Expandable access device and system

Abstract

An expandable access device and system for isolating a left atrial appendage (LAA) from a left atrium (LA), the device comprising: a channel shaped and dimensioned to pass within a working channel of a catheter and for delivering a vacuum, the expandable access comprising an expandable structure configured to receive a vacuum from the working channel of the catheter; and an expandable structure having a distal opening shaped and dimensioned to be positioned about an opening of a left atrial appendage, the expandable structure being configured to be in a collapsed state within the working channel of the catheter, expand upon exiting the working channel into the left atrial atrium, the left atrium is in contact with a wall of the left atrium around the opening of the left atrial appendage so as to isolate the left atrial appendage from the left atrium; and a closable fastener ring, the closable fastener ring being configured to be closed and released from the expandable inlet.

Description

[0001] This application is a divisional application of application number 202080059309.1 (PCT application number is PCT / IL2020 / 050737), application date July 2, 2020, and invention name “Left Atrial Appendage Manipulation”.

[0002] Related Applications

[0003] This application claims priority under Section 119(e) of U.S. Provisional Patent Application No. 62 / 869,603, filed on July 2, 2019, the contents of which are incorporated herein by reference in their entirety.

[0004] Technical field and background technology of the present invention

[0005] The present invention, in some embodiments thereof, relates to closure of a lumen, and more particularly, but not exclusively, to closure of a left atrial appendage (LAA). Summary of the invention

[0006] Some examples of some embodiments of the present invention are listed below. Several features of one example can be combined with several features of other examples:

[0007] Example 1: A device with an expandable inlet for isolating a left atrial appendage (LAA) from a left atrium (LA), the device comprising:

[0008] a passageway terminating in an expandable inlet, wherein the passageway is shaped and sized to pass within a working channel of a catheter and to deliver a vacuum, wherein the expandable inlet comprises an expandable structure having a distal opening, wherein the distal opening is shaped and sized to be positioned around an opening of a left atrial appendage, wherein the expandable structure is configured to be in a collapsed state within the working channel of the catheter, to expand when exiting the working channel into the left atrium, and to be positioned around the opening of the left atrial appendage in contact with a wall of the left atrium to isolate the left atrial appendage from the left atrium, wherein the maximum width of the expandable inlet is in a range of 10 mm to 50 mm; and

[0009] A closable fastener ring is coupled to an inner surface of the expandable structure surrounding the distal opening, the expandable structure surrounding the distal opening, wherein the closable fastener ring is configured to close and release from the expandable access port.

[0010] Example 2: The device of Example 1, wherein an edge of the expandable inlet surrounding the distal opening and configured to contact the wall of the left atrium is flexible.

[0011] Example 3: The device of Example 1, wherein the expandable structure comprises an expandable mesh frame coated with a coating, wherein the fastener ring is coupled to the expandable mesh frame and / or the coating.

[0012] Example 4: The device of Example 3, characterized in that the expandable mesh frame is made of one or more shape memory alloy wires coated with the coating.

[0013] Example 5: The device of Example 4, characterized in that the fastener ring is coupled to the inner surface of the expandable structure at a distance of at least 1 mm from a circumferential edge portion of the expandable structure, and the circumferential edge portion is configured to contact the wall of the left atrium.

[0014] Example 6: The device of Example 1, wherein when expanded, the expandable structure has a cup-like or cone-like shape.

[0015] Example 7: The method of any of the preceding examples, wherein the channel is a vacuum channel configured to apply a vacuum through the expandable inlet.

[0016] Some examples of some embodiments of the present invention are listed below. Several features of one example can be combined with several features of other examples:

[0017] Example 1: A device with an expandable inlet, the device comprising:

[0018] a passageway terminating in an expandable inlet, wherein the passageway is shaped and sized to pass within a working channel of a catheter, wherein the expandable inlet comprises an expandable structure having a distal opening shaped and sized to be positioned about an opening of a left atrial appendage, wherein the expandable structure is configured to be in a collapsed state within the working channel of the catheter and to expand upon exiting the working channel into the left atrium and contacting a wall of the left atrium, wherein the expandable inlet has a maximum width in a range of 10 mm to 50 mm when expanded; and

[0019] A closeable fastener ring is coupled to the expandable structure.

[0020] Example 2: A device as in Example 1, further comprising an elongated fastener manipulator shaped and sized to pass through the working channel and connectable to the fastener ring, wherein rotation, tightening and / or advancement of the elongated fastener manipulator closes the closable fastener ring.

[0021] Example 3: The device of Example 1, wherein the closable fastener ring is connected to an inner surface of the expandable structure and is configured to be released from the expandable structure when closed.

[0022] Example 4: The device of Example 1, wherein an edge of the expandable inlet surrounding the distal opening and configured to contact the wall of the left atrium is flexible.

[0023] Example 5: The device of Example 1, wherein the expandable structure comprises an expandable mesh frame coated with a coating, wherein the fastener ring is coupled to the expandable mesh frame and / or the coating.

[0024] Example 6: The device of Example 5, characterized in that the expandable mesh frame is made of one or more shape memory alloy wires coated with the coating.

[0025] Example 7: The device of Example 1, wherein the channel is configured to deliver a vacuum.

[0026] Example 8: The method of any of Examples 1 to 7, wherein the closable fastener ring is coupled to the expandable structure at a distance of up to 20 mm from an edge of the expandable access port, the expandable access port being configured to contact the wall of the left atrium.

[0027] Some examples of some embodiments of the present invention are listed below. Several features of one example can be combined with several features of other examples:

[0028] Example 1: A system, comprising:

[0029] an expandable structure shaped and sized to extend at least partially into the left atrial appendage from within an opening of a catheter working channel through an opening of the left atrial appendage, wherein the expandable structure is configured to expand within the left atrial appendage and contact a wall of the left atrial appendage while applying a radial force for anchoring an outer surface of the expandable structure to the wall of the left atrial appendage; and

[0030] A suction channel passes through the working channel and terminates in a vacuum inlet that can extend from the working channel, the vacuum inlet including a distal opening and configured to apply a vacuum to the left atrial appendage through the distal opening when the expandable structure contacts the wall of the left atrial appendage.

[0031] Example 2: In the system of Example 1, the expandable structure is introduced into the left atrial appendage to a distance of 1 mm to 50 mm from the opening of the left atrial appendage in the left atrium.

[0032] Example 3: The system of Example 1, wherein the vacuum inlet applies the vacuum with a force sufficient to cause at least a portion of the left atrial appendage to collapse into the expandable structure of the left atrial appendage.

[0033] Example 4: A system as in Example 1, wherein the vacuum inlet comprises an expandable mesh frame coated with a coating, and wherein the vacuum inlet is configured to contact a left atrial wall surrounding the opening of the left atrial appendage, wherein a width of the distal opening of the vacuum inlet is greater than a width of the opening of the left atrial appendage.

[0034] Example 5: A system as described in any of Examples 1 to 4, characterized in that the expandable structure includes one or more anchors, and the anchors are configured to penetrate the wall of the left atrial appendage when the expandable structure is expanded within the left atrial appendage.

[0035] Some examples of some embodiments of the present invention are listed below. Several features of one example can be combined with several features of other examples:

[0036] Example 1: A method for closing a left atrial appendage, the method comprising the following steps:

[0037] placing a left atrial appendage remodeler in contact with a left atrial appendage wall or close to the left atrial appendage wall;

[0038] invaginate at least a portion of the left atrial appendage into the left atrium;

[0039] reshaping the left atrial appendage by the left atrial appendage remodeler during the invagination;

[0040] securing at least a portion of the invagination of the left atrial appendage; and

[0041] The left atrial appendage remodeler is withdrawn from the left atrial appendage.

[0042] Example 2: The method as described in Example 1 includes the following steps: extending a suction channel terminating in a vacuum inlet into the left atrium, and positioning the vacuum inlet in contact with a left atrium wall surrounding or near an opening of the left atrial appendage.

[0043] Example 3: The method of Example 2, comprising the step of applying a vacuum to the left atrial appendage during the invagination step and the remodeling step.

[0044] Example 4: As in the method of Example 3, the step of applying a vacuum includes the following steps: applying the vacuum from the left atrium to the left atrial appendage.

[0045] Example 5: The method of any one of Examples 3 or 4, comprising the step of at least partially collapsing the left atrial appendage inwardly by the applied vacuum.

[0046] Example 6: The method of Example 5, wherein the at least partially collapsing inwardly step comprises the step of at least partially collapsing the left atrial appendage inwardly onto the left atrial appendage remodeler by the applied vacuum.

[0047] Example 7: The method of Example 2, wherein the placing step comprises the step of expanding the left atrial appendage remodeler at least partially within the left atrial appendage, and wherein the remodeling step comprises the step of applying a force to the left atrial appendage wall by the left atrial appendage remodeler from within the left atrial appendage.

[0048] Example 8: The method of Example 7, wherein the retracting step comprises the step of retracting the left atrial appendage remodeler into the left atrium while applying the force during the invagination.

[0049] Example 9: The method of Example 8, comprising the step of applying a vacuum on the left atrial appendage during the retraction.

[0050] Example 10: The method as described in any one of Examples 3 or 9, wherein the step of applying vacuum includes the following steps: high pressure vacuum in a range of 400 mmHg to 900 mmHg.

[0051] Example 11: The method of any of the preceding examples, wherein the placing step comprises the step of inserting the left atrial appendage remodeler 30 mm into the left atrial appendage.

[0052] Example 12: The method of any one of Examples 1 to 10, wherein the placing step comprises the step of inserting the left atrial appendage remodeler into the left atrial appendage by 10 mm.

[0053] Example 13: The method of any of the preceding examples, wherein the placing step comprises the step of placing the left atrial appendage remodeler in contact with a proximal portion of the left atrial appendage adjacent to the left atrial appendage opening.

[0054] Example 14: A device for closing a left atrial appendage, the device comprising:

[0055] a catheter that can be introduced into the left atrium and includes a working channel having a distal opening configured to face the left atrium;

[0056] a left atrial appendage remodeler, the left atrial appendage remodeler being extendable from the distal opening through an opening of the left atrial appendage at least partially into the left atrial appendage;

[0057] an aspiration channel extending through the working channel and terminating in a vacuum inlet extendable from the working channel, the vacuum inlet configured to contact a wall of the left atrium surrounding the left atrial appendage opening and apply a vacuum on the left atrial appendage; and

[0058] At least one tissue fastener is extendable from within the working channel into the left atrium and is configured to fasten at least a portion of the left atrial appendage.

[0059] Example 15: The apparatus of Example 14, wherein the left atrial appendage remodeler is coupled to the vacuum inlet.

[0060] Example 16: The device of any one of Examples 14 or 15, wherein the left atrial appendage remodeler is configured to extend forward from the vacuum inlet into the left atrial appendage by 10 mm.

[0061] Example 17: In the device of any one of Examples 14 to 16, a maximum width of the left atrial appendage remodeler is smaller than a maximum width of the vacuum inlet.

[0062] Example 18: In the device of any one of Examples 14 to 17, a surface of the left atrial appendage remodeler comprises a plurality of openings, wherein the shapes and sizes of the plurality of openings are designed to apply a vacuum from an inner cavity of the left atrial appendage remodeler to the left atrial appendage wall through the plurality of openings.

[0063] Example 19: In the device as described in any one of Examples 14 to 18, the left atrial appendage remodeler is designed to be in a cone shape, and wherein an apex of the cone is located at the distal side of the suction channel.

[0064] Example 20: The device of Example 19, wherein the conical apex extends at least partially through the left atrial appendage opening into the left atrial appendage.

[0065] Example 21: In the device as described in any one of Examples 19 or 20, a distance between the apex of the cone and a base of the cone is adjustable.

[0066] Example 22: The apparatus of Example 14, wherein the left atrial appendage remodeler is configured to be reversibly attachable to a wall of the left atrial appendage from within the left atrial appendage.

[0067] Example 23: The apparatus of Example 22, wherein the LAA remodeler comprises an expandable LAA remodeler, wherein the expandable LAA remodeler is shaped and sized to obtain a collapsed state within the working channel of the catheter and to expand within the LAA to contact the LAA wall.

[0068] Example 24: The device of Example 23, wherein the expandable left atrial appendage remodeler includes a distal opening facing the left atrial appendage, and the shape and size of the distal opening are designed to allow vacuum to be applied through the distal opening to several portions of the left atrial appendage that are not in contact with the left atrial appendage remodeler.

[0069] Example 25: The device of any one of Examples 23 or 24, wherein the expandable LAA remodeler is shaped and sized to achieve the collapsed state within the suction channel and to extend from within the vacuum inlet into the LAA.

[0070] Example 26: The device of any one of Examples 22 to 25, wherein a surface of the LAA remodeler comprises a plurality of openings, the plurality of openings being shaped and sized to apply a vacuum from a lumen of the LAA remodeler to the LAA wall through the plurality of openings.

[0071] Example 27: The apparatus of Example 26, wherein the LAA remodeler comprises a mesh, and wherein the plurality of openings are pores of the mesh.

[0072] Example 28: The device of any one of Examples 22 to 27, wherein the left atrial appendage remodeler is retractable into the working channel of the catheter while being attached to the left atrial appendage wall to evert at least a portion of the left atrial appendage into the left atrium.

[0073] Example 29: The device of any one of Examples 22 to 27, wherein the LAA remodeler is retractable into the vacuum inlet while attached to the LAA wall to at least partially evert the LAA into the left atrium.

[0074] Example 30: The device of any one of Examples 14 to 29, wherein the vacuum is applied through the vacuum inlet having a pressure sufficient to collapse a portion of the left atrial appendage onto the left atrial appendage remodeler and at least partially evert the portion into the left atrium.

[0075] Example 31: The device of any one of Examples 28 to 30, wherein the at least one tissue fastener is shaped and sized to fasten the everted portion of the left atrial appendage located in the left atrium.

[0076] Example 32: The device of Example 31, wherein the at least one tissue fastener comprises a closable fastener ring shaped and dimensioned to be positioned around the everted left atrial appendage portion.

[0077] Example 33: The device of Example 32, wherein the at least one tissue fastener comprises a fastener manipulator shaped and dimensioned to pass through the working channel and connectable to the fastener loop, wherein the fastener manipulator is configured to close the fastener loop.

[0078] Example 34: The device of Example 33, wherein the fastener manipulator is shaped and sized to pass through the suction passage.

[0079] Example 35: The device of any of Examples 33 or 34, wherein the fastener manipulator is releasable from the fastener ring in response to a signal from outside the body.

[0080] Example 36: The device of any one of Examples 32 to 35, wherein the fastener ring is coupled to an inner surface of the vacuum inlet.

[0081] Example 37: The device of any of Examples 32 to 35, wherein the fastener ring is coupled to an outer surface of the vacuum inlet.

[0082] Example 38: The device of any of Examples 32-34, the fastener loop coupled to the vacuum inlet by one or more of a hook, a wire, an elastic wire, a cord, and / or an elastic cord.

[0083] Example 39: The device of any of Examples 36 to 38, the fastener ring being configured to release from the vacuum inlet when closed around the everted left atrial appendage portion.

[0084] Example 40: The device of any of Examples 32 to 39, wherein the fastener loop comprises a wire.

[0085] Example 41 The device of any of Examples 32 to 39, wherein the fastener loop comprises a strap.

[0086] Example 42: The device of any of Examples 32 to 41, wherein the fastener ring is configured to exert a force of up to 30 Newtons on the everted left atrial appendage portion when the fastener ring is closed.

[0087] Example 43: The device of any one of Examples 32 to 42, wherein the fastener ring is made of polytetrafluoroethylene, polypropylene, peek and / or polyurethane.

[0088] Example 44: In a device as described in any of Examples 32 to 43, a surface of the fastener ring configured to contact the left atrial appendage tissue is covered with one or more of ridges, protrusions and projections, the shape and size of which are designed to increase the contact surface between the fastener ring and the left atrial appendage tissue.

[0089] Example 45: In the device of any one of Examples 14 to 44, a width of a distal opening of the vacuum inlet facing the left atrial appendage is greater than a width of the left atrial appendage opening.

[0090] Example 46: In the device of Example 45, a width of the vacuum inlet is in a range of 10 mm to 50 mm.

[0091] Example 47: The device of any one of Examples 14 to 46, wherein at least a portion of the vacuum inlet configured to contact the left atrial appendage wall is flexible.

[0092] Example 48: The device of any one of Examples 14 to 47, further comprising one or more sensors configured to sense electrical characteristics of at least one of the left atrium and the left atrial appendage.

[0093] Example 49: As a device of Example 48, the electrical characteristic includes one or more of impedance and conductivity.

[0094] Example 50: The device of any of Examples 14 to 49, further comprising one or more pressure sensors configured to sense pressure exerted by the vacuum inlet on the wall of the left atrium around the left atrial appendage opening.

[0095] Example 51: The device of any one of Examples 14 to 50, further comprising one or more vacuum sensors configured to sense a vacuum level applied to left atrial appendage tissue through at least one of the suction channel and the vacuum inlet.

[0096] Example 52: A method for positioning a left atrial appendage remodeling tool adjacent to a hole in the left atrial appendage, the method comprising the steps of:

[0097] placing a left atrial appendage remodeler into contact with a wall of the left atrial appendage via a left atrial appendage remodeler guide;

[0098] reshaping the left atrial appendage by the left atrial appendage remodeler during or after the placement;

[0099] advancing a left atrial appendage remodeling tool along the left atrial appendage remodeling device guide, the left atrial appendage remodeling tool being configured to evert and / or fix at least a portion of the left atrial appendage everted into the left atrium toward a hole of the left atrial appendage located in the left atrium;

[0100] attaching the left atrial appendage remodeling tool to a wall of the left atrium surrounding the opening or to the left atrial appendage wall; and

[0101] The left atrial appendage remodeler is removed from the left atrial appendage after the attaching.

