Patent Grant
9089668
1. Field of the Invention
The present invention relates to methods and systems for treating blood vessels. More particularly, the invention relates to methods and systems for treating vascular malformations, such as aneurysms. Even more particularly, the present invention relates to methods and systems for treating an aneurysm with a microcatheter and an embolic agent.
2. State of the Art
An aneurysm is a localized, blood-filled balloon-like bulge in the wall of a blood vessel. Aneurysms can commonly occur in arteries at the base of the brain, i.e., at the circle of Willis. Another common type of aneurysm is an aortic aneurysm in the main artery carrying blood from the left ventricle of the heart.
The development of an aneurysm causes a turbulent blood flow within the vessel localized at bulge which in turn increases wall stress at bulge and consequent increased dilation. In hemodynamic terms, the coupling of aneurysmal dilatation and increased wall stress is approximated by the Law of Laplace. The Law of Laplace applied to a cylinder states that the (arterial) wall tension is equal to the pressure times the radius of the arterial conduit (T=P×R). As diameter increases, wall tension increases, which contributes to more increase in diameter. When the size of an aneurysm increases, there is a significant risk of rupture, resulting in severe hemorrhage, other complications or death. Eventually all aneurysms will, if left to complete their evolution, rupture without intervention. Current treatments seek to fill the aneurism to thereby reduce the wall stress at the aneurysm in response to the stress induced as the blood flows through the vessel.
In one method, a microcatheter is advanced directly into the aneurysm, and embolic beads or other embolic agents are infused directly into the aneurysm. However, infusion with a standard microcatheter routinely leads to non-targeted delivery of the embolic agent, either downstream (antegrade) or backwards (reflux), which can lead to mild to severe complications.
Another method of treatment includes placing a stent in the blood vessel across the aneurysm. Once the vessel is stented, a catheter is advanced through the stent and laterally into the aneurysm. With the catheter in position, endovascular coils are advanced from the catheter and into the aneurysm until no additional coils can be placed; i.e., the aneurysm is completely occluded with the coils flush with the vessel wall and outer surface of the stent. The coils initiate a clotting or thrombotic reaction within the aneurysm that, when successful, eliminates the aneurysm. An advantage of this method is that it can be performed without occluding the blood vessel to blood flow. The stent separates the occlusion zone from the blood flow within the vessel and blood flow is maintained while the coils are advanced into the aneurism. However, the method is only suitable for use on larger vessels that can accommodate being stented. In addition, the method requires that the stent remain implanted permanently. It is generally undesirable to have a permanent implant where an option exists for treatment without an implant.
It is also known to treat an aneurysm by filling the aneurysm with a slow setting liquid embolic agent such as ethylene vinyl alcohol copolymer dissolved in the organic solvent dimethyl sulfoxide (DMSO). Such an liquid embolic agent is available from EV3 of Irvine, Calif. under the brand ONYX™. Such current method includes positioning a PTFE balloon within the blood vessel so that it extends across the aneurysm. A microcatheter is also positioned within the blood vessel and enters the aneurysm. Such microcatheter may extend alongside the balloon or be partly carried by the balloon. The balloon is inflated to segregate the aneurysm from the blood vessel, and the liquid embolic agent is injected through the microcatheter into the aneurysm. As the aneurysm is filled with the embolic agent, the balloon keeps the embolic agent within the aneurysm. The microcatheter is withdrawn once the aneurysm is filled. Once the embolic agent cures, the balloon is removed. The balloon defines a very smooth repair to the vessel wall. A successful treatment operates to reduce the wall stress at the aneurism. However, because the balloon completely occludes blood flow during the treatment and the liquid agent requires a significant amount of time to set as a solid, there is the opportunity for inducing a local ischemic event due to a lack of blood supply during the treatment time.
