WO2016155847A1 - Modular occlusion device for closing the left atrial appendage (laa) and production thereof - Google Patents

Abstract

The invention relates to a modular intravascular closure devices (1) for treating defects in the heart of a patient, in particular for closing the left atrial appendage (5), wherein the occlusion instrument (1) is composed of at least two modular units (21), wherein the proximal modular unit (cover) (2) closes the atrial appendage inlet (6) from the left atrium (4) and at least one distal modular unit (main body) (3) is positioned in the retaining region of the atrial appendage (5) and is firmly anchored in the atrial appendage (5) by means of corresponding hooks (26). The cover (2) and the main body (3) are produced predominantly by means of a suitable laser machining method. Materials used are metal or metal alloys such as nitinol or from non-resorbable plastics selected from the group of the polyesters, polyamides, polyolefins, polyurethanes and polyhalogenolefins, or bioresorbable polymers as polyesters such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and other polyesters, polyanhydrides and polyamino acids having cleavable bonds such as amide, ester, or acetal bonds, and both the lasered casing (33) and the patches (25) have a degradation duration between 5 and 50 weeks.

Description

 Modular occlusion device for closure of the left atrial appendage (LAA) and its production

description

The present invention relates to a flexible modular intravascular occlusion device (occlusion device, occluder) for the interventional closure of the left atrial appendage. LAA stands for left atrial appendage, a German left atrial appendage, and a manufacturing process for such an occlusion device.

Usually, a common occlusion device is brought into a defined starting shape by means of transformation and heat treatment and introduced into the cardiovascular system through a catheter or a sluice. The catheter or sluice introduced from the right groin vein into the right atrium is transseptically punctured of the atrial septum into the left atrium of the heart. The corresponding occlusion device is first drawn or loaded into the same from the distal end of a short sluice (loader, to German loader) by means of a corresponding insertion wire or insertion system, whereby the occlusion instrument assumes an elongate shape, which in its outer form passes through the cylindrical body the lock is determined. In a second step, the short sluice or loader is coupled to the proximal end of a long sluice and over the insertion wire in the

Sluice or catheter guided in the left atrium. Upon exiting the catheter tip, the occlusion device in the atrial appendage assumes its predetermined initial shape, is checked there for its anchoring by a slight movement and released. After only a few hours, first endothelial cells settle on the surface of the occluder. After about 12 weeks to 6 months, endothelialization is usually complete. This means that the surface of the Occluder is completely populated with a layer of endothelial cells.

Worldwide, there is a stroke every ten seconds as a result of atrial fibrillation. In Germany, about 1.8 million people suffer Atrial fibrillation, of which about 40000-50000 of them suffer a stroke. About one in four people over the age of 40 will be affected by atrial fibrillation during their lifetime. If the disease remains untreated, the risk of stroke increases up to 8 percent per year. This means that up to 8 out of every 100 people with atrial fibrillation get a stroke every year.

 Echocardiographic studies have shown that embolisms responsible for the increased risk of stroke in people with atrial fibrillation originate from the left ear in more than 90% of cases. Since this left atrial protuberance is a remnant of embryonic development and has no function, it is natural to occlude it. However, an open heart surgery would be too risky an intervention.

State of the art

 So far, the following different closure devices have been used to close the left atrial appendage:

 With the Percutaneous LAA Transcatheter Occlusion (PLAATO) device from EV3 Inc.) see also EP 1 852 141 A2), the left auricle was successfully closed in 2000 in approximately 100 patients. In particular, due to various perforations of the pericardium caused by located on the implant barbs, but there were no further applications. Starting from the PLAATO device, such closure systems are referred to as LAA occluders.

 In a subsequent LAA closure system, the Watchman Occluder Boston Scientific, such perforations can not be excluded. Added to this is the problem of inadequate localization. The Watchman Occluder tends to slide too deep into the heart. From AGA Medical Corp. At the end of 2008, an LAA occluder was approved for Europe. With this device, however, only a certain number of heart ears with an optimal shape can be closed.

From the documents WO 2007/140797 AI, DE 10 2005 053 906 AI and WO 2008/125689 AI the company Occlutech GmbH occlusion instruments are described for closing a cardiac ear, for example Nitinol, which consist of a hollow braid of thin wires. However, such Occlusionsinstrumente can only develop in the free environment of blood, such. For example, conclusion of atrial septal defects. In the very narrow envelope of the left atrial appendage of the Occlusionsinstruments is severely hampered in the initial form, also the distal retention areas according to WO2007 / 125689 AI (one or two hat-shaped brims) and WO 2008/125689 AI (spherical shape, hat and funnel shape) not suitable for safely anchoring the occlusion device in the auricle. The application of a fixative according to WO 2007/140797 A1 with a polymer network preferably formed in the atrial appendage of the patient from a drainable poly-reaction mechanism for forming a frictional connection between the mesh of the occlusion device and the atrial appendage, ie the use of a plastic adhesive, is from a medical point of view differentiated and has not led to any practical deviations.

 The complete form of an occlusion device according to DE 10 2012 003 021.5 does not exclude misplacements in the left atrial appendage.

