Patent Description:
The left atrial appendage is reported to become a risk for heart thrombosis in <NUM>% cases for patients with non-rheumatoid atrial fibrillation (AF) and in <NUM>% cases for patients with rheumatic heart diseases.

<NUM>% to <NUM>% of AF patients over <NUM> years of age suffer from thromboembolic strokes annually, which represents a major economic problem for the health care system and society as a whole.

For the prevention of cardiogenic thromboembolism in AF patients, operations are made to isolate the left atrium orifice, both in the open heart and thoracoscopically using endovideosurgical techniques.

For LAA isolation, a number of different clip designs are used with appropriate delivery systems, e.g., a loop-shaped clip [<CIT>] or a stapled seam using stitching machines [<CIT>]. The use of a loop and stitching machine to isolate the left atrial appendage from the left atrium features several disadvantages. When a loop is applied, LAA wall corrugates, the loop fails to be placed at the appendage base, but more distal from LAA base, which serves a background for thrombosis.

When using stitching devices, microbleeds occur along the suture line, requiring the evacuation of blood residues by suction. Foci of micronecrosis and microthrombus are often identified in the sewn suture line area. When stitching, the left atrial appendage tissue is crushed by the stitching machine, which sometimes leads to LAA self-amputation, accompanied by life-threatening bleeding.

Also well-known are designs of LAA isolation clips in the form of a bifurcated plug, made to push the device onto the indicated LAA base from the open side and to clamp it with an additional component, which is also pulled outwardly [<CIT>], [<CIT>], [<CIT>]. The disadvantage of this kind of device is the unevenness of LAA base isolation, possible partial "slipping" of LAA tissue from the open side of the clip.

The frame-shaped designs feature no disadvantages of the one-sided clip design [<CIT>], [<CIT>], [<CIT>]. Such designs require stitching to delivery devices and removal of the threads following the device application to LAA base or the manipulation of the device with surgical forceps or the hands of the surgeon for delivery, which makes the surgery process more complicated and increases the risk of injury during the operation.

The most similar technology for both the LAA isolation system and LAA isolation clip device is given in [<CIT>]. The known technical solution includes a clip device for LAA isolation, formed by first and second jaws, designed so that they are parallel in the closed position and overlap each other in length, and spring elements installed between the first ends of the first and second jaws and between the second ends of the first and second jaws, which are designed to move the first and second jaws from the diverged position to the clamping position and to hold the first and second jaws in the clamped position. The known technical solution also incorporates a control device configured to install the clip device so that LAA is positioned between the first and second jaws by using the frame to which the clip is attached, previously placed to the diverged position. To turn to the clamped position, the threads should be removed, then, under the action of spring elements, the jaws move to the clamped position, pressing the left atrial appendage base.

The disadvantages of this technical solution is, firstly, the sharp changeover (with a blow) of the first and second jaws from the diverged position to the clamped position under the action of spring elements, which can lead to LAA tissue injury and even to its amputation, and, secondly, unregulated force of compression of the jaws on LAA base, which can lead to LAA tissue necrosis and inflammatory processes.

This invention is aimed to create a system for left atrial appendage isolation with clip therefor to ensure a smooth and shockless effect of changeover of the first and second jaws from the diverged position to the clamped position with the control option of the impact force upon closing, as well as to mitigate the impact of the clamped position over time.

The set objective for the left atrial appendage isolation system, which incorporates a clip device formed by first and second jaws, designed so that they are parallel in the closed position and overlap each other in length, and clamping element installed between the first ends of the first and second jaws and between the second ends of the first and second jaws, which are designed to move the first and second jaws from the diverged position to the clamping position and to hold the first and second jaws in the clamped position, as well as configured to install the clip device so that LAA is positioned between the first and second jaws, is solved by equipping the clip with a connecting device, wherein the clamping element is designed to contain the first hinge, and the connecting device comprises the second hinge, the first and second hinges being connected to the corresponding ends of the first jaw and are designed to rotate the specified first jaw relative to the second jaw made fixed, at an angle ranging <NUM>° to <NUM>°, while the first hinge is made controllable and the control device comprises the first hinge actuator adapted to couple detachably with tension to fit with the said first hinge.

Preferably, the first and second ends of the second jaw are rigidly fixed in the clamping element and connecting device, respectively.

Each of the first and second jaws can have Π-shaped design, preferably made of a biocompatible metal coated with porous polytetrafluoroethylene.

The clamping element may comprise a collet on the first hinge, as well as a threaded lock nut mounted on the axis of the first hinge and configured to clamp the collet to avoid the relief motion, while the control device in such case is made with a second actuator configured to be detachable with the specified threaded lock nut.