[0102] Example 53. The method of Example 52, wherein the remodeling step comprises the step of applying a force through an outer surface of the left atrial appendage remodeler on the left atrial appendage wall, the force being sufficient to anchor the left atrial appendage remodeler within the left atrial appendage during the advancing step and the attaching step.

[0103] Example 54. The method of Example 53, wherein the applying step comprises the step of applying a force of up to 30 Newtons on the left atrial appendage wall via the left atrial appendage remodeler.

[0104] Some additional examples of some embodiments of the present invention are listed below. Several features of one example can be combined with several features of other examples.

[0105] Example 1: A method for closing a left atrial appendage, the method comprising the following steps:

[0106] placing a left atrial appendage remodeler in contact with a left atrial appendage wall or close to the left atrial appendage wall;

[0107] invaginate at least a portion of the left atrial appendage into the left atrium;

[0108] reshaping the left atrial appendage by the left atrial appendage remodeler during the invagination;

[0109] securing at least a portion of the invagination of the left atrial appendage; and

[0110] The left atrial appendage remodeler is withdrawn from the left atrial appendage.

[0111] Example 2: The method of Example 1, comprising the step of applying a vacuum to the left atrial appendage during the invagination step and the remodeling step.

[0112] Example 3: The method of Example 2, wherein the applying step comprises the step of applying a vacuum on the left atrial appendage via the left atrial appendage remodeler during the invagination step and the remodeling step.

[0113] Example 4: A method as described in any of Examples 2 and 3, comprising the steps of extending a suction channel terminating in a vacuum inlet into the left atrium, and bringing the vacuum inlet into contact with a left atrium wall surrounding or near an opening of the left atrial appendage.

[0114] Example 5: The method of Example 4, wherein the applying step comprises the following step: applying a vacuum on the left atrial appendage through the vacuum inlet after the placing step and during the invagination step and the remodeling step.

[0115] Example 6: As in the method of Example 5, the step of applying a vacuum includes the step of applying the vacuum from the left atrium to the left atrial appendage.

[0116] Example 7: The method of any one of Examples 2 to 6, comprising the step of at least partially collapsing the left atrial appendage inwardly by the applied vacuum.

[0117] Example 8: The method of Example 7, wherein the at least partially collapsing inwardly step comprises the step of at least partially collapsing the left atrial appendage inwardly onto the left atrial appendage remodeler by the applied vacuum.

[0118] Example 9: The method of any one of Examples 2 to 8, wherein the placing step comprises the step of expanding the left atrial appendage remodeler at least partially within the left atrial appendage, and wherein the remodeling step comprises applying a force to the left atrial appendage wall by the left atrial appendage remodeler from within the left atrial appendage.

[0119] Example 10: The method of Example 9, wherein the retracting step comprises the step of retracting the left atrial appendage remodeler into the left atrium while applying the force during the invagination.

[0120] Example 11: The method of Example 10, comprising the step of applying a vacuum on the left atrial appendage during the retracting step.

[0121] Example 12: The method of any one of Examples 2 to 11, wherein the applied vacuum comprises a high pressure vacuum in a range of 400 mmHg to 900 mmHg.

[0122] Example 13: According to the method of any one of the preceding examples, the placing step comprises the step of inserting the left atrial appendage remodeler into the left atrial appendage by 30 mm.

[0123] Example 14: The method according to any one of the preceding examples, wherein the placing step comprises the step of inserting the left atrial appendage remodeler into the left atrial appendage by 10 mm.

[0124] Example 15: According to any one of the preceding examples, the placing step comprises the step of placing the left atrial appendage remodeler in contact with a proximal portion of the left atrial appendage adjacent to the left atrial appendage opening.

[0125] Example 16: According to the method of any of the preceding examples, the invagination step comprises the following steps: invaginate at least a portion of the left atrial appendage into the left atrial appendage remodeler and close to a fastener, the fastener being reversibly coupled to the left atrial appendage remodeler; and wherein the fastening step comprises the following steps: fastening at least a portion of the invaginated left atrial appendage by the fastener.

[0126] Example 17: The method of Example 16, comprising the following steps:

[0127] The fastening step separates the fastener from the left atrial appendage remodeling device.

[0128] Example 18: A device for closing a left atrial appendage, the device comprising:

[0129] a catheter that can be introduced into the left atrium and includes a working channel having a distal opening configured to face the left atrium;

[0130] a left atrial appendage remodeler, the left atrial appendage remodeler being extendable from the distal opening through an opening of the left atrial appendage at least partially into the left atrial appendage;

[0131] an aspiration channel extending through the working channel and terminating in a vacuum inlet extendable from the working channel, the vacuum inlet configured to contact a wall of the left atrium surrounding the left atrial appendage opening and apply a vacuum on the left atrial appendage; and

[0132] At least one tissue fastener is extendable from within the working channel into the left atrium and is configured to fasten at least a portion of the left atrial appendage.

[0133] Example 19: The apparatus of Example 18, wherein the left atrial appendage remodeler is coupled to the vacuum inlet.

[0134] Example 20: The device of any one of Examples 18 or 19, wherein the left atrial appendage remodeler is configured to extend forward from the vacuum inlet into the left atrial appendage by 10 mm.

[0135] Example 21: The device of any one of Examples 18 to 20, wherein a maximum width of the left atrial appendage remodeler is smaller than a maximum width of the vacuum inlet.

[0136] Example 22: The device of any one of Examples 18 to 21, wherein a surface of the LAA remodeler comprises a plurality of openings, wherein the plurality of openings are shaped and sized so as to apply a vacuum from a lumen of the LAA remodeler to the LAA wall through the plurality of openings.

[0137] Example 23: The device as described in any one of Examples 18 to 22, wherein the left atrial appendage remodeler is designed to be in a cone shape, and wherein an apex of the cone is located at the distal side of the suction channel.

[0138] Example 24: The apparatus of any one of Examples 18 to 23, wherein the left atrial appendage remodeler is configured to be reversibly attachable to a wall of the left atrial appendage from within the left atrial appendage.

[0139] Example 25: The apparatus of Example 24, wherein the LAA remodeler comprises an expandable LAA remodeler, wherein the expandable LAA remodeler is shaped and sized to obtain a collapsed state within the working channel of the catheter and to expand within the LAA to contact the LAA wall.

[0140] Example 26: The apparatus of Example 25, wherein the expandable left atrial appendage remodeler comprises a distal opening facing the left atrial appendage, wherein the shape and size of the distal opening are designed to allow vacuum to be applied through the distal opening to portions of the left atrial appendage that are not in contact with the left atrial appendage remodeler.

[0141] Example 27: The device of any one of Examples 25 or 26, wherein the expandable left atrial appendage remodeler has a cylindrical or conical shape in an expanded state, with a distal opening facing the left atrial appendage.

[0142] Example 28: The device of Example 27, wherein a maximum width of the distal opening of the expandable left atrial appendage remodeler in an expanded state is 30 mm.

[0143] Example 29: The device of any one of Examples 25 to 28, wherein a surface of the expandable left atrial appendage remodeler is at least partially coated with a coating, wherein the coating is configured to form a sealed flow path between the left atrial appendage and the catheter.

[0144] Example 30: The device of any one of Examples 25 to 29, wherein the expandable LAA remodeler is shaped and sized to achieve the collapsed state within the suction channel and extend from within the vacuum inlet into the LAA.

[0145] Example 31: The device of any one of Examples 24 to 25, wherein a surface of the LAA remodeler comprises a plurality of openings, wherein the plurality of openings are shaped and sized so as to apply a vacuum from a lumen of the LAA remodeler to the LAA wall through the plurality of openings.

[0146] Example 32: The apparatus of Example 31, wherein the left atrial appendage remodeler comprises a mesh, and wherein the plurality of openings are a plurality of pores of the mesh.

[0147] Example 33: The device of any one of Examples 24 to 32, wherein the left atrial appendage remodeler is retractable into the working channel of the catheter while being attached to the left atrial appendage wall to evert at least a portion of the left atrial appendage into the left atrium.

[0148] Example 34: The apparatus of any one of Examples 24 to 32, wherein the LAA remodeler is retractable into the vacuum inlet when attached to the LAA wall to at least partially evert the LAA into the left atrium.

[0149] Example 35: The device of any of Examples 18 to 34, wherein the vacuum is applied through the vacuum inlet having a pressure sufficient to collapse a portion of the left atrial appendage onto the left atrial appendage remodeler and at least partially evert the portion into the left atrium.

[0150] Example 36: The device of any one of Examples 33 to 35, wherein the at least one tissue fastener is shaped and sized to fasten the everted portion of the left atrial appendage located in the left atrium.

[0151] Example 37: The device of Example 36, wherein the at least one tissue fastener comprises a closable fastener ring shaped and dimensioned to be positioned around the everted left atrial appendage portion.

[0152] Example 38: The device of Example 37, wherein the at least one tissue fastener comprises a fastener manipulator shaped and dimensioned to pass through the working channel and be connectable to the fastener loop, wherein the fastener manipulator is configured to close the fastener loop.

[0153] Example 39: The device of Example 38, wherein the fastener manipulator is shaped and sized to pass through the suction passage.

[0154] Example 40: The device of any of Examples 38 or 39, wherein the fastener manipulator is releasable from the fastener ring in response to a signal from outside the body.

[0155] Example 41: The device of any one of Examples 37 to 40, wherein the fastener ring is coupled to an inner surface or an outer surface of the vacuum inlet.

[0156] Example 42: The device of Example 41, wherein the fastener ring is configured to release from the vacuum inlet when closed around the everted left atrial appendage portion.

[0157] Example 43: The device of any of Examples 37 to 40, wherein the fastener ring is releasably coupled to an inner surface or an outer surface of the left atrial appendage remodeler.

[0158] Example 44: The AA device of Example 43, wherein the fastener ring is configured to be released from the LAA remodeler when closed around the everted LAA portion.

[0159] Example 45: The device of any one of Examples 37 to 44, wherein the fastening loop comprises a wire or a belt.

[0160] Example 46: The device of any of Examples 37 to 45, wherein the fastener ring is configured to exert a force of up to 30 Newtons on the everted left atrial appendage portion when the fastener ring is closed.

[0161] Example 47: In the device of any one of Examples 18 to 46, a distal opening of the vacuum inlet facing the left atrial appendage has a width that is greater than a width of the left atrial appendage opening.

[0162] Example 48: In the device of Example 47, a width of the vacuum inlet is in a range of 10 mm to 50 mm.

[0163] Example 49: The device of any one of Examples 18 to 48, wherein at least a portion of the vacuum inlet configured to be placed in contact with the left atrial appendage wall is flexible.

[0164] Example 50: A device for closing a left atrial appendage, the device comprising:

[0165] a catheter that can be introduced into the left atrium and includes a working channel having a distal opening configured to face the left atrium;

[0166] an expandable left atrial appendage remodeler, the expandable left atrial appendage remodeler being extendable from the distal opening at least partially through an opening of the left atrial appendage into the left atrial appendage and being expandable within the left atrial appendage, wherein the left atrial appendage remodeler comprises a distal opening facing the left atrial appendage;

[0167] an aspiration channel extending through the working channel and terminating at the expandable left atrial appendage remodeler, the expandable left atrial appendage remodeler being configured to expand and contact a plurality of walls of the left atrial appendage and apply a vacuum on the left atrial appendage through the distal opening; and

[0168] At least one tissue fastener is extendable from within the working channel into the left atrium and is configured to fasten at least a portion of the left atrial appendage.

[0169] Example 51: The device of Example 50, wherein the at least one tissue fastener is reversibly coupled to the expandable left atrial appendage remodeler.

[0170] Example 52: The device of any one of Examples 50 or 51, wherein the expandable left atrial appendage remodeler is at least partially coated with an air-impermeable coating to form a sealed flow path between the left atrial appendage and the working channel.

[0171] Example 53: A method for positioning a left atrial appendage remodeling tool adjacent to a hole in the left atrial appendage, the method comprising the steps of:

[0172] placing a left atrial appendage remodeler into contact with a wall of the left atrial appendage via a left atrial appendage remodeler guide;

[0173] reshaping the left atrial appendage by the left atrial appendage remodeler during or after the placement;

[0174] advancing a left atrial appendage remodeling tool along the left atrial appendage remodeling device guide, the left atrial appendage remodeling tool being configured to evert and / or fix at least a portion of the left atrial appendage everted into the left atrium toward a hole of the left atrial appendage located in the left atrium;

[0175] attaching the left atrial appendage remodeling tool to a wall of the left atrium surrounding the opening or to the left atrial appendage wall; and

[0176] The left atrial appendage remodeler is removed from the left atrial appendage after the attaching.

[0177] Example 54: As described in Example 53, the remodeling step includes the following steps: applying a force through an outer surface of the left atrial appendage remodeler on the left atrial appendage wall, the force being sufficient to anchor the left atrial appendage remodeler in the left atrial appendage during the advancing step and the attaching step.

[0178] Example 55: The method of Example 54, wherein the applying step comprises the following step: applying a force of up to 30 Newtons on the left atrial appendage wall by the left atrial appendage remodeler.

[0179] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as those generally understood by those of ordinary skill in the art to which the invention belongs. Although methods and materials similar or equivalent to the methods and materials described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In the event of a conflict, the patent specification (including definitions) shall prevail. In addition, these materials, methods and examples are illustrative only and are not necessarily meant to be limiting. BRIEF DESCRIPTION OF THE DRAWINGS

[0180] Some embodiments of the present invention are described in detail herein with specific reference to the accompanying drawings and images, emphasizing that the details shown are for the purpose of illustrative discussion of the embodiments of the present invention. In this regard, it will be apparent to those skilled in the art how several embodiments of the present invention can be practiced in conjunction with the description of the accompanying drawings and images.

[0181] In the several figures:

[0182] Figure 1 is a general flow chart of a process for closing a unitary cavity according to some exemplary embodiments of the present invention;

[0183] Figure 2A and Figure 2B are several block diagrams of an apparatus for closing an integral cavity according to some exemplary embodiments of the present invention;

[0184] Figure 3 is a detailed flow chart for closing the left atrial appendage according to some exemplary embodiments of the present invention;

[0185] Figure 4A is a schematic diagram of an integrated cavity closure device aligned with an integrated cavity according to some exemplary embodiments of the present invention;

[0186] FIG. 4B to FIG. 4F is a schematic diagram of left atrial appendage invagination according to some exemplary embodiments of the present invention;

[0187] FIG. 5A to FIG. 5E are several schematic diagrams of directional left atrial appendage invagination according to some exemplary embodiments of the present invention;

[0188] FIG. 6A to FIG. 6I are several schematic diagrams of a process for left atrial appendage invagination and closure according to some exemplary embodiments of the present invention;

[0189] 7A to 7C are several schematic diagrams of a vacuum inlet frame according to some exemplary embodiments of the present invention;

[0190] Fig. 8A and Figure 8B are several schematic diagrams of a fastener according to some exemplary embodiments of the present invention;

[0191] 9A to 9E are several schematic diagrams and several images of a vacuum inlet coupled to a fastener according to some embodiments of the present invention;

[0192] Fig.9F is an image of a vacuum inlet with an integrated fastener according to some embodiments of the present invention;

[0193] FIG. 10A to FIG. 10C are several schematic diagrams of a coupling mechanism between a vacuum inlet and a fastener according to some exemplary embodiments of the present invention;

[0194] Fig.11A and Fig. 11B are several schematic diagrams of a left atrial appendage remodeler that is optionally used to be at least partially anchored within the left atrial appendage according to some exemplary embodiments of the present invention;

[0195] Fig. 11C According to some exemplary embodiments of the present invention, at least part of the left atrial appendage Fig. 11B A schematic diagram of the left atrial appendage remodeler shown;

[0196] Fig.11D is a schematic diagram of a left atrial appendage remodeler, optionally for guiding at least a portion of the left atrial appendage to collapse into a vacuum inlet, according to some exemplary embodiments of the present invention;

[0197] Fig.11E According to some exemplary embodiments of the present invention, Fig.11D Several schematic diagrams of a vacuum inlet of the left atrial appendage remodeler shown in ;

[0198] FIG. 12A to FIG. 12B is an image of a left atrial appendage closure device according to some exemplary embodiments of the present invention;

[0199] FIG. 13A to FIG. 13C are several images of a left atrial appendage closure device having a left atrial appendage remodeler having a distally extending guide according to some exemplary embodiments of the present invention;

[0200] FIG. 14A to FIG. 14I are several schematic diagrams showing the closure of the left atrial appendage according to some exemplary embodiments of the present invention;

[0201] Fig.15 is a flow chart of a process for closing a left atrial appendage by a ligator (eg, fastener) coupled to a left atrial appendage remodeler according to some exemplary embodiments of the present invention; and

[0202] 16A to 16H are several schematic diagrams showing closure of the left atrial appendage by a ligator coupled to a left atrial appendage remodeler according to some exemplary embodiments of the present invention. DETAILED DESCRIPTION

[0203] The present invention, in some embodiments thereof, relates to closure of a lumen, and more particularly, but not exclusively, to closure of a left atrial appendage (LAA).

[0204] An aspect of some embodiments relates to remodeling left atrial appendage tissue. In some embodiments, the left atrial appendage tissue is remodeled during the process of at least a portion of the left atrial appendage being invaginated into the left atrium. Alternatively or additionally, the left atrial appendage tissue is remodeled during the collapse of the left atrial appendage, such as an inward collapse of the left atrial appendage. As used herein, an inward collapse of the left atrial appendage is a collapse of the left atrial appendage wall into the left atrial appendage cavity. The left atrial appendage is located in the left atrium of the heart and has a maximum length of up to about 40 mm, such as up to about 30 mm, up to about 20 mm, or any intermediate, smaller or larger value. The left atrial appendage has a maximum wall thickness of up to about 1 mm, such as up to about 0.8 mm, up to about 0.5 mm, or any intermediate, smaller or larger value. The left atrial appendage opening in the left atrium has a width in a range of 5 mm to 40 mm, such as 5 mm to 20 mm, 10 mm to 30 mm, 26 mm to 40 mm, or any intermediate, smaller or larger value.

