Arrhythmias are abnormal heart rhythms that may cause the heart to function less effectively. Atrial fibrillation (AF) is the most common abnormal heart rhythm. In AF, the two upper chambers of the heart (i.e., the atria) quiver rather than beat and, consequently, fail to entirely empty of blood. As blood stagnates on the walls of the atria, it may form thrombi (i.e., clots). Under certain circumstances, these thrombi can re-enter the circulation and travel to the brain, causing a stroke or a transient ischemic attack (TIA).
Research has indicated that as many as ninety (90) percent of all thrombi formed during AF originate in the left atrial appendage (LAA). Referring to
The high rate of thrombus formation in the LAA is believed to be attributable to its physical characteristics; blood easily stagnates, and thereafter clots, in the long, tubular body of the LAA or at its narrow ostium. In contrast, a right atrial appendage (RAA), which is a wide, triangular appendage connected to the right atrium by a broad ostium, is infrequently the site of thrombus formation. Thrombus formation in the LAA is further promoted by the numerous tissue folds (i.e., crenellations) on its interior surface. These crenellations are particularly hospitable to blood stagnation and clotting, especially when the heart is not functioning at maximum capacity. Thrombi formed in the LAA can re-enter the circulation upon conversion of AF to normal rhythm (i.e., cardioversion).
Certain patient subsets are considered to be at an abnormally high risk of thrombus formation. Such patients include those over seventy-five (75) years of age, as well as those presenting with a history of thromboembolism, significant heart disease, decreased LAA flow velocity, increased LAA size, spontaneous echogenic contrast, abnormal coagulation, diabetes mellitus, and/or systemic hypertension. For these high-risk patients, prophylactic intervention may be recommended.
Some embodiments described here include a plug or insert that occludes the left atrial appendage (LAA), thus preventing blood from entering. In preferred embodiments, the plug is formed in one piece without separately movable parts, and may be monolithic. Embodiments also include a device that can maintain its position without the use of anchors that penetrate the cardiac tissues. The material used for the device is desirably highly biocompatible and may over time simply become part of the cardiac structure itself.
There are a number of aspects for devices, uses, and methods. These aspects include, without limitation, the use of a plug in a LAA; the use of a monolithic plug or other insert in a LAA; the use of a highly, bio-compatible material for the plug; the use of a porous material for the plug; the use of porous-surface silicone (PSS) for a plug; a plug for use in a LAA with a hollow portion; the use of a plug that fits into a 3 mm inner diameter catheter and yet expands to a 20 mm outer diameter, and the use of a plug with folds or grooves to aid in compression and expansion of a plug.
Clot formation during AF can also be reduced through localized delivery of agents, such as anti-platelet or anti-coagulant agents, within the LAA. Localized delivery can be accomplished by several approaches, including a coating applied to a wall, implanted one or more drug pellets, or implanting a drug delivery device. An advantage of localized drug delivery devices is that they would not obstruct or distort the LAA, as would occur with obliteration. Minimal levels of anti-coagulants and/or anti-platelet agents enter systemic circulation because the drugs are delivered for maximum benefit where and when needed. The positive effects of the drug delivery can extend to the entire left atrium, not just the LAA. The LAA is not obstructed by a device or obliterated through surgery. The risk of clot formation is reduced by delivering clot disrupting drugs locally within the LAA. The majority of proposed solutions seek to obstruct or remove the LAA significantly changing the heart structure.
Other features and advantages will become apparent from the following detailed description and drawings.
Embodiments of the device include a single piece plug of material that is inserted into the left atrial appendage (LAA) cavity to occlude it and seal it off from the blood flow that passes through the left atrial chamber. The profile of the plug is similar to that of the LAA itself so that the device will seat in the LAA and conform to the anatomy of the LAA. Its cross section could be axisymmetric or non-uniform.
Referring to
The plug can also have other configurations that range from a completely solid device as illustrated in
For either the hollow or composite designs, the diameter and depth of the lumen can be controlled as deemed necessary. For example, the geometry of the lumen may be designed in such a way as to minimize hemodynamic factors (e.g., flow disturbances) that may initiate thrombosis. Regardless of the geometry of the lumen, however, the profile of the plug should retain the LAA-like shape.