The closure devices mentioned above have significant disadvantages:

 In these closure devices, the bulging of the left auricle and friction between the occlusion devices and the pericardium can cause very painful inflammation of the pericardium. The hooks used to fix the occlusion devices may cause perforation of the pericardial sac. The risk of thrombosis due in part to the far left atrium protruding coupling at the proximal end of Occlusionsinstrumente is relatively high. The Watchman device also has localization problems. Furthermore, these devices have the disadvantage that the catheter is in its final position in the left atrial appendage due to its positioning in the left atrium in the direction of its longitudinal axis at an unfavorable angle to the position of the occlusion device, i. both axes are almost at right angles to each other. This positioning leads to significant disability during the course of implantation and can lead to perforation of the left pericardium by piercing the wall of the left atrial appendage.

Due to the great diversity of different cardiac ear morphologies, it is often the case that deficits regarding the appropriate occluder size and shape become visible or the device used does not become visible until the implantation phase optimal closure of the auricle. This applies to all the above-mentioned embodiments.

task

 The object of the invention is therefore to avoid the disadvantages described in the prior art and in particular to provide an improved, easily and safely implantable occlusion device. Another object is a simple and cost-effective method for producing such an occlusion device.

The object is achieved by an occlusion device according to claim 1 and a manufacturing method according to claim 12. Advantageous embodiments can be found in the dependent claims. The occlusion device according to the invention for closing a cardiac ear comprises at least two modular parts. A proximal unit for closing the Herzohreingangs and a distal unit for fixation in the holding area of a cardiac ear. Closure by the occlusion device is achieved by releasing the distal main body (distal modular unit) in the holding area of a cardiac ear by means of a suitable catheter or sheath. An optimal localization is achieved by placing the guide wire in the middle of the device. The geometry of the distal body is largely determined by the morphology of the auricle. In its dimensioning, this results in a ball-like body. In a second step, subsequently, the proximal unit, in shape, a narrow circular disc (lid), which is equally pushed over its central passage over the guide wire, placed in the left atrium and placed directly at the atrial appendage. There are several differently sized lids available, they differ in their diameter and thickness. The cover is then moved towards the base body by means of a slight thrust movement, the two mechanical coupling elements, located distally on the proximal modular unit and proximal on the distal modular unit, mechanically connect. This coupling also causes the lid and body to align axially independently according to the nature of the atrial appendage. A membrane located at the distal end of the distal base body is able to realize a certain length compensation. The membrane preferably has a longitudinal structure on its lateral side and a mesh or lattice structure on its front side. The front side thus enables a stable cover (stamping function). The lateral sides are very easy to compress in length and indeed by a slight pressure on the distal end region or twist only to reduce the longitudinal strain. For example, in this way, the diaphragms arranged above or behind one another act mechanically like a spring (but the spring action can also be achieved by other design adaptations), which contract by a slight axial pressure. Thus, the Occiusionsinstrument fits exactly to the depth of the heart ear, which is different for each cardiac ear, regardless of the diameter of the Herzohreingang, which in turn decisively supports the firm anchoring of the occlusion device in the auricular region. It has been found that different heart ears differ significantly from one another by an individual morphology. In particular, the ratio of atrial appendage diameter divided by the length of the atrial appendage is not a constant. This means that atrial ears with a comparable atrial appendage (diameter) can be different in depth (length). To compensate for this mismatch, the Occiusionsinstrument present here has a corresponding membrane, which causes at a lower reaction force from the direction of the distal Herzohrendes that the Occiusionsinstrument can reduce in length, so that the located at the opposite proximal end lid the Herzohreingang exactly closes, but in turn ultimately only possible because the coupling located between the cover and body causes additional length compensation and compensated by the possible inclination of the lid a corresponding deviation of the longitudinal axes of the lid and body.

The basic form of a cardiac ear occlusion instrument results from the basic conditions of the anatomy of such a cardiac ear. Based on this, a classification into three different types of heart ear is possible:

(1) The diameter of the Herzohreingang is smaller than the largest diameter in the Herzohr (type Collar). (2) The diameter of the Herzohreingang is larger than the largest diameter in the subsequent Herzohr (funnel-shaped Herzohr).

 (3) The diameter of the Herzohreingang is about the same size as in the behind the Herzohr (tubular Herzohr).

The occlusion device used in the present invention is able to realize, as far as possible, the closure of all the types of auricular ear listed above, from the combination of different and two independent coupling systems with a corresponding base body. In this sense, the modular intravascular closure device for the left auricle is universally applicable. This mode of action significantly distinguishes the occlusion device according to the invention from all previously known occlusion devices.

An exemplary occlusion device composed of the modular units is rotationally symmetrical in its basic form and has a circular flat stepped lid at the proximal end in order to close off the transition of the left atrium to the entrance of the left atrial appendage. In the proximal retention area adjoining the lid, a diameter reduction results initially, which corresponds approximately to the diameter of the atrial appendage. Subsequently, the circumference of the Occiusionsinstruments increases such that the volume of the Occiusionsinstruments in this central area approximately fills the corresponding part of the cardiac ear with the largest inner diameter. The occlusion device is compressed to approx. 12% of the diameter in this area due to an external pressure effect from the atrial appendage.

