Patent Description:
The present invention relates to a device for treating valvular insufficiency and to a catheter system for delivering the device into a heart. Embodiments of the present invention relate to a device that includes a trans-valvular spacer attached to a non-traumatic anchor positionable within the atrium.

Valvular insufficiency is a cardiac disease characterized by the failure of a cardiac valve to fully close leading to valvular regurgitation or leakage.

Anatomically, the valves are part of the dense connective tissue of the heart known as the cardiac skeleton and are responsible for the regulation of blood flow through the heart and great vessels. Valvular insufficiency due to failure or dysfunction can result in diminished heart functionality and a decrease in blood flow through the body. Treatment of damaged valves may involve medication alone, surgical valve repair (valvuloplasty) or replacement (insertion of an artificial heart valve).

Atrioventricular valvular insufficiency can lead to blood leakage or flow from the ventricle back into the atrium (regurgitation), rather than being forced out of the ventricle upon contraction.

Mitral regurgitation is a common valvular insufficiency and is typically treated via mitral valve replacement or mitral valve repair through open heart surgery or a minimally invasive (percutaneous) procedure. Percutaneous procedures for mitral valve repair include percutaneous mitral valve replacement, enhanced mitral coaptation, edge-to-edge-percutaneous mitral valve repair (plication), percutaneous chordal repair, percutaneous mitral annuloplasty, and left ventricle remolding.

While percutaneous mitral valve replacement/repair is less traumatic to the patient and can be used in patient populations that are not candidates for open heart surgery (due to age or co-morbidities), there are still challenges with delivering, and positioning the implant and with the stability and function of the implant in the heart over extended time periods.

<CIT> describes a heart implant comprising a tubular attachment element for attaching a sheath.

<CIT> describes a method of reducing the risk of clinical sequelae to catheter induced vascular injuries may include introducing a guide wire into a vascular sheath residing in a blood vessel.

<CIT> describes a heart implant comprising an attachment element, particularly a tubular attachment element for attaching a sheath.

<CIT> describes devices for anchoring catheter systems, such as an atrioventricular heart valve regurgitation reduction system with a coapting element or spacer positioned within the atrioventricular valve leaflets.

There is thus a need for, and it would be highly advantageous to have, a device for correcting valvular insufficiency and a system for delivering same devoid of the limitations of presently used approaches.

The invention is directed to a device for treating valvular regurgitation as defined in independent claim <NUM>.

According to the present invention the flexible column is laminated with a polymer sheath.

According to embodiments of the present invention the balloon is bonded to the polymer sheath.

According to embodiments of the present invention the plurality of struts are attached around a proximal end portion of the flexible column.

According to embodiments of the present invention the balloon is fillable with the fluid when the flexible column is mounted over a guidewire.

According to embodiments of the present invention a distal end of the flexible column includes a seal for sealing around the guidewire.

The present invention is of a device which can be used to correct valvular insufficiency. Specifically, the present invention can be used to percutaneously treat valvular insufficiencies by delivering, positioning and anchoring a device that includes a trans-valvular spacer attached to a non-traumatic atrial anchor.

The principles and operation of the present invention may be better understood with reference to the drawings and accompanying descriptions.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details set forth in the following description or exemplified by the Examples.

Implants and approaches for correcting valvular insufficiencies that result from incomplete leaflet coaptation have been described in the prior art. Such devices include atrial or ventricular anchors attached to spacers that are positioned within the valve opening to seal against the native valve leaflets when closed. Such implants are generally effective in sealing against the closed leaflets but are oftentimes delivered or anchored in a manner that is traumatic to heart tissue.

While reducing the present invention to practice, the present inventors have devised an implant and delivery system that address these limitations of prior art devices while providing numerous additional benefits in function and long term stability.

The present invention is characterized by:.

Thus, according to one aspect of the present invention there is provided a device (implant) for treating valvular insufficiency. As used herein, the phrase "valvular insufficiency" relates to any valve leaflet dysfunction that leads to valvular leakage and regurgitation. Valvular insufficiency can be caused by, for example, congenital heart disease, infection, leaflet stenosis, widening or stretching of the valve annulus, chordae rupture, dilated cardiomyopathy or valve prolapse.

The device of the present invention includes an expandable anchor designed for transitioning from a linear configuration (collapsed) to a crown-like configuration (expanded). Such transitioning includes a radial expansion phase in which ends of the anchor curl out away from a center line (of the device) and an inversion phase in which ends of the anchor curl towards the center line. Such a transition between the collapsed and expanded states of the anchor ensures that when expanded in the atrium, the (free) ends of the anchor do not contact the inner walls of the atrium during any stage of expansion.