A flow directional infusion device includes a catheter operating in conjunction with a filter valve. An embolic agent in the form of beads, liquid, coils, or any other suitable form can be delivered through the catheter. The filter valve is located adjacent a distal end portion of the catheter and includes a passage between the proximal and distal ends of the filter valve through which the embolic agent can be delivered. The filter valve constrains delivery of the embolic agent to the locus of the aneurysm. In addition, the filter valve permits and directs blood flow within the blood vessel about the aneurysm during the treatment without obstructing the vessel and without allowing retrograde flow of the embolic agent in the vessel upstream of the aneurysm. To that end, the filter valve dynamically moves within the vessel between an expanded valve-open configuration and a collapsed valve-closed configuration depending on the local blood flow conditions about the valve within the blood vessel. When the filter valve is in the valve-open configuration the filter valve is impermeable to the embolic agent, and when the filter valve is in the valve-closed position the filter valve permits antegrade blood flow about the filter valve. The filter valve preferably automatically expands from the valve-closed configuration to the valve-open configuration in less than one second, and more preferably less than one-tenth of second, in an at-rest fluid having a viscosity approximating the viscosity of blood. In addition, the filter valve automatically collapses into the valve-closed configuration during systole and automatically expands into the valve-open configuration during diastole and low flow conditions.
One manner of achieving the rapid transition required between valve-open and valve-closed states is via a preferred construction of the filter valve. The valve is preferably made from a plurality of elongate first filaments each having a diameter of 0.025 mm to 0.127 mm. These filaments may be round in cross-section, flat in cross-section, may be formed in pairs of filaments, or other means of reducing the wall thickness of the filter valve. In addition, in the valve-open configuration, the first filaments preferably cross one another at an angle of 100° to 150°, and said first filaments preferably have a Young's modulus of elasticity greater than 100 MPa.
In addition, a filter is provided to the braided first filaments. The filter is preferably formed by electrostatically depositing or spinning polymeric second filaments onto the braided first filaments. The deposition of the second filaments preferably defines a pore size in the filter not exceeding 500 μm.
In certain embodiments, first filaments are secured relative to each other about the distal end of the catheter. Such catheter to which the proximal ends of the first filaments are secured may either be a delivery catheter through which an injection microcatheter extends, or the distal end of the microcatheter itself, as described herein. The remaining length of the braided first filaments are non-fixed relative to each other such that the first filaments are movable relative to each other. The valve is expandable from the valve-closed configuration to the valve-open configuration by way of an inherent spring-bias of the first filaments which biases the first filaments radially apart from one another so as to flare outward relative to their secured proximal ends. The filaments may define a radial or other lateral opening for lateral passage of a portion of the microcatheter outside the filter valve and into the aneurysm. The lateral opening may be formed by an elongate opening, such as a slit in the valve or break in the filaments, extending completely from the proximal to distal ends of the valve, or may be an opening defined along of portion of the valve extending partially between, but not fully along the length of the valve.
In other embodiments, both the proximal ends of the first filaments are secured relative to each other at the distal end of a catheter, and the distal ends of the first filaments are secured relative to each other at a distally displaced location relative to the distal end of the catheter such that the braid of first filaments extends between the first and second hubs in a tubular form. The filter of second filaments is applied to the braid of first filaments between their first and second ends about an axis of rotation less than 360° around the tubular form and thereby defining a non-filtering portion of the valve about at least a portion of the braid of first filaments intended to face the aneurysm during injection of an embolic agent. In this manner, the non-filtering portion of the valve is permeable to the embolic agent permitting embolic agent transfer from within the space defined by the tubular form of the braid of first filaments into the aneurysm in a directed manner. Where a tubular form braid is defined, the ends of the first filaments may be coupled at their proximal and/or distal ends to a respective hub. The distal hub is particular useful to allow physical displacement of the distal ends of the first filaments relative to the proximal ends in order to elongate the filter valve and minimize its diameter during insertion into the blood vessel. The distal hub may include a self-closing valve, permitting the embolic agent to be injected through the catheter and then directed out of the agent-permeable portion of the filter valve. Alternatively, the distal hub may not be sealed, and a second smaller catheter (microcatheter) is advanced through the catheter and directed to inject the embolic agent toward the agent-permeable portion of the filter valve and into the aneurysm. The microcatheter may be advanced completely through an opening in the filamentary braid to assist in placement of the embolic agent within the aneurysm and thereafter withdrawn. Alternatively, the microcatheter may be formed to direct the embolic agent at an appropriate course into the aneurysm while the microcatheter remains located within the braid. The braid is biased to expand outward and upon systolic conditions of anterograde blood flow automatically radially collapses into the valve-closed configuration, and during diastolic conditions of retrograde fluid flow and low flow conditions, automatically radially expand to permit the filter to capture any embolic agent from backflow within the vessel.
