WO2022054066A1

WO2022054066A1 - Device and minimally invasive method for managing cardiac valve regurgitation

Info

Publication number: WO2022054066A1
Application number: PCT/IL2021/051115
Authority: WO
Inventors: Yoav Turgeman; Eran Hirszowicz; Amit TURGEMAN
Original assignee: Mor Research Applications Ltd.
Priority date: 2020-09-14
Filing date: 2021-09-13
Publication date: 2022-03-17

Abstract

The present invention is directed to a system for reducing cardiac valve regurgitation, wherein said system is adapted for endovascular delivery, and comprises: a) an anchoring net of a size and shape such that it may be placed over the annulus of the cardiac valve being treated, wherein said net is perforated by a series of apertures; and b) one or more occluding plugs, each of which is of a size and shape such that it may be inserted into one of the apertures in the anchoring net, and become retained therewithin, thereby sealing said aperture. The invention also encompasses a method for reducing cardiac valve regurgitation using this system.

Description

Device and minimally invasive method for managing cardiac valve regurgitation

Field of the invention

This present invention is related to a device for use in interventional cardiology. More specifically, the invention is directed to a device for use in the reduction of cardiac valve regurgitation, particularly in the atrioventricular (tricuspid and mitral) valves. The device is constructed such that it may be deployed by means of a minimally invasive, endovascular approach

Background of the invention

Significant atrioventricular valve regurgitation with symptoms of either left or right heart failure is generally associated with a poor quality of life and a high mortality rate [Agricola E, et al. Euro J Heart Fail 2012;14:902-8], Most of the symptomatic patients with tricuspid regurgitation (TR) are adults having left -sided valve pathologies, pulmonary hypertension, atrial fibrillation, right ventricle (RV) dilatation and/or severe comorbidities.

The vast majority of this population are unable to be treated by cardiac surgeons due to a high perioperative mortality rate. For example, among the 1,600,000 patients in the US suffering from severe TR, only 8000 patients each year undergo surgical valve repair or replacement procedures [Nath, J. et al.; J. Amer. Coll. Cardiol. 2004;43: 405-9]. The yearly incidence of TR is about 200,000 in the United States and about 300,000 in Europe

There is thus a large unmet clinical need for a minimally invasive treatment for patients with severe TR who are unable to undergo surgery. The present invention meets this unmet need. Summary of the invention

The present invention is primarily directed to a system for reducing or eliminating cardiac valve regurgitation, particularly (although not exclusively) of an atrioventricular valve, wherein said system comprises two interacting components - (a) an anchoring net, and (b) an occluding plug, wherein said plug is used to occlude one of the apertures in said anchoring net. Both of these elements are adapted for deployment via an endovascular approach to the cardiac valve in need of treatment. This is facilitated by the third component of the system, which is a delivery system, into which the other two components are loaded and delivered to the cardiac valve in need of treatment. The anchoring net is constructed such that it does not interfere with blood flow, nor disturb atrio-ventricular (A- V) valve function or cause damage to the surrounding structures.

Thus, in its most general form, the first element of the system of the present invention is an anchoring net element, in the form of a sheet, sized and shaped such that it may be implanted superiorly to the cardiac valve being treated, wherein said anchoring net is punctured by a series of full-thickness apertures across its surface.

The second element of the system is an occluding plug which is sized and shaped such that it may be inserted into one of the aforementioned apertures in the anchoring net element.

Thus, in one aspect, the present invention is primarily directed to a system for reducing cardiac valve regurgitation, wherein said system is adapted for endovascular delivery, and wherein said system comprises: a) an anchoring net of a size and shape such that it may be placed over the annulus of the cardiac valve being treated, wherein said net is perforated by a series of apertures; and b) one or more occluding plugs, each of which is of a size and shape such that it may be inserted into one of the apertures in the anchoring net, and become retained therewithin, thereby sealing said aperture. In one embodiment of this system, the anchoring net further comprises a split region leading to a small opening, wherein said opening is of a size and shape suitable to allow the passage of a pacemaker lead. In some - but not all - implementations of this embodiment, the split region extends from the center of the anchoring net to the outer perimeter thereof.