The device of the present invention further includes a transvalvular spacer attached to the distal end (opposite from delivery side) of the anchor. The spacer can be a solid spacer, a foam spacer or any other spacer that can provide a coaptation surface to valve leaflets (e.g., seal against the leaflets of a valve when closed). An embodiment of a spacer that includes a flexible column enclosed in an inflatable balloon is further described hereinbelow.

In order to enable controlled delivery of the device and maintain control over the anchor when expanded in the atrium, the present device further includes a ball-like graspable element at a proximal end. Such an element is graspable via a grasper and locking sleeve mechanism positioned at a distal end of a delivery catheter.

The ball like graspable element has multiple functions:.

These functions allow the anchor freedom to rotate while remaining axially attached to the delivery system and maintaining the fluid seal. This is of particular importance during delivery as the implant has to navigate bends in the DS which results in implant rotation. It also allows the anchor to rotate within the anatomy to a position of least energy during deployment.

Delivery of the device of the present invention is carried out using a dedicated catheter system (delivery system) having several unique features.

The catheter system includes three co-axial catheters each separately movable longitudinally. The distal end of the middle and outer catheters (also referred to herein as second and third catheters respectively) include the grasper (middle catheter) and locking sleeve (outer catheter) mechanism for grasping and releasing the anchor (and device). The distal end of the middle catheter also includes a seal for sealing against a fluid port positioned in the graspable element of the device. Such a seal enables filling and emptying of the balloon component of the spacer through a dedicated balloon valve that is actuated from the catheter system.

Referring now to the drawings, <FIG> illustrate one embodiment of the present device which is referred to herein as device <NUM>.

<FIG> illustrates anchor <NUM> portion of device <NUM> in the expanded state. Anchor <NUM> includes struts <NUM> that are connected to a central column <NUM>. In the embodiment shown in <FIG>, adjacent struts <NUM>' and <NUM>" of each strut pair (<NUM> pairs shown) follow a parallel path away from central column <NUM> to diverge (branch) at <NUM> and converge (rejoin) at <NUM>. Each strut pair ends in a spoon-like portion <NUM> that includes a pinhole <NUM>. Pinhole <NUM> can be used as attachment points for controlled strut deployment. The spoon-like portion <NUM> of the crown tips is constructed specifically to prevent the leading edge of the crown tip from making contact with the inner lumen of the catheter when the implant is sheathed. The increased surface area of the crown tips (in comparison to the crown arms themselves) is to reduce the likelihood of the tip causing any damage to tissue either during or following deployment.

Struts <NUM> are fabricated from Nitinol or stainless steel by, for example laser cutting a tube or sheet. Struts <NUM> are <NUM>-<NUM> in width and <NUM>-<NUM> in thickness. Anchor <NUM> is <NUM>-<NUM> (e.g., <NUM>) in outer diameter (OD) and <NUM>-<NUM> (e.g., <NUM>) in height when expanded and <NUM>-<NUM> (e.g., <NUM>) in OD and <NUM>-<NUM> (e.g., <NUM>) in length when collapsed.

<FIG> illustrates anchor <NUM> and attached balloon <NUM>. Balloon <NUM> and column <NUM> are collectively referred to herein as spacer <NUM>.

Struts <NUM> are pre-shaped such that when transitioning from a collapsed configuration (linearized within a delivery catheter) to a fully expanded configuration, the ends of struts <NUM> (e.g., spoon-like portion <NUM>) do not contact the inner surface of the atrium.

<FIG> illustrate movement of struts and the ends thereof throughout expansion, spacer <NUM> and balloon <NUM> are also shown in these Figures. When anchor <NUM> first exits the delivery catheter, ends <NUM> of struts <NUM> move radially outward (away from the longitudinal centerline of device <NUM>). At this point, the diameter of partially expanded anchor <NUM> is <NUM>-<NUM> which is far less than that of the atrial space in patients with moderate to severe valvular insufficiency. <FIG> illustrates maximal diameter with ends <NUM> pointed outward (<NUM>-<NUM> diameter), at this stage anchor dimeter is still less than that of the atrium. Further expansion (<FIG>) sees ends <NUM> curl radially inward (towards centerline of device <NUM>) to expand anchor to a final diameter of <NUM>-<NUM> without the risk of ends <NUM> contacting the inner walls of the atrium. In the expansion phases shown in <FIG>, ends <NUM> follow a curved path that corresponds to the radius of curvature of the struts exiting the catheter tip.

