Heart valve annuloplasty

Abstract

An annuloplasty device configured to mechanically strain annulus tissue while delivering structural disruption energy to induce plastic deformation. In some embodiments, the mechanical distortion includes vacuum-induced attachment to the tissue, optionally with or without additional manipulation to tension or stretch the tissue. In some embodiments, the mechanical distortion includes torsional deformation of the tissue. Optionally, the torsional deformation is limited by the device to a predetermined torsional angle, e.g., in the range of 60° to 120°. In some embodiments, the torsional deformation includes rotating an axis extending between tissue-implanting pins of the device from a first angle oblique to a local circumferential direction, through an intermediate angle perpendicular to the local circumferential direction, to a second such angle. In some embodiments, a non-penetrating transducer delivers structural disruption energy via a surface that contacts the annulus tissue.

Description

[Technical Field]

[0001] Related Applications This application claims the benefit of priority under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 63 / 433,510, filed December 19, 2022, and U.S. Provisional Patent Application No. 63 / 523,680, filed June 28, 2023, the entire contents of each of which are incorporated by reference as if fully set forth herein in their entirety.

[0002] The present invention, in some embodiments thereof, relates to the field of structural heart disease, and more particularly, but not exclusively, to heart annuloplasty. [Background technology]

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

[0004] As the valve circumference decreases, the leaflets come closer together and therefore achieve a better seal (coaptation) to reduce or eliminate valve regurgitation.

[0005] International Patent Publication No. WO2002 / 097130, filed May 4, 2021, which lists the inventors of the present disclosure as inventors, is incorporated herein by reference in its entirety. International Patent Publication No. WO2002 / 097130 describes annuloplasty devices that use structural disruption energy combined with mechanical manipulation, and methods of using them. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] J. Matilda et al., J Cardiovasc Electrophysiol. 2017 Mar;28(3):298-303. Pulmonary Vein Stenosis After Second-Generation Cryoballoon Ablation [Non-patent document 2] Pulmonary Vein Stenosis After Catheter Ablation, Electroporation Versus Radiofrequency by Vincent JAM et al., Circ Arrhythm Electrophysiol. 2014 Aug; 7(4):734-8 Summary of the Invention [Means for solving the problem]

[0007] According to aspects of some embodiments of the present disclosure, there is provided an annuloplasty device configured to deliver structural disruption energy to a tip terminating at a distal end of a catheter body of the device, the annuloplasty device including: a tip housing extending between a proximal side connected to the catheter body and a distal side; and a plurality of pins, each extending distally from a position fixed at the tip within the housing and sized and sharpened to penetrate collagen tissue of a human heart valve annulus; and while the pins are inserted into the collagen tissue, the pins are configured to rotationally move relative to the annulus with sufficient force to twist a portion of the collagen tissue at least 45°, wherein movement of the inserted pins to twist the collagen tissue also rotates the pins and the collagen tissue relative to the housing.

[0008] According to some embodiments of the present disclosure, movement of the inserted pin rotates collagen tissue extending along an axis connecting two of the pins.

[0009] According to some embodiments of the present disclosure, the annuloplasty device is configured to limit rotation of tissue extending along the axis to a predetermined maximum rotation relative to the housing of less than 180°.

[0010] According to some embodiments of the present disclosure, the predetermined maximum rotation is less than about 110°.

[0011] According to some embodiments of the present disclosure, the predetermined maximum rotation is greater than about 70°.

[0012] According to some embodiments of the present disclosure, the plurality of pins consists of exactly two pins.

[0013] According to some embodiments of the present disclosure, two of the plurality of pins are arranged such that the distance between their axes is 1 to 2 mm.

[0014] According to some embodiments of the present disclosure, the annuloplasty device includes a control operable from the proximal side of the catheter body to induce twisting of the collagen tissue portion and movement of the pin relative to the proximal-distal axis of the housing.

[0015] According to some embodiments of the present disclosure, the control includes a manually adjusted element, and the annuloplasty device limits the movement of the manually adjusted element, thereby limiting rotation of the pin and collagen tissue relative to the housing.

[0016] According to some embodiments of the present disclosure, the control unit operates by releasing stored energy to effect rotation, and the annuloplasty device limits rotation of the pin and collagen tissue relative to the housing by limiting the amount of stored energy.

[0017] According to some embodiments of the present disclosure, the distal surface of the housing includes at least one opening through which at least one of the pins passes, and the annuloplasty device limits rotation of the pin and collagen tissue relative to the housing by interference between at least one of the pins and the periphery of the opening.

[0018] According to some embodiments of the present disclosure, the distal surface of the housing includes a plurality of openings through each of which a respective pin extends, and the annuloplasty device limits rotation of the pin and collagen tissue relative to the housing by interference between at least one of the pins and the periphery of the respective opening.

[0019] According to some embodiments of the present disclosure, rotation of the pin relative to the housing is limited by interference contact with a stop element within the housing.

[0020] According to some embodiments of the present disclosure, the interference contact with the stop element includes interference between the assembly that rotates the pin and a portion of the housing of the assembly that acts as the stop element.

[0021] According to some embodiments of the present disclosure, rotation of the plurality of pins relative to the housing exerts a torque on the collagen tissue of at least 0.01 N·m.

[0022] According to some embodiments of the present disclosure, the multiple pins exert a torque on the collagen tissue sufficient to drag a portion of the collagen tissue through a rotation comparable in magnitude to the rotation of an axis extending between two of the pins, the rotation being relative to the proximal-distal axis of the housing.

[0023] According to some embodiments of the present disclosure, the rotational actuation force is transmitted along the catheter body by rotation of the control member.

[0024] According to some embodiments of the present disclosure, the annuloplasty device limits rotation by limiting rotation of the control member.

[0025] According to some embodiments of the present disclosure, the rotational actuation force is transmitted along the catheter body by longitudinal translation of a control member through the catheter body.

[0026] According to some embodiments of the present disclosure, the annuloplasty device limits rotation by limiting translation of the control member.

[0027] According to some embodiments of the present disclosure, the pins maintain a constant distance from each other during rotation.

[0028] According to some embodiments of the present disclosure, the pins change distance from one another during rotation.

[0029] According to some embodiments of the present disclosure, the structural disruption energy comprises RF energy transmitted to the tip along a conductive wire.

[0030] According to some embodiments of the present disclosure, the pin is an electrode interconnected with a proximal power connection of the annuloplasty device via a conductive wire.

[0031] According to some embodiments of the present disclosure, the conductive wire is operable to transmit RF energy to an electrode positioned alongside the pin in contact with the tissue when the pin is inserted into collagenous tissue.

[0032] According to some embodiments of the present disclosure, the pin is retractable and extendable relative to the housing.

[0033] According to some embodiments of the present disclosure, the annuloplasty device includes a steering sheath through which the catheter is configured to be advanced to reach the target collagen tissue.

[0034] According to some embodiments of the present disclosure, the steering sheaths are configured to adopt a curl and move cooperatively to bend out of the plane of the curl as the steering sheaths are actuated.

[0035] According to some embodiments of the present disclosure, the steering sheath is configured to bend from a straight configuration to form a segment of the steering sheath into a helical shape.

[0036] According to some embodiments of the present disclosure, the helical shape includes a distal segment of the steering sheath attached to a more proximal segment of the steering sheath, which bends from a straightened configuration to form a curve while remaining substantially within the plane of the curve.

[0037] According to some embodiments of the present disclosure, the plurality of pins comprise a radiopaque material, and the housing includes at least one radiopaque marker disposed alongside the pin to indicate a state of distal advancement of the pin relative to the radiopaque marker.

[0038] According to some embodiments of the present disclosure, the at least one radiopaque marker on the housing includes two radiopaque markers positioned on opposite sides of the housing to indicate the orientation of the housing according to the angular distance between the two radiopaque markers when viewed in a fluoroscopic image.

[0039] According to some embodiments of the present disclosure, the annuloplasty device includes an arrangement of electrical contacts in electrical communication with an indicator configured to indicate the position of the plurality of pins relative to the housing based on the relative positions of the electrical contacts.

[0040] According to some embodiments of the present disclosure, the electrical contact arrangement includes at least one first electrical contact fixed to the housing and at least one second electrical contact that moves with the pin, and illumination of the indicator indicates a contact state between the first and second at least one electrical contacts.

[0041] According to aspects of some embodiments of the present disclosure, there is provided an annuloplasty device configured to deliver structural disruption energy to a tip portion terminating a distal end of a catheter body, the annuloplasty device including a first pin and a second pin, each extending distally from a location fixed to the tip portion and having a size and sharpness to penetrate collagen tissue of a human heart valve annulus, the first pin and the second pin being fixed to a first support and a second support, respectively, the first support occupying an inner lumen of the second support, and the first support and the second support rotating relative to one another.

[0042] According to some embodiments of the present disclosure, the first support and the second support move the pin relative to one another with sufficient force to twist a portion of the collagen tissue at least 45° while the pin is inserted into the collagen tissue.

[0043] According to some embodiments of the present disclosure, the rotation of the first support and the second support relative to each other is limited to a maximum of less than 180°.

[0044] According to some embodiments of the present disclosure, the structural disruption energy comprises RF energy transmitted to the tip along a conductive wire.

[0045] According to some embodiments of the present disclosure, the pin is an electrode interconnected with a proximal power connection of the annuloplasty device via a conductive wire.

[0046] According to some embodiments of the present disclosure, the pin is configured to be retractable and extendable relative to a sheath through which the first support and second support are advanced to reach the target collagenous tissue.

[0047] According to some embodiments of the present disclosure, the sheath includes a steering mechanism.

[0048] In accordance with an aspect of some embodiments of the present disclosure, there is provided an annuloplasty device configured to deliver structural disruption energy to a tip portion terminating at a distal end of a catheter body, the annuloplasty device including: an opening at the tip portion configured to be in pressure communication with a controllable vacuum source through the catheter body, the opening configured for positioning against collagen tissue of a human cardiac valve annulus and having a shape, size, and position for engaging and deforming a portion of the collagen tissue upon activation of vacuum from the vacuum source; and a transducer attached to a conductive wire configured to transmit structural disruption energy from an electrical energy source to the transducer, the transducer positioned within the opening sufficient to transmit the structural disruption energy to the deformed portion of the collagen tissue.

[0049] According to some embodiments of the present disclosure, the opening is elongated.

[0050] According to some embodiments of the present disclosure, the transducer is an electrode.

[0051] According to some embodiments of the present disclosure, the transducer includes an acoustic energy transducer or a thermal energy transducer.

[0052] According to some embodiments of the present disclosure, the minimum radius of curvature of the opening is greater than or equal to about 0.25 mm.

[0053] According to some embodiments of the present disclosure, the transducer at least partially defines a perimeter of the opening.

[0054] According to some embodiments of the present disclosure, the transducer is positioned in contact with a surface of the portion of collagenous tissue that is drawn into the opening.

[0055] According to some embodiments of the present disclosure, the transducer is positioned in contact with a surface of the portion of collagen tissue adjacent at least a circumferential portion of the opening.

[0056] According to some embodiments of the present disclosure, the transducer includes portions disposed on at least two opposing sides of the opening.

[0057] According to some embodiments of the present disclosure, the transducer and the aperture are configured to move relative to one another along a proximal-distal axis.

[0058] According to aspects of some embodiments of the present disclosure, there is provided a method of annuloplasty of a human cardiac valve annulus, the method comprising: attaching a tip of an annuloplasty device to a portion of collagen tissue of the annulus; pulling the attached portion of the tip of the annuloplasty device while pushing against the tissue with a transducer, wherein the combined pulling and pushing acts to deform the tissue between the transducer and the attached portion; and supplying structural disruption energy through the transducer such that the attached portion undergoes plastic deformation toward its deformed shape.

[0059] According to some embodiments of the present disclosure, the attachment comprises vacuum attachment to the section of collagenous tissue.

[0060] According to some embodiments of the present disclosure, the pulling includes pulling the portion of collagen tissue into the recess.

[0061] According to aspects of some embodiments of the present disclosure, there is provided a method of annuloplasty of a human cardiac valve annulus, the method including: positioning a distal surface of a tip of an annuloplasty device against a portion of collagen tissue of the annulus, the distal surface including a transducer surface configured to deliver structural disruption energy; attaching to the collagen tissue to form an attachment with the collagen tissue; manipulating the attachment to distort the collagen tissue; and delivering the structural disruption energy through the transducer surface to plastically deform the attachment portion.

[0062] According to some embodiments of the present disclosure, the straining pulls a first portion of the collagen tissue to a first position proximal to the second position, while holding a second portion of the collagen tissue in the second position.

[0063] According to some embodiments of the present disclosure, the second location includes two regions, each on opposite sides of the first portion.

[0064] According to aspects of some embodiments of the present disclosure, there is provided a method of annuloplasty of a human cardiac valve annulus, the method including positioning a transducer of an annuloplasty device in contact with a superficial surface of a portion of collagen tissue of the annulus, inserting a plurality of pins through the superficial surface while the transducer remains in contact with the superficial surface, moving the pins to distort the collagen tissue, and delivering structural disruption energy via the transducer.

[0065] According to some embodiments of the present disclosure, positioning the transducer also positions at least one opening adjacent to the transducer in contact with the surface, and when inserting the multiple pins, the multiple pins extend from the at least one opening.

[0066] According to aspects of some embodiments of the present disclosure, there is provided a method of annuloplasty of a human cardiac valve annulus, the method comprising: inserting first and second pins of an annuloplasty device into a portion of collagen tissue of the annulus so that an axis extending therebetween and along a surface of the collagen tissue has a first orientation; moving at least one of the first and second pins to rotate the axis extending therebetween to a second orientation; and supplying structural disruption energy to plastically deform the tissue distorted by the movement, wherein the first and second pins are inserted into the collagen tissue of the annulus at an angle within 55° of a mean plane of the circumference of the annulus.

[0067] According to aspects of some embodiments of the present disclosure, there is provided a method of annuloplasty of a human cardiac valve annulus, the method comprising: inserting first and second pins of an annuloplasty device into a portion of collagen tissue of the annulus such that an axis extending therebetween along a surface of the collagen tissue has a first orientation; moving at least one of the first and second pins to rotate the axis extending therebetween to a second orientation; and supplying structural disruption energy to plastically deform the tissue distorted by the movement, wherein a plane parallel to a height axis of the annulus is within approximately 15° of bisecting an angle defined by the first and second orientations.

[0068] According to some embodiments of the present disclosure, the height axis extends from a first side of the annulus to a second side of the annulus and is perpendicular to a plane having a maximal uniform distance from the circumference of the annulus.

[0069] According to some embodiments of the present disclosure, attaching the tip of the annuloplasty device to collagen tissue of the annulus includes attaching to the circumference of the annulus at an angle of no more than 55° from the mean plane of the circumference.

[0070] According to some embodiments of the present disclosure, attaching the tip of the annuloplasty device to the collagen tissue portion of the annulus includes attaching it to the circumference of the annulus at an angle of no more than 55° from the mean plane of the circumference.

[0071] According to some embodiments of the present disclosure, positioning the transducer to contact a superficial surface of the collagen tissue portion of the annulus includes contacting the circumference of the annulus at an angle of less than 55° from the mean plane of the circumference.

[0072] According to some embodiments of the present disclosure, inserting the first and second pins of the annuloplasty device also includes inserting the pins at an angle of no more than 55° from the mean plane of the circumference of the annulus.

[0073] According to some embodiments of the present disclosure, the interference contact with the stop element includes interference between the assembly that rotates the pin and a portion of the housing of the assembly that acts as the stop element.

[0074] According to some embodiments of the present disclosure, the method includes measuring impedance during delivery and terminating delivery upon sensing an impedance above a threshold, the threshold being selected from the range of 1800 to 2500 Ω.

[0075] According to some embodiments of the present disclosure, the threshold is 2250 ohms.

[0076] According to some embodiments of the present disclosure, the method includes approaching a portion of collagenous tissue while measuring impedance, and performing insertion while measuring impedance in the range between 220 Ω and 500 Ω.

[0077] According to some embodiments of the present disclosure, the method includes measuring impedance during insertion and initiating movement after insertion when an impedance in the range of between 240 Ω and 360 Ω is measured.

[0078] According to an aspect of some embodiments of the present disclosure, there is provided a steering sheath for an annuloplasty device configured to interconvert between a straight configuration and a curved configuration upon receiving a steering control, the curved configuration including a helical shape at a distal end of the steering sheath.

[0079] According to some embodiments of the present disclosure, the steering sheath includes a spiral-shaped distally leading segment that assumes a curve in the curved configuration that remains substantially within the plane of the curve.

[0080] In accordance with aspects of some embodiments of the present disclosure, there is provided an annuloplasty device configured to deliver structural disruption energy to a device tip terminating at a distal end of a catheter body, the annuloplasty device including: a transducer configured to deliver structural disruption energy to a plurality of sites at locations around the circumference of a cardiac valve annulus; and an elongated, steerable body tilted by the transducer and including an elongated control member, the control member operable to cooperatively curl the steerable body and bend the steerable body out of the plane of curl.

[0081] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this disclosure pertains.Although methods and materials similar or equivalent to those described herein can be used in the implementation or testing of embodiments of this disclosure, exemplary methods and / or materials are described below.In case of conflict, the patent specification, including definitions, shall prevail.In addition, materials, methods, and examples are merely illustrative and are not necessarily intended to be limiting.

[0082] As will be appreciated by those skilled in the art, aspects of the present disclosure may be embodied as a system, method, or computer program product. Accordingly, aspects of the present disclosure may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, microcode, etc.), or an embodiment combining software and hardware aspects, all of which may be generally referred to herein as a "circuit," "module," or "system" (e.g., a method may be implemented using "computer circuitry"). Furthermore, some embodiments of the present disclosure may take the form of a computer program product embodied in one or more computer-readable medium(s) having computer-readable program code embodied thereon. Implementation of the methods and / or systems of some embodiments of the present disclosure may involve performing and / or completing selected tasks manually, automatically, or a combination thereof. Furthermore, depending on the actual instrumentation and equipment of some embodiments of the methods and / or systems of the present disclosure, some selected tasks may be implemented by hardware, software, or firmware, and / or a combination thereof, for example, using an operating system.

[0083] For example, hardware for performing selected tasks according to some embodiments of the present disclosure may be implemented as a chip or circuit. As software, selected tasks according to some embodiments of the present disclosure may be implemented as a plurality of software instructions executed by a computer using any suitable operating system. In some embodiments of the present disclosure, one or more tasks performed in the method and / or system are performed by a data processor (also referred to herein as a "digital processor," referring to a data processor that operates using groups of digital bits), such as a computing platform for executing a plurality of instructions. The instruction execution elements of the processor may comprise, for example, one or more microprocessor chips, ASICs, and / or FPGAs. Optionally, the data processor includes volatile memory for storing instructions and / or data, and / or non-volatile storage, e.g., a magnetic hard disk and / or removable media, for storing instructions and / or data. Optionally, a network connection is also provided. A display and / or user input devices, such as a keyboard or mouse, are also optionally provided. Any of these implementations are more generally referred to herein as an instance of a computer circuit.

[0084] Some embodiments of the present disclosure may utilize any combination of one or more computer-readable media. The computer-readable medium may be a computer-readable signal medium or a computer-readable storage medium. The computer-readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination thereof. More specific examples (non-exhaustive list) of computer-readable storage media include an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the above. As used herein, a computer-readable storage medium may be any tangible medium that can contain or store a program for use by or in connection with an instruction execution system, apparatus, or device. A computer-readable storage medium may also contain or store information for use by such programs, e.g., data structured in a manner recorded by the computer-readable storage medium so that the computer program can access it, for example, as one or more tables, lists, arrays, data trees, and / or other data structures. Here, a computer-readable storage medium that records data in a retrievable format as groups of digital bits is also referred to as a digital memory. It should be understood that in some embodiments, a computer-readable storage medium is optionally also used as a computer-writable storage medium in the case of a computer-readable storage medium that is not inherently read-only and / or in a read-only state.

[0085] Here, a data processor is said to be "configured" to perform data processing operations to the extent that it is coupled to a computer-readable medium, receives instructions and / or data therefrom, processes them, and / or stores the results of the processing on the same or another computer-readable medium. The operations to be performed (optionally on data) are specified by instructions, and the processor operates in accordance with the instructions. Processing operations may additionally or alternatively be referred to by one or more other terms, such as comparing, estimating, determining, calculating, identifying, associating, storing, analyzing, selecting, and / or transforming. For example, in some embodiments, a digital processor receives instructions and data from a digital memory, processes the data in accordance with the instructions, and / or stores the results of the processing in the digital memory. In some embodiments, "providing" the results of the processing includes one or more of transmitting, storing, and / or presenting the results of the processing. Presenting optionally includes displaying, sounding, printing on a printout, or otherwise providing the results in a form accessible to human sensory capabilities.

[0086] A computer-readable signal medium may include a propagated data signal having computer-readable program code embodied therein, for example, as part of a baseband or carrier wave. Such a propagated signal may take any of a variety of forms, including, but not limited to, electromagnetic, optical, or any suitable combination thereof. A computer-readable signal medium is not a computer-readable storage medium and may be any computer-readable medium that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.

[0087] The program code embodied on the computer readable medium and / or data used thereby may be transmitted using any suitable medium, including but not limited to wireless, wired, fiber optic cable, RF, etc., or any suitable combination of the foregoing.

[0088] Computer program code for carrying out operations according to some embodiments of the present disclosure may be written in any combination of one or more programming languages, including object-oriented programming languages ​​such as Java, Smalltalk, C++, and conventional procedural programming languages ​​such as the "C" programming language. Additionally or alternatively, logical operation sequences (optionally logical operations corresponding to computer instructions) may be incorporated into the design of an ASIC and / or the configuration of an FPGA device. The program code may execute entirely on the user's computer, partially on the user's computer as a standalone software package, partially on the user's computer and partially on a remote computer, or entirely on a remote computer or server. In the latter scenario, the remote computer may be connected to the user's computer via any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be to an external computer (e.g., via the Internet using an Internet Service Provider).

[0089] Some embodiments of the present disclosure may be described below with reference to flowchart diagrams and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the present disclosure. It will be understood that each block of the flowchart diagrams and / or block diagrams, and combinations of blocks in the flowchart diagrams and / or block diagrams, may be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general-purpose computer, a special-purpose computer, or other programmable data processor to produce a machine, and the instructions, executed via the processor of the computer or other programmable data processor, may form means for performing the functions / acts specified in one or more blocks of the flowchart diagrams and / or block diagrams.

[0090] These computer program instructions may also be stored on a computer-readable medium that can direct a computer, other programmable data processor, or other device to function in a particular way to produce an article of manufacture, where the instructions stored on the computer-readable medium include instructions that implement the functions / acts specified in one or more blocks of the flowcharts and / or block diagrams.

[0091] Computer program instructions may also be loaded into a computer, other programmable data processor, or other device to cause the computer, other programmable apparatus, or other device to perform a series of operational steps to create a computer-implemented process, such that the instructions, which execute on the computer or other programmable apparatus, provide a process for performing the functions / acts specified in one or more blocks of the flowcharts and / or block diagrams.