While in some embodiments all of the apertures in the anchoring net have the same size and shape, in one preferred embodiment, the apertures are not all of equal size or shape. For example, some of said apertures may be square in outline, while others may be round, elliptical and/or polygonal. In other embodiments, the apertures may all have the same shape, but may differ in diameter. Thus, in one preferred embodiment, the apertures are smaller in the central region of the anchoring net and larger in its peripheral region.

The occluding plugs of the system disclosed and claimed herein may have various different shapes and forms. In one preferred embodiment, however, each occluding plug comprises an upper element and a lower element mutually connected by a waist region which is smaller in diameter than both of said elements. In such an embodiment said upper and lower elements in a single occluding plug may either be of equal size and/or shape. In other implementations however, said upper and lower elements of a single occluding plug may differ from each other in size and/or shape. In one preferred embodiment of the system disclosed herein, one or both of the occluding plug upper and lower elements is fitted with a retrieval element selected from the group consisting of an open ring, a closed ring and a hook.

In one preferred embodiment, the occluding plug and the anchoring net are both constructed from Nitinol®, and one or both are optionally covered or coated with a biocompatible polymer. In other embodiments, the occluding plug and/or the anchoring net are constructed from other biocompatible metals such as cobalt-chrome alloys or from flexible polymers, such as polyester. In another aspect, the present invention is directed to a method for reducing or eliminating cardiac valve regurgitation in a patient in need of such treatment, wherein said method comprises the steps of: a) delivering, by endovascular means, an anchoring net element, to a location within the atrium, superior to, and in close approximation with, the annulus of the valve being treated, wherein said net element is perforated by a series of apertures; b) identifying the region between at least two valve leaflets in which regurgitation is occurring (vena contracta) by means of one or more cardiac imaging techniques; c) selecting an occluding plug of suitable size and shape to be inserted into the anchoring net aperture that is located opposite and above the regurgitation region identified in step (b); d) delivering, by endovascular means, the occluding plug selected in step (c), to one surface of the anchoring net element deployed in step (a) and inserting said plug into the anchoring net aperture that is located opposite and above the regurgitation region identified in step (b), such that said plug becomes retained within said net aperture, and thereby seals said aperture.

In this way, the presence of the plug in close proximity to the site of regurgitation serves to seal the blood leakage at said site when the valve leaflets are in their closed position.

In one preferred embodiment of the above-defined method, the cardiac imaging techniques used in step (b) comprise fluoroscopy together with an ultrasound or echocardiographic method such as transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE).

In one preferred embodiment of the method, the endovascular means employed in steps (a) and (d) involve the use of one or more of a delivery catheter, introducer sheath and guidewire. In one embodiment, the method of the present invention further comprises the steps of: e) retrieving the occluding plug from the anchoring net aperture; and f) re-inserting said occluding plug in the same or a different anchoring net aperture; wherein said retrieval and reinsertion are performed using the same endovascular means (i.e., delivery system) used in steps (a) and (d).

These additional, optional steps may be implemented, for example, in a situation in which the plug has not been correctly inserted within an aperture and needs to be correctly reinserted in the same aperture. Another scenario in which such steps may be employed is in the case that it becomes apparent that a better clinical outcome would be obtained by means of plugging a different aperture.

In another preferred embodiment, the method of the present invention further comprises the steps of: ee) retrieving the occluding plug from the anchoring net aperture and removing said plug from the body; and ff) retrieving the anchoring net and removing said net from the body; wherein said retrieval steps are performed using the same endovascular means (i.e., delivery system) used in steps (a) and (d) as defined hereinabove.

The last-mentioned embodiment may be employed, for example, when the method of the present invention is intended to be used for the temporary treatment of cardiac regurgitation, such that steps (ee) and (ff) are both performed at an interval of several days to several weeks following the insertion of the occluding plug within the anchoring net aperture, as defined in method step (d) hereinabove.

In any of the embodiments described above which require the retrieval of the occluding plug, said retrieval may be facilitated by the presence of a retrieval element fitted to said plug. In most cases, said retrieval element will project from either the upper portion (upper element) of the plug or from the lower portion (lower element) thereof. In some cases, two such retrieval elements may be fitted to the plug, with one being attached to the upper element and one to the lower element. Said retrieval element may have any suitable shape and size that is compatible with the guidewire or other comparable element in the delivery system. Preferably, the occluding plug retrieval element will have a shape selected from the group consisting of an open ring, a closed ring, a hook, an S-shaped hook, and so on.

