Cardiac valve ablation catheter

Abstract

Cardiac annuloplasty methods and devices are based on delivering tissue ablation energy to a cardiac valve annulus, thereby inducing a reduction in the circumference of the annulus. In some embodiments, the reduction is induced by tissue contraction in response to the ablation, potentially similar to the tissue contraction involved in pulmonary vein stenosis induced by cardiac ablation to treat atrial fibrillation. In some embodiments, the annulus tissue is deformed before the ablation energy is applied, potentially resulting in plastic deformation separate from the tissue contraction. The deformation is performed using electrodes, which optionally also operate as sharp-tipped jaws of pliers, inserted into the tissue in a more widely spaced configuration, reduced in distance to a more closely spaced tissue-compressing configuration, and manipulated to ablate the compressed tissue. Upon removal of the electrodes, the compressed tissue retains its new shape as a result of the ablation-induced plastic deformation.

Description

Technical Field

[0001] [Related Applications] This application claims the benefit of priority under 35 USC § 119(e) to U.S. Provisional Patent Application No. 63 / 111,033, filed on November 8, 2020, the content of which is hereby incorporated by reference in its entirety.

Background Art

[0002] In some embodiments, the present invention relates to the field of structural heart disease, and more particularly, but not limited to, cardiac annuloplasty.

[0003] Patients suffering from insufficient cardiac valve function (e.g., of the mitral valve) may undergo implantation of an annuloplasty ring sutured to the fibrous ring tissue of the cardiac valve. The purpose is to reduce and / or stabilize the circumference of the valve. The procedure can be performed as an open-heart surgery or with some devices via an endovascular (trans-catheter) approach.

[0004] As the circumference of the valve is reduced, the valve leaflets come closer together, thus achieving a better seal (junction) to reduce or eliminate valve regurgitation.

Summary of the Invention

Means for Solving the Problems

[0005] According to one aspect of some embodiments of the present disclosure, there is provided a method of performing a cardiac annuloplasty procedure, including delivering energy around a cardiac valve in an amount sufficient to structurally disrupt tissue and induce contraction around the annulus to reduce regurgitation through the cardiac valve.

[0006] According to some embodiments of the present disclosure, the structural disruption of tissue includes a change to the fibrous structure of the tissue.

[0007] According to some embodiments of the present disclosure, the energy disrupts the tissue while the tissue of the cardiac annulus is in its mechanically deformed state.

[0008] According to some embodiments of the present disclosure, mechanically deforming includes compressing tissue.

[0009] According to some embodiments of the present disclosure, compressing tissue includes piercing the tissue with at least one sharp element and manipulating the sharp element to apply compression.

[0010] According to some embodiments of the present disclosure, at least one sharp element also includes an element used to deliver structural disruption energy to the tissue.

[0011] According to some embodiments of the present disclosure, the element is an electrode.

[0012] According to some embodiments of the present disclosure, the electrode disrupts the tissue structure by transmitting RF energy into the tissue.

[0013] According to some embodiments of the present disclosure, the electrode disrupts the tissue structure by inducing cell death.

[0014] According to some embodiments of the present disclosure, the electrode disrupts the tissue structure by coagulation.

[0015] According to some embodiments of the present disclosure, compressing includes sandwiching the tissue between a plurality of at least one sharp element.

[0016] According to some embodiments of the present disclosure, compressing includes applying torsion to the tissue using at least one sharp element.

[0017] According to some embodiments of the present disclosure, the reduction around the valve annulus includes tissue contraction as a result of delivery of tissue ablation energy.

[0018] According to some embodiments of the present disclosure, the reduction around the valve annulus includes plastic deformation of the tissue as a result of the delivery of tissue ablation energy while the tissue is mechanically deformed.

[0019] According to some embodiments of the present disclosure, delivering tissue ablation energy includes delivering high-frequency energy into the tissue punctured through the electrode.

[0020] According to some embodiments of the present disclosure, delivering tissue ablation energy includes delivering high-frequency energy into the tissue contacted through the electrode.

[0021] According to some embodiments of the present disclosure, the tissue ablation energy is provided by at least one of the group consisting of high-frequency energy, focused ultrasonic energy, and cryogenic cooling.

[0022] According to some embodiments of the present disclosure, the tissue to be resected includes at least one of the group consisting of the fibrous tissue of the valve annulus and the tissue of the heart wall adjacent to the fibrous tissue of the valve annulus.

[0023] According to some embodiments of the present disclosure, the valve annulus is the valve annulus of the mitral valve or the tricuspid valve.

[0024] According to some embodiments of the present disclosure, the method includes repeating the delivery of tissue ablation energy at a plurality of sites along the perimeter of the heart valve annulus.

[0025] According to some embodiments of the present disclosure, the method includes selecting a patient having an enlarged heart valve perimeter, planning a targeted reduction around the heart valve annulus including selecting locations along the heart valve annulus targeted for reduction during systole, and delivering energy at each of the selected locations.

[0026] According to some embodiments of the present disclosure, at least a portion of the systole occurs during a heart valve annuloplasty procedure.

[0027] According to some embodiments of the present disclosure, at least a portion of the shrinkage occurs after a cardiac annuloplasty procedure.

[0028] According to one aspect of some embodiments of the present disclosure, a method of performing cardiac annuloplasty is provided, the method comprising piercing tissue along the perimeter of a cardiac valve using at least one electrode, applying a mechanical force to the at least one electrode to deform the pierced tissue and reduce the perimeter of the cardiac valve, delivering tissue ablation energy through the electrode to thereby induce plastic deformation of the deformed tissue, and releasing the mechanical force to leave a cardiac valve annulus having a reduced perimeter.

[0029] According to some embodiments of the present disclosure, applying the mechanical force includes applying torsion to the pierced tissue.

[0030] According to some embodiments of the present disclosure, applying the mechanical force includes compressing the pierced tissue.

[0031] According to some embodiments of the present disclosure, the tissue ablation energy is high-frequency energy.

[0032] According to some embodiments of the present disclosure, delivering the tissue ablation energy induces plastic deformation by coagulation.

[0033] According to some embodiments of the present disclosure, the reduced perimeter draws the valve leaflets of the cardiac valve into a position that reduces backflow of the valve.

[0034] According to some embodiments of the present disclosure, reducing the backflow includes repairing the junctions between the valve leaflets of the cardiac valve.

[0035] According to some embodiments of the present disclosure, the plastic deformation includes shrinkage of the deformed tissue.

[0036] According to one aspect of some embodiments of the present disclosure, there is provided an apparatus for valve formation treatment, comprising a catheter sized to be inserted transvessularly from a percutaneous incision into a heart chamber and reach the heart valve annulus thereof, and at least one tissue penetrating element at a distal end of the catheter, wherein at least one penetrating element moves relative to a body of the catheter and acts to deliver tissue destruction energy to the penetrating tissue of the heart valve annulus.

[0037] According to some embodiments of the present disclosure, at least one penetrating element comprises a plurality of penetrating elements whose relative distances are adjustable while being inserted into the tissue of the heart valve annulus.

[0038] According to some embodiments of the present disclosure, each of at least one tissue penetrating element is an electrode that is electrically interconnected to a connection portion remaining outside the percutaneous incision when the catheter is inserted into the heart chamber.

[0039] According to some embodiments of the present disclosure, each of the plurality of penetrating elements operates as an ablation electrode.

[0040] According to some embodiments of the present disclosure, the penetrating elements are inserted into the tissue at a relatively wide distance and are spaced apart to be adjusted to a narrower distance.

[0041] According to some embodiments of the present disclosure, the relative distance of the penetrating elements is adjusted by rotation of a gear.

[0042] According to some embodiments of the present disclosure, the gear is rotated by a control element leading to the proximal side of the catheter.

[0043] According to some embodiments of the present disclosure, the control element also acts to provide an electrical interconnection between at least one of the tissue penetrating elements and a power source remaining outside the percutaneous incision.

[0044] According to some embodiments of the present disclosure, the relative distance of the penetrating elements is adjusted by a temperature change of an actuator including a shape memory alloy.

[0045] According to some embodiments of the present disclosure, the shape memory alloy is arranged such that a temperature change is induced by heating as a result of its operation as an electrode of the through element.

[0046] According to some embodiments of the present disclosure, the shape memory alloy is shaped to move the through element from an initial distance to a relatively narrow distance when heated.

[0047] According to some embodiments of the present disclosure, the device includes a device reset operable to restore the distance of the through element prior to the temperature change while the device remains inserted in the heart chamber.

[0048] According to some embodiments of the present disclosure, the device includes an inner component that terminates distally within an energy delivery segment and is housed within an outer tube, the outer tube being sized for insertion from within a guide catheter into a heart chamber, the outer tube having a predetermined distal bend that is assumed when not restricted by the guide catheter and becoming straight when the outer tube is retracted into the guide catheter.

[0049] According to some embodiments of the present disclosure, at least one through element has a non-circular cross-section that engages the tissue into which it is inserted and induces torsion therein when subjected to torque applied via a catheter.