The first actuator of the control device can be made in the form of a first elongated cylindrical element for applying rotational motion to said first hinge with controlled rotation of the first jaw relative to the second jaw, and the second actuator of the control device can be made in the form of a second elongated cylindrical element as a concentric tube installed over the first elongated cylindrical element to apply rotational motion on the specified threaded lock nut.

The first and second actuators of the control device can be equipped with first and second levers fixed at <NUM>° angle, respectively, each shaped as a torque arm, with an option of controlled rotation of the respective actuator.

The first and second tubes of the actuators of the control device can be curved.

The set objective of the clip device for the left atrial appendage isolation formed by first and second jaws, designed so that they are parallel in the closed position and overlap each other in length, and clamping element installed between the first ends of the first and second jaws, which is designed to move the first and second jaws from the diverged position to the clamping position and to hold the first and second jaws in the clamped position, is solved by equipping the clip with a connecting device, wherein the clamping element is designed to contain the first hinge, and the connecting device comprises the second hinge, the first and second hinges being connected to the corresponding ends of the first jaw and are designed to rotate the specified first jaw relative to the second jaw made fixed, at an angle ranging <NUM>° to <NUM>°, while the first hinge is made controllable.

The clamping element may integrate a collet on the first hinge, as well as a threaded lock nut mounted on the axis of the first hinge and configured to clamp the collet to avoid the relief motion.

The essence of the claimed invention is explained in detail at the following non-restrictive drawings, where:.

The system for LAA isolation, shown at <FIG> and <FIG>, contains a clip device <NUM>, formed by the first <NUM> and second <NUM> jaws, made Π-shaped, as an example, so that they are parallel and overlap in length in their closed position (see <FIG>), and the control device.

Clip device <NUM>, shown enlarged at <FIG>, contains a clamping element <NUM> with first hinge <NUM>, as well as a connecting device <NUM>. The clamping element <NUM> is connected with the first ends of the first <NUM> and second <NUM> jaws so that the first end of the first jaw <NUM> is connected with the first hinge <NUM> installed in the housing <NUM> of the clamping element <NUM> to rotate the first jaw <NUM> relative to the second jaw <NUM> at an angle ranging <NUM>° to <NUM>°, while the first end of the second jaw <NUM> is rigidly fixed in the housing <NUM> of the clamping element <NUM>. The second end of the first jaw <NUM> is connected to the second hinge <NUM> installed in the housing of the connecting device <NUM> so that the first jaw <NUM> can be rotated relative to the second jaw <NUM> at an angle ranging <NUM>° to <NUM>°, while the second end of the second jaw <NUM> is rigidly fixed in the housing of the connecting device <NUM>.

The clamping element <NUM> comprises a collet <NUM> located on the first hinge <NUM>. As shown in <FIG>, <FIG>, the clamping element <NUM> is equipped with a threaded lock hexagonal nut <NUM> (see <FIG>) made to move along the thread (not shown at the drawings) in the housing <NUM> of the clamping element <NUM> for fixing the collet <NUM>.

The first <NUM> and second <NUM> jaws are made of a biocompatible metal, e.g. titanium, with a porous PTFE coating <NUM>, as schematically shown in <FIG>.

The control device <NUM> (see <FIG>, <FIG>, <FIG>) comprises the first actuator and the second actuator. The first actuator of the control device <NUM> is shaped as a first elongated cylindrical element, e.g., the first tube <NUM> with a lever <NUM> attached at <NUM>° angle for applying torque to said first hinge. The first elongated cylindrical element of the first actuator can also be made in the form of a rod. The second actuator of the control device <NUM> is made in the form of a second tube <NUM> with a lever <NUM> fixed at <NUM>° angle for applying torque to the said threaded lock nut <NUM>. Levers <NUM> and <NUM> are each shaped as a torque arm, with an option of controlled rotation of the respective actuator (in the present example).

The proximal end <NUM> of the first tube <NUM> is made (in the present example) with a square cross-section, which can be detachably connected to the axis <NUM> of the first hinge <NUM>, due to the tension created by the geometrical parameters of the proximal end <NUM>, allowing both to hold the clip device <NUM> on the control device <NUM> and to disconnect, using the allowable force, with the control actuator, leaving the fixed clip device <NUM> on the body of the left atrium appendage <NUM>.

The claimed system and clip device function as follows.

