U.S. patent application number 10/284044 was filed with the patent office on 2004-04-29 for devices and methods for treating aortic valve stenosis.
Invention is credited to Constantz, Brent R., Johansson, Peter K..
Application Number | 20040082910 10/284044 |
Document ID | / |
Family ID | 32107582 |
Filed Date | 2004-04-29 |
United States Patent
Application |
20040082910 |
Kind Code |
A1 |
Constantz, Brent R. ; et
al. |
April 29, 2004 |
Devices and methods for treating aortic valve stenosis
Abstract
Devices and methods for their use in increasing the aortic valve
flow of a stenotic aortic valve are provided. The subject devices
include an aortic valve isolation element and an aortic valve
flushing element. The aortic valve isolation element is made up of
a ventricular side aortic valve occlusion element, coronary ostia
occlusion elements and an ascending aorta occlusion element. The
aortic valve flushing element is made up of a dissolution 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 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.
Inventors: |
Constantz, Brent R.; (Menlo
Park, CA) ; Johansson, Peter K.; (Campbell,
CA) |
Correspondence
Address: |
BOZICEVIC, FIELD & FRANCIS LLP
200 MIDDLEFIELD RD
SUITE 200
MENLO PARK
CA
94025
US
|
Family ID: |
32107582 |
Appl. No.: |
10/284044 |
Filed: |
October 29, 2002 |
Current U.S.
Class: |
604/101.04 |
Current CPC
Class: |
A61M 25/10 20130101;
A61B 17/320708 20130101; A61B 2017/22082 20130101; A61B 17/22
20130101; A61M 25/1011 20130101; A61M 2025/1015 20130101; A61M
2025/1052 20130101; A61B 2017/22097 20130101; A61M 2025/1013
20130101 |
Class at
Publication: |
604/101.04 |
International
Class: |
A61M 029/00 |
Claims
What is claimed is:
1. A device for use in increasing the aortic valve area of a
stenotic aortic valve, said device comprising: (a) a valve
isolation element that includes: (i) a ventricular side aortic
valve occlusion element; (ii) coronary ostia occlusion element; and
(iii) an ascending aorta occlusion element; and (b) an aortic valve
flushing element for flushing an isolated aortic valve with a
dissolution fluid.
2. The device according to claim 1, wherein said flushing element
includes: (a) a first fluid introducing element; and (b) a fluid
aspiration element.
3. The device according to claim 2, wherein said flushing element
further comprises a second fluid introducing element.
4. The device according to claim 3, wherein said first and second
fluid introducing elements are at least substantially
coterminus.
5. The device according to claim 3, wherein said first and second
fluid introducing elements are not coterminus.
6. The device according to claim 2, wherein said first fluid
introducing element is in fluid communication with a source of
stenotic dissolution fluid.
7. The device according to claim 6, wherein said stenotic
dissolution fluid is an acidic dissolution fluid.
8. The device according to claim 3, wherein said first fluid
introducing element is in fluid communication with a source of
stenotic dissolution fluid and said second fluid introducing
element is in fluid communication with a source of stenotic
dissolution fluid attenuating fluid.
9. The device according to claim 8, wherein said stenotic
dissolution fluid is an acidic dissolution fluid and said stenotic
dissolution fluid attenuating fluid is a pH elevating fluid.
10. The device according to claim 9, wherein said pH elevating
fluid is a buffer.
11. The device according to claim 1, wherein said device further
includes an element that provides for blood flow through an aortic
valve isolated with said valve isolation element.
12. The device according to claim 1, wherein said ventricular side
aortic valve occlusion element is a balloon.
13. The device according to claim 1, wherein said coronary ostia
occlusion elements are balloons.
14. The device according to claim 1, wherein said ascending aorta
occlusion element is a balloon.
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; (ii) coronary
ostia occlusion elements; and (iii) 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 isolating step
comprises activating said ventricular side aortic valve occlusion
element followed by activating said coronary ostia and ascending
aorta occlusion elements.
17. 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.
18. The method according to claim 17, wherein said dissolution
fluid is an acidic dissolution fluid.
19. The method according to claim 17, wherein said method further
comprises contacting said isolated stenotic aortic valve with a
dissolution fluid attenuating fluid.
20. The method according to claim 19, wherein said dissolution
fluid is an acidic dissolution fluid and said dissolution fluid
attenuating fluid is a pH elevating fluid.