[0092] Some of the methods described herein are generally designed for use by a computer only and may not be feasible or practical for purely manual execution by a human expert. A human expert attempting to manually perform a similar task, such as inspecting an object, would be expected to use an entirely different method, e.g., leveraging expert knowledge and / or the pattern recognition capabilities of the human brain, which would be far more efficient than manually performing the steps of the methods described herein. [Brief explanation of the drawings]

[0093] Certain embodiments of the present disclosure are herein described, by way of example only, with reference to the accompanying drawings. Referring now specifically to the drawings in detail, it is emphasized that the particulars shown are by way of example and for illustrative purposes of explanation of embodiments of the present disclosure. In this regard, the description taken together with the drawings will make apparent to those skilled in the art how embodiments of the present disclosure may be practiced. [Figure 1A] 1A-1C are schematic illustrations of a cardiac annuloplasty device operable to form annulus tissue using a vacuum, according to some embodiments of the present disclosure. [Figure 1B] 1B is a schematic flowchart of a method of performing an annuloplasty procedure using the device of FIG. 1A, according to some embodiments of the present disclosure. [Figure 1C] 1B illustrates a schematic diagram of the operation of the device of FIG. 1A according to some embodiments of the present disclosure. [Figure 1D] 1B illustrates a schematic diagram of the operation of the device of FIG. 1A according to some embodiments of the present disclosure. [Figure 1E] 1B illustrates a schematic diagram of the operation of the device of FIG. 1A according to some embodiments of the present disclosure. [Figure 1F] 1B is a schematic illustration of damage caused by the device of FIG. 1A, according to some embodiments of the present disclosure. [Figure 2A] 10A-10C are photographs of ex vivo damage caused to a pig tricuspid heart valve using a device according to some embodiments of the present disclosure. [Figure 2B]1 is a pre-injury photograph of an injury area created ex vivo in a pig tricuspid heart valve using a device according to some embodiments of the present disclosure. [Figure 2C] 10A-10C are photographs of post-lesioning lesion areas created ex vivo in a pig tricuspid heart valve using a device according to some embodiments of the present disclosure. [Figure 2D] 1 is a pre-injury photograph of an injury area created ex vivo in a pig tricuspid heart valve using a device according to some embodiments of the present disclosure. [Figure 2E] 10A-10C are photographs of post-lesioning lesion areas created ex vivo in a pig tricuspid heart valve using a device according to some embodiments of the present disclosure. [Figure 2F] 1 is a photograph of a sectioned lesion created ex vivo in a porcine tricuspid cardiac valve using a device according to some embodiments of the present disclosure. [Figure 2G] 2F schematically illustrates an area corresponding to the feature in the photograph of FIG. 2F, according to some embodiments of the present disclosure. [Figure 2H] 10A-10C are photographs of a series of lesions created ex vivo in a porcine heart mitral valve using a device according to some embodiments of the present disclosure. [Figure 2I] 10A-10C are photographs of a series of lesions created ex vivo in a porcine heart mitral valve using a device according to some embodiments of the present disclosure. [Figure 2J] 1 is a photograph of a sectioned lesion sequence created ex vivo in a porcine heart mitral valve using a device according to some embodiments of the present disclosure. [Figure 3A] 1A-1C are schematic diagrams of a distal end of a cardiac annuloplasty device according to some embodiments of the present disclosure. [Figure 3B] 1 is a schematic diagram of a distal perspective view of a tip of a cardiac annuloplasty device, according to some embodiments of the present disclosure. [Figure 3C] 1A-1C are schematic diagrams of handles and connection regions of a cardiac annuloplasty device, according to some embodiments of the present disclosure. [Figure 4A] 1A-1C schematically illustrate a distal end of a heart annuloplasty device with a vacuum attachment element in an advanced position, according to some embodiments of the present disclosure. [Figure 4B] 1A-1C schematically illustrate a distal end of a heart annuloplasty device with a vacuum attachment element in a retracted position, according to some embodiments of the present disclosure. [Figure 4C] 4A-4B, according to some embodiments of the present disclosure. [Figure 5A] 1A-1C are schematic illustrations of a cardiac annuloplasty device operable to shape annulus tissue using needle penetration and twisting, according to some embodiments of the present disclosure. [Figure 5B] 5B is a schematic flowchart of a method of performing an annuloplasty procedure using the device of FIG. 5A, according to some embodiments of the present disclosure. [Figure 5C] 5B illustrates a schematic diagram of the operation of the device of FIG. 5A according to some embodiments of the present disclosure. [Figure 5D] 5B illustrates a schematic diagram of the operation of the device of FIG. 5A according to some embodiments of the present disclosure. [Figure 5E] 5B illustrates a schematic diagram of the operation of the device of FIG. 5A according to some embodiments of the present disclosure. [Figure 5F] 5B illustrates a schematic diagram of the operation of the device of FIG. 5A according to some embodiments of the present disclosure. [Figure 5G] FIG. 5B is a schematic illustration of damage caused by the device of FIG. 5A, according to some embodiments of the present disclosure. [Figure 6A] 5B is a pre-lesion photograph of a lesion area created ex vivo in a pig heart using the device of FIG. 5A, according to some embodiments of the present disclosure. [Figure 6B] 5B is a post-lesion photograph of a lesion area created ex vivo in a pig heart using the device of FIG. 5A, according to some embodiments of the present disclosure. [Figure 6C] 6C is a photograph of the pre-sectioning appearance of the lesion of FIG. 6B according to some embodiments of the present disclosure. [Figure 6D] 6C is a photograph of the appearance of the lesion of FIG. 6B after sectioning, according to some embodiments of the present disclosure. [Figure 6E]5B is a pre-injury photograph of the area of ​​the injury created ex vivo in a pig heart using the device of FIG. 5A, according to some embodiments of the present disclosure. [Figure 6F] 5B is a photograph of the region of the injury created ex vivo in a pig heart using the device of FIG. 5A after injury, according to some embodiments of the present disclosure. [Figure 6G] 6F after sectioning, according to some embodiments of the present disclosure. [Figure 6H] 6C depicts estimated movement of tissue and pin electrode positions superimposed on the lesion image of FIG. 6B, according to some embodiments of the present disclosure. [Figure 6I] 6C illustrates the estimated movement of FIG. 6B according to some embodiments of the present disclosure. [Figure 7A] 1A-1C schematically illustrate a distal end of a heart annuloplasty device in different operating states, according to some embodiments of the present disclosure. [Figure 7B] 1A-1C schematically illustrate a distal end of a heart annuloplasty device in different operating states, according to some embodiments of the present disclosure. [Figure 7C] 7C schematically illustrates an end view of the operational state of FIG. 7B according to some embodiments of the present disclosure. [Figure 7D] 1A-1C schematically illustrate a distal end of a heart annuloplasty device in different operating states, according to some embodiments of the present disclosure. [Figure 7E] 7D, according to some embodiments of the present disclosure. [Figure 8A] 1A-1C schematically illustrate a distal end of a heart annuloplasty device in different operating states, according to some embodiments of the present disclosure. [Figure 8B] 1A-1C schematically illustrate a distal end of a heart annuloplasty device in different operating states, according to some embodiments of the present disclosure. [Figure 9] 8A-8B in use during ex vivo lesioning of a porcine heart valve, according to some embodiments of the present disclosure. [Figure 10A]1A-1C schematically illustrate a distal end of a heart annuloplasty device in different operating states, according to some embodiments of the present disclosure. [Figure 10B] 1A-1C schematically illustrate a distal end of a heart annuloplasty device in different operating states, according to some embodiments of the present disclosure. [Figure 10C] 1A-1C schematically illustrate a distal end of a heart annuloplasty device in different operating states, according to some embodiments of the present disclosure. [Figure 11] 1A and 1B illustrate schematic diagrams of a distal end of a cardiac annuloplasty device according to some embodiments of the present disclosure. [Figure 12A] 10A-10C schematically depict a casing of a distal end of an annuloplasty device, according to some embodiments of the present disclosure. [Figure 12B] 10A-10C schematically depict a casing of a distal end of an annuloplasty device, according to some embodiments of the present disclosure. [Figure 12C] 10A-10C schematically depict a housing at the tip of an annuloplasty device, according to some embodiments of the present disclosure. [Figure 13A] 1A-1C are schematic representations of a partially assembled tip of an annuloplasty device, according to some embodiments of the present disclosure. [Figure 13B] 1A-1C schematically illustrate a partially assembled tip of an annuloplasty device with an added housing, according to some embodiments of the present disclosure. [Figure 13C] 1A-1C schematically illustrate a partially assembled tip of an annuloplasty device with an added housing, according to some embodiments of the present disclosure. [Figure 13D] 10A-10C schematically illustrate a distal end of an annuloplasty device with an additional catheter casing, according to some embodiments of the present disclosure. [Figure 14] 1 shows a fluoroscopic (X-ray) image of the distal tip of an annuloplasty device in situ (i.e., within a chamber of the heart) according to some embodiments of the present disclosure. [Figure 15A] 1A and 1B illustrate schematic diagrams of a horizontal (transverse) cross section through the left side of the heart, including the left atrium and left ventricle, according to some embodiments of the present disclosure. [Figure 15B]1 shows a 3D reconstructed ultrasound image looking down on a valve and a horizontal (transverse) cross section from above, according to some embodiments of the present disclosure. [Figure 15C] 1A and 1B illustrate schematic diagrams of a horizontal (transverse) cross section through the left side of the heart, including the left atrium and left ventricle, according to some embodiments of the present disclosure. [Figure 15D] 1A and 1B illustrate schematic diagrams of a coronal (frontal) cross section through the left side of the heart, including the left atrium and left ventricle, according to some embodiments of the present disclosure. [Figure 15E] 1 shows a planar ultrasound image providing a coronal cross-section (corresponding to a coronal slice) of a valve (eg, showing the valve leaflets), according to some embodiments of the present disclosure. [Figure 15F] 1A and 1B illustrate schematic diagrams of a coronal (frontal) cross section through the left side of the heart, including the left atrium and left ventricle, according to some embodiments of the present disclosure. [Figure 16A] 10A-10C show a sequence of 3D reconstructed ultrasound images obtained at different tip positions and / or articulations as the pin element is moved around the circumference of the mitral valve annulus, according to some embodiments of the present disclosure. [Figure 16B] 10A-10C show a sequence of 3D reconstructed ultrasound images obtained at different tip positions and / or articulations as the pin element is moved around the circumference of the mitral valve annulus, according to some embodiments of the present disclosure. [Figure 16C] 10A-10C show a sequence of 3D reconstructed ultrasound images obtained at different tip positions and / or articulations as the pin element is moved around the circumference of the mitral valve annulus, according to some embodiments of the present disclosure. [Figure 16D] 10A-10C show a sequence of 3D reconstructed ultrasound images obtained at different tip positions and / or articulations as the pin element is moved around the circumference of the mitral valve annulus, according to some embodiments of the present disclosure. [Figure 16E] 10A-10C show a sequence of 3D reconstructed ultrasound images obtained at different tip positions and / or articulations as the pin element is moved around the circumference of the mitral valve annulus, according to some embodiments of the present disclosure. [Figure 16F] 10A-10C show a sequence of 3D reconstructed ultrasound images obtained at different tip positions and / or articulations as the pin element is moved around the circumference of the mitral valve annulus, according to some embodiments of the present disclosure. [Figure 16G] 10A-10C show a sequence of 3D reconstructed ultrasound images obtained at different tip positions and / or articulations as the pin element is moved around the circumference of the mitral valve annulus, according to some embodiments of the present disclosure. [Figure 16H] 10A-10C show a sequence of 3D reconstructed ultrasound images obtained at different tip positions and / or articulations as the pin element is moved around the circumference of the mitral valve annulus, according to some embodiments of the present disclosure. [Figure 16I] Various positions in Figures 16A to 16H are superimposed on one image. [Figure 17A] 1 shows a fluoroscopic (X-ray) image of a pin assembly (which may include a radiopaque material such as tantalum) in situ (i.e., within a chamber of the heart) associated with a radiopaque marker, and a schematic diagram thereof, according to some embodiments of the present disclosure. [Figure 17B] 1 shows a fluoroscopic (X-ray) image of a pin assembly (which may include a radiopaque material such as tantalum) in situ (i.e., within a chamber of the heart) associated with a radiopaque marker, and a schematic diagram thereof, according to some embodiments of the present disclosure. [Figure 18A] 1A-1C schematically depict views of a pin assembly and radiopaque marker in different rotational positions, according to some embodiments of the present disclosure. [Figure 18B] 10A-10C show x-ray images of a distal tip, including views of the pin from different rotation angles, according to some embodiments of the present disclosure. [Figure 18C] 10A-10C show x-ray images of a distal tip, including views of the pin from different rotation angles, according to some embodiments of the present disclosure. [Figure 18D] 10A-10C show x-ray images of a distal tip, including views of the pin from different rotation angles, according to some embodiments of the present disclosure. [Figure 19A] 10A-10C are schematic representations of an overtube assuming compound bending that imparts both curvature and out-of-plane displacement, according to some embodiments of the present disclosure. [Figure 19B] 10A-10C are schematic representations of an overtube assuming compound bending that imparts both curvature and out-of-plane displacement, according to some embodiments of the present disclosure. [Figure 19C] 10A-10C are schematic representations of an overtube (or the catheter itself similarly configured for steering) in relation to a generally saddle-shaped valve annulus, according to some embodiments of the present disclosure. [Figure 19D] 10A-10C are schematic representations of an overtube (or the catheter itself similarly configured for steering) in relation to a generally saddle-shaped valve annulus, according to some embodiments of the present disclosure. [Figure 20] 1 is a schematic flow chart illustrating targeted and / or expected thresholds and / or ranges of bioimpedance in ohms (Ω) for various stages and / or conditions during an annuloplasty procedure, according to some embodiments of the present disclosure. [Figure 21] 1 is a schematic flow chart depicting a method of operating an annuloplasty device, according to some embodiments of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0094] The present invention in some embodiments thereof relates to the field of structural heart disease, and more particularly, but not exclusively, to heart annuloplasty.

[0095] overview A broad aspect of some embodiments of the present disclosure relates to annuloplasty performed using energy-induced tissue contraction and / or remodeling applied to the region of the annular ring of a valve. Examples of valves treated in some embodiments of the present disclosure include, but are not limited to, the tricuspid valve and the mitral valve.

[0096] Currently, the primary method for treating atrial fibrillation is ablation using RF energy along the left atrial wall surrounding the pulmonary veins. Pulmonary vein stenosis (PVS) has been reported as a side effect of this procedure. PVS can also result from ablation procedures performed using other methods, such as cryoablation (for example, as reported by Non-Patent Document 1).

[0097] PVS is caused by pulmonary vein constriction induced by the contraction of the ablated tissue area. The physiological mechanism by which ablation causes pulmonary vein stenosis is due to scarring of the connective tissue surrounding the pulmonary veins, as described, for example, in Non-Patent Document 2.

[0098] The inventors describe herein an endovascular approach that utilizes tissue contraction induced by the application of structural disruptive energy to treat leaky heart valves. Leakage is characterized by the failure of the heart valve leaflets to fully close (coapt) in response to back pressure. This allows for backflow of blood, impairing the efficiency of the heart's pumping.

[0099] In some embodiments of the present disclosure, tissue around the periphery of the annulus is remodeled by application of structural disruptive energy in combination with application of mechanical forces that deform the tissue.

[0100] In some embodiments, this includes energy sufficient to induce fibrosis in the tissue. In some embodiments, the energy is provided in the form of radiofrequency (RF) electromagnetic power, which causes localized heating of the tissue, e.g., to the extent that fibrosis is induced. In some embodiments, another form of energy delivery that produces heating is used. It is potentially advantageous for the energy to be provided in a form that can be converted to produce significant levels of heating only upon delivery to the target site and / or that can be focused on the target without producing significant heating effects outside the region of focus. For example, acoustic energy (e.g., focused ultrasound) or laser energy is used. The effect on tissue by the application of structurally disruptive energy is also referred to herein as "lesioning." Such treatments may also be referred to as "ablation," to the extent that, for example, cell death occurs in a portion of the treated tissue. The delivery of energy may directly damage the valve annulus tissue (i.e., damage the collagen tissue of the annulus) and / or damage nearby tissue, e.g., the atrial wall above the mitral or tricuspid valve.

[0101] Some embodiments of the present disclosure are configured and operated to impose a mechanical force at a treatment site where construct-disrupting energy is also applied. Briefly, tissue is mechanically deformed (e.g., compressed, but not necessarily only compressed) in the energy delivery region, changing its shape. When construct-disrupting energy is applied and released, at least a portion of the mechanical deformation remains imprinted on the tissue (plastic deformation).

[0102] When properly placed and optionally repeated at multiple sites, it may potentially coapt the leaflets of a regurgitating heart valve, or if coaptation is not achieved, reduce the severity of the regurgitation by reducing the gap remaining between the leaflets in their fully closed state. In some cases, the loss of previously normal leaflet coaptation may itself be caused by reshaping (lengthening) the valve annulus. Thus, annular reduction treatments may restore the heart valves to their original relationship with each other.

[0103] The plastic deformation effect does not necessarily require cell death (or at least not complete cell death) induced by the application of structural disruption energy. For example, at sub-ablation thresholds, the fibrotic structure of tissue can become more malleable by heating it and / or by changing its pH through the passage of an electrolytic current. This structural disruption that results in malleability can optionally be induced simultaneously with or separately (in time) from the mechanical manipulation. However, because the duration of plastic malleability is very short, mechanical deformation must first be induced and then maintained while the structural disruption energy is applied.

[0104] The effects of plastic remodeling due to mechanical forces described in embodiments herein are generally acute, occurring during the course of a procedure using an instrument to apply the mechanical force, during the application of the structural disruptive energy, or shortly thereafter.

[0105] Without being bound by any particular theory, this sensitive effect can be understood as being influenced by the disordering effect of solidification, which acts to relieve stress and / or strain in tissues deformed by external mechanical forces. This effect effectively gives the solidified tissue a new "preferred shape" even after the external mechanical force is removed (i.e., plastic deformation). It is possible that mechanisms other than solidification may influence plastic deformation when structural disruption energy is applied to tissues deformed by external forces. For example, it has been proposed that electrolysis of water in tissues generates free protons, which temporarily affect the self-bonding of the collagen matrix, making it more susceptible to plastic deformation.

[0106] In addition to the above, disruption by structural disruptive energy may itself induce contraction, resulting in a corresponding reduction in the overall annular circumference. Without being bound by any particular theory, contraction may result from, for example, loss of cellular structure, relaxation of internal stresses in connective fibers, degenerative (coagulative) effects on tissue structure that persist after energy delivery, and / or the effects of healing processes that occur after treatment.

[0107] Contraction can have immediate or near-immediate effects (eg, due to loss of fluid or shrinkage of cellular components) or slower effects due to induced atrophy and / or healing processes.

[0108] There are two types of ablation performed on cardiac tissue to treat atrial fibrillation: thermal ablation, using radiofrequency (RF) or ultrasound energy, and cryoablation. Both types of ablation are associated with pulmonary vein stenosis. However, differences in the two mechanisms may result in different tissue remodeling effects. For example, the effects of thermal ablation include coagulation, which directly affects cellular structural components, whereas the primary effect of cryoablation is to disrupt cellular organization and processes, leading to downstream degeneration of cellular structural components that may be under biological control. Electroporation is another cell ablation mechanism, whose initial effect is primarily destructive rather than denaturing (coagulating). As mentioned above, electrolysis of tissue water has also been proposed as a mechanism for disrupting the collagen matrix by partially acidifying it. In some embodiments, other mechanisms for applying structurally disruptive energy are provided, such as acoustic energy (e.g., focused ultrasound) or laser energy. Direct application of thermal energy, for example, via electrical heating of a heating element in contact with the tissue to be remodeled, is not excluded. However, modes of energy application that involve penetration into tissue before conversion to heat offer potential advantages with respect to uniformity of energy distribution, avoidance of hot spots (e.g., scorching or other "overcooking"), and / or safety.

[0109] In some embodiments of the present disclosure, annuloplasty, performed by structural tissue destruction, reduces the overall valve circumference by up to approximately 5-10%, or potentially more. The annular remodeling can be targeted to any selected portion of the annular circumference. For example, tissue destruction can be performed at approximately equally spaced sites, or alternatively, tissue destruction can be performed at sites grouped in one or more specific regions around the circumference. The tissue involved in an individual injury may be reduced in size by significantly more than 5-10%. For example, in the in vitro experiments described herein, it was found that a localized treatment area of ​​approximately 5 mm can induce a reduction of 20% or more, up to approximately 40%. These values ​​do not represent an upper limit.

[0110] Aspects of some embodiments of the present disclosure relate to annuloplasty devices that combine the use of structural disruption energy coupled with torsional mechanical manipulation.

[0111] For example, it can be seen from the teachings of International Patent Publication No. WO2002 / 097130 that torsion applied to tissue can provide a manner of applying mechanical deformation to tissue that can be plastically set by the application of structural disruption energy.

[0112] In further studies, the inventors found that for the same overall device diameter, torsion-induced mechanical contraction can result in greater contraction than pinch-type compression, where the pins are closer together. For example, the contraction per injury site induced to an average of 1.9 mm using a pinch-type compression device can be increased to approximately 2.5 mm using a torsion-induced device.

[0113] In some embodiments of the present disclosure, twisting is achieved by rotation of two separately penetrating operating elements about a common center, where such operating elements are also referred to as pins (more specifically, when the functions of both electrode and mechanical operation are shared by the same element, the term "pin electrode" may also be applied).

[0114] For example, compared to direct pin-to-pin compression (pinching), torsion offers the potential advantage of exerting mechanical compression on the tissue beyond the pins, potentially extending approximately along the axis extending between the two pins. Conversely, direct compression between the two pins may be somewhat reduced (e.g., unless the pins are close to each other). Different patterns of tissue contraction may result in a more even distribution of internal forces, which may help reduce the likelihood of tearing during application of structural disruption energy and / or may help reduce undesirable distortion of the treated annulus. Greater distribution of contraction may also reduce the peak amount of induced deformation, ultimately resulting in a relatively smooth surface, even if the amount of contraction introduced is comparable, the same, or even greater. For example, a single, large central pinched region could be replaced with a lower central bulge, with additional peripheral crimping as needed to further accommodate the induced deformation.

[0115] Furthermore, because there are limitations to how much contraction can be achieved on a given tissue surface, mechanical deformation methods that distribute contraction over a wider area offer potential advantages. Contraction of the valve annulus is preferably concentrated in areas near the sites where the valve leaflets must cooperate. Therefore, there is potential value in being able to achieve relatively large contractions within a single lesion. Given the limited circumferential space available at the preferred placement location(s), each treatment site there can preferably receive as much contraction as can be reliably achieved. In either case, this may allow fewer treatment sites to be accessed overall, potentially simplifying and / or shortening the annuloplasty procedure. This may also facilitate the design of procedures that avoid approaching sensitive and / or functionally critical regions of tissue, such as the atrioventricular node (e.g., in the case of tricuspid annuloplasty), by concentrating contraction in areas away from such sensitive and / or functionally critical regions.

[0116] By twisting the tissue, it may be possible to use a smaller device footprint to achieve the same distance of effective contraction per treatment site. For example, instead of reducing a footprint with an initial width of approximately 4 mm by approximately 2 mm (e.g., by pinching), using a rotational (twisting) motion may allow the same amount of effective contraction to be achieved with a fixed initial width of 1.5 mm. This may allow for more treatment sites to be placed in a single procedure and achieve greater overall contraction. Treatment sites may be placed more centrally (linearly and tightly) to focus annular remodeling in areas most likely to promote coaptation and / or to avoid risk areas, such as areas near the atrioventricular node or other sensitive areas. Furthermore, it may be possible to leave more unmodified tissue available for correction in future procedures, for example, if the valve continues to remodel over time and / or if the initial procedure proves not to have achieved complete or intended results. This also potentially allows physicians the freedom to be less aggressive in the initial annuloplasty procedure, leaving more room for a second annuloplasty if necessary.

[0117] In the pinching / squeezing approach, it is the compression and / or displacement of tissue within the initial "bite" distance of the manipulating element that determines the degree of contraction. The "bite" distance sets a temporary maximum amount of contraction per site, but in practice, the tissue is not expected to contract or displace sufficiently for the engaging "jaws" (e.g., needles, pins, or other grasping and / or penetrating elements) to fully converge. As a result, the maximum amount of contraction can be much less than the initial bite distance.

[0118] However, with torsional distortion, tissue regions displaced in opposite directions are also offset from one another and therefore do not move directly toward one another (i.e., colliding). Thus, for example, a 90° rotation can shorten some distances along at least some axes (e.g., the distance between two tissue regions circumferentially around the annulus) by approximately the full distance between the pins. Not all regions are affected in this way; for example, twisting can also produce complementary deformations in other tissues (e.g., tissue previously positioned "vertically" becomes more "horizontal," i.e., displaced further along the annulus circumference). However, the overall pattern of tissue distortion due to torsion can deviate from perfect radial symmetry (e.g., predominantly contraction along the annulus circumference and less contraction along the annulus height) through appropriate initial placement of the manipulating elements and selection of the rotation angle.

[0119] Additionally, twisting also induces a tissue compression component, as it tends to draw the tissue generally radially inward. This compression may be lower in peak percentage terms than the compression exerted on the "pinched" tissue, for example, but may be distributed over a larger area (e.g., including compression of areas along but beyond the diameter of the "engagement" established by the manipulating elements), resulting in a net effect on circumferential size that may be similar to or greater than that achieved by throttling at the same diameter of the "engagement."