The method of the present invention may be used to treat regurgitation any in of the cardiac valves, namely, the tricuspid valve, the mitral valve, the aortic valve and/or the pulmonary valve. In one preferred embodiment, the valve being treated is the tricuspid valve. In another preferred embodiment, the valve being treated is the mitral valve. In another preferred embodiment, the valve being treated is the aortic valve. In another preferred embodiment, the valve being treated is the pulmonary valve.

In most preferred embodiments of the method of the present invention, the patient is a human patient. The present invention, however, also encompasses the use of the claimed method to treat non-human (veterinary) patients.

Brief description of the drawings

Fig. 1 illustrates one embodiment of a device of the present invention.

Fig. 2 depicts an embodiment of the anchoring net of the device of the present invention, in which set net comprises a split region and small central aperture.

Fig. 3 provides, in its upper portion, a schematic side view of one embodiment of the occluding plug of the present invention, and in its lower portion the same occluding plug inserted into an aperture in the anchoring net.

Fig. 4 provides a cut-away view of a human heart and indicates the position of an anchoring frame of the device of the present invention which has been deployed above the tricuspid valve. Fig. 5 depicts three different embodiments of the system of the present invention, each one comprising an anchoring net that provides less than complete coverage of the annular region.

Detailed description of preferred embodiments of the present invention

The general principle by which the system of the present invention operates in order to reduce valve regurgitation in a patient in need of such treatment is as follows: a) The anchoring net is placed within the atrium (on the side of the heart being treated), immediately above the upper surface of the valve leaflets, and in contact with said leaflets when they are in their closed position. In most embodiments of the invention, the area (and hence diameter(s)) of the anchoring net will be slightly greater than that of the valve annulus, such that said net can be supported in its lateral portions by at least one portion of the atrial wall, and in some embodiments, anchored or secure thereto.

In some embodiments, the aforementioned anchoring net is attached at its periphery to an anchoring frame, the purpose of which is to provide support for said net.

The size and arrangement of the apertures in the anchoring net is such that a very large percentage of the surface area of said net is occupied by the apertures, with only a very small percentage being occupied by the material of the net that forms the boundaries of, and thus located between, said apertures. In this way, the anchoring net does not reduce the volume of blood that passes through the open valve annulus into the ventricle, and similarly does not introduce any local regions of turbulent flow which were not already present prior to deployment of the device. The apertures of the anchoring net generally have a diameter in the range of 4-12 mm. However, these figures are not limiting, and in some circumstances the apertures may be either larger or smaller than the limits of this range. The shape of the anchoring net - and hence also of the optional anchoring frame - generally approximates to the elliptical shape of the cardiac valve annuli. The areas of the net and frame will generally be slightly larger than the areas of the relevant cardiac valve (e.g., about 6-9cm² for the tricuspid valve and about 4-8 cm²for the mitral valve). b) Following deployment of the anchoring net element in the supravalvular position, the region(s) in which the valve regurgitation occurs will be located beneath one or more of the apertures in said net element. After the relevant aperture has been identified, an occluding plug is inserted into said aperture. The lower surface of said plug will thus present a flat or appropriately curved surface to the aperture formed between the incompletely closed valves leaflets at the regurgitation point, thereby partially or completely sealing said aperture when the leaflets reach their closed position. In this way, regurgitation (i.e., the passage of blood in a retrograde fashion into the atrium upon ventricular contraction) is reduced, or in some cases, completely eliminated.

It may be appreciated, from the foregoing general description, that the system of the present invention works on a 'finger in hole' principle, that is, regurgitation is reduced by means of determining which hole or aperture (in the anchoring net) overlays the region of valve regurgitation, and then plugging that hole with the second, occluding element.

It therefore follows that, in one aspect, the present invention is primarily directed to a system for reducing cardiac valve regurgitation, wherein said system is adapted for endovascular delivery, and wherein said system comprises: a) an anchoring net of a size and shape such that it may be placed over the annulus of the cardiac valve being treated, wherein said net is perforated by a series of apertures; and b) one or more occluding plugs, each of which is of a size and shape such that it may be inserted into one of the apertures in the anchoring net.