[0050] According to some embodiments of the present disclosure, the device has an inner component that terminates distally within a tissue ablation segment and is housed within an outer tube, the outer tube being sized for insertion from within a guide catheter into a heart chamber, the outer tube having a predetermined distal bend that is assumed when not restricted by the guide catheter and becoming straight when the outer tube is retracted into the guide catheter.

[0051] According to some embodiments of the present disclosure, the non-circular cross-section includes a rectangular blade.

[0052] According to some embodiments of the present disclosure, the non-circular cross-section includes three or more blades extending radially from a central axis.

[0053] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present disclosure, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

Brief Description of the Drawings

[0054] Some embodiments of the present invention are described by way of illustration only with reference to the accompanying drawings. Referring now to the drawings in detail, it is emphasized that the specific matters shown are illustrative and for the purpose of describing embodiments of the present invention. In this regard, the description using the drawings will clarify to those skilled in the art how embodiments of the present invention can be implemented.

[0055]

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[0056] In some embodiments, the present invention relates to the field of structural heart disease, and more particularly, but not limited to, cardiac annuloplasty.

[0057] **Summary** One aspect of some embodiments of the present disclosure relates to annuloplasty performed using tissue contraction and / or remodeling induced by energy applied to an area of an annular ring of a valve.

[0058] Currently, the gold standard of care for treating atrial fibrillation is the use of RF energy to ablate an area along the left atrial wall around the pulmonary veins. A reported side effect of this procedure is pulmonary vein stenosis (PVS).

[0059] PVS can also be the result of ablation procedures performed using other methods, such as cryoablation (as reported, for example, by J. Matsuda et al., J Cardiovasc Electrophysiol. 2017 Mar;28(3):298 - 303. Pulmonary vein stenosis after second - generation cryoballoon ablation).

[0060] PVS is caused by contraction of the pulmonary veins induced by contraction of the ablated tissue area. The physiological mechanism by which ablation causes stenosis in the pulmonary veins is due to scarring of the connective tissue surrounding the pulmonary veins, as described, for example, by Vincent JA et al., Circ Arrhythm Electrophysiol. 2014 Aug;7(4):734 - 8. Pulmonary vein stenosis after catheter ablation, electroporation versus radiofrequency.

[0061] The inventors herein describe an intravascular approach that uses the phenomenon of tissue contraction induced by applying structural disruption energy to treat cardiac valve leakage. Leakage is characterized by an incomplete junction of the valve leaflets of a cardiac valve and does not close completely in response to backpressure. This allows blood flow reversal and impairs the efficiency of pumping by the heart.

[0062] In some embodiments of the present disclosure, the tissue around the valve annulus is reconstructed by the application of structural disruption energy. In some embodiments, this includes energy sufficient to cauterize the tissue. Cauterization may directly damage (lesion) the valve annulus tissue (i.e., ablation damage to the fibrous tissue of the valve annulus), and / or damage adjacent tissue, such as the atrial wall over the mitral or tricuspid valve.

[0063] Ablation induces contraction and a corresponding reduction throughout the circumference of the valve annulus. This can potentially reduce the severity of regurgitation by bringing the leaflets of the heart valve in regurgitation into a coaptation state, or reducing the remaining gap between them in their most closed state if coaptation is not achieved. In some cases, the initial loss of normal leaflet coaptation was itself caused by remodeling (elongation) of the valve annulus. Thus, treatment to contract the valve annulus may return the heart valves to their original relationship to each other.

[0064] As used herein, reference to "ablation" of tissue refers to the delivery of structural disruption energy to the tissue that induces at least cell death in the tissue while generally maintaining the integrity of the tissue's connective structure (although it may be altered). Further, within the context of the embodiments described herein, the ablation performed has at least one of the following two: · The ablated tissue contracts. · The ablated tissue is plastically remodeled into a shape that is affected by mechanical forces applied to the tissue during and / or after ablation.

[0065] Without being committed to a particular theory, these effects can result, for example, from loss of cell structure, relaxation of internal stresses on the connective fibers, the effect of denaturation (coagulation) on the tissue structure that persists after ablation, and / or the effect of the healing process that occurs after ablation.

[0066] Shrinkage can include effects that occur immediately or almost immediately (e.g., due to loss of body fluid or shrinkage of cellular components), as well as slower effects, e.g., due to induced atrophy and / or the healing process.

[0067] In some embodiments, the application of structural disruption energy is optionally sub-ablation. For example, the fibrous structure of tissue can be made more malleable by heating and / or by adjusting its pH by passing an electrolytic current. The structural disruption that results in this malleability can be induced simultaneously with or separately from tissue shrinkage.

[0068] The effects of plastic remodeling under mechanical forces described in the embodiments herein are generally acute, i.e., they occur during the application of structural disruption energy or during a subsequent period while the procedure of using a tool to apply mechanical force is in progress. Without commitment to a particular theory, these acute effects can be understood to be influenced by the disaggregation effect of coagulation that acts to relieve stress and / or strain in the tissue deformed by the external mechanical force. This effectively gives the tissue a new "preferred shape" that is in a coagulated state even after the external mechanical force has been removed (i.e., plastically deformed). When applying structural disruption energy to tissue deformed by an external force, it is not excluded that there may be non-coagulation mechanisms that affect plastic deformation. For example, a mechanism has been proposed in which electrolysis of water in the tissue region results in the production of free protons, which temporarily affects the self-association of the collagen matrix, resulting in the collagen matrix becoming more malleable.

[0069] Two major types of ablation performed on heart tissue to treat atrial fibrillation are, for example, thermal ablation using radiofrequency (RF) energy or ultrasonic energy, and cryoablation. Both types of ablation are associated with pulmonary vein stenosis. However, as a result of the differences between the two mechanisms, there may be differences in tissue remodeling effects. For example, the thermal ablation effect involves coagulation that acts directly on the structural cell components, while the main effect of cryoablation is to disrupt the cellular tissue and processes that potentially lead to downstream degeneration of the structural cell components under biological control. Electroporation is another cellular ablation mechanism that is mainly destructive in its initial effect rather than denaturation (coagulation). Tissue electrolysis has also been proposed as a mechanism for disrupting the collagen matrix by partially acidifying it.

[0070] In some embodiments, valvuloplasty performed by structural disruption of tissue reduces the perivalvular area by about 5-10%. The remodeling of the valve annulus can target the site of any selected portion around the valve annulus, for example, by disrupting tissue at approximately evenly spaced locations or, alternatively, by disrupting tissue at locations grouped in one or more specific regions of the perimeter.

[0071] One aspect of some embodiments of the present disclosure relates to methods and devices for applying structural disruption energy to mechanically deform tissue while contracting and / or making the tissue more malleable. In some embodiments, the tissue is deformed by the application of mechanical force. In some embodiments, the deformation is used to affect the tissue remodeling effect of ablation or the sub-ablation application of structural disruption energy to perform valve annulus formation.

[0072] The effects of mechanical tissue deformation can be distinguished from the effects of structural damage energy delivery as long as the mechanical tissue deformation (when applied without additional structural damage energy) reverses when the mechanical force that induces it is removed. In other words, mechanical tissue deformation is elastic by itself, while the application of structural damage energy "plasticizes" the tissue, making it malleable into a new non - elastically reversible shape by the deformation, and / or directly induces plastic deformation in the tissue. References herein to "disruption" of tissue refer to non - elastic structural disruption of the tissue, with or without cell death. It should be understood that the disruption referred to is a partial disruption that modifies but maintains the overall structural integrity of the tissue.

[0073] (RF ablation and / or application of current, etc.) Modalities that supply structural damage energy to tissue can induce remodeling of the tissue deformed by mechanical force into a new shape that persists when the mechanical force causing the tissue deformation is removed. This type of plastic deformation is different from plastic deformation due to shrinkage of ablated tissue, and both effects can occur.

[0074] In some embodiments, the mechanical force is applied by compressing the tissue between a plurality of laterally separated elements. Each of these is also referred to herein as a "jaw" and is also referred to herein as operating together as a tissue plier. The jaws have a cross - section, for example, with a maximum width of less than 0.2 mm, less than 0.4 mm, less than 0.8 mm, or less than 1 mm (e.g., 0.4 mm×0.4 mm cross - section) and a length of about 1 - 10 mm, e.g., 2 mm, 3 mm, or 4 mm, sized for the operation of a valve annulus. The maximum distance between the jaws can be, for example, in the range of about 2 - 10 mm, e.g., 2 mm or 4 mm.

[0075] Joe of the tissue pliers may be applied to the tissue surface or may pierce the tissue surface. As Joe moves towards each other, the tissue is compressed, and as a result, its shape is deformed. The energy applied to the tissue in this state (e.g., in the form of heating, cooling, and / or formation of electrical energy) tends to relieve the internal forces of the deformed shape as the tissue components are changed, e.g., coagulated and / or dissociated.

[0076] Joe of the tissue pliers is optionally actuated by a rotational movement commanded through a wire or shaft that connects the tissue pliers through a catheter to a control actuator remaining outside the body (e.g., outside a percutaneous incision where a catheter is inserted). For example, a rack and pinion arrangement can convert the rotation of a pinion gear into a linear movement of Joe. Alternatively, Joe is connected by a bond to a central member that is rotated by a wire or shaft and is spring-loaded so that it remains separated until the central member rotates, winding the bond shorter and bringing Joe together.

