CLOSURE DEVICE SUITABLE FOR CLOSING THE ATRIAL APPENDAGE

Abstract

A medical closure device that is configured to be inserted into a patient's LAA (left atrial appendage) cavity comprises a closure member and at least one fixing member, wherein the closure member comprises a lid part and a body part one following the other in a proximal-distal direction. The lid part comprises a cover portion and a ring portion, the ring portion being configured to be circumferentially disposed along the rim of an individual LAA ostium, thus sealing the LAA ostium completely. The medical closure device is designed individually for each patient. A method of manufacturing the medical closure device includes the step of forming an LAA model based on computer graphic data of the patient. The LAA model is made by 3-D printing and is an exact reproduction of the patient's LAA. The medical closure device is then preformed using the LAA model.

Claims

1. A medical closure device configured to be inserted into a patient's left atrial appendage (LAA) cavity, comprising a closure member and at least one fixing member, the closure member comprising a lid part and a body part one following another in a proximal-distal direction, the lid part comprising a cover portion and a ring portion, the ring portion being configured to be circumferentially disposed along a rim of an individual LAA ostium, thus sealing the LAA ostium completely.

2. The closure device according to claim 1, wherein the closure device is formed of metal or biocompatible polymer or a combination thereof.

3. The closure device according to claim 1, wherein the closure device is formed of shape memory material.

4. The closure device according to claim 1, wherein the closure device is formed of Nitinol.

5. The closure device according to claim 1, wherein the body part of the closure member is configured to adjoin tissue of an individual LAA cavity.

6. The closure device according to claim 1, to wherein the closure member is a metal braid.

7. The closure device according to claim 1, wherein the closure member comprises a body part in a form of a polymer balloon and a lid part made of a polymer or of a metal braid.

8. The closure device according to claim 6, wherein the braid comprises at least one layer of occluding material in a form of a coating or a patch.

9. The closure device according to claim 1, wherein the fixing member is hook-shaped and comprises at least one wire element or tape element made of shape memory material.

10. The closure device according to claim 1, wherein the fixing member comprises 2 to 10 wire elements, preferably 3 to 6 wire elements, connected to and grouped evenly around [[the]] a distal end of the body part of the closure member.

11. The closure device according to claim 10, wherein the wire elements of the fixing member have different lengths with respect to one another.

12. The closure device according to claim 1, further comprising a tension member placed between the closure member and the fixing member.

13. The closure device according to claim 12, wherein the fixing member comprises 2 to 10 wire elements, preferably 3 to 6 wire elements (8), connected to and grouped evenly around a distal end of the tension member.

14. The closure device according to claim 12, wherein the tension member is a coil spring.

15. The closure device according to claim 1, further comprising a thread or double thread at a proximal end of the closure member.

16. The closure device according to claim 1, wherein the closure member has a central lumen extending through the lid part and the body part with a valve placed therein, said valve sealing the lumen.

17. The closure device according to claim 1, wherein the whole closure device is made of Nitinol, including the closure member, the fixing member and a tension member, wherein the closure member is a braid comprising at least 30 wire elements having a diameter of about 0.03 to 0.15 mm, said braid defining the lid part and the body part, wherein the fixing member comprises 2 to 10 wire elements grouped evenly around a distal end of the tension member, wherein the tension member is a coil spring, said coil spring being attached to the distal end of the body part of the closure member.

18. A method of manufacturing a closure device that is configured to be inserted into a patient's left atrial appendage (LAA) cavity, the method comprising the following steps: a) generating a three-dimensional computer graphic of the patient's (LAA based on medical images of the LAA; b) transferring data of the computer graphic to a 3-D printer device; c) forming an LAA model by 3-D printing, said model being an exact reproduction of the patient's LAA; and d) manufacturing the closure device by pre-fabricating a closure member comprising a lid part and a body part one following another in a proximal-distal direction and pre-fabricating a fixing member and forming at least the lid part of the closure member according to the LAA model obtained in step c) to obtain a pre-formed closure device with at least the lid part of the closure member conforming in size and shape to the patient's LAA ostium, and attaching the fixing member to the closure member either before forming the closure member or after forming the closure member.