In the latter embodiments, an elongate member is insertable into the catheter and to the distal hub, to contact a portion of the distal hub and displace the distal hub relative to the proximal hub to forcibly reduce the valve filter diameter to aid in advancement of the valve filter into the blood vessel. Such elongate member may be removable from the catheter to allow automatic operation of the valve filter. Alternatively, the microcatheter may function as the elongate member.
Referring to
It should be appreciated by those skilled in the art that the catheter 202 can be any catheter known in the art. Typically, the catheter will be between two and eight feet long, have an outer diameter of between 0.67 mm and 3 mm (corresponding to catheter sizes 2 French to 9 French), and will be made from a liner made of fluorinated polymer such as polytetrafluoroethylene (PTFE) or fluorinated ethylene propylene (FEP), a braid made of metal such as stainless steel or titanium, or a polymer such as polyethylene terephthalate (PET) or liquid crystal polymer, and an outer coating made of a polyether block amide thermoplastic elastomeric resin such as PEBAX®, polyurethane, polyamide, copolymers of polyamide, polyester, copolymers of polyester, fluorinated polymers, such as PTFE, FEP, polyimides, polycarbonate or any other suitable material, or any other standard or specialty material used in making catheters used in the bloodstream.
The catheter 202 is preferably provided with a sleeve or outer catheter 206 comprised of a material capable of holding the valve 204 in a cylindrical space over the catheter 202 and capable of sliding over the valve 204 and the catheter 202. The sleeve or outer catheter 206 can be comprised of polyurethane, polyamide, copolymers of polyamide, polyester, copolymers of polyester, fluorinated polymers, such as PTFE, FEP, polyimides, polycarbonate or any other suitable material. The sleeve or outer catheter 206 may also contain a braid composed of metal such as stainless steel or titanium, or a polymer such as PET or liquid crystal polymer, or any other suitable material. The wall thickness of sleeve or outer catheter 206 is preferably in the range of 0.05 mm to 0.25 mm with a more preferred thickness of 0.1 mm-0.15 mm.
The valve 204 is comprised of one, two, or more metal (e.g., stainless steel or Nitinol) or polymer first filaments 208, which form a substantially frustoconical shape when not subject to outside forces. The filaments may be round in cross-section, flat in cross-section, may be formed in pairs of filaments, or other means of reducing the wall thickness of the valve. Where polymeric filaments are utilized, the filaments may be comprised of PET, polyethylene-napthalate (PEN), liquid crystal polymer, fluorinated polymers, nylon, polyamide or any other suitable polymer. If desired, when polymeric filaments are utilized, one or more metal filaments may be utilized in conjunction with the polymeric filaments. According to one aspect of the invention, where a metal filament is utilized, it may be of radio-opaque material such that it may be tracked in the body. The valve is capable of expanding in diameter while reducing in length, and reducing in diameter while expanding in length. The valve is preferably comprised of shape memory material that is formed and set in a large diameter orientation. As previously mentioned, the valve is preferably held in a small diameter orientation until it is released, and when released by removing the sleeve or other restricting component 206, the distal end of the valve expands to a larger diameter. In an embodiment in which the valve is comprised of multiple first filaments 208-1, 208-2, the proximal ends 208a of the filaments 208 may be constrained relative to each other and the catheter 202. It is preferred that the filaments not be bonded to each other along their lengths or at their distal ends 208b so to enable the valve to rapidly automatically open and close in response to dynamic flow conditions, as hereinafter described.
In the preferred embodiment, the valve 204 is constrained only at its proximal end where it is coupled to the catheter 202, while the remainder of the valve can either be constrained (retracted state) by the sleeve or catheter 206, or partially unconstrained (partially deployed state) or completely unconstrained (completely deployed state). When in the partially or completely unconstrained conditions, depending upon the flow conditions in the vessel, the valve 204 may either reach the walls of the vessel or it may not.
As previously mentioned, the filter valve diameter should automatically change in response to local flow conditions so as to enable forward flow, but capture embolic agents in brief or prolonged periods of reverse flow. For simplicity, the valve can be considered to exist in two conditions. In a “closed” condition, the valve is not sealed against the vessel wall and blood may flow around in at least a proximal to distal direction. In an “open” condition, the valve expands against the vessel wall 102 and blood must pass the valve if it is to flow past the valve within the vessel in either direction; in the “open” condition embolic agent is prevented from passing upstream (or in a distal to proximal direction) of the valve (
At least three parameters help define the performance and novel nature of the valve: the radial (outward) force of the valve, the time constant over which the valve changes condition from closed to open, and the pore size of the valve.