The lid preferably has a z. B. arranged in the center of the coupling, which is formed at the proximal end as a ball to be connected to a suitable insertion system. The intravascular occlusion device is designed so that the occlusion device in the folded state by means of a catheter in the body of the patient is minimally invasive insertable and positionable in the heart of the patient via the modular units in two stages. The catheter inserted into the left atrium is usually at an acute angle to the direction of the atrial appendage. The occlusion Instrument closes flush with its lid the Herzohreingang (ie exactly in the direction of the catheter). The first coupling between the insertion system and the cover enables a first axial directional compensation and the second time (if necessary) via the second coupling to connect the modular units cover and body.

A preferred occlusion device is self-expandable, is lasered from a nit-inol tube and then converted by suitable shaping and heat treatment process in a targeted final form.

However, this may not be enough to firmly anchor the occlusion device in the auricular region. Therefore, there is preferably a certain number of hook elements with a length of approximately 3 mm each on the outer shell of the exemplary occlusion device, more preferably in the transition of the proximal retention area to the distal retention area or in the area of the atrial appendage, which firmly anchor the occlusion instrument in the left auricle can support. The production of the barbs is done so that lasered transverse webs are lasered at one longitudinal end and then placed in the radial direction by bending. The positioning and / or the short length of the barbs prevents perforation of the cardiac pouch.

From the exemplary dimensions of the atrial appendage with a diameter of 10 to 26.5 mm in the atrial appendage and a usable depth of the main canal of the pectoralis of 14 to 30 mm, suitably stepped sizes of suitable cardiac appendage instruments are obtained From an example suitable metallic nitinol tube lasered Occlusionsinstrument compressed in the compressed state.

Superelastic metal alloys such. As nitinol, a titanium-nickel alloy with an elasticity of 7% maximum elongation to the initial length are particularly well suited to produce such a shaped body. For example, on the output side, a thin-walled nitinol tube of 1 to 3.5 mm in diameter is used. By using a suitable laser different slots are introduced into the metal tube. After lasering, the metal tube with a mechanical device expanded and brought into shape by heat treatment. The heat treatment time is feasible at temperatures of 350 to 600 ° C and a holding time of half an hour to 2 minutes (the shorter times at higher temperatures). The laser, stretching and heat treatment steps are carried out several times in succession until the final shape of the occlusion device has been reached. By a possible laser cutting width of up to 15 μιτι can be performed on the circumference of such a metal tube more than 150 sections parallel to the longitudinal axis.

In the case of the present occlusion device according to the invention, one or more layers of medically suitable and / or medically active materials are preferably located in the region of the atrial appendage, eg. As patches to seal the blood flow between the left atrium and the left atrial appendage so that it can no longer pass through the heart ear in the direction of the left atrium. As a material is z. As Dacron, under the chemical name PET (polyethylene terephthalate), suitable.

embodiment

 Fig. 1 (a) is a schematic representation of the front view of the modular units lid and body according to the invention;

 Fig. 1 (b) is a schematic representation of the front view of the occlusion device according to the invention, according to FIG. 1 (a);

 Fig. 2 (a) is a schematic representation of the front view of the modular units basic body and varied lid according to the invention;

Fig. 2 (b) is a schematic illustration of the front view of the lidded occlusion instrument of the invention shown in Fig. 2 (a);

 Fig. 3 (a) is a schematic view of the front view of the modular units basic body and reduced lid according to the invention;

Fig. 3 (b) is a schematic front elevational view of the reduced cover occlusion device of Fig. 3 (a) according to the present invention;

Fig. 4 (a) is a schematic representation of the front view of the occlusion device according to the invention according to FIG. 1 (a) and 1 (b); a schematic representation of the bottom view of Occlusionsinstruments invention Fig. 1 (a) and Fig. 1 (b);

a further schematic representation of the front view of Occlusionsinstruments invention with varied basic body; a schematic representation of the side view of an occlusion device according to the invention of Figure 5 (a).

a schematic representation of the bottom view of the invention Occlusionsinstruments of Figure 5 (a) with an elliptical shape of the base.

a schematic sectional view of the side view left atrium and left atrial appendage;

a schematic partial sectional view of the left atrium with atrial appendage during a first phase of the invention to be implanted LAA occluder in the left atrial appendage;

a schematic partial sectional view of the left atrium with atrial appendage of Figure 7 (a) with released main body in the left auricle.

 Detailed view of a schematic representation of the side view in the region of the coupling at the distal end insertion system to the proximal end of the base body;

 Detailed view of a schematic representation of the side view at the proximal coupling end of the body to the distal coupling end of the delivery system;

a schematic representation of the side view with partial section of the clutch in the engaged state of Fig. 8 (a) and (b):

a schematic partial view of the side view in the left atrial appendage in an advanced implantation phase of the invention to be implanted Occlusionsinstruments with released cover in the left atrium following on representation Fig. 7 (b)

a schematic partial sectional view of the side view of another phase of the invention to be implanted LAA occluder in the connection of Figure 10 (a) with the lid left in the left atrium. a schematic partial sectional view of the side view of a further implantation phase in connection with FIG. 10 (b) with the cover coupled to the base body;

a sectional view of the schematic view of the side view in the proximal end of the lid (ball coupling) to the distal end of the lid (coupling element for coupling to the main body) of the occlusion device according to the invention;

a sectional view of the detailed view of the coupling elements located at the proximal end of the main body for coupling to the main body of Figure 11 (a).

a sectional view of the molded elements produced by laser machining of the coupling in the side view corresponding to Figure 11 (a), distal end.