Optionally, in one embodiment, the anchoring net may be attached at its outer periphery to an anchoring frame. In one embodiment of the system of the invention, the anchoring net (and where present, the optional anchoring frame) has an outline shape similar to that of the annulus of the valve being treated, and a surface area that is slightly larger than said annulus, such that the peripheral region of said anchoring net will, following implantation, be in contact with, and supported by the atrial wall tissue surrounding the annulus. In such an embodiment, the anchoring net will, following implantation, cover all of the surface area of the valve annulus.

In another embodiment, the anchoring net (and where present, the frame) may be sized and shaped such that it is capable of being implanted such that the anchoring net covers less than 100% of the surface area of the valve annulus. In this type of embodiment, the net element and/or frame (if present) may be partially circumferential, with a semi-circular, crescent-shaped, or other outline shape, that is sized such that at least two of the peripheral regions of said anchoring frame are capable of extending beyond the margins of the valve annulus following implantation, and thereby used to stabilize the anchoring net. In one preferred group of embodiments (as shown in Fig. 5, and discussed hereinbelow), the partial coverage net comprises a closed, ring-shaped peripheral region having a shape similar to the valve annulus being treated, and a size (diameter and area) which is slightly larger than said annulus. In this way, the peripheral ring can provide complete circumferential support for the partial net. This type of anchoring net geometry may be chosen for use, for example, in patients suffering from significant TR in whom a permanent pacemaker lead has previously been implanted.

Both the anchoring net element (and where present, the optional anchoring frame) may be constructed from Nitinol or a similar biocompatible metallic alloy having shape memory and/or superelastic properties. In one embodiment, the anchoring net element is constructed such that the individual apertures have a circular outline shape. In another embodiment, the outline aperture shape may be polygonal, for example hexagonal, rhomboid, or square. In some cases, it is possible to select the anchoring net having the most appropriate aperture size and shape for the specific patient being treated. This selection can be made on the basis of the pre-interventional imaging. The area of each aperture is generally in the range of 0.1 - 3.0 cm², preferably in the range of 0.5 to 1.5 cm²- more preferably in the range of 0.75 to 1.0 cm². However, in some embodiments, the aperture size may be either smaller or greater than the limits of these ranges, which are brought by way of example only.

It is to be noted that in some embodiments of the anchoring net, the aperture size need not be the same across the entire net. Thus, in one embodiment, the central portion of the anchoring net will contain relatively small apertures, while the peripheral portions may contain relatively large apertures. This difference in aperture size arises because of the fact that a smaller aperture size in the central region of the anchoring net (i.e., opposite the regurgitation zone) permits the more accurate placement of the occluding plug at the required position. Conversely, the peripheral region of the net will not need to be occluded with a plug, since the primary purpose of this region is the anchoring of the device to the tissues around the annulus. There is therefore no need for small apertures in this region.

The boundaries of each of the apertures will, in most embodiment, be formed from Nitinol wires, preferably having a diameter in the range of 0.4-1.5 mm. In other embodiments, said wires may be formed from other suitable biocompatible metals, such as cobalt-chrome alloys, or from flexible polymers, such as polyester.

In some embodiments in which the anchoring net is connected at its periphery to a metal anchoring frame, said frame may be covered with a covering material such as silicone rubber or another biocompatible polymer.

The anchoring net may be folded down to a size small enough to be loaded into a delivery device (such as an introducer sheath and/or delivery catheter) having a diameter of about 12 -20 French.

In some embodiments, the anchoring net is constructed such that the array of apertures is interrupted by the presence of a split or fissure. The reason for this feature is to allow the implantation of the present device in patient in whom a pacemaker lead, or other indwelling cardiac device has already been implanted. This split will thereby allow for deployment of the device around the pacemaker leads. Following implantation of the present device, said leads will pass through a small central aperture located at one end of the split. In one embodiment, the split may extend from the outer circumference of the anchoring net to approximately the center of said net, where said split may optionally end in a small central aperture. This, however, is just one possible implementation of this feature: in other embodiments, the split or fissure need not be radially oriented, and need not pass from the center of the net to the outer ci rcumference thereof.