[0077] In some embodiments, the movement of Joe is automatically induced by heating of the device during its operation to deliver energy to the target tissue. This may be embodied, for example, using a shape memory alloy spring that is initialized in a first state (e.g., a Joe-separated state) while being soft and below its transition temperature. The preset shape of the spring in the superelastic state (above the transition temperature of the alloy) is selected to drive Joe to a closer position. After cooling, the device can be reset, for example, by using a reshaping device such as a wedge. Alternatively, a second elastic member may be provided, which is weaker than the shape memory alloy spring when the shape memory alloy spring exceeds its transition temperature but stronger when the shape memory permissive spring is below its transition temperature.

[0078] Additionally or alternatively, in some embodiments, mechanical force is applied by inducing torsion (twisting) in the tissue region. The torsion can be applied by twisting a plier engaged with the tissue (effectively using it as a wrench such that the plier jaw doubles as a wrench jaw). In another wrench-like configuration, a plurality of fixed jaws (not used as pliers as they are fixed) can be re-engaged with the tissue (e.g., by piercing it). By twisting these jaws around a common center, torsion is induced in the surrounding tissue.

[0079] Optionally, a single rod-like element is used as a wrench for applying torsion to the surrounding tissue. This can include an element for piercing the tissue and has a cross-sectional profile such that a portion of its surface is pressed against the tissue when the single element is rotated. This can result from some portions of the cross-sectional profile having adjacent regions around the perimeter at a rapidly exaggerated relative radial measurement distance from the center of the cross-sectional profile (i.e., a rapid transition from wider to narrower). A narrow rectangular cross-section (e.g., blade-like) provides an example. Since the tissue is somewhat elastic, there may be a limit to the blade torque force sufficient to rotate the blade without dragging the tissue along with it before the opening opens. Related cross-sectional shapes that can be used are cross-sectional or star shapes (e.g., having three, four, or more blades radiating from a common central axis, and flat blades can be considered to have two blades each radiating from a common center). This can allow for somewhat higher torque levels before slippage occurs. The maximum diameter of the portion of the device inserted into the tissue can be, for example, about 2 - 6 mm.

[0080] In some embodiments, delivery of the structural disruption energy is performed using at least one of the same elements comprising the plier and / or wrench jaw, e.g., one or more of the jaws also operate as ablation electrodes.

[0081] Energy may alternatively be performed by an energy delivery element (e.g., an electrode of an electrode probe, a focused ultrasound probe, or a cryoablation probe) disposed over or within tissue deformed by another tool. This provides potential advantages by allowing the region of highest applied force to be optionally separated from the region receiving the highest energy. The region receiving the most structurally disruptive energy may also be the region that is thereby weakened the most, which weakening can result in unintended tearing.

[0082] Before detailing at least one embodiment of the present disclosure, it is to be understood that the present disclosure is not necessarily limited to the details of the construction and arrangement of components and / or methods described in the following description and / or shown in the drawings in its application. Features described in this disclosure, including features of the invention, may be embodied in other embodiments or may be implemented or carried out in various ways.

[0083] Background Reference is now made to FIGS. 1A and 1B, which are flowcharts schematically illustrating a method of cardiac annulus treatment according to some embodiments of the present disclosure. The operations of the blocks of FIGS. 1A and 1B are substantially the same except that FIG. 1B adds block 111 for the operation of deforming the annulus tissue.

[0084] In block 110, in some embodiments, an energy delivery tool (e.g., an ablation electrode or other probe capable of delivering structurally disruptive energy) is placed at a predetermined location along the perimeter of the annulus. This location includes contact with the annulus tissue, which contacted annulus tissue is tissue to be contracted as part of an annuloplasty procedure intended to improve valve function by reducing the entire perimeter of the annulus.

[0085] The energy delivery tool may comprise, for example, an electrode configured to deliver radio frequency (RF) energy to tissue, a focused ultrasound transducer, or a cryoablation probe. Examples of ablation systems are described, for example, in connection with FIGS. 2A, 2B, and 30. Other figures illustrate embodiments of probes used to deliver structural disruption energy. FIGS. 3 - 8D and 29 in particular show probes with degrees of control that allow access to different portions around the valve annulus by contact with the energy delivery portion (e.g., the electrode) of a catheter.

[0086] The placement of block 110 may include positioning one or more electrodes on the tissue targeted for modification and / or inserting one or more electrodes into the tissue targeted for modification. FIGS. 9 - 20 show different electrode probe designs, some of which are inserted into tissue, some of which rest on tissue, and some of which combine two different electrodes and / or electrode portions.

[0087] In block 111, in some embodiments (FIG. 1B), the tissue targeted for modification (e.g., around the valve annulus) is mechanically deformed. In some embodiments, this is accomplished by manipulating the position of one or more electrodes already inserted into the target tissue in block 110. For example, the electrodes can be squeezed together, and the tissue between them can also be squeezed. Preferably, the electrodes are oriented (e.g., substantially tangentially with respect to the valve annulus) and squeezing them together shortens the circumference of the valve annulus. Additionally or alternatively, the electrodes are rotated (individually and / or as a group) to distort the tissue such that the distance along the valve annulus is shortened.

[0088] FIGS. 21A - 28, 31A - 32, and 35A - 37C show probes operable to deform target tissue by squeezing the target tissue between two electrodes. FIGS. 33 - 34D illustrate probes with electrodes that can be rotated to deform the target tissue.

[0089] In block 112, in some embodiments, the tissue undergoes ablation by application of a structural disruption, such as radio frequency (RF) energy, or another structural disruption energy provided by a probe. Optionally, the operations of blocks 112 and 111 are performed at least partially simultaneously. In some embodiments, as the energy delivery progresses, the tissue may be partially "plasticized," enabling more movement by mechanical deformation. In some embodiments, the heating induced by the delivery of structural disruption energy is also used to drive the induced mechanical deformation, for example, by using a probe that includes a shape memory alloy that activates to move a heating electrode when it itself is heated above its transition temperature.

[0090] Using the same member to mechanically deform and structurally disrupt the tissue has potential advantages for simplifying the structure and / or operation of the device. In this case, at least one of the electrodes can also act as a piercing element, which can then be a jaw that acts to stretch and / or compress the tissue and / or is rotated to twist the tissue.

[0091] However, in the method of FIG. 1B, it is not particularly limited that the mechanical distortion of the tissue is performed by the same electrode used to deliver the structural disruption energy. For example, pliers operated through a catheter different from the catheter to which the structural disruption energy is applied can be used to collect the tissue. In this case, the application of the structural disruption energy can be performed using, for example, either a surface contact electrode or an electrode that penetrates (pierces) the tissue itself.

[0092] In some embodiments, Joe the player who deforms the tissue is inserted into the tissue at a location outside the target zone of structural disruption and is compressed to deform the tissue including the target zone itself, and then energy is applied to structurally disrupt the tissue within the target zone. This has the potential advantage of concentrating mechanical forces on healthy, rather than potentially weakened by the application of structural disruption energy, tissue.

[0093] Referring now to FIG. 2A, which schematically shows an electro-monopolar ablation system 90. Also refer to FIG. 2B, which schematically shows a bipolar ablation system 91. Ablation systems of this general type are known to be used in ablating heart tissue for the treatment of heart conditions such as atrial fibrillation.

[0094] The method of FIG. 1 is optionally performed using an RF ablation electrode as known in the art, such as an RF ablation electrode configured as generally described in connection with FIGS. 2A-2B.

[0095] In some embodiments, ablation systems 90, 91 include an RF generator 71 configured to generate radio frequency (RF) energy for use in performing ablation and to define parameters of the RF energy, such as its voltage and / or current, and / or the amplitude, frequency, and / or pulse shape of the delivered RF energy.

[0096] The RF generator 71 is electrically connected (wired connection) to the ablation catheter 100. The ablation catheter 100 includes an ablation electrode 101, and the ablation RF energy is delivered to the target tissue via a conductor 74, and the ground is through an electrical interconnection with a conductive (e.g., metal) ground electrode 72 (FIG. 2A), or a secondary catheter electrode 101B (and conductor 75; FIG. 2B). The ground electrode 72 may include, for example, a plate placed under a reclining patient during a medical procedure; or one or more conductive pads attached around the patient's arm / hand, for example.

[0097] The RF systems of FIGS. 2A-2B are described as an example of equipment that can be used to perform valvuloplasty. Ablation can be performed using another system that induces tissue scarring, for example, via cryoablation, or thermal ablation using focused ultrasound. Optionally, the RF systems of FIGS. 2A-2B are operated in a sub-ablation mode that disrupts the tissue structure without necessarily inducing cell death.

[0098] Referring now to FIGS. 3-5, which schematically illustrate the distal element of the steerable catheter 301 (optionally, an example of the RF ablation catheter 100, or an ablation catheter using another type of ablation energy, such as a cryoablation catheter or a focused ultrasound ablation catheter) used to deliver structural disruption energy according to some embodiments of the present disclosure.