19. A method of manufacturing a closure device that is configured to be inserted into a patient's left atrial appendage (LAA) cavity, the method comprising the following steps: a) generating a three-dimensional computer graphic of the patient's (LAA based on medical images of the LAA; b) transferring the data of the computer graphic to a 3-D printer device; c) forming an LAA model by 3-D printing, said model being an exact reproduction of the patient's LAA; and d) manufacturing the closure device by pre-fabricating a closure member comprising a lid part and a body part one following another in a proximal-distal direction, and pre-fabricating a fixing member, filling the closure member with a heat-resistant material and forming the closure member by placing it into the LAA model obtained in step c) to obtain a pre-formed closure device which conforms in size and shape to the patient's LAA ostium and the LAA cavity, and attaching the fixing member to the closure member either before forming the closure member or after forming the closure member.

20. A method of manufacturing a closure device that is configured to be inserted into a patient's left atrial appendage (LAA) cavity, the method comprising the following steps: a) generating a three-dimensional computer graphic of the patient's (LAA based on medical images of the LAA; b) transferring the data of the computer graphic to a 3-D printer device; c) forming an LAA model by 3-D printing, said model being an exact reproduction of the patient's LAA; and d) manufacturing the closure member and forming the closure member by first forming a metal ring according to an opening of the LAA model and fixing the closure member to the metal ring to shape it.

21. The method according to claim 18, wherein the medical image is an X-ray image, a CT scan, an MRI scan, or an ultrasound image.

22. The method according to claim 18, wherein 3-D printing is 3-D laser printing and the LAA model is made of metal.

23. The method according to claim 18, wherein 3-D printing is 3-D polymer printing and the LAA model is made of polymer.

24. The method according to claim 18, wherein the closure device is made of a shape memory alloy, the method further comprising step e) comprising: e) heat-treating the LAA model together with the closure member or closure device placed therein to a transformation temperature of the shape memory alloy to obtain a pre-formed closure device with at least the lid part of the closure member conforming in size and shape to the patient's LAA ostium.

Description

FIGURES

[0114] FIG. 1 is an overview drawing showing the transseptal access to a patient's LAA.

[0115] FIGS. 2 and 3 show the braided closure member during its manufacturing before forming the braid.

[0116] FIG. 4 schematically shows the layout of the closure device.

[0117] FIGS. 5 to 9 show the forming of the closure member using the LAA model.

[0118] FIGS. 10 to 15 schematically show various embodiments of the braided closure device inserted in the patient's LAA.

[0119] FIG. 16 illustrates the closure of an LAA of the so called chicken wing type using a braid or a polymer device.

[0120] FIG. 17 shows the insertion of the closure device via a delivery catheter.

[0121] FIG. 18 shows the insertion and implantation process of the closure device.

[0122] FIG. 19 schematically shows another embodiment of the braided closure device inserted in the patient's LAA.

[0123] FIG. 20 schematically shows still another embodiment of the braided closure device inserted in the patient's LAA.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0124] FIG. 1 is an overview drawing showing a patient's heart with the left atrial appendage (LAA) 100 and the transseptal access to the LAA via the septum 101 and the left atrium 102. A delivery catheter 31 is guided to the LAA. Positioning threads 9 ensure safe positioning of the closure device (not shown).

[0125] FIG. 2 shows a braided closure member 1 during its manufacturing. The manufacture of the closure member 1 starts by braiding a core. As shown in FIG. 2a, the manufacture of the closure member 1 may start by braiding a tube-shaped or sleeve-shaped mesh. The ends of the wires of the braided core will then be brought together and connected, for example by a connection part 14, which may be a sleeve or the like. Connection of the wire ends may be achieved without a connection part by directly connecting the wire ends, e.g. by welding, adhesive or other suitable method. As shown in FIG. 2b, the wire ends are connected at the distal end of the closure member 1.