The occluding plug is, in some embodiments, in the form of a frame constructed from Nitinol or a similar biocompatible superelastic / shape memory alloy and is preferably covered with silicone rubber or another biocompatible polymer (e.g., PEBAX, Polyurethane, etc.). The flexible frame structure of the plug permits it to be folded into a much smaller volume, such that it can pass through the lumen of a, for example, 12 French sized introducer device and/or delivery sheath, for the purposes of delivery and deployment.

Since the occluding plug needs to fit snugly within one of the apertures of the anchoring net element, the diameter and outline shape of the plug and aperture needs to be very similar. In one preferred embodiment the plug has an undercut section (or waist), such that upon the application of force, the plug is caused to enter the aperture and then remain there, held in place by the larger portions that are above and below the undercut region. In side view, the outline shape of the plug is not necessarily symmetrical, such that the upper and lower faces of said plug may have different diameters. Also, the narrow waist region of the plug is not necessarily placed at the midpoint between the upper and lower faces thereof but may be located closer to one of said faces than to the other. The occluding plug may have a circular outline shape, or a polygonal (e.g., hexagonal) outline shape. In one preferred embodiment, one of the two opposing faces of the plug may be flat, while the other one is conical, for ease of insertion. In yet further embodiments, one or both of the opposing faces of the plug may be non-flat (concave or convex). Furthermore, in some embodiments, one or both of the opposing faces of the plug may be orientated such that it is at an angle of other than 90 degrees in relation to the central axis of the plug that connects said opposing faces (i.e., said faces may be tilted). In general, different plug shapes can be selected or adjusted for different aperture shapes, as determined by pre procedure echocardiography.

Fig. 1 illustrates one embodiment of a device 10 of the present invention. As may be seen from this figure, the device comprises a net element 14 which, in this embodiment is attached at its outer perimeter to an anchoring frame 12. It is to be noted, however, that, as explained hereinabove, said anchoring frame is optional, and in other embodiments the anchoring net will not be attached to a frame. This figure also shows an occluding plug element 16, inserted into one of the apertures of anchoring net 14.

Fig. 2 illustrates an embodiment of the anchoring net 24, such as disclosed hereinabove, in which said net contains a split region 27, leading to a central small aperture 29, through which pacemaker (or similar) leads may be passed.

Fig. 3 shows, in its lower portion, a side-view schematic illustration of an anchoring net 31 of the present invention, into which has been inserted an occluding plug 35. The waist 38, upper element 36 and lower element 37 of occluding plug 35 are shown in detail in the upper part of the figure, while the same plug is shown in situ, within an aperture of the anchoring net 35 in the lower portion of the figure.

As explained hereinabove, in some embodiments, the anchoring net provides only partial coverage of the annular region. That is, the net may be sized and shaped such that it is capable of being implanted such that the anchoring net covers less than 100% of the surface area of the valve annulus. In this type of embodiment, the net element may have various different shapes: for example, partially circumferential, with a semi-circular, crescent-shaped or other outline shape. In one preferred group of embodiments, as shown in Fig. 5, the partial coverage net comprises a closed, narrow, ring-shaped peripheral region having a shape similar to the valve annulus being treated, and a size (diameter and area) which is slightly larger than said annulus. In this way, the peripheral ring can provide complete circumferential support for the partial net. Thus, the upper drawing in Fig. 5 shows one embodiment of this type, comprising a complete outer ring 52, with the net 54a being confined to one end of the elliptical area enclosed by said ring. This figure also shows an occluding plug 56 inserted into one of the apertures in net 54a. Another possibility is shown in the middle drawing, in which the net containing the apertures 54b is confined to a relatively narrow central region of the area enclosed by the outer ring. One additional embodiment is shown in the lower drawing of the figure. In this case, the anchoring net 54c is in the form of a cross having two shorter arms and two longer arms, which meet in a central portion of the area enclosed by the perimeter ring.

The precise type and geometry (e.g., full coverage or partial coverage with different net shapes) of the anchoring net may be chosen by the clinician in accordance with the position of the regurgitation region (vena contracta). For example, a partial net having the shape shown in the upper drawing of Fig. 5 may be particularly useful in the case that the regurgitation region is situated towards the periphery of the coaptation region of the heart valve being treated.