There are several mechanisms that can be employed, either independently or in tandem, to acutely secure the plug in LAA. These include a friction/interference fit; biologically functional adhesive; a balloon expandable annular member; the use of hooks and/or barbs; or a self-expanding annular member.
One approach to securing the plug in the LAA is to use a friction/interference fit. In this case, the dimensions of the plug are slightly oversized, e.g., 10% to 20%, relative to the LAA cavity. When the plug is inserted into the LAA cavity, the material that comprises the plug is compressed and the compressive force persists so long as the plug remains in the LAA. This residual compressive force acts in tandem with the friction that intrinsically exists at the tissue/material interface to secure the plug in place in the LAA. In this embodiment and others, the amount of friction that exists at the tissue/material interface can be controlled by modifying the surface roughness of the plug. A rougher surface generally increases the amount of friction at an interface.
The plug can be coated with an adhesive, such as a biologically functional adhesive (e.g., fibrin glue). The adhesive is applied to surfaces that will come with contact with tissue, and bonds the material of the plug to the tissue. Using biologically active adhesives can also provide additional benefits in the form of an accelerated healing response.
In another embodiment, the balloon expandable annular member is replaced with a self expanding annular member that includes a shape memory material. In this case, a balloon catheter is not explicitly required to expand the proximal section of the plug.
In still another embodiment, the plug is chronically secured and relies on tissue integration into the device such that the device becomes permanently anchored in the LAA.
Another aspect of the LAA plug is the material used to construct the device. Based on the design and deployment considerations previously presented, it would be desirable for material to be biocompatible and readily accepted by the host with no adverse immunological or inflammatory responses. The material should solicit a normal and healthy healing response. The material should, over time, become integrated into the surrounding tissue milieu. Integration of the device into the tissue will ensure long term efficacy of the implant and all but eliminate the potential for embolization. The material should have an expansion ratio and/or mechanical properties that in some fashion permit the device to be advanced through a catheter lumen that is smaller than the LAA and then, when deployed, expand to plug the LAA.
One material that meets these criteria is a porous-surface silicone (PSS). PSS is a silicone-based material that has a controlled degree of porosity throughout the material. PSS material has been found to be nearly ideal matrix for tissue engineering because it is highly biocompatible and readily integratable into the tissue milieu. Animal studies have indicated that the PSS material does not induce fibrous encapsulation and neo-vascularization into the material the readily occurs. The term that is presented by the researchers to describe these phenomena is “true biointegration.”
With respect to the healing response and thrombogenicity of the plug, any and all surfaces could be modified with bioactive molecules to impart the implant with superior efficacy. Surfaces that come into contact with the circulating blood of the left atrial chamber could be coated with anti-thrombotic agents such as heparin. Tissue contacting surfaces could be coated with molecules that aid the healing response including, but not limited to, growth factors, collagen, ligands, and platelets.
The PSS is manufactured using a molding method that is amenable to fabricating components of almost any shape, size, and surface roughness. Therefore, the plug could be made in a variety of sizes and/or shapes in order to fit essentially any type of LAA.
In terms of mechanical properties, PSS, from its porous nature, is a compliant material. The compliance of PSS can also be controlled through the manufacturing process by selecting a medical grade silicone resin with the desired mechanical properties (e.g., durometer).
The plug could be delivered percutaneously via the venous circulation using common catheter practices. In an exemplary procedure, a distal end delivery catheter is delivered to the right atrium from one of several sites, such as the femoral, jugular, or brachial veins. The delivery sheath is used to deliver a need-type catheter which is used to puncture the atrial septum to gain access to the left atrium. The distal end of the delivery sheath is then passed through the atrial septum into the left atrium, and is then positioned at the LAA. The plug is collapsed into a proximal lumen of the delivery sheath and tracked to the distal end of the sheath. The plug is then deployed out of the sheath and into the LAA.