a plan view of the side view of the coupling elements of Figure 12 (a).

a sectional view of the molded elements produced by laser machining of the coupling in a side view corresponding to Figure 11 (b), proximal end.

a plan view of the coupling elements of FIG. 13 (a);

a schematic representation of a lateral section of the latched according to the detail views Fig. 11 (a) and (b) coupling of an occlusion device according to the invention;

a schematic partial sectional view of the side view of FIG. 10 (c) subsequent implantation phase of the LAA occluder to be implanted with retracted lock and uncoupled delivery system;

a schematic partial sectional view of the side view of FIG. 15 (a) subsequent implantation phase of the LAA Occluders to be implanted with returned insertion wire;

a schematic partial sectional view of the side view of an implantation according to Figure 15 (b) subsequent implantation with further return of the lock or catheter and completion of the implantation process; a schematic partial sectional view of the side view of an implantation process according to the invention LAA Occluders according to the invention in the left atrial appendage, but with a funnel-shaped atrial appendage and thus enlarged cover according to FIG. 15 (c);

a schematic partial sectional view of the side view of an according to Fig. 15 (c) implantation process of Occiusungsinstruments invention, but with much smaller Herzohreingang and correspondingly adapted smaller lid;

a schematic partial sectional view of the side view of an according to Figure 15 (c) implantation process of the Occiusionsinstruments invention, but with a funnel-shaped heart ear and without cover;

a schematic representation of the front view of Occiusungsinstruments invention of Figure 1 (a) and (b) but with a differentiated coupling between the lid and the base. a schematic representation of the bottom view of another Occiusungsinstruments invention of Figure 17 (a).

a schematic representation of the front view of the invention LAA Occluders with coupled delivery system;

a further schematic representation of the occlusion device shown in Fig. 8 (a) with the coupled delivery system; a schematic representation of the partial view of the coupling of Figure 8 (a).

 Detailed view of a schematic representation of the side view at the proximal coupling end of the body to the distal end of the coupling of the delivery system, but for a further coupling solution according to Fig. 17 (a).

a schematic representation of the side view with partial section of the clutch in the engaged state of Figure 19 (a) and (b).

a sectional view of the schematic view of the side view in the area coupled insertion system at the proximal end of the lid (ball coupling) to the distal end of the lid with another smaller ball coupling of FIG. 17 (a) for Coupling to the main body of another Occlusionsinstruments invention;

 Fig. 21 (b) is a sectional view of the detailed view of the coupling elements located at the proximal end of the main body for coupling to the main body according to Fig. 21 (a) and

 22 shows a schematic illustration of a lateral section of the further inventive coupling of an occlusion device according to the invention engaged according to the detail views in FIGS. 21 (a) and (b).

Fig. L (ab) show a schematic representation of a first preferred embodiment of Occluders invention (Occiusionsinstrument) (1) with the corresponding modular units (21) as shown in Fig. 1 (a) with a correspondingly suitable cover (2) and the Spherical modular unit of the main body (3) with the diaphragm (27) located on the distal end (11) for axial length compensation and in the coupled state according to FIG. 1 (b).

FIGS. 2 (a-b) and 3 (a-b) embody further embodiments of the modular series of a specific size of the modular unit of the base body (3) with differently sized cover units (2). Due to different sized heart ears (5), the main body (3) are also sized in different sizes.

In FIG. 4 (a-b), it can be seen in the lower view (15) in FIG. 4 (b) that the membrane (27) has a circular opening (44) at the distal end (11). This makes it possible for the occluder (1) to optimally adapt to the depth of the atrial appendage (5) in its axial longitudinal extent. For this purpose, it is also necessary that laser elements with a longitudinal structure (36) are preferably used for shaping the membrane (27) and laser elements with mesh or lattice structure (37) for stabilization at the distal end of the membrane (27).

Decreases z. B. in the adjustment phase during the implantation process, the total height of Occiuders (1), the open end of the membrane (44) will shrink in its total area. Should the morphology of the atrial appendage (5) be designed such that the depth of the heart tube from the holding area (7) to the heart 6 occurs larger, it comes to a length compensation in the region of the underside of the lid (2) in the direction of the coupling type II (23) of FIG. 4 (a) and equally below also with ball coupling type III ( 24) as shown in Fig. 17 (a). This length compensation in the axial direction is used to extend (increase) the total length of the occluder (1) by means of further laser elements with a longitudinal structure (36) on the underside of the cover (2) for type II and type III coupling.

For particularly flat-shaped heart ears, it is useful to design the distal modular base body (3) so that FIG. 5 (c) makes the basic body unit (3) oval, as shown in the bottom view (15), and thus a further embodiment according to the invention represents.

For firm anchoring of the occlusion device (1) in the atrial appendage (5) are according to the invention

for all embodiments according to Fig. L (a-b) to Fig. 5 (a-c) hook elements (26) formed on the outer periphery of the base body (3). As is shown in FIGS. 1 (a-b) to 3 (a-b) and 4 (a), these hooks (26) are bent back to the occluder longitudinal axis by a little more than 180 °. On the one hand, this makes it possible to transport the occluder (1) in the sluice or catheter (31) in both directions without the hooks (26) being able to settle in the inner wall of the sluice or of the catheter. Likewise, a perforation of the pericardium is almost impossible.