It is to be noted that the net element is referred to herein as an 'anchoring net' even in the partial coverage embodiments in which support for the device against the cardiac tissues is provided partly by said net element and partly by the outer ring. It is also to be noted that this outer ring may either be a distinct frame (as described hereinabove) to which the net is attached, or it may be a continuation of the net region itself. This later situation may be conceptualized as an elliptical attachment net in which most of the woven net portion is 'missing'.

Both the anchoring net and the occluding plug elements of the presently claimed system may be manufactured using any of the standard manufacturing techniques well known to skilled artisans in this field, including laser cutting and welding, soldering, milling, additive manufacturing and so on. In another aspect, the present invention is directed to a method for reducing or eliminating cardiac valve regurgitation in a patient in need of such treatment, wherein said method comprises the steps of: a) delivering, by endovascular means, an anchoring net as disclosed hereinabove, to a location within the atrium, superior to, and in close approximation with, the annulus of the valve being treated; b) identifying the region between the valve leaflets at which regurgitation is occurring (vena contracta) by means of one or more standard cardiac imaging procedures, as well known in the art. In one preferred embodiment, the imaging procedures used will be fluoroscopy (as used in most cardiac catherization techniques) together with an echocardiographic technique, such as transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE); c) selecting an occluding plug of suitable size and shape to be inserted into the anchoring net aperture that is located opposite and above the regurgitation region identified in step (b); d) delivering, by endovascular means, an occluding plug, as disclosed hereinabove, to the upper surface of the anchoring net element deployed in step (a) and inserting said plug into the anchoring net aperture that is located opposite and above the regurgitation region identified in step (c). In this way, said plug becomes firmly retained within the anchoring net aperture, and (following implantation into the patient and deployment at its working position) will provide a fluid seal for said aperture - that is, blood will not be able to pass through the plugged aperture.

In some embodiments, the anchoring net element is supported by, and attached at its periphery to an anchoring frame. In such embodiments, the optional securing or anchoring of the net element to the atrial wall tissue (step (b), above), may involve anchoring of the frame element instead of, or in addition to, anchoring of the net itself. However, it is to be noted that in many cases, the anchoring net will be entirely self-supported on the upper surface of the peri-annular tissues by virtue of its size and shape, assisted by the hemodynamic forces applied thereon as the blood passes down from the atrium into the ventricle through the open valve.

In one embodiment, the method of the present invention is used to reduce regurgitation in an atrioventricular valve. In one preferred embodiment, the atrioventricular valve is the tricuspid valve. In another preferred embodiment, the atrioventricular valve is the mitral valve.

In another embodiment, the method of the present invention is used to reduce regurgitation in one of the semilunar valves, i.e., either the pulmonary or the aortic valve.

While, in some cases, it may be possible to completely eliminate valve regurgitation using the above-disclosed method, in general, success of said method is defined as a 60-70% reduction of the regurgitant volume.

In one embodiment, separate delivery catheters and introducers may be employed in order to sequentially deploy the anchoring net and occluding plug elements, in steps (a) and (d) of the above-defined method. The introducers may be inserted into the cervical or femoral veins, or into any other suitable site chosen by the clinician. Guide wires, control wires and other elements well known to the skilled artisan into this field may be used in order to control the delivery of the system elements in steps (a) and (d), and their deployment. Deployment of these elements is generally achieved by means of causing them to leave the confines of the introducer (unsheathing), and thereby, to move between a closed (i.e., folded) delivery conformation and an open, working conformation.

All stages of device implantation are reversible. Thus, following implantation (but preferably before significant tissue ingrowth into the device has taken place), the occluding plug may, in some embodiments, be retrieved from the device, that is removed from its location within an anchoring net aperture, e.g., by means of a custom retrieval device. Such retrieval may be performed at any time following deployment, for example over a timescale of a few days to a few weeks.

Similarly, in embodiments comprising an anchoring frame, the anchoring net may be removed, in situ, from said frame and re-attached. Alternatively, following removal, a new net may be attached to the frame.

The third principal element of the presently disclosed system (i.e., in addition to the anchoring net and the occluding plug) is the delivery system, which will now be described in general terms.

