element are: (1) a
ventricular side valve occlusion element; and (2) aortic side valve
occlusion element. Each of these elements is now described in
greater detail separately.
[0029] Ventricular Side Valve Occlusion Element
[0030] The ventricular side valve occlusion element serves to
occlude blood flow through the aortic valve by blocking or
occluding the upstream side of the valve, i.e., the ventricular
side of the valve, thereby forcing blood to flow through the shunt
element, described in greater detail below. This occlusion element
also serves to anchor or stabilize the distal end of the device at
the ventricular side of the aortic valve. This occlusion element
may be any convenient type of occlusion element that can
effectively occlude or block the ventricular site of the aortic
valve. By effectively occlude or block is meant that fluid, e.g.
blood, flow past the occlusion element upon activation is reduced
by at least 95%, usually by at least 97% and more usually by at
least 99%, where in preferred embodiments, fluid flow is reduced by
100% such that the fluid flow from the ventricle into the isolated
valve site is substantially, if not completely, inhibited.
Representative occlusion elements include inflatable balloons,
expandable membranes or analogous materials that assume the form of
a funnel (e.g., as shown in FIGS. 3, 4 and 5), etc.
[0031] In certain embodiments, the occlusion element is an
expandable or inflatable balloon. In these embodiments where the
occlusion element is a balloon, the balloon is generally an
expandable balloon that is capable of going from a first,
compressed state to a second, expanded state, e.g., by introduction
of a fluid or gas into the interior of the balloon, e.g., via an
inflation lumen in fluid communication with the interior of the
balloon. While the inflatable balloon may be one that is designed
to be inflated with a gas or liquid, of particular interest in many
embodiments are those that are configured to be inflated with a
liquid, e.g. a pH elevating solution as described in greater detail
infra. Balloons suitable for use in vascular devices, e.g.,
catheter devices, cannula devices, etc., are well known to those of
skill in the art and may be readily adapted for use in devices of
the present invention.
[0032] In yet other embodiments, the anchor is a structure that can
assume a funnel configuration when deployed, such as is shown in
FIGS. 3, 4 and 5. The funnel structure may be deployable, for
example where the anchor structure uses a shape memory, e.g., NiTi,
hoop attached to a thin silicone "Funnel". In such an embodiment,
the funnel may be attached to the central shunt lumen. This funnel
structure may then be collapsed by pulling one end of it in the
longitudinal direction of the device and withdrawing the structure
into the sheath. In a variation of this particular embodiment, the
deployable funnel structure may be one that uses an adjustable hoop
in a lasso-type configuration. Further details of such embodiments
are depicted in the figures of the figures of priority provisional
application No. 60/531,473, the disclosure of such details being
specifically incorporated herein by reference.
[0033] Aortic Side Valve Isolation Element
[0034] The next component of the isolation system is the aortic
side valve isolation element, also referred to herein as the
ascending aorta occlusion element. This element serves to isolate
the aortic side of the aortic valve from the remainder of the aorta
and thereby prevent fluid flow from the isolated valve into the
ascending aorta downstream of its deployment, as well as the
coronary ostia. As such, this isolation element is one that
substantially, if not completely, impedes fluid flow from the
isolated region of the valve past its site of deployment downstream
into the aorta, as well into the coronary ostia. The isolation
element (also referred to as the "isolation bell" is, in many
embodiments, an expandable element, such as the wire scaffolded
membranous isolation element, as depicted in FIGS. 1 to 5. In
representative embodiments, the isolation element allows for
natural perfusion of the coronary arteries, such that is configured
not to block the coronary arteries from blood present on the aortic
side of the isolation element, e.g., blood that has been shunted
from the ventricle. In certain embodiments, the isolation element
has a double lip seal to provide for the desired isolation. Further
details of such a double lip seal are provided in priority
provisional application No. 60/531,473, the disclosure of such
details being specifically incorporated herein by reference.
[0035] Shunt Element
[0036] As summarized above, the subject devices also include a
shunt element that provides for blood flow through the region of
isolation from the ventricular side of the valve to the aorta.
Typically, the shunt is one that expands upon deployment to provide
for desirable blood flow. The shunt element may be any convenient
structure which provides a passageway that conveys blood from the
left ventricle through the isolated area to a position downstream
of the aortic side valve isolation element. In certain embodiments,
this shunt element is a shunt lumen that includes one or more
distal blood inflow ports and one or more proximal blood outflow
ports, where the blood outflow ports may include a one-way valve
component that provides for one-way fluid flow out of the shunt
lumen. Such an embodiment is depicted in FIG. 1. In yet other
embodiments, the shunt element may include a single, larger
ventricular opening and integrated aortic valve, such as the shunt
embodiment depicted in FIGS. 2 and 3.