[0205] According to some embodiments, the left atrial appendage is reshaped during invagination, for example to control the shape, size and / or volume of an invaginated portion of the left atrial appendage. In some embodiments, the left atrial appendage is reshaped during invagination, for example by controlling the forces applied to the left atrial appendage (for example, a plurality of suction forces and / or mechanical forces applied to the left atrial appendage). In some embodiments, the plurality of forces are applied to the left atrial appendage from the left atrium or from within the left atrial appendage cavity. In some embodiments, the intensity of the plurality of forces is controlled, for example, to reshape the left atrial appendage without damaging the wall of the left atrial appendage. In some embodiments, a direction of the plurality of forces is controlled, for example, to allow a portion of the left atrial appendage having a desired shape, size and / or volume to invaginate into the left atrium.

[0206] According to some embodiments, the left atrial appendage is reshaped during the inward collapse of the left atrial appendage, for example to control the size of the collapsed area. Alternatively or additionally, the left atrial appendage is reshaped in order to control the degree of collapse, for example the depth of collapse and / or whether the collapse is a complete collapse or a partial collapse of the left atrial appendage.

[0207] According to some embodiments, the left atrial appendage is reshaped by positioning a left atrial appendage remodeler at least partially within the left atrial appendage cavity. In some embodiments, the left atrial appendage remodeler is introduced into the left atrial appendage cavity into the left atrial appendage up to a maximum distance of 70 mm from the left atrial appendage opening, such as up to 70 mm, up to 50 mm, up to 40 mm, up to 20 mm, up to 10 mm from the left atrial appendage opening in the left atrium, or any intermediate, smaller, or larger distance. In some embodiments, the left atrial appendage remodeler is introduced into the left atrial appendage cavity at least 1 mm, such as at least 1 mm, at least 5 mm, at least 10 mm, at least 20 mm, or any intermediate, smaller, or larger distance into the left atrial appendage cavity.

[0208] According to some embodiments, the LAA remodeler is placed in contact with a surface of the LAA wall located at the LAA cavity. In some embodiments, the LAA remodeler comprises an expandable LAA remodeler configured to expand and contact the LAA wall from within the LAA cavity. In some embodiments, the LAA remodeler is pushed against the surface of the LAA wall within the LAA cavity. Alternatively or additionally, the LAA remodeler penetrates from within the LAA cavity to the LAA wall by 2.5 cm, such as by 2 cm, by 1.5 cm, by 0.5 cm, by 0.1 cm, or any intermediate, smaller, or larger value. In some embodiments, the LAA remodeler is pushed against the LAA wall and / or penetrates from within the LAA cavity to at least partially anchor the LAA remodeler within the LAA cavity. Optionally, the LAA remodeler is reversibly anchored within the LAA cavity and configured to detach from the LAA wall, e.g., in response to a signal from outside the body. In some embodiments, the LAA remodeler is reversibly anchored by acquiring an expanded state configured to contact the LAA wall during the anchoring step and a collapsed state configured to detach the LAA remodeler from the LAA wall. In some embodiments, during the anchoring (e.g., reversible anchoring), the LAA remodeler applies a force of up to 30 Newtons, e.g., up to 25 Newtons, up to 20 Newtons, up to 15 Newtons, up to 10 Newtons, or any intermediate, lesser, or greater value, on the LAA wall.

[0209] According to some embodiments, when the left atrial appendage remodeler contacts the left atrial appendage wall, the left atrial appendage remodeler is retracted into the left atrium, causing at least a portion of the left atrial appendage to be invaginated. In some embodiments, the invaginated portion is completely located within the left atrial appendage cavity. Alternatively, the invaginated portion of the left atrial appendage is at least partially introduced into the left atrium. In some embodiments, the invaginated portion of the left atrial appendage is completely invaginated into the left atrium. In some embodiments, during the retraction of the left atrial appendage remodeler into the left atrium, the left atrial appendage remodeler is separated from the left atrial appendage wall.

[0210] According to some embodiments, when suction is applied to the left atrial appendage cavity, the left atrial appendage remodeler contacts the left atrial appendage wall, such as an interior portion of the left atrial appendage. In some embodiments, the plurality of vacuum forces applied by the suction force induce an inward collapse of the left atrial appendage on a portion of the left atrial appendage remodeler located within the left atrial appendage cavity. In some embodiments, the left atrial appendage remodeler is in fluid communication with a suction channel. In some embodiments, the vacuum is applied through a plurality of openings (e.g., a plurality of adjustable openings) positioned to direct the collapse of the left atrial appendage on the left atrial appendage remodeler. In some embodiments, the collapse of the left atrial appendage onto the left atrial appendage remodeler reversibly attaches the left atrial appendage remodeler to the left atrial appendage wall. In some embodiments, the step of retracting the left atrial appendage remodeler into the left atrial cavity at least partially invaginates the collapsed left atrial appendage into the left atrium. Optionally, retracting the left atrial appendage remodeler into the left atrium separates the left atrial appendage wall of the collapsed left atrial appendage from the left atrial appendage remodeler.

[0211] According to some exemplary embodiments, the LAA remodeler is configured to extend from a distal opening of a working channel of a catheter or from an aspiration channel positioned within the working channel. In some embodiments, the LAA remodeler extends at least partially into the LAA through the LAA opening, for example up to 20 mm, up to 15 mm, up to 10 mm, or any intermediate, smaller or larger value from the LAA opening in the left atrium. In some embodiments, the LAA remodeler is configured to be reversibly attached to a wall of the LAA from within the LAA, for example by expansion and collapse of the LAA remodeler within the LAA. In some embodiments, the LAA remodeler is reversibly attached to the LAA by friction alone, without any anchors penetrating into the LAA tissue. Alternatively, the left atrial appendage is reversibly attached to the left atrial appendage by inserting one or more anchors (e.g., hooks) into the left atrial appendage tissue during expansion of the left atrial appendage remodeler and removing one or more anchors from the left atrial appendage tissue during collapse of the left atrial appendage remodeler.

[0212] An aspect of some embodiments relates to aligning a catheter with a body cavity orifice, such as an opening of the left atrial appendage. In some embodiments, the catheter is aligned with the body cavity orifice, such as by aligning the left atrial appendage remodeler with the left atrial appendage opening at least partially anchored in the left atrial appendage cavity. In some embodiments, the left atrial appendage remodeler is mechanically connected to the catheter, such as mechanically connected to a working channel of the catheter. Alternatively, the left atrial appendage remodeler extends into the catheter, such as into the working channel of the catheter. In some embodiments, the step of at least partially anchoring the left atrial appendage remodeler in the left atrial appendage cavity creates a guide path between the catheter, such as a working channel of the catheter, and the left atrial appendage cavity or the left atrial appendage opening located in the left atrium.

[0213] An aspect of some embodiments relates to invagination of a body cavity (e.g., the left atrial appendage) by applying a plurality of suction forces from outside the body cavity. In some embodiments, the plurality of suction forces are applied to the left atrial appendage cavity from outside the left atrial appendage cavity (e.g., from the left atrium). In some embodiments, the plurality of applied suction forces invaginate at least a portion of the left atrial appendage, at least partially into the left atrium.

[0214] According to some embodiments, suction forces are applied from a vacuum inlet (e.g., a suction cup) of a suction channel positioned in the left atrium to attach the vacuum inlet to the left atrium wall around the left atrial appendage opening. In some embodiments, the vacuum inlet is securely attached to the left atrial wall with forces sufficient to form a sealed flow path between the suction channel and the left atrial appendage cavity. In some embodiments, the vacuum inlet is attached to the left atrial wall around the left atrial appendage opening without damaging the left atrial wall.

[0215] An aspect of some embodiments relates to sealing the left atrial appendage from within the left atrial appendage prior to manipulation of the left atrial appendage. In some embodiments, the left atrial appendage is sealed by a left atrial appendage remodeler configured to reshape the left atrial appendage during invagination of the left atrial appendage. In some embodiments, the left atrial appendage is invaginated using a vacuum applied through an opening (e.g., a distal opening of the sealed left atrial appendage remodeler). Optionally, an external seal (e.g., the vacuum inlet placed in the left atrium around the left atrial appendage opening) is used in conjunction with the sealed left atrial appendage remodeler.

[0216] According to some embodiments, a coupled fastener (e.g., reversibly coupled to the left atrial appendage remodeler) is used to fasten the left atrial appendage. In some embodiments, the fastener is used to fasten a portion of the left atrial appendage that is everted and / or to the left atrial appendage remodeler. In some embodiments, during the fastening, the fastener is separated from the left atrial appendage remodeler.

[0217] Before explaining at least one embodiment of the present invention in detail, it should be understood that the present invention is not necessarily limited to the several components and / or methods described in the following description and / or method and / or the construction details and configurations described in the several drawings and / or the several examples in its application. The present invention can have several other embodiments or can be practiced or implemented in various ways.

[0218] Exemplary Process for Invaginating a Body Cavity

[0219] According to some exemplary embodiments, a lumen closure device is configured to close a lumen, for example to prevent blood from entering the blood lumen and / or a number of blood clots or other floating particles from exiting the body lumen into the blood stream. Figure 1 , Figure 1 A general process for closing an integral cavity, such as a left atrial appendage, is depicted according to some exemplary embodiments of the present invention.

[0220] According to some exemplary embodiments, the body cavity closure device is aligned with an opening of the body cavity, such as the left atrial appendage opening at block 102. In some embodiments, a guide instrument (e.g., a catheter) of the body cavity closure device is aligned with the left atrial appendage opening. In some embodiments, the catheter is inserted (e.g., transseptally inserted) into the left atrium. In some embodiments, a left atrial appendage remodeler is advanced from a distal opening of a working channel of the catheter and is at least partially anchored within the left atrial appendage. In some embodiments, the left atrial appendage remodeler is connected to the catheter by an elongated left atrial appendage remodeler guide. Alternatively, the left atrial appendage remodeler is an expandable section, such as a distal expandable section of the left atrial appendage remodeler guide. In some embodiments, the step of anchoring the catheter to the left atrial appendage allows, for example, one or more tools (e.g., tissue manipulation tools) to be advanced into the left atrial appendage opening in the left atrium and / or into the left atrial appendage.

[0221] According to some exemplary embodiments, at block 104, a vacuum is applied to the body cavity, such as to the left atrial appendage. In some embodiments, a vacuum is applied to the left atrial appendage cavity from outside the left atrial appendage cavity. Alternatively, a vacuum is applied to the left atrial appendage cavity at least partially from within the cavity. In some embodiments, a vacuum inlet is advanced from the catheter toward the left atrial appendage, such as along the left atrial appendage remodeler guide. In some embodiments, the vacuum inlet comprises an expandable vacuum inlet configured to expand from the working channel of the catheter. In some embodiments, the vacuum inlet is attached to the left atrial wall around the left atrial appendage opening. In some embodiments, the vacuum inlet applies a vacuum to the left atrial appendage, such as to attach at least a portion of the vacuum inlet to the left atrial wall around the left atrial appendage opening. Alternatively or additionally, a vacuum is applied through the vacuum inlet to invaginate at least a portion of the left atrial appendage into the left atrial appendage or into the left atrium.

[0222] According to some exemplary embodiments, at least a portion of the body cavity (e.g., the left atrial appendage) is invaginated at box 106. In some embodiments, the left atrial appendage is at least partially invaginated into the left atrium. Alternatively, the left atrial appendage is completely invaginated into the left atrium. In some embodiments, two or more portions of the left atrial appendage are invaginated into the left atrium, for example, two portions, three portions, four portions, or five portions of the left atrial appendage are invaginated into the left atrium. In some embodiments, at least a portion of the left atrial appendage is invaginated by applying a vacuum from outside the left atrial appendage or at least partially from inside the left atrial appendage. In some embodiments, a vacuum is selectively applied to cause several specific portions of the left atrial appendage to be invaginated.

[0223] According to some exemplary embodiments, the body cavity (e.g., the left atrial appendage) is reshaped during the invagination and / or during the application of vacuum at block 108. In some embodiments, the left atrial appendage is reshaped by inducing the collapse of selected portions of the left atrial appendage (e.g., applying vacuum on some portions of the left atrial appendage while supporting other portions of the left atrial appendage). Alternatively or additionally, the left atrial appendage is reshaped by invagination of selected portions of the left atrial appendage into the left atrium, such as described at block 106.

[0224] According to some exemplary embodiments, the two or more invaginated portions of the body cavity are fastened at block 110. In some embodiments, the two or more invaginated portions of the left atrial appendage are fastened in the left atrium, for example, by placing a tissue fastener, such as a tissue fastener, including a ring fastener or a band fastener that partially or completely surrounds the plurality of invaginated portions.

[0225] Exemplary devices for invagination of a cavity

[0226] According to some exemplary embodiments, a device for invagination of a lumen (e.g., the left atrial appendage) is sufficiently thin and flexible to allow the device to be introduced through multiple blood vessels to multiple remote organs. Figure 2A , Figure 2A An integral cavity closure device according to some exemplary embodiments of the present invention is depicted.

[0227] According to some exemplary embodiments, a device for invagination of a body cavity, such as device 200, includes an elongated catheter 202 having an internal working channel 204 and a distal opening 206 of the working channel. In some embodiments, a distal opening of the catheter is an opening facing the body cavity or an opening positioned adjacent to the body cavity opening. In some embodiments, one or more proximal openings located at a distance from the body cavity are located outside the body. In some embodiments, the distal opening 206 has a maximum width in a range of 1 mm to 20 mm, such as 1 mm to 10 mm, 5 mm to 15 mm, 12 mm to 20 mm, or any intermediate, smaller or larger range of values.

[0228] According to some exemplary embodiments, the elongated conduit (e.g., elongated conduit 202) has an outer diameter in the range of 1 mm to 20 mm, such as 1 mm to 10 mm, 5 mm to 15 mm, 12 mm to 20 mm, or any intermediate, smaller, or larger range of values. In some embodiments, a thickness of a wall of the elongated conduit (e.g., elongated conduit 202) is in the range of 0.5 mm to 1.5 mm, such as 0.5 mm to 1.2 mm, 0.9 mm to 1.5 mm, or any intermediate, smaller, or larger range of values.

[0229] According to some exemplary embodiments, the catheter shape and size are designed to be introduced into the left atrium (LA), for example, introduced into the left atrium through the septum (transseptally introduced into). In some embodiments, a width of the catheter 202 is less than 24mm, for example, less than 20mm, less than 15mm or any intermediate, smaller or larger width. In some embodiments, a width of the catheter (for example, an outer width of the catheter) is less than 30French, for example, less than 20French, less than 10French, less than 7French or any intermediate, smaller or larger value. In some embodiments, the width of the catheter is less than 24mm, for example, to allow the catheter to be introduced into the right atrium (RA) through the superior vena cava or the inferior vena cava. In some embodiments, a width of a catheter portion introduced into the left atrium through the septum is in a range of 6French to 30French, for example, 6French to 15French, 10French to 20French, 19French to 30French or any intermediate, smaller or larger range of values.

[0230] According to some exemplary embodiments, the device 200 includes an elongated left atrial appendage remodeler guide 208 having a left atrial appendage remodeler 210 at a distal end 222 of the guide 208. In some embodiments, the elongated guide 208 is shaped and sized to pass within the catheter 202 (e.g., within the working channel 204 of the catheter 202). In some embodiments, the elongated guide can extend from the distal opening 206 of the working channel 204. In some embodiments, the elongated guide is at least partially elastic and / or bendable, thereby allowing the elongated guide 208 to pass within the catheter 202, for example, when the catheter is bent within the body (e.g., within several blood vessels).

[0231] According to some exemplary embodiments, the LAA remodeler 210 is shaped and sized to be introduced into the LAA. In some embodiments, the LAA guide 208 and the LAA remodeler 210 extend forward from the distal opening 206 into the left atrium and the LAA. In some embodiments, the LAA remodeler 210 is expandable. In some embodiments, the LAA remodeler 210 moves between a collapsed state (e.g., when the LAA remodeler is within the working channel 204 of the catheter 202) and an expanded state (e.g., within the LAA). In some embodiments, in a collapsed state, a width 211 of the LAA remodeler is less than a width of the LAA opening, e.g., to allow the LAA remodeler 210 to be at least partially inserted into the LAA cavity. In some embodiments, a maximum width of the left atrial appendage remodeler (e.g., the left atrial appendage remodeler 210) in a collapsed state is in a range of 1 mm to 30 mm, such as 1 mm to 10 mm, 5 mm to 15 mm, 10 mm to 20 mm, 18 mm to 30 mm, or any intermediate, smaller, or larger range of values. In some embodiments, a maximum width of the left atrial appendage remodeler (e.g., the left atrial appendage remodeler 210) in an expanded state is in a range of 5 mm to 50 mm, such as 5 mm to 15 mm, 10 mm to 25 mm, 20 mm to 35 mm, 30 mm to 50 mm, or any intermediate, smaller, or larger range of values.

[0232] According to some exemplary embodiments, the expandable LAA remodeler is formed of a mesh of wires configured to expand when extending forward from the distal opening 206 of the working channel (e.g., within the LAA). In some embodiments, the LAA remodeler expands within the LAA and applies pressure, such as radial pressure against the LAA wall. In some embodiments, for example Figure 2B As shown, the device (eg, the device 200) is configured to utilize WATCHMAN TMThe device acts as a remodeler (e.g., the left atrial appendage remodeler 210). In some embodiments, the expandable left atrial appendage remodeler has a cylindrical shape having an inner lumen. In some embodiments, a distal opening of the left atrial appendage remodeler in an expanded state is closed. Alternatively, a distal opening of the left atrial appendage remodeler in an expanded state is open. In some embodiments, the left atrial appendage remodeler is at least partially formed of a shape memory alloy, such as Nitinol. According to some exemplary embodiments, the left atrial appendage remodeler (e.g., the left atrial appendage remodeler 210) includes one or more anchors configured to anchor the left atrial appendage remodeler in an expanded state to the left atrial appendage wall. In some embodiments, when the left atrial appendage remodeler is in a collapsed state, the plurality of anchors are folded, for example, to prevent damage to the left atrial appendage remodeler. In some embodiments, when the left atrial appendage remodeler is expanded, one or more anchors unfold and optionally face the left atrial appendage wall. In some embodiments, one or more anchors include at least one hook and / or at least one pin.