Thus, since the anchoring net, optional frame and occluding plugs are all intended to be delivered by a non-invasive endovascular route, it is convenient to use a delivery system to deliver and deploy these elements. Either a single delivery system may be used to deliver all of the aforementioned elements, ortwo or more separate delivery systems may be used for the separate delivery and employment the optional anchoring frame, net and occluding plugs. As previously mentioned, the occluding plug, once deployed, may also be retrieved - for example in situations in which the clinician wishes to adjust the position of the occluding plug, that is to place a plug in a different aperture, in order to improve the clinical result.

The delivery method (regardless of the number of separate delivery systems used) is performed as follows:

1. The anchoring net is delivered via a delivery system (introducer, sheath, catheter etc.) to the annulus region of the valve to be treated. In the case of atrioventricular valves, the anchoring frame and net are delivered endovascularly, such that they leave the confines of the sheath on the atrial side of the valve to be treated, just above the annulus. 2. An occluding plug is then delivered via the delivery system to the region of the implanted anchoring frame and net. The distal end of the delivery cable or guidewire passes through the aperture which has been selected for occlusion. Then, the cable or wire is pulled backwards, in a proximal direction and the occluding plug is unsheathed and thereby released into the chosen aperture.

The delivery system of the present invention may be used to perform one or more of the following functions:

• Deployment of anchoring frame (if present) and anchoring net as a single unit

• De-deployment of the anchoring net and/or frame

• Deployment of occluding plug

• Retrieval of occluding plug

In this way, the same delivery system may be used to both deliver and re-position the device of the present invention. Furthermore, this reversibility of function is also advantageous in situations when the system of the present invention is used as a temporary measure, for example over a time span of a few days to a few weeks.

The delivery system of the present invention may comprise a loader into which the anchoring frame, that and occluding plug may be loaded, and a release cable for controlling the deployment of the devices during un-sheathing. The delivery system may also comprise further components including a sheath and a dilator (for minimizing tissue trauma).

Examples of suitable commercially available delivery systems that be used to deliver and deploy the treatment system of the present invention include (but are not limited to) the Amplatzer™ Trevisio™ intravascular delivery system (Abbott Laboratories, IL, USA), having a sheath length of 60-80 cm, a lumen size of 6-13 French, and a distal curve of 45°. Another suitable example of a delivery system for use with the present invention includes the Occlutech delivery set (Occlutech, Schaffhausen, Switzerland), having a sheath length of 80 -110 cm, a 7-14 French lumen and a distal curve of 45-180°. The delivery and implantation of both the anchoring net and occluding plug elements is performed while being monitored using conventional Fluoroscopic and Echocardiographic (TTE or TEE) methods in the catheterization laboratory.

In the case of implantation of the system in the tricuspid valve {TV), the anchoring net will be placed and optionally attached or attached to the surrounding area of the atrial wall above the level of the TV, without interference to the blood flow, or to adjacent structures such as the coronary sinus or A-V node.

In certain cases, the system of the present invention may assist in reducing valve regurgitation mainly by blocking the source of the regurgitating blood jet (i.e., the 'finger in hole' approach), and also additionally by means of providing a rigid platform in the coaptation zone, thereby resulting in a more normal closure of the valve leaflets. This is particularly useful when the valve being treated has one or more flail or prolapsed leaflets.

Fig. 4 provides a cut-away view of the human heart. As seen in this figure, an anchoring net 42 (with associated anchoring frame; not seen) of the present invention has been deployed above the tricuspid valve 44, the peripheral region of said anchoring net making contact with the lower region of the inner atrial wall. As a result of the presence of the device of the present invention, any previously existing regurgitation occurring through tricuspid valve 44 during contraction of ventricle 48, will now be significantly reduced.

The system and method of the present invention have a number of significant advantages, including:

1. The system and method are suitable for both TR & MR.

2. The method is easy to practice in the Cath Lab using standard equipment that is familiar to clinicians, insertion of the system being achieved via either a cervical or a femoral venous approach. 3. In addition to its primary use as a permanent treatment forTR or MR, the system of the present invention can also be implanted into a patient temporarily, and then later removed. This latter strategy may be adopted, for example, in stabilized patients with acute MR or TR, and used to assess suitability of borderline patients for subsequent valve surgery. A further indication for the temporary use of the system is the assessment of left ventricle or right ventricle function of cardiac patients undergoing medical therapy.