Central column <NUM> covers the length of device <NUM> and is configured with lateral flexibility (at a proximal portion <NUM> thereof) to provide a balloon <NUM> (<FIG>) attached thereto with tiltable (angle side-to-side, e.g., like a pendulum) flexibility. This enables a spacer <NUM> (central column <NUM> and balloon <NUM>) to accommodate for asymmetrical leaflet closure and for off centerline anchor <NUM> placement. Central column <NUM> can be a polymer or Nitinol tube with sidewall cutouts <NUM> at proximal portion <NUM> (helical, double helix or a bow-tie shape). Central column <NUM> experiences cyclic axial loading throughout its life cycle due to the cyclic pressure differential between the ventricle and atrium the cutouts allow for flexibility of the central column during delivery but maintains sufficient axial rigidity to prevent buckling when under axial loading. <FIG> illustrates a helical sidewall cutout pattern in proximal portion <NUM> of central column <NUM>. Central column <NUM> can be <NUM>-<NUM> (e.g., <NUM>) in length and <NUM>-<NUM> OD x <NUM>-<NUM> ID (WT = <NUM>) in diameter. An inner lumen <NUM> (<FIG> and <FIG>) running the length of central column <NUM> can be <NUM>-<NUM> in diameter.

Central column <NUM> or a distal portion <NUM> thereof (portion surrounded by balloon <NUM>, <FIG> and <FIG>) is covered with a polymeric (e.g., Carbothane 55D) sheath <NUM> (<FIG> and <FIG>) to which balloon <NUM> is bonded. Distal portion <NUM> of central column <NUM> can include a plug <NUM> for sealing around a guidewire.

Tube <NUM> includes an inward angled tab <NUM> for facilitating access to a valve <NUM> of balloon <NUM> (<FIG> and <FIG>). Valve <NUM> can be a silicone tube stretched over a portion of central column <NUM> that includes an opening into a volume of balloon <NUM>. Valve <NUM> can be opened (forced away from the opening in central column <NUM>) by guiding a valve actuating mechanism <NUM> (e.g., dedicated elongated element <NUM>, <FIG>) through lumen <NUM> (e.g., from the delivery catheter) and under tab <NUM> (<FIG>). Once valve <NUM> is opened, balloon <NUM> can be filled through lumen <NUM> with the distal end plugged with plug <NUM>. Plug <NUM> seals in the presence or absence of a guidewire running through lumen <NUM> and out therethrough.

Proximal end <NUM> of central column <NUM> includes a graspable element <NUM> for securing device <NUM> to a catheter system (further describe hereinbelow).

Graspable element <NUM> (best seen in <FIG>) is designed to be graspable within an actuatable grasper that includes at least two semi hemispherical halves that are configured to cup element <NUM>. Element <NUM> is generally ball-shaped with a flat proximal end <NUM>.

Graspable element <NUM> includes an opening at a proximal end <NUM> and thus also functions as a fluid port for filling balloon <NUM> of spacer <NUM> when device <NUM> is secured to the catheter system.

Balloon <NUM> can be bonded to sheath <NUM> with ends turned outward (as is shown in <FIG> and <FIG>) or alternatively, a distal end <NUM> of balloon <NUM> can be inverted inward and bonded to sheath <NUM> (<FIG>). Such a configuration ensures that potentially traumatic implant edges do not face tissue.

Balloon <NUM> is fabricated from a semi-compliant polymer using approaches well known in the art. Balloon <NUM> can be <NUM> ±<NUM> in parallel length and <NUM> in diameter (when fully inflated). The pressure range for balloon <NUM> can be from <NUM> atmospheres (atm) to <NUM> atm within normal operation.

The wall of balloon <NUM> can be non-permeable or semi-permeable (e.g., permeable to a fluid such as water but not cells). A permeable balloon wall can be used for osmotic filling as is described herein below.

Balloon <NUM> can be filled with a fluid (e.g., saline or an osmotic solution) through the fluid port at graspable element <NUM>. Filling through the port at graspable element <NUM> (through tube valve at <NUM>) is described above and is further described hereinbelow with respect to the catheter system used for delivery of device <NUM>.

Balloon <NUM> can be filled to a final volume and pressure following delivery of device <NUM> (i.e. following expansion of anchor <NUM>). Due to the atraumatic nature of the anchorage system, the device can be fully deployed and the efficacy of the treatment can be assessed immediately. Should the device not result in a satisfactory reduction in regurgitation, the balloon can be deflated and the entire device retrieved into the sheath and removed from the patient.

The efficacy of balloon <NUM> in leaflet coaptation can be tested prior to device implantation. This can be achieved by simply using a similarly sized "off-the-shelf" balloon and advancing it into place along a guidewire across the valve. The clinician can then assess the efficacy of the spacer treatment before using the device. This has the potential to reduce the risk of treating patients who would not respond optimally to a spacer based valve repair.