[0037] Valve Flushing Element
[0038] Also present in the subject devices is an aortic valve
flushing element for flushing an isolated aortic valve with at
least a dissolution fluid. By "flushing" is meant that fresh
dissolution solution is contacted with the target valve surface one
or more times, including continuously, during the treatment period,
as described in further detail below, where in certain
representative embodiments of the subject methods, the surface of
the target valve surface, typically the aortic side of the aortic
valve, is continuously contacted or flushed with the dissolution
fluid. In other words, the acidic dissolution fluid is introduced
in a manner such that a continuous flow of the dissolution fluid
across the surface of the valve is achieved.
[0039] In flushing the isolated target valve, in certain
representative embodiments the pressure in the local environment
which includes the isolated target valve remains substantially
isometric. By substantially isometric is meant that the pressure in
the local environment does not vary by a significant amount, where
the amount of variance over the treatment period does not vary by
more than about 50%, usually by not more than about 10% and more
usually by not more than about 5%. In other words, the local
environment remains substantially isobaric during the treatment
period. Accordingly, the device includes a flushing element that
dynamically contacts the target valve with dissolution fluid and
simultaneously removes fluid from the local environment of the
isolated valve, such that the overall volume of fluid in the local
environment remains substantially constant, where any difference in
volume at any two given times during the treatment period does not
exceed about 50%, and usually does not exceed about 10%.
[0040] To provide for the above function, the flushing element of
the subject devices typically includes a fluid introduction element
and a fluid removal (i.e., aspiration) element, which elements are
capable of introducing fluid into and removing fluid from the
isolated local environment of the target aortic valve such that the
aortic valve, or at least the aortic side thereof, is flushed with
the introduced fluid. The fluid introduction and removal elements
may take a variety of different configurations, so long as they
serve their intended purpose of introducing fluid into and removing
fluid from the isolated local environment of the target aortic
valve. Representative configurations include, but are not limited
to: two separate tubes or analogous fluid conveyance structures,
where the tubes may or may not be concentric; two separate lumens
of a single tube, e.g., a tube having a dividing partition running
the length of the tube to define two separate fluid conveyance
lumens; etc. As the fluid introduction and removal elements
introduce and remove fluid from the local environment, they have
distal openings that are positioned on the device upstream or
distal from the ascending aorta occlusion element. Depending on the
particular configuration of the device, the distal openings of the
fluid introduction and removal elements may or may not be
positioned at the same location relative to the target valve.
[0041] The fluid introduction element is further characterized by
having a proximal end that is either directly, or through a linking
fluid conveyance structure, attached to a source of a dissolution
fluid, e.g., a reservoir having a volume of dissolution fluid
present therein, such that the interior of the fluid introduction
means is in fluid communication with a volume of dissolution fluid.
The proximal end of the fluid introduction element typically
includes a valve or other flow control means for controlling the
amount of the fluid that enters the lumen of the fluid introduction
element from the reservoir of dissolution fluid.
[0042] The fluid removal or aspiration element is further
characterized in that the fluid removal element is attached at its
distal end, either directly or through a fluid conveyance linking
element, e.g., tube, to a reservoir for waste fluid. In addition, a
negative pressure element that provides for suction of fluid from
the isolated local environment at the distal end of the fluid
removal element into the fluid removal element is also present,
where representative negative pressure elements include pumps,
vacuums, etc.
[0043] In addition to the above fluid introduction and removal
elements, in certain representative embodiments the subject devices
include a second fluid introduction element for introducing a
second fluid into the isolated local environment of the target
valve, where the second fluid delivery element is often an element
for delivering a dissolution fluid attenuating fluid. When present,
the second fluid delivery element may be positioned or configured
relative to the above-described first fluid delivery and removal
elements in a number of different ways. For example, the second
fluid delivery element may be a separate tube or analogous
structure, where the tube may or may not be present in one or more
of the first fluid delivery element or aspiration element, or vice
versa, e.g., the different elements may be concentric with each
other. Alternatively, the second fluid delivery element may be a
lumen present in a multi-lumen structure, where other lumens may be
the aspiration and/or first fluid delivery elements.
[0044] The second fluid introduction element is further
characterized by having a proximal end that is attached, either
directly or through a linking fluid conveyance structure, to a
source of a second fluid, e.g., a reservoir having a volume of
dissolution fluid attenuating fluid present therein, such that the
interior of the second fluid introduction means is in fluid
communication with a volume of dissolution fluid attenuating fluid.
The proximal end of the fluid introduction element typically
includes a valve or other flow control element for controlling the
amount of the fluid that enters the lumen of the second fluid
introduction element from the reservoir of dissolution fluid
attenuating fluid.