For sealing the blood flow, in all the embodiments according to the invention the occluder (1) is in each case two patches (25) made of PET, as shown, for example, in the first embodiment according to the invention FIG. 1 (a-b).

A preferred embodiment according to the invention of the occluder (1) Fig. L (ab) to Fig. 5 (ac) is materially constructed so that the modular units base body (3) and lid (2) consists essentially of a suitable metallic material and preferably of nitinol , a titanium-nickel alloy. Both base body (3) and lid (2) are produced from a nitinol tube by using and combining suitable laser and heat treatment processes. provides. In a first laser processing step, corresponding cuts are made in the wall of the nitinol tube with a suitable laser. The laser cut image is projected from the unwinding of the outer cylinder of the Nitinol tube (3D) onto a surface (2D). In certain areas on the underside of the lid (2) and in the region of the membrane (27) are predominantly pattern for later laser elements with longitudinal structure (36) and otherwise predominantly pattern for later laser elements with mesh or grid structures (37) specified. In a subsequent step, the 2D cut pattern (laser construction) is projected back onto the outer contour of the Nitinol tube in the "3D space". A 3D laser processing center then brings the pattern into the Nitinol tube for the base body (3) or cover (2) in a form-fitting manner in one machining step. At the proximal end of the laser-machined nitinol tubes, a 1.5 to 2 mm short tube section remains free from the laser production. These two sections are later used to hold the corresponding coupling elements for all covers (2), the ball coupling (22) to which the insertion (30) can be attached and the main body (3) depending on the design of coupling II (23) and coupling III (24), which will be described below. Subsequently, now the lid (2) and body (3) each from the distal end of the modular units (21) introduces a mandrel, which expands the laser-machined Nitinolrohr. After removing the mandrel, the expanded Nitinol tube is introduced in a heat treatment process as described above to stabilize the first intermediate form. Then the next steps repeat. With a larger mandrel, the expanded nitinol tube is further extended, followed by the heat treatment process, etc. These operations can be performed multiple times.

If the laser-machined nitinol tube is stretched far enough, the final shape of the modular units (21) is now produced. For example, the cover (2) is now moved as follows:

An elongated thin bolt is inserted through the proximal pipe end (11) until the cap of the bolt (shape like a screw head) abuts the pipe end. Then, from the distal end of the bolt, a circular disc with a hole in the center is placed on the bolt. ben, the already pushed on stretched Nitinolrohr over it and continues to stretch. If the circular disc, which corresponds to the outer shape of the cover (2), adjusted until shortly before the end of the bolt in the direction of the bolt cap, then the stretched on nitinol tube toward the distal end (11) is pressed together by an annular tool shape. The inner diameter of the ring tool corresponds to the outer diameter, for example, in Fig. 1 (a). Figs. 2 (a) and 3 (a) show the outer diameter of the waist (45) at the distal end (11) of the proximal modular unit (lid) (2). Subsequently, there is another heat treatment step. Analog manufacturing steps result for the distal modular (basic body) (3). Before the last electropolishing operation, the ball coupling I (22) is placed in the proximal end (11) of the cover (2). The ball coupling I (22) has an axial through bore (38) of FIG. 11 (a). to push them later with the occluder (1) over the guidewire (29) and a continuous central transverse bore, through which, as shown in Fig. 11 (a) can be seen, through a lasered opening of Nitinolrohrendstück a fastening pin left ( 34) and a fixing pin on the right (35) for secure attachment of the ball coupling I (22) on the cover (2) are introduced. The mounting pins (34), (35) are also made of Nitinol and are fixed by laser welding to the proximal end tube piece from the proximal end (9) of the lid (2). The ball coupling I (22) is made of medical-approved stainless steel for technological reasons, since the process ball grinding hardly can be technically realized with the material Nitinol.

In the modular units (21) basic body (3) and lid (1) according to Fig. L (a-b) to Fig. 5 (a-c) at least one or more Dacron patches (25) can be incorporated to seal the blood stream.

In further embodiments of the occlusion device (1) according to the invention, corresponding to FIGS. 1 (ab) to 5 (ac), 16 (ac) and 17 (ab) and in connection with embodiments according to the invention with specific coupling systems II (23 ) According to Fig. 14 and III (24) of Fig. 20. Fig. 21 (ab) and Fig. 22 all metallic parts are replaced by bioresorbable materials. Overall, the following biodegradable synthetic polymers can be used: a) polyesters, such as poly (lactic acid) PLA, poly (glycolic acid) PGA, poly (3-hydroxybutyric acid) PBA, poly (4-hydroxyvaleric acid) PVA or poly (s-caprolaton) PCL or corresponding copolymers, b) polyanhydrides which consist of dicarboxylic acids such as. For example, glutaric, succinic or sebacic acid are formed o- c) poly (amino acid) s or polyamides such. As poly (serine ester) or poly (aspartic acid). These biodegradable materials or polymers contain fissile bonds under physiological conditions, such as amide, ester or acetal bonds. When surface degradation at z. For example, poly (anhydrides) n or poly (orthoester) s, the hydrolysis of chemical bonds takes place exclusively on the surface. In the case of poly (hydroxycarboxylic acids), such as poly (lactic acid) or poly (glycolic acid) or corresponding copolymers, the polymer degradation takes place in the entire volume. In addition, polymers with shape memory properties can also be used. Such biodegradable thermoplastic amorphous polymer networks with shape-memory properties describe, for. Lendlein et al. A. Alteheld, Y. Feng, S. Kelch, A. Lendlein, Angew Chem Chem Int Ed 44 (2005) 1188). Here, amorphous polyurethane copolyester polymer networks with shape memory properties with a glass transition temperature T _g between 48 and 66 ° C are used. By heating these networks about 20 ° C above this switching temperature to form rubber-elastic materials that can be deformed between 50 and 265% to a temporary shape. Cooling down to room temperature resulted in deformed shape-memory polymer networks, which show a significantly higher tensile modulus of elasticity. Furthermore, biodegradable shape memory polymers based on covalent networks based on oligo (ε-caprolactone) dimethacrylate and butyl acrylate are known (A. Lendlein, A. M. Schmidt, R. Langer, Proc. Natl. Acad (2001) 842). The network synthesis is done by photopolymerization. The molar mass of the macromolecular oligo (ε-caprolactone) dimethacrylate and the comonomer n-butyl acrylate content can be used to control the switching temperature and mechanical properties of the covalent network.