[0233] According to some exemplary embodiments, the expandable left atrial appendage remodeler comprises an inflatable balloon configured to be inflated within the left atrial appendage, for example, to apply force to the left atrial appendage wall. In some embodiments, the left atrial appendage remodeler guide comprises an inflation channel configured to inflate the left atrial appendage remodeler with a fluid (e.g., liquid or gas).

[0234] According to some exemplary embodiments, the left atrial appendage remodeler 210 (e.g., the expandable left atrial appendage remodeler) includes one of a plurality of anchors configured to reversibly anchor the left atrial appendage remodeler to the left atrial appendage wall within the left atrial appendage. In some embodiments, one or more anchors are hidden or folded anchors configured to be hidden or folded within the catheter and exposed or deployed when the left atrial appendage remodeler is located within the left atrial appendage.

[0235] According to some exemplary embodiments, the device 200 includes an elongated suction channel 212 shaped and sized to pass within the working channel 204 of the catheter 202. In some embodiments, the diameter or width of the suction channel 212 is less than the internal width or inner diameter of the working channel 204. In some embodiments, the elongated suction channel 212 terminates at a vacuum inlet 216 at a distal end of the suction channel 212 facing the left atrial appendage. In some embodiments, the vacuum inlet 216 includes an expandable inlet configured to be in a collapsed state within the working channel 204 and expand within the left atrium and / or when exiting from the distal opening 206 of the working channel 204.

[0236] According to some exemplary embodiments, the vacuum inlet 216 is at least partially elastic, for example to allow attachment of the vacuum inlet 216, for example one or more lips surrounding an opening of the vacuum inlet 216 to the left atrial appendage wall. In some embodiments, one or more lips of the vacuum inlet 216 are at least partially elastic. In some embodiments, the vacuum inlet 216 is at least partially elastic, for example at least partially reversibly deformable, to allow attachment of the vacuum inlet 216 to the left atrial wall around the left atrial appendage opening.

[0237] According to some exemplary embodiments, a width (e.g., a maximum width) of the vacuum inlet is greater than the maximum width of the left atrial appendage opening, for example to allow the vacuum inlet to attach to the left atrial wall and around the left atrial appendage opening. In some embodiments, a maximum width is a maximum width of the vacuum inlet when the vacuum inlet is in a fully expanded state. In some embodiments, a maximum width of the vacuum inlet is greater than the width of the catheter 202. In some embodiments, a maximum width of the vacuum inlet 216 is in a range of 10 mm to 50 mm, for example 10 mm to 20 mm, 15 mm to 30 mm, 25 mm to 40 mm, 35 mm to 50 mm, or any intermediate, smaller, or larger range of values.

[0238] According to some exemplary embodiments, the vacuum inlet 216 in an expanded state has a narrow proximal section 214 connected to the suction channel 212, and a wider forward-facing distal section 221. In some embodiments, the maximum width or diameter 221 of the wider distal section is greater than the maximum width of the left atrial appendage opening. In addition, the maximum width or diameter of the wider distal portion 221 is greater than the distal opening 206 of the catheter 202 and / or the width of the catheter 202. In some embodiments, a maximum width of the wider distal portion 221 is in a range of 10 mm to 50 mm, for example 10 mm to 20 mm, 15 mm to 30 mm, 25 mm to 40 mm, 35 mm to 50 mm, or any intermediate, smaller or larger range of values.

[0239] According to some exemplary embodiments, a distal end of the vacuum inlet (e.g., an edge of the vacuum inlet surrounding a wide distal opening of the vacuum inlet) is configured to be attached to the left atrium at a distance around the left atrial appendage opening in a range of 1 mm to 15 mm (e.g., 1 mm to 7 mm, 5 mm to 10 mm, 8 mm to 15 mm) from the left atrial appendage opening. In some embodiments, the vacuum inlet (e.g., a frame of the vacuum inlet) is formed of one or more of nitinol, stainless steel, silicone, polyurethane and / or rubber. In some embodiments, the frame of the vacuum inlet is covered with a medical grade coating, such as silicone or other sealing fabric. In some embodiments, an inner surface of the coating includes a plurality of bulges or a plurality of bumps, for example to increase friction with tissue.

[0240] According to some exemplary embodiments, the device (e.g., the vacuum inlet) includes one or more sensors configured to sense the amount of the invaginated tissue, for example by measuring several electrical properties of the invaginated tissue. In some embodiments, the several electrical properties include one or both of impedance and conductivity. Alternatively or additionally, one or more sensors include a pressure sensor configured to sense contact with the left atrium wall or the left atrial appendage wall. Alternatively or additionally, one or more sensors are configured to sense at least one parameter related to conductivity, for example to check that the invagination process does not damage the electrical conductivity of the heart. In some embodiments, the body cavity closure device includes at least one vacuum sensor, for example to sense the vacuum level applied to the tissue (e.g., on the left atrial appendage tissue) through the suction channel and / or through the vacuum inlet. In some embodiments, one or more sensors are configured to sense several electrical properties of the left atrium, for example to sense contact of the vacuum inlet with the left atrial wall.

[0241] According to some exemplary embodiments, the device comprises one or more pressure sensors configured to sense, for example, pressure applied by the left atrial appendage remodeler on the left atrial appendage tissue and / or pressure applied by the vacuum inlet on a wall of the left atrium around the left atrial appendage opening.

[0242] According to some exemplary embodiments, one or more electrodes of the device (e.g., electrodes coupled to the vacuum inlet) are configured to sense electrical properties of the tissue, such as impedance, before, during, and / or after the invagination process. In some embodiments, a control circuit connected to one or more electrodes measures the conductivity and / or conductivity changes of the heart based on the sensed electrical properties.

[0243] According to some exemplary embodiments, the vacuum inlet has a symmetrical or asymmetrical shape. In some embodiments, the shape and size of the vacuum inlet changes, for example, by contracting the portion of the vacuum inlet by the catheter (e.g., catheter 202). In some embodiments, the shape and / or size of the vacuum inlet in an expanded state changes when the plurality of vacuum inlet portions are introduced into the inner lumen of the catheter (e.g., catheter 202).

[0244] According to some exemplary embodiments, the LAA remodeler guide 208 and the LAA remodeler 210 are shaped and sized to pass through the suction channel 212. In some embodiments, a width or a diameter of the guide 208 is less than the width or the diameter of the suction channel. In some embodiments, a maximum width of the LAA remodeler 210 (e.g., in a collapsed state) is less than a width of the suction channel. In some embodiments, the maximum width or the diameter of the suction channel is in a range of 1 mm to 15 mm, such as 1 mm to 7 mm, 5 mm to 12 mm, 10 mm to 15 mm, or any intermediate, smaller or larger range of values.

[0245] According to some exemplary embodiments, the device 200 includes a tissue fastener, such as a fastener 224. In some embodiments, the fastener includes a ring fastener, such as a band fastener. In some embodiments, the fastener (e.g., fastener 224) is configured to fasten one or more recessed portions of the left atrial appendage. In some embodiments, the fastener 224 is shaped and sized to be fastened around one or more recessed portions of the left atrial appendage. In addition, the fastener 224 is configured to be tightened around one or more recessed portions of the left atrial appendage. In some embodiments, the step of tightening the fastener around two or more recessed portions of the left atrial appendage closes the left atrial appendage opening and / or any other flow path between the left atrium and the left atrial appendage.

[0246] According to some exemplary embodiments, the fastener 224 includes a fastener ring 218 and a fastener manipulator 220 connected to the fastener ring 218. In some embodiments, the fastener ring 218 is elastic, foldable and / or collapsible to be positioned within a working channel 204 of the catheter 202. In addition, the fastener manipulator is thin and / or has a cross-section that is smaller than a width of the working channel 204.

[0247] According to some exemplary embodiments, the fastener ring 218 in an open state has a width or a diameter greater than the maximum width of one or more recessed portions of the left atrial appendage. In some embodiments, the maximum width or maximum diameter of the fastener ring 218 in an open state is in a range of 10 mm to 50 mm, such as 10 mm to 20 mm, 15 mm to 30 mm, 25 mm to 40 mm, 35 mm to 50 mm, or any intermediate, smaller or larger range of values. In some embodiments, the fastener ring 218 in an open state has a width greater than the maximum width of the vacuum inlet 216, such as to allow the fastener to pass through the vacuum inlet. Alternatively, the fastener ring 218 in an open state has a width less than the maximum width of the vacuum inlet 216, such as to allow one or more recessed portions of the left atrial appendage to be fastened from within the vacuum inlet 216.

[0248] According to some exemplary embodiments, the fastener ring 218, for example in an open state, is connected to the distal section 221 of the vacuum inlet 216. In some embodiments, the fastener ring 218, for example in an open state, is positioned inside the vacuum inlet 216. Alternatively, the fastener ring 218 is located outside the vacuum inlet 216. In some embodiments, the fastener ring 218 comprises a wire and / or a string. In some embodiments, the fastener ring 218 comprises a mesh, for example a mesh of wires.

[0249] According to some exemplary embodiments, the fastener manipulator 220 is shaped and sized to be positioned inside the working channel 204 and outside the aspiration channel 212. Alternatively, the fastener manipulator 220 is shaped and sized to be positioned inside the aspiration channel 212. In some embodiments, the fastener manipulator 220 is rigid enough to be moved, e.g., retracted and / or advanced, from outside the body. In some embodiments, the fastener manipulator 220 is moved from outside the body to open and / or tighten the fastener (e.g., fastener ring 218).

[0250] According to some exemplary embodiments, the fastener ring is coupled to the vacuum inlet by one or more of hooks, wires, elastic wires, cords, and / or elastic cords. In some embodiments, the fastener ring is made of ePTFE, polypropylene, peek, and / or polyurethane. In some embodiments, the fastener ring has a thickness in a range of 0.1 mm to 2 mm, such as 0.1 mm to 0.8 mm, 0.5 mm to 1.5 mm, 1.2 mm to 2 mm, or any intermediate, smaller or larger range of values. In some embodiments, the outer surface of the fastener (e.g., the fastener ring) is covered with one or more of bumps, bulges, and protrusions, such as to allow for improved contact and / or friction between the fastener ring and the tissue. Optionally, the one or more of the plurality of bumps, bulges and protrusions are formed of a hardened material. In some embodiments, the one or more of the plurality of bumps, bulges and protrusions are located on an outer surface of a sleeve covering the fastener ring.

[0251] According to some exemplary embodiments, the force applied by the fastener ring on the left atrial appendage tissue is up to 35 Newtons (N), for example up to 25N, up to 20N, up to 15N, up to 10N or any intermediate, smaller or larger value.

[0252] According to some exemplary embodiments, one or more of the catheter (e.g., catheter 202), the left atrial appendage remodeler guide (e.g., left atrial appendage remodeler guide 208), the left atrial appendage remodeler (e.g., left atrial appendage remodeler 210), the suction channel (e.g., suction channel 212), the vacuum inlet (e.g., vacuum inlet 216), the fastener manipulator (e.g., fastener manipulator 220), the fastener (e.g., fastener ring 218) is coated with or at least partially includes one or more radiopaque materials configured to increase X-ray detection. In some embodiments, the one or more radiopaque materials include one or more of barium sulfate, bismuth compounds, tungsten, or any other material, such as a metal that absorbs X-rays.

[0253] Alternatively or additionally, one or more of the catheter (e.g., catheter 202), the left atrial appendage remodeler guide (e.g., left atrial appendage remodeler guide 208), the left atrial appendage remodeler (e.g., left atrial appendage remodeler 210), the suction channel (e.g., suction channel 212), the vacuum inlet (e.g., vacuum inlet 216), the fastener manipulator (e.g., fastener manipulator 220), and the fastener (e.g., fastener ring 218) are coated with or at least partially include one or more highly echogenic materials, such as metal, plastic, or any other material that increases ultrasound detection.

[0254] Exemplary detailed procedure for closing the left atrial appendage

[0255] According to some exemplary embodiments, the left atrial appendage is closed, for example to prevent blood from flowing from the left atrium into the left atrial appendage and to prevent blood clots from forming and being released from the left atrial appendage cavity into the left atrium and the blood flow. In some embodiments, the left atrial appendage is closed by a device (e.g. Figure 2A and Figure 2B The device 200 shown in FIG. 2 is closed by the device 200, i.e., is introduced into the left atrium, for example by passing through the septum from the right atrium into the left atrium. Referring now to Figure 3 , Figure 3 A detailed process for closing the left atrial appendage according to some exemplary embodiments of the present invention is depicted.

[0256] According to some exemplary embodiments, a catheter (e.g. Figure 2A and 2B The catheter 202 shown in FIG. 2 is advanced into the left atrium at block 302. In some embodiments, the catheter is introduced into the right atrium, for example, through the superior vena cava or the inferior vena cava. In some embodiments, the catheter is transeptally introduced into the left atrium through the septum.

[0257] According to some exemplary embodiments, a left atrial appendage remodeler (e.g. Figure 2A and 2B The left atrial appendage remodeler 210 shown is at least partially advanced into the left atrial appendage through the left atrial appendage opening at block 304. In some embodiments, the left atrial appendage remodeler is anchored within the left atrial appendage. In some embodiments, the left atrial appendage remodeler is expanded within the left atrial appendage, such as to contact the left atrial appendage wall within the left atrial appendage with sufficient force to anchor the left atrial appendage remodeler.

[0258] According to some exemplary embodiments, at block 306, a suction channel terminating at the vacuum inlet is advanced toward the left atrial appendage opening. In some embodiments, the vacuum inlet exits through a distal opening of the catheter and expands within the left atrium. Alternatively or additionally, the vacuum inlet expands upon reaching the left atrial appendage opening. In some embodiments, the expansion of the vacuum inlet is controlled from outside the body.

[0259] According to some exemplary embodiments, the vacuum inlet is placed above the left atrial appendage opening. In some embodiments, the vacuum inlet is attached to the left atrial wall around the left atrial appendage opening. In some embodiments, several lips of a distal section of the vacuum inlet are attached to the left atrial wall around the left atrial appendage opening. In some embodiments, the vacuum inlet is attached to the left atrial wall while applying a vacuum (e.g., a low-pressure vacuum). In some embodiments, a vacuum (e.g., a low-pressure vacuum) is applied to firmly attach the vacuum inlet to the left atrial wall. In some embodiments, the low-pressure vacuum is in a range of 0 mmHg to 500 mmHg, for example, 0 mmHg to 200 mmHg, 150 to 350 mmHg, 300 mmHg to 450 mmHg, 380 mmHg to 500 mmHg, or any intermediate, smaller or larger range of values.

[0260] According to some exemplary embodiments, a vacuum is applied at block 310 through the vacuum inlet on the left atrial appendage cavity. In some embodiments, a high pressure vacuum is applied to the left atrial appendage cavity. In some embodiments, a high pressure vacuum is in a range of 400 mmHg to 900 mmHg, such as 400 mmHg to 600 mmHg, 550 mmHg to 800 mmHg, 650 mmHg to 900 mmHg, or any intermediate, smaller or larger range of values. In some embodiments, the high pressure vacuum is applied at a pressure value sufficient to cause one or more (e.g., two, three, four, or any number) portions of the left atrial appendage to at least partially collapse into the left atrium. Alternatively or additionally, a vacuum is applied to prevent floating material (e.g., blood clots and / or debris) from being released from the left atrial appendage into the left atrium.

[0261] According to some exemplary embodiments, the LAA remodeler is retracted at block 312. In some embodiments, the LAA remodeler is retracted while applying a vacuum to the LAA, such as described at block 310. In some embodiments, the LAA remodeler is retracted into the left atrium while applying a force to the LAA wall. Alternatively or additionally, the LAA remodeler is retracted into the left atrium while in contact with the LAA wall.

[0262] According to some exemplary embodiments, the left atrial appendage is at least partially invaginated at block 314. In some embodiments, the left atrial appendage is at least partially invaginated into the left atrium. In some embodiments, one or more portions of the left atrial appendage (e.g., two, three, four, five, or any number of portions of the left atrial appendage) are invaginated into the left atrium. In some embodiments, the left atrial appendage is invaginated into the left atrium by the steps of applying the vacuum to the left atrial appendage cavity and retracting the left atrial appendage remodeler into the left atrium. Optionally, the left atrial appendage is invaginated into the left atrium using only the step of retracting the left atrial appendage remodeler, wherein the applied vacuum is used to remove floating particles during the left atrial appendage operation.

[0263] According to some exemplary embodiments, the left atrial appendage collapses at block 320. In some embodiments, the vacuum applied to the left atrial appendage cavity causes the collapse, such as internal collapse of one or more segments of the left atrial appendage. In some embodiments, the one or more collapsed segments are segments that are not supported by a left atrial appendage remodeler positioned within the left atrial appendage cavity. Optionally, the left atrial appendage remodeler prevents collapse of a plurality of left atrial appendage segments in contact with the left atrial appendage remodeler.

[0264] According to some exemplary embodiments, the collapsed segments collapse on the left atrial appendage remodeler, for example when the left atrial appendage remodeler is at least partially placed within the left atrial appendage and not in contact with the left atrial appendage. In some embodiments, a vacuum applied by the left atrial appendage remodeler on the left atrial appendage wall causes collapse of several left atrial appendage segments on the left atrial appendage remodeler.

[0265] According to some exemplary embodiments, the left atrial appendage is at least partially invaginated into the left atrium at block 322. In some embodiments, the vacuum applied to the left atrial appendage cavity causes one or more portions (e.g., two, three, four, or any number of left atrial appendage portions) to invaginate into the left atrium. In some embodiments, the plurality of collapsed segments of the left atrial appendage, such as described at block 320, are at least partially invaginated into the left atrium. In some embodiments, the collapse of the left atrial appendage on the left atrial appendage remodeler positions one or more portions of the left atrial appendage at least partially within the left atrium.