[0045] Additional General Features of the Device
[0046] In certain embodiments, the device may include a fluid flow
modulator which, upon deployment of the device, modifies blood flow
exiting the shunt into the aorta. A representative embodiment of
such an element is further described in connection with the
description of the specific embodiment depicted in FIGS. 4 and 5,
below.
[0047] In certain embodiments, the device may include an integrated
particle capture element, e.g., mesh, netting or other suitable
structure, that can prevent particles, tissue debris or other
undesired structures that may be produced during practice of the
subject methods to enter the systemic vasculature of the subject or
patient.
[0048] In certain embodiments, the devices may include an
integrated introducer element. The integrated introducer element is
characterized by being capable of assuming first and second
configurations depending on the particular time point during
deployment, such that at an initial time point during entry of the
device into the vascular it is contiguous with the distal end of
the device, e.g., where the above described valve isolation,
flushing and shunt elements are positioned. At a second time period
as the distal end is progressed to the remove valve site, the
distal end separates from the introducer element, such that the
integrated introduce and distal end of the device are no longer
contiguous. A representative embodiment of such a device is further
described in connection with FIGS. 6A and 6B, below. While such an
integrated introducer element is described in this application
primarily in connection with the particular catheter devices
described herein, it is to be understood that this integrated
introducer element is readily adaptable to other catheter devices
that benefit from introduction by use of an introducer, and such
other catheter devices modified to have an integrated introducer
element fall within the scope of certain embodiments of the
invention. As such, certain embodiments of the invention have a
scope sufficiently broad to include any catheter device that is
modified to include an integrated introducer element.
[0049] The device may be a device in which all of the elements are
statically positioned relative to each other such that no relative
movement is possible between any two elements of the device, or two
or more of the subject elements may be movable relative to each
other in the device. For example, the fluid introduction element
may be slidably positioned inside of the fluid removal element; the
ventricular side occlusion means may be adjustably movable relative
to the remainder of the device to provide for an adjustable
isolated local environment; etc.
[0050] The components of the subject devices, as described above,
may be fabricated from any convenient material. The materials must
be able to withstand contact with any fluids introduced or removed
thereby and should be physiological compatible, at least for the
period of time in which they are being used. Suitable materials
include biocompatible polymers, e.g. polyimide, PBAX.TM.,
polyethylene, and the like. Any glues or fittings that are employed
must also be able to meet the same criteria. Any convenient
fabrication protocol may be employed, where numerous suitable
protocols are known to those of skill in the art.
[0051] Representative Specific Embodiment
[0052] A representative embodiment of the subject devices is
depicted in FIG. 1. Percutaneous catheter device 10 includes
ventricular side occlusion balloon 12 and aortic side occlusion
"bell" 14. The device further includes shunt 16 that has distal
inflow ports 16a and proximal outflow ports 16b covered by one-way
valves 16c. Not shown is the isolated valve-flushing element, that
comprises fluid inflow and outflow lumens housed in structure 18.
During delivery, the distal end of the device can be retracted into
sheath 19 for a suitable low-profile for delivery to the target
site. As evidenced from the depiction, the device is configured and
dimensions to isolate an aortic valve following percutaneous
delivery of the distal end of the device to the target valve site
via the vasculature. A variety of specific dimensions for the
device and components thereof may be chosen to meet the above
general parameters, and such dimensions are readily determined by
those of skill in the art.
[0053] An alternative specific embodiment have a modified
shunt/valve configuration is depicted in FIG. 2. In FIG. 2, device
20 includes certain features that are the same as those shown in
the device depicted in FIG. 1. For example, device 20 includes a
ventricular side balloon 12 and an isolation bell 14. However,
shunt element 16 has been replaced with a modified shunt element 22
which has a single distal opening for blood inflow 24 and a single
proximal fluid outflow port 26 through which fluid flow is
modulated or controlled by an integral one-way valve, not shown. As
depicted in this embodiment, the valve element is much closer to
the isolation bell than it is in the device shown in FIG. 1. In the
device shown in FIG. 2, fluid flow lumens 28 are clearly visible
proximal to the isolation bell.
[0054] Yet another specific embodiment of the device is shown in
FIG. 3, which is a further variation of the device shown in FIG. 2.
In FIG. 3, device 30 differs from device 20 in FIG. 2 in that the
ventricular side occlusion balloon has been replaced by an
occlusion funnel element 32, which is positioned at the distal end
of the shunt and serves to anchor the distal end of the device as
the target site.
[0055] Yet another specific embodiment of the device is shown in
FIG. 4, which is a further variation of the device shown in FIG. 3.