[0099] In some embodiments of the system used to perform the method of FIG. 1, catheter steering is provided to assist in guiding the energy delivery probe to contact a portion of the valve annulus targeted for structural modification. It can be appreciated that the steering angles required can be acute, especially when relatively limited space is provided compared to most of the target area. Further, the steering angle can preferably be selected such that the catheter approaches the target surface area at a perpendicular or nearly perpendicular angle. This makes it easier to establish a reliable contact surface and / or pressure that enables the transmission of RF energy, and at the same time, reduces the tendency for the probe to "slip" along the target surface when the two meet at a more oblique angle. Additionally, the presence of stiffness in the steering system steering that provides a firm and reliable contact with the target tissue is a potential advantage.

[0100] FIGS. 3 - 5 show elements of how such a steering system having such characteristics can optionally be provided in some embodiments of the present disclosure.

[0101] FIG. 3 shows, for example, the distal portion of an outer tube 200 made of an electrically insulating material (e.g., PTFE, Pbax, or another electrically insulating material). Its distal tip 201 is pre - formed to take relatively sharp bends, e.g., bends of at least 70°, 90°, 145°, or 180° when unrestrained. Optionally, the distal tip 201 comprises a spring element, such as a nitinol strip / element (completely covered inside the wall of the outer tube 200), to increase its elastic and / or mechanical stiffness properties.

[0102] Additionally or alternatively, the outer tube 200 includes an articulation mechanism, e.g., an embedded traction wire that slides through a lumen inside the wall of the outer tube 200 and is rigidly connected to its tip, thus enabling control of the articulation angle.

[0103] Figure 4 shows the internal component 300. In the example of Figure 4, the internal component 300 is used for RF delivery of structural disruption energy. The illustrated example of the internal component 300 includes a metal / alloy conductive component 320 (made of, for example, stainless steel, nitinol, or another metal). The conductive component 320 is covered by an insulating layer 310 (made of, for example, PTFE, PEEK, polypropylene, polyamide, polyimide, Pbax, or another electrical insulating material), leaving at least a distal exposed region 320A acting as a source for transmitting RF energy exposed. The electrical interconnection (for example, with the RF generator 71) is made via a connector 330. The internal component 300 is optionally structured to be suitable for another energy type, for example, it may be a cryoablation catheter or a focused ultrasound ablation catheter. Other designs of the internal component 300 for use in RF ablation of tissue are described, for example, in connection with Figures 9 - 20.

[0104] Figure 5 shows a catheter 301 having an inner component 300 slidably disposed within an outer tube 200. When the inner component 300 is connected to an RF generator (using the connector 330), its distal tip is activated, and as a result, the target location can be disrupted. Other inner component types may be connected to different sources of disruptive energy and / or materials, for example, cryogenic fluid in the case of a cryoablation catheter or an ultrasound transducer control unit in the case of a focused ultrasound ablation catheter.

[0105] The material of the distal tip 201 is rigid enough to deflect the internal component 100, but is sufficiently elastic and flexible so that it can be reversibly straightened itself, for example, when being slidably withdrawn into the guide catheter 302 (as shown in FIGS. 6-7 for example). As the distal tip 201 is released from confinement (for example, by advancement from the guide catheter 302), it resumes its pre-formed bend. In some embodiments, the curvature diameter of the distal tip 201 is 10-35 mm. In some embodiments, the curvature begins approximately 3-15 mm proximal to the tip.

[0106] Now refer to FIGS. 6-7 which schematically show the manipulation of the catheter 301 within the cardiac chamber (left atrium 50) according to some embodiments of the present disclosure. Further, refer to FIGS. 8A-8D which schematically show additional configurations of the catheter 301 from various ones that enable delivery of structural disruption energy at any position along the valve annulus.

[0107] FIG. 6 shows the catheter 301 inserted into the left atrium through a guide catheter 302 (disposed within the septum). By the linear and rotational movement of the outer tube 200, and the linear movement of the inner component 300, the physician can position the energy delivery segment 602 (which can be, for example, the conductive component 320) against the target tissue (such as the valve annulus or the atrial / myocardial wall) and activate it to disrupt the tissue. In some embodiments (as described in relation to FIGS. 9, 14, and / or 18 for example), the physician can also rotate / torque the inner component 200 when the inner component 200 has a spiral or drill-like tip shape that enables intracorporeal disruption.

[0108] Thereafter, the physician can direct the energy delivery segment to another position on the valve annulus (as shown in FIG. 7) and disrupt its structure.

[0109] By controlling / positioning the outer tube 200 and the inner component 300, a physician can reach any position along the valve annulus and destroy it. FIGS. 8A-8C show the configuration of the catheter in other states of sheath detachment: · Completely unsheathed (FIG. 8A), so the outer tube 200 rotates, for example, a full 90°. Optionally, another completely unsheathed angle is configured. For example, the example of FIG. 8D shows an outer tube 200 that bends a full 180° when not sheathed from the guide catheter 302. By bending the outer tube 200, the distal opening 202 of the outer tube 200 is also reoriented to a new angle with respect to the longitudinal axis of the distal portion of the guide catheter 302. · Partially unsheathed (FIG. 8B), allowing partial deflection (e.g., diagonal, but if the maximum bend angle is greater than 90°, the partial deflection can be a 90° deflection) of the outer tube 200 away from the longitudinal axis of the tip of the guide catheter 302. · Completely sheathed or nearly completely sheathed (FIG. 8C) such that the distal opening 202 remains oriented perpendicular to the longitudinal axis of the tip of the guide catheter 302.

[0110] Referring now to FIGS. 9-20, which schematically illustrate an alternative design of the inner component 300 for use with an RF ablation system according to some embodiments of the present disclosure. In some embodiments, the design of the internal component 300 described in connection with FIGS. 9-20 is provided as an alternative implementation of the energy delivery electrode 100 in the system of FIGS. 2A-2B.

[0111] In summary, each of the examples of FIGS. 9-10 shows at least an inner component 300 having one or more conductive components 320 that can be attached to RF power by respective connectors 330, 331. Over most of their length, the conductive components 320 are covered by an electrical insulator 310 and optionally include one or more polymeric tubes of a lumen and / or an electrical insulating coating. The designs shown differ from each other in details such as how the conductive components 320 are terminated at their tips (which are in each case the electrodes to which the RF energy is delivered), how many conductive components 320 are provided, and / or how they are arranged. In addition to the specific combinations shown, the illustrated features can be combined from different embodiments as long as they are compatible with each other. For example, different tip types (e.g., helical tip, conical tip, screw tip, blunt tip, and round tip) can be provided in any combination for the conductive components 320 (e.g., monopolar, bipolar coaxial, and bipolar non-coaxial).

[0112] In FIG. 9, the inner component 300 includes a helical tip portion 302 that can be attached to RF power by a monopolar connector 330 via a conductive component 320.

[0113] Rotating the inner component 300 while advancing it screws the helical tip portion 302 into the target tissue (e.g., into the connective tissue of the valve annulus). This may be performed as a preliminary to ensure stable contact and / or deeper scar penetration before ablation is performed by supplying RF energy through the helical tip portion 302. Optionally, the helical tip portion 302 is sharp to facilitate entry into the target position (e.g., by engaging the tissue and then rotating the inner component 300 relative to the outer tube 200).

[0114] Optionally, the inner component 300 includes a distal surface 340 that limits the depth of penetration of the energy delivery tip (e.g., tip 302 of FIG. 9) into the target tissue. The distal surface 340 is also shown in each of FIGS. 10 - 15 and 17 - 20 and serves the same depth - limiting function for electrode tips that are intended to penetrate tissue to at least a certain depth.

[0115] FIG. 10 schematically shows a monopolar inner component 300 having a distal tip 305 that is sharp and can penetrate linearly into tissue.

[0116] FIG. 11 schematically shows a bipolar inner component 300 with two electrodes 308, 309 at the tip.

[0117] FIG. 12 schematically shows a bipolar inner component 300 having a tubular electrode 317 (that does not penetrate the tissue) and an electrode 318 (having a sharp tip that penetrates the tissue). The tubular electrode 317 may comprise a solid wall, a helical structure, and / or a conductive mesh structure.

[0118] FIG. 13 schematically illustrates a bipolar inner component 300 having electrodes 315 and 316 that engage the target tissue by end - contact of a conductive component 320 without penetrating the tissue.

[0119] FIG. 14 schematically shows a bipolar inner component 300 having a tubular electrode 304 that does not penetrate the target tissue and an electrode 303 having a distal helical tip with a sharp end that penetrates the target tissue. The tubular electrode 304 may have a solid wall, a helical structure, and / or a conductive mesh structure.

[0120] FIG. 15 schematically shows a monopolar inner component 300 having a single conductive component 320 that terminates at an electrode contact surface 321 in the same plane as the surface 340.

[0121] FIG. 16 schematically shows a monopolar inner component 300 having a single conductive component 320 that terminates distally with a non - traumatic rounded segment 324.

[0122] FIG. 17 schematically shows a bipolar inner component 300 having a pair of inner components 320 terminated distally by non-traumatic rounded segments 327.

[0123] FIG. 18 schematically shows a monopolar inner component 320 having an electrode with a distal threaded sharp tip 328. The helical groove 329 potentially mitigates preactivation penetration into the target tissue by rotation and drilling.