[0120] Considering another optional priority, it may be potentially advantageous to distribute the contraction of the annulus as evenly as possible, for example, to reduce the level of intervention at any one location and / or to avoid introducing irregularities in the shape or function of the annulus, which may shift the emphasis to evenness of treatment effect and correspondingly to strategically controlling how much contraction occurs at each location.

[0121] In some embodiments of the present disclosure, an annuloplasty device is provided that is configured to exert torsional strain through a limited range of motion provided on the pin, with the motion limited by the device to a predetermined maximum angle or otherwise specified maximum distance. This limit may be absolute or may be self-limiting and dependent on the device operating in its intended mode. In some embodiments, the total available range of motion is also the typically preferred or user-selected amount used to collect tissue. In some embodiments, the range of motion is selectable, for example, by selecting which particular annuloplasty device is used and / or by adjusting settings (e.g., slot size, protrusions or other interfering elements, or controlled range of motion) that impose desired limits on the range of motion. Partial rotation within the limited available range is also an option in some embodiments, with the rotation limit acting as a safety limit, for example.

[0122] The rotation limits can be set, for example, by stops with physically interfering structures that, when contacted, prevent further movement. Such stop locations can be provided on the tip of the device (e.g., to directly prevent rotation beyond a certain angle) and / or to limit the movement of a control element. Additionally or alternatively, sensing can be provided to indicate rotational position, for example, using electrical contacts or another form of electronically and / or mechanically implemented position encoding. The sensing status can be indicated to the user by an LED, a tactile vibrator, a buzzer and / or speaker, a display presented on a screen, or other methods.

[0123] Ensuring a predetermined range of rotational motion has the potential advantage of applying torsion in a manner sufficient to achieve contraction, but not excessive enough to cause tearing or other unintended damage upon application of force and / or delivery of structure-disrupting energy. For example, application of heating by RF energy delivery can weaken tissue to the point that it can induce tissue tearing under excessive stress. Thus, there may be a preferred (e.g., effective) maximum amount of rotation that is safely tolerated.

[0124] Additionally (and related to the above type of problem), a predetermined range of rotational motion helps to apply twist in a predictable and / or reproducible manner. A surgical plan may target a specific amount of perivalvular reduction and / or other remodeling, for example, using a specific number of treatment sites. The ability to set (or select) a reduction target using an annuloplasty device is a potential advantage and, in itself, aids in achieving that goal.

[0125] In some embodiments of the present disclosure, an annuloplasty device is provided that is configured to exert torsional strain by rotation of two separately penetrating operating elements about a common center disposed medially therebetween. Additionally or alternatively, in some embodiments of the present disclosure, an annuloplasty device is provided that is configured to exert torsional strain by rotation of two separately penetrating operating elements about a common center disposed closer to one of them. Optionally, the common center is also along the axis of one of the penetrating operating elements. In some embodiments, the torsion occurs in conjunction with direct compression exerted by pins that are adjacent to each other. Optionally, the direct compression is transient (e.g., the two pins slide past each other but eventually return to their original distance from each other).

[0126] Although different offsets of the rotation axis may slightly change how forces are exerted through the tissue as the pin rotates, this makes little, if any, difference since the redistribution of forces may ultimately displace the effective axis to the same final position (if not otherwise locked in place).

[0127] When the pins initially penetrate the tissue, changes in the orientation of another axis centered on and extending through both pins can be associated with significant differences in the resulting pattern of tissue deformation. This can be roughly explained as follows: tissue in surface regions angularly closer to the initial penetration axis defined above tends to be relatively more drawn around its center (i.e., tangentially), while tissue in surface regions further away tends to be relatively drawn toward the center (i.e., radially). Thus, depending on the orientation of the initial penetration axis, along one axis (e.g., along the annular circumference), all four quadrants may have a significant component of contraction, while along an orthogonal axis (e.g., along the annular height axis), only two of them contract. In other words, there exists a "contraction ratio" between the two axes, which is not necessarily equal to 1, and is also referred to herein as contraction anisotropy. The actual contraction anisotropy may depend on the amount of angular twist imparted to the pin and may be particularly relevant for rotations significantly smaller than a full rotation (e.g., less than 180° or less than 90°). In some embodiments, the pins can rotate at least 45° while inserted into tissue. The pins are proximally fixed to provide sufficient rigidity to overcome tissue forces that tend to resist deformation. For example, the pins can be fixed to a common base that rotates within the housing, or to respective bases that rotate or otherwise move relative to the housing. In some embodiments, one of the pins is fixed to the housing, while the base that fixes the other pin is movable relative to the housing.

[0128] It should also be noted that for large (potentially maximal) contractions in a selected direction (e.g., between points A and B), the initial axis of penetration may be angled relative to a midplane perpendicular to AB and bisecting AB, such that the midplane bisects the angle at which the pin establishing the penetration angle sweeps from its initial position to its final position. For example, if the sweep angle is approximately 90°, the initial axis of penetration is at an angle of approximately 45° from the bisecting midplane. To target approximately maximal contractions around the circumference of the annulus, the midplane can be selected to extend parallel to the valve height axis (e.g., an axis extending from a first side of the annulus to a second side of the annulus, perpendicular to the plane having the greatest uniform distance from the circumference of the annulus). To account for expected anatomical variations and / or to implement these instructions, the midplane is preferably selected within 15° of the actual bisecting angle, or at another angle, e.g., 10°, 20°, or 25°.

[0129] Thus, in some embodiments, torsional deformation involves rotating an axis extending between the tissue-implanting pins of the device from a first angle oblique to the local circumferential direction, through an intermediate angle perpendicular to the local circumferential direction, to a second such angle. In some embodiments, the first angle and the second angle are approximately equal from the intermediate angle, e.g., offset by within 15° of each other. In some embodiments, the first angle and the second angle differ from each other by about 60° to 120°.

[0130] To resolve discrepancies in the application of the aforementioned instructions, a circumferential definition that more closely approximates the primary valve circumference is preferred in the results (when comparisons are available) or definitions (when not). The primary valve circumference extends along the surface of the collagen tissue of the annulus and around its periphery in a closed curve. The primary valve circumference is located at equal distances between the collagen tissue edges. For practical calculations, the edge distance is measured at several clearly identifiable landmarks around the circumference, preferably eight, preferably equally spaced, and preferably only one fixed at the widest part of the annulus. Intermediate positions are smoothly interpolated by spline fitting. If a specific cardiac phase must be selected to resolve the circumference definition with sufficient precision, a phase in which the cardiac annulus is more planar is preferred. These considerations are generally applied arbitrarily to resolve discrepancies arising from the geometric specification of the valve circumference.

[0131] Potential benefits of annuloplasty include control of contraction anisotropy. Potentially different from "pinch" methods of introducing mechanical deformation, torsion-induced deformation is omnidirectional in its effect, tending to draw tissue inward at least partially from all sides. This may result in torsion-induced contraction along the annular height axis, which may be a by-product of potential benefits in contraction uniformity, contraction distribution, and / or stress relaxation (e.g., relative to pinch-type deformation), but is not necessarily therapeutically meaningful in itself. Thus, some embodiments of the present disclosure provide methods of control and manipulation that help manage how contraction anisotropy is introduced into target tissue.

[0132] In some embodiments of the present disclosure, the rotating pins are configured to rotate in response to actuation of a control distal to the elongate element (e.g., an elongate tubular element, also referred to herein as a catheter) to which they are attached. The control optionally comprises, for example, a button, knob, slider, lever, or other mechanism. The control optionally operates, for example, as a release (e.g., of spring tension). Optionally, the control rotates the pin through an angle having a magnitude corresponding to the degree of movement imparted to the control. The rotating pins are configured to rotate while implanted in the annulus tissue, such that the annulus tissue surrounding the pin moves with the pin. Thus, the control exerted thereon is configured to transmit a torque amount significantly greater than that required to rotate the pin in free fluid, for example, at least 0.002 N·m, 0.005 N·m, 0.01 N·m, 0.02 N·m, or another torque amount. In some embodiments, the twisting is sufficient to deform the tissue according to one or more of various criteria. For example, the rotation of the pins moves the tissue relative to one of the pins (the reference pin) by at least 90% of the distance (e.g., between two points on a circle centered on the reference pin) moved by another pin (the moving pin in a given reference frame) relative to the reference pin. The tissue may be in direct contact with the moving pin, or it may be another tissue, e.g., tissue at least 25%, 50%, 75%, or 100% of the inter-pin distance from the moving pin. This criterion uses the reference pin to define a rotational reference frame for measurement purposes. The actual rotation imparted (i.e., relative to a reference frame containing a fixed object at a distance) is not necessarily a rotation of one pin around another pin, but may even be a rotation of the reference pin around a nominally "moving" pin. This criterion can be modified to include a minimum threshold of relative angular movement of the pins, e.g., at least 30°, at least 45°, at least 60°, or at least 90°. If the relative distance of the pins also changes, the same criteria can be applied, modified as necessary to account for relative linear motion.

[0133] The pins are preferably short to maintain stability during rotation, yet long enough to accommodate their role in manipulating tissue. For example, the pins may be approximately 2-6 mm, 2-8 mm, or other lengths. Furthermore, the pins are stably secured (e.g., attached to a mounting block) so that they can transmit manipulation torque to the tissue without deforming themselves, e.g., no more than 10° of deflection, preferably less. The pins may be spaced, for example, approximately 1-2 mm, e.g., approximately 1.3 mm, apart. This distance range is appropriate for use with pins having a maximum diameter of approximately 0.6 mm (e.g., 0.4 mm x 0.4 mm square cross-section) and an overall catheter having a maximum outer diameter of approximately 5 mm. In some embodiments, the pins are spaced a greater distance apart, e.g., approximately 3 mm, approximately 4 mm, or another distance apart. This distance is preferably no greater than the axial height of the valve annulus (e.g., a circumferentially continuous ring of collagenous tissue). In some embodiments, the distance is less than 80%, less than 66%, less than 50% of this height, or another maximum relative distance. Larger distances may be less traumatic to achieve a desired degree of contraction, but may tend to unacceptably deform the annulus along the axial height axis. However, such deformation may be acceptable and manageable in some circumstances, such as alternating clockwise and counterclockwise deformations. For example, it may even be desirable to distort the annulus more in the same direction to restore the valve shape, particularly from a deformed annular shape.

[0134] In some embodiments, the pins are alternately extendable and retractable along the proximal-distal axis of their housings (i.e., the housing can be extended / advanced and / or the pins can be advanced / retracted). In the retracted state, the pins can be moved within the body without catching on unintended structures. For example, during positioning, the pins can be moved into contact with the valve annulus in the retracted state, avoiding the risk of damaging or entanglement of the valve leaflets. When the pins are extended (e.g., after the proximal end of the housing containing the pins is placed against the annular tissue to be treated), the pins are operable to engage the annular tissue.

[0135] In some embodiments, the housing comprises a distal portion of an elongated tubular element (also referred to herein as a catheter) and / or a separate element attached to the distal end of the catheter. In some embodiments, the housing comprises a portion of an overtube used to introduce a pin into a region. Optionally, the housing is specialized for the function of the distal end of the annuloplasty device. For example, the distal portion optionally has a different cross-sectional shape and / or size than the distally extending catheter, which houses one or more elements of a mechanism that actuates pin movement and / or the pin itself. In some embodiments, the housing comprises echogenic structures, such as grooves, cross-hatching, or another surface texture, potentially improving visualization of the location under echocardiography. In some embodiments, the housing comprises radiopaque structures (e.g., made from tantalum, gold, and / or tungsten) to enhance its visualization. In some embodiments, at least one of the pins is movable relative to the housing in a manner that imparts torsion to tissue as the pin is inserted into that tissue.

[0136] In some embodiments, actuation of the pin rotation is controlled to occur by a predetermined amount for each corresponding amount of exerted controlled movement and / or force. This is a potential advantage for providing feedback ("feel") to the device operator that enables them to determine the condition of the tip, for example, whether it is exerting enough resistance to indicate correct insertion into the tissue, whether it is experiencing a loss of resistance that may indicate tearing and / or loss of engagement, and / or whether it is exerting excessive resistance that may indicate jamming or jamming or insertion into unexpected resistance (e.g., already treated, previously fibrotic, and / or calcified tissue).

[0137] Actuation may include, for example, converting linear motion of an elongate control member (e.g., a wire or string) into rotational motion at the tip, for example, by spooling or unspooling from a pin attachment and rotating, optionally against a restoring force such as a tension spring. In some embodiments, the control member is also a member, e.g., a conductive wire, through which structural disruption energy is transmitted to the tip.

[0138] In some embodiments, the control member actuates a gear or pulley positioned to provide a mechanical advantage to rotate the pin mount. In some embodiments, the control member actuates rotation by rotating itself (about its longitudinal axis) and is sufficiently torsionally stiff and / or reproducible in effect (e.g., by being preloaded to overcome rotational resistance in at least one direction) so that the angle of rotation of the pin is predictable under the resistance that the pin inserted into tissue is expected to absorb from the annulus tissue.

[0139] In some embodiments, the rotationally actuating linkage is elastic and / or flexible (rotationally and / or longitudinally) to the extent that the actual rotation of the tissue-implanting pin achieved per unit of control actuation applied is variable and / or nonlinear. Thus, actuation force can build up as the flexible linkage partially absorbs (by deforming) and partially transmits force until sufficient force is transferred to the pin through the stable attachment to rotate the pin. Pin rotation in such cases can be achieved in increments as the control is moved and / or all at once by triggered release of energy already stored within the device, such as energy stored in a spring.

[0140] Whether under predictable or nonlinear / poorly repeatable control, determining the final amount of twist can be achieved by limiting the range of available rotational motion, for example, as described above. Providing a hard limit on rotation has the potential advantage that nonlinearity and / or repeatability errors in actual motion compared to the commanded motion may become insignificant during operation once the full range of motion is achieved. Partial rotation through the available range of motion may induce a smaller amount of contraction per introduced injury, which may be appropriate depending on the design of a particular treatment procedure.

[0141] At least two additional types of controls can be distinguished that can be manipulated to control the directionality of the tissue manipulation introduced by twisting. First, in some embodiments of the present disclosure, the device can be steered to maintain control of its orientation. For example, the device can be advanced along the valve's elevation axis (e.g., near, but not necessarily near, the center of the valve) and then bent away from the axis toward the valve's periphery. As the bent device (including the steering sheath or other steering mechanism) is rotated about the elevation axis, the alignment of the distal face of the device's tip retains its initial orientation relative to the valve's elevation axis no matter where it is rotated. Furthermore, as the tip is rotated about its longitudinal axis (proximal-to-distal axis), the distal face of the device's tip changes its rotation relative to the valve's elevation axis. With appropriate indicators provided to indicate the current relative rotational state of the steering sheath and the annuloplasty device it steers, tip orientation can be known and controlled. The indicators can include, for example, markings on the handle controls, radiopaque markings, echogenic features, detents, and / or optical or electronic encoders.

[0142] Second, in some embodiments of the present disclosure, the degree of twist applied (before and / or after pin insertion) can affect the direction and / or magnitude of anisotropy and the overall amount of tissue strain exerted. For example, to change the orientation of contraction anisotropy, the pin's rotation can be partially actuated before insertion into the tissue. This may involve actuation of a separate control from, or the same control as, the control used to actuate the pin's rotation during tissue manipulation. For example, rotation of the entire catheter body can be used to change the orientation of the pin before insertion, and a separate control can be used to rotate the pin relative to the catheter body after insertion. Furthermore, applying a larger or smaller twist relative to the starting orientation can affect the level of contraction anisotropy (although this may also affect the overall amount of mechanically induced contraction). Features and methods related to controlling the angle of twist of the device have been described above.

[0143] To explain the context of anisotropy control in more detail, the target outcome of annuloplasty is to shrink the circumference of the treated valve annulus (or valve ring), perhaps by a few percent (e.g., 5–10%). Normal circumferences, for example, are approximately 8–9 cm for the human mitral valve and approximately 12–14 cm for the human tricuspid valve. However, the axial height of the collagenous (fibrous) tissue of the annulus is only a few millimeters (e.g., less than 10 mm). Therefore, the induced contraction may be a much larger percentage of the axial height than the actual targeted circumference (on average, or even most of it). Therefore, it is potentially advantageous to center the axis of maximum contraction along the circumference while imposing a relatively low contraction along the axial height of the annulus.

[0144] However, rotating the contraction anisotropy to a different orientation may nevertheless be useful, for example, to equalize contraction and avoid introducing shape irregularities into the annulus. For example, direct control of the axis of contraction anisotropy can potentially help avoid or reduce the occurrence and / or worsening of valve shape irregularities, including abrupt variations in annular height, irregularities in the axial position of the annulus (e.g., induced annular bending), reduced flexibility, and / or modified flexibility that functionally interferes with the shape dynamics of the annulus.

[0145] During cardiac motion, the annulus may flex, for example, between a relatively flat and a relatively saddle-shaped configuration. During annuloplasty, it may be preferable to induce contraction along the hinge region of the saddle (the region where the annulus reverses its flexion) differently from other locations to encourage (or at least avoid hindering) flexion in the correct direction. For example, regions where contraction is preferentially induced along the valve's height axis (compared to the local circumferential axis) may offer less resistance to the flexion that occurs during normal annular mechanics.

[0146] It should be noted that a normal valve annulus is capable of significant dynamic remodeling (although this may already be impaired by the time an annuloplasty procedure is required). When feasible, it may be desirable to leave residual tissue flexibility intact, as long as it is appropriate for the purpose of promoting valve coaptation. Conversely, in some uses and / or embodiments of the present disclosure, the goal may be to introduce a curvature or kink into the annulus. For example, this may be to introduce a contralateral curvature or kink that is not addressed (or not fully addressed) by circumferential size reduction alone. In such cases, controlling contraction anisotropy can provide the surgeon with a tool to aid in shaping the annulus. It should be noted that contraction anisotropy is not measured solely as relative contraction along orthogonal intersecting axes, but can also apply to the directionality of deformation along a single axis (e.g., superior or inferior), induced, for example, by offsetting the location of the lesion. For example, it may be preferable to pull axially superior tissue into an axially inferior position, or vice versa.

[0147] The consequences of torsional contraction of annular tissue can be better understood by describing the torsional effects on the tissue for illustrative purposes, and without adhering to a particular model of tissue deformation under torsional forces. The torsional contraction pattern tends to retract the tissue to some extent from all or nearly all radial directions, as some component of the generated force is converted into a tangential stress, which tends to pull at least partially inward in regions farther away than the tangent circle. However, when the rotation is significantly less than a full rotation, e.g., less than half a rotation (more like a quarter rotation is typical in some embodiments of the present disclosure), the contraction pattern tends to be dominated by movement along the initial direction of movement, particularly in regions that can be directly pulled in that direction by one of the moving pins. Comparing this movement under tension with movement on the side of the pin where the tissue is most directly pushed, the tissue may be more amenable to contraction of its flat surface equivalent area under compression than expansion under tension. A reduction in flat surface equivalent area can be accommodated by bulging and / or wrinkling, even if the actual surface and / or volume remains largely unchanged. However, expansion under tension is limited by the elasticity of the fibrous tissue, and to the extent that such elasticity exists, it may be relatively low compared to the tissue's ability to compress laterally by swelling / wrinkling.

[0148] In some embodiments, two or more pins are used, e.g., three, four, five, or more pins. Whether two or more pins are provided, any number of pins may also be operable as electrodes to which ablation energy is delivered and / or as sensing electrodes (e.g., sensing impedance to aid in detecting insertion and / or tissue condition status). With more than two pins, the strain pattern introduced tends to be less anisotropic. For example, a four-fold strain pattern (for four pins) repeats every 90° rather than every 180° (for a two-fold strain pattern). The peak force concentrated on an individual pin may be reduced. If three or more pins are also used as electrodes, the peak heating concentrated on an individual pin may be reduced (for the same total energy and / or power). Using two pins has potential advantages, for example, to concentrate the insertion force over a smaller surface area and / or to package the device in a smaller delivery size.

[0149] There is no particular restriction that all pins must have the same shape. For example, one pin may have a small radius / maximum dimension and a second pin may have a large radius / maximum dimension. The pins may optionally be square in cross section (e.g., 0.4 mm x 0.4 mm cross section) or have other cross-sectional shapes, such as circular, triangular, or other shapes. A flat cross section (e.g., preferably oriented with the flat surface facing the circumferential direction of rotation) offers a potential advantage for providing a uniform surface over which torsional forces are distributed. A circular cross section offers a potential advantage for avoiding concentration of ablation energy when the pin is also used as an electrode. The pins optionally have a uniform or non-uniform cross section. Regions of non-uniform cross section may offer advantages for penetration, such as, for example, a taper to sharpen the tip of the pin. In some embodiments, the pin taper may be relatively short (e.g., less than the distal 25%, 20%, or 10% of the overall pin length). Optionally, the pin taper is longer (e.g., 30%, 40%, 50%, or more of the overall pin length). This allows the base of the pin to be significantly wider while still allowing for easy penetration. This potentially benefits from redistributing the contact surface area to the larger pin periphery to avoid fractures when applying force to the tissue during rotation to deform the tissue or during delivery of structural disruptive energy. It can also strengthen the pin itself. The taper need not necessarily be radially isotropic; for example, the taper may change from a first cross-sectional shape to a second cross-sectional shape that is not simply a scaled version of the first cross-sectional shape.

[0150] It is not particularly limited that all or any of the pins be straight. For example, the pins may be curved (e.g., as hooks). In some embodiments, a curved pin may enter tissue along a path that follows its curvature, or there may be some distortion between the shape of the pin and the path of its entry. This may increase the attendant resistance to pin penetration, but may also result in some deformation as a result of pin penetration alone (e.g., pinching).

[0151] Even in the case of straight pins, it is not limited that any or all of the pins may be advanced into the tissue while moving parallel to the longitudinal (proximal-distal) axis of the device that contacts the pins with the tissue. For example, the pins may enter the tissue at an angle, and optionally, may enter in different directions from one another so that the tips of the pins converge or diverge as they enter.

[0152] Non-parallel paths of pin / hook advancement offer potential advantages for maintaining the penetration attachment during further tissue manipulation, for example, in some embodiments using vacuum attachment to the tissue, such as those described in conjunction with this specification, to apply a force to pull the tissue against the surface electrode surface.

[0153] Aspects of some embodiments of the present disclosure relate to annuloplasty devices that combine the use of structural disruption energy combined with mechanical manipulation using a vacuum.

[0154] In some embodiments, mechanical contraction of the tissue prior to application of the structural disruption energy is achieved by vacuum fixation of the tissue surface. A vacuum opening is applied to the tissue in the area to be contracted, and the vacuum is activated. In some embodiments, the resulting pressure reduction is at least, for example, about 50 mmHg, 75 mmHg, 100 mmHg, 150 mmHg, or other pressure values.

[0155] As a result, the tissue is drawn into the opening. At the same time, the planar equivalent area of ​​the drawn tissue effectively shrinks. For example, if the planar equivalent area is defined as the cross-sectional area of ​​the vacuum opening, the actual surface area is that area plus the area required for the tissue to bulge into the low-pressure vacuum opening. Application of construct disruption energy fixes the deformation and causes the tissue to shrink. In some embodiments, the construct disruption energy is provided in the form of radio frequency (RF) energy, for example, at a power of 8 to 12 watts for a time period of 12 to 24 seconds. In some embodiments, the 8 watt power is:

[0156] A potential advantage of this mechanical fixation method is that fixation can be confirmed by changes in vacuum pressure and / or displacement. For example, in some embodiments, a pressure sensor is placed (e.g., at the tip of the device) to determine the stability of the vacuum engagement from the ambient pressure.

[0157] In some embodiments, the vacuum opening has a rectangular shape, which can increase the local contraction of the tissue along the short side of the vacuum opening. For example, if the bulge shape is approximated as a hemisphere divided in the middle by a straight section, the ratio of the actual surface length to the effective flat surface length along the short distance d1 of the straight section can be, for example, approximately π / 2. In the orthogonal direction, the surface along the longest distance d2 can be increased by this ratio, considering only the ends of the two hemispheres, while leaving the ratio of the straight section between them unchanged, resulting in a decrease in the overall ratio. In some embodiments, the ratio of the height (major axis) to the width (minor axis) of the vacuum opening is approximately 1.5:1, 2:1, 2.5:1, 3:1, or another ratio.