In FIG. 4, device 40 differs from device 30 in FIG. 3 in that the
distal end of the device further includes a fluid flow diverter 42.
Flow diverter 42 is a conical tipped element which provides for a
number of advantages. During introduction of the distal end of the
device to the target site, the flow diverter 42 is contiguous with
a delivery sheath 44 as shown in FIGS. 5 and 6, such that the
device has a blunt end which provides for various advantages during
delivery, such as reduced collateral tissue damage. During use of
the subject device when the target valve is isolated is blood in
shunted from the ventricle to the aorta, the flow diverter 42 may
be retracted to a position proximal the blood outflow port of the
shunt, and thereby divert flow away from the device and provide for
improved blood flow in the aorta and rest of the vasculature.
Methods
[0056] The above-described devices find use in methods of flushing
an aortic valve with at least one fluid composition. In the
broadest sense, the subject catheter systems may be employed to
introduce any active agent in a fluid delivery vehicle to an aortic
valve by flushing the aortic valve with such a fluid composition.
The subject systems achieve local delivery of active agents in
fluid delivery vehicles by irrigating or flushing an isolated
aortic valve with the fluid agent composition.
[0057] Of particular interest are methods of using the subject
devices to percutaneously flush an isolated aortic valve of a
beating heart, particularly a stenotic aortic valve, with a
dissolution fluid, where the dissolution fluid may be an organic
matter dissolution fluid or an inorganic matter dissolution fluid,
or a fluid that is capable of both inorganic matter and organic
matter dissolution. Representative dissolution fluids are In U.S.
Pat. No. 6,533,767; the disclosure of which is herein incorporated
by reference.
[0058] In many embodiments, the dissolution fluid employed in the
subject methods is an inorganic matter dissolution solution. In
many of these embodiments, the inorganic matter dissolution fluid
is an acidic dissolution fluid. A variety of different types of
acidic dissolution solutions may be employed in the subject
methods. The acidic treatment solutions that find use in the
subject methods generally have a pH of less than about 6.5, where
the pH is usually less than about 4.0 and more usually less than
about 3.0. In representative embodiments, the pH ranges from 0 to
2, and usually 0 to 1. The acidic treatment solution can include a
number of different types of acids, where the acids may or may not
include a hydrocarbon moiety, i.e., a hydrogen bonded directly to a
carbon atom. Suitable acids that lack a hydrocarbon moiety include
halogen acids, oxy acids and mixtures thereof, where specific acids
of interest of this type include, but are not limited to,
hydrochloric, nitric, sulfuric, phosphoric, hydroboric,
hydrobromic, carbonic and hydroiotic acids. For such acids, the
acid can be a concentrated acid, or can be diluted. Upon dilution,
the concentration of an inorganic acid will generally be from about
10 N to about 0.01 N, preferably between 5 N to 0.1 N. Also of
interest are acids that include a hydrocarbon moiety, where such
acids include, but are not limited to, any organic acid of one to
six (C.sub.1 to C.sub.6) carbons in length. Organic acids of this
type include, but are not limited to, formic, acetic, propionic,
maleic, butanoic, valeric, hexanoic, phenolic,
cyclopentanecarboxylic, benzoic, and the like. For an organic acid,
the acid can be in concentrated form, or can be diluted. The acidic
treatment solution can be composed of either a monobasic or a
polybasic acid. Acids are "monobasic" when they have only one
replaceable hydrogen atom and yield only one series of salts (e.g.,
HCl). Acids are "polybasic" when they contain two or more hydrogen
atoms which may be neutralized by alkalies and replaced by organic
radicals.
[0059] In many embodiments of the subject invention, the acid
solution is hypertonic, by which is meant that the osmolarity of
the solution is greater than that of whole blood, i.e. the
osmolarity is greater than 300 mosmol. The solution may be rendered
hypertonic by including any convenient component or components in
the solution which provide for the desired elevated osmolarity.
[0060] Any convenient agent that is capable of increasing the
osmolarity of the solution may be employed, where suitable agents
include salts, sugars, and the like. In many embodiments, the agent
that is employed to render the solution hypertonic is one or more,
usually no more than three, and more usually no more than two,
different salts. Generally, the salt concentration in these
embodiments of the solution is at least about 100 mosmol, usually
at least about 200 mosmol and more usually at least about 300
mosmol, where the concentration may be as high as 3000 mosmol or
higher, depending on the particular salt being employed to render
the solution hypertonic, where the solution may be saturated with
respect to the salt in certain embodiments. Salts that may be
present in the subject solutions include: NaCl, MgCl.sub.2,
Ringers, etc. where NaCl is preferred in many embodiments.