During the operation, prior to the application of the clip device, the control device <NUM> and the clip device <NUM> are taken from the sterile package. The control device <NUM> is attached to the clip device <NUM>. For this purpose, the square cross-section proximal end <NUM> is fitted with an overpressure into the matching orifice, made in the longitudinal direction in the axis <NUM> of the first hinge <NUM>. At the same time, the proximal end of the second tube <NUM> of the control device's second actuator is mounted on the nut <NUM>.

The convergence of the clip device's jaws <NUM> and <NUM> is performed gradually and with a controlled effort, not exceeding the allowable limits, thus avoiding the traumatic clamping of LAA body <NUM> with the jaws. For a gradual convergence of the jaws <NUM> and <NUM>, a step mechanism is provided, made (in the present example) in the form of a ratchet - see <FIG>, represented by a wheel <NUM> with cut-out grooves <NUM> with a large pitch for positioning the jaws on LAA and small grooves <NUM> for micro-movements when clamping the jaws, as well as a tooth <NUM> to lock the mechanism when it hits the grooves <NUM> or <NUM>.

The claimed clip device <NUM> can be clamped / decompressed for exact positioning and fixing of the clip jaws on LAA body - see <FIG>.

Upon reaching the necessary clamping force of the jaws <NUM> and <NUM> on the appendage <NUM>, the jaws are fixed in their position.

For a strong fixation of the jaws <NUM> and <NUM> position relative to each other, as well as to avoid their release, the device uses the collet <NUM>, tightened by the nut <NUM> (<FIG>, <FIG>). By actuating the lever <NUM> of the second actuator of the control device <NUM>, the rotation of the second tube <NUM> is imparted to transmit the torque to the said threaded lock nut <NUM>. The nut <NUM> moves along the thread (not shown on the figures) inside the housing <NUM> of the element <NUM>, advances on the collet <NUM>, pressing it to the axis <NUM> and fixing the axis <NUM> of the hinge <NUM>, and, therefore, avoiding the jaw <NUM> rotation. Since the thread on the nut <NUM> and the housing <NUM> are made with a locking feature, as shown in <FIG>, the back motion of the nut is prevented, and any release of the installed clip device <NUM> is also avoided.

After fixing the clip device <NUM>, the proximal end <NUM> is withdrawn from the hole in the axis <NUM> by force action on the lever <NUM> of the control device <NUM> and moving in the distal direction, and then, by moving the entire control device in the distal direction, the second tube <NUM> is withdrawn from the nut <NUM>, and the control device is removed from the surgical field.

The following processes and methods are to be understood only as means to better understand the invention and are not within the scope of the appended claims.

Following the cardiopulmonary bypass and cardioplegic cardiac arrest during open-heart surgery via sternotomy, enucleation and heart (left ventricle) rotation to the right shall be made for proper visualization of the appendage <NUM> (see <FIG>). The clip device <NUM> is supplied in the full (sufficiently) open position (see <FIG>, <FIG> and <FIG>), positioned and closed so that the jaws <NUM> and <NUM> are located at the appendage <NUM> base (see <FIG>).

The clamping position control shall be effected by using transesophageal echocardiography.

Minithoracotomy or thoracoscopy is performed is such case. For thoracoscopy, a special endoscopic instrument shall be used for opening the pericardium, three thoracoports are to be made in the left half of the chest:.

The pericardium shall be opened <NUM> below the phrenic nerve under the video control. The pericardium shall be taken by the holders and pulled apart for better access to the appendage <NUM>.

The control device <NUM> with the clip device <NUM>, preferably in the fully clamped position (see <FIG>), shall be supplied through the lower thoracoport. By turning the first tube <NUM> under the actuation of the lever <NUM>, the jaw <NUM> shall be taken aside from the jaw <NUM> to allow the required opening, up to <NUM>°, preferably <NUM>°.

No special tool-based manipulations are needed for the clip device <NUM> placement on the appendage <NUM> body, since the clip device <NUM> passes freely through the top of the appendage <NUM>, and the gradual convergence of the jaw <NUM> to the jaw <NUM> (by turning the first tube <NUM> under the action of the lever <NUM> with controlled force) makes it possible to arrange the jaws <NUM> and <NUM> close to the appendage <NUM> base without any contact with the surrounding tissues and structures.

The clip device <NUM> placement and clamping is controlled by transesophageal Echo-CG.

The clip device <NUM> of the claimed design can be placed to the appendage <NUM> (including a thrombus-affected one), if the thrombus does not extend from LAA into the cavity of the left atrium beyond the jaws and does not exceed their width.