[0158] The vacuum openings optionally have rounded contours to avoid sharp internal corners. For example, the vacuum openings may be circular, elliptical, oval, or square or rectangular with rounded corners. For example, the minimum radius of curvature may be about 0.25 mm, or about 0.5 mm or greater. This offers the potential advantage of avoiding excessive stress on the tissue at the corners, which may tend to impede inward retraction of the tissue and / or result in mechanical damage to the tissue.

[0159] In some embodiments, the electrode or other transducer that passes the structurally disruptive energy (e.g., RF energy, acoustic energy, and / or thermal energy directly) through the tissue itself forms part or all of the vacuum opening. For example, the electrode may form the vacuum opening. It should be understood that, particularly with respect to embodiments described that use vacuum to mechanically deform the tissue, the electrode used as the transducer for introducing the structurally disruptive energy into the tissue may optionally be replaced with another transducer type, for example, a transducer that converts power from an electrical energy source into a structurally disruptive form of energy.

[0160] In some embodiments, the vacuum opening and electrode (or other energy transducer) are separately defined elements, e.g., the electrode can apply RF energy through electrical contacts made external to the vacuum opening and / or any chamber located behind it. In some embodiments, mechanical contraction of the tissue prior to fixation by energy application depends not only on the entry of the vacuum opening into the tissue, but also on the further mechanical movement of the vacuum opening.

[0161] In some embodiments, for example, a vacuum opening is advanced to create suction contact with the tissue, and then the tissue is withdrawn while being pulled further into a deformed shape. Deformation may be limited by a support, such as a protrusion that remains in more distal contact with the tissue while the vacuum opening is withdrawn. In some embodiments, the protrusion is a tube through which the vacuum opening is withdrawn. In some embodiments, the tube is slitted, resulting in potential folds or wrinkles that are confined by surrounding the slit in one axial direction but can extend beyond the tube / slit boundary in the other axial direction. This allows for particularly large shrinkage ratios per lesion formed along one direction (e.g., the circumferential direction) while remaining relatively low in other directions. For example, the maximum shrinkage ratio in one direction can be up to 2:1, 3:1, 4:1, or more. The maximum shrinkage ratio in the perpendicular direction may be at least 25%, 50%, 75%, or another percentage lower.

[0162] A potential advantage of vacuum-formed mechanical distortion is that the electrode (or other energy transducer) operates from a superficial position. This may result in a more uniform thickness of excised tissue (at least ignoring the vacuum-induced "bump") than would be possible with pin electrodes. For example, a continuous, healthy sheet of collagen tissue may remain beneath the lesion. Additionally or alternatively, there may be less tendency for local defects, such as shape distortions or weak spots, to occur.

[0163] However, optionally or alternatively, pin manipulation uses one or more superficially acting electrodes (or other energy transducers) other than the pins themselves to mechanically deform the tissue before supplying energy to plastically set the tissue into a new shape. In particular, with respect to embodiments described that provide superficially exposed contact electrodes (i.e., electrodes separate from the pins or other elements used to mechanically deform the tissue), it should be understood that the electrodes used as transducers for introducing structural disruption energy into the tissue may optionally be replaced with other transducer types, e.g., transducers that convert power from an electrical energy source into a form of structural disruption energy, e.g., as acoustic energy, light energy, thermal energy, or other forms of energy.

[0164] In some embodiments, the pins may be provided so that they interdigitate, linearly slide relative to one another, are rotatable, or otherwise movable to compress and / or otherwise deform the tissue. Additionally or alternatively, the tissue may be secured for deformation by one or more releasable hooks, e.g., hooks with reversibly expanding barbs and / or hooks that pass into the tissue along a path that at least partially curves back proximally. Two or more hooks curved in opposite directions optionally reduce the minimum bending angle of each, e.g., so that when the hooks are pulled, the tissue resists deformation to a degree sufficient to slip over the end of the hook. In some embodiments, straight hooks (which may be straight pins) are driven into the tissue along non-parallel directions (e.g., converging or diverging directions). For example, the tissue may be hooked by capturing a wider area of ​​superficial tissue at the deeper, narrower convergence of the pin. However hooked and / or trapped, the penetrated tissue is mechanically pulled into a deformed position that contacts an electrode configured to deliver structural disruption energy. For example, the hooks draw tissue into recesses whose inner surfaces at least partially comprise the electrode surface area, and structural disruption energy is delivered through the surface of the tissue that is brought into contact with the superficially acting surface area of ​​the electrode while the pins and / or hooks act to mechanically deform the tissue.

[0165] Guidance characteristics and methods Aspects of some embodiments of the present disclosure relate to positioning and operational guidance features of annuloplasty devices and / or methods of using these features, according to some embodiments of the present disclosure. In some embodiments, the annuloplasty devices operate according to the principles of tissue contraction through a combination of twisting / torsion and the application of structural disruptive energy (e.g., as described in connection with FIGS. 5A-11 herein). A complete annuloplasty procedure generally involves performing mechanical distortion and energy application at multiple sites around the annulus, referred to as treatment locations.

[0166] It is a potential advantage for an annuloplasty device operated via a minimally invasive catheter to include features that assist the operator in achieving and / or maintaining a firm awareness of the current state of the annuloplasty device itself and / or its positional relationship to the annulus being treated. Related tasks may include, for example, one or more of the following: Moving the annuloplasty device to a selected location around the annulus to begin treatment, including ensuring that the device is correctly positioned, e.g., at the correct initial orientation and / or offset relative to the annulus. · Moving an annuloplasty device between multiple treatment locations where it is mechanically distorted and subjected to structure-disrupting energies. At each such location, the annuloplasty device is properly positioned so that it is ready to mechanically engage the annulus tissue, starting from a predictable insertion angle and / or to a predictable extent. Actual mechanical engagement of tissue by the device, optionally including verification that the device is properly engaged to perform the mechanical strain. Performing mechanical distortion, for example by twisting and / or by applying a vacuum, optionally including verification that the mechanical distortion is occurring as intended. Applying structural disruptive energy to tissue, optionally including verification that the energy is accepted by the tissue as intended and / or that the tissue is disrupted as intended. Withdraw the device from the tissue and proceed to the next of multiple treatment locations.

[0167] Minimizing the complexity and / or uncertainty of each of these tasks is a potential advantage. For example, task complexity may be minimized by reducing the number of degrees of freedom (e.g., device motion and / or device state) manipulated during the task. Other ways in which task complexity may be simplified include reducing the extent to which the available degrees of freedom require adjustment, ordering the manipulation of degrees of freedom (e.g., one at a time), and / or "quantizing" one or more of the available degrees of freedom.

[0168] In this context, the term "quantized" should be understood to indicate that the device's implementation and / or sensing of degrees of freedom allows an operator to select at least one distinct, predefined state, such as, for example, a fully withdrawn needle, a fully advanced needle, a non-rotated needle, and / or a fully rotated needle. Partial states may also be quantized through sensing and / or the use of mechanical methods such as detents. For example, a half-rotated and / or half-advanced needle state may be defined.

[0169] This quantization can be implemented by imposing physical constraints on the degrees of freedom themselves, for example, by mechanical interference from stops and / or detents (detents define optionally transient zones where there is increased, but not necessarily complete, resistance to further movement). In such cases, the operator may be relieved of the need to attend to granular judgments regarding, for example, whether sufficient twisting has been applied or sufficient longitudinal advancement has occurred. Instead, reaching a stop / detent (e.g., feeling increased resistance to further twisting / advancement) potentially provides a sufficient indication. Additionally or alternatively, sensing and / or indication (e.g., electronic sensing and / or indication) may be used to detect and / or indicate to the operator the state of the device's degrees of freedom.

[0170] In some embodiments, the annuloplasty device is configured to tend to follow a path around the valve annulus as it is advanced by manipulation of several degrees of control. For example, the distal portion of the device may curve in a predetermined manner as it is advanced from the constraints of the overtube. The curvature may be selected so that the tip of the device points successively to different regions around the annulus circumference as the degrees of control are actuated. In some embodiments, there may also be a predetermined degree to which the tip of the device curves toward the plane of the annulus, starting from a location out of plane, such as the insertion point from the fossa ovalis of the intra-atrial septum into the left atrium. Such a configuration may significantly simplify the problem of positioning the device in three spatial dimensions to largely one of advancement or retraction. However, one or more additional controls operable to change the path (position) of the tip of the device (e.g., to allow for fine adjustment) may be provided.

[0171] The sensing itself need not be quantized. However, having at least one indication of a "yes / no" type is a potential advantage. For example, an on or off light can aid in on-the-spot decision-making. Additionally or alternatively, a graduated indication of the sensed state can be provided, such as a light that gradually changes intensity and / or color as the sensed property changes. The sensed property can include the distance and / or angle of device actuation. For example, this can be accomplished using electrical contacts and / or sensing resistance that changes with movement. Additionally or alternatively, the sensor can be configured to measure local electrical impedance, which can be used to confirm the insertion of a needle into tissue and / or the state of tissue as structure-disrupting energy is delivered to the tissue.

[0172] In some embodiments, the annuloplasty device includes one or more elements that aid in its visualization, regardless of the imaging modality, such as x-ray and / or ultrasound. For example, the annuloplasty device can include one or more radiopaque markers shaped and positioned to assist in determining the orientation of the tip of the annuloplasty device. This potentially helps ensure that the tip of the annuloplasty device is inserted at a preferred angle. For example, the preferred angle can include two needles of the device defining an axis between them that is oriented at an oblique angle relative to the circumferential direction of the annulus. The oblique angle can be approximately half the total amount of angular change the needles undergo when twisting and distorting tissue. For example, the needles can first be twisted by the amount of the oblique angle until they are oriented with an axis perpendicular to the circumferential direction of the annulus, and then further twisted by approximately the same angle.

[0173] In some embodiments, the tip of the device is rotated in situ (e.g., while positioned within the ventricle adjacent to the valve to be treated) until two radiopaque markers attached to opposite sides of the tip of the device reach a maximum or minimum distance (depending on the viewpoint and / or how the device is configured). This may be the operating orientation of the device, or it may be used to calibrate the device orientation, from which an offset can be added to select a target operating orientation. In some embodiments, once the operating orientation is set, the direction of the axis extending between the needles of the device forms the aforementioned oblique angle with respect to the circumferential direction of the annulus. Optionally, the operating orientation is changed for different treatment locations, for example, to adjust the amount of contraction applied at each treatment location and / or to adjust the overall shape of the annulus (e.g., to bend more or less toward a particular direction through a series of treatment locations). Optionally, the position of the needles relative to the radiopaque markers can also be visualized fluoroscopically. This can be used to confirm the relative advancement and / or retraction from the tip of the device and / or rotation.

[0174] In some embodiments, one or more portions of the tip of the device comprise structures that modify (e.g., increase) its ultrasound detectability, e.g., sound-scattering structures such as raised and / or inlaid stripes and / or divots. Optionally, these structures vary in different portions of the device, e.g., along its elongated longitudinal extent and / or around a portion of its circumference. The contrast structures potentially assist in identifying (by ultrasound) what the orientation of the device is (e.g., relative to the ultrasound sensor and relative to the valve annulus over time with knowledge of the relative position of the ultrasound wave relative to the heart). These may be useful, for example, to distinguish the housing and / or needle of the device from other portions of the device.

[0175] Optionally, the tip of the device is configured for enhanced ultrasound ("echo") imaging based on the extrusion of fluid into the surrounding blood. In some embodiments, the tip of the device is supplied with fluid (e.g., infusion fluid) proximally via a lumen. The stream of droplets at the tip of the device can be identified by ultrasound, allowing visualization of the location of the tip of the device.

[0176] In some embodiments, bioimpedance is measured during the procedure. This measurement can be used, for example, to assess the state of tissue disruption induced by device contact with the annular tissue, needle penetration into the annular tissue, and / or application of structural disruption energy. Optionally, this measurement can be used to confirm that the tissue being contacted, penetrated, and / or disrupted is indeed annular tissue (e.g., to the extent that the bioimpedance of this tissue is different from other nearby tissues, such as the valve leaflet tissue and / or myocardium).

[0177] Approach angle One aspect of some embodiments of the present disclosure relates to the operation of an annuloplasty device using mechanical deformation and application of structural disruption energy following needle penetration so that the needle approaches (and penetrates) the annulus from a direction directed largely outward from the center of the annulus, potentially from positions above or below the circumference of the annulus, to a lesser extent.

[0178] As a frame of reference, the direction from the needle penetration site to the geometric center of the valve annulus can be defined as 0° (the "shallowest" angle). The 90° / -90° orthogonal directions (the "steepest" angles) represent directions pointing "up" or "down" from the valve circumference. The "up" and "down" directions may be perpendicular or nearly perpendicular to the mean plane of the annulus (more specifically, the mean plane of the valve circumference). This mean plane is optionally defined as having the shortest average distance to the annulus circumference (e.g., as measured from the midpoint of the annulus thickness or another reference point). For example, in the case of the mitral valve, "up" generally refers to the left atrium, and "down" refers to the left ventricle. Relative to this angular axis, in some embodiments, the needle is oriented to penetrate tissue within a range of ±55°. For example, when approaching the mitral valve from within the left atrium, the needle penetrates tissue within a range of 0° to 55°, e.g., after entering the left atrium through the fossa ovalis and interatrial septum. In practice, there may be a lower limit to the angle of approach, e.g., a lower limit in the range of about 20° to 30°. Optionally, a different range of angles is used, e.g., limited to shallower angles (e.g., within ±50°, ±45°, or ±40°) or including steeper angles (e.g., within ±60°). In some embodiments, the approach angle varies somewhat depending on the circumferential position of the treatment site, with the shallowest angles being no greater than about 15°, 20°, 25°, or 30°. The steepest angles optionally do not exceed 45° and / or 60°. The 30° to 40° range may be considered "typical," e.g., in some embodiments, at least half of all treatment regions are approached at angles within this range.

[0179] A potential advantage of using a shallower approach angle is that the device is less likely to accidentally slip off the annulus periphery as it presses against the annulus. Furthermore, a shallower approach may help ensure penetration into relatively thicker portions of the target. This may result in a lower risk of injury to other tissues and / or a larger volume of annular tissue available for the changes induced by the annuloplasty treatment. A shallower approach (e.g., from the atrial side of the mitral valve) may also have a potential advantage in that it is more likely to slide over the leaflets rather than end up inadvertently pressed against them. This reduces the likelihood of injuring the leaflets.

[0180] In some embodiments, as described elsewhere herein, the needle can further engage the valve annulus such that the axis extending between the annulus is oriented obliquely relative to the valve circumference, e.g., at an approximately 45° angle relative to the valve circumference. In this case, a 90° rotation preferably results in a final orientation of approximately 45° after the axis passes through a position perpendicular to the valve circumference and extending up and down the valve circumference. The inclination of the axis in the radial direction is dependent on the shallowness of the approach angle, as described above, and therefore is generally not a straight up and down orientation. Other explanations herein relate to these same considerations using different explanatory approaches. These explanations should be understood as relating to mutually compatible terms, at least insofar as one of them can clarify how another should be understood if there is substantial doubt about some aspect of the latter. Furthermore, explanations can be combined (e.g., with respect to the specific angle ranges and / or defined entities mentioned).

[0181] The oblique angle relative to the circumference is optionally selected to be greater or less than 45° (i.e., provision for more or less than 90° of total rotation). Optionally, the arc of rotation is not equal on either side of an axis perpendicular to the circumference, i.e., the midpoint is not necessarily perpendicular to the circumference of the valve. "Asymmetric" rotation in this sense may be selected, e.g., toward a more planar or less planar configuration, to potentially adjust how the annuloplasty affects the valve's in-plane bending.

[0182] Similarly, the clockwise or counterclockwise twisting direction is not necessarily selected identically for all treatment locations. Optionally, for example, opposite directions are selected for a pair of treatment locations that sandwich the (intended) leaflet coaptation site. For example, the leaflet roots beneath the treatment location are biased toward each other, although the tissue on the opposite side may be somewhat stretched. Again, to the extent that some tension potentially remains on the "stretched" side even after plastic remodeling due to the application of structural disruption energy and / or develops during subsequent recovery, this has the potential benefit of further increasing mechanical stabilization of coaptation, particularly at the site marking the interface between the leaflets. It is also not excluded that effects related to the (at least initially) "stretched" side may optionally be induced on the leaflet root side in some embodiments. For example, this may reduce bulging distortion and / or help smooth the root region near where coaptation occurs (or is likely to occur). Controlling the pattern of clockwise versus counterclockwise twisting potentially facilitates leaflet shape spreading and / or contraction and / or the degree of valve circumferential undulation (i.e., undulation of the valve circumference in and out of the mean valve plane). Greater undulation may be selected to potentially increase effective circumferential shortening, but such distortion should generally be controlled so that overall function (e.g., coaptation) is not compromised.

[0183] In some embodiments, treatment locations are positioned so as to be relatively biased toward the outer or inner portion of the annular circumference of one or more leaflets (i.e., toward or away from their coaptation edges). This may help tailor the effect of the annuloplasty on the shape adopted by the leaflets during the cardiac cycle (cooperative coaptation). In this regard, it should be noted that the specific positioning of the pins relative to the circumferential midpoint and / or the shallowness of the approach angle to the annulus may tailor the amount of twisting the leaflet base adopts and, accordingly, potentially affect coaptation. This discussion regarding the potential effects of treatment location selection, twist arc (amount and / or direction of twist), and / or twist direction on coaptation and / or other therapeutic effects should not be considered as adhering to a particular theory and should be considered in combination with (i.e., for some embodiments of the present disclosure, built upon) other discussions regarding the effects of annuloplasty presented herein without necessarily limiting or being limited by the teachings of those discussions.

[0184] Before describing at least one embodiment of the present disclosure in detail, it is to be understood that the present disclosure is not necessarily limited in its application to the details of construction and the arrangement of components and / or methods set forth in the following description and / or illustrated in the drawings. Features described in the present disclosure, including inventive features, can be implemented or carried out in other embodiments or in various ways.

[0185] Vacuum aspiration annuloplasty device Reference is now made to FIG. 1A, which is a schematic illustration of a cardiac annuloplasty device 100 operable to shape annulus tissue using vacuum, according to some embodiments of the present disclosure. In some embodiments, the annuloplasty device 100 comprises a tip 13 including an electrode 10 and a chamber 12. The chamber 12 opens distally. The chamber 12 is further in selectable pressure communication with a vacuum source 35 via a hollow catheter 15. Selection is made, for example, by operation of an (optional) valve 34, by operation of a valve (not shown) in the vacuum source 35, and / or by actuation of the vacuum source 35 itself. In some embodiments, the valve 34 is part of the handle 25. In some embodiments, the handle 25 includes appropriate pass-through conduits and valves to allow for separate routing of power and vacuum.

[0186] An electrode 10 is also provided at the distal end of tip 13. Electrode 10 is in electrical communication with (i.e., receives power to induce fibrosis from) a radio frequency (RF) generator 33 via conductive wire 17 and optional impedance matching module 31.

[0187] In some embodiments, steering of catheter 15 (ie, steering tip 13 to position the target region of the valve annulus prior to inducing fibrosis) is accomplished by a steerable guide sheath 19.

[0188] Alternatively or additionally, catheter 15 itself includes a steering mechanism. Optionally, in such an embodiment, guide sheath 19 is omitted. Handle 25 optionally includes controls for steering steerable guide sheath 19 and / or catheter 15.

[0189] Optionally, one or more sensors 11 are located at the tip and may be connected to an optional sensor controller 36, for example, via additional wires 17. In some embodiments, the sensor 11 includes a pressure sensor, which may be used to detect positive engagement with tissue. Optionally, control of the RF generator (e.g., interlock control) is applied based on sensing pressure generated at the tip 13 consistent with positive vacuum engagement with tissue. Pressure and / or flow sensors may be located elsewhere in pressure communication with the compartment under vacuum, for example, along the catheter 15, in the handle 25, with the valve 34, and / or as a component of the vacuum source 35.

[0190] In some embodiments, sensor 11 includes a temperature sensor, the output of which may also be used to help control operation of RF generator 33 to activate electrode 10. In some embodiments, sensor 11 comprises an impedance sensing electrode (and / or electrode 10 itself is used as an impedance sensing electrode), and the sensed impedance is used to help control operation of RF generator 33. For example, if the sensed impedance is not at or near a level expected for collagenous annular tissue, RF power generation may be locked out and / or the device may enter an alarm state. In some embodiments, the expected impedance is distinguished from, for example, the impedance of blood and / or the impedance of the valve leaflets. Also, note that the applied vacuum may draw relatively thin, freely moving leaflets into tip 13 more than relatively thick, fixed annular tissue. In some embodiments, this is detected using one or more sensors 11 in chamber 12, for example, by placing the sensor in a location where the leaflets can reach but the annular tissue cannot.

[0191] Reference is now made to Figure 1B, which is a schematic flow chart of a method of performing an annuloplasty procedure using device 100 of Figure 1A, according to some embodiments of the present disclosure. Reference is further made to Figures 1C-1E, which are schematic illustrations of the operation of device 100 of Figure 1A, according to some embodiments of the present disclosure.

[0192] At block 110, in some embodiments, the tip 13 of the annuloplasty device 100 is pressed against tissue (e.g., heart valve annulus tissue 200) targeted for fibrosis and contraction induction. This corresponds, for example, to the situation shown in FIG. 1C , which illustrates the tip 13 positioned (in cross section) against tissue 8. In the illustrated example, the electrode 10 is positioned within the chamber 12. In some embodiments, other relative positions of the electrode 10 and the chamber 12 are provided, for example, as described in connection with FIGS. 4A-4B .

[0193] The pressure need not be large, nor constant (eg, to account for cardiac motion), as long as it is momentarily sufficient to allow the operation of block 112, described next.

[0194] Positioning the tip 13 may also include adjusting its orientation circumferentially and / or relative to the axial height axis of the annulus. If the electrode 10 (and / or the opening therethrough) is relatively elongated in one direction, the resulting contraction in the treatment region may be greater (and / or more uniform) in one direction than in another. This is potentially important for achieving predictable results. It also has potential applications for tailoring treatment outcomes. Adjusting the orientation helps control this difference. In some embodiments, adjustment is controlled by rotating the entire handle of the device. In some embodiments, adjustment involves rotating a knob or other control element. Note that the same fixed orientation of the device may be appropriate for treating one region of the annulus but not necessarily for treating a region 90° away from it along the annulus circumference (depending on how steering is performed). Providing specific controls for managing rotation may help the operator track the state of the device. In some embodiments, a preferred steering method is selected to maintain the same orientation of the tip no matter which side of the valve it is navigated to. For example, it may be preferable to navigate the catheter to the center of the valve, introduce a bend at the distal end of the tip that has a predetermined relationship to the shape orientation, and then rotate the entire catheter while the steering angle remains bent to select different regions of the circumference. Rotating the catheter (e.g., by twisting its handle and / or motion controls thereon) a set amount can predictably adjust the orientation to enable its use, for example, as a way to control how much contraction occurs circumferentially around the valve annulus.

[0195] In block 112, in some embodiments, a vacuum is applied to chamber 12, for example, from vacuum source 35 through the lumen of catheter 15. This results in pulling tissue of heart valve annulus 200 facing the opening of chamber 12, as shown, for example, in FIG. 1D. In FIG. 1D, the vacuum force within chamber 12 is represented by arrow 35A, and as a result, the greater pressure existing outside chamber 12 pushes tissue portion 8A of tissue 8 into chamber 12.

[0196] Note that the resulting bulging of tissue portion 8A has a larger surface area than the surface area previously beneath chamber 12 (e.g., as shown in FIG. 1C ). This is not entirely due to deformation of the tissue beneath chamber 12; rather, deformation is induced both there and in the adjacent area of ​​tissue 8. Accordingly, there is at least a small contraction of the surface adjacent tissue 8, which, in some embodiments, comprises part of the shape change induced by the annuloplasty being performed.

[0197] In block 114, in some embodiments, RF power is delivered through the annuloplasty device. More particularly, in some embodiments, the RF generator 33 is activated and / or a switch connecting the RF generator 33 to the electrode 10 via the wire 17 is closed. In some embodiments, an impedance module 31 is provided to match the impedance of the RF generator 33 to the impedance of an electrical sub-circuit including the wire 17 and the electrode 10.

[0198] The RF energy is supplied at a frequency that interacts with tissue portion 8A and / or surrounding tissue 8 to heat tissue 8. The energy is applied to an extent sufficient to denature the tissue, causing plastic deformation and / or shrinkage, an effect that persists even after the vacuum is released and tip 13 is removed.