[0124] FIG. 19 schematically shows the inner component 300 together with the outer tube 200, allowing various selectable penetration depths of the electrode tip 362A. The conductive component 320 can slide longitudinally relative to the distal surface 340 of the insulating tube 363 (the insulating tube 363 is an example of the insulating layer 310) and is optionally locked in place, for example, by locking a control element on the proximal side of the device. The slide makes it possible to define different penetration depths by adjusting the distance 1901 between the distal surface 340 and the most distal tip of the electrode 362A.

[0125] A potential advantage of this is to be able to vary the desired depth of disruption for each location selected for energy delivery, depending on, for example, the depth of the annulus connective tissue, the angle of approach to the tissue, and / or nearby coronary arteries, etc., in the vicinity of structures that should not be disrupted.

[0126] FIG. 20 schematically shows the inner component 300 having a selectable depth, where in this case the depth of penetration (distance 2002) is selected by adjusting the relative longitudinal position of the most distal tip of the electrode 362A relative to the distal surface 340 of the outer tube 200.

[0127] This configuration allows penetration of the tissue beyond the non-insulated depth 2001 of the tip 362A while maintaining control of the penetration depth. The layer of tissue above the non-insulated depth 2001 of the tip 362A potentially relatively avoids damage during delivery of the structural disruption energy.

[0128] Optionally, any of the internal components 300 (e.g., of FIGS. 9-20) includes one or more lumens operable as working channels useful, for example, for translation of guide wire(s), injection of irrigation fluid, aspiration, and / or injection of radiopaque liquid. Thermocouple sensors are optionally provided at or near their tips on any of the internal components 300 and are wired distally along the internal component to a connection to an external controller. This enables monitoring having the potential advantage of allowing a physician to stop delivery of energy when the tissue is heated to a particular threshold temperature. Optionally (using a controller), destruction can be automatically stopped when the tissue reaches a particular threshold temperature.

[0129] Additionally or alternatively, tissue impedance is optionally measured via one or more electrodes used for delivery of energy to track progression of the ablation. For example, a change in tissue impedance (generally, an increase of about 7-fold, for example) can be used to determine when ablation is complete or when an intermediate state of tissue destruction has been reached.

[0130] The change is optionally used to automatically stop the disruption of tissue after a specific impedance threshold (e.g., greater than about 2200 Ω) has been reached and / or after a change in impedance of a specific magnitude (e.g., an increase in the magnitude of impedance of about 1800 Ω to 1900 Ω, or an increase by a factor of 5, 6, 7, 8, or another factor) has occurred. The impedance can be measured at an RF frequency, e.g., a frequency of about 500 kHz. Additionally or alternatively, the impedance can be used to confirm the initial penetration of the electrode into the tissue (e.g., a decrease in impedance, e.g., a decrease to about 400 Ω) and / or to confirm that the distance between the electrodes has been closed to a smaller distance (e.g., a decrease in the magnitude of impedance, e.g., a decrease to about 100 Ω and / or a decrease to a value of about 300 Ω). Also, using an electrode that supplies structural disruption energy for measurement has the potential advantage of eliminating the need to provide additional signal wiring to the device.

[0131] The value of a given impedance change was observed in tissue using an electrode having a cross-section of about 0.4×0.4 mm and a penetration depth of about 4 mm and using an RF frequency of about 500 kHz. Different values can be observed using different electrodes and / or operating conditions.

[0132] Tissue remodeling by structurally disrupting mechanically deformed tissue Refer to FIGS. 21A - 21B, FIG. 22, FIG. 23, FIGS. 24A - 24B, and FIG. 25, which schematically show a method of shaping tissue by delivering structural disruption energy while the tissue is mechanically deformed.

[0133] Cross-sectional view 21A and top view 21B show scarring region 2100 resulting from activation of device 1000 (e.g., by transmission of RF energy) while disposed within tissue 2000. The disruption zone can be approximately characterized by the depth of disruption 2000, and the diameter of disruption 2101. Although treated as cylindrical for purposes of illustration, it should be understood that the disruption zone is not necessarily cylindrical, and that tissue and heat transfer are not necessarily uniform. The illustrated scenario is similar to scenarios created by any of the embodiments of internal component 300 with tissue penetrating electrodes. After disruption, disruption zone 2100 tends to contract (e.g., potentially as a result of fluid loss, cell death, and / or coagulation).

[0134] From the results of those in vivo and ex vivo experiments, the inventors have recognized additional effects that can be utilized both to fix and / or contract (or shape) tissue, such as tissue of the cardiac valve annulus. Tissue that is originally (prior to disruption) elastic can be forced to undergo a certain amount of plastic deformation (in addition to that normally induced by its own contraction) by placing it under mechanical deformation while administering disruptive energy (more specifically, disruptive energy that creates coagulation). In particular, the use of compression offers potential advantages for applications of annuloplasty by enabling sufficient contraction around the valve, for example, using fewer applications and / or a smaller area of tissue disruption.

[0135] Figures 22 - 24B show one method of creating plastic deformation by compressing tissue during a lesion.

[0136] In Figure 22, in some embodiments, electrodes 1010 and 1020 are inserted into tissue 2000 with a distance 2201 therebetween.

[0137] In Figure 23, the distance between the electrodes is reduced to a shorter distance 2202, while the electrodes remain within tissue 2000. This creates mechanical compression of the tissue between electrodes 1010, 1020.

[0138] Next, damage is performed. FIGS. 24A and 24B illustrate respective zones of destruction 2110 and 2120 for electrodes 1010 and 1020 during those operations (e.g., transmission of RF energy) to destroy nearby tissue. The distance and energy delivery parameters are optionally selected such that zones 2110 and 2120 share a common section 2200, resulting in a continuous zone of destruction.

[0139] A lesion can have the effect of destroying a portion of tissue elasticity (e.g., by lysis of cells), while other effects tend to constrict and harden cell components and / or extracellular components (e.g., by denaturing proteins), such that they resist return to their original shape. In effect, the lesion fixes the tissue in a new preferred configuration, which is more similar to the compressed shape used during the lesion than the shape the tissue had prior to being treated.

[0140] Upon release of the external force (e.g., relaxation of the compression between electrodes 1010 and 1020), the tissue potentially assumes a new equilibrium state, e.g., a state in which the distance 2203 between electrodes 1010 and 1020 (FIG. 25) is shorter than distance 2201. As long as any elastic memory of the original tissue shape remains, distance 2203 is typically greater than distance 2202. Removal of the electrodes leaves behind the damaged and compression-reconstructed tissue.

[0141] If the electrodes overly compress the tissue therebetween (or overly stretch the tissue), there is a risk that the structural destruction of the tissue will result in a cutting lesion that can potentially negate the intended result.

[0142] Alternatively, if the level of the applied energy (e.g., RF energy) is too low, the destruction zone may not extend into some of the most deformed regions (e.g., the destruction zone may not be continuous between the electrodes). This can result in a reduction in the magnitude of the target effect. However, it is important to select an energy level that is safe and does not induce electrical disturbances (e.g., ventricular fibrillation) in the patient. Generally, selecting a lower power for a longer duration is safer (e.g., 10 watts for 12 seconds is safer than an alternative energy level that delivers 30 watts for 4 seconds).

[0143] Effective potential settings and parameters for tissue destruction include inserting into the tissue electrodes at an initial distance of about 4 mm 2201, compressing the tissue between them until their distance is about 1.7 mm, and destroying the tissue structure with RF energy at a power of 7 watts for 16 seconds. These parameters were derived from experiments using electrodes having a width of 0.4 mm and an intrusion into the tissue of about 4 mm.

[0144] Note that each of the electrodes 1010, 1020 is shown in FIGS. 22-25 with a beveled tip 1021. This gives side characteristics to the electrode cutting surface. Orienting the beveled surface with the non-cut (or less cut) side 1021A facing inward potentially reduces the risk of cutting the compressed tissue.

[0145] Now refer to FIGS. 26 and 27A-27B, which schematically show an electrode plier 1100 according to some embodiments of the present disclosure.

[0146] The pincer 1100 can be provided at the distal tip of a low-profile flexible catheter for use in the destruction of tissue structures via an intravascular approach.

[0147] In some embodiments, the pincers 1100 (FIG. 26) include electrodes 1010, 1020 and, in the illustrated example, also act as tissue grasping (grasping and squeezing) elements of the pliers 1100. Further, the electrodes 1010, 1020 are shaped to penetrate the tissue to be grasped. Optionally, some portions along the lengths of the electrodes 1010, 1020 are insulated to enable selective disruption of tissue at a particular depth, as described in connection with FIG. 20, for example.

[0148] Typically, the cover 1130 is rigidly connected to the frame 1120. FIGS. 27A-27B show one cover 1130 removed from the pliers 1100 and illustrate the internal operation of the pliers 1100.

[0149] In some embodiments, a rack and pinion arrangement (FIGS. 27A-27B) is used to operate the electrodes. In the illustrated example, each electrode 1010, 1020 separately includes a rack (linear gear) 1160 to which it is rigidly attached. The pinion 1150 may be a spur gear that rotates to move the rack and translate the electrodes towards or away from each other. The frame 1120 and cover 1130 are shaped to hold and guide these components, for example, to hold them within recesses 1121 and guide the movement of the electrodes along slots 1122.