Accordingly, by combining physical or covalent shape-memory polymer networks with known biodegradable polymer segments, biodegradable shape-memory polymer networks for the novel be made modularly shaped Herzohroccluder. By carefully selecting the components, it is possible to set the optimum parameters for the respective application, such as the mechanical properties, the deformability, the phase transition temperatures and above all the switching temperature, as well as the degradation rate of the polymers. Furthermore, the modular Herzohroccluder can be produced by generative manufacturing processes, in particular two methods are suitable, on the one hand, the stereolithography (SL) and on the other hand, the printing (2D or 3D). In SL, layered liquid resin monomers are cured by photopolymerization and cured by irradiation by means of a laser (laser scanner method) or high-performance beamer or UV lamp (mask method). In this case, the molding is made by solidification due to photopolymerization of commercially available monomers which may contain other additives and fillers. Particularly suitable as polymerizable resin monomers are mixtures of monofunctional or polyfunctional acrylates or methacrylates which rapidly cure upon irradiation in the presence of suitable free-radical-forming photoinitiators by radical polymerization. Examples of mono- or polyfunctional (meth) acrylates are methyl, benzyl, tetrahydrofurfuryl or

Isobornyl (meth) acrylate, ethoxy- or propoxylated bisphenol-A-di (meth) acrylate, urethane di (methacrylates, di-, tri- or tetraethylene glycol di (meth) acrylate, trimethylolpropane tri (meth) lat as well as glycerol di- and tri (meth When using polymerisable resins, the applied material is uniformly polymerized (polymer printing) When thermoplastic polymers are used, solidification is achieved by cooling the polymer melt The most frequently used polymers are polyamide, ABS or polycarbonate, which are based on .RTM Bioresorbable polymers can also be used in the case of so-called 3D printing, solid layers are produced by bonding granules with a binder.

In Fig. 6 we find a schematic representation of the left ear (5) of the type Collar, as described above. About 70% of all types of heart ear conform to this form. It is characteristic that the diameter of the Herzohreingangs (6) is smaller than the diameter (8) of the holding portion (7) of the atrial appendage (5). For such a shaped heart ear (5) corresponding Oc 1 (ab), FIG. 4 (ab) and FIG. 5 (ac) with the coupling systems II (23) according to FIGS. 14 and III (24) according to FIG. 17 (ab), FIGS Fig. 22 can be used.

The interventional atrial appendage closure is based on a venous, transseptal approach, via which a self-expanding device is introduced into the LAA after fluoroscopic imaging. Preoperatively, the patient is treated with antiplatelet or anticoagulant substances.

 After puncturing the femoral vein, we advanced the occlusion device over the right atrium with the aid of a feeder system and into the left atrium after a transseptal puncture and finally released it from the sluice at the LAA. In this case, the distal spherical body expands in the LAA, while the proximal lid seals the entrance of the LAAs from the outside. After checking the positioning in the LAA, the occluder can be decoupled from the feeder system. The entire procedure is under constant TEE control, with the patient in mild anesthesia (sleep state, where respiratory and circulatory functions are kept stable). To avoid thrombi, anticoagulants (blood thinning medication) must be taken postoperatively, initially for 24 hours. After complete endothelialization, a 6-month dose of ASA and / or clopidogrel is required. This serves to avoid blood clot formation. Optionally, the patient is examined echocardiographically at defined intervals.

In all known feeder systems and competitive devices, the lock system with the dilator is guided over the guide wire into the atrial appendage. When the mouth of the sheath or catheter is securely placed in the atrial appendage, the dilator and guide wire are removed from the atrial appendage. Since the atrial appendage is not yet occluded, this early return of the guidewire is especially problematic because thrombi can be expelled during this return procedure, which can lead to a stroke.