[0199] During a global annuloplasty procedure, the procedure of FIG. 1B (e.g., as illustrated by FIGS. 1C-1E) is repeated multiple times, e.g., to form a line or row of lesions 6 along the area of ​​the annulus 200 undergoing shape and / or flexibility remodeling. The row may extend partially or entirely around the circumference of the annulus 200. Optionally, the row is divided into multiple row sections, indicated by relatively large inter-lesion gaps between them. Examples of lesion rows are described, for example, in connection with FIGS. 2H-2J.

[0200] Reference is now made briefly to FIG. 1F, which is a schematic illustration of lesion 6 created by device 100 of FIG. 1A, according to some embodiments of the present disclosure. The vacuum-induced bulging of tissue portion 8A shown in FIGS. 1D-1E leaves behind an upward bulge 6E occupying the center of lesion 6. A "contoured" region 6F of bulge 6E may also be created corresponding to the location where the distal surface of tip 13 contacts tissue 8. Furthermore, lesion 6 typically extends outward along surface 6C beyond the electrode contact area shown in FIGS. 1D-1E, e.g., having a depth profile corresponding to region 6D. The diamond-shaped bulge of lesion 6, in some embodiments, corresponds to the shape of the lesion formed by annuloplasty device 100 as described in connection with FIGS. 3A-3C. While contraction may occur in and / or toward the center of lesion 6 from all directions, relative contraction due to tissue movement in the direction of arrow 201 may be greater toward either long edge of bulge 6E. Potential reasons for this are discussed, for example, in connection with FIGS. 3A-3C.

[0201] Reference is now made to FIG. 2A, which is a photograph of a lesion 6 created ex vivo in a porcine cardiac tricuspid valve using device 100, according to some embodiments of the present disclosure. More particularly, the lesion was created using cardiac annuloplasty device 100 constructed with tip 13 as described in connection with FIGS. 3A-3C. Lesion 6 was created in tissue 8 according to the method of FIG. 1B, more particularly in the region of annulus tissue 200 that is part of cardiac valve 202. Shapes corresponding to bulge 6E and surrounding contour 6F are clearly visible.

[0202] Reference is now made to Figures 2B-2E, which are photographs of pre-lesion (Figures 2B, 2D) and post-lesion (Figures 2C, 2E) regions of lesion 6 created ex vivo in a porcine tricuspid heart valve using device 100, according to some embodiments of the present disclosure. The 4 mm scale bar shown in Figure 2B also applies to Figures 2C-2E. The fiducial mark 207 in each of these figures is itself 4 mm across. In each of Figures 2B and 2D, dotted line 208A represents the surface width of the tissue before lesioning shown in Figures 2C and 2E, respectively. In each of Figures 2C and 2E, dotted line 208B represents the corresponding post-lesion width of the region indicated by the corresponding line 208A. Lesion 6 occupies the center of the contracted region, revealing features corresponding to bulge 6E (approximately 2.3 mm wide and 4.3 mm high) and outline 6F, as shown in Figure 1F. The extent of the lesion, corresponding to surface extent 6C of lesion 6, can be identified by the extent of a slightly discolored area with reduced luster surrounding the central bulge.

[0203] In the example performed as shown in Figures 2A-2F, the relative shrinkage of the area corresponding to line 208A was determined to be in the range of 20.5% to 26.5%, which corresponds to an absolute nominal shrinkage of 1.2 to 2.1 mm (depending on the overall size of the affected area). The ablation power used was 8 watts and the duration was 18 seconds.

[0204] Reference is now made to FIG. 2F, which is a photograph of a sectioned lesion 6 created ex vivo in a porcine tricuspid cardiac valve using device 100, in accordance with some embodiments of the present disclosure. Reference is further made to FIG. 2G, which schematically illustrates regions corresponding to features in the photograph of FIG. 2F, in accordance with some embodiments of the present disclosure. For clarity, only contour lines 210, 212 are shown in FIG. 2F. These can be used to aid orientation for identifying the features labeled in FIG. 2G.

[0205] The tricuspid valve element shown in the photograph corresponds more generally to heart valve 202 .

[0206] Lesion 6B comprises approximately half of the lesion 6 bulge on one side of a slit 216 that penetrates lesion 6 generally along a line (upper as shown) corresponding to line 208B in FIGS. 2C and 2E. Lesion 6A corresponds to the other half of the lesion bulge. Looking down into slit 216, the relatively dark and / or shiny slit wall 214 corresponds to the undamaged area of ​​tissue. The lighter and / or less shiny region 6D indicates the depth profile of the lesion through the exposed cross section, having a width of approximately 7.2 mm and a depth of approximately 1.5 mm from surface 2C. Lesion 6B bulge rises approximately 1.5 mm from surface 2C. Contour lines 212, 212 approximately define the superficial extent of the lesion (on either half of the divided lesion), corresponding to surface 6C of the entire lesion 6 shown in FIG. 1F. Region 215 comprises the exposed floor of slit 216.

[0207] Reference is now made to Figures 2H-2I, which are photographs of a row of lesions 6 created ex vivo in a porcine mitral heart valve using device 100, according to some embodiments of the present disclosure. Reference is also made to Figure 2J, which is a photograph of a sectioned row of lesions 6 created ex vivo in a porcine mitral heart valve using device 100, according to some embodiments of the present disclosure.

[0208] The mitral heart valve elements shown in the photograph correspond more generally to heart valve 202, e.g., annulus 200 is the annulus of the mitral valve. Lesion 6 corresponds to a lesion created with 8-12 watts of power over a period of 12-18 seconds. Generally, shorter times are associated with correspondingly higher wattages, with the overall energy used remaining fairly constant at between approximately 144 and 162 joules.

[0209] In the illustrated example, the long axis of each lesion 6 is oriented along the axis of blood flow through the valve. Optionally, the lesions are positioned side-by-side with a spacing between the raised bulges of about 2 mm (e.g., about 85% of the width of an individual bulge). Optionally, larger or smaller spacings are used.

[0210] The depth of the damage can again be seen in the depth of the relatively light region 6D which extends laterally (left to right) above the dark region 215 which itself is shown above the slit floor 215 in FIG. 2J.

[0211] However, the damage that occurs does not necessarily have to be continuous.

[0212] In this example, the lesion region 6C is substantially contiguous. Placing the lesion 6 close enough that at least the affected tissue regions are in contact helps ensure the maximum amount of contraction available through a particular circumferential section of the annulus 200. However, this is optional, based, for example, on whether using the full extent of available annulus remodeling is necessary to ensure coaptation. In particular, it should be noted that an annuloplasty procedure may be targeted to specifically reduce the annular circumference in the region bridging two mal-coapted leaflets, while reducing the annular circumference in another region may not be effective in reducing regurgitation.

[0213] Diminishing returns are expected if lesions are placed close enough together to create "double lesioning" (multiple exposures to fibrosis-inducing levels of heating) in the shared area between lesions, at least insofar as lesion shrinkage is a function of changes, including tissue shrinkage itself, that are not additive with repeated treatments. Nevertheless, vacuum-induced shape changes (e.g., contraction of surface area represented by bulging) may result in some additional valve circumference reduction as lesions become more closely spaced.

[0214] Reference is now made to Figure 3A, which is a schematic illustration of the distal end of a cardiac annuloplasty device 100, according to some embodiments of the present disclosure. Reference is also made to Figure 3B, which is a schematic illustration of the distal direction of the tip of a cardiac annuloplasty device 100, according to some embodiments of the present disclosure. Reference is also made to Figure 3C, which is a schematic illustration of the handle and connection region of a cardiac annuloplasty device 100, according to some embodiments of the present disclosure.

[0215] The annuloplasty device design of Figures 3A-3C was used to create the lesions shown in and / or described with respect to Figures 2A-2J. Figure 3A shows the distal end of catheter 15 with adhesive 14 used to secure it to tip 13. Tip 13 is a generally conical design, initially circular in cross section and slightly narrowing in diameter from proximal to distal. Further distally, the cross section flattens on two opposing sides, terminating in a rectangular cross section with fully rounded corners (i.e., the rounded corners of the periphery meet on the short side of the rectangle). In some embodiments, tip 13 is made of PEEK or another material (e.g., another polymer) that offers good electrical insulation combined with heat resistance. By improving one or both of these material properties, tip 13 can be made with relatively thin walls, potentially reducing its overall size.

[0216] Inserted into this distal section of tip 13 is a similarly shaped (but smaller) electrode 10, which is open in the center to provide access to chamber 12. The inner opening through electrode 10 is approximately 2 x 4 mm. In some embodiments, electrode 10 has, for example, a wall thickness of about 0.5 mm and a wall height (extending proximally) of about 1 mm.

[0217] The inner opening may be slightly smaller than the actual resulting lesion bulge 6E (e.g., 2.3 x 4.3 mm), potentially due to slight relaxation of the lesion tissue after the vacuum hold is released. The wall thickness of the electrode 10, together with the wall thickness around the tip 13, helps define the size of the perilesional region 6F.

[0218] The inner opening shape of the electrode 10 in FIG. 3A has a rectangular aspect ratio (aspect ratio >1, e.g., approximately 2). This aspect ratio greater than 1 potentially helps promote greater relative shortening of the annulus across the shorter dimension compared to the longer dimension. For example, if the penetration of tissue portion 8A under vacuum across the shorter dimension is approximately 2 mm through a circular cross-section, the ratio of bulge circumference to bulge width is approximately 1.6. Along the longer dimension, the ratio (assuming a quarter-turn circle at each end) approaches 1.3. As a result, less longitudinal remodeling per unit length is required to create a given shape. This is useful, for example, when the long axis of the inner opening of the electrode 10 is oriented along the direction of blood flow through the valve and the annulus is short compared to its circumferential length. For example, this may help reduce distortion in that direction due to non-uniform contraction, reducing the overall distance required to "equalize" such differences. It should be noted that the actual shrinkage achieved overall may be somewhat less than just stated, for example, due to relaxation after treatment and / or because portions of the lesion lie outside the lesion bulge.

[0219] The rounded corners of the inner opening of the electrode 10 offer potential advantages, such as allowing tissue to be drawn smoothly into the chamber 12 under suction. For example, cutting and / or compression of the encroaching tissue at the corners of the opening may be reduced.

[0220] 3B, a portion of wire 17 is shown as comprising a wound cable of strands and is attached (e.g., crimped, soldered, and / or welded) to the remainder of wire 17 proximally via connector 17A. Distally, wire 17 is attached (e.g., crimped, soldered, and / or welded) to extension 10B, which may be an integrally formed extension with electrode 10 (e.g., cast together and / or cut from the same stock). Optionally, extension 10B is itself attached to electrode 10 but formed separately.

[0221] FIG. 3C shows the proximal portion of the annuloplasty device 100 with the handle 25. The handle body 300 is sized to be held in the hand. A knob 301 may be used (e.g., adjusted with a finger) to adjust an adjustable valve that controls whether a vacuum is currently applied to the chamber 12. In some embodiments, the vacuum is received from a vacuum source 35 via a tube 35B. An isolation valve 302 attaches the tube 35B to the handle body 300, for example, on the proximal side of the handle or in another convenient location to keep it out of the way during operation of the handle 25. The isolation valve 302 also allows the wire 17 to pass through it on its way to its connection with the RF generator 33 (e.g., via the impedance module 31). Handles with these (and optionally additional) features may optionally be provided on any embodiment of the annuloplasty device 100, such as the device of FIGS. 4A-4B.

[0222] Reference is now made to Figures 4A-4B, which schematically illustrate the distal end of a cardiac annuloplasty device 100 with a vacuum attachment element 403 in an advanced position (Figure 4A) and a retracted position (Figure 4B), according to some embodiments of the present disclosure.

[0223] In general, the annuloplasty device 100 of Figures 4A-4B includes the features generally described for the annuloplasty device 100 in connection with Figure 1A and is used as generally described in connection with the method of Figure 1B. However, in comparison to the embodiment of Figures 3A-3C, for example, the electrode 10 and chamber 12 are movable relative to one another. In the illustrated example, the chamber 12 is defined by a movable element 403 that translates longitudinally along a proximal-distal axis relative to the electrode 10.

[0224] Upon distal advancement, the vacuum applied to chamber 12 secures the tissue attached to chamber 12, as described with respect to block 110 of FIG. 1B. An additional operation can then be performed, whereby element 403 is withdrawn proximally, thereby drawing the secured tissue deeper into tip 13, into recess 402, which has a size somewhat larger than element 403. In fact, withdrawing element 403 may extract a deeper bulge than the example of FIGS. 3A-3C. Because recess 402 optionally takes the form of a slit, the tissue shape along one axis is relatively unconstrained, while the tissue shape along the other axis is more extensively deformed.

[0225] The electrode 10, in some embodiments, extends from the distal region that contacts the tissue into the slot 402. Accordingly, lesioning can be performed along the electrode 10's contact with the deformed tissue substantially anywhere outside of the chamber 12. This potentially results in the formation of lesion bulges that appear as pinched folds or plications in the tissue that rise relatively sharply (and high) from the base surface when moving along the valve circumference, but rise more gradually when moving along the blood flow axis, as shown, for example, in FIG.

[0226] Reference is now made to FIG. 4C, which schematically illustrates a lesion 6 caused by the device 500 of FIGS. 4A-4B, according to some embodiments of the present disclosure.

[0227] Lesion 6 may be somewhat higher than shown in Figure 1F. This lesion may be covered by a nodule 6G formed by tissue completely drawn into chamber 12, potentially still damaged (and therefore plastically deformed) despite not being in direct contact with electrode 10. The surface of region 6H (surrounded by periphery 6I) is in direct contact with electrode 10 most of the time when it is injured, and is pulled into contact with electrode 10 by traction from the tissue at nodule 6G, but is not itself directly exposed to vacuum. Region 6I forms the remainder of the pleats. This may contain a mixture of damaged tissue (more central) and undamaged tissue (periphery) that is passively drawn into a new shape by traction from other collapsed regions. Region 6C shows that the surface of the lesion may extend well beyond the area in direct contact with electrode 10. Front and side cross-sectional views of region 6D show the depth of the lesion.

[0228] The "folded" shape of such lesions has the potential advantage of allowing for greater changes in annular circumference overall and / or concentrating changes in valve circumference in particularly critical areas, such as at and / or around the intercusp coaptations.

[0229] Annuloplasty device using rotational distortion Reference is now made to FIG. 5A, which is a schematic illustration of a cardiac annuloplasty device 500 operable to shape annulus tissue using needle penetration and twisting, according to some embodiments of the present disclosure.

[0230] In some embodiments, the annuloplasty device 500 comprises a distal end 501 including pin electrodes 20 that are optionally recessed until they extend from the distal end 501. The pin electrodes 20 are in electrical communication with (i.e., receive RF power from) a radio frequency (RF) generator 33 via conductive wires 17 and an optional impedance matching module 31. In some embodiments, the pins 20 are stabilized so that they can exert sufficient torque on the annular tissue to deform it without excessively deforming themselves. For example, the pins 20 are mounted to a mounting block 21. The mounting block 21 can hold the pins at a fixed distance from each other while allowing them to rotate about a common axis. In some embodiments, the pins 20 are rotated under control exerted via a control member 18, for example, from a control on the handle 25. For example, the control member 18 can pull on the mounting block 21 to rotate it. Optionally, the functions of the control member 18 and the wire 17 are combined. Actuation for rotating pin 20 can utilize mechanical advantage, for example, via gears, levers, and / or pulley mechanisms. This mechanism can be embedded within tip 501 itself, embedded within the mechanism of handle 25, or distributed. For example, a pulley mechanism can be provided that includes multiple lengths of control member 18 passing up and down catheter 15 to provide the mechanical advantage.

[0231] In some embodiments, the handle 25 includes suitable controls for mechanically manipulating the pin electrodes, for example, to extend or retract the pin electrodes and / or to rotate the pin electrodes about the longitudinal (proximal-distal) axis of the tip 501.

[0232] In some embodiments, steering of catheter 15 (i.e., to position tip 501 at a target region of the valve annulus prior to treatment) is achieved by steerable guide sheath 19. Alternatively, or additionally, catheter 15 itself includes a steering mechanism. Optionally, guide sheath 19 is omitted in such embodiments. Handle 25 optionally includes controls for steering steerable guide sheath 19 and / or catheter 15.

[0233] Optionally, one or more sensors 11 are provided on the tip 501, optionally in communication with a sensor controller 36, which operates to help control the operation of the RF generator 33 to provide power to the pin electrodes 20. The sensors 11 may, for example, sense temperature and / or impedance. The influence on the control of the operation of the RF generator 33 may, for example, be as described in relation to FIG. 1A.

[0234] Reference is now made to Figure 5B, which is a schematic flow chart of a method of performing an annuloplasty procedure using device 500 of Figure 5A, according to some embodiments of the present disclosure. Reference is further made to Figures 5C-5F, which are schematic illustrations of the operation of device 500 of Figure 5A, according to some embodiments of the present disclosure.

[0235] At block 510, in some embodiments, the tip 501 of the annuloplasty device 500 is pressed against the tissue to be contracted (e.g., heart valve annulus tissue 200). This corresponds, for example, to the situation shown in FIG. 5C , which shows the tip 501 (in cross section) positioned against tissue 8. In the illustrated example, the electrode 20 is recessed within the housing of the tip 501 and is mounted, for example, to a retractable mounting block 21. In some embodiments, the mounting block 21 is also rotatable under the control of the handle 25. This and other tip configurations are described, for example, in connection with FIGS. 7A-7E, 8A-8B, and 10A-10C.

[0236] Optionally, in block 512, in some embodiments, the pin electrode 20 is extended into the tissue 8. This corresponds, in some embodiments, to the situation shown in FIG. 5D , in which the pin electrode 20 is inserted into the tissue at position 20A (for this figure and the remainder of FIGS. 5D-5G, the illustration of the remainder of the annuloplasty device is reduced for clarity). In some embodiments (e.g., as described in connection with FIG. 11 ), the inserted element mechanically manipulates the tissue but is not itself conductive to RF energy, for example, as described in connection with pin 1102 of FIG. 11 . In some embodiments and / or uses, the pin electrode 20 is not retracted or remains extended, and block 512 is optional. However, it is a potential advantage for the pin electrode to be retractable during navigation and / or positioning, such as the positioning of block 510.

[0237] Notably, once the pin electrode 20 is inserted into tissue, none of the housing of the tip 501 needs to remain in direct contact with the target area, and for example, the pin electrode 20 may be withdrawn slightly while at least a portion of it remains in place. This can be used, for example, to adjust the depth of the lesion.

[0238] In block 514, in some embodiments, torsion (twisting) is exerted on the tissue 8 through the pin electrodes 20 to rotate a portion of the tissue 8, for example, by up to about 60°-120° about the proximal-distal axis of the tip portion 501. In some embodiments, the pin electrodes 20 themselves rotate, e.g., the pin electrodes 20 may rotate about a common center. Alternatively, in some embodiments, the pin electrodes 20 do not rotate but instead translate (e.g., translate toward each other). However, they translate such that a twist is induced in the tissue, e.g., as described in connection with FIGS. 10A-10C.

[0239] The operation of block 514 corresponds, for example, to the illustration of FIG. 5E , where pin electrode 20 moves from position 20A to position 20B by moving generally around a circular path indicated by arrow 520. This action causes a twisting and “twisting” in tissue 8, which tends to compress tissue 8, as discussed, for example, in connection with FIG. 5G . A flat (e.g., square) cross-sectional shape of the pin electrode potentially assists in gripping tissue to impart twisting, although circular or other cross-sections are optionally used in some embodiments of the present disclosure.

[0240] In block 516, in some embodiments, RF power is applied. RF power may include RF energy applied through pin electrodes. This corresponds, in some embodiments, to the situation illustrated in FIG. 5F, where field lines 531 represent RF transmission in a region sufficiently concentrated to induce damage. Dotted line 530 represents the damage area. The effects of the damage include converting transient deformation due to torsion into more permanent plastic deformation (and net contraction). The damage itself may also cause volumetric contraction of the tissue.

[0241] The damaging energy used can be, for example, in the range of about 100-200 joules, e.g., 140-160 joules. Examples of power and time combinations within this range include, for example, 8 watts for 18 seconds, 10 watts for 15 seconds, and 12 watts for 12 seconds. Using a relatively high power can concentrate the damaging effect (e.g., avoiding energy loss through thermal conduction). Conversely, using a relatively low power can potentially expand the area of ​​effect without causing charring.

[0242] Reference is now made briefly to FIG. 5G, which is a schematic illustration of the lesion 7 created by the device 500 of FIG. 5A, in accordance with some embodiments of the present disclosure. The boundary of the lesion is defined by dotted line 530. Perforations 20C indicate the lesion left by the pin electrode 20. In the illustration, perforations 20C are positioned to coincide with pin electrode locations 20B, although in reality, some repulsion may occur as the uninjured tissue attempts to return to an equilibrium state.

[0243] Arrows 535 indicate the direction of compression due to torsion. Compression is manifested mostly (but not exclusively) as wrinkles on the tissue surface. Contraction may also be amplified by the volumetric effect of damage to the tissue structure. Arrows 535 are drawn transverse to the local direction of wrinkles 532 shown in FIG. 5G to provide an example of how tissue deforms as a result of torsion.

[0244] As the advancing tissue near each pin electrode 20 is compressed against the relatively stationary tissue ahead, some tissue "piles" into wrinkles 532 ahead of the rotating pin electrode 20. In this position, the longitudinal directions of the wrinkles 532 peaks and valleys tend to lie near the tangent to a circle centered on the nearby pin electrode 20. Tissue pulled behind the pin electrode 20 is under tension along an axis toward the pin electrode 20, but is also compressed along a (nearly) perpendicular axis as it is pulled partially inward as it follows. In these positions, the wrinkles 532 tend to be oriented closer to the radial direction. Note that tension mechanisms play a large role in shaping the deformation patterns caused by twisting (torsion). Even some of the compression in the pattern is potentially due to tissue under tension in one direction "flocking together" (e.g., wrinkling) in the orthogonal direction as tension realigns it. While compressive mechanisms are prone to unstable buckling even within the limits of material integrity (e.g., small bends create larger structural weaknesses, resulting in larger flexures), tensile mechanisms lack this failure mode. This may increase the reproducibility of twist pattern results and may help avoid, for example, the "jumping" (and potential disruption of control and / or "feel") that can occur when compressed tissue suddenly buckles into a new configuration.

[0245] The resulting deformation of the tissue may promote torsional contraction (e.g., as manifested by tissue wrinkling) along a specific axis (anisotropy). This may be particularly true locally and accentuated when the electrode pin rotation is much less than one revolution (e.g., approximately 90° or less). For example, in some embodiments, "pull-back" wrinkle fanning tends to distribute the tensile force over a wide area, which may include the outer region of the eventual injury. "Push-forward" wrinkles tend to concentrate the tissue strain more locally. Accordingly, in some embodiments (e.g., for approximately 90° twist), the axis of greatest contraction is approximately parallel to the axis drawn between the start and end positions of each pin electrode. In the case of Figure 5G, horizontally extending axes may contract more than vertically extending axes, for example.

[0246] Reference is now made to Figures 6A-6B, which are photographs of the area of ​​lesion 7 created ex vivo in a pig heart using device 500 of Figure 5A before (Figure 6A) and after (Figure 6B) lesioning, according to some embodiments of the present disclosure.

[0247] In this example, two dye-stained marks 612, 611 were formed in tissue 8 prior to lesion creation. Line 603 (FIG. 6A) represents the distance between them before lesion creation, and line 604 (FIG. 6B) represents the distance between them after lesion creation. The difference in magnitude was determined to be approximately 41%, or approximately 1.5 mm. In both relative and absolute terms, this is highly advantageous compared to, for example, contraction induced using vacuum techniques, while resulting in a potentially lower profile lesion area (less raised relative to the surrounding tissue). A lower lesion profile has the potential advantage of, for example, reducing the risk of hemodynamic disruption through the valve.

[0248] In Figure 6B, lesion 7 is centered around punctures 601, 602, spaced approximately 2.0 mm apart. Ablation was performed at 8 watts for 18 seconds. Fiducial mark 207 indicates a scale size of 4 mm (e.g., as depicted by the scale bar associated with Figure 6A).