[0126] FIG. 3 shows another braided closure member 1 during its manufacturing. In contrast to FIG. 2, the wires of the upper part of the braid are drawn inside the braid, brought together and connected, thus forming a closure member 1 with a double braid structure.

[0127] FIG. 4 shows schematically the layout of the closure device before the forming process. The closure device comprises the braided closure member 1 having a lid part 3 and a body part 4, a tension member 5 and a fixing member 2. The lid part 3 has a cover portion 6 and a ring portion 7. The tension member 5 is placed between the closure member 1 and the fixing member 2. The tension member is a coil spring which is fixed to the closure member 1 at its distal end. In this embodiment, the fixing member comprises five wire elements 8 being grouped around the proximal end of the tension member 5. The wire elements 8 are hook-shaped at their distal end. FIG. 4 (i.e. FIGS. 4a, 4b) shows two examples of a hook-shaped layout. FIG. 4a shows a semicircular hook 15. FIG. 4b shows a barbed hook 16.

[0128] FIGS. 5 to 9 illustrate the forming of the closure member 1 using a LAA model.

[0129] FIG. 5 is a photograph of the LAA model 10 with the braided closure member 1 pressed therein. FIG. 5 mainly illustrates how the lid part 3 of the braided closure member 1 with its ring portion 7 is formed by pressing the braid into the LAA model 10, followed by a heat treatment. It can be seen that the lid part 3 of the closure member 1 conforms in size and shape to the opening of the LAA model 10 and thus to the patient's individual LAA ostium.

[0130] FIG. 6 is a photograph of the LAA model 10 in a side view with the braided closure member 1 having a lid part 3 pressed therein. FIG. 6 shows how the complex morphology of the patient's LAA is reproduced by the LAA model 10. Due to the complex anatomy, the length of the fixing member (not shown) has to be adjusted accordingly.

[0131] FIG. 7 is a photograph of the LAA model 10 with the braided closure member 1 pressed therein. The braided closure member 1 is filled with heat-resistant filling material such as ceramic wool 17. Due to the ceramic wool, the body part of the braided closure member 1 is pressed against the inner wall of the LAA model 10 to form the body part according to the LAA cavity.

[0132] FIG. 8 is a photograph of the LAA model 10 illustrating the fixing of the braided closure member 1 in the LAA model before heat treating. The LAA model 10 is equipped with a metal lid 11 and at least one metal rod 12 to fix the lid 11. It will be appreciated that other mechanisms for fixing the lid 11 are possible. The closed LAA model 10 together with the closure member 1 pressed therein is then heated through the transformation temperatures of the braiding material to attain the shape memory effect. In the case of Nitinol the heating temperature is 400 to 600° C.

[0133] FIG. 9 is a longitudinal three dimensional view of the LAA model 10 with the closure device as shown in FIG. 4 pressed therein after the heat-treatment. The closure device has its final shape. The LAA model is cut open to show how the closure device is arranged therein. The closure member 1 is with its lid part 3 in direct and close contact to the rim 18 of the LAA model 10 and in direct contact to the upper part 19 of the inner wall of the LAA cavity. The wire elements 8a, 8b of the fixing member have different lengths according to the different branches of the LAA cavity. Wire element 8a anchored in an LAA branch is longer than wire element 8b anchored in the central part of the LAA.

[0134] FIGS. 10 to 15 show various embodiments of the braided closure device inserted in the patient's LAA. FIG. 10 is a cross section of the patient's LAA 20 with the closure device of FIG. 4 inserted therein. A tension member 5 in the form of a coil spring is attached to the distal end of the braided closure member 1. Wire elements 8 of different length are attached to the coil spring, the wire elements being firmly anchored in the inner wall of the LAA cavity 21. A double filament 9 is attached to the lid part 3 of the closure member 1. The closure member 1 is in direct and close contact to the patient's LAA ostium 22 and to the upper part 23 of the inner wall of the patient's LAA cavity 21. In the case of repositioning, a double filament 9 is attached to the lid part 3 of the closure member 1 to withdraw the closure member 1 back into the delivery catheter. The filament 9 continues to the proximal end of the handle of the delivery catheter (see FIG. 1). After the final position of the closure device is reached, the double filament 9 is completely withdrawn from the closure device by pulling at one filament.