In the embodiments according to the invention, here for the heart tube type collar, the guide wire (29) remains in place during the entire implantation procedure left atrial appendage (5). In Fig. 7 (a) we see an early stage of implantation of the occluder (1). It can be seen the guide wire (29) with the distal end (11) in the heart ear. The lock or catheter (31) comes from the left atrium (4), wherein the distal end of the lock (31) is also placed in the LAA (5). The lock (31) and the insertion system (30) located therein run centrally over the guide wire (29). In this first implantation phase, the delivery system (30) is firmly connected to the distal modular base body (3), which already partially unfolds in the retention area of the atrial appendage (7). In Fig. 7 (b), the main body (3) has already fully unfolded. Fig. 8 (a) is a detail view of the gripper (pliers system) (32) at the distal end of the delivery system (30). Fig. 8 (b) is a further detail view of the proximal end (9) tied to the delivery system (30) as shown in Fig. 9.

 In Fig. 10 (a), the base body (3) is already released in the atrial appendage (5), the guide wire (29) still remaining in the base body (3). Further, in Fig. 10 (a), the lid (2) is partially released in the left atrium (4). By the guide wire (29) cover (2) and body (3) remain in an axial connection. After the lid (2) is completely released in Fig. 10 (b), the lid (2) and base body (3) can be connected to each other by a slight pushing movement. The coupling elements at the distal end of the cover from FIG. 11 (a) and detail view in FIG. 12 (ab) connect to the coupling part II (cover / main body) (23) according to FIG. 11 (b) and detailed view in FIG. 13 (ab), as can be seen in the end position in FIG. 14.

In Fig. 15 (a-c), the individual operations for removing the lock (31), the uncoupling of the insertion system (30) and the lead out of the guide wire (29) are shown schematically. In Fig. 15 (a), first, the sluice (31) is returned a little from the occlusion device (1) and the delivery system (30) is separated from the occluder. The guidewire (29) is in the atrial appendage (5). The occluder (1) aligns in the end position and, according to FIG. 15 (b), the guide wire (29) can now likewise be guided into the sheath (31) outside the patient.

In Fig. 15 (c), finally, the lock (31) is returned. The implantation process is virtually complete. In Fig. 16 (a) we see a modular LAA occluder (1) for a funnel-shaped heart ear (5), in Fig. 16 (b) a heart ear (5) type collar with a very small diameter of the atrial appendage (6) and 16 (c) shows a specific form of a cardiac ear (5) into which a modular basic body (3) without a cover (2) has been implanted.

In Fig. 17 (ab) we find another preferred embodiment of the invention LAA Occluders (1) with a ball coupling I (insertion / lid) (22) and another ball coupling III (cover / body) (24) with an even larger Mobility between cover (2) and body (3).

 In a first implantation step, first the insertion system (30) and the base body (3) must be connected again, as shown in FIG. 20. After releasing the base body (3) analogous to FIG. 7 (b), the cover (2) with integrated ball coupling type III (cover / main body) (24) in still separated state Fig. 21 (ab) cover (2) and body (3) coupled as shown in Fig. 22 can be seen. For Occiusionsinstrumenten (1) with the type ball coupling III (24) also continuous through holes (38) are involved.

The guide wire (29) remains in the atrial appendage (5) until the end of the implantation procedure. In particular, by the coupling systems used ball coupling I (22) in the transition insertion system (30) with cover (2) and coupling II (23) in the transition cover (2) to the base body (3) or ball coupling I (22) with ball coupling III in the transition cover (2) to the main body (3) of a corresponding embodiment of an occluder (1) according to the invention a high flexibility of the delivery system (30) is achieved in the coupled state to the Occluder (1), as shown schematically in Fig. 19 (ab). In the addition of the tilt angle 1 (41) by coupling (23) or (24) in the transition cover (2) and base body (3), the tilt angle 2 (42) through the ball coupling (22) in the transition transition insertion system (30) and Lid (2) and the tilt angle of the controllable lock (catheter) (31) results in an angle of more than 180 °, which has a significantly more positive effect on a more effective implantation process. LIST OF REFERENCE NUMBERS

1 closure device (Occiusionsinstrument or Occiuder)

2 proximal modular unit lids

 3 distal modular unit bodies

 4 left atrium

 5 left auricular (LAA)

 6 diameter Herzohreingang

 7 holding area Herzohr

 8 largest diameter in the holding area Herzohr

 9 proximal end

 10 proximal retention area

 11 distal end

 12 front view

 13 front view

 14 top view

 15 bottom view

 16 side view

 17 sectional view

 18 partial section

 19 detailed view

 20 schematic view

 21 modular units

 22 ball coupling i (insertion system / cover)

 23 Coupling II (cover / body)

 24 Coupling III (cover / body)

 25 patch

 26 hooks

 27 membrane

 28 heart outer wall

 29 guidewire

 30 insertion system

 31 lock (catheter)

32 grippers lasered case

Fixing pin left

Fixing pin right

Laser element with longitudinal structure

Laser element with mesh or grid structure Through hole

Ball Stud with Through Hole Area Extension Ball Stud

Tilt angle 1

Tilt angle 2

Tilt angle 3

open end of the membrane

Waist (bridge)