The precise aspects of the deployment of the plug are ultimately dependent upon its design. For instance, if the design of the plug utilizes the balloon expandable annular member (depicted in
In terms of delivery and deployment, it is desirable for the plug to be able to easily fit into a lumen of a delivery catheter, and preferably 10 French (F) or smaller delivery catheter and then, upon exiting the delivery catheter, expand to fit the LAA. The catheter could have one of a number of sizes, such as 6 F-14 F. The way the plug expands could be derived from sources already described (i.e., the intrinsic elasticity of the PSS itself or from a “stent” like device). Regardless of the source or means of expansion, the problem of how to fit the plug into the delivery catheter still remains. The size difference between the delivery catheter and the LAA can be significant; a lumen of a 10 F delivery catheter is on the order of 3 mm inner diameter whereas the LAA can be as large as 20 mm in diameter. This means that the plug should be able to fill a 20 mm diameter cavity, while also fitting into a 3 mm inner diameter lumen on delivery. With a larger diameter catheter, the plug's diameter would be reduced at least about 75% for delivery, and about 85% for delivery through a 3 mm catheter. Although PSS is highly compliant, it may not be sufficiently compliant to undergo deformations on the order of 500% or more. The plug may fit in the delivery catheter if the device is designed as an entirely hollow part as depicted in
PSS can achieve elongations on the order of 400%, thereby aiding the delivery and deployment by allowing the plug to be elongated during delivery. To further aid delivery of a plug that cannot be elongated enough without further modification, the geometry and/or porosity of the device could be modified as needed to make the device easier to deliver and deploy but yet still retain the clinical utility of the device. For instance, the tissue contacting surface of the plug can have undulations as depicted in
The plug could be designed with any number of the previously mentioned designs to facilitate folding or collapsing of the device into the delivery sheath and subsequent deployment to the LAA.
As indicated above, the plug can be coated with ant-thrombotic agents such as heparin. The potential for clot formation during AF can be reduced through localized delivery of agents, such as anti-platelet or anti-coagulant agents, within the LAA, without the use of a plug. Localized delivery can be accomplished by several approaches as described in conjunction with
Referring to
Referring to
The drug released pellets can be timed to slowly release a small amount of a drug, such as an anti-coagulant, over a sustained period of time. At some point, the drug will be used up. While the anchor could be made of a non-bioresorbable material, such as nitinol, it could alternatively be made of a bioresorbable material that is slowly resorbed, so that the drug has an opportunity to be fully released before the anchor is resorbed into the tissue and/or bloodstream. Alternatively, one or more pellets with drugs could be embedded in a side wall of the LAA without anchors.
While the drug released material is described as being a pellet, it could take any shape or form that allows some form of time release, such as in the shape of a ribbon. As a further alternative, the drug could be provided as a coating on a substrate, such as a bioresorbable substrate, such that the coating is released into the system before the substrate has an opportunity to decay into the bloodstream. The substrate could be formed as a tube or tubular mesh within the walls of the LAA, like a stent. Such substrates could be delivered through a catheter or provided during surgery, such as during another procedure.
Referring to
The device could be triggered from another device within the body, such as an implanted pacemaker or defibrillator, or the signal could come from outside the body. Signaling can be accomplished through the use of inductive energy to a small coil in the drug delivery device, or through a radio frequency (RF) signal. An implantable pacemaker or defibrillator could be provided with a mechanism for providing a signal that is detectable by the drug delivery device. For example, small coils and other circuit components can be integrated onto very small semiconductor chips and tuned to be responsive to particular signals that could cause a valve, such as a small diaphragm or shutter, to release small amounts of agents. The agents could be provided in liquid or fine powdered form. Preferably, the release is benign if done at a time when not strictly needed.
The LAA would not be significantly distorted or damaged by the drug delivery device, and the device provides minimal obstruction.
These options can be placed within the LAA structure through minimally invasive means. The LAA is not obstructed by a device or obliterated through surgery in preferred embodiments. The risk of clotting is reduced by delivering the clot disrupting drugs locally within the LAA. Minimal levels of anti-coagulants and/or anti-platelet agents enter systemic circulation because the drugs are delivered for maximum benefit where and when needed. The positive effects of the drug would extend to the entire left atrium, not just the LAA.
Having described certain embodiments, it should be apparent that modifications can be made without departing from the scope of the invention. For example, while PSS is described as a useful material, other materials with one or more of the useful aspects that PSS has could be used, such as polyvinyl alcohol, collagen, polyurethane foam.
This application claims priority to provisional application Ser. Nos. 60/557,611, filed Mar. 30, 2004; and 60/557,484, filed Mar. 30, 2004; each of which is incorporated herein by reference.
Number | Date | Country | |
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60557611 | Mar 2004 | US | |
60557484 | Mar 2004 | US |