[0266] According to some exemplary embodiments, the indented left atrial appendage is fastened at box 316. In some embodiments, the one or more indented portions of the left atrial appendage are fastened at box 316. In some embodiments, the left atrial appendage is fastened by placing a fastener, such as a fastener ring 218 of a fastener 224 around one or more (e.g., two, three, four, or any number of indented portions. In some embodiments, the left atrial appendage is closed by the fastening of the several indented portions of the left atrial appendage. Alternatively or additionally, the left atrial appendage opening in the left atrium is closed by the fastening of the several indented left atrial appendage portions.

[0267] According to some exemplary embodiments, once the LAA is invaginated into the left atrium and / or secured, the LAA remodeler is retracted into the working channel of the catheter. In some embodiments, the LAA remodeler collapses into the working channel of the catheter or collapses into the aspiration channel (e.g., Figure 2A and Figure 2B In the suction channel 212 shown in ).

[0268] According to some exemplary embodiments, the catheter is retracted at block 318. In some embodiments, once the plurality of invaginated portions of the left atrial appendage are secured, the vacuum inlet is retracted into the working channel of the catheter. In addition, the vacuum inlet is collapsed or folded into the working channel of the catheter. In some embodiments, the catheter is retracted from the left atrium and the body at block 318.

[0269] Exemplary alignment of a catheter and closure of a lumen

[0270] According to some exemplary embodiments, a catheter is aligned with an opening of a body cavity, such as the left atrial appendage opening, prior to a body cavity procedure, such as the body cavity and / or closure of the body cavity opening. 4A to 4F , 4A to 4F Depicted is the alignment of a catheter of the body cavity closure device to a cavity opening and the body cavity closure according to some exemplary embodiments of the present invention.

[0271] According to some exemplary embodiments, for example Figure 4A As shown, a catheter 401 of a cavity closure device 400 is introduced into the body cavity (e.g., left atrium 406). In some embodiments, the left atrial appendage remodeler 414 is at least partially advanced from the working channel 402 of the catheter 401 to the left atrial appendage cavity 412. Optionally, the left atrial appendage remodeler is advanced from a suction channel 418 located in the working channel 402.

[0272] According to some exemplary embodiments, the left atrial appendage remodeler 414 is anchored within the left atrial appendage cavity 412, for example, by contacting the wall 416 of the left atrial appendage cavity 412. In some embodiments, the left atrial appendage remodeler 414 is expanded within the left atrial appendage cavity 412. In some embodiments, the expansion of the left atrial appendage remodeler 414 within the left atrial appendage cavity 412 pushes the outer surface of the left atrial appendage remodeler against the wall 416 of the left atrial appendage cavity 412 with a number of forces sufficient to anchor the left atrial appendage remodeler without tearing or damaging the wall 416.

[0273] According to some exemplary embodiments, a vacuum inlet 420 (e.g., a conical vacuum inlet or a concave vacuum inlet) at a distal end of the suction channel 418 expands when leaving the working channel 402 of the catheter 401. In some embodiments, the expanded vacuum inlet 420 is advanced toward the left atrial appendage opening 410 along a left atrial appendage remodeler guide 408, and the left atrial appendage remodeler guide 408 is connected to the anchored left atrial appendage remodeler 414 and the catheter 401. Optionally, the catheter 401 is advanced along the guide 408 toward the left atrial appendage opening.

[0274] According to some exemplary embodiments, for example Figure 4B As shown, the vacuum inlet 420 is placed in contact with the left atrial wall 422 around the left atrial appendage opening 410. In some embodiments, one or more lips of the vacuum inlet 420 (facing the left atrial wall) are pushed against the left atrial wall. In some embodiments, a vacuum 424 (e.g., a low pressure vacuum) is applied during the connection of the vacuum inlet 420 to the left atrial wall 422, for example, to ensure a close interaction between the left atrial wall and the vacuum inlet 420. In some embodiments, once the vacuum inlet is in contact with the left atrial wall 422, the left atrial appendage remodeler 414 is released from the left atrial appendage cavity and retracted into the working channel 402 of the catheter 401. Optionally, the left atrial appendage remodeler 414 is retracted into the suction channel 418. In some embodiments, the left atrial appendage remodeler 414 collapses when retracted into the working channel 402 or the suction channel 418. In some embodiments, when a low-pressure vacuum and / or a high-pressure vacuum is applied through the vacuum inlet 420 on the left atrial appendage, blood clots in the left atrial appendage are aspirated and moved out of the left atrial appendage into the aspiration channel 418 .

[0275] According to some exemplary embodiments, for example Figure 4CAs shown in FIG. 4 , a vacuum (e.g., a high-pressure vacuum) is applied from the vacuum inlet 420 on the left atrial appendage (e.g., on the left atrial appendage cavity 412). In some embodiments, the high-pressure vacuum invaginates two or more portions (e.g., portions 426 and 428) of the left atrial appendage into the left atrium 406. In some embodiments, the two or more portions are invaginated into the vacuum inlet 420.

[0276] Alternatively and according to some exemplary embodiments, for example Figure 4D As shown, the left atrial appendage 412 is completely invaginated into the left atrium 406. In some embodiments, the left atrial appendage 412 is completely invaginated into the vacuum inlet 420. In some embodiments, the left atrial appendage 412 is completely invaginated by the application of high pressure vacuum.

[0277] According to some exemplary embodiments, for example Figure 4E As shown, a fastener (e.g., a fastener ring 432) is positioned around the two or more recessed portions, such as portions 426 and 428, of the left atrial appendage 412. In some embodiments, the fastener ring 432 is coupled to the inner surface of the vacuum inlet 420. Alternatively, the fastener ring 432 is coupled to the outer surface of the vacuum inlet 420.

[0278] According to some exemplary embodiments, the fastener ring 432 is mechanically connected to a fastener manipulator 430. In some embodiments, the fastener manipulator is located outside the vacuum inlet 420. In some embodiments, the fastener manipulator 430 comprises an elongated fastener manipulator shaped and sized to be advanced from within the working channel 402 of the catheter into the left atrium 406. In some embodiments, the fastener manipulator (e.g., fastener manipulator 430) is shaped and sized to be advanced from within the suction channel 418 into the left atrium 406. Optionally, the fastener manipulator 430 is at least partially rigid to allow manipulation of the fastener ring 432 from outside the body. In some embodiments, the retraction or advancement of the fastener manipulator 430 fastens the fastener ring 432 around the two or more invaginated portions of the left atrial appendage. Alternatively, the rotation of the fastener manipulator 430 fastens the fastener ring 432 around the two or more invaginated portions of the left atrial appendage.

[0279] According to some exemplary embodiments, for example Figure 4FAs shown, once the several indented portions of the left atrial appendage are secured within the left atrium, the device 400 is retracted from the left atrium. In some embodiments, after the indentation and the securing, up to 50% of the left atrial appendage tissue (e.g., up to 30%, up to 10%, up to 5%, or any intermediate, smaller, or larger percentage of the left atrial appendage tissue) is located within the left atrium. In some embodiments, the non-indented portion of the left atrial appendage collapses. In some embodiments, the securing of the several indented portions of the left atrial appendage closes the left atrial appendage opening. In addition, the securing of the indented left atrial appendage portion isolates the left atrial appendage 412 from the left atrium 406.

[0280] Exemplary left atrial appendage remodeling during vacuum application

[0281] According to some exemplary embodiments, the LAA remodeler is located within the LAA and regulates the flow of suction forces within the LAA cavity, such as to cause specific regions of the LAA to collapse. Alternatively or additionally, the LAA remodeler maintains an open flow path into the LAA, such as by preventing specific regions of the LAA from collapsing during vacuum application. Referring now to FIG. 5A to FIG. 5E , FIG. 5A to FIG. 5E Depicted is the regulation of suction forces and / or collapse of the left atrial appendage during vacuum application according to some exemplary embodiments of the present invention.

[0282] According to some exemplary embodiments, for example Figure 5A As shown, a left atrial appendage remodeler 514 is positioned within the left atrial appendage 412. In some embodiments, the left atrial appendage remodeler 514 expands and applies force to the left atrial appendage wall from within the left atrial appendage. In some embodiments, a vacuum inlet 520 of the device 500 located at a distal end of a suction channel 518 is attached to a left atrial appendage opening 410, and vacuum is optionally applied from the vacuum channel 518 on the left atrial appendage through the vacuum inlet 520.

[0283] According to some exemplary embodiments, for example Figure 5BAs shown, the vacuum 531 applied to the LAA affects portions of the LAA wall that are not supported by the LAA remodeler 514, such as portions 533 and 535. In some embodiments, the LAA remodeler 514 has a front closed end and / or one or more closed portions that allow up to 30%, such as up to 10%, up to 7%, up to 5%, or any intermediate, lesser, or greater percentage of vacuum to enter distal portions of the LAA. In some embodiments, preventing the application of vacuum to distal portions of the LAA maintains an open LAA while allowing portions of the LAA closer to the LAA opening to indent.

[0284] According to some exemplary embodiments, for example Figure 5C As shown, two or more portions (e.g., portions 533 and 535) of the left atrial appendage 412 are invaginated into the left atrium 506. In some embodiments, the two or more portions are invaginated into the vacuum inlet 520. In some embodiments, the two or more portions are invaginated while maintaining at least a portion of the left atrial appendage supported by the left atrial appendage remodeler 514. In some embodiments, the support of the left atrial appendage by the left atrial appendage remodeler 514 prevents collapse of the plurality of supported portions by the applied vacuum.

[0285] According to some exemplary embodiments, for example Figure 5D As shown, the left atrial appendage remodeler 514 is retracted into the vacuum inlet 520, while several left atrial appendage regions contacting the left atrial appendage remodeler are sunken into the left atrium 506 and / or the vacuum inlet 520. In some embodiments, the left atrial appendage remodeler 514 is separated from the left atrial appendage wall during the retraction of the left atrial appendage remodeler 514 into the vacuum inlet 520. In some embodiments, when the left atrial appendage remodeler 514 is retracted into the suction channel 518 through the vacuum inlet 520, the left atrial appendage remodeler 514 collapses or folds to fit into the suction channel 518.

[0286] According to some exemplary embodiments, during and / or after the invagination of the left atrial appendage into the left atrium, a fastener (e.g., a fastener ring 532) is advanced toward the invaginated portions of the left atrial appendage (e.g., portions 533 and 535). Alternatively, the fastener ring 532 is connected or coupled to the vacuum inlet 520. In some embodiments, the fastener ring 532 is positioned around the invaginated portions of the left atrial appendage.

[0287] According to some exemplary embodiments, for example Figure 5EAs shown, the fastener ring 532 secures the plurality of inverted portions of the left atrial appendage, such as the plurality of portions 533 and 535, while disconnecting from the device 500. In some embodiments, the fastener ring 532 is disconnected from the device 500 after securing the plurality of inverted portions of the left atrial appendage.

[0288] Exemplary left atrial appendage remodeling during invagination

[0289] According to some exemplary embodiments, the left atrial appendage is reshaped during invagination into the left atrium. In some embodiments, a left atrial appendage remodeler positioned within the left atrial appendage reshapes the left atrial appendage by contacting the plurality of contact areas of the left atrial appendage and moving it into the left atrium. Alternatively or additionally, the left atrial appendage remodeler is reshaped by controlling the collapse and / or shrinkage of the plurality of left atrial appendage areas that are not invaginated into the left atrium. Now referring to FIG. 6A to FIG. 6I , FIG. 6A to FIG. 6I Left atrial appendage remodeling during invagination is depicted according to some exemplary embodiments of the present invention.

[0290] According to some exemplary embodiments, for example Fig. 6A As shown, a distal portion 608 of the left atrial appendage remodeler guide 610 is at least partially introduced from the left atrium 602 through the left atrial appendage opening 604 into the left atrial appendage (e.g., left atrial appendage cavity 606). In some embodiments, the left atrial appendage remodeler guide 610 is introduced into the left atrial appendage cavity 606 by a distance of 35 mm from the left atrial appendage opening 604, such as by 30 mm, by 20 mm, by 15 mm, by 10 mm, or any intermediate, smaller, or larger distance from the left atrial appendage opening 604.

[0291] According to some exemplary embodiments, for example Figure 6BAs shown, a left atrial appendage remodeler 612 located at a distal section of the left atrial appendage remodeler guide 610 is at least partially expanded within the left atrial appendage cavity 606. In some embodiments, the left atrial appendage remodeler 612 is an integral part of the left atrial appendage remodeler guide 610. Alternatively, the left atrial appendage remodeler 612 is functionally connected or coupled to the left atrial appendage remodeler guide 610. In some embodiments, the expansion of the left atrial appendage remodeler 612 within the left atrial appendage cavity 606 pushes an outer surface 612 of the left atrial appendage remodeler against several areas of the left atrial appendage wall (e.g., areas 623 and 624 of the left atrial appendage wall). In some embodiments, the left atrial appendage remodeler 612 is formed by a mesh of several wires, such as several bio-compatible wires. Optionally, the mesh is at least partially formed by a shape memory alloy, such as Nitinol. In some embodiments, in an expanded state, the left atrial appendage remodeler 612 acquires a substantially cylindrical shape having a diameter that is equal to or greater than a diameter or width of the left atrial appendage cavity 606, for example to allow contact between the left atrial appendage remodeler 612 and the left atrial appendage wall from within the left atrial appendage cavity 606.

[0292] According to some exemplary embodiments, a catheter of a closure device 600 having a working channel 603 is advanced along the LAA remodeler guide 610 toward the left atrial opening 604. In some embodiments, the LAA remodeler guide 610 is advanced into the LAA cavity 606 from the working channel 603 of the catheter located in the left atrium, such as Fig. 6A as shown in .

[0293] According to some exemplary embodiments, for example Figure 6C As shown, a vacuum inlet 620 at a distal end of a suction channel 618 is advanced from the working channel 603 of the catheter toward the left atrial appendage opening 604. In some embodiments, the vacuum inlet 620 comprises an expandable vacuum inlet configured to expand when leaving the working channel 603.

[0294] According to some exemplary embodiments, the expanded vacuum inlet 620 is shaped as a cone, cup, or any other geometric shape, having a wider distal end facing the left atrial appendage opening and a narrow proximal end connected to the suction channel 618, including entering the suction channel 618 through the wider distal end and the narrow proximal end from the outside of the vacuum inlet 620. In some embodiments, an edge or lips of the wider distal end are attached to the left atrial wall 622 and surround the left atrial appendage opening 604.

[0295] According to some exemplary embodiments, the step of attaching the vacuum inlet 620 to the left atrial wall 622 around the left atrial appendage opening 604 isolates the left atrial appendage 606 from the left atrium 602, for example to prevent blood clots, floating particles, tissue fragments, or any other biological floating materials from the left atrial appendage 606 from entering the left atrium 602 and entering the bloodstream. In some embodiments, the blood clots, floating particles, tissue fragments, or any other biological floating materials within the left atrial appendage are drawn into the suction channel 618 of the device 600 by the applied vacuum. In some embodiments, the vacuum inlet 620 is attached to the left atrial wall 622 around the left atrial appendage opening 604 while the vacuum is applied, for example to increase a close interaction between the edge or lips of the vacuum inlet 620 and the left atrial wall 622.

[0296] According to some exemplary embodiments, for example Fig.6D As shown, the left atrial appendage remodeler 612 is retracted into the left atrium while a vacuum is applied to the left atrial appendage 606. In some embodiments, the retraction of the left atrial appendage remodeler 612 and the application of vacuum cause two or more portions of the left atrial appendage (e.g., portions 623 and 624) to be invaginated into the left atrium 602 and / or the vacuum inlet 620. Alternatively or additionally, the applied vacuum is used to maintain the isolation of the left atrial appendage from the left atrium during invagination and / or to remove floating particles or any other floating matter that flows out of the left atrial appendage during invagination.

[0297] According to some exemplary embodiments, the LAA remodeler 612 comprises a mesh structure, such as a mesh structure configured to allow vacuum to enter the LAA through a plurality of holes of the mesh structure. In some embodiments, the applied vacuum causes a collapse of the LAA, such as an inward collapse. In some embodiments, the LAA remodeler 612 prevents the collapse of a plurality of LAA regions supported by the LAA remodeler 612.

[0298] According to some exemplary embodiments, for example Fig. 6E and 6F As shown, the applied vacuum causes a continuous collapse of the LAA cavity 606 while the vacuum inlet 620 is normally positioned around the LAA opening 604. In some embodiments, the vacuum inlet 620 is elastic and configured to bend inwardly following the remodeling of the LAA and / or the remodeling of the plurality of invaginated portions of the LAA attached to the vacuum inlet 620. In some embodiments, the vacuum inlet 620 is elastic to allow the LAA remodeler 612 to bend during collapse of the LAA and / or during LAA shrinkage, like the left atrial wall surrounding the LAA opening.

[0299] According to some exemplary embodiments, for example Figure 6G As shown, the invaginated portion of the left atrial appendage is fastened using a fastener assembly (e.g., fastener mechanism 636). In some embodiments, a fastener assembly includes a fastener (e.g., fastener ring 640) and a fastener manipulator (e.g., fastener manipulator 638 connected to the fastener ring 640 and a cover (e.g., sleeve 639). In some embodiments, the fastener manipulator 638 includes a line configured to transmit a mechanical force to the fastener ring, for example, to allow closure and / or tightening of the fastener ring around tissue. In some embodiments, the sleeve 639 is shaped and sized to cover the fastener manipulator 638 (e.g., within the working channel of the catheter). In some embodiments, the sleeve 639 is shaped and sized to cover the fastener ring 640 and the fastener manipulator 638 (e.g., within the working channel of the catheter).