[0150] The spur 1160 is rigidly connected to an elongate member 1140 (e.g., a rod or wire). When the pliers' electrodes 1110, 1120 are embedded in tissue and the remainder of the pliers 1100 body is fixed, the rotating elongate member 1140 rotates the pinion 1150. Additionally or alternatively, as described in connection with FIGS. 28A-28C, the elongate member 1140 may itself be housed within a tube 300 to enable adjustment of the electrode distance by rotation of the elongate member 1140 relative to the device casing, even when there is no external resistance to rotation.

[0151] In FIG. 27A, the electrodes 1020, 1010 are arranged at their widest spacing, and in FIG. 27B, the rotation of the pinion 1150 brings them closer together by engaging the linear gear 1160. Whether the device causes tissue extension or compression depends on how it is used. Invasion in the widely spaced configuration of FIG. 27A, followed by a decrease in the electrode spacing (FIG. 27B), tends to compress the tissue. Invasion in the narrowly spaced configuration of FIG. 27B, followed by an increase in the electrode spacing (FIG. 27A), tends to stretch the tissue.

[0152] In some embodiments, the components of the plier 1100 are metallic and are manufactured, for example, by laser cutting of planar stock to produce plates, gearing, and / or electrodes. In some embodiments, electrical insulation from the surroundings is provided by the tip casing 1310, as described in connection with FIGS. 28A - 28C. Optionally, electrical insulation of one or more of the covers 1130, the frame 1120, and / or the elongate members 1140 from the surroundings and / or from components that transmit RF energy is provided by coating the surfaces of these elements with an electrical insulating polymer (e.g., perylene - c or PTFE).

[0153] Optionally, the frame 1120 and the cover 1130 are made entirely of an insulating material (e.g., polymer). If the pinion 1150 itself is a conductive part, the pinion can be used to transmit RF power to the electrodes 1010, 1020 via electrical conduction through the respective (conductive) linear gears. Alternatively, the electrodes 1010, 1020 may be directly connected to power leads. In this case, the pinion 1150 is optionally itself formed from a polymer and enables the electrodes 1010, 1020 to operate in bipolar mode rather than as two different parts of a monopolar electrode (if each has its own power lead).

[0154] The combination of the plier function and the electrode function within electrodes 1010, 1020 has potential advantages when simplifying the device design. It can also simplify the operation of the device. However, it should be understood that these functions are optionally performed by separate components.

[0155] For example, grasping is optionally performed by a plier that is first operated to grasp (with or without an initial penetration of the tissue) and reform (e.g., compress) the tissue. Once the tissue is reformed, the electrode can be placed on or inserted into the tissue and operated to disrupt it. This has potential advantages by arbitrarily separating the region of maximum damage energy from the region of maximum mechanical stress and potentially reducing the likelihood of tearing due to weakening of the tissue during or after structural disruption of the tissue.

[0156] Referring now to FIGS. 28A - 28C, which schematically show a coated catheter tip casing that houses the mechanisms of FIGS. 27A - 27C, according to some embodiments of the present disclosure. This can be used to sheath electrodes 1010, 1020, for example, during navigation of the catheter to the target tissue, to avoid damage by the sharp tips of the electrodes. Once electrodes 1010, 1020 are exposed, the distance can be adjusted as needed.

[0157] In some embodiments, the tip casing 1310 includes a metal (e.g., stainless steel, titanium, and / or another biocompatible metal) having a polymer (e.g., PEEK, PTFE, etc.) and / or a polymer coating (e.g., perylene - c or PTFE).

[0158] As a result, the casing 1310 is electrically insulated (thus, there is some electrical leakage to non-target tissue during the application of structural break energy). Further, in embodiments where the tip 1310 is made of polymer (not radiopaque), the electrodes 1010, 1020 (which are metallic and relatively radiopaque) are well observed under fluoroscopy. Optionally, the tip casing 1310 includes radiopaque markers, enabling observation under fluoroscopy of the positioning of the electrodes 1010, 1020 relative to the casing 130 (e.g., inside or outside the casing 1310).

[0159] To assist with ultrasonic visualization, the casing 1310 can be provided with surface textures such as grooving that can enhance its echogenic properties. Optionally or additionally, a slow flow of fluid (e.g., saline) through the casing 1310 is used to increase echo generation and help localize the position of the casing 1310.

[0160] In the retracted configuration (e.g., for use in navigation), the tip 1310 covers the electrodes (Figure 28A). When the tip of the casing 1310 is positioned relative to the target tissue, the electrode 1010 is removed, for example, by advancing from the casing 1310 and / or pulling the casing 1310 rearward. For example, the tube 1300 is rigidly connected to the tip 1310, and by pulling it out, the electrodes 1010, 1020 are exposed (Figure 28B).

[0161] When the electrodes 1010, 1020 are positioned inside the target tissue, the operator can reduce the distance between them, as shown in Figure 28C (e.g., using the inner drive mechanism 1100 described in relation to Figures 27A - 27C). The device is activated, for example, using RF energy.

[0162] Regarding other aspects of this configuration, it is as follows. In some embodiments, the tube 1300 comprises a polymeric material (e.g., Pbax or PTFE). Optionally, the polymeric material is metal reinforced (e.g., using a metal braid or helix) to support the necessary mechanical and electrical properties of the catheter (i.e., operability / flexibility, rotational / torque ability, pushability, and electrical insulation).

[0163] In some embodiments, the casing 1310 includes a tip taper 1330 and a proximal taper 1340 and has the potential advantage of assisting the smooth back-and-forth movement of the catheter through the guide sheath (and / or body lumen). The casing 1310 includes a slit 1320 through which the electrodes 1010, 1020 can protrude when not covered and slide along it in accordance with a remotely actuated command. The width of the slit 1310 matches the width of the electrodes 1010, 1020 (e.g., within an allowable range of about 0.1 - 0.2 mm around the electrodes, which themselves can be, for example, about 0.4 mm wide). The resulting small opening size may allow a minimal amount of blood to penetrate the tip. This potentially helps to reduce leakage of electrical RF energy (such leakage is basically noise that complicates the ability to apply structural breaking energy in a repeatable, durable, and / or stable manner). In some embodiments, sealing is assisted by a sliding and / or elastic gasket provided inside the slit 1320 through which the electrodes 1010, 1020 penetrate when not encased.

[0164] Casing 1310 provides another potential advantage by preventing accidental penetration of the valve tip or other non-target tissue by electrodes 1010, 1020 while casing 1301 is being moved within the body. For example, electrodes 1010, 1020 are extended directly into the tissue after verifying (e.g., using transesophageal echocardiography or intracardiac echocardiography) that casing 1310 is positioned relative to the annulus tissue targeted for remodeling. After the tissue structure is disrupted, electrodes 1010, 1020 are retracted into casing 1310 before being moved again (e.g., to a new treatment position or withdrawn from the body). Optionally, the distance between electrodes 1010, 1020 is reset to a wide position after being withdrawn from the tissue and while they are being drawn into casing 1310.

[0165] Referring now to FIG. 29, which schematically illustrates positioning via an intravascular approach of the distal portion of a catheter used for annuloplasty of the mitral valve 48 according to some embodiments of the present disclosure.

[0166] In some embodiments, a transseptal guide catheter 302 is introduced into the right atrium 46 via the inferior vena cava 45. The guide catheter 302 is directed to penetrate the atrial septum 46 (preferably via the fossa ovalis) to obtain low-invasive access to the left atrium 44. A catheter including an outer tube 200 and an inner component 300 (including the energy delivery element 1310) is inserted into the left atrium 44 through the guide catheter 302. Alternatively, in some embodiments, access to the heart is via the superior vena cava 43. This may be potentially advantageous for treatments targeting the tricuspid valve annulus.

[0167] Optionally or alternatively, the guide catheter 302 itself comprises a distal steering section (instead of a curved preformed configuration) and / or the sleeve 1400 has a curved preformed distal segment (instead of the steering segments described above).

[0168] The controllable degrees of freedom of the outer tube 300 include rotation R1 with respect to the guide catheter 302 and longitudinal advancement / retreat E1 with respect to the guide sheath 1500.

[0169] In some embodiments, the outer tube 300 also includes a steering segment S that bends through a range of angles, for example, by active steering (e.g., controlled by shortening a control wire) and / or through a preformed curved shape coating, as described in connection with FIGS. 3-8D. In some embodiments, the steering is performed by a steering mechanism provided to guide the catheter 302 itself.

[0170] The controllable degrees of freedom of the inner component 300 include linear translation E2 with respect to the sleeve 302 and rotation R1 with respect to the outer sleeve tube 200. In combination, the controllable degrees of freedom enable the distal tip 1310 of the catheter to be positioned at a selected position, orientation, and angle along the valve annulus from where the electrodes can be deployed to penetrate the valve annulus and effect structural disruption of the tissue.