Should the initial implantation of the clip device <NUM> fail (see <FIG>), it is possible to reposition the clip device <NUM> numerously. After the clip device <NUM> has been positioned properly (see <FIG>), the fixation process is performed. The use of a torque actuator makes it possible to avoid pinching the appendage body, which may otherwise result in soft tissue necrosis.

For fixing the clip device <NUM>, the second tube <NUM> of the control device <NUM> shall be rotated, thus allowing the threaded lock nut <NUM> to advance along the thread (not shown on the figures) inside the housing <NUM> of the clamping element until the collet <NUM> fixed on the first hinge <NUM> is locked. The thread (e.g. <FIG>) prevents from motions in the direction opposite to winding, thus, the rotation of the first hinge <NUM>, and, consequently, the retraction of the first jaw <NUM> from the second jaw <NUM> is prevented following the implantation of the clip device <NUM>.

Then, the control device <NUM> shall be removed. For this purpose, the proximal end <NUM> of the first tube <NUM> is distally moved out of the hole in the axis <NUM>, and then, by moving the entire control device in the distal direction, the second tube <NUM> is withdrawn from the nut <NUM>, releasing the clip device <NUM> fixed on LAA body <NUM> - see <FIG>. Then, the control device <NUM> can be removed from the thoracoport.

The clip device <NUM> remains fitted to the appendage <NUM> base (see <FIG>, <FIG>). Due to the phenomenon of PTFE recrystallization following the clamping of the clip device <NUM> jaws on LAA <NUM> benefits to the load relief on LAA tissue.

Polytetrafluoroethylene is a well-known material, used for many applications for a long time [<NPL>]. This aforesaid property of this material is also known as "cold flow under load", "creep" (same reference, p. <NUM>) or "pseudo flow" [<NPL>]. This means that, even under minor mechanical loads at room temperature, a product made of PTFE is subject to recrystallization process, followed by internal deformations. Within <NUM>-<NUM> hours, polytetrafluoroethylene in contact with LAA tissue is deformed due to recrystallization, its thickness decreases, and the pressure on LAA surface decreases abruptly, with LAA isolation being preserved. The blood circulation in the LAA surface layer is fully restored, thus reducing the risk of infection, necrosis.

Then, LAA tissue penetrates inside the porous PTFE coating <NUM> of jaws <NUM>, <NUM> of the clip device <NUM>, thus forming a permanent connection and ensuring the reliability and durability of the left atrial appendage isolation.

<NUM> dogs weighing <NUM> and <NUM>. Premedication given on the operating table.

Operation process: The dog was laid on the right side, with its forelimbs placed apart and fixed. The operating field was treated by iodonates. In the <NUM>th intercostal space, a lateral thoracotomy of about <NUM> was performed. The lung was set aside with a special hook for accessing the pericardium.

The pericardium was opened by a T-shaped incision and taken on the handles. The left atrial appendage was visualized directly in the surgical wound. Using the grip, the appendage was inserted into the clip device <NUM>, the latter was positioned at LAA base and fixed by controlled compression until the blood flow stopped (the appendage's apical part was cut to control the blood flow cessation).

No heart rhythm disturbances were noted (ECG control). The pericardial cavity was sutured. No drainage of cavities was made. The layer-by-layer wound closure with the left lung reexpansion was performed to avoid pneumothorax.

The implant was clearly visualized at LAA. The clip device <NUM> was made of titanium and covered with porous PTFE coating <NUM> (X-ray picture - see <FIG>). The hematology analysis made it possible to assess the post-operation recovery dynamics.

An increase in band neutrophils and monocytes after <NUM> month post-operation evidenced that the tissue repair processes were accompanied by activation of the body protective functions. The eosinophil count normalized by the <NUM>th week, evidencing no allergic reactions, which is an important prognostic indicator of the implant survival rate. The placement of implants did not affect the platelet count in the dog's blood.

The sampling of heart tissues to study the peculiarities of the implant-surrounding tissue formation was made approximately <NUM> months following the operation, upon reaching normal hematological parameters.

The activity of enzymes characterizing the metabolic activity of cells, i.e. succinate and lactate dehydrogenase (SDH and LDH), was determined by Lloyd's method. The enzyme activity was estimated by the optical density of the reaction product in the cytoplasm of cells (formazan) using Image J data processing software. Microscopic examination, morphometry and microphotography were carried out using an MPV-<NUM> light microscope with integrated software and computer (manufactured by Leitz, Germany ).