[0135] FIG. 11 is a cross section of the patient's LAA 20 with the closure device of FIG. 4 inserted therein. In contrast to FIG. 10, there is shown a braided closure member 1 whose body part 4 is not in direct contact to the tissue of the patient's LAA cavity 21. The lid part 3 of the closure member 1 with ring part 7 seals the LAA ostium 22.

[0136] FIG. 12 is a cross section of the patient's LAA 20 with a further embodiment of the closure device inserted therein. In contrast to FIG. 10, this alternative closure device has no tension member between closure member 1 and fixing member 2, the wire elements 8 of the fixing member 2 thus being directly grouped around the distal end of the braided closure member 1.

[0137] FIG. 13 is a cross section of the patient's LAA 20 with the closure device of FIG. 4 inserted therein as illustrated in FIG. 11. In addition to the device shown in FIG. 11, a guide wire 13 has been placed before insertion of the closure device to facilitate insertion. The closure member 1 and the tension member 5 have a central lumen 24 extending through the device and equipped with a valve 25 to seal the lumen 24. The lumen 24 provides the possibility of using a guidewire or guiding catheter.

[0138] FIG. 14 is a cross section of the patient's LAA 20 with a further embodiment of the closure device inserted therein. The closure device comprises a first closure member 1, a tension member 5 being distally attached to the closure member 1, and a double filament 9 being attached to the lid part 3 of the closure member 1. Between the tension member 5 and the fixing member 2 there is an additional braid functioning as an additional closure disc 26. The wire elements of the fixing member 2 are grouped around the distal end of the additional closure disc 26. The closure member 1 and the tension member 5 have a central lumen 24 extending through the device and equipped with a valve 25 to seal the lumen 24. The lumen 24 provides the possibility of placing a guide wire or guiding catheter as shown in FIG. 13 or of inserting anchoring members as shown in FIG. 15.

[0139] FIG. 15 is a cross section of the patient's LAA 20 with the closure device of FIG. 14 inserted therein. In contrast to the device shown in FIG. 14, a screw-in type coil 27 acting as an additional fixing member has been inserted.

[0140] FIG. 16 illustrates the closure of an LAA of the so called chicken wing type. The LAA ostium 22 is elongated and narrow and the LAA lobe is of the chicken wing type with an obvious bend in the end part. FIG. 16 makes the advantage of the invention particularly apparent, as the bent lobe with the elongated opening cannot be sealed with known occluders which are mainly circular.

[0141] FIG. 16a is a computer graphic made on the basis of the patient's LAA. FIG. 16b is the corresponding cross section with a Nitinol braid, as described in FIG. 12, inserted therein.

[0142] Regarding FIG. 16c, the closure member 1 is formed of biocompatible plastic. The fixing member is a T-bar 28 which is positioned at the distal end of the closure member 1. The closure member 1 comprises a lid part 3 and a body part in the form of a balloon 29, said balloon 29 being in close and direct contact to the patient's LAA cavity. The balloon 29 is filled with liquid or foam 30 made of silicone or polyurethane. The lid part 3 comprises a cover portion and a ring portion formed according to the patient's LAA ostium and sealing the LAA ostium 22. The lid part 3 and the balloon 29 have a central lumen extending through the device and equipped with a valve 25 to seal the lumen.

[0143] FIG. 17 shows how the closure device is guided into the heart. FIG. 17a shows the delivery catheter 31 with the closure member 1, fixing member 2 and tension member 5 in the release position. FIG. 17b is a cross section of the delivery catheter 31 showing the folded closure member 1, the tension member 5 and the fixing member 2. Guide wire 13 facilitates the placement of the device.