[0061] Of particular interest in many embodiments is the use of a
hydrogen chloride solution. In hydrogen chloride solutions that
find use in the subject invention, the concentration of HCl in the
solution ranges from about 0.001 to 1.0 N, usually from about 0.01
to 1.0 N and more usually from about 0.1 to 1.0 N. In many
embodiments, the hydrogen chloride solution will further include
one or more salts which make the solution hypertonic, as described
above. In certain preferred embodiments, the salt is NaCl, where
the concentration of NaCl in the solution is at least 0.05 M,
usually at least 0.10 M, and more usually at least 0.15 M, where
the concentration may be as high as 0.25 M or higher. In certain
embodiments, the solution will be saturated with NaCl.
[0062] Of particular interest are aqueous hydrogen chloride
solutions that consist of water, hydrogen chloride and NaCl. The
concentration of hydrogen chloride in these solutions of particular
interest ranges from about 0.01 to 1.0 N, usually from about 0.05
to 0.5 N and more usually from about 0.075 to 0.25 N. The
concentration of NaCl in these solutions of particular interest
ranges from about 0.05 to 0.25 M, usually from about 0.05 to 0.10
M.
[0063] In certain embodiments of the subject methods, e.g., those
embodiments in which a device having two fluid delivery elements,
in addition to the dissolution solution, the target aortic valve is
also contacted with a dissolution solution attenuating fluid. The
nature of the dissolution solution attenuating fluid necessarily
depends on the nature of the dissolution fluid, where
representative pairs of fluids and their attenuating counterparts
are described in U.S. Pat. No. 6,533,767, the disclosure of which
is herein incorporated by reference.
[0064] Where the dissolution fluid is an acidic dissolution fluid,
attenuating fluids of particular interest are pH elevating fluids.
By pH elevating solution is meant any solution that, upon
combination with the acidic dissolution solution, produces a
solution with an elevated pH with respect to the acidic dissolution
solution. In principle, any fluid that, upon combination of with
the acid dissolution fluid produces a solution having a pH higher
than that of the acidic dissolution fluid, may be employed, so long
as the fluid is biocompatible, at least for the period of time that
it is present in the target vascular site. The pH elevating
solution should have a pH of at least about 4, usually at least
about 6 and more usually at least about 8. As such, pH elevating
fluids of interest include water, physiological acceptable buffer
solutions, etc., where in many embodiments, the pH elevating
solution is a buffer solution. Representative buffer solutions of
interest include: phosphate buffered saline, sodium bicarbonate and
the like.
[0065] In practicing the subject methods, the first step is to
prepare the host or patient for the procedure. Following
preparation of the host/patient/subject, the device is placed in
position such that, upon deployment, the target aortic valve can be
isolated from the remainder of the vasculature with the device.
[0066] To place the device in position, the device is
percutaneously introduced to the target site from a remote site,
e.g., via femoral access, as is known in the art. The device may be
introduced over a guide wire. The percutaneously introduced device
is advanced in a retrograde fashion such the distal end of the
device extends through the aortic valve into the left ventricle.
Following proper positioning of the distal end of the device into
the left ventricle, the isolation elements of the device are then
deployed in a manner sufficient to substantially, if not
completely, isolate the to be treated aortic valve from the
remainder of the vasculature of the host. The particular manner of
deployment necessarily depends on the nature of the isolation
system of the device. For example, where the ventricular side
occlusion element of the isolation system of the device is an
inflatable balloon, the isolation step includes a step of inflating
the balloon. Where the aortic side isolation element is an
expandable aortic isolation element, the isolation step includes a
step of expanding the aortic side isolation element. Isolation of
the valve results in blood flow through the shunt element under the
force of the still beating heart.
[0067] The above protocol results in an isolated target aortic
valve. Following isolation of the aortic valve, the isolated aortic
valve is then flushed with at least the dissolution fluid, e.g., an
acidic dissolution fluid. As the isolated valve is flushed with the
dissolution fluid, it is dynamically contacted with the dissolution
fluid. By "dynamically contact" is meant that the fresh dissolution
solution is contacted with the surface of valve one or more times,
including continuously, during the treatment period. In certain
embodiments of the subject methods, the surface of the valve is
continuously contacted or flushed with the acidic dissolution
fluid. In other words, the acidic dissolution fluid is introduced
in a manner such that a continuous flow of the acidic dissolution
fluid across the surface of the valve is achieved. While both the
ventricular and aortic surfaces of the valve may be contacted with
the dissolution fluid, in many embodiments the aortic surface and
commissures are contacted with the dissolution fluid, with
substantially less fluid contact of the ventricular surface of the
valve, if any.