[0171] FIG. 30 shows an optional proximal side of the catheter (positioned outside the patient's body). The outer tube 300 is inserted within the guide catheter 302 and includes a handle 1450 used to control longitudinal advancement and steering (angling) of its distal segment with respect to the guide catheter 302.

[0172] The inner component 300 is then positioned inside the outer tube 200. The handle 1350 controls longitudinal advancement and rotation of the inner component 300 with respect to the outer tube 200.

[0173] In some embodiments, the handle 1260 drives the deployment of the electrodes 1020, 1010 by moving longitudinally relative to the tip casing 1310, for example via connection with the tube 1250, and then connects distally to the tube 1300. Rotation of the handle 1180 rotates the elongate member 1140 to drive the electrodes 1010, 1020 laterally, as described, for example, in connection with FIGS. 26-27B.

[0174] Further, the handle 1260 (or handle 1180) includes a hole through which the electrical cable 1710 passes, enabling connection of the electrodes 1010, 1020, and the RF generator 1700.

[0175] Referring now to FIGS. 31A-31E, which schematically illustrate different configured layers of an adjustable-width catheter according to some embodiments of the present disclosure. In the cross-section depicted in FIG. 31A, the wire 1140 is shown rigidly connected at its proximal side to the distal side of the tube / shaft 1170. The rigid connection can be made, for example, by crimping the tube 1170 onto the wire 1140, by adhering them, and / or by welding them using laser cutting techniques.

[0176] In some embodiments, the tube 1170 is constructed from a metal (e.g., stainless steel or nitinol) and includes a flexible segment 1175. The segment 1175 can be made flexible, for example, by forming laser cutouts (e.g., slits, or an interlock pattern as described, for example, in connection with FIG. 32) in a walled tube. Alternatively, the segment 1175 may be made flexible by construction from a metal braid and / or one or more wire spirals. In some embodiments, the metal braid and / or wire spirals reinforce a polymeric structure tube (e.g., PEEK, polyimide, PTFE, and / or Pbax).

[0177] Figure 31B shows the following outer layer. Tube 1200 is assembled over tube (or shaft) 1170 and rigidly connected to cover 1130 (e.g., using laser welding). Rotating tube / shaft 1170 relative to tube 1200 drives electrodes 1010, 1020 laterally to move them closer together or farther apart. Tube 1200 includes, for example, flexible segment 1210 manufactured as described for flexible segment 1175.

[0178] At least one of tubes or shafts 1170, 1200 is made of metal and is capable of conducting electrical energy to electrodes 1010 and 1020 along the catheter (e.g., via proximal cover 1130).

[0179] Figure 31C shows insulating sleeve 1250 assembled over and rigidly connected to tube 1200. Sleeve 1250 is made of a polymer (e.g., PTFE or polyolefin) to electrically insulate the conductive inner tube. In some embodiments, sleeve 1250 is a heat shrink tube and has the potential advantage of simplifying the assembly process.

[0180] Tube 1300 (Figure 31D) is assembled over sleeve 1250 and rigidly connected to tip casing 1310 (e.g., using an adhesive). Tube 1300 can slide forward / backward over sleeve 1250, allowing electrodes 1010, 1020 to be covered or exposed.

[0181] In some embodiments, outer tube 200 (Figure 31E) is sequentially assembled over tube 1300. Tube 1300 can be advanced / retracted / rotated relative to outer tube 200. In some embodiments, the distal tip of sleeve 200 includes a steering segment to allow it to be bent, for example, to support the motions and configurations described in connection with Figure 29.

[0182] Referring now to FIG. 32, which shows a developed view of the self - locking pattern 3200 cut to provide flexibility to the tube 1170 and / or tube 1200, according to some embodiments of the present disclosure. The cuts (preferably manufactured using laser cutting technology) create a series of discrete but geometrically connected links. The individual links allow for slight movement, while the collective links can create larger - angle bends. By making the cuts using the connecting elements 3201, 3202, the tube is prevented from coming apart. As a result, the tube supports a high level of maneuverability (i.e., can pass through geometric shapes with a small radius of curvature while having good push and pull capabilities) while retaining a high level of torque - carrying capacity (required to transmit torque driving the electrodes laterally along the tube).

[0183] Twist contraction Referring now to FIG. 33, which schematically depicts an electrode configuration that inserts into tissue, twists, and then disrupts its structure, according to some embodiments of the present disclosure. The inner component 1900 is an example of an inner component 300 that includes a single electrode 1910 protruding from an insulating sleeve 1901 that fits within the outer tube 200 itself. The electrode 1910 is shaped to pull the surrounding tissue together when inserted into and twisted in the tissue. The amount of twist may be, for example, about 45°, 90°, 135°, or another angle. However, the twist should remain below the level of force that would induce the tissue to return to its untwisted state.

[0184] In some embodiments, this is achieved using an outer perimeter shape that extends radially farther from the central axis of the electrode at some locations compared to other locations on the radially closer outer perimeter. This creates a tissue surface that is pressed against (rather than simply passed over) as the electrode rotates, creating torsion in the surrounding tissue. A simple example of such a perimeter is a rectangular cross-sectional shape. Triangular waves and cross-sections of cross-sectional shapes provide alternatives. Additionally or alternatively, the electrode(s) may comprise a plurality of discrete shapes inserted into the tissue, such as two, three, four, or more spikes, flat blades (e.g., radially oriented from a common center), or other shapes. A larger total surface area is potentially preferred, reducing the accumulation of focal stress that increases the risk of tissue tearing.

[0185] Now refer to FIGS. 34A - 34D showing a method of torsion and disruption of perivalvular reduction according to some embodiments of the present disclosure.

[0186] FIG. 34A shows a cross-section of electrode 1910 inserted into a block of tissue 2000. FIG. 34B shows the same scenario from a perspective looking down on the surface 2001 of tissue 2000. Distance 3401 represents the initial distance between two locations 3402, 3403 disposed along the perimeter of the annulus tissue to be adjusted.

[0187] In FIG. 34C, electrode 1910 is twisted, resulting in the movement of the twisted tissue indicated by the arrows leading from location 3402 to 3402A and from location 3403 to 3403A. The non-compressible tissue volume can be diverted in response to the stress to the swelling of the tissue (e.g., into the open area adjacent to tissue 2000). This potentially shortens the overall perimeter when being "wound up", including pulling out tissue portions at locations somewhat closer than before at locations 3402, 3403, including pulling in tissue portions at locations 3402A, 3402B.

[0188] Figure 34D shows the situation after the destruction of region 2100 and the removal of electrode 1910. The tissue at locations 3402A and 3403A partially relaxes back to locations 3402B and 3403B, but due to plastic deformation as a result of scarring, it does not fully relax back to its original location. The contraction of the tissue further reduces the direct distance (distance 3406 is shorter than distance 3405, for example). In the circumferential direction, locations 3402B and 3403B are separated by distance 3407, which is even shorter. The difference between distance 3407 and 3401 is somewhat greater than the overall circumferential reduction because part of the volume of the twisted tissue is redirected laterally outward by the twist even when other tissue is being pulled laterally inward. Nevertheless, while the tissue is held in a twisted configuration, there can be an overall combined effect of circumferential shortening due to both "sets" of tissue contraction and tissue plastic remodeling.

[0189] Note that, for example, the pinching type of compression described in connection with FIGS. 21A - 25 is optionally performed together with the torsional compression described in connection with FIGS. 33 - 34D. This potentially increases the amount and / or extent of circumferential contraction that can be induced from a particular site of destructive energy delivery.

[0190] Reference is now made to FIGS. 35A - 35B, which schematically illustrate the configuration of an electrode assembly comprising two needle electrodes 1010, 1020 interconnected by a loop spring 1600, according to some embodiments of the present disclosure.

[0191] Electrodes 1010, 1020 are connected to opposite sides of a loop spring 1600 that itself includes a shape memory alloy such as nitinol. The loop spring 1600 is used as an actuator of the device. Optionally, another actuator including a shape memory alloy, for example, a separate leaf spring or coil spring, is used.

[0192] When the transition temperature of this alloy is exceeded and the loop spring 1600 relaxes, the electrodes 1600 are brought closer to each other (Figure 35B), i.e., "normally closed". When the loop spring 1600 is held in the open (unclosed) state, the electrodes 1010, 1020 are separated. This element is optionally used, for example, instead of the rack and pinion mechanism described in connection with Figures 26 - 27B.

[0193] In some embodiments, the shape memory alloy used is set to a transition temperature above body temperature, for example, in the range of 37°C to 60°C. This results in the loop spring 1600 being "soft" before use. The loop spring 1600 begins to cool below the transition temperature and is bent into the open state. Due to the properties of the shape memory alloy, the shape memory alloy remains in that state until heated. The electrodes can be inserted into the tissue in this configuration and then operated to perform tissue disruption.

[0194] During operation, the temperature of the electrodes rises and the heating loop spring 1600 exceeds its transition temperature. Additionally or alternatively, the loop spring 1600 self - heats due to its electrical resistance to the current flowing through it. Upon heating, the electrodes collapse towards the closed state, pulling the electrodes towards each other. This is another way to apply an external force to affect the plastic deformation effect of the tissue, as described, for example, in connection with Figures 21A - 25.