21. The method according to claim 20, wherein said pH elevating
fluid is a buffer.
22. The method according to claim 19, wherein said stenotic
dissolution fluid is contacted with the aortic side of said
stenotic aortic valve and said dissolution fluid attenuating fluid
is contacted with the ventricular side of said stenotic aortic
valve.
23. The method according to claim 15, wherein said stenotic aortic
valve is present in a heart of a mammalian host.
24. The method according to claim 23, wherein said mammalian host
is a human.
25. The method according to claim 24, wherein said method further
comprises arresting said heart prior to said isolating step.
26. A method of at least reducing the amount of calcium mineral
present on a calcified aortic valve, said method comprising: (a)
isolating said calcified aortic valve with a valve isolation
element that includes: (i) a ventricular side aortic valve
occlusion element; (ii) coronary ostia occlusion elements; and
(iii) an ascending aorta occlusion element; and (b) flushing said
isolated calcified aortic valve with an acidic dissolution fluid
for a period of time sufficient to at least reduce the amount of
calcium mineral present on said calcified aortic valve.
27. The method according to claim 26, wherein said isolating step
comprises activating said ventricular side aortic valve occlusion
element followed by activating said coronary ostia and ascending
aorta occlusion elements.
28. The method according to claim 26, wherein said flushing
comprises contacting said isolated calcified aortic valve with said
acidic dissolution fluid and-removing fluid from said isolated
calcified aortic valve.
29. The method according to claim 28, wherein said method further
comprises contacting said isolated calcified aortic valve with a pH
elevating fluid.
30. The method according to claim 29, wherein said pH elevating
fluid is a buffer.
31. The method according to claim 29, wherein said acidic
dissolution fluid is contacted with the aortic side of said
calcified aortic valve and said pH elevating fluid is contacted
with the ventricular side of said calcified aortic valve.
32. A system for increasing the aortic valve flow of a stenotic
aortic valve, said system comprising: (i) a device according to
claim 1; and (ii) a volume of stenosis dissolution fluid.
33. The system according to claim 32, wherein said system further
comprises a negative pressure element.
34. The system according to claim 32, wherein said system further
comprises a dissolution fluid attenuating fluid.
35. The system according to claim 32, wherein said dissolution
fluid is an acidic dissolution fluid.
36. The system according to claim 34, wherein said dissolution
fluid attenuating fluid is a pH elevating fluid.
37. A kit for use in increasing the aortic valve flow of a stenotic
aortic valve, said kit comprising: a device according to claim 1;
and instructions for practicing the method of claim 15.
38. The kit according to claim 37, wherein said kit further
includes a stenotic dissolution fluid or reagents for use in
producing the same.
39. The kit according to claim 38, wherein said dissolution fluid
is an acidic fluid.
40. The kit according to claim 37, wherein said kit further
includes a dissolution fluid attenuating fluid or reagents for use
in producing the same.
41. The kit according to claim 40, wherein said dissolution fluid
attenuating fluid is a pH elevating fluid.
42. The kit according to claim 41, wherein said attenuating fluid
is a buffer.
Description
FIELD OF THE INVENTION
[0001] The field of this invention is cardiology.
BACKGROUND OF THE INVENTION
[0002] 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.
[0003] 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.
[0004] 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%.
[0005] 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.
[0006] As such, there is a continued interest in the development of
new protocols for treating aortic valve stenosis.
[0007] Relevant Literature
[0008] See e.g., WO 01/15767; WO 01/13985; WO 00/03651; and WO
01/39783.
SUMMARY OF THE INVENTION
[0009] Devices and methods for their use in increasing the aortic
valve flow of a stenotic aortic valve are provided. The subject
devices include an aortic valve isolation element and an aortic
valve flushing element. The aortic valve isolation element is made
up of a ventricular side aortic valve occlusion element, coronary
ostia occlusion elements and an ascending aorta occlusion element.
The aortic valve flushing element is made up of a dissolution 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 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
[0010] FIG. 1 provides an illustration of a device according to the
subject invention.
[0011] FIG. 2 provides an illustration of the device depicted in
FIG. 1 in use.
[0012] FIG. 3 provides a depiction of a prototype device according
to the subject invention.
DETAILED DESCRIPTION OF THE INVENTION
[0013] Devices and methods for their use in increasing the aortic
valve flow of a stenotic aortic valve are provided. The subject
devices include an aortic valve isolation element and an aortic
valve flushing element. The aortic valve isolation element is made
up of a ventricular side aortic valve occlusion element, coronary
ostia occlusion elements and an ascending aorta occlusion element.