[0300] According to some exemplary embodiments, the fastener (e.g., a fastener ring 640) is positioned around the two or more indented portions of the left atrial appendage. In some embodiments, the fastener is positioned around the several indented left atrial appendage portions near the left atrial wall. In some embodiments, the fastener is positioned at a distance of up to 20 mm from the left atrial wall, for example, up to 20 mm, up to 15 mm, up to 10 mm, or to an intermediate, smaller, or larger distance from the left atrial wall. In some embodiments, the fastener ring 640 is positioned within the vacuum inlet 620. Optionally, the fastener ring 640 is attached to the interior of the vacuum inlet 620.

[0301] According to some exemplary embodiments, a fastener manipulator 638 connected to the fastener ring 640 is configured to allow the fastener ring 640 to be fastened around the plurality of invaginated portions of the left atrial appendage from outside the body. In some embodiments, a pulling step or retraction step (retraction) of the fastener manipulator 638, such as within the cannula 639, tightens the fastener ring 640 around the plurality of invaginated portions of the left atrial appendage. In some embodiments, the fastener ring 640 is tightened, optionally while retracting the vacuum inlet 620, disconnecting the fastener ring 640 from the vacuum inlet 620. In addition, the retraction step of the vacuum inlet 620 disconnects the fastener manipulator 638 from the fastener ring 640.

[0302] According to some exemplary embodiments, for example Figure 6H As shown, once the fastener ring 640 is disconnected from the fastener manipulator 638, the fastener manipulator 638 is retracted into the sleeve 639, and then the covered fastener manipulator 638 is retracted into the working channel of the catheter ( Figure 6H not shown).

[0303] According to some exemplary embodiments, for example Fig.6I As shown, the catheter is retracted from the left atrium 602 and the body. In some embodiments, the fastener ring 640 fastened around the two or more indented portions of the left atrial appendage (e.g., portions 623 and 624) remains in the left atrium 602. In some embodiments, the fastening of two or more portions by the fastener causes the two or more indented left atrial appendage portions to be attached (e.g., tightly attached) together. In some embodiments, the tight attachment of the two or more indented left atrial appendage portions closes the left atrial appendage opening and prevents blood from entering the left atrial appendage 606 from the left atrium 602. Optionally or additionally, the tight attachment of the two or more indented left atrial appendage portions prevents a number of floating particles from flowing out of the left atrial appendage into the left atrium.

[0304] Exemplary Vacuum Inlet

[0305] According to some exemplary embodiments, a vacuum inlet is located at a distal end of a suction channel, forming a sealed flow path between the vacuum inlet and the suction channel. In some embodiments, the vacuum inlet has an expandable structure that is configured to be in a collapsed state within a working channel of a catheter and expand when leaving the working channel.

[0306] According to some exemplary embodiments, the vacuum inlet comprises a conical vacuum inlet or a hemispherical vacuum inlet, such as a concave vacuum inlet. In some embodiments, the concave vacuum inlet has a wide opening facing forward and a narrow opening connected to the suction channel. In some embodiments, a width of the wide opening is greater than a width of the left atrial appendage opening, such as to allow the forward-facing wide opening to be positioned around the left atrial appendage opening. Now referring to 7A to 7C , 7A to 7C A vacuum inlet frame according to some exemplary embodiments of the present invention is depicted.

[0307] According to some exemplary embodiments, the vacuum inlet (e.g., vacuum inlet 700) includes a frame, such as frame 702. In some embodiments, the frame 702 is an expandable frame. In some embodiments, the frame 702 includes a mesh-like structure, such as a net-like structure, optionally formed by one or more wires, one or more tubes connected together, and / or a perforated sheet. In some embodiments, the frame is made of a shape memory alloy, such as Nitinol.

[0308] According to some exemplary embodiments, the frame 702 comprises a hemispherical mesh structure, such as a concave or a conical structure. In some embodiments, the frame 702 (optionally a net-like frame) comprises, for example, a wide opening 712 in an expanded state, which is shaped and sized to be positioned around the left atrial appendage opening or at least partially within the left atrial appendage, and a narrow opening 704 functionally connectable to the suction channel.

[0309] According to some exemplary embodiments, the frame 702 includes two or more distally extending protrusions 706 surrounding the wide opening 712. In some embodiments, at least some of the plurality of protrusions 706 include a flat end 708 configured to be placed in contact with the left atrium wall. In some embodiments, the flat end 708 is bent, for example, inwardly or outwardly from the wide opening 712. In some embodiments, each flat end 708 is bent to be positioned at an acute angle relative to the left atrium wall, for example, to disperse a pressure applied to the left atrium wall over a larger surface area. In some embodiments, the pressure applied to the left atrium wall is dispersed, for example, to allow the vacuum inlet to be pressed against the left atrium wall while minimizing the risk of injury to the left atrium wall. In some embodiments, at least some of the flat ends include one or more openings (e.g., opening 710) for connecting a fastener (e.g., a fastener ring) to the vacuum inlet around the wide opening.

[0310] According to some exemplary embodiments, one or more of the plurality of distally extending projections are configured to couple a fastener to the vacuum inlet. In some embodiments, at least some of the plurality of projections are identical to one another. In some embodiments, at least some of the plurality of projections are different from one another. In some embodiments, the plurality of projections configured to couple the fastener to the vacuum inlet are different from the remaining plurality of projections. Optionally, at least some of the plurality of projections configured to connect the fastener to the vacuum inlet are identical to one another.

[0311] According to some exemplary embodiments, the frame 702 is covered with a thin sheet, such as a film. In some embodiments, the sheet is airtight. In some embodiments, the sheet covers an inner surface of the frame 702. Alternatively, the sheet covers an outer surface of the frame 702.

[0312] Exemplary Fasteners

[0313] Now refer to Fig. 8A and Figure 8B , Fig. 8A and Figure 8B A fastener assembly, such as fastener mechanism 800, is depicted according to some exemplary embodiments of the present invention.

[0314] According to some exemplary embodiments, a fastener (e.g., a fastener ring 802) is removably coupled to a fastener manipulator 804. In some embodiments, a retraction step or advancement step of the fastener manipulator 804, e.g., within a cannula 805, tightens or loosens the fastener ring 802. Alternatively or additionally, rotation of the fastener manipulator 804 (e.g., rotation of the fastener manipulator within the cannula 805) tightens or loosens the fastener ring 802. In some embodiments, retraction, advancement, and / or rotation of the fastener manipulator 804 releases the fastener manipulator 804 from the fastener ring 802, e.g., Figure 8B shown.

[0315] According to some exemplary embodiments, the fastener manipulator 804 includes a hook 808 configured to removably couple the fastener manipulator 804 to the fastener ring 802 .

[0316] According to some exemplary embodiments, the fastener loop 802 comprises one or more wires or strings. In some embodiments, the fastener loop 802 comprises a braided cable.

[0317] Exemplary Vacuum Inlet-Fastener Assembly

[0318] According to some exemplary embodiments, the fastener (e.g., a fastener ring) is coupled to the vacuum inlet of the suction channel. In some embodiments, the fastener ring is connected to the inner surface of the vacuum inlet. Alternatively, the fastener ring is connected to the outer surface of the vacuum inlet. In some embodiments, the coupling between the fastener ring and the vacuum inlet allows, for example, to introduce them together into the left atrium and position them near the left atrial appendage opening in a single step. In addition, the step of coupling the fastener ring to the vacuum inlet allows, for example, to have a desired relative alignment between the fastener ring and the vacuum inlet to ensure that the fastener ring surrounds the (several) indented left atrial appendage portions positioned within the vacuum inlet. Now referring to 9A to 9E , 9A to 9E Depicted is a coupling between a fastener and a vacuum inlet of an integral cavity closure device according to some exemplary embodiments of the present invention.

[0319] According to some exemplary embodiments, a sheet of material (e.g. Fig.9D and Fig.9E The flexible sheet 906 shown covers an inner surface of the concave vacuum inlet frame 702. In some embodiments, a fastener (e.g., a fastener ring 802) is located within the vacuum inlet. In some embodiments, the fastener ring 802 is coupled to the inner surface of the flexible sheet 906.

[0320] According to some exemplary embodiments, the flexible sheet 906 obtains a cup-like shape based on the shape of the frame 702. In some embodiments, the fastener ring 802 is coupled to the sheet 906 at a distance of at least 1 mm (e.g., 2 mm, 5 mm, 8 mm, or any intermediate, smaller, or larger distance) from the circumference of the cup-shaped vacuum inlet. In some embodiments, the fastener ring 802 is coupled to the cup-shaped vacuum inlet at a distance from the circumference of the vacuum inlet, for example, to allow uninterrupted movement of the fastener ring when the vacuum inlet is pressed against the left atrium wall.

[0321] According to some exemplary embodiments, for example Fig. 10A and Fig. 10B As shown, the fastener ring 802 is coupled to the inner surface of the sheet by one or more wires 1002, and the wires 1002 pass through several openings in the sheet and surround the fastener ring 802, connecting the fastener ring to the frame 702, for example, to the several flat ends 708 of the frame 702.

[0322] According to some exemplary embodiments, for example Fig. 10C As shown, the fastener manipulator 804 is located outside the vacuum inlet 700. Alternatively, the fastener manipulator is located inside the vacuum inlet 700. In some embodiments, the fastener manipulator 804 is connected to the fastener ring 802 located inside the vacuum inlet via an adapter 1004. In some embodiments, the adapter 1004 is configured to convert a retraction step or advancement step of the fastener manipulator 804 in a first plane into a tightening of the fastener ring 802 in a second plane perpendicular to the first plane. Additionally or alternatively, the adapter 1004 is configured to transfer a force and / or a movement of the fastener manipulator 804 outside the vacuum inlet to the fastener ring 802 inside the vacuum inlet, optionally without interference caused by the interaction between the left atrium wall and the vacuum inlet 700.

[0323] Now refer to Fig.9F , Fig.9F A vacuum inlet with an integrated fastener is depicted according to some exemplary embodiments of the present invention.

[0324] According to some exemplary embodiments, a vacuum inlet (e.g., vacuum inlet 920) includes a frame, such as a frame 922 covered with a sheet 924. In some embodiments, the vacuum inlet 920 includes a fastener (e.g., a fastener ring 926). In some embodiments, the fastener ring 926 is integrated with the vacuum inlet 920, such as the fastener ring 926 is positioned in a channel 928 formed in the vacuum inlet 920. In some embodiments, the channel 928 is formed by folding the sheet 924. Alternatively, the channel is formed by at least partially attaching a sheet of a second layer to the sheet 924. In some embodiments, the channel is located around a distal, forward-facing opening 930 of the vacuum inlet 920. In some embodiments, the channel 928 is located at a distance of up to 10 mm, such as up to 8 mm, up to 5 mm, or up to 2 mm from the opening 930. In some embodiments, the channel 928 includes one or more openings or gaps.

[0325] Exemplary Left Atrial Appendage Remodeler

[0326] Now refer to FIG. 11A to FIG. 11E , FIG. 11A to FIG. 11E A left atrial appendage remodeler according to some exemplary embodiments of the present invention is depicted.

[0327] According to some exemplary embodiments, a left atrial appendage remodeler (e.g., left atrial appendage remodeler 1100 and left atrial appendage remodeler 1106 are a plurality of expandable left atrial appendage remodelers) is configured to expand when exiting from a working channel of a catheter or when exiting from an inner lumen of a cannula. In some embodiments, the left atrial appendage remodeler 1100 is configured to expand into a porous mesh cylinder 1102. In some embodiments, the left atrial appendage remodeler 1100 expands into a closed mesh cylinder. In some embodiments, the cylindrical body is connected to an elongated left atrial appendage remodeler guide 1104. Optionally, the guide 1104 is formed by a hollow tube.

[0328] According to some exemplary embodiments, the LAA remodeler (e.g., LAA remodeler 1106) is configured to expand to a porous concave or cup-shaped mesh body 1108 having an anterior opening 1110. In some embodiments, the LAA remodeler 1106 is connected to a distal end of an elongated LAA remodeler guide 1112.

[0329] According to some exemplary embodiments, the LAA remodeler (e.g., LAA remodeler 1100 and LAA remodeler 1106) is formed of one or more wires, cables, or strands, which are optionally made of a shape memory alloy such as Nitinol. In some embodiments, the LAA remodeler guide (e.g., LAA remodeler guide 1104 and LAA remodeler guide 1112) comprises one or more elongated stainless steel tubes. In some embodiments, the LAA remodeler guide comprises a bendable tube configured to bend elastically, for example to allow the LAA remodeler connected to the guide to be guided to a plurality of different locations within the left atrium. In some embodiments, the LAA remodeler guide is movable within a cover, such as a cannula or an inner lumen of a channel. In some embodiments, when placed within the cover, the LAA remodeler is in a collapsed state. In some embodiments, the retracting step of the cover or the advancing step of the LAA remodeler guide moves the LAA remodeler (e.g., LAA remodeler 1106) to the outside of the cover and at least partially into the LAA 1113, e.g. Fig. 11C In some embodiments, the LAA remodeler 1106 expands within the LAA 1113 and applies force to the LAA wall, while the LAA remodeler guide 1112 remains connected to the LAA remodeler 1106 and located in the left atrium 1114 .

[0330] According to some exemplary embodiments, Fig.11D and Fig.11EAs shown, the left atrial appendage remodeler is used to reshape several portions of the left atrial appendage that have been invaginated into the vacuum inlet. In some embodiments, the left atrial appendage remodeler has a conical shape with an inner lumen. In some embodiments, a surface of the conical left atrial appendage remodeler includes a plurality of openings, and the plurality of openings are shaped and sized to allow vacuum to be applied from within the lumen of the conical left atrial appendage remodeler. In some embodiments, an apex of the conical left atrial appendage remodeler is located distal to a suction channel. In addition, a bottom of the conical left atrial appendage remodeler is connected to a vacuum inlet of the suction channel. In some embodiments, a distance between the apex and the bottom of the conical left atrial appendage remodeler is adjustable, for example, based on a signal transmitted from outside the body. In some embodiments, the apex of the conical left atrial appendage remodeler at least partially extends into the left atrial appendage, and optionally, the bottom remains outside the left atrial appendage, for example in the left atrium. Alternatively, the apex and the bottom of the left atrial appendage remodeler are both retained outside the left atrial appendage in the left atrium.

[0331] According to some exemplary embodiments, for example Fig.11D As shown, the left atrial appendage remodeler (e.g., left atrial appendage remodeler 1120) includes one or more elongated strips, such as strip 1126 having a longitudinal axis, a distal end 1121, and a proximal end 1123. Optionally, the strip 1126 is vertical. In some embodiments, the left atrial appendage remodeler 1120 has a conical shape, wherein a distal end 1121 of the strip 1126 is the apex of the conical shape. In some embodiments, the term "distal end" refers to an end located closer to the left atrial appendage, and the term "proximal end" refers to an end located farther away from the left atrial appendage. In some embodiments, the left atrial appendage remodeler 1120 includes one or more rods (e.g., two, three, four, five, six, seven, eight rods, or any greater number of rods, such as rod 1124), one end of which is connected to the strip 1126 and extends laterally from the plurality of strips 1126, such as to contact an inner surface of a vacuum inlet, such as Fig.11E In some embodiments, the plurality of contact points between the tapered LAA remodeler, such as the plurality of contact points between the plurality of rods forming the tapered shape and the vacuum inlet, define a bottom of the tapered LAA remodeler.

[0332] According to some exemplary embodiments, the one or more rods (e.g., rods 1122 and 1124) are connected to the strip 1126 near the distal end 1121 of the strip 1126, for example, at a distance of up to 10 mm from the distal end 1121. In some embodiments, the rods are connected to the strip at several locations on the circumference of the strip 1126 having a similar axial position and different circumferential positions. In some embodiments, an angle (e.g., angle 1127) between one or more rods and a portion of the rod 1126 between the connection point of the rod to the strip and the proximal end of the rod, such as portion 1125, is an acute angle less than 90 degrees. In some embodiments, one end of each rod is connected to the strip, and a second end of each rod is connected to an inner surface of a vacuum inlet, such as Fig.11E The vacuum inlet 1140 is shown in FIG.

[0333] According to some exemplary embodiments, the elongated rod 1126 is axially movable. In some embodiments, each rod (e.g., several rods 1122 and 1124) is pivotally connected to the elongated strip 1126, for example, to allow the angle 1127 to be changed. In some embodiments, changing the angle 1127 allows, for example, to control the volume and / or size of the left atrial appendage tissue in the left atrium that has been invaginated into the vacuum inlet 1140. In some embodiments, reducing the angle 1127 allows, for example, by allowing more left atrial appendage tissue to penetrate into the vacuum inlet 1140, a larger volume and / or size of the left atrial appendage to be invaginated into the vacuum inlet 1140. Alternatively, increasing the angle 1127 allows, for example, to reduce the amount and / or volume of invaginated left atrial appendage tissue that enters the vacuum inlet 1140.

[0334] According to some exemplary embodiments, for example Fig.11E As shown, the left atrial appendage remodeler 1120 is positioned within the vacuum inlet, such as vacuum inlet 1140. In some embodiments, the vacuum inlet is shaped as a hollow cone having a longitudinal axis 1142, a wide distal section, and a narrow proximal portion. In some embodiments, the wide distal portion and the narrow proximal portion are aligned along the longitudinal axis 1142 of the vacuum inlet 1140.

[0335] According to some exemplary embodiments, a central elongated strip of a left atrial appendage remodeler (e.g., strip 1126) is axially aligned along the longitudinal axis 1142 of the vacuum inlet 1140. In some embodiments, the strip 1126 is movable in and out of a suction inlet channel connected to an opening in the proximal narrow portion of the vacuum inlet 1140. Alternatively, the left atrial appendage remodeler 1120 is an integral part of the inner lumen of the vacuum inlet 1140.

[0336] According to some exemplary embodiments, within the vacuum inlet 1140 lumen, a central portion of the left atrial appendage remodeler, such as the distal end 1121 of the strip 1126, is moved away from several other portions of the left atrial appendage remodeler (such as several strips 1122 and 1124), for example to guide the collapse of several side walls within the left atrial appendage into the vacuum inlet lumen while keeping a central vacuum flow path open.