[0195] Referring now to Figures 36A - 36E, which schematically illustrate the configuration of a mechanically actuated electrode assembly comprising two needle electrodes 1010, 1020 interconnected by a loop spring 1600, according to some embodiments of the present disclosure.

[0196] Regardless of the transition temperature of the material of the loop spring 1600, the loop spring 1600 can also be opened by mechanical force.

[0197] Figure 36A shows the elements of such a mechanism, which operates by the movement of the wedge 1610 to forcibly open the opening of the loop spring 1600. The mechanism includes two side plates 1615 on both sides of the wedge 1610. The side plates 1615 are coupled to both sides of the loop spring 1600, such that when they are separated, the opening of the loop spring 1600 also opens, resulting in a lateral separation of the electrodes 1010, 1020.

[0198] With the wedge 1610 in its withdrawn position (Figure 36A), the side plates 1615 are freely pulled into their laterally folded state by the normally closed loop spring 1600. Add a cover plate 1630 to the elements of Figures 36A and 36B that serves to maintain the wedge 1610 aligned with the side plates 1615. Figure 36C adds a shaft 1190 that is rigidly attached to the wedge 1610. Figure 36D adds an outer tube 1290 and has a cutout showing internal details such as how the plates 1620 are arranged within the outer tube 1290 to which they are rigidly attached. The shaft 1190 can translate longitudinally through the outer tube 1290 to move the wedge 1610 longitudinally.

[0199] Figure 36E shows the same view as Figure 36D, without the cutout, and adds an end cover 1295 with a slot 1296 along which the electrodes move when displaced by the opening of the loop spring 600 of the electrodes 1010, 1020.

[0200] Now refer to Figures 37A - 37C, which schematically show the operation of the mechanically actuated electrode assembly of Figures 36A - 36E, according to some embodiments of the present disclosure. In each of these figures, the display of the outer tube 1290 is suppressed along with one of the cover plates 1620.

[0201] Comparing Figures 37A and 37B, it can be seen that the plate 1615 slides freely as the loop 1600 transitions between the folded configuration and the open configuration. This can occur as a result of a temperature - induced phase transition, for example, as described in connection with Figures 35A - 35B.

[0202] Figure 37C shows the wedge 1610 in the position advanced in the longitudinal direction, separating the plate 1615. This in turn results in forcing the loop spring 1600 to its open position, and the electrodes 1610, 1620 are laterally separated by a wider distance than when the spring 1600 is in its closed position.

[0203] This is understood as a “reset” mechanism that allows the loop 1600 to return to its open state again after being cooled below its transition temperature. When the device is reset, the wedge 1610 can be retracted again. The loop spring 1600 remains in its open position until it is heated again. This has the potential advantage of enabling the operation of the shaft 1190 as an instantaneous “push button” switch, which can immediately bounce back to the configuration of Figure 37A and the loop spring 1600 is reset.

[0204] Alternatively, the device of FIGS. 36A - 37C can comprise a loop spring 1600 made of a superelastic material having a transition temperature below body temperature (e.g., below 37°C). This allows it to always remain fully elastic. In such an embodiment, the opening and closing of the opening of the loop spring 1600 is set by the position of the wedge 1610 relative to the plate 1615 regardless of the operating temperature.

[0205] General As used herein with respect to a quantity or numerical value, the term “about” means “within ±10%”.

[0206] “Comprises”, “comprising”, “includes”, “including”, “having” and their conjugates mean including but not limited to.

[0207] “Consisting of” means “including and limited to”.

[0208] The term "consisting essentially of" means that a composition, method, or structure may include additional ingredients, steps, and / or components, but only if the additional ingredients, steps, and / or components do not materially alter the basic and novel characteristics of the composition, method, or structure recited in the claims.

[0209] As used herein, the singular forms "a", "an", and "the" include plural references unless the context clearly dictates otherwise. For example, the term "compound" or "at least one compound" can include a plurality of compounds including mixtures thereof.

[0210] The terms "example" and "exemplary" are used herein to mean "serving as an example, instance, or illustration." Any embodiment described as "example" or "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments and / or does not necessarily exclude the incorporation of features from other embodiments.

[0211] The term "optionally" is used herein to mean "provided in some embodiments and not provided in other embodiments." Any particular embodiment of the present disclosure may include a plurality of "optional" features, unless such features are mutually inconsistent.

[0212] As used herein, the term "method" refers to methods, means, techniques, and procedures for accomplishing a given task, including, but not limited to, those that are known or readily developed from known methods, means, techniques, and procedures by those skilled in the fields of chemistry, pharmacology, biology, biochemistry, and medicine.

[0213] As used herein, the term "treating" includes arresting, substantially inhibiting, delaying or reversing the progression of a condition, substantially ameliorating clinical or aesthetic symptoms of a condition, or substantially preventing the appearance of clinical or aesthetic symptoms of a condition.

[0214] Throughout this application, various embodiments of the invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the individual numerical values and all sub-ranges within that range. For example, a range description such as from 1 to 6 should be considered to specifically disclose sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as the individual numerical values within that range, for example, 1, 2, 3, 4, 5, 6, etc. This applies regardless of the breadth of the range.

[0215] Whenever a numerical range (e.g., "10 - 15", "10 - 15", or any number of pairs linked by such other similar range notations) is shown herein, unless the context clearly states otherwise, it is meant to include any numerical value (fractional or integral) cited within the indicated range. As used herein, the expressions "range between / through" a first indicated number and a second indicated number, and "range from" a first indicated number "to" a second indicated number are used interchangeably and are meant to include the first and second indicated numbers, and all fractional and integral numbers therebetween.

[0216] Although the description of the present disclosure is provided in relation to specific embodiments, it will be apparent to those skilled in the art that many alternatives, modifications, and variations are possible. Accordingly, the present invention is intended to embrace all such alternatives, modifications, and variations that fall within the spirit and broad scope of the appended claims.

[0217] For clarity, certain features of the invention that are described in the context of separate embodiments may be provided in combination in a single embodiment, and conversely, for brevity, various features of the invention that are described in the context of a single embodiment may also be provided separately, or in any suitable partial combination, or in other described embodiments of the invention as appropriate. Specific features described in the context of various embodiments are not considered essential features of those embodiments, except where the embodiments would not function without those elements.

[0218] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. Also, the documents cited or identified in this application should not be construed as an admission that such documents are available as prior art to the present invention. To the extent that section headings are used, they should not necessarily be construed as limiting. Also, the priority documents of this application are incorporated herein by reference in their entirety.

Claims

**Claim 1** An apparatus for annuloplasty treatment, comprising: a catheter sized to be inserted transvessularly from a percutaneous incision into a cardiac chamber of the heart and to reach the cardiac annulus; at least one tissue penetrating element at a distal end of the catheter; a rotational movement mechanism extending from a proximal end of the catheter to the distal end of the catheter and coupled to the at least one tissue penetrating element; wherein the at least one tissue penetrating element is operative to move relative to a body of the catheter and to deliver tissue disrupting energy to tissue penetrated by the cardiac annulus; the at least one tissue penetrating element having a non-circular cross-section and being operative to engage tissue into which it is inserted and to induce torsion in the tissue when receiving torque applied through the catheter by the rotational movement mechanism. **Claim 2** The apparatus of claim 1, wherein the at least one tissue penetrating element comprises a plurality of penetrating elements adjustable in their relative distance while inserted into the tissue of the cardiac annulus. **Claim 3** The apparatus of claim 1, wherein each of the at least one tissue penetrating element is an electrode electrically interconnected to a connection portion remaining outside the percutaneous incision when the catheter is inserted into the cardiac chamber. **Claim 4** The apparatus of claim 2, wherein each of the plurality of penetrating elements operates as an ablation electrode. **Claim 5** The apparatus of claim 2, wherein the plurality of penetrating elements are inserted into the tissue at a relatively wide distance and spaced apart to adjust to a narrower distance. **Claim 6** The apparatus of claim 2, wherein the relative distance of the plurality of penetrating elements is adjusted by rotation of a gear. **Claim 7** The apparatus of claim 6, wherein the gear is rotated by a control element communicating with a proximal side of the catheter. **Claim 8** The apparatus of claim 7, wherein the control element also operates to provide an electrical interconnection between at least one of the at least one tissue penetrating element and a power source remaining outside the percutaneous incision. **Claim 9** The apparatus of claim 2, wherein the relative distance of the plurality of penetrating elements is adjusted by a temperature change of an actuator comprising a shape memory alloy. **Claim 10** The apparatus of claim 9, wherein the shape memory alloy is arranged such that the temperature change is induced by heating as a result of operation of the plurality of penetrating elements as electrodes. **Claim 11** The device according to claim 9, wherein the shape memory alloy is shaped to move the plurality of through elements from an initial distance to a relatively narrow distance when heated.

12. The device according to claim 9, comprising a device reset operable to restore the distance of the plurality of through elements prior to the temperature change while the device remains inserted in the heart cavity.

13. The device according to claim 1, wherein the non-circular cross-section includes a rectangular blade.

14. The device according to claim 1, wherein the non-circular cross-section has a shape comprising three or more blades extending radially from a central axis.

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