[0068] In flushing with the dissolution fluid, the pressure in the
local environment which includes the aortic valve may be maintained
substantially isometric. By substantially isometric is meant that
the pressure in the local environment does not vary by a
significant amount, where the amount of variance over the treatment
period does not vary by more than about 50%, usually by not more
than about 10% and more usually by not more than about 5%. In other
words, the local environment remains substantially isobaric during
the treatment period. Accordingly, where fluid is dynamically
contacted with the surface of the aortic valve surface, fluid is
also simultaneously removed from the local environment, such that
the overall volume of fluid in the local environment remains
substantially constant, where any difference in volume at any two
given times during the treatment period does not exceed about 50%,
and usually does not exceed about 10%. As such, the dissolution
fluid is introduced into the local environment of the isolated
valve in a manner such that the local environment remains
substantially isovolumetric.
[0069] When flushing the aortic valve with the dissolution fluid,
the dissolution fluid is introduced in a manner such that the flow
rate of the dissolution solution through the local environment is
generally at least about 10 cc/min, usually at least about 20
cc/min and more usually at least about 60 cc/min, where the flow
rate may be as great as 120 cc/min or greater, but usually does not
exceed about 1000 cc/minute and more usually does not exceed about
500 cc/minute, where by "volume" is meant the local environment of
the isolated aortic valve, as defined above. The total amount of
dissolution fluid that is passed through the local environment
during the treatment period typically ranges from about 100 to 1000
cc, usually from about 200 to 800 cc and more usually from about
400 to 500 cc. The solution is generally pressurized to achieve the
desired flow rate, as described supra. As such, the pressure at the
distal end of the dissolution fluid delivery element through which
the dissolution fluid is introduced into the local environment
typically ranges from about 50 to 1200 psi, usually from about 100
to 600 psi and more usually from about 200 to 400 psi. It is
important to note that the overall pressure in the local
environment is maintained in certain embodiments at substantially
isometric or isobaric conditions. As such, the negative pressure at
the entrance to the aspiration element or fluid removal means is of
sufficient magnitude to provide for substantially isobaric
conditions. In certain embodiments, the overall pressure in the
local environment is maintained at a value ranging from about 0.1
to 3 psi, usually from a bout 0.5 to 2.5 psi and more usually from
about 1 to 2 psi.
[0070] The isolated aortic valve is flushed with at least the
dissolution fluid, and in certain embodiments the dissolution fluid
attenuating fluid, for a period of time sufficient to achieve the
desired result. In representative embodiments, the dissolution
fluid and dissolution attenuating fluid are cycled through the
isolated region, with the isolated valve being flushed with the
dissolution fluid first, followed by flushing with the dissolution
fluid attenuating fluid. The desired result necessarily depends on
the application being performed, where representative desired
results are described below in the section entitled "Utility."
While the period of time that the valve is flushed may vary, the
period of time typically ranges from about 15 minutes to about 2
hours, usually from about 20 minutes to about 30 minutes and more
usually from about 25 minutes to about 30 minutes.
[0071] Following treatment with the dissolution fluid, the isolated
local environment is, in certain embodiments, flushed with a
dissolution fluid attenuating fluid, e.g., a pH elevating
solution.
[0072] Following flushing for the desired period of time, the
device is then removed from the patient.
[0073] In certain embodiments, a device with an integrated
introducer, such as the device depicted in FIGS. 6A and 6B, may be
employed. In the device shown in FIGS. 6A and 6B, device 60 is
shown being introduced into a patient at access point 50. Device 60
includes sheath element 44 in which is housed the distal end
elements of the device, fluid diverter element 42, guidewire 62 and
introducer 64, which include hemostasis element 66. Central lumen
or catheter 68 provides fluid communication between the distal end
of the device and fluid reservoirs, aspiration elements, steering
mechanisms and other device control elements present at the
proximal end of the device and outside of the patient. In FIG. 60,
sheath 44 and introduce 64 are shown in a contiguous configuration,
which is the configuration employed to initially introduce the
device into the vascular system of the patient by access point 50.
As the distal end of the device is moved in the direction of arrow
69 to the target valve site, sheath 44 and introducer 64 separate
from each other.
[0074] Optional Method Steps
[0075] In a number of embodiments of the subject methods, the
above-described methods may be modified to include a number of
additional method steps. Additional method steps that may be
present in the overall process include: rendering the local
environment of the isolated aortic valve bloodless, washing or
rinsing the isolated local environment of the aortic valve,
applying external energy to the aortic valve during treatment;
imaging the isolated vascular site; and the like.