The detection of AChE-positive nerve fibers in the myocardium was performed according to Karnovsky-Roots method, as modified by El-Badawi and Schenk. The final product of the reaction, which occurs with acetylcholinesterase enzyme participation, was determined in the form of copper ferrocyanide precipitates, which stain cholinergic nerve formations - nerve fibers and endings - in brown.

The detection of LDH and SDH enzymes was performed in cardiac myocytes of the atrial appendage and cardiomyocytes penetrating into porous PTFE coating of the clip jaws. The presence of enzymes in the myocardium was evidenced by a dark blue precipitate of formazan formed during the recovery of tetrazolium salts and localized in the sarcoplasm of cardiomyocytes (mainly localized in inner mitochondrial membrane and outgoing cristae, sarcoplasmic reticulum).

<FIG> shows micrographs characterizing the activity of lactate dehydrogenase detected in the sarcoplasm of cardiomyocytes germinating from LAA into porous PTFE coating of the clip jaws (a) and in the sarcoplasm of cardiomyocytes of the intact atrial appendage (b). Magnification x400.

Mean LDH activity in LAA cardiomyocytes = <NUM> ± <NUM> IU, which is significantly different from LDH activity of cardiomyocytes germinating in porous PTFE, mean value = <NUM> ± <NUM> IU.

The decrease in LDH activity in cardiomyocytes germinating in porous PTFE, as compared with that of LAA cardiomyocytes, indicates a weakening intensity of the energy processes occurring in the myocardium under these conditions.

<FIG> shows micrographs characterizing the activity of succinate dehydrogenase detected in the sarcoplasm of cardiomyocytes germinating from LAA into porous PTFE coating of the clip jaws (a) and in the sarcoplasm of cardiomyocytes of the intact atrial appendage (b). Magnification x400.

Mean SDH activity in cardiomyocytes germinating in porous PTFE = <NUM> ± <NUM> IU, which is significantly different from SDH activity of cardiomyocytes of intact LAA tissue, mean value = <NUM> ± <NUM> IU.

A significant decrease in SDH activity in cardiomyocytes germinating in porous PTFE, as compared with that in LAA cardiomyocytes, indicates the inhibition of metabolic processes in the cardiac muscle, which are responsible for its energy supply under the test conditions. When analyzing the changes in LDH and LDH mean activity in cardiac myocytes of the intact atrial appendage and in cardiomyocytes germinating in porous PTFE, it can be clearly found that SDH activity in cardiomyocytes in all considered cases was significantly lower than LDH activity, which serves the manifestation of a lower metabolic activity of this enzyme in LAA cardiomyocytes. Lower values of SDH activity were reported in cardiomyocytes germinating in porous PTFE, which indicates a depressed functional activity of myocardium in this area.

<FIG> shows micrographs characterizing AChE-positive nerve fibers in LAA myocardium, germinating in porous PTFE, Magnification x400 (a), and AChE-positive nerve fibers in the intact atrial tissue, Magnification x400.

<FIG> shows micrographs characterizing the germination of LAA muscle fibers in porous PTFE. MF - muscle fiber. Staining by hematoxylin-eosin. Magnification x250.

<FIG> shows micrographs characterizing (a) the germination of cardiomyocytes from the ear of the atrium in the porous PTFE (CMC - cardiomyocyte. Staining by hematoxylin-eosin. Magnification x250) and (b) myocardial architectonics of intact LAA tissue (CMC - cardiomyocyte. Staining by hematoxylin-eosin. Magnification x250).

Reference to the histological and histochemical studies of the atrial appendage with an implanted clip covered with porous PTFE, it can be concluded that:.

Claim 1:
A clip device (<NUM>) for left atrial appendage (<NUM>) isolation, formed by first (<NUM>) and second (<NUM>) jaws, designed so that they are parallel in a closed position and overlap each other in length, and a clamping element (<NUM>) installed between the first ends of the first (<NUM>) and second (<NUM>) jaws, which is designed to hold the first (<NUM>) and second (<NUM>) jaws in a clamped position, wherein the clip device (<NUM>) is equipped with a connecting device (<NUM>), wherein the clamping element (<NUM>) is designed to contain a first hinge (<NUM>), and the connecting device (<NUM>) comprises a second hinge (<NUM>), the first (<NUM>) and second (<NUM>) hinges being connected to the corresponding ends of the first jaw (<NUM>), characterized in that the clamping element is further designed to move the first (<NUM>) and second (<NUM>) jaws from a diverged position to the clamped position and to rotate the specified first jaw (<NUM>) relative to the second jaw (<NUM>) made fixed, at an angle ranging <NUM>° to <NUM>°, while the first hinge (<NUM>) is made controllable.