4. The method and system are suitable for use in the treatment of both functional TR & organic TR.

5. The system can be inserted even in the presence of a permanent pacemaker (partial net & ring types).

Claims

1. A system for reducing cardiac valve regurgitation, wherein said system is adapted for endovascular delivery, and wherein said system comprises: a) an anchoring net of a size and shape such that it may be placed over the annulus of the cardiac valve being treated, wherein said net is perforated by a series of apertures; and b) one or more occluding plugs, each of which is of a size and shape such that it may be inserted into one of the apertures in the anchoring net, and become retained therewithin, thereby sealing said aperture.

2. The system according to claim 1, wherein the anchoring net further comprises a split region leading to a small opening, wherein said opening is of a size and shape suitable to allow the passage of a pacemaker lead.

3. The system according to claim 2, wherein the split region extends from the center of the anchoring net to the outer perimeter thereof.

4. The system according to claim 1, wherein the apertures in the anchoring net are not all of equal size or shape.

5. The system according to claim 4, wherein the apertures are smaller in the central region of the anchoring net and larger in its peripheral region.

6. The system according to claim 1, wherein the anchoring net has a size and shape such that it is capable of covering less than 100% of the surface area of the valve annulus following implantation.

7. The system according to claim 1, wherein the occluding plug comprises an upper element and a lower element mutually connected by a waist region which is smaller in diameter than both of said elements.

8. The system according to claim 7, wherein the upper and lower elements of the occluding plug differ from each other in size and/or shape.

9. The system according to claim 7, wherein one or both of the upper and lower elements is fitted with a retrieval element selected from the group consisting of an open ring, a closed ring and a hook.

10. The system according to claim 1, wherein the occluding plug and the anchoring net are both constructed from Nitinol®, and one or both are optionally covered or coated with a biocompatible polymer.

11. A method for reducing or eliminating cardiac valve regurgitation in a patient in need of such treatment, wherein said method comprises the steps of: a) delivering, by endovascular means, an anchoring net element, to a location within the atrium, superior to, and in close approximation with, the annulus of the valve being treated, wherein said net element is perforated by a series of apertures; b) identifying the region between at least two valve leaflets in which regurgitation is occurring (vena contracta) by means of one or more cardiac imaging techniques; c) selecting an occluding plug of suitable size and shape to be inserted into the anchoring net aperture that is located opposite and above the regurgitation region identified in step (b); d) delivering, by endovascular means, the occluding plug selected in step (c), to one surface of the anchoring net element deployed in step (a) and inserting said plug into the anchoring net aperture that is located opposite and above the regurgitation region identified in step (b), such that said plug becomes retained within said net aperture, and thereby seals said aperture.

12. The method according to claim 11, wherein the cardiac imaging techniques used in step (b) comprise fluoroscopy together with either transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE).

13. The method according to 11, wherein the endovascular means employed in steps (a) and (d) involve the use of an intravascular delivery catheter, sheath and/or introducer.

14. The method according to claim 11, further comprising the steps of: e) retrieving the occluding plug from the anchoring net aperture; and f) re-inserting said occluding plug in the same or a different anchoring net aperture; wherein said retrieval and reinsertion are performed using the same endovascular means used in steps (a) and (d).

15. The method according to claim 11, further comprising the steps of: ee) retrieving the occluding plug from the anchoring net aperture and removing said plug from the body; and ff) retrieving the anchoring net and removing said net from the body; wherein said retrieval steps are performed using the same endovascular means used in steps (a) and (d) as defined in claim 11.

16. The method according to claim 15, for use in the temporary treatment of cardiac regurgitation, wherein steps (ee) and (ff) are performed at an interval of several days to several weeks following the insertion of the occluding plug within the anchoring net aperture, as defined in step (d) of claim 11.

17. The method according to any one of claims 14 to 16, wherein the retrieval of the occluding plug by the delivery system is facilitated by the presence of a retrieval element fitted to said occluding plug, and wherein said retrieval element is selected from the group consisting of an open ring, a closed ring and a hook.

18. The method according to claim 11, wherein the valve being treated is the tricuspid valve.

19. The method according to claim 11, wherein the valve being treated is the mitral valve.

20. The method according to claim 11, wherein the valve being treated is the pulmonary valve.

21. The method according to claim 11, wherein the valve being treated is the aortic valve.