[0337] Exemplary Left Atrial Appendage Closure Devices

[0338] Now refer to FIG. 12A to FIG. 12B , FIG. 12A to FIG. 12B A left atrial appendage closure device according to some exemplary embodiments of the present invention is depicted.

[0339] According to some exemplary embodiments, a left atrial appendage closure device (e.g., closure device 1200) includes a catheter (e.g., catheter 1202) having an internal working channel, the internal working channel having a distal end configured to be guided into the left atrium and a proximal opening (e.g., proximal opening) located outside the body. In some embodiments, an elongated suction channel terminating with an expandable vacuum inlet 700 is disposed within the working channel of the catheter 1202.

[0340] According to some exemplary embodiments, the left atrial appendage closure device (e.g., closure device 1200) includes a fastener mechanism 800. In some embodiments, the fastener mechanism 800 includes a fastener (e.g., fastener ring 802) connected to a fastener manipulator 804. In some embodiments, in some embodiments, the fastener is placed in a cannula 805. In some embodiments, the fastener ring 802 is coupled to an inner surface or an outer surface of the vacuum inlet, e.g., Fig.9D and Fig.9E Alternatively, the fastener ring is separated from the vacuum inlet, and the fastener ring is shaped and sized to pass through the vacuum inlet and fasten one or more recessed portions of the left atrial appendage. Alternatively, the fastener ring is separated from the vacuum inlet, and the fastener ring is shaped and sized to fasten one or more recessed portions of the left atrial appendage from within the vacuum inlet.

[0341] According to some exemplary embodiments, a left atrial appendage remodeler (e.g., an expandable left atrial appendage remodeler 1106) is connected to a distal end of a left atrial appendage remodeler guide 1112, which passes within the aspiration channel within the working channel of the catheter or outside the aspiration channel.

[0342] According to some exemplary embodiments, when the catheter 1202 enters the left atrium, the left atrial appendage remodeler is advanced in a collapsed state within the working channel of the catheter 1202. In some embodiments, the left atrial appendage remodeler is then at least partially inserted into the left atrial appendage and expanded therein. In some embodiments, the expandable vacuum inlet 700 is advanced within the working channel, for example along the left atrial appendage remodeler guide. In some embodiments, the vacuum inlet 700 expands within the left atrium and contacts the left atrial wall around the left atrial appendage opening. In some embodiments, the vacuum inlet 700 is at least partially flexible and / or elastic, for example to allow close contact between the inner surface of the vacuum inlet and a non-planar surface, such as several curved regions of the left atrium.

[0343] According to some exemplary embodiments, a vacuum is applied through the vacuum inlet 700 on the left atrial appendage cavity, for example to allow close contact between the inner surface of the vacuum inlet 700 and the left atrial wall and / or to cause one or more portions of the left atrial appendage to be invaginated. In some embodiments, a fastener ring 802 is positioned around the several invaginated portions and is fastened, for example, by retraction of the fastener manipulator 804 (optionally retracted into a cannula 805). In some embodiments, the cannula 805 and / or the fastener manipulator 804 pass within the suction channel. Alternatively, the fastener manipulator 804 and / or the cannula 805 pass outside the suction channel within the working channel of the catheter 1202.

[0344] According to some exemplary embodiments, if the fastener ring is coupled to the vacuum inlet, e.g. Fig.9D and Fig.9E As shown, the tightening of the fastener ring 802 separates the fastener ring 802 from the vacuum inlet. In some embodiments, the left atrial appendage remodeler 1106 is retracted into the vacuum inlet 700 during the invagination process. In some embodiments, the left atrial appendage remodeler guide 1112 is configured to be retracted into the suction channel, for example to allow the left atrial appendage remodeler 1106 to be retracted into the vacuum inlet 700.

[0345] According to some exemplary embodiments, once at least some of the invaginated portion of the left atrial appendage is secured, the vacuum inlet 700 and the fastener are retracted into the working channel of the catheter, such as catheter 1202 .

[0346] According to some exemplary embodiments, for example Fig.13A As shown, a left atrial appendage closure device includes an elongated suction channel (e.g., suction channel 1322), which terminates at a vacuum inlet 1320. In some embodiments, the vacuum inlet 1320 has a concave shape with a forward opening 1324. In some embodiments, the forward opening 1324 is located at a distal end of the vacuum inlet 1320, away from the suction channel 1322.

[0347] According to some exemplary embodiments, the vacuum inlet 1320 includes a frame 1326, such as a collapsible frame. In some embodiments, the frame 1326 is formed of a shape memory alloy, such as Nitinol. In some embodiments, the frame 1326 is configured to expand outward from a working channel of a catheter, such as into the left atrium, and collapse into the working channel when the left atrial appendage invagination process is completed. In some embodiments, the frame 1326 is formed by one or more wires that are bent to form the concave shape.

[0348] According to some exemplary embodiments, an inner surface and / or an outer surface of the frame is covered with a sheet, such as sheet 1328. In some embodiments, the sheet is at least partially formed of silicon or polyurethane. In some embodiments, the sheet is at least 80% sealed, such as at least 85% sealed, at least 90% sealed, or any intermediate, lesser or greater percentage to allow vacuum to be applied from the suction channel 1322 through the vacuum inlet 1320. Alternatively, the sheet 1328 is completely sealed.

[0349] According to some exemplary embodiments, a fastener (e.g., a fastener ring 1330) is coupled to the vacuum inlet 1320. In some embodiments, the fastener ring is formed by a wire or a thread. In some embodiments, for example Fig.13AAs shown, the fastener ring 1330 is coupled to the vacuum inlet 1320 by passing the fastener ring 1330 through one or more slits (e.g., slit 1332) in the sheet 1328. The sheet 1328 is at least partially folded over the fastener ring 1330. In some embodiments, the one or more slits in the sheet 1328 through which the fastener ring 1330 passes are shaped and sized to be cut, for example, when the fastener ring 1330 is fastened to allow the fastener ring 1330 to be separated from the vacuum inlet 1220.

[0350] According to some exemplary embodiments, for example Fig. 13B and Fig. 13C As shown, a left atrial appendage remodeler (e.g., left atrial appendage remodeler 1340) is connected to a left atrial appendage remodeler guide, such as guide 1342. In some embodiments, the guide comprises an elongated rod (optionally, a flexible elongated rod). In some embodiments, the left atrial appendage remodeler 1340 comprises a wire, a braided wire, a wire mesh, or a slotted tube, which is shaped to form a closed or an open tubular structure. In some embodiments, the left atrial appendage remodeler 1340 is formed of one or more shape memory alloy wires, such as nitinol. In some embodiments, the left atrial appendage remodeler 1340 is configured to be in a collapsed state within the working channel of the catheter or within the aspiration channel 1222, such as when the catheter is inserted into the left atrium. In addition, the left atrial appendage remodeler 1340 is configured to expand to an expanded state at least partially within the left atrial appendage. In some embodiments, in an expanded state, a maximum dimension of the left atrial appendage remodeler 1340 (e.g., a maximum width 1341 of the left atrial appendage remodeler 1340) is greater than a width of the suction channel, such as the width of the suction channel 1322 or the working channel of the catheter. Fig. 13C As shown, a maximum dimension of the LAA remodeler 1340 is smaller than a width of the opening 1324 of the vacuum inlet 1320, such as to allow the LAA remodeler 1340 to move in and out when the vacuum inlet 1320 is in an expanded state.

[0351] According to some exemplary embodiments, a portion (eg, portion 1343 ) of the guide 1342 passes through the left atrial appendage remodeler 1340 . In some embodiments, a portion (eg, portion 1344 ) of the guide 1342 further extends out of the left atrial appendage remodeler 1340 .

[0352] Exemplary left atrial appendage closure

[0353] Now refer to FIG. 14A to FIG. 14I , FIG. 14A to FIG. 14I Closure of the left atrial appendage according to some exemplary embodiments of the present invention is depicted.

[0354] According to some exemplary embodiments, for example Fig.14A As shown, a catheter (e.g., catheter 1402) of an integrated cavity closure device is introduced into the left atrium 1404. In some embodiments, the catheter 1402 is introduced into the left atrium 1404 transseptally from the right atrium (not shown). In some embodiments, the catheter is advanced into the left atrial appendage 1408 through the left atrial appendage opening 1406, for example, to place the distal opening 1410 of the catheter 1402 within the left atrial appendage 1408. In some embodiments, the distal opening 1410 of the catheter 1402 is inserted to a distance of up to 20 mm from the left atrial appendage opening 1406, for example, up to 15 mm, up to 10 mm, or any intermediate, smaller, or larger value.

[0355] According to some exemplary embodiments, for example Fig. 14B As shown, a left atrial appendage remodeler 1412 is at least partially expanded in the left atrial appendage 1408. In some embodiments, the left atrial appendage remodeler is at least partially expanded in the left atrial appendage opening 1406. In some embodiments, a guide 1414 of the left atrial appendage remodeler 1412 comprises an elongated rod (optionally a flexible elongated rod), and an expandable left atrial appendage remodeler 1412 is provided at a distal end of the guide 1414. In some embodiments, the guide 1414 and the left atrial appendage remodeler 1412 are advanced in an internal working channel of the catheter 1402 to the distal opening 1410 of the catheter 1402.

[0356] According to some exemplary embodiments, the guide 1414 and the LAA remodeler 1412 are advanced through the distal opening 1410 into the LAA 1408. Alternatively or additionally, the catheter 1402 is retracted, for example to expose the LAA remodeler 1412. In some embodiments, the LAA remodeler 1412 is at least partially expanded within the LAA 1408, for example to prevent floating materials and a number of particles from entering the left atrium 1404 from the LAA 1408 through the LAA opening 1406. In some embodiments, the LAA remodeler 1412 is semicircular. Permeable, for example, to prevent blood clots and cell debris from passing but allowing blood to pass between the left atrium 1404 and the LAA 1408.

[0357] According to some exemplary embodiments, the LAA remodeler 1412 comprises one or more openings having a maximum dimension (e.g., a maximum width or a maximum diameter) in the range of 5 μm to 1000 μm, such as 50 μm to 200 μm, 100 μm to 500 μm, 300 μm to 500 μm, 400 μm to 800 μm, 600 μm to 1000 μm, or any intermediate, smaller or larger range of values. In some embodiments, the LAA remodeler 1412 comprises a mesh having a plurality of holes having a maximum dimension, such as a maximum width or a maximum diameter in the range of 5 μm to 1000 μm, such as 50 μm to 200 μm, 100 μm to 500 μm, 300 μm to 500 μm, 400 μm to 800 μm, 600 μm to 1000 μm, or any intermediate, smaller or larger range of values.

[0358] According to some exemplary embodiments, for example Fig. 14C As shown, an elongated suction channel 1418 terminating in a vacuum inlet 1416 is advanced from within the internal working channel of the catheter 1402 and through the distal opening 1410 of the catheter 1402 into the left atrium 1404. In some embodiments, the vacuum inlet 1416 comprises an expandable vacuum inlet configured to expand upon exiting through the distal opening 1410. In some embodiments, the vacuum inlet 1416 expands within the left atrium.

[0359] According to some exemplary embodiments, for example Fig.14D As shown, the vacuum inlet 1416 (e.g., a distal opening of the vacuum inlet 1416 facing the left atrial appendage) is pushed against the left atrium wall around the left atrial appendage opening 1406. In some embodiments, the vacuum inlet 1416 is pushed against the left atrium wall with a force sufficient to form the sealed passage between the suction channel 1418 and the left atrial appendage 1408. In some embodiments, the sealed passage restricts at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 95%, or any intermediate, smaller, or larger percentage) of the passage between the left atrium 1408 and the left atrium 1404.

[0360] According to some exemplary embodiments, a fastener, such as a fastener ring 1426, is coupled to the vacuum inlet 1416. In some embodiments, the fastener ring 1426 is coupled to the vacuum inlet 1416 around the distal opening of the vacuum inlet 1416. In some embodiments, the fastener ring 1426 is coupled to the vacuum inlet 1416 at a distance of up to 20 mm, such as up to 15 mm, up to 10 mm, up to 5 mm, from a contact site between the vacuum inlet 1416 and the left atrium wall.

[0361] According to some exemplary embodiments, for example Fig.14E As shown, vacuum 1411 is applied to the left atrial appendage 1408 through the vacuum inlet 1416. In some embodiments, the vacuum 1411 applies a force of up to 30 Newtons (N), such as up to 10N, up to 15N, up to 20N, up to 25N, up to 30N, or any intermediate, lesser, or greater value on the left atrial appendage tissue. In some embodiments, the applied vacuum causes a collapse, such as an inward collapse of the left atrial appendage. In some embodiments, the vacuum is applied while the vacuum inlet 1416 is in contact with the left atrial wall surrounding the left atrial opening 1406. In some embodiments, the left atrial appendage remodeler 1412 is retracted into the catheter 1402 while the vacuum is applied to the left atrial appendage 1408.

[0362] According to some exemplary embodiments, for example Fig.14F As shown, the applied vacuum causes at least a portion of the left atrial appendage (e.g., portion 1420) to collapse into the vacuum inlet 1416 located in the left atrium 1404. In some embodiments, at least 5%, such as at least 10%, at least 15%, or any intermediate, smaller, or larger percentage range of the left atrial appendage 1408 collapses into the left atrium 1404.

[0363] According to some exemplary embodiments, for example Figure 14GAs shown, a fastener (e.g., the fastener ring 1426 coupled to the vacuum inlet 1416) is positioned around the recessed portion of the left atrial appendage, such as portion 1420. In some embodiments, the fastener is positioned around a bottom of the recessed portion 1420 within the vacuum inlet 1416. In some embodiments, the fastener ring 1426 is fastened around the recessed portion 1420, and the recessed portion 1420 is at least partially within the vacuum inlet 1416. In some embodiments, the fastener (e.g., fastener ring 1426) includes one or more anchors (not shown), such as a hook or a pin, which are shaped and sized to penetrate the recessed portion 1420 of the left atrial appendage. In some embodiments, the one or more anchors are configured to anchor the fastener to the recessed portion. Optionally, the one or more anchors are configured to irreversibly anchor the fastener to the recessed portion of the left atrial appendage. In some embodiments, the fastener is fastened around the invaginated portion by a force that closes the left atrial appendage opening, for example, permanently closing the left atrial appendage opening.

[0364] According to some exemplary embodiments, for example Fig.14H As shown, when fastened around the recessed portion 1420, the fastener (e.g., fastener ring 1426) is decoupled from the vacuum inlet 1416. In some embodiments, when the fastener is anchored to the recessed portion 1420, the fastener is decoupled from the vacuum inlet 1416. Additionally or alternatively, when the suction channel 1418 and the vacuum inlet 1416 are retracted into the working channel of the catheter 1402, the fastener is decoupled from the vacuum inlet 1416.

[0365] According to some exemplary embodiments, for example Fig.14I As shown, the vacuum inlet 1416 collapses and is retracted into the working channel of the catheter 1402. In some embodiments, the vacuum inlet 1416 collapses and is retracted into the working channel of the catheter 1402, while the fastener remains fastened inside the left atrium around the invaginated portion of the left atrial appendage. In some embodiments, once the vacuum inlet 1416 is within the catheter 1402, the catheter is retracted from the patient's heart.

[0366] Exemplary left atrial appendage closure by a remodeler coupled to a ligator

[0367] Now refer to Fig.15 and 16A to 16H , which depicts a process of closing the left atrial appendage by a remodeler coupled to a ligator according to some exemplary embodiments of the present invention.

[0368] According to some exemplary embodiments, at block 302 a catheter is introduced into the left atrium, e.g. Figure 3 As described in.

[0369] According to some exemplary embodiments, at block 1530, a remodeler (e.g., a left atrial appendage remodeler) is inserted into the left atrial appendage through the left atrial appendage opening. In some embodiments, the left atrial appendage remodeler is inserted into the left atrial appendage opening in a collapsed state. In some embodiments, the remodeler is at least partially introduced into the left atrial appendage through the left atrial appendage opening, e.g., a distance of 1 cm, 2 cm, 4 cm, 5 cm, or any intermediate, lesser, or greater distance from the inner wall of the left atrium surrounding the left atrial appendage opening. In some embodiments, the penetration distance of the left atrial appendage remodeler into the left atrial appendage determines the percentage of the remodeled left atrial appendage tissue after invagination. Optionally, the penetration distance is adjusted according to a size and / or shape of the left atrial appendage in a subject.

[0370] According to some exemplary embodiments, and optionally at block 1532, the left atrial appendage is sealed from the outside. In some embodiments, the left atrial appendage is sealed from the outside, for example, by attaching a seal (e.g., a vacuum inlet) to the left atrium wall around the opening of the left atrial appendage. In some embodiments, a vacuum inlet (e.g., the vacuum inlet 420, shown in FIG. 4 ) is attached to the left atrial appendage. Fig. 6A The vacuum inlet 620 and / or Fig. 12A The vacuum inlet 700 shown is several examples of an external seal for the left atrial appendage opening. In some embodiments, the left atrial appendage is sealed by applying a vacuum after attachment of the seal around the left atrial appendage opening. In some embodiments, the vacuum applied by the seal allows, for example, better attachment of the seal to the left atrium wall. In some embodiments, the seal is applied continuously from the outside, for example until at least a portion of the left atrial appendage is invaginated and secured. Alternatively, the vacuum applied by the seal is until the invagination step is complete.

[0371] According to some exemplary embodiments, to create a seal from the outside, a vacuum level of at least 5 mmHg, such as at least 10 mmHg, at least 15 mmHg, or any intermediate, lesser, or greater pressure level, is applied.

[0372] According to some exemplary embodiments, and optionally, the left atrial appendage is sealed from the inside at box 1534. In some embodiments, the left atrial appendage is sealed by placing an inner seal at least partially within the left atrial appendage. In some embodiments, the inner seal is attached to the walls of the left atrial appendage. Additionally or alternatively, the inner seal is attached to the walls of the left atrial appendage opening. In some embodiments, the inner seal is an expandable inner seal configured to expand to contact the walls of the left atrial appendage and / or the walls of the left atrial appendage opening. In some embodiments, the inner seal at box 1530 is the inserted left atrial appendage remodeler.