The aortic valve flushing element is made up of a dissolution 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 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.
[0014] 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.
[0015] 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.
[0016] 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.
[0017] 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
[0018] 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.
[0019] 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.
[0020] Devices
[0021] 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.
[0022] The subject devices are also characterized in that they are
dimensioned to be introduced into the aortic arch through a
transverse aortotomy positioned upstream of the brachiocephalic
trunk and downstream of the coronary ostia. As such, the size of
the devices in many embodiments may not be sufficiently small for
introduction into the vascular from a remote location, e.g.,
femoral approach, but is just small enough for insertion to an
aortotomy as described above. Generally, the devices are
dimensioned to be capable of insertion through an aortotomy that
ranges in length from about 1 cm to 3 cm.
[0023] As summarized above, the subject devices include an aortic
valve isolation element or system and a valve flushing element.
Each of these elements is now described separately in greater
detail.
[0024] Valve Isolation Element
[0025] 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 three
different sub-elements that make up the valve isolation element
are: (1) a ventricular side valve occlusion element; (2) coronary
ostia occlusion elements; and (3) an ascending aorta occlusion
element. Each of these elements is now described in greater detail
separately.
[0026] Ventricular Side Valve Occlusion Element
[0027] 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. 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, etc. In many
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.
[0028] Coronary Ostia Occlusion Means
[0029] The next component of the isolation system is the coronary
ostia occlusion element. This element blocks or occludes the
coronary ostia at their opening into the aortic sinuses. More
specifically, this occlusion element substantially, if not
completely, blocks the flow of fluid from the aortic sinuses into
the right and left coronary arteries by occluding the openings of
these arteries. This occlusion element may be any convenient
occlusion element, where representative occlusion elements of
interest include, but are not limited to: balloons, non-porous
membranes, elements for delivering degradable blocking
compositions, e.g., biodegradable polymeric compositions, etc. In
many embodiments, the coronary ostia occlusion element is made of
two deployable balloons that are dimensioned for insertion into the
entrance of the left and right coronary arteries and deployment
upon insertion in a manner that substantially, if not completely,
blocks fluid flow into the left and right coronary arteries.
[0030] Ascending Aorta Occlusion Element
[0031] The final sub-element of the isolation element is the
ascending aorta occlusion element. This element serves to occlude
fluid flow from the isolated valve into the ascending aorta
downstream of its deployment. As such, the ascending aorta
occlusion element is one that substantially, if not completely,
impedes fluid flow past its site of deployment downstream into the
aorta. Therefore, the occlusion means must be dimensioned upon
deployment to substantially, if not completely, occlude the
ascending aorta. This occlusion element is typically deployed at a
location upstream of the brachiocephalic trunk, typically at least
about 2 cm, usually at least about 20 mm upstream of the
brachiocephalic trunk. Representative occlusion elements of
interest include, but are not limited to: balloons, deployable
non-porous membranes, etc.
[0032] Additional, Optional Features of the Valve Isolation
Element
[0033] In addition to the above features, the valve isolation
system may further include one or more of the following optional
features. One optional feature of interest in certain embodiments
is the provision of an element that provides for blood flow through
the region of isolation. For example, the isolation element may
further include a fluid passageway that conveys blood from the left
ventricle through the isolated area to a position downstream of the
ascending aorta occlusion element. Representative elements for
accomplishing blood flow through the isolated region include, but
are not limited to: tubes, and the like.
[0034] Valve Flushing Element
[0035] 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 many preferred
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.
[0036] In flushing the isolated target valve, it is preferred that
the pressure in the local environment which includes the isolated
target valve (i.e. the area bounded by the ventricular side aortic
valve occlusion means, the vessel walls of the aortic sinuses and
that part of the aortic arch upstream from the ascending aorta
occlusion means and the ascending aorta occlusion means) 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%.
[0037] 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 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.
[0038] 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.
[0039] 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.
[0040] In addition to the above fluid introduction and removal
elements, in many 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, as described in greater detail
below. 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.
[0041] 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.
[0042] Additional General Features of the Device
[0043] 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.
[0044] 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.