Claims

claims 1. Modular intravascular closure devices (1) for the treatment of defects in the heart of a patient, in particular for closing the left atrial appendage (5),  wherein the occlusion device (1) is composed of at least two modular units (21), each of which in its basic form consists of a solid composite of a reticulated envelope (33) with a portion of shaped elements with longitudinal structure (36) and a portion of shaped elements with grid structure (37). are composed, wherein the Occlusionsinstrument (1) is characterized in that  a proximal modular unit (cover) (2) or proximal retention area (10) through a web (waist) (45) of a distal modular unit (basic body) (3) or membrane (27) at its end, is limited to the distal retention area (12), characterized by at least one respective tissue insert (patch) (25) in the respective modular units (21) required for complete closure of the left atrial appendage (5), the two retention areas (10) , (12) by a mostly interventional intervention before and behind the atrial appendage (6) in the atrial appendage (5) come to rest, the proximal modular unit (cover) (2) from the left atrium (4) ago the Herzohreingang (6) closes and at least one distal modular unit (basic body) (3) is positioned in the holding area of the atrial appendage (5) and firmly anchored in the atrial appendage (5) by means of corresponding hooks (26). 2. Modular occlusion device (1) according to claim 1,  characterized in that  the shaped elements (36), (37) of the reticulated sheath (33) are made of metal or metal alloys such as nitinol or non-absorbable plastics selected from the group of polyesters, polyamides, polyolefins, polyurethanes and polyhalogenolefins. 3. Modular occlusion device (1) according to claim 1, characterized in that the modular units (21) and bioresorbable polymer patches (25) are formed as polyesters such as poly (lactic acid) PLA, poly (glycolic acid) PGA and other polyesters, polyanhydrides and polyamino acids with cleavable bonds such as amide, ester or acetal bonds and both the lasered shell (33) and the patches (25) have a degradation time between (5) and (50) weeks. 4. Modular occlusion device (1) according to claim 1 and claim 3.  characterized in that  the bioresorbable polymer has a glass transition point of at least 41.5 ° C and is a fermentatively produced polyhydroxyalkanoate or a synthetically resorbable polymer, optionally formed from the monomer building blocks lactide, glycolide, e-caprolactone, p-dioxanone and trimethylene carbonate, wherein the resorbable Polymer may be either a homopolymer, a random co-polymer or a block co-polymer, wherein a co-polymer is understood to mean a polymer composed of at least two of said monomer units. 5. Modular occlusion device (1) according to claim 1, claim 3 and claim 4,  characterized in that  the resorbable polymer comprises from 70% by weight to 97% by weight of L- or DL-lactide, preferably from 80% by weight to 95% by weight of L- or DL-lactide and particularly preferably from 88% by weight to 93% by weight % L- or DL-lactide, wherein the balance to 100 wt .-% of glycolide, e-caprolactone, p-dioxanone, trimethylene carbonate or a combination of these monomers may be formed. 6. Modular occlusion device (1) according to claim 1,  characterized in that  the modular units (21) and the patches (25) of bioresorbable polymers with shape-memory properties  characterized in that such biodegradable amorphous polymer networks as amorphous polyurethane-co-polyester polymer networks have a glass transition temperature between 48 and 66 "C,  characterized in that  By heating these networks to about 20 ° C above this switching temperature form rubber-elastic materials that can be deformed between 50 and 265 ° C to a temporary shape  characterized in that  By cooling to room temperature, polymers with significantly higher tensile moduli of elasticity are formed. 7. Modular occlusion device (1) according to claim 1 according to one of the preceding claims  characterized in that  for a given distal modular unit (main body) (3) different sized proximal modular units (cover) (2) can be assigned. 8. Modular occlusion device (1) according to claim 1 according to one of the preceding claims 1 to 6,  characterized in that any suitable form-stamped distal modular units (basic body) (39) are assigned to a predetermined proximal modular unit (cover) (2) corresponding to the cardiac ear forms of the left atrial appendage (5). 9. Modular occlusion device (1) according to claim 1 according to one of the preceding claims  characterized in that  the proximal modular unit (cover) (2) with a universal for  Insert coming ball coupling I (22) with both the coupling II (23) or ball coupling III (24) with the distal modular unit (main body) (3) can be connected. 10. Modular occlusion device (1) according to claim 1 according to one of the preceding claims 1 to 6, that in a special shaping of the auricular (5) the distal modular Unit (body) (3) can effectively close the designated atrial appendage (5) alone. 11. occlusion device (1) according to claim 1 according to one of the preceding claims  characterized in that  the modular units (21) cover (2) and body (3) can be tapered to the diameter of a lock (catheter) used in the interventional procedure. 12. A method for producing an occlusion device (1) according to one of claims 1 to 11,  characterized by the following process steps:  a) Preparation of cylindrical body and machining with suitable laser method with laser elements with longitudinal structure (36) and those with mesh or grid structure (37) and  b) forming the modular units (21) cover (2) and base body (3). 13. The method according to claim 12,  marked by  the method step of forming a ball coupling I (22) at the proximal end of the proximal modular unit (cover) (2). 14. The method according to claim 12 and claim 13,  characterized in that  the method step of forming the final shape of the modular units (21) cover (2) and base body (3) comprises a transformation and / or heat treatment. 15. A method for producing an occlusion device (1), according to claims 1, 2 and 7 to 14.  characterized in that a final one when using metallic materials Electropolishing for finishing and preservation of the surface takes place. Method of manufacturing an occlusion device (1) according to claims 1 to 13, characterized in that the modular units (21) lid (2) and basic body (3) can generally be produced in their characteristic properties by generative methods, the application of such methods not only to such as the application of Steriolithogarfie (SL) and on the other hand the 2D and 3D printing should be limited