[0373] According to some exemplary embodiments, the left atrial appendage is at least partially invaginated onto the remodeler at block 1536. In some embodiments, the left atrial appendage is at least partially invaginated into the left atrial appendage remodeler at block 1536. In some embodiments, the left atrial appendage is invaginated by applying a vacuum, such as on the left atrial appendage cavity and / or the plurality of left atrial appendage inner walls. In some embodiments, the left atrial appendage is invaginated by applying a vacuum level of at least 5 mmHg, such as at least 10 mmHg, at least 15 mmHg, or any intermediate, lesser, or greater pressure level.

[0374] In some embodiments, the left atrial appendage is at least partially invaginated into the left atrium. Alternatively, the invaginated left atrial appendage is located outside the left atrium. In some embodiments, the vacuum is applied through the external seal, such as the vacuum inlet positioned outside the left atrial appendage. Alternatively or additionally, the vacuum is applied through the left atrial appendage remodeler at least partially located within the left atrial appendage.

[0375] According to some exemplary embodiments, the invaginated portion of the left atrial appendage is fastened at block 1538. In some embodiments, the invaginated portion of the left atrial appendage is fastened by a fastener coupled (e.g., reversibly coupled) to the left atrial appendage remodeler. In some embodiments, the invaginated portion of the left atrial appendage is fastened, e.g., by collapsing the fastener onto the invaginated portion of the left atrial appendage. Alternatively or additionally, the invaginated portion of the left atrial appendage is fastened, e.g., by constricting the fastener.

[0376] According to some exemplary embodiments, at block 1540, the fastener is optionally disconnected from the remodeler. Alternatively, at block 1538, the fastening step of the LAA disconnects the fastener from the remodeler. In some embodiments, at block 1540, the fastener is disconnected from the remodeler, such as by pulling a string, the string including a tear region configured to tear by application of force (e.g., a region in the string where the string structure is weakened), optionally by a cut that reduces coupling to the fastener.

[0377] According to some exemplary embodiments, at block 1542, the remodeler is withdrawn from the left atrium. In some embodiments, the remodeler is withdrawn into the lumen of the catheter. In some embodiments, the remodeler is withdrawn once the invagination step and / or the securing step are completed. In some embodiments, the remodeler is collapsed to fit into the inner lumen of the catheter.

[0378] According to some exemplary embodiments, at block 1544, the outer seal is optionally retracted. In some embodiments, the outer seal is retracted from the left atrium, such as through the inner lumen of the catheter. In some embodiments, at block 1544, the outer seal is collapsed, such as to fit into the inner lumen of the catheter.

[0379] According to some exemplary embodiments, for example Fig.16A As shown, a catheter 1502 is introduced into the left atrium 1504. In some embodiments, a distal opening 1508 of the catheter, such as an opening at a distal end of the catheter (facing the tissue), is at least partially advanced through the left atrial appendage opening 1506 into the left atrial appendage 1509. In some embodiments, the catheter distal opening 1508 is positioned in the left atrial appendage 1509 or in the left atrial appendage opening 1506 at a location suitable for deploying a left atrial appendage remodeler.

[0380] In some embodiments, the catheter is introduced up to 6 cm into the left atrial appendage, for example up to 5 cm, up to 3 cm, up to 1 cm into the left atrial appendage.

[0381] According to some exemplary embodiments, a diameter or a maximum width of the left atrial appendage opening is up to 6 cm, for example up to 5 cm, up to 3 cm, up to 2 cm or any intermediate, smaller or larger value.

[0382] According to some exemplary embodiments, for example Fig. 16BAs shown, an external seal (e.g., a vacuum inlet 1512) is deployed in the left atrium 1504. In some embodiments, the external seal is advanced through the inner lumen 1503 of the catheter and expanded through the distal opening 1508 of the catheter in the left atrium. In some embodiments, the external seal 1512 is coupled to a proximal passage 1516 that travels through the inner lumen 1503 of the catheter. In some embodiments, the proximal passage and the external seal form a closed and sealed passage, for example to allow a vacuum to be applied. In some embodiments, the proximal passage 1516 is connected to a vacuum source located outside the patient's body.

[0383] According to some exemplary embodiments, for example Fig. 16B As shown, a left atrial appendage remodeler 1510 is at least partially deployed within the left atrial appendage 1508. In some embodiments, the left atrial appendage remodeler 1510 is deployed out from a distal opening of the outer seal 1512, such as from the proximal channel 1516 of the outer seal 1512. In some embodiments, the left atrial appendage remodeler 1510 is at least partially expanded within the left atrial appendage 1508, such as to contact the walls of the left atrial appendage.

[0384] According to some exemplary embodiments, for example Fig. 16C and Fig.16D As shown, the left atrial appendage remodeler 1510 is an expandable left atrial appendage remodeler formed by a mesh. In some embodiments, the mesh is formed by one or more wires. In some embodiments, the left atrial appendage remodeler 1510 has a cylindrical shape, which has a wide distal opening 1511 configured to face the left atrial appendage and be positioned away from the catheter in an expanded state and a proximal narrower proximal opening 1513 connected to a remodeler guide 1516, which travels within the lumen of the catheter. Optionally, the remodeler guide 1516 is located within the channel of the external seal 1512.

[0385] According to some exemplary embodiments, the outer surface and / or the inner surface of the left atrial appendage remodeler 1510 is at least partially coated, for example, with a sheet or a film. In some embodiments, the remodeler 1510 is coated to form an at least partially sealed path between the remodeler channel 1511 and the left atrial appendage 1509. In some embodiments, the remodeler coating is made of polyurethane, expanded polytetrafluoroethylene (ePTFE), nylon, or any type of coating or film.

[0386] According to some exemplary embodiments, for example Fig.16D In some embodiments, a fastener 1518 is coupled (e.g., reversibly coupled) to the left atrial appendage remodeler 1510. In some embodiments, the fastener 1518 is coupled to the outer surface of the remodeler 1510. Alternatively, the fastener 1518 is coupled to the inner surface of the left atrial appendage remodeler 1510. In some embodiments, the fastener 1518 is coupled to the left atrial appendage remodeler 1510, for example, around the distal opening 1511. Alternatively, the fastener 1518 is coupled to the left atrial appendage remodeler 1510, for example, along the circumference of the left atrial appendage remodeler 1510. In some embodiments, the fastener 1518 is coupled to the remodeler 1510 at a distance of up to 6 cm, for example, up to 5 cm, up to 3 cm, or any intermediate, smaller or larger distance from the distal opening 1511. In some embodiments, the fastener 1518 comprises a lariat, a lasso, or a clamp.

[0387] According to some exemplary embodiments, for example Fig.16D As shown, the fastener 1518 is coupled to a fastener manipulator (e.g., fastener actuator 1520) via a releasable coupling portion 1519. In some embodiments, the fastener actuator 1520 includes a string, and the releasable coupling portion 1519 includes a tear region 1520 between the fastener actuator and the fastener 1518.

[0388] According to some exemplary embodiments, for example Fig.16E As shown, once the left atrial appendage remodeler 1510 is at least partially positioned within the left atrial appendage 1508, a vacuum is applied to the left atrial appendage 1518 through the distal opening 1511 of the remodeler 1510. In some embodiments, the vacuum is applied through the channel of the outer seal 1512, such as the vacuum inlet connected to the left atrium wall. Alternatively or additionally, the vacuum is applied through the channel of the remodeler 1510. Fig.16F As shown, the applied vacuum causes the left atrial appendage 1508 to shrink in volume.

[0389] According to some exemplary embodiments, for example Figure 16G As shown, at least a portion of the left atrial appendage 1508 is recessed into the remodeler 1510. Alternatively or additionally, the at least a portion of the left atrial appendage 1508 is recessed onto an inner surface of the left atrial appendage remodeler 1510. In some embodiments, the at least a portion of the left atrial appendage 1508 is at least partially recessed into the left atrium. In some embodiments, the at least a portion of the left atrial appendage 1508 is recessed near the fastener 1518 coupled to the remodeler 1510.

[0390] According to some exemplary embodiments, for example Figure 16G In some embodiments, the penetration distance 1521 of the remodeler 1510 into the left atrial appendage 1508 determines the size of the left atrial appendage portion invaginated onto the remodeler 1510. In some embodiments, the penetration distance 1521 is a minimum distance between the distal remodeler opening and the left atrial wall around the left atrial appendage opening. In some embodiments, the penetration distance 1521 is adjusted according to at least one of the left atrial appendage shape, the left atrial appendage volume, the left atrial appendage opening width or diameter.

[0391] According to some exemplary embodiments, the fastener comprises a roeder knot, such as described in JJ Hage, Surg Laparosc Endosc Percutan Tech, 2008 Feb; 18(1): 1-7, allowing for tightening of the fastener, such as around the recessed portion of the left atrial appendage.

[0392] According to some exemplary embodiments, for example Fig.16H As shown, the fastening step of the fastener 1518 around the invaginated left atrial appendage causes the fastener 1518 to be separated from the remodeler 1510. In some embodiments, after fastening the fastener 1518 around the invaginated left atrial appendage portion, the fastener 1518 is disconnected from the fastener actuator 1520. In some embodiments, the fastener actuator 1520 disconnects from the fastener by applying a force on the releasable coupling portion 1519, which causes, for example, tearing of the tear region of the releasable coupling portion 519. Alternatively, the fastener actuator 1520 and / or the fastener 1518 includes a cutting mechanism, such as a SureCUT TM Suture cutter.

[0393] It is expected that during the period of expiration of the patent applied for herein, many related vacuum inlets and fasteners will be developed; the scope of the term vacuum inlet and fastener is intended to include all such a priori new technologies.

[0394] As used herein, with respect to quantities or values, the term "about" means "within ±10%."

[0395] The terms "including", "comprising", "having" and their conjugated words mean "including but not limited to".

[0396] The term "consisting of" means "including and limited to."

[0397] The term "consisting essentially of" means that the composition, method or structure may include additional ingredients, steps and / or parts, but the additional ingredients, steps and / or parts do not materially change the essential and novel characteristics of the claimed composition, method or structure.

[0398] 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" may include a plurality of compounds, including mixtures thereof.

[0399] Throughout this application, embodiments of the present invention may be presented with reference to a range format. It should be understood that the description of the range format is only for convenience and brevity and should not be construed as an inflexible limitation on the scope of the present invention. Therefore, the description of a range should be considered to have specifically disclosed all possible sub-ranges and each numerical value within the range. For example, the description of a range such as "from 1 to 6" should be considered to have explicitly disclosed "from 1 to 3", "from 1 to 4", "from 1 to 5", "from 2 to 4", "from 2 to 6", "from 3 to 6", etc.; and single numbers (e.g., 1, 2, 3, 4, 5, and 6) within the range. This applies regardless of the width of the range.

[0400] Whenever a numerical range is indicated herein (e.g., "10-15," "10 to 15," or any pair of numbers linked by such another such range indication), any numerical (fractional or integer) indicated range limits (including such range limits) are meant to be included within the range unless the context clearly dictates otherwise. The phrases "range / ranging / ranges between" a first indicated number and a second indicated number, "from" a first indicated number "to / up to / until / to" (or another such range indicating term) a second indicated number are used interchangeably herein and are intended to include the first and second indicated numbers and all decimals and integers therebetween.

[0401] Unless otherwise indicated, the numbers used herein and any numerical ranges based thereon are approximations within reasonable measurement precision and rounding error as understood by those skilled in the art.

[0402] As used herein, the term "method" refers to ways, means, techniques and procedures for accomplishing a given task, including but not limited to those ways, means, techniques and procedures that are known or readily developed from known ways, means, techniques and procedures employed by practitioners in the fields of chemistry, pharmacology, biology, biochemistry and medicine.

[0403] As used herein, the term "treating" includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetic symptoms of a condition, or substantially preventing the appearance of clinical or aesthetic symptoms of a condition.

[0404] It should be understood that, for the sake of clarity, certain features of the invention described in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, for the sake of brevity, various features of the invention described in the context of a single embodiment may also be provided individually or in any suitable sub-combination or suitable for any other described embodiment of the invention. Certain features described in the context of various embodiments should not be considered essential features of those embodiments, unless the embodiment is invalid without these elements.

[0405] Although the present invention has been described in conjunction with its specific embodiments, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Therefore, it is intended to encompass all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

[0406] All publications, patents and patent applications mentioned in this specification are hereby incorporated by reference in their entirety into this specification, to the extent that each individual publication, patent or patent application is specifically and individually indicated to be incorporated by reference herein. In addition, the citation or identification of any reference in this application should not be construed as an admission that such reference can be used as prior art of the present invention. With respect to the use of section headings, they should not be construed as necessarily limiting. In addition, any priority document of the present application is hereby incorporated by reference in its entirety herein.

Claims

1. A device with an expandable inlet for isolating a left atrial appendage (LAA) from a left atrium (LA), characterized in that: The device comprises: a passageway terminating in an expandable inlet, wherein the passageway is shaped and sized to pass within a working channel of a catheter and to deliver a vacuum, wherein the expandable inlet comprises an expandable structure having a distal opening, wherein the distal opening is shaped and sized to be positioned around an opening of a left atrial appendage, wherein the expandable structure is configured to be in a collapsed state within the working channel of the catheter, to expand when exiting the working channel into the left atrium, and to be positioned around the opening of the left atrial appendage in contact with a wall of the left atrium to isolate the left atrial appendage from the left atrium, wherein the maximum width of the expandable inlet is in a range of 10 mm to 50 mm; and A closable fastener ring is coupled to an inner surface of the expandable structure surrounding the distal opening, the expandable structure surrounding the distal opening, wherein the closable fastener ring is configured to close and release from the expandable access port.

2. The device according to claim 1, characterized in that An edge of the expandable access port surrounding the distal opening and configured to contact the wall of the left atrium is flexible.

3. The device according to claim 1, characterized in that The expandable structure includes an expandable mesh frame coated with a coating, wherein the fastener ring is coupled to the expandable mesh frame and / or the coating.

4. The device according to claim 3, characterized in that The expandable mesh frame is made of one or more shape memory alloy wires coated with the coating.

5. The device according to claim 4, characterized in that The fastener ring is coupled to the inner surface of the expandable structure at a distance of at least 1 mm from a circumferential edge portion of the expandable structure, the circumferential edge portion being configured to contact the wall of the left atrium.

6. The device according to claim 1, characterized in that When expanded, the expandable structure has a cup-like or cone-like shape.

7. A device as claimed in any one of the preceding claims, characterised in that The channel is a vacuum channel configured to apply a vacuum through the expandable inlet.

8. A device with an expandable inlet, characterized in that: The device comprises: a passageway terminating in an expandable inlet, wherein the passageway is shaped and sized to pass within a working channel of a catheter, wherein the expandable inlet comprises an expandable structure having a distal opening shaped and sized to be positioned about an opening of a left atrial appendage, wherein the expandable structure is configured to be in a collapsed state within the working channel of the catheter and to expand upon exiting the working channel into the left atrium and contacting a wall of the left atrium, wherein the expandable inlet has a maximum width in a range of 10 mm to 50 mm when expanded; and A closeable fastener ring is coupled to the expandable structure.

9. The device according to claim 8, characterized in that The device further includes an elongated fastener manipulator shaped and dimensioned to pass within the working channel and connectable to the fastener ring, wherein rotation, tightening and / or advancement of the elongated fastener manipulator closes the closable fastener ring.

10. The device according to claim 8, characterized in that The closable fastener ring is coupled to an inner surface of the expandable structure and is configured to be released from the expandable structure when closed.

11. The device according to claim 8, characterized in that An edge of the expandable access port surrounding the distal opening and configured to contact the wall of the left atrium is flexible.

12. The device according to claim 8, characterized in that The expandable structure includes an expandable mesh frame coated with a coating, wherein the fastener ring is coupled to the expandable mesh frame and / or the coating.

13. The device according to claim 12, characterized in that The expandable mesh frame is made of one or more shape memory alloy wires coated with the coating.

14. The device according to claim 8, characterized in that The channel is configured for conveying a vacuum.

15. The device according to any one of claims 8 to 14, characterized in that The closeable fastener ring is coupled to the expandable structure at a distance of up to 20 mm from an edge of the expandable access port, the expandable access port being configured to contact the wall of the left atrium.

16. A system, characterized in that: The system comprises: an expandable structure shaped and sized to extend at least partially into the left atrial appendage from within an opening of a catheter working channel through an opening of the left atrial appendage, wherein the expandable structure is configured to expand within the left atrial appendage and contact a wall of the left atrial appendage while applying a radial force for anchoring an outer surface of the expandable structure to the wall of the left atrial appendage; and A suction channel passes through the working channel and terminates in a vacuum inlet that can extend from the working channel, the vacuum inlet including a distal opening and configured to apply a vacuum to the left atrial appendage through the distal opening when the expandable structure contacts the wall of the left atrial appendage.

17. The system of claim 16, wherein: The expandable structure is introduced into the left atrial appendage to a distance of 1 mm to 50 mm from the opening of the left atrial appendage in the left atrium.

18. The system of claim 16, wherein: The vacuum inlet applies a vacuum with a force sufficient to cause at least a portion of the left atrial appendage to collapse into the expandable structure of the left atrial appendage.

19. The system of claim 16, wherein: The vacuum inlet comprises an expandable mesh frame coated with a coating, and wherein the vacuum inlet is configured to contact a left atrial wall around the opening of the left atrial appendage, wherein a width of the distal opening of the vacuum inlet is greater than a width of the opening of the left atrial appendage.

20. The system according to any one of claims 16 to 19, characterized in that The expandable structure includes one or more anchors configured to penetrate the wall of the left atrial appendage when the expandable structure is expanded within the left atrial appendage.

Images