[0249] In the example of FIG. 6B, one of the electrode pins 20 that shaped the tissue prior to inducing fibrosis is stationary, while the other moves circumferentially around it, e.g., as described in connection with the embodiment of FIGS. 8A-8B. This type of movement can aid in the predictability of the resulting contraction pattern for users, who often rely on indirect visualization methods such as X-ray and / or ultrasound imaging, which provide unclear and / or partial information about what is occurring in actual use. For example, one pin electrode can be visualized as moving in a substantially straight line (even if it is actually curved) between its start and end points, while the other pin can be visualized as fixed. This can make it more apparent to the device operator in advance how the tissue is dragged behind the moving pin electrode along a distance approximately equal to the start / end point distance, while the tissue ahead of it is compressed.

[0250] However, the resulting tissue distortion pattern may be quite similar, and potentially indistinguishable, from elements of the wrinkle pattern described in connection with the symmetric twisting described in connection with FIG. 5G. For example, there is a fan of relatively small wrinkles (alternating light and dark bands) extending from the top of the image. Proximal to electrode puncture 601, larger wrinkles characteristic of "pushed" compression appear to the right and below, and extend to the left and between punctures 601 and 602, connecting with the compression wrinkles associated with puncture 602. Torsional tissue movement patterns that may occur in some embodiments of the present disclosure are also described, for example, in connection with FIGS. 6H-6I.

[0251] Reference is made briefly to Figures 6C-6D, which are photographs of the pre-sectioning (Figure 6C) and post-sectioning (Figure 6D) appearance of lesion 7 of Figure 6B, according to some embodiments of the present disclosure.

[0252] Figure 6C generally reproduces the situation of Figure 6B with fiducial mark 207 removed from the frame. Cut line 613 represents the sectioning line that resulted in cut 613A, shown open in Figure 6D. The depth of lesion 6 can be determined, for example, from the depth extent of the less shiny portion of tissue extending downward from about the location of puncture 602.

[0253] Reference is now made to Figures 6E-6F, which are pre-lesion (Figure 6E) and post-lesion (Figure 6F) photographs of an area of ​​lesion 7 created ex vivo in a pig heart using device 500 of Figure 5A, in accordance with some embodiments of the present disclosure. Reference is also made to Figure 6G, which is a post-section photograph of lesion 7 of Figure 6F, in accordance with some embodiments of the present disclosure.

[0254] Line 623 (Figure 6E) defines the pre-treatment distance between the dye-stained marks 612, 611, scaled by the 4 mm wide fiducial mark 217; this distance is also indicated by the 4 mm scale bar associated with Figure 6E. In Figure 6F, line 624 shows the reduction in the same distance after treatment with the method of Figure 5B from the location indicated by punctures 601 and 602, which were placed approximately 1.8 mm apart from each other. The average reduction over six such trials was approximately 2.5 mm, or 46% across the width of the lesion. The ablation power used was 8-10 watts, and the duration was 18-20 seconds.

[0255] The slit opening region 615 separating the dye stain marks 611, 612 in Figure 6G indicates the depth of damage caused to the tissue 8, shown in this case as a darkened region 614 visible at the central lower edge of the opening of the slit opening region 615. This fibrotic region itself is slightly lighter in color than the surrounding, much darker region that is only partially affected by the treatment.

[0256] Reference is now made to FIG. 6H, which depicts estimated movement of tissue and pin electrode positions superimposed on the lesion image of FIG. 6B, in accordance with some embodiments of the present disclosure.

[0257] The same features as shown in Figure 6B are shown with an overlay (except that line 604 has been suppressed). The overlay shows original pin electrode location 602A, which moves during rotation through the connecting arc (dotted line) shown to puncture location 602. Also shown are dotted outlines showing the original locations 611A, 612A of dye marks 611, 612, as well as the final locations of the dye marks, also outlined.

[0258] Arrows 650 connect several anterior-posterior positions. The reference frame used for rotation is the position of the puncture 601. For the purpose of assigning relative placement of the anterior-posterior positions, the two images were aligned as if all rotations occurred around this point. Choosing a different rotation center as the reference frame (e.g., as shown in Figure 6I) is compatible with the same pin electrode position, the same anterior-posterior state, but the motion attributions will be distributed differently.

[0259] While the reference frame choice of Figure 6H is not the only one available (e.g., as discussed in connection with Figure 6I), it may help understand what can happen to tissue structure when rotation compresses tissue. As pin location 602A swings clockwise relative to puncture 602, the pin drags the tissue to the right, as indicated, for example, by the movement of outline 611A toward the outline of dye-stained mark 611. The arrow 650 connecting the two is approximately the same length as the distance between 602A and 602A. If the tissue were more elastic, it could be shorter. For example, it could be longer if there was sufficient "disk-like" (rigid) circumferential movement at a radius larger than the radius of pin electrode movement. In this example, there is relatively little of this.

[0260] In contrast, the tissue from the location of outline 612 has moved mostly up and to the left in this frame of reference. This can be understood in part as the tissue being compressed to the left by the movement of the pin electrode, but the tissue further to the left is supported enough to resist being moved. The tissue has also rotated somewhat here (due to the upward movement), creating a contraction component partially perpendicular to the movement from 611A to 611B, but this is with respect to the tissue further up (e.g., above stain mark 612), which is relatively fixed (in this frame of reference) by the presence of the pin in puncture 601.

[0261] Reference is now made to FIG. 6I, which illustrates the estimated movement of the tissue and pin electrode positions using a different frame of reference relative to the movement of FIG. 6B, according to some embodiments of the present disclosure.

[0262] In this case, the center of rotation 651 selected for use in aligning the before and after images is the midpoint of the + sign of the segment joining the punctures 601, 602. The punctures 601, 602 are shown in their final position after rotating approximately 90° from positions 601B, 602B in the direction indicated by the curved arrow 652.

[0263] Contours 611A, 612A are the same as in Figure 6H and are replicated rotated 180° for purposes of explanation and visualization. Contours 611B, 612B are the contours of dye stain marks 611, 612 according to their relative positions in, for example, Figure 6B. Arrows 650 connect the front and back positions of various points on the contours of the stain marks, indicating specific directions and distances of movement that differ from Figure 6H due to the selected reference frame. The starting and ending states are the same.

[0264] In this reference frame, the motion is symmetrized so that both pin electrodes are perceived as moving in the same clockwise direction about a common midpoint. Because the pin motion is symmetric, the original positions of contours 612A, 611A, 612B, and 611B (bottom) can be treated as approximately repeated in a similar manner as above. In practice, deviations from symmetry are likely due to, for example, uneven distribution of forces exerted by tissue 8 on itself.

[0265] The pattern shown particularly highlights how the tissue moved relative to the axis 653, which intersects with the original pin electrode locations 601B and 602B. In the lower right quadrant, the tissue moved mostly to the left (symmetrically, in the upper left quadrant, it moved to the right). Some (but relatively little) radial inward movement was observed. In contrast, in the lower left, the movement was upward and to the right (slightly upward), with radial movement dominating the circumferential deflection. The opposite movement is repeated in the upper right to complete the view. Considering the resulting net effect, there is clear inward movement toward the center of rotation 651 in all quadrants, but in the lower right / upper left quadrants, the movement is almost entirely horizontal, and in the lower left / upper right quadrants, the movement is almost equally horizontal and vertical (slightly more vertical). This suggests that tissue compression is strongest horizontally and weakest vertically.

[0266] The resulting contraction anisotropy is controlled in some embodiments so that maximum contraction occurs along the circumference of the annulus. For example, axis 653 is set so that rotation from positions 601B, 602B to positions 601, 602 is symmetrical about a vertical axis. In the illustrated case, a movement of approximately 90° results in an angle of approximately 45° offset from the vertical axis.

[0267] Reference is now made to Figures 7A, 7B, and 7D, which schematically illustrate the distal end of the cardiac annuloplasty device 500 in different operating states, according to some embodiments of the present disclosure, and Figures 7C and 7E, which schematically illustrate end views of the operating states of Figures 7B and 7D, respectively, according to some embodiments of the present disclosure.

[0268] In this exemplary embodiment of annuloplasty device 500, tip 501 includes a housing 505 that is attached proximally to catheter 15 and terminates distally in a frustoconical taper. The distal face of tip 501 includes two slotted openings 702. Each slotted opening 702 is elongated along a portion of the circumference of the distal face of tip 501, as shown in FIG. 7B, and is wide enough to accommodate a pin electrode 20.

[0269] In FIG. 7A, the pin electrodes 20 are retracted, which facilitates navigation of the device to the treatment site, and optionally even positioning the device relative to the target treatment site (i.e., corresponding to block 510 in FIG. 5B).

[0270] In Figure 7B, the pin electrodes 20 each extend through a separate respective slot opening 702 and are positioned near the counterclockwise edge of that slot opening 702 when viewed from the distal side (left for the top pin electrode 20, right for the bottom pin electrode 20) (e.g., corresponding to the operation of block 512 in Figure 5B). This also corresponds to the configuration shown in the view of Figure 7C, looking proximally along the proximal-distal axis of tip 501, which also shows support 703 within housing 505 of tip 501 to which each pin electrode 20 is attached.

[0271] Rotation of the support 703 within the housing 505 can be actuated (e.g., under control from the handle 25) to move each pin electrode 20 to the opposite (clockwise end) side of each slot opening 702, as shown in FIG. 7D and the corresponding view of FIG. 7E looking proximally along the proximal-distal axis of the tip 501.

[0272] During operation of block 514 of FIG. 5B, the support 703 and its supported pin electrode 20 are rotated (either clockwise or counterclockwise) between the configurations of FIGS. 7B-7C and 7D-7E. This imparts torsion to the tissue, e.g., as described with respect to the lesions of FIGS. 6B and 6F. The slot opening 702 limits the range of rotational motion to approximately 90°, which is a potential advantage for providing a reproducible effect, e.g., reliable in terms of geometric effect (e.g., degree of contraction), and / or performance reliability (e.g., reducing the likelihood of tearing, slippage, and / or excessive deformation).

[0273] In some embodiments, multiple annuloplasty devices 500 are provided (e.g., as a kit), each with slot openings 702 extending through a different full range of angles (e.g., to allow for limited pin electrode 20 movement from about 45° to about 120°). Any suitable number of options may be provided, such as between four and eight options. This can be useful for tailoring the procedure to achieve a consistent amount of annular contraction per treatment site. For example, a surgeon can calculate the product of the number of treatment sites and the contraction rate per treatment site to achieve a surgical plan expected to result in a viable and desired amount of remodeling. Additionally or alternatively, in some embodiments, the slot openings 702 are themselves adjustable, for example, by rotating two slotted plates relative to each other. Perfect alignment of the slots may result in the largest available slot opening, or the slots may be slightly misaligned to limit the available range of motion. Optionally, the slot alignment is set prior to inserting the catheter into the target site. In some embodiments, alignment of the slots is performed by manipulation of controls remote from tip 501, such as available on handle 25.

[0274] In some embodiments, the slot opening 702 is always provided to be large enough, and the range of motion is otherwise selected to be smaller. For example, a control may be provided on the handle 25 that can be rotated to a specific position before insertion. Whatever amount of rotational range remains in the slot opening 702 after the pin is inserted into tissue at that angle will set the available range of motion.

[0275] The slotted opening does not necessarily play a role in setting the range of rotation, as described in connection with the type of embodiment described with reference to FIGS. 8A-8B, for example. Movement may be determined entirely by the operator's selection at the moment of rotation, or movement may be limited by stops on the controlling and / or controlled elements. Using a stop that directly limits the movement of the pin electrodes 20 (by contacting the pin electrodes 20 and / or their rigidly attached supports 703) has potential advantages, for example, insofar as the distance it allows is insensitive to backlash that may occur through the control linkage. In some embodiments, in addition to and / or instead of a slotted opening, another stop element may be provided as part of the tip 501, such as one or more internal protrusions interfering between the housing 505 and the support 703, one or more internal protrusions on the housing 505 that directly interfere with the pin electrodes 20, or another stop arrangement. The stop arrangement may also provide tactile feedback, allowing the operator to feel when a limit has been reached. In some embodiments, one or more intermediate detents are provided that allow tactile sensing of a partial rotation state and / or provide confirmation that rotation is occurring.

[0276] Noting that the pin electrodes 20 are conductive, their movement may be confirmed via one or more electrical contacts made with a sense conductor electrically interconnected with the proximal side of the device, thereby providing a sense switch that may be directly or indirectly coupled to the activation of an audible and / or visual indicator, such as an LED. In some embodiments, rotation is sensed with a resolution capable of distinguishing one or more intermediate rotational states, for example, using a Hall Effect sensor, multiple encoding contacts, a potentiometer (rotary variable resistor), or another method.

[0277] It should be noted that applying a twist to the entire handle 25 can potentially transmit the twist along the catheter 15. Thus, if the need to apply additional twist is recognized in a particular case, bypassing the self-limiting mode of operation remains an option available, at least in principle.

[0278] Also, note that the relative orientation of the axis extending through the two pins and the circumferential and / or axial height directions of the annulus is optionally adjusted, for example, in this manner.

[0279] 8A-8B, which are schematic illustrations of the distal end of a cardiac annuloplasty device 500 in different states of operation, according to some embodiments of the present disclosure. Also, refer to FIG. 9, which is a photograph of the cardiac annuloplasty device 500 of FIGS. 8A-8B being used during ex vivo lesioning of a porcine heart valve, according to some embodiments of the present disclosure.

[0280] In this example, tip 901 comprises a cylindrical housing 905 that is proximally attached to catheter 15 and is distally open. Electrode pin 20 is shown already extended, but may be retractable, for example, as described with respect to block 512 of FIG. 5B and / or the embodiment of FIGS. 7A-7E.

[0281] In some embodiments, relative rotation of the housing 905 with respect to the support 902 (e.g., under control from the handle 25) changes the relative positions of the two pin electrodes 20, optionally to any relative angle.

[0282] For example, a rotation of approximately 180° is shown in the difference between the configurations of FIGS. 8A and 8B. Optionally, a different rotation is performed, e.g., a rotation in the range of 60° to 120°, e.g., a rotation of approximately 90°. In some embodiments, the pin electrode 20 within the lumen of the support 902 is rotatably fixed. It is confined by the lumen of the support 902, but does not necessarily rotate about its own axis thereby. The outer pin electrode 20 (occupying the space between the support 902 and the housing 905) may be attached to the housing 905 and move with the rotation of the housing 905 (e.g., as shown), or it may be attached to the support 902. In the latter case, the case housing 905 may be configured to rotate relative to the catheter 15 as the support 902 rotates, so that the support 902 and the housing 905 rotate together. Alternatively, the housing 905 may be provided as a cylinder without the bulge shown that houses the outer pin electrodes 20, allowing the support 902 to rotate eccentrically within the housing 905 to change the relative position of the pin electrodes 20. Optionally, the housing 905 is rotatable relative to the catheter 15, while the support 902 (and the pins 20 that it supports) remains fixed.

[0283] Note that in the embodiment of FIGS. 8A-8B, the center about which the pin electrodes 20 rotate is effectively the center of one of the pin electrodes 20. For example, such an embodiment was used to create the lesion of FIG. 6B. Thus, in contrast to the example shown in FIGS. 5D-5G, one pin electrode 20 (e.g., occupying puncture 601) may remain in place while the other pin electrode 20 (e.g., occupying lesion 602) rotates around it, appearing to "wrap" the tissue around the stationary pin. This may result in some differences in the appearance of the resulting wrinkle pattern due to different tissue motions induced relative to the stationary tissue reference frame. For example, if puncture 601 is taken as the central reference, puncture 602 will appear to rotate counterclockwise around it.

[0284] 9 shows a portion of an annuloplasty device 500 including the distal end of the catheter 15 and tip 901, with the pin electrodes 20 extended and partially inserted into the tissue 8 in preparation for twisting and lesioning. Also visible nearby are several lesions 6 with diamond-shaped protrusions, created separately by another annuloplasty device 100.

[0285] Reference is now made to FIGS. 10A-10C, which schematically illustrate the distal end of a heart annuloplasty device 500 in different operating states, according to some embodiments of the present disclosure.

[0286] In this example, the tip 1001 of the annuloplasty device 500 comprises a housing 1005 proximally attached to the catheter 15 and has two linear slot openings 1003 distally through which the electrode pins 20 can be optionally retracted (FIG. 10A) or extended (FIGS. 10B-10C). When retraction is not performed, the electrode pins 20 remain extended. The two electrode pins 20 are positioned on opposite sides of the respective slot openings 1003.

[0287] Actuation of the device (e.g., from the handle 25) causes the electrode pins 20 to alternate sides. The movement of the electrode pins 20 is linear, but the impact on the tissue imparts a torsion. When the electrode pins 20 cross over each other, there is an intermediate period of linear compression combined with torsion. Optionally, actuation is stopped at an intermediate position before the structure-disrupting energy is applied.

[0288] Annuloplasty Device Using Surface Electrodes - Patent application Reference is now made to FIG. 11 , which schematically illustrates the distal end of a cardiac annuloplasty device 1100, according to some embodiments of the present disclosure. This example has a tip 1101 that separates the functions of electrical energy conduction and tissue placement. Pins 1102 travel within slotted openings 1104 in a tip housing 1105 (e.g., while embedded in tissue as described herein for pin electrodes). They close together from an initial, separated position, with the pins at the outer edge of the slotted openings 1104, to the compressed position shown in FIG. 11 . The tissue into which the pins are inserted is likewise compressed, and the compressed shape is retained during treatment-induced plastic deformation.

[0289] However, RF energy is delivered separately through the tissue via electrodes 1103. These electrodes are in contact with the tissue surface adjacent to pins 1102 during operation. This separation has the potential advantage of avoiding placing the highest temperatures (which can weaken tissue) at the locations of greatest mechanical stress. This potentially allows for greater compression to be applied, for example, shrinking a 5 mm wide area to a width of 2.0-2.5 mm.

[0290] Another advantage of this method is that it decouples the lesion geometry from the design of the tissue shaping device. For example, electrode pins generate lesions along their penetration depth, while surface electrodes can be engineered to limit lesions to more superficial layers. This may also help the deeper tissue around the inserted pins maintain its mechanical integrity during treatments that induce more superficial fibrosis.

[0291] Because surface electrodes do not need to withstand mechanical stress, they can be narrow (e.g., 0.5 mm or less) and produce correspondingly narrow lesions. Additionally or alternatively, the surface electrodes can be larger in width than is appropriate for pin electrodes (e.g., they can together occupy more than half the width of the probe, resulting in a total width of, e.g., 4-7 mm). This may allow for a more even distribution of current across the treated area. This, in turn, may help reduce damage from excessive local heating and / or improve the homogeneity of the lesions produced. Potentially, the applied energy (e.g., power or operating time) can be shorter. This may be due, for example, to a larger contact patch that distributes energy more evenly and / or to a reduced need to reliably reach areas more than a short distance from the probe (e.g., on the order of 1 millimeter).

[0292] Construction of an annuloplasty device using rotational distortion 12A-12B, which schematically depict a casing 1200 of a distal portion 1300 of an annuloplasty device 500, according to some embodiments of the present disclosure. For example, the casing 1200 is provided as a component of the annuloplasty device 500 of FIGS. 7A-7E and operates in conjunction with the support 702.

[0293] In some embodiments, the casing 1200 comprises a generally cylindrical body 1205, the wall of which has an opening 1209 open along one side to an angular range (e.g., as described in connection with FIG. 13A ) corresponding to the angular range over which the pin 20 (e.g., pin electrode) can be rotated when mounted in the body 1205. The body 1205 comprises a non-conductive, and preferably heat-resistant, material, such as PEEK or another polymeric material.

[0294] Also provided in some embodiments is a sensing electrode 1206 electrically coupled to a sensing circuit (e.g., sensor controller 36 of FIG. 5A ) proximal to the annuloplasty device 500 (e.g., operating as further described in connection with FIG. 13A ). In some embodiments, the sensing electrode 1206 is formed in a C-ring shape. In some embodiments, the sensing electrode 1206 is electrically coupled via a conductive strip 1207 (bridge) and a connecting junction 1208 leading therefrom to the connector 1204. The connecting junction 1208 may be secured using, for example, laser welding. Optionally, the sensing electrode 1206 and the conductive strip 1207 comprise a stainless steel material. The conductive strip 1207 may be disposed within a slot in the body 1205.

[0295] In some embodiments, the sensing electrode 1206 includes one or more portions 1206A, 1206B, each having a surface positioned to contact the pin 20 at a position or positions within its range of rotational and / or longitudinal movement.

[0296] In some embodiments, the casing 1200 includes one or more cavities 1210 sized and shaped to accommodate a portion of a radiopaque marker 1311 (e.g., as shown in FIG. 13D ). In some embodiments, two cavities 1210 are diametrically disposed around the circumference of the casing 1200.

[0297] Reference is now made to FIG. 12C , which schematically illustrates a housing 1220 of a distal portion 1300 of an annuloplasty device 500, according to some embodiments of the present disclosure. For example, the housing 1220 may be provided as a component of the annuloplasty device 500 of FIGS. 7A-7E , corresponding to the housing 505, including a curved slot opening 1222 in a distal surface 1223 corresponding to the slot opening 702. The curved slot opening 1222 defines a track along which the pins 20 of the pin element 1301 travel. The width of the slit opening 1222 may be sized to match the width of the pins 20 (e.g., approximately 0.4 mm), thus providing the pins with some mechanical support to help prevent them from breaking due to stress concentrations where they join the base 1307 ( FIG. 13A ). However, the pins 20 are preferably long enough so as not to exert force on the pins 20 when they are in their fully rotated position, restricting their rotational movement. Instead, the force is captured by a portion of the base 1307 (eg, the constricted region 1305 ) interfering with the casing 1200 .

[0298] Also shown are distally tapered body portion 1224, cylindrical body portion 1226, and cavity 1228. Optionally, cavity 1228 is one of a plurality of cavities 1228, for example, two cavities diametrically spaced around the circumference of housing 1220. In some embodiments, cavity 1228 is positioned such that radiopaque marker 1311 inserted through cavity 1228 is also inserted into cavity 1210 of casing 1200, acting as a pin to secure them together.

[0299] In some embodiments, the housing 1220 comprises a polymeric, electrically insulating material, preferably heat resistant, such as PEEK.

[0300] Reference is now made to Figure 13A, which schematically illustrates a partially assembled tip portion 1300 of an annuloplasty device 500, according to some embodiments of the present disclosure. For example, tip portion 1300 corresponds to tip portion 501 of annuloplasty device 500 of Figures 7A-7E.

[0301] The partially assembled components shown include casing 1200, pin support 1303 (e.g., corresponding to support 703 in FIGS. 7A-7E), pin element 1301, and connecting cable 1302. Connecting cable 1302 is flexible, e.g., outer casing 1302A of connecting cable 1302 has slots 1302B to increase its flexibility. In some embodiments, outer casing 1302A comprises stainless steel, optionally with an electrically insulating sleeve such as polymer shrink tubing.

[0302] The pin element 1301, in some embodiments, comprises a plurality of pins 20, each including a pin body 1304 and a sharp tip 1306. The pin body 1304 may be quadrilateral (e.g., square) in cross section. The pins 20 may be coupled to one another via a base 1307 that connects them to the pin support 1303. The base 1307 is electrically connected to the proximal side of the annuloplasty device 500 via one or more conductors of a connecting cable 1302.

[0303] The pins 20 may be electrically connected to each other or individually via a connecting cable 1302. Optionally, the connection is made through the (conductive) body of the outer casing 1302A, e.g., via a connection made using laser welding. The pins 20, via their electrical connection(s), are optionally configured as pin electrodes 20 (e.g., in a monopolar or bipolar configuration), e.g., for delivering RF, microwave frequency, and / or electroporation energy to tissue. As shown, the pin elements 1301 also include contact regions 1305. Optionally, all of the pin elements 1301 are made from a single piece of metal, e.g., a piece stamped or laser cut from sheet stock, or a 3D printed part. In some embodiments, the pin elements 1301 comprise tantalum, which provides both electrical conductivity and fluoroscopic radiopacity.

[0304] The pin support 1303 is rotatable relative to the casing 1200 and movable relative to the casing 1200 along the proximal-distal axis, for example, by movement of the connecting cable 1302 and / or mechanical elements extending within the outer casing 1302A. Because contact is prevented by mechanical interference with the base 1307 of the pin element 1301, the more fragile tip regions of the pin element (e.g., pin body 1304) are protected from excessive torque that could cause them to bend, pull out of the tissue, and / or lead to other adverse events.