Referring to
The radial force of expansion of a braid is described by Jedwab and Clerc (Journal of Applied Biomaterials, Vol. 4, 77-85, 1993) and later updated by DeBeule (DeBeule et al., Computer Methods in Biomechanics and Biomedical Engineering, 2005) as:
where K1, K2, K3 are constants given by:
and I and Ip are the surface and polar moments of inertia of the braid filaments, E is the Young's modulus of elasticity of the filament, and G is the shear modulus of the filament. These material properties along with the initial braid angle (β0), final braid angle (β), stent diameter (D0), and number of filaments (n) impact the radial force of the braided valve.
In one embodiment, with a valve arrangement as shown in
According to one aspect of the invention, the valve 204 opens and closes sufficiently quickly to achieve high capture efficiency of embolic agents in the presence of rapidly changing flow direction. In one embodiment, the valve 204 moves from a fully closed (undeployed) position to a fully open position in a static fluid (e.g., glycerin) having a viscosity approximately equal to the viscosity of blood (i.e., approximately 3.2 cP) in 0.067 second. For purposes herein, the time it takes to move from the fully closed position to the fully open position in a static fluid is called the “time constant”. According to another aspect of the invention, the valve 204 is arranged such that the time constant of the valve in a fluid having the viscosity of blood is between 0.01 seconds and 1.00 seconds. More preferably, the valve 204 is arranged such that the time constant of the valve in a fluid having the viscosity of blood is between 0.05 and 0.50 seconds. The time constant of the valve may be adjusted by changing one or more of the parameters described above (e.g., the number of filaments, the modulus of elasticity of the filaments, the diameter of the filaments, etc.).
As will be appreciated by those skilled in the art, the braid geometry of filaments 208-1, 208-2, etc., and the material properties thereof are intimately related to the radial force and time constant of the valve 204. Since, according to one aspect of the invention, the valve is useful in a variety of arteries of different diameters and flow conditions, each implementation can have a unique optimization. By way of example only, in one embodiment, the valve has ten filaments, whereas in another embodiment, the valve has forty filaments. Preferably, the filament diameter is chosen in the range of 0.025 mm to 0.127 mm, although other diameters may be utilized. Preferably, the pitch angle (i.e., the crossing angle assumed by the filaments in the fully open position—the shape memory position) is chosen in the range of 100° to 150°, although other pitch angles may be used. Preferably, the Young's modulus of the filament is at least 100 MPa, and more preferably at least 200 MPa.
According to another aspect of the invention, a filter structure 210 is formed on the braided filament structure (or filaments 208) to form a composite filter valve 204. The schematic illustrations are intended to indicate such a composite filter valve. The filter 210 can be placed onto the braid structure of filaments 208 by spraying, spinning, electrospinning, bonding with an adhesive, thermally fusing, mechanically capturing the braid, melt bonding, or any other desired method. The filter 210 can either be a material with pores such as ePTFE, a solid material that has pores added such as polyurethane with laser drilled holes, or the filter can be a web of very thin second filaments that are laid onto the braid. Where the filter is a web of thin second filaments, the characteristic pore size of the filter can be determined by attempting to pass beads of different diameters through the filter and finding which diameter beads are capable of passing through the filter in large quantities. The very thin second filaments can be spun onto a rotating mandrel with the aid of an electrostatic field or in the absence of an electrostatic field or both. Electrospinning of filaments with the aid of an electrostatic field is described in U.S. Pat. No. 4,738,740, which is hereby incorporated by reference herein. The filter thus formed can be adhered to the braid structure with an adhesive or the braid can be placed on the mandrel and the filter spun over it, or under it, or both over and under the braid to essentially capture it. The filter can have some pores formed from spraying or electrospinning and then a secondary step where pores are laser drilled or formed by a secondary operation. In the preferred embodiment a material capable of being electrostatically deposited or spun is used to form a filter on the braid, with the preferred material being capable of bonding to itself. The filter may be made of polyurethane, pellethane, polyolefin, polyester, fluoropolymers, acrylic polymers, acrylates, polycarbonates, or other suitable material. The polymer is spun onto the braid in a wet state, and therefore it is desirable that the polymer be soluble in a solvent. In an embodiment, the filter is formed from polyurethane which is soluble in dimethylacetamide. The polymer material is spun onto the braid in a liquid state, with a preferred concentration of 5-10% solids for an electrostatic spin process and 15-25% solids for a wet spin process.