[0076] Rendering the Local Environment Bloodless
[0077] In many preferred embodiments, as described above, the local
environment of the aortic valve is rendered substantially bloodless
prior to introduction of the acidic dissolution fluid. In these
embodiments, the isolation system is deployed to physically isolate
the local environment from the remainder of the circulatory system
and then the local environment is flushed with a physiologically
acceptable solution, such that substantially all of the blood
present in the solution is removed. Typically, a washing solution
will be employed in this step of rendering the local environment
bloodless. Examples of washing solutions that may find use in these
embodiments include: water for injection, saline solutions, e.g.
Ringer's, phosphate buffered saline, or other physiologically
acceptable solutions. The washing solution may include an
anti-clotting factor in many embodiments, where anticlotting
factors of interest include heparin and the like. The washing
solution can also contain chelating agents.
[0078] Application of External Energy
[0079] In certain embodiments, external energy is applied to the
target aortic valve to promote mechanical break-up of the calcified
deposits into particles or debris that can be easily removed from
the vascular site. Any means of applying external energy to the
aortic valve may be employed. As such, jets or other such means the
device which are capable of providing varying external forces to
the target deposits cause the target deposit to break up or disrupt
may be employed. Of particular interest in many embodiments is the
use of ultrasound. The ultrasound can be applied during the entire
time of contact of the cardiovascular tissue with the acidic
treatment solution, or the ultrasound can be applied for only part
of the treatment period. In one embodiment, ultrasound is applied
for several short periods of time while the dissolution treatment
solution is contacted with the target occlusion. There are several
devices for the application of ultrasound to cardiovascular tissue
known to those of skill in the art. See e.g. U.S. Pat. No.
4,808,153 and U.S. Pat. No. 5,432,663, the disclosures of which are
herein incorporated by reference.
[0080] Another means that may be employed to apply external energy
to the lesion during the dissolution process is to use a mechanical
means of applying external energy. Mechanical means of interest
include moving structures, e.g. rotating wires, guidewires, which
physically contact the target occlusion and thereby apply physical
external energy to the target lesion.
[0081] Imaging
[0082] In addition, it may be convenient to monitor or visualize
the vascular site prior to or during treatment. A variety of
suitable monitoring means are known to those of skill in the art.
Any convenient means of invasive or noninvasive detection and/or
quantification may be employed. Such means include plain film
roentgenography, coronary arteriography, fluoroscopy, including
digital subtraction fluoroscopy, cinefluorography, conventional,
helical and electron beam computed tomography, intravascular
ultrasound (IVUS), magnetic resonance imaging, transthoracic and
transesophageal echocardiography, rapid CT scanning, antioscopy and
the like. Any of these means can be used to monitor the vascular
site before, during or after contact with the dissolution
fluid.
[0083] In many embodiments, an imaging agent is employed, where the
imaging agent may or may not be present in the acidic dissolution
solution. Imaging agents of particular interest include: non-ionic
imaging agents, e.g. CONRAY.TM., OXILAN.TM., and the like.
Utility
[0084] The above-described methods and devices find use in any
application in which it is desired to contact an isolated aortic
valve with a fluid, e.g., a fluid composition of a therapeutic
agent. The subject devices and methods are particularly suited for
use in the treatment of aortic stenosis. The term "aortic stenosis"
is used broadly to refer to any condition that is characterized by
disease and narrowing of the valve such that fluid flow through the
valve is impeded. In many instances, the target aortic stenosis
condition of the subject methods is characterized by having
calcification present on the valve leaflets that reduces or impedes
mobility of the leaflets. Of particular interest is the treatment
of aortic stenosis characterized by calcified deposits on the
leaflet surface in which the calcification results in a aortic
valve flow (as measured by the cardiac catheterization technique
known in the art as the gold standard for evaluating aortic
stenosis) that is less then 3.0, often less than about 2.5 and more
often less than about 2.0, where in many embodiments the aortic
valve flow may be less than 1.0.
[0085] Treatment of aortic stenosis according to the subject
invention results in at least a reduction in the amount of calcium
phosphate mineral present on a stenotic valve surface, i.e., the
aortic side leaflet surface. The amount of reduction that is
achieve with the subject invention is typically at least about 10%,
usually at least about 20% and more usually at least about 30% by
weight.
[0086] In many embodiments, treatment according to the subject
methods results in an increase in aortic valve flow, as determined
using the cardiac catheterization protocol described above. The
amount of increase that is achieve is generally at least about 0.5
units, usually at least about 1.0 unit. In many embodiments, the
aortic valve flow is improved to a value that is at least about 1,
preferably at least about 1.5 and more preferably at least about
2.0, where one may achieve even higher values, including the normal
3.0, in certain embodiments.
[0087] Treatment also typically results in amelioration of one or
more symptoms associated with, e.g., caused by, aortic stenosis,
including but not limited to: chest pain, fainting, shortness of
breath, delayed upstroke and lower intensity of the carotid pulse,
heart murmur, abnormal EKG patterns, etc.