[0045] Representative Specific Embodiment
[0046] A representative embodiment of the subject devices is
depicted in FIGS. 1 and 2. FIG. 1 provides a view of a device
according to the subject invention prior to deployment. Device 100
includes fluid removal or aspiration tube 102. Aspiration element
or tube 102 has an outer diameter ranging from about 3 mm to about
14 mm, usually from about 5 mm to about 9 mm; and an inner diameter
ranging from about 2.75 mm to about 13.5 mm, usually from about 4
mm to about 8 mm.
[0047] Positioned on the outer surface of aspiration element 100 is
the ascending aorta occlusion balloon 104 which is inflated and
deflated by means of inflation lumen 106.
[0048] Concentrically and slidably positioned inside of aspiration
element 102 is first fluid delivery element 110, which serves to
introduce a dissolution fluid to the isolated aortic valve during
use. The volume to which balloon element 104 should be expandable
is sufficient to occlude the ascending aorta upon deployment, and
typically ranges from about 10 mm to about 35 mm, usually from
about 22 mm to 28 mm. In certain embodiments, it is desirable to
limit the volume to which the balloon may be expanded so that
tissue/vessel damage does not inadvertently occur upon
deployment/use, where this volume limit generally does not exceed
about 20 cc and usually does not exceed about 10 cc.
[0049] Concentrically and slidably positioned within aspiration
element 102 is first fluid delivery element 110. The outer diameter
of first fluid delivery element typically ranges from about 2.5 mm
to about 12 mm, usually from about 3 mm to about 7 mm; while the
inner diameter typically ranges from about 2 mm to about 11.5 mm,
usually from about 2.5 mm to about 6.5 mm.
[0050] Slidably though not concentrically positioned within first
fluid delivery element 110 are coronary ostia occlusion elements
120a and 120b. Each of these elements includes a balloon at their
distal end, 122a and 122b, and a guidewire, 124a and 124b. In many
embodiments, these occlusion elements can be retracted or extended
from the lumen of the first fluid delivery element 110 in order to
position the occlusion balloons at the entrances of the coronary
ostia.
[0051] Concentrically and slidably positioned within first fluid
delivery element 110 is second fluid delivery element 120. This
fluid delivery element has an outer diameter ranging from about
1.75 mm to about 11 mm, usually from about 2 mm to about 6 mm; and
an inner diameter ranging from about 1.5 mm to about 10.5 mm,
usually from about 1.75 mm to about 5.75 mm.
[0052] Concentrically and slidably positioned within second fluid
delivery element 120 is ventricular side aortic valve occlusion
element 130, which includes balloon 132. The outer diameter of this
element typically ranges from about 1.25 to about 11 mm, usually
from about 1.5 mm to about 6.5 mm. The volume to which balloon
element 132 should be expandable is sufficient to occlude the
ventricular side of the aortic valve from the remainder of the left
ventricle upon deployment, and typically ranges from about 20 mm to
about 40 mm, usually from about 25 mm to 30 mm. Guidewire 134 is
also shown.
[0053] Methods
[0054] 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.
[0055] Of particular interest are methods of using the subject
devices to flush an isolated aortic valve, 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 described in copending U.S. patent application Ser. No.
09/774,469, the disclosure of which is herein incorporated by
reference.
[0056] 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 many preferred 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.
[0057] 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
osomolarity 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.
[0058] 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.
[0059] 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.
[0060] 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.
[0061] 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. patent application Ser. No. 09/774,469, the
disclosure of which is herein incorporated by reference.
[0062] 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.
[0063] In practicing the subject methods, the first step is to
prepare the host or patient for the procedure. In many embodiments,
the host is prepared by placing the host on cardio pulmonary bypass
followed by arrest of the heart, e.g., via introduction of a
cardoplegia solution to the heart. These procedures are well known
to those of skill in the art in the field of cardiology, particular
coronary artery bypass graft (CABG) surgery. See e.g., U.S. Pat.
No. 6,190,357; the disclosure of which is herein incorporated by
reference.
[0064] 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. In this step, access is first provided to the
ascending aorta so that the requisite aortotomy used to introduce
the distal end of the device into the aortic root can be cut.
Access can be provided using any convenient protocol, including via
open chest, an opening produced through the appropriate ribs, etc.
Once access is provided, the aortotomy is produced. The aortotomy
is produced in the wall of the ascending aorta a point upstream
from the brachiocephalic trunk. The length of cut made in the
aortic wall may vary depending on the dimensions of the device
being employed, but typically ranges in many embodiments from about
5 mm to about 15 mm, usually from about 7 mm to about 12 mm and
more usually from about 8 mm to about 10 mm.