[0305] These movements change the nature of the electrical contact that contact area 1305 has with sensing electrode 1206. In the example shown, contact area 1305 makes electrical contact with sensing electrode 1206 when pin 20 is fully advanced and rotated to its maximum extent to one side or the other of opening 1209.

[0306] This allows sensor controller 36 to detect these particular states and, optionally, indicate them by other indicators, such as, for example, illumination of an LED and / or audible, tactile, and / or other types of visually presented indications. Optionally, one or more other positions on case 1200 are electrically interconnected with sensing electrode 1206 to enable sensing of other positions, such as one or more fully extracted positions of pin element 1301. Of the multiple positions that can be detected through the same sensing device (and indicated in the same way), an operator can determine which is actually relevant, knowing, for example, which side he has turned pin element 1301 to and / or whether he is extracting or advancing pin element 1301.

[0307] In some embodiments, the sensing device itself is configured to distinguish between different positions. For example, different contact areas on the casing 1200 are connected to the sensor controller 36 via resistances of different values. Optionally, a variable resistor-type configuration is provided, whereby electrical contact between the pin element 1301 and the casing 1200 is made via a resistive element, e.g., a lining of the casing 1200 that includes polymer-embedded carbon particles, resistive paste, or another material. This potentially allows for gradual detection of the response to an input movement command, allowing, for example, to distinguish and / or assess partial rotations and / or distances of pin advancement along the proximal / distal axis.

[0308] 13B-13C, which schematically illustrate a partially assembled tip 1300 of annuloplasty device 500 with the addition of housing 1220, according to some embodiments of the present disclosure. As shown, pin 20 of pin element 1301 is fully extended. From the proximal view of FIG. 13B, it can be seen that connector 1204 is exposed where it may be connected during final assembly.

[0309] Reference is now made to FIG. 13D , which schematically illustrates the distal end 1300 of the annuloplasty device 500 with the addition of a catheter casing 1310, according to some embodiments of the present disclosure. Optionally, a radiopaque element 1311 is used as a pin to interconnect the housing 1220 and the casing 1200, and optionally the catheter casing 1310 is also interconnected (e.g., through holes in the casing material). Optionally, the catheter casing 1310 can be adhered to the housing 1220 and / or the casing 1200, for example, using adhesive and / or melting. It should be noted that in the illustrated assembly, the connector cable 1302 and the catheter casing 1310 are rotatable relative to one another, and thus the pin element 1301 is rotatable relative to the housing 1220. In some embodiments, the assembly includes a steering element (e.g., a longitudinally elongated element, not shown) connected to one or more sides of the assembly and that can be shortened or otherwise manipulated to redirect the distal end of the device.

[0310] 14, which illustrates a fluoroscopic (X-ray) image of the distal tip 1300 of an annuloplasty device 500 in situ (i.e., within a chamber of the heart), according to some embodiments of the present disclosure. Particularly shown in the image are the location of the pin assembly 1301, the radiopaque markers 1311 (e.g., two), the housing 1220, and the passage of the connecting cable 1302 through the catheter casing 1310 and the guide sheath 1401.

[0311] For effective annuloplasty, it is a potential advantage to include device features and / or methodological approaches that allow the operator to find and maintain a clear and unambiguous understanding of the relative positions of the device and tissue target. For example, the positions of the radiopaque markers 1311 can be adjusted by rotation until they are presented at their widest (as shown) or narrowest distance, allowing the orientation of the distal tip 1300 to be calibrated to one or more known and / or predefined fluoroscopic viewing angles (views). Optionally, the reference viewing angle can be shifted depending on which region of the annulus is being worked on. For example, different respective angles (e.g., different positions of the fluoroscope's "C" arm) can be selected for different circumferential regions along the mitral annulus, and different views can be selected for the P1, P2, and / or P3 regions along the posterior side of the annulus, for example.

[0312] Manipulation of an annuloplasty device using rotational strain 15A and 15C, which schematically illustrate a horizontal (transverse) cross-section 16 through the left side of the heart, including the left atrium 41 and left ventricle 43, in accordance with some embodiments of the present disclosure. Also shown (FIG. 15A) are the locations of the foramen ovale 42 (often used in minimally invasive cardiac procedures as a passageway between the right and left atria), the mitral valve 200, and the mitral annulus 202. Icon 1501 in FIG. 15C provides a more global view of the situation, with plane 16 intersecting heart 50 at a location near the bottom of left atrium 41 (shown with diagonal lines and hidden behind heart 50 from this perspective).

[0313] 15B, which shows a 3D reconstructed ultrasound image of the valve 200 looking down on the horizontal (transverse) cross section 16, according to some embodiments of the present disclosure. Also visible as a generally cylindrical body is the distal tip 1300 of the annuloplasty device 500.

[0314] 15D and 15F, which schematically illustrate a coronal (frontal) cross section 17 through the left side of the heart, including the left atrium 41 and left ventricle 43, in accordance with some embodiments of the present disclosure. Also shown are the locations of the foramen ovale 42, mitral valve 200, and mitral annulus 202 (FIG. 15D). Icon 1502 in FIG. 15F provides a more global view of how plane 17 traverses heart 50.

[0315] 15E, which shows a planar ultrasound image providing a coronal cross-section (corresponding to coronal cross-section 17) of valve 200 (e.g., showing valve leaflets 200A), according to some embodiments of the present disclosure. Also visible as a longitudinally elongated body is distal tip 1300 of annuloplasty device 500, which traverses over the valve to position housing 1220 in contact with valve annulus 202.

[0316] Reference is now made to Figures 16A-16H, which illustrate a sequence of 3D reconstructed ultrasound images acquired at different positions and / or articulations of the tip 1300 as the pin element 1301 moves around the circumference of the mitral valve annulus 202, in accordance with some embodiments of the present disclosure. The tip 1300 enters the left atrium at the foramen ovale 42. The approximate position and longitudinally elongated shape followed by the tip 1300 in each image is indicated by a hollow black line. See also Figure 16I, which overlays the various positions of Figures 16A-16H into a single image.

[0317] At each such location, the tip 1300 of the device was manipulated to insert and twist the pin 20 into the tissue of the annulus 202, and then induce plastic deformation by the supply of energy (in this case by supplying RF energy through the pin 20 acting as a pin electrode, and optionally microwave and / or electroporation energy).

[0318] From ultrasound and / or fluoroscopic images of the type shown and / or described in Figures 14-16I, it can be seen that while the general situation can be understood, potential problems remain in determining exactly where the targeted annular tissue is and how to manipulate the tip 1300 so as to properly manipulate the targeted annular tissue and deliver structural disruption energy through the tip 1300.

[0319] Operational characteristics of a rotational strain-based annuloplasty device Reference is now made to FIGS. 17A-17B, which illustrate fluoroscopic (X-ray) images and schematic diagrams of a pin assembly 1301 (which may comprise a radiopaque material such as tantalum) in situ (i.e., within a heart chamber) associated with a radiopaque marker 1311, according to some embodiments of the present disclosure. FIG. 17B images a device configuration in which the pin assembly 1301 is fully retracted into a housing, such as housing 1220 of FIG. 12C. This configuration can be identified by the relative position of the radiopaque marker 1311, which is directly aligned with the pin 20. FIG. 17A images the pin 20 in an extended position, advanced significantly beyond the longitudinal position of the radiopaque marker 1311.

[0320] Reference is now made to Figure 18A, which schematically depicts views of pin assembly 1301 and radiopaque marker 1311 in different rotational positions, in accordance with some embodiments of the present disclosure. Reference is also made to Figures 18B-18D, which show x-ray images of distal tip 1300 including views of pin 1301 from different rotational angles, in accordance with some embodiments of the present disclosure.

[0321] In Figure 18A, the view associated with angle 1701 shows the pin assembly 1301 and radiopaque marker 1311 at their widest separation (plan view). The view associated with rotation angle 1702 adds a 45° rotation, and the view associated with rotation angle 1703 adds a 90° rotation. Adding another 45° rotation results in the view again looking like the view associated with rotation 1702.

[0322] The view at angle 1702 corresponds, in some embodiments, approximately to the oblique view seen in FIGS. 18B and 18D, while the view at angle 1703 corresponds to a rotation of angle 1703. Thus, the series of images from FIGS. 18B through 18D corresponds to approximately a 90° rotation from one to the other. While ambiguous in a still image, the two 45° rotation angles can be distinguished by observing the time lapse of the transition and / or by knowing how much and in what direction control was applied to cause the positional movement. Note that opaque marker 1311 is shown somewhat closer to pin assembly 1301 in this embodiment than it is shown in FIGS. 18A-18D.

[0323] Reference is now made to FIGS. 19A-19B, which schematically depict overtube 1901 pre-positioned to assume a compound bend that imparts both curvature and out-of-plane displacement, in accordance with some embodiments of the present disclosure. In some embodiments, the pre-positioned bend is assumed when constraint from overtube 1901, e.g., by an additional outer tube, e.g., tube 1900, is removed. Alternatively, in some embodiments, the shape shown is an "extreme" bend of overtube 1901 with steering fully actuated. When steering is not actuated (or conversely actuated), overtube 1901 straightens. Optionally, overtube 1901 is biased to bend, and steering is actuated to further bend overtube 1901 or, optionally, straighten it away from the biased bend. The minimum radius of curvature can be, for example, radius 1903. In some embodiments, the catheter device itself is configured to be steerable in the same manner as described for overtube 1901.

[0324] The view of overtube 1901 in FIG. 19A depicts an end view of a curled portion including segment 1905, which is pre-positioned to bend out-of-plane (i.e., out of the plane of the curl or assume a helical shape) a distance 1902 as it curls. Optionally, the curl and / or out-of-plane displacement is assumed, at least in part, upon expansion of overtube 1901 from constraint by segment 1900, which may be provided as an additional overtube. The additional (or reduced) curl and / or out-of-plane displacement is optionally provided by a steering input. Alternatively, segment 1900 may be provided as part of overtube 1901, with the curl being essentially entirely controlled by the steering input. The steering input may be provided, for example, via a longitudinally elongated element (not shown) attached to tip 1904, extending along the body of tube 1901, and returning along segment 1900. The element is attached to tip 1904 such that tension on the element induces a steering motion as shown. In particular, the elongate element can partially wrap around the circumference of segment 1905 as it extends toward tip 1904, so that when it is longitudinally shortened, it pulls tip 1904 out of plane through distance 1902 and induces curl to major radius of curvature 1903. Note that gradual adjustment of the major curvature and out-of-plane bending has potential advantages for addressing generally saddle-shaped annulus such as the mitral valve, as discussed in connection with FIG. 19C .

[0325] In some embodiments, the tip 1904 of the overtube 1901 is also steerable, at least in part, independent of the overall bending, for example to allow adjustment of the out-of-plane distance 1902 .

[0326] It should be noted that the curvatures shown and discussed in connection with Figures 19A-19B are potentially well-suited for shallow angles of incidence around the circumference of the annulus, relative to angles above or below the (local) plane of the valve. For example, the angle can be within 60° of this plane, within 45°, within 35°, within 30°, or within 25° of this plane. In some embodiments, the angle is within 30°-50° of the local plane of the valve, optionally less than that, but preferably no more than that. To the extent that the valve may have a non-planar shape (e.g., saddle-shaped), the "local" plane of the valve refers to a plane that includes (e.g., at least to some extent) some approximate portion of the overall annulus. Shallow entry angles offer potential advantages for avoiding leaflet injury and / or for achieving repeatable positioning and / or engagement with the annular tissue.

[0327] Reference is now made to FIGS. 19C-19D, which schematically depict an overtube 1901 (or a catheter similarly configured for steering) relative to a generally saddle-shaped valve annulus 200, according to some embodiments of the present disclosure. In FIG. 19C, a slight steering input (tensioning) results in a relatively slight circular bend and a relatively slight out-of-plane bend away from the location of the foramen ovale 42. For example, a 10-20 mm out-of-plane displacement may be required to reach the valve tissue. In FIG. 19D, a stronger steering input (more tensioning) results in a relatively tighter circular bend and a relatively larger out-of-plane bend away from the location of the foramen ovale 42. For example, a 35-45 mm out-of-plane displacement may be required to reach the valve tissue. In some embodiments, the position in FIG. 19C corresponds to accessing region P1 (the distal portion of the posterior annulus) of the mitral valve annulus for treatment. In some embodiments, the position in FIG. 19D corresponds to accessing region P3 (the proximal portion of the posterior annulus) of the mitral valve annulus for treatment.

[0328] Bioimpedance Heuristic Reference is now made to FIG. 20, which is a schematic flow chart illustrating targeted and / or expected thresholds and / or ranges of bioimpedance in ohms (Ω) for various stages and / or conditions during an annuloplasty procedure, according to some embodiments of the present disclosure.

[0329] The values ​​shown were experimentally developed using pin 20, an electrode that delivers structural disruptive energy at RF frequencies. The pin electrode was constructed of stainless steel with a square cross section of approximately 0.4 mm x 0.4 mm. However, similar values ​​are expected for other (conductive) electrode materials, such as tantalum. The values ​​apply for electrode-to-electrode distances ranging from approximately 1 to 2 mm and tissue penetration distances ranging from approximately 4 mm. Furthermore, the values ​​shown are optionally used with operating parameters of delivering 8 to 10 watts of RF power for approximately 8 to 25 seconds. In some embodiments, impedance measurements are performed at frequencies ranging from 25 to 75 kHz (e.g., 50 kHz). Frequency sampling is preferably performed above the corresponding Nyquist frequency (e.g., at approximately 2 MHz). At a measurement frequency of 50 kHz, for example, 60 microseconds of data (120 samples) can be used to capture three complete waveforms, which may be useful for filtering out noise. In some embodiments, results are displayed at approximately 1-second intervals (optionally faster or slower).

[0330] Block 2000 depicts the time when the electrodes are in a pre-exposed state (e.g., retracted into housing 1220) and in contact with blood but not tissue. Typical bioimpedance measured in this state was greater than about 750 Ω.

[0331] In block 2002, upon contacting the device tip with tissue and initiating electrode insertion, a measured drop in bioimpedance occurs, determined to be typically in the range of approximately 220 Ω to 500 Ω as insertion progresses. In some embodiments, this range is used as an indication that the device tip is in a position where the pins (e.g., pin electrodes) can be extended to insert into the annular tissue. Optionally, the upper limit of this expected range is lowered, e.g., to 400 Ω, potentially increasing the reproducibility of treatment results but also potentially increasing the need for longer and / or repeated attempts to position the device tip. If the expected range is not generally achieved and / or maintained during insertion, this may indicate failed penetration and / or loss of penetration.

[0332] In block 2004, final annular penetration with adequate force to initiate structural disruption (as the pins 20 extend into the tissue) typically (but not always) resulted in a narrowing of the bioimpedance from the more common range associated with such insertion. Depending on the initial conditions, this has been observed to variably result in a slight rise or fall from the initial range, typically within the range of 240 Ω to 360 Ω. In some embodiments, the impedance is in the range of 200 Ω to 400 Ω. Optionally, achieving an impedance in this range is used as a gating condition for further manipulation and / or as confirmation of a "good fit" between the device and tissue, as the tissue can be manipulated (e.g., rotationally distorted) with the pins inserted, potentially without loss of electrical contact and / or damage to the device pins. A particularly low impedance may indicate that the expansion pins are not through the tissue but are instead exposed to each other across the blood-filled open volume. Pushing the device forward may increase the impedance, indicating correct placement. Optionally, the upper limit of the "good fit" range is lowered, e.g., to 320 Ω, and / or the lower limit of this range is raised, e.g., to 280 Ω. Such a range reduction potentially increases the reproducibility of the procedure, but also potentially increases the need for longer and / or repeated attempts to position the tip of the device.

[0333] Block 2006 (together with its sub-blocks) illustrates several potential bioimpedance states resulting from the application of structural disruption energy. Block 2007 illustrates a target range of approximately 1000 Ω to 2250 Ω, corresponding to the range of bioimpedance corresponding to successful delivery of structural disruption energy. Above 2250 Ω (block 2008), delivery of structural disruption energy is optionally terminated, in the illustrated example, even if the planned power delivery time (e.g., within a range of 15 to 30 seconds) has not yet been reached. Optionally, a termination threshold is selected from a range of 1800 to 2500 Ω. The upper limit of this range is optionally lowered, e.g., to 2400 Ω, potentially increasing a safety margin. Additionally or alternatively, the lower limit of this range is optionally raised, e.g., to 2000 Ω, potentially reducing the occurrence of unnecessary system self-shutdown. In some embodiments, automatic termination occurs when the selected termination threshold is reached. Optionally, automatic termination is linked to a time course characteristic of impedance change. For example, abrupt impedance changes relative to the normal time course of structural disruption (hundreds of milliseconds instead of seconds) are optionally filtered from triggering a stop until a more physiologically relevant period has passed. Block 2009 indicates that bioimpedance remains at (or suddenly returns to) a level below about 400 ohms while structural disruption energy is being delivered. This is optionally considered to be indicative of poor or lost attachment, regardless of what other bioimpedance display history may have indicated.

[0334] In some embodiments, bioimpedance measurements are used in conjunction with imaging and / or another measurement type to confirm that device operation is proceeding according to an expected sequence of events.

[0335] Method of operating an annuloplasty device Reference is now made to Figure 21, which is a schematic flow chart depicting a method of operating an annuloplasty device, according to some embodiments of the present disclosure. In some embodiments, the annuloplasty device operates according to the principles of tissue contraction by a combination of twisting / torsion (e.g., as described in connection with Figures 5A-11 herein) and the application of structural disruption energy.

[0336] In summary, the method includes operations enclosed within the larger blocks shown. Block 2101 includes initial device positioning and optional calibration of the positioning. Block 2109 includes engagement of the annuloplasty device to the treatment location. Block 2115 includes deformation and structural disruption (plastic deformation) of the treatment location. Block 2121 includes evaluation of results and (while relevant) continuation to the next treatment location. The various sub-blocks are provided as non-limiting examples of categories of operations (further examples are described below) that may occur within each of the larger blocks.

[0337] In block 2100, in some embodiments, an annuloplasty device is inserted into a body cavity adjacent to the valve to be treated, for example, into the left atrium via the fossa ovalis of the atrial septum for treatment of the mitral valve. In some embodiments, another heart valve (e.g., the tricuspid valve) is to be treated.

[0338] In block 2102, in some embodiments, the rotational orientation of the annuloplasty device is calibrated. This is particularly relevant to the pin-torsion embodiments of Figures 5A-11, but also optionally applies to vacuum-using embodiments of Figures 1A-4C, for example, where the lesion formed is longer in one dimension than another and / or configured to preferentially pinch tissue along a particular axis.

[0339] In some embodiments, calibrating the rotational orientation of the annuloplasty device includes rotating the annuloplasty device under image visualization until the configuration of the device (as viewed from the angle of visualization) matches a known rotational state. In some embodiments, this includes rotating a portion of the device including at least two radiopaque markers until the markers reach a maximum or minimum distance in the fluoroscopic image that visualizes them. Optionally, the radiopaque markers include pins that are themselves used in mechanically manipulating and / or energetically modifying tissue under analysis. Optionally, the radiopaque markers include elements affixed to the tip of the device in a known and / or determinable relationship to the orientation of the pins.

[0340] In some embodiments, calibration uses another method, for example, ultrasound scattering and / or reflection patterns that return a characteristic signal when directed at the location of the ultrasound detector and / or ultrasound energy source.

[0341] When fluoroscopy and / or ultrasound visualization are readily available, direct imaging of the annuloplasty device itself may provide a preferred method for determining device orientation, as it offers the potential advantage of providing a direct and intuitive understanding of how the annuloplasty device is positioned. However, it is potentially advantageous to calibrate and / or monitor device orientation using non-imaging methods, for example, to reduce procedural complexity and / or reduce radiation exposure.

[0342] Using such a method, the orientation of the annuloplasty device itself is optionally detected directly. Optionally, the orientation of another element (e.g., an overtube or specialized measurement device) is determined, and this information can be transmitted via known spatial and / or additional measurement constraints to apply the annuloplasty device. Note that indirect methods have the potential advantage of not adding sensor bulk directly to the annuloplasty device, although the sensing element(s) may optionally be placed somewhat proximal to the tip itself, where there is potentially more available space. To the extent that the annuloplasty device itself directly senses and / or is sensed, there is a potential advantage for real-time and / or more clearly localized sensing of the device's orientation and / or position.

[0343] Non-imaging sensing principles for determining device orientation optionally include, for example, one or more of magnetic field orientation sensing, acceleration sensing (e.g., weight sensing), pressure sensing (e.g., differential pressure of blood, e.g., on opposite sides of a sensing head), flow sensing (e.g., of blood), and strain sensing (e.g., to determine twist along the device). Additionally or alternatively, physical constraints may be used to help determine orientation and / or to help convey known orientation information about an element to the annuloplasty device. Examples include:

[0344] In some embodiments, magnetic field emitters and / or detectors associated with the pins of the annuloplasty device in a known and / or determinable orientation are used, with corresponding detectors / emitters placed elsewhere to sense / activate the emitters / detectors associated with the pins. For example, a guidewire containing one or more small magnets and / or electromagnets is optionally placed in the circumflex and / or coronary sinus around the annulus. This is detected by the tip of the device (e.g., using a MEMS Hall effect detector) and potentially even used to magnetically attract the tip of the device toward the annulus.

[0345] In some embodiments, orientation is determined at least in part by noting the direction of bending when the steering degree of freedom is manipulated to move (i.e., bend) the tip. The determination of direction may be based on changes in a measured parameter (e.g., the direction of acceleration determined with respect to gravity) and / or in relation to the physical constraints of the movement itself (e.g., steering may be more associated with distance limitations in some directions than in others).

[0346] In some embodiments, it may be advantageous to directly determine the orientation of the overtube rather than the annuloplasty device itself. For example, the orientation of the overtube can be known by imaging and / or tracking used to steer the overtube into position, after which imaging can optionally be discontinued or reduced, at least to the extent that the orientation of the overtube can be transferred to information regarding the orientation of the annuloplasty device (e.g., as described below). In some embodiments, the history of how the overtube was steered into position (e.g., by steering and / or twisting) is tracked. The overtube is relatively resistant to twisting about its longitudinal axis (e.g., because it is larger), its general location and course through the body are known, and the orientation of the proximal portion of the overtube may be known. Optionally, the overtube is actually subject to twisting, but calibrated sensing (e.g., via a strain gauge arrangement such as a fiber optic strain gauge) is used to determine the amount of twisting.

[0347] As a means of conveying orientation information, in some embodiments, an overtube used with an annuloplasty device includes a stenosis (e.g., at its distal opening and / or at another location proximate to the distal opening) that creates a non-circular ("keyed" or "warded") shape (e.g., the shape is recessed from circular on one or more sides) through which the annuloplasty device passes. The non-circular shape is selected so that the cross-sectional shape of the annuloplasty device can pass through the stenosis only in one or more specific matching orientations. Optionally, a detent-type interaction between the overtube and the annuloplasty device is used (e.g., a ridge in the overtube's lumen and a receiving recess in the annuloplasty device), resulting in a mechanical "hesitation" that the operator can feel at certain orientations and no such hesitation at other angles. In some embodiments, electrical sensing (e.g., tactile and / or resistive) is used to determine the relative orientation of the overtube (which serves as a reference frame) and the annuloplasty device.

[0348] Optionally, a sensing probe advanced through the overtube prior to use of the annuloplasty device determines the orientation of the overtube, e.g., based on any of the sensing principles described above, and this information is transferred to help determine the orientation of the annuloplasty device when the annuloplasty device itself is inserted, e.g., via a "keying" or detent-type mechanism to the orientation of the overtube and from there to the annuloplasty device itself.