As is mentioned hereinabove, balloon <NUM> can be semi-permeable to allow for osmotic filling. Balloon <NUM> can be partially inflated with an osmotic solution (e.g., saline contrast solution) having an osmotic potential that is greater than that of blood (e.g., osmolarity of <NUM>-<NUM> milliosmols/L).

The osmotic potential of blood is fixed. Therefore the osmotic potential of the solution used to fill balloon <NUM> will precisely determine the final pressure within the balloon. The osmosis mechanism ensures that the pressure with the balloon is consistent. In addition, the pressure that the balloon is filled with to intraoperatively does not need to be accurate since the osmotic mechanism will account for differences and will reach an equilibrium.

In the months and years leading up to the intervention, the patient's cardiovascular system compensates for deteriorating valve function. When the intervention is carried out, valve function is restored but the cardiovascular system is not accustomed to this change. Therefore, patients undergoing valve repair and/or replacement often suffer from symptoms due to pressure overloading. A potential treatment for this would be to underfill the balloon intraoperatively. In this manner the balloon would only partially improve valve function acutely. This would allow the cardiovascular system to remodel over the following weeks and months as the osmotic action of the balloon slowly increased the internal pressure/diameter which would further improve valve function.

As is mentioned hereinabove, device <NUM> of the present invention is configured for correcting incomplete leaflet coaptation in a heart valve. Device <NUM> can be used for correcting atrioventricular valve coaptation (bicuspid or tricuspid) by delivering device <NUM> using a catheter system. An example would be to treat the tricuspid valve. For this approach, the device would be delivered via a transcatheter approach either from the jugular vein through the superior vena cava or alternatively from the femoral vein and then into the inferior vena cava. In the case of the mitral valve, the preferred approach would be via a transseptal puncture to gain access to the left atrium and therefore the mitral valve.

<FIG> illustrate one embodiment of a catheter system which is referred to herein as system <NUM>.

Catheter system includes <NUM> coaxial catheters, an outer catheter <NUM>, a mid-catheter <NUM> and an inner catheter <NUM>.

Catheter <NUM> includes an elongation compensation mechanism to compensate for the elastic nature of the polymer tubes of the delivery system and the length of the polymer tubes. Because elasticity is determined by percentage, this elastic property can amount to a large change in absolute length at the distal end of catheter <NUM>. The resultant changes in length can cause relative motion between components at the distal end which can be compensated for by spring loading a part of the system.

The compensation mechanism includes two parts, locking cup <NUM> and grasper <NUM>, which act together to grip graspable element <NUM> of device <NUM>. As catheter <NUM> can be under large tensile loads during implant deployment and retrieval, a compression spring (in the handle) is used to allow locking cup <NUM> to maintain its position relative to grasper <NUM>. In this manner locking cup <NUM> and grasper <NUM> stay locked in the closed position at the distal end of catheter <NUM> and graspable element <NUM> of device <NUM> remains securely attached within locking cup <NUM>. An O-ring <NUM> positioned within grasper <NUM> maintains a seal against a front face <NUM> of graspable element <NUM>.

Catheter system <NUM> is used to deliver device <NUM> as follows. Prior to delivery, system <NUM> is prepared on a benchtop sterile area by laying out system <NUM> components and accessories and testing each as well as the overall system. Device <NUM> is removed from packaging and loaded onto catheter system via graspable element <NUM> and pulled into inner steerable catheter <NUM>. Inner steerable catheter <NUM> with sheathed implant <NUM> can then be loaded into outer catheter <NUM>.

In an exemplary trans-septal approach, a jugular vein access is created and an 18F introducer is positioned through the jugular vein access. A femoral vein access is created and a 6F introducer is placed therethrough. A Trans Esophageal Echo (TEE) or Trans Thoracic Echo (TTE) probe is then placed according to standard procedure to assess tricuspid valve functionality. Under fluoroscopy, a compliant <NUM> balloon catheter is inserted through the 18F introducer and advanced to the right atrium, through the tricuspid valve and right ventricle and into the pulmonary artery. A <NUM> (<NUM>") ' guidewire is inserted through the balloon catheter into the pulmonary artery and the balloon catheter is retrieved while holding wire in place. A contrast agent is injected though the 6F introducer to identify chambers outline and the tricuspid valve level. Under fluoroscopy, a <NUM> diameter off-the-shelf balloon catheter is threaded over the wire until the balloon is positioned across the tricuspid valve. The balloon is inflated and the regurgitant flow within the valve is assessed under echocardiography. If a satisfactory reduction in regurgitation is evident, the balloon is retrieved and the procedure is continued, otherwise the balloon is retrieved and the procedure is aborted.