According to one aspect of the invention, the filter 210 of the filter valve 204 has a characteristic pore size between 10 μm and 500 μm. More preferably, the filter portion has a characteristic pore size between 15 μm and 100 μm. Even more preferably, the filter portion 210 has a characteristic pore size of less than 40 μm and more preferably between 20 μm and 40 μm. Optionally, the filter portion 210 is provided with a characteristic pore size that will permit blood and contrast agent to pass therethrough while blocking passage of embolizing agent therethrough. However, it is appreciated that the filter need not be constructed to allow either blood or contrast agent to pass through in the upstream ‘reflux’ direction.
In accord with one aspect of the invention, the filter valve 204 includes a longitudinal opening (or circumferential discontinuity) 212 located between its proximal and distal ends; i.e., at a location somewhere between the proximal ends 208a of the first filaments 208 and the distal free ends 208b of the first filaments. In the embodiment shown in
Turning back to
Once the distal portion of the infusion device is at the proper location (preferably relatively coextending with the aneurysm 106), the catheter 202 and sleeve 206 are longitudinally displaceable relative to each other to effect retraction of the sleeve 206 from the filter valve 204 permitting the filter valve to operate in accord with its inherent properties, described above. As will be appreciated, sleeve retraction can be accomplished with a dedicated handle (not shown) that is coupled to the proximal ends of the each of the catheter 202 and the sleeve 206 (e.g., when the sleeve is an outer catheter or via a control member such as a wire extends between the sleeve and the handle) and facilitates such respective movement, or by having the proximal ends of the respective components manually displaceable by an operator. As shown in
As also shown
Turning now to
A microcatheter 322 is provided for advancement through the catheter 302 and into the filter valve 304. The microcatheter 322 can be advanced through the radial opening 320 and into the aneurysm 106 in the vessel wall 102. A guidewire 324 may additionally be advanced within the microcatheter 322 to steer the microcatheter through the radial opening 320 and into the aneurysm 106.
In use, once the infusion device is at the proper location (preferably relatively coextending with the aneurysm 106), the catheter 302 and sleeve 306 are longitudinally displaceable relative to each other to effect retraction of the sleeve 306 from the filter valve 304 and thereby permitting the filter valve to operate in accord with its inherent properties, described above. As shown in
Turning now to
Referring to
Referring now to
The guidewire 624 extends through outer catheter 602, filter valve 604 and bore 626b in the hub 626. With the device 600 arranged relative to the guidewire 624, and the microcatheter 620 extending over the guidewire, the microcatheter is retained in a straightened configuration and can be forcibly butt against the proximal face 626a of the hub 626 to thereby physically displace the hub 626 relative to the distal end 602a of the outer catheter 602. The microcatheter may include longitudinal stiffening to aid in displacement of the hub relative to the catheter. Such stiffening may be along its length or provided at its distal end. It is also appreciated that in the alternative an element other than the microcatheter can be used to retain the elongated configuration of the filter valve during introduction through the blood vessel. This stretches the braid of the filter valve, and the diameter of the tubular form of the filter valve is consequently reduced to thereby facilitate its insertion into the blood vessel. Referring to
Turning now to
Turning now to
There have been described and illustrated herein several embodiments of a flow directional infusion device and methods of using the same. While particular embodiments of the invention have been described, it is not intended that the invention be limited thereto, as it is intended that the invention be as broad in scope as the art will allow and that the specification be read likewise. Thus, while the device and method have been described with particular application to infusing an embolic agent for treatment of an aneurysm, it is appreciated that an infusate other than an embolic agent may be infused or injected through the device and that the device may have application beyond treatment of aneurysms. In addition, it is contemplated that aspects of the various embodiments can be combined. It will therefore be appreciated by those skilled in the art that yet other modifications could be made to the provided invention without deviating from its spirit and scope as claimed.
This application claims the benefit of U.S. Ser. No. 61/540,109, filed Sep. 28, 2011, which is hereby incorporated by reference herein in its entirety.
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| Number | Date | Country | |
|---|---|---|---|
| 20130079731 A1 | Mar 2013 | US |
| Number | Date | Country | |
|---|---|---|---|
| 61540109 | Sep 2011 | US |