[0349] At block 2104, in some embodiments, the orientation of the annuloplasty device is adjusted from a known / calibrated position to a target position, optionally appropriate for the intended orientation of the device pins relative to the annulus. This is optionally done “blindly” by a fixed amount of offset from the calibrated orientation. Optionally, sensory feedback continues to be provided during adjustment. The preferred orientation at the target position optionally depends on the type of device. For example, vacuum-type devices that create a diamond-shaped lesion (e.g., FIGS. 1A-4C ) are preferably oriented with the long axis of the diamond perpendicular to the circumferential direction of the annulus. Regardless of the orientation of the diamond-shaped portion of the lesion (if present), pinching-type vacuum-type devices may be preferentially oriented so that the direction of greatest shortening due to pinching is the circumferential direction. The pin-type “torsion” devices of FIGS. 5A-11 may preferably be oriented so that the axis extending between the two pins (e.g., their tips) is oblique to the circumferential direction of the annulus. In embodiments combining vacuum and torsional deformation, the preferred orientation may be oblique, similar to pin-type torsional devices. This also applies to vacuum-activated embodiments that also include pins used, for example, to prevent slippage and / or to facilitate deeper penetration of the lesion by acting as energy delivery electrodes.

[0350] In some embodiments, once the rotational orientation has been calibrated by a first method, device, and / or principle in block 2102, the rotational position may be further tracked by another method, device, and / or principle. For example, the rotation of an electrode relative to a resistive membrane may be measured. In some embodiments, an electrode is placed on a surface of the annuloplasty device that contacts a portion of the lumen of the resistive membrane-lined overtube, and changes in resistance are used to track changes in orientation. Additionally or alternatively, an operator may set a marker on the handle of the annuloplasty device to a “calibrated” position and then record the offset from this position, e.g., relative to the overtube or general surroundings, thereby enabling the orientation to be determined, at least approximately.

[0351] The rotational adjustment operation optionally includes adjusting the angle of incidence above or below the plane of the valve that the annuloplasty device assumes relative to the tissue of the annulus.

[0352] In block 2106, in some embodiments, the annuloplasty device is brought to a first selected location around the valve annulus to begin treatment. Optionally, an operation to assess the orientation of the device (e.g., as described in connection with blocks 2102-2104) is determined during the operations of this block.

[0353] In some embodiments, the operations of block 2106 are performed under live image-assisted guidance (e.g., ultrasound and / or fluoroscopy, as described in connection with the images shown in any of FIGS. 14-18D). Additionally or alternatively, in some embodiments, non-imaging measurements are performed to determine and / or confirm device positioning. For example, bioimpedance measurements are performed, for example, as described in connection with FIG. 20.

[0354] In some embodiments, the relevant anatomical shape of the valve to be treated is known from previous imaging, e.g., pre-treatment imaging or imaging at an earlier stage of the current treatment. The anatomical shape can be determined, for example, by segmentation of (3D) MRI or CT images. Optionally, the shape is determined from 2D fluoroscopic images based, for example, on images of the distribution of injected contrast agent, and optionally, the 3D shape is reconstructed from stereoscopic constraints of images taken from different directions. The insertion position of the annuloplasty device near the valve can be determined, for example, from image-based detection of the position of the fossa ovalis relative to the valve and / or by recording the position of the annuloplasty device during the procedure via brief imaging.

[0355] To the extent that the annuloplasty device assumes a predictable shape in response to steering inputs and / or longitudinal device advancement, the magnitude of such control inputs (optionally measured by a suitable encoder in some embodiments) is optionally used to infer the device's position. In some embodiments, the general outcome of these inferences is optionally confirmed and / or corrected under guidance from other measurements. Again, for example, this correction may follow a bioimpedance heuristic as described in connection with FIG. 20 . Monitoring changes in bioimpedance measurements over time as the annuloplasty device is manipulated may also optionally assist in locating a treatment location, for example, maneuvering the device to position it at a local minimum or maximum of the measured bioimpedance. Other sensing options that may assist in locating the device relative to anatomical structures near the annulus include, for example, force sensing (e.g., of contact), flow sensing, and / or pressure sensing. Flow sensing and pressure sensing potentially indicate conditions characteristic of blood movement near the periphery of the valve (and annulus) compared to conditions characteristic of high blood flow regions near the center of the valve. Potentially, flow and / or pressure sensing can distinguish the regions separating the leaflets (ie, locate and / or confirm the boundaries of the leaflets).

[0356] In some embodiments, a device including one or more electrodes placed in (e.g., along) the coronary sinus is used to assist in locating the annuloplasty device, which may operate based on electrical sensing of an electrode component of the annuloplasty device, such as a pin, and / or another electrode at the tip of the annuloplasty device, within the context of an electric field transmitted by / to the electrode(s) within the coronary sinus.

[0357] Optionally, the model of the anatomical scenario (e.g., based on imaging and / or other data) is adjusted and / or recalibrated in response to sensed information. For example, it is adjusted in response to the location where force is detected (e.g., by a contact force sensor on the tip of the annuloplasty device), bioimpedance measurements, and / or sensed changes in fluid flow and / or pressure. Optionally, the anatomical scenario is adjusted and / or recalibrated in response to changes caused by an ongoing annuloplasty procedure that reshapes the annulus according to one or both of the imaged changes, changes indicated by non-imaging sensors, and / or the expected effect of the procedure on valve shape.

[0358] In block 2108, in some embodiments, the annuloplasty device is properly positioned so that it is ready to mechanically engage the annulus tissue, starting from a predictable insertion angle and / or to a predictable extent. This block emphasizes refinement of the general goal of block 2106—finding a treatment start position—and may be performed simultaneously. In the torsion pin-type embodiment of FIGS. 5A-11 , at least two parameters are particularly emphasized. First, proper alignment with the annulus tissue (contact with the flat distal surface) should be achieved so that, upon actuation, penetration by the pin 20 occurs at the intended depth, e.g., 4 mm. The bioimpedance heuristic of FIG. 20 provides an example of a measurement that can be used to assess proper positioning. Second, positioning at a proper angle is required. The proper angle may be selected (e.g., preselected) by operations of blocks 2102-2104. Optionally, further adjustments may be made, for example, to the extent that the device orientation is changed by operations of block 2106. In some embodiments, a suitable angle includes an axis extending between two pins of an annuloplasty device, such as an angle of about 45° to the circumferential direction of the annulus, for example, as described herein with examples of pin placements.

[0359] In vacuum-type devices, the application of suction is expected to improve alignment.

[0360] In block 2110, in some embodiments, a pin of the annuloplasty device is advanced from its housing to engage the tissue in which the device is placed. In some embodiments, the pin has a shaft cross section of about 0.4 mm by 0.4 mm, a length of about 4 mm, and a pointed tip to aid in penetration of tissue.

[0361] In a vacuum type device, suction is applied at block 2110 .

[0362] At block 2112, in some embodiments, for embodiments using pins, proper engagement of the pin with the annular tissue is optionally verified. This may include, for example, testing heuristics related to measurements such as those described in connection with FIG. 20 . Additionally or alternatively, fluoroscopic images of the contrast injection may indicate that the pin is properly implanted in an area not reached by the contrast. Additionally or alternatively, ultrasound images may potentially assist in confirming pin penetration. In some embodiments, a surface electrode (e.g., a flat electrode positioned on the distal surface of the housing at the tip of the annuloplasty device) is used to take bioimpedance measurements, which are evaluated to confirm that this surface maintains tissue contact. Evidence of such contact, along with evidence consistent with penetration, potentially increases confidence that successful penetration has been achieved.

[0363] As previously mentioned, for vacuum-type devices, suction is applied at block 2110. To the extent that this promotes contact, it may have a noticeable effect on bioimpedance measurements (if used) and / or the amount of negative pressure generated within the device, which in some embodiments is used for validation at block 2112.

[0364] At block 2114, in some embodiments, the pins of the annuloplasty device are rotated (e.g., as described in connection with FIGS. 5A-11 ) to mechanically deform the tissue with which they engage. Because they are thin, the pins are delicate, and therefore it is potentially advantageous for the pins to be supported and / or protected by the device in various ways (e.g., by stops, senses, and / or appropriately sized slots, as described in connection with FIGS. 12A-13D ). The intended amount of rotation (twist imparted to the annulus) can be approximately 90°. In some embodiments, the intended amount of rotation is an angular value within the range of approximately 80°-115°.

[0365] In some embodiments, the correct amount of rotation is achieved when the pins of the device are rotated through their entire available range, e.g., from a starting position relative to a first stop to a final position relative to a second stop. In some embodiments, sensing (e.g., electrical sensing) at the tip is used to electrically communicate at least one of these stop positions, e.g., as described in connection with FIGS. 12A-13A. Optionally, more positions are sensed and / or identified, optionally discretely or continuously. Optionally, for some treatment positions, the rotation is submaximal. This may allow for the introduction of lower local strain, with the tradeoff being that more treatment positions are needed to achieve the same level of overall valve circumference reduction, for example.

[0366] Operation of block 2114 is not necessarily performed in pure vacuum-type embodiments, but can introduce additional mechanical deformation, for example, by pulling against bracing contact with tissue, as described in connection with Figures 4A-4C. In some embodiments, vacuum-type embodiments (with or without pins) can be subjected to torsion, potentially blending the characteristics of the injury produced by the embodiments of Figures 1A-4C and 5A-11.

[0367] In block 2116, in some embodiments, structural disruption energy is delivered while the pins mechanically distort the inserted tissue. For example, approximately 120 J is delivered over a period of approximately 8 to 25 seconds. In some embodiments, the energy delivery rate ranges from 6 to 12 watts. Surface and / or penetrating (pin) electrodes are optionally used for energy delivery. In some embodiments, the total energy delivered ranges from approximately 40 J to approximately 300 J. In animal studies, the inventors have found that these levels of power and energy are clearly effective and safe, at least to the extent that they do not cause harm to the circumflex or coronary sinus adjacent to the lesion. The inventors have also discovered that changes in tissue acoustic impedance are potentially detectable over the time course of ablation under ultrasound imaging. Thus, ablated areas appear in ultrasound images as, for example, "white dots" of increased acoustic reflectivity, allowing for assessment of the effectiveness of individual lesion placement as well as spacing and / or overall contraction. For example, two initial lesions can be spaced apart, with further lesions placed in between, and the more extreme lesions gradually spaced closer together.

[0368] In some embodiments, the annuloplasty device is removed from the tissue at block 2118. Optionally, this includes fully retracting the pin (if present) into its housing in preparation for further movement.

[0369] In block 2120, in some embodiments, the results achieved in block 2116 are optionally evaluated, for example, using bioimpedance heuristics as described in connection with FIG. 20. Additionally or alternatively, a thermometer sensor (e.g., located on the front of the tip housing of the annuloplasty device) is used to verify that energy delivery resulted in the expected amount of heating. Evaluation is optionally performed before and / or after the release of block 2118. The vacuum-applied lesion may acquire a characteristic raised shape, potentially detectable in bioimpedance or other electrical signals, by slightly withdrawing the electrode from the surface of the annulus and moving the tip back and forth over the raised area. Mechanical interference with the motion may also be noticeable.

[0370] At block 2122, in some embodiments, the annuloplasty device is moved to the next target area for lesioning. Optionally, movement is accomplished under full image guidance, e.g., fluoroscopic guidance and / or ultrasound guidance. In some embodiments, movement is simplified by the design of the device, e.g., the device is simply advanced or retracted a small amount to reach the new treatment location. Optionally, additional steering is provided to allow for fine adjustments, which may be informed by sensing and / or modeling information, e.g., as described in connection with block 2106. Changes in device orientation may be introduced, e.g., as described and / or referenced in connection with block 2104.

[0371] Twisting (e.g., of a pin) again in the same direction (clockwise or counterclockwise) as before resets the device rotation. Alternatively, the twisting direction may alternate. Optionally, movements between treatment sites are first planned using dry-run survey movements of the device around the annulus to ensure that conditions appear suitable for operation and match the plan at each step of advancement (during the survey). Optionally, these movements are replicated during the actual annuloplasty treatment. Because it is expected that the valve shape will change (e.g., shorten) during the actual treatment, replicating the movements may include compensatory adjustments (optionally predetermined shortening adjustments).

[0372] If it is determined that a particular treatment location was not successful, the treatment plan can be adjusted. If the problem was, for example, a sudden loss of engagement, a repetition may be necessary. If engagement is difficult to achieve and / or there is repeated loss of engagement in a location, the treatment location plan can be appropriately modified to compensate for the loss of the site.

[0373] As long as target treatment locations remain to be treated, the method continues (block 2124) by repeating the operations of blocks 2108-2122, or else stops.

[0374] General When used herein in reference to an amount or value, the term "about" means "within ±10%."

[0375] The terms "comprises," "comprising," "includes," "including," "having," and their conjugations mean "including, but not limited to."

[0376] The term "consisting of" means "including and limited to."

[0377] "Consisting essentially of" means that the composition, method, or structure may include additional components, steps, and / or moieties, but only if the additional components, steps, and / or moieties do not materially alter the basic and novel characteristics of the claimed composition, method, or structure.

[0378] As used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" can include a plurality of compounds, including mixtures thereof.

[0379] The words "example" and "exemplary" are used herein to mean "serving as an example, instance, or illustration." An embodiment described as "example" or "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments and / or to exclude the incorporation of features from other embodiments.

[0380] The word "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 multiple "optional" features, except where such features contradict each other.

[0381] As used herein, the term "method" refers to manners, means, techniques and procedures for accomplishing a given task, including but not limited to those known by those skilled in the art of chemistry, pharmacy, biology, biochemistry and medicine or readily developed from known methods, means, techniques and procedures.

[0382] As used herein, the term "treating" includes arresting, substantially inhibiting, slowing, or reversing the progression of a condition, substantially ameliorating the clinical or cosmetic symptoms of a condition, or substantially preventing the appearance of clinical or cosmetic symptoms of a condition.

[0383] Throughout this application, embodiments may be presented with reference to 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 description of the present disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all possible subranges as well as individual numerical values ​​within that range. For example, a description of a range such as "1 to 6" should be considered to have specifically disclosed subranges such as "1 to 3," "1 to 4," "1 to 5," "2 to 4," "2 to 6," "3 to 6," etc., and individual numerical values ​​within that range, e.g., 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0384] Whenever a range of values ​​is given herein (e.g., a pair of values ​​connected by "10 to 15," "10 to 15," or another such range designation), it is meant to include any number (fractional or integer) within the stated range limits, inclusive, unless the context clearly dictates otherwise. The terms "range / ranging / ranges between" a first indicated value and a second indicated value, and "range / ranging / ranges" from a first indicated value "to," "up to," "until," or "through" a second indicated value (or other such range designation term), are used interchangeably herein and are meant to include the first and second indicated values ​​and all fractional and integer values ​​therebetween.

[0385] While the description of this disclosure is provided in conjunction with specific embodiments, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art. Accordingly, the present disclosure is intended to embrace all such alternatives, modifications, and variations that fall within the spirit and broad scope of the appended claims.

[0386] It will be understood that certain features that are, for clarity, described in this disclosure in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features that are, for brevity, described in the context of a single embodiment may also be suitably provided separately or in any suitable subcombination, or in any other described embodiment of the present disclosure. Certain features described in the context of various embodiments are not considered essential features of those embodiments, unless the embodiment is inoperable without those elements.

[0387] It is the intention of the applicants that all publications, patents, and patent applications referenced herein be incorporated by reference in their entireties to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. Furthermore, citation or identification of a reference in this application shall not be construed as an admission that such reference is available as prior art to the present disclosure. To the extent section headings are used, they should not be construed as necessarily limiting. Additionally, the priority documents of this application are incorporated herein by reference in their entireties.

Claims

1. 1. An annuloplasty device configured to deliver structural disruption energy to a tip terminating at a distal end of a catheter body of the device, a housing of the tip portion extending between a proximal side connected to the catheter body and a distal side; A plurality of pins, each pin comprising: extending distally from a location within the housing secured to the tip; having a size and sharpness that allows it to penetrate the collagen tissue of the annulus of a human heart; the plurality of pins; Including, the pin is configured to rotate relative to the annulus with sufficient force to twist a portion of the collagen tissue at least 45° while the pin is inserted into the collagen tissue; movement of the inserted pin to twist the collagen tissue also rotates the pin and the collagen tissue relative to the housing. Annuloplasty devices.

2. The annuloplasty device of claim 1 , wherein the movement of the inserted pin rotates collagen tissue extending along an axis connecting two of the plurality of pins.

3. The annuloplasty device of claim 2 , configured to limit rotation of the collagen tissue extending along the axis to a predetermined maximum rotation relative to the housing of less than 180°.

4. The annuloplasty device of claim 3 , wherein the predetermined maximum rotation is less than about 110°.

5. The annuloplasty device of claim 3 , wherein the predetermined maximum rotation is greater than about 70°.

6. The annuloplasty device of claim 2 , wherein the plurality of pins consists of exactly two pins.

7. The annuloplasty device of claim 2 , wherein two of the plurality of pins are arranged such that the distance between their axes is 1 to 2 mm.

8. 8. The annuloplasty device of claim 1, further comprising a control operable from a proximal side of the catheter body to induce the twisting of the portion of collagen tissue and the movement of the pin relative to the proximal-distal axis of the housing.

9. 9. The annuloplasty device of claim 8, wherein the control includes a manually adjusted element, and the annuloplasty device limits rotation of the pin and collagen tissue relative to the housing by limiting movement of the manually adjusted element.

10. 9. The annuloplasty device of claim 8, wherein the control unit operates by releasing stored energy to effect the rotation, and the annuloplasty device limits the rotation of the pin and the collagen tissue relative to the housing by limiting the amount of stored energy.

11. 9. The annuloplasty device of claim 2, wherein the distal surface of the housing includes at least one opening through which at least one of the pins passes, and the annuloplasty device limits rotation of the pin and the collagen tissue relative to the housing by interference between at least one of the pins and a periphery of the opening.

12. 12. The annuloplasty device of claim 11, wherein the distal surface of the housing includes a plurality of openings through each of which a respective pin extends, and the annuloplasty device limits rotation of the pin and collagen tissue relative to the housing by interference between at least one of the pins and the periphery of the respective opening.

13. 7. The annuloplasty device of claim 1, wherein rotation of the pin relative to the housing is limited by interference contact with a stop element within the housing.

14. The annuloplasty device of claim 13 , wherein the interference contact with a stop element comprises interference between an assembly that rotates the pin and a portion of the housing of the assembly that acts as the stop element.

15. 13. The annuloplasty device of claim 1, wherein the rotation of the plurality of pins relative to the housing exerts a torque on the collagen tissue of at least 0.01 N·m.

16. 16. The annuloplasty device of claim 1, wherein the plurality of pins exert a torque on the collagen tissue sufficient to drag a portion of the collagen tissue through a rotation comparable in magnitude to the rotation of an axis extending between two of the pins, the rotation being relative to a proximal-distal axis of the housing.

17. 17. The annuloplasty device of claim 1, wherein the rotational actuation force is transmitted along the catheter body by rotation of a control member.

18. 18. The annuloplasty device of claim 17, wherein the annuloplasty device limits rotation by limiting rotation of the control member.

19. 17. The annuloplasty device of claim 1, wherein the rotational actuation force is transmitted along the catheter body by longitudinal translation of a control member through the catheter body.

20. 20. The annuloplasty device of claim 19, wherein the annuloplasty device limits the rotation by limiting the translation of the control member.

21. 19. The annuloplasty device of any one of claims 1 to 18, wherein the pins maintain a constant distance from each other during the rotation.

22. 19. The annuloplasty device of claim 1, wherein the pins change distance from one another during the rotation.

23. 23. The annuloplasty device of any one of claims 1 to 22, wherein the structural disruption energy comprises RF energy transmitted to the tip along a conductive wire.

24. 24. The annuloplasty device of claim 23, wherein the pin is an electrode interconnected with a proximal power connection of the annuloplasty device via the conductive wire.

25. 24. The annuloplasty device of claim 23, wherein the conductive wire is operable to transmit the RF energy to an electrode positioned in contact with the tissue alongside the pin when the pin is inserted into the collagen tissue.

26. 25. The annuloplasty device of any one of claims 1 to 24, wherein the pin is retractable and extendable relative to the housing.

27. 27. The annuloplasty device of any one of claims 1 to 26, including a steering sheath through which the catheter is configured to be advanced to reach the target collagen tissue.

28. 28. The annuloplasty device of claim 27, wherein the steering sheaths are configured to adopt a curl and move in concert to bend out of the plane of the curl as the steering sheaths are actuated.

29. 28. The annuloplasty device of claim 27, wherein the steering sheath is configured to bend from a straight configuration to form a segment of the steering sheath into a helical shape.

30. 30. The annuloplasty device of claim 29, wherein the spiral shape includes a distal segment of the steering sheath attached to a more proximal segment of the steering sheath, the more proximal segment of the steering sheath bending from the straight configuration to form the curve while remaining substantially in the plane of the curve.

31. 1. An annuloplasty device configured to deliver structural disruption energy to a tip terminating a distal end of a catheter body, comprising: a first pin and a second pin, each said pin comprising: extending distally from a location fixed to the tip; It has the size and sharpness to penetrate the collagen tissue of a human heart valve annulus, the first pin and the second pin; the first pin and the second pin are fixed to a first support and a second support, respectively; the first support occupies an inner cavity of the second support, and the first support and the second support rotate relative to one another; Annuloplasty devices.

32. 32. The annuloplasty device of claim 31, wherein the first support and the second support move the pin relative to one another with sufficient force to twist a portion of the collagen tissue at least 45 degrees while the pin is inserted into the collagen tissue.

33. 33. The annuloplasty device of any one of claims 31 to 32, wherein rotation of the first support and the second support relative to one another is limited to a maximum of less than 180 degrees.

34. 34. The annuloplasty device of any one of claims 31 to 33, wherein the structural disruption energy comprises RF energy transmitted to the tip along a conductive wire.

35. 35. The annuloplasty device of claim 34, wherein the pin is an electrode interconnected with a proximal power connection of the annuloplasty device via the conductive wire.

36. 36. The annuloplasty device of any one of claims 31 to 35, wherein the pin is retractable and extendable relative to a sheath, and the first support and the second support are configured to advance through the sheath to reach target collagen tissue.

37. 37. The annuloplasty device of claim 36, wherein the sheath includes a steering mechanism.

38. 1. An annuloplasty device configured to deliver structural disruption energy to a tip terminating a distal end of a catheter body, comprising: An opening in the tip, configured to be in pressure communication with a controllable vacuum source through the catheter body; and a tubular member configured, sized, and positioned to be positioned against collagenous tissue of a human heart valve annulus and to attach to and deform a portion of the collagenous tissue upon application of a vacuum from the vacuum source; the opening; A transducer comprising: attached to a conductive wire configured to transmit structural disruption energy from an electrical energy source to the transducer; positioned within an opening sufficient to conduct structural disruption energy to said deformed portion of collagen tissue; the transducer; 1. An annuloplasty device comprising:

39. 39. The annuloplasty device of claim 38, wherein the opening is elongated.

40. 40. The annuloplasty device of any one of claims 38 to 39, wherein the transducer is an electrode.

41. 40. The annuloplasty device of any one of claims 38 to 39, wherein the transducer comprises an acoustic energy transducer or a thermal energy transducer.

42. 42. The annuloplasty device of any one of claims 38 to 41, wherein the opening has a minimum radius of curvature of about 0.25 mm or greater.

43. 43. The annuloplasty device of any one of claims 38 to 42, wherein the transducer at least partially defines a periphery of the opening.

44. 44. The annuloplasty device of any one of claims 38 to 43, wherein the transducer is positioned to contact a surface of the portion of collagen tissue drawn into the opening.

45. 45. The annuloplasty device of any one of claims 38 to 44, wherein the transducer is positioned to contact a surface of the portion of collagen tissue adjacent at least a circumferential portion of the opening.

46. 43. The annuloplasty device of any one of claims 38 to 42, wherein the transducer includes portions located on at least two opposite sides of the opening.

47. 43. The annuloplasty device of any one of claims 38 to 42, wherein the transducer and the opening are configured to move relative to one another along a proximal-distal axis.

48. A steering sheath for an annuloplasty device, the steering sheath configured to convert between a straight configuration and a curved configuration upon receiving a steering control, the curved configuration including a spiral shape at a distal end of the steering sheath.

49. 49. The steering sheath of claim 48, including a segment leading distally to the helical shape that, in the curved configuration, exhibits a curvature that remains substantially within the plane of the curvature.

50. 1. An annuloplasty device configured to deliver structural disruption energy to a device tip terminating at a distal end of a catheter body, comprising: a transducer configured to deliver structural disruption energy to a plurality of sites at locations around the circumference of the heart valve annulus; an elongated, steerable body supported at its tip by said transducer and including an elongated control member; Including, the control members are operable to cooperatively curl the steerable bodies and bend the steerable bodies out of the plane of the curl; Annuloplasty devices.

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