[0088] A variety of hosts are treatable according to the subject
methods. Generally such hosts are "mammals" or "mammalian," where
these terms are used broadly to describe organisms which are within
the class mammalia, including the orders carnivore (e.g., dogs and
cats), rodentia (e.g., mice, guinea pigs, and rats), lagomorpha
(e.g. rabbits) and primates (e.g., humans, chimpanzees, and
monkeys). In many embodiments, the hosts will be humans.
Systems
[0089] Also provided by the subject invention are systems for
practicing the subject methods, i.e. for flushing an aortic valve
with a fluid, e.g., to treat an aortic valve stenosis as described
above. The subject systems at least include the subject devices as
described above, a fluid reservoir for storing acidic dissolution
fluid, optionally a fluid reservoir for storing a pH elevating
fluid and a negative pressure element for providing aspiration or
suction during use of the system. The systems may further include a
number of optional components, e.g. guidewires, pumps for
pressurizing the dissolution fluid, and the like. See e.g. U.S.
patent application Ser. No. 09/384,860, the disclosure of which is
herein incorporated by reference.
Kits
[0090] Also provided by the subject invention are kits for use in
treating a patient suffering from aortic stenosis. The subject kits
at least include a device as described above. The kits may further
include one or more additional components and accessories for use
with the subject devices, including tubing for connecting the
various components with fluid reservoirs, syringes, pumping means,
etc., connectors, one or more guidewires, dilators, vacuum
regulators, etc.
[0091] In certain embodiments, the kits further include one or more
solutions, or precursors thereof, where in such embodiments the
kits at least include an acidic dissolution fluid, such as a
hydrochloric acid solution, as described above, where the solution
may be present in a container(s), e.g. a flexible bag, a rigid
bottle, etc. For kits that are to be used in methodologies in which
the fluid is flushed through the local environment of the lesion,
the amount of dissolution fluid present in the kit ranges from
about 0.5 to 500 liters, usually from about 0.5 to 200 liters and
more usually from about 0.5 to 100 liters. In many embodiments, the
amount of dissolution fluid in the kit ranges from 0.5 to 5 liters,
usually from about 0.5 to 2.0 liters and more usually from about
0.5 to 1.5 liters. Alternatively, the kit may comprise precursors
of the dissolution-solution for use in preparing the solution at
the time of use. For example, the precursors may be provided in dry
form for mixing with a fluid, e.g. water, at the time of use. In
addition to the dissolution fluid or precursors thereof, the kit
may further comprise one or more additional fluids (or dry
precursors thereof), such as a priming solution, a washing
solution, contrast medium, and the like. In many embodiments, the
kits further include at least a pH elevating solution, e.g. a
buffer solution such as phosphate buffered saline.
[0092] Other elements that may be present in the subject kits
include various components of the systems, including manifolds,
balloon inflation means, e.g. syringes, pumping means, negative
pressure means etc.
[0093] In addition to above-mentioned components, the subject kits
typically further include instructions for using the components of
the kit to practice the subject methods with the subject devices.
The instructions for practicing the subject methods are generally
recorded on a suitable recording medium. For example, the
instructions may be printed on a substrate, such as paper or
plastic, etc. As such, the instructions may be present in the kits
as a package insert, in the labeling of the container of the kit or
components thereof (i.e., associated with the packaging or
subpackaging) etc. In other embodiments, the instructions are
present as an electronic storage data file present on a suitable
computer readable storage medium, e.g. CD-ROM, diskette, etc. In
yet other embodiments, the actual instructions are not present in
the kit, but means for obtaining the instructions from a remote
source, e.g. via the internet, are provided. An example of this
embodiment is a kit that includes a web address where the
instructions can be viewed and/or from which the instructions can
be downloaded. As with the instructions, this means for obtaining
the instructions is recorded on a suitable substrate.
[0094] It is evident from the above discussion and results that
improved methods of treating aortic stenosis are provided. The
subject methods and devices provide for significant advantages in
the treatment of this condition in that prosthetic elements need
not be employed, as the subject's own aortic valve is maintained
and restored to function. In addition, the subject methods may be
less traumatic to the patent that convention valve replacement
protocols. Additional advantages include a delay in the need for
valve replacement. As such, the subject invention represents a
significant contribution to the field.
[0095] Although the foregoing invention has been described in some
detail by way of illustration and example for purposes of clarity
of understanding, it is readily apparent to those of ordinary skill
in the art in light of the teachings of this invention that certain
changes and modifications may be made thereto without departing
from the spirit or scope of the appended claims.
* * * * *