The proximal tip of the guidewire is inserted through device <NUM> and catheter system <NUM>. While maintaining the guidewire stationary relative to the anatomy, system <NUM> is advanced until at approximately the level of mid atrium. The steerable catheters <NUM> & <NUM> can be used to correctly orientate the system relative to the patients anatomy. Once satisfactorily positioned, the tips of anchor <NUM> are expanded into the right atrium under fluoroscopic guidance in a controlled fashion and under continuous echocardiography assessment of valve functionality. Once anchor <NUM> is deployed, leaflet motion and device <NUM> position is assessed under echocardiography and/or fluoroscopy using contrast agent injection through the 6F catheter. If the tricuspid valve shows typical motion the procedure continues otherwise the tips of anchor <NUM> are retracted and repositioned and deployment is repeated.

A <NUM>-<NUM> syringe filled with (<NUM> - <NUM>%) <NUM>% saline/sterile water contrast media solution is attached to the inflation valve/port of balloon <NUM>, the guidewire is retracted just enough to leave the distal plug sealed and balloon <NUM> is then filled under fluoroscopy. As balloon <NUM> approaches its fill volume, cyclic indentations due to the closing valve leaflets should be clearly visible and the balloon is further inflated until the leaflets no longer cause indentations on the balloon and it has reached its nominal diameter. Catheters <NUM> and <NUM> are then retracted such that catheter <NUM> is fully extended to allow maximum implant movement in-situ. Echocardiography is then used to verify the position of balloon <NUM> and efficacy in reducing regurgitation.

If balloon <NUM> is not efficient in reducing regurgitation, device <NUM> is collected and system <NUM> and attached device <NUM> are removed. If the position of device <NUM> is not satisfactory, balloon <NUM> can be deflated via vacuum and device <NUM> can be repositioned.

If device <NUM> position and function is satisfactory, balloon <NUM> diameter and shape are monitored under fluoroscopy while unlocking and retracting the valve actuating mechanism to seal the spacer balloon. Device <NUM> can then be released from catheter system <NUM> and the guidewire and catheter system <NUM> are then removed.

Once anchor <NUM> is positioned in an atrium and balloon <NUM> is inflated, spacer <NUM> of device <NUM> seals against the partially closed valve leaflets during systole (<FIG>) and enables blood flow through the valve during diastole (<FIG>) when the leaflets are fully open.

Additional objects, advantages, and novel features of the present invention will become apparent to one ordinarily skilled in the art upon examination of the following examples, which are not intended to be limiting.

Reference is now made to the following example, which together with the above descriptions, illustrate the invention in a non-limiting fashion.

Animal studies were conducted in order to evaluate the clinical safety and performance of the present device and delivery system in a healthy swine model in a chronic setting. The device was implanted in <NUM> animals with follow-up periods of <NUM> days.

The objectives of the animal studies were to evaluate safety and sizing of the device.

Implant delivery and placement was performed in each of the animals using the steps described hereinabove. Histopathological results and long term clinical results were used to demonstrate the safety of the system.

The <NUM> animals were monitored via angiographic imaging at <NUM> week, <NUM> month, <NUM> month and <NUM> month post procedure. The animals were sacrificed following the last monitoring stage. Thorough evaluation of the treated animals revealed no clinically significant device related effects. The implant was intact and well positioned.

Post animal sacrifice the heart was explanted and sent to histology analysis to evaluate safety parameters such as structural impairment, tissue growth, thromboses and the like.

Claim 1:
A device (<NUM>) for treating valvular regurgitation comprising:
(a) an expandable anchor (<NUM>) including a plurality of struts (<NUM>) designed for transitioning from a linear configuration when trapped within a delivery tube to a crown-like configuration when released from said tube, said transitioning includes a radial expansion phase in which ends of said struts curl out away from a center line of said crown-like configuration and an inversion phase in which ends of said struts curl towards said center line of said crown-like configuration; and
(b) a transvalvular spacer (<NUM>) configured for providing a coaptation surface to valve leaflets and being attached to said expandable anchor (<NUM>), said transvalvular spacer (<NUM>) including a flexible column (<NUM>) enclosed in an inflatable balloon (<NUM>), said flexible column is laminated with a polymer sheath, said polymer sheath includes an opening covered by a tube valve (<NUM>), said balloon is fillable with a fluid through said tube valve, wherein said flexible column (<NUM>) includes a tab (<NUM>) for guiding an actuating mechanism to said tube valve (<NUM>).