[0065] Following production of the aortotomy, the device is
inserted through the opening into the lumen of the aortic
root/ascending aorta. The inserted 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 isolation elements that make up the
isolation system of the device are inflatable balloons, the
isolation step includes a step of inflating the various balloons.
The balloons may be inflated simultaneously or sequentially, as may
be desired or indicated depending on the particular procedure being
performed. For example, the ventricular side aortic valve occlusion
balloon may be inflated first, followed by inflation of the
ascending aorta occlusion balloon and the coronary ostia occlusion
balloons.
[0066] The above protocol results in an isolated target aortic
valve. FIG. 2 provides an illustration of an isolated target aortic
valve produced by deployment of a device in accordance with the
subject invention. As seen in FIG. 2, cutaway view of the ascending
aorta/aortic root 200 shows device 100 positioned therein, where
the device has been inserted via an aortotomy (not shown).
Ventricular side occlusion element 132 is inflated on the
ventricular side of aortic valve 210. Ascending aorta occlusion
balloon is also inflated so as to prevent fluid flow beyond the
balloon into the remainder of the aorta. Finally, ostia occlusion
balloons 122a and 122b are inflated and positioned over the
coronary ostia so as to preclude fluid flow into the coronary
ostia. As such, the aortic valve is isolated from the remainder of
the vasculature of the patient.
[0067] 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, and in many embodiments is simultaneously
flushed with the dissolution fluid and a dissolution, fluid
attenuating 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 many
preferred 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 commissurs 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, it is preferred that
the pressure in the local environment which includes the aortic
valve, i.e. the area bounded by the walls of the aortic root and
the occlusion means of the isolation element, 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, 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 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 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.
Preferably, 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] In many embodiments, a feature of the subject methods is
that the isolated local environment is flushed with a dissolution
fluid attenuating fluid, e.g., a pH elevating solution,
concomitantly or simultaneously with the acidic dissolution fluid
in a manner sufficient such that only the aortic surface of the
artic valve, and not the remainder of the tissue present in the
isolated local environment, is contacted with a low pH solution. As
such, the remainder of the isolated local environment or vascular
site is contacted with a fluid that has a pH well above that of the
acidic dissolution fluid, where the lowest pH to which the
remainder of the target vascular site is subjected is not less than
4, preferably not less than 5 and more preferably not less than 6.
In other words, only the aortic surface of the target valve is
contacted with the low pH acid dissolution fluid while the
remainder of the target vascular site, e.g., the ventricular side,
the coronary ostia, the intimal surface of the aortic sinuses,
etc., is contacted with a solution the pH of which is not less than
4, preferably not less than 5 and more preferable not less than
6.
[0071] FIG. 2 provides an illustration of an isolated aortic valve
being flushed with an acidic dissolution fluid and a buffer
simultaneously. In FIG. 2, arrows 222 and 224 show acidic
dissolution fluid leaving the distal opening of the dissolution
fluid delivery tube 110. As can be seen, dissolution fluid leaves
the distal end opening of tube 110 and contacts the aortic side of
isolated valve 210. In addition, second fluid delivery element
delivers buffer solution indicated by arrows 226 and 228 to the
ventricular side of the isolated aortic valve 210. Fluid is also
removed from the isolated local environment as indicated by arrows
229 and 230 into the distal end of aspiration element 102.
[0072] The isolated aortic valve is flushed with at least the
dissolution fluid, and in many embodiments the dissolution fluid
attenuating fluid, for a period of time sufficient to achieve the
desired result. 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.
[0073] Following flushing for the desired period of time, the
device is then removed from the patient. The device may be removed
using any convenient protocol. In one representative protocol, the
occlusion balloons are deflated and then the device is removed from
the ascending aorta through the aortotomy. The patient may then be
removed from heart/lung bypass and the heart may be started using
conventional procedures, followed by surgical closing and
post-operative care standard to those of skill in the art.
[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
anticlotting 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. Nos.
4,808,153 and 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.
[0084] Utility
[0085] 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.
[0086] 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.
[0087] 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.
[0088] 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.
[0089] 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.
[0090] Systems
[0091] 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, a fluid reservoir for storing a pH elevating fluid and a
negative pressure means 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.
[0092] Kits
[0093] 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.
[0094] 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.
[0095] 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.
[0096] 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.
[0097] 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.
[0098] 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.
* * * * *