[0144] With continuing reference to FIG. 18, an exemplary insertion method is described. It will be appreciated that the method can be carried out using a guide wire as described in connection with FIG. 17. FIG. 18a shows a cross-section of the delivery catheter with the closure device in an initial configuration. In particular, the closure member 1 is in a compressed configuration. Likewise, the fixation member 2 is in a compressed configuration. The tension member connects the closure member 1 and the fixation member 2. The insertion catheter 31 is open at its distal end so that the closure device can be advanced from the catheter 31 by means of a pusher 32. The valve 25 prevents blood from flowing in a proximal direction through the lumen of the closure device. The closure device is completely pushed out of the insertion catheter 31 by means of the pusher 32. A thread 9 can be used to reposition the closure device if necessary.

[0145] FIG. 18b shows the insertion catheter 31 inserted into the patient's LAA 20. The fixation elements 2 have been pushed out of the catheter 31 and radially expanded. Because of their hook-shaped ends they have anchored to the internal wall of the LAA cavity 21. The closure device is secured to the LAA 20 and the tension member 5 is about to exit the catheter 31.

[0146] FIG. 18c shows the progress of implantation. The insertion catheter 31 has been further retracted and the braided closure member 1 has expanded. The lumen 24 is closed by the valve 25. Because the fixation elements 2 are anchored to the internal wall of the patient's LAA 20, the tension member 5 is tensioned by pulling the closure member 1 in a proximal direction during retraction of the catheter 31. This tension causes the closure member 1 to be biased against the LAA ostium 22 to thereby close and seal the LAA ostium 22. If desired or necessary, the closure member 1 can be repositioned with the help of the thread 9 by pulling the closure member 1 out of the ostium 22, rotating the closure member 1 and releasing the thread 9. The thread 9 may be a double thread and is removed after implantation of the closure device.

[0147] FIG. 19a is a cross section of the patient's LAA 20 with another embodiment of a closure device inserted therein. The fixing member is an adhesive layer 33 of a tissue adhesive being applied to the surface of the closure device. A protective layer 34 which is applied to the surface of the adhesive layer 33 protects the closure device from being glued to the LAA tissue during the insertion of the device. The lid 3 has a central lumen 24 extending through the device equipped with a valve 25 to seal the lumen 24. A screw-in type coil 27 acting as temporary fixing member is inserted through said lumen 24.

[0148] FIG. 19b shows the removal of the protective layer 34 and the gluing process. The protective layer 34 which is attached to a ring 35 is removed by pulling the ring 35 to thereby successively release the adhesive layer 33 to create an adhesive joint between the surface of closure device and the LAA tissue. After the adhesive process has been completed the temporary fixing member (coil spring 27) is removed.

[0149] FIG. 20 is a cross section of the patient's LAA 20 with another embodiment of a closure device inserted therein. A tension member 5 in the form of a coil spring is attached to the distal end of the braided closure member 1. Wire elements 8 with different lengths are attached to the coil spring 5, the wire elements 8 being firmly anchored into the inner wall of the LAA cavity 21. The lid has a connector 37 for a cable, such as an internal thread, so that an extension cable (not shown) can be attached to the closure device acting as an indifferent pole for a pacemaker or cardioverter. At the distal end of the closure device, between the closure member 1 and the coil spring 5, there is a bearing 36 so that the closure member 1 can be rotated in order to allow fine adjustment of the closure member 1 without removing the wire elements 8. It will be appreciated that the connector for a cable or the bearing may be included also in the other embodiments.

[0150] Some preferred embodiments of the invention are described in the following enumerated items 1 to 12. However, the invention is defined in the appended claims. [0151] 1. A medical closure device that is suitable for closing the left atrial appendage (LAA) consisting of a braid made of a shape memory material, a tension spring and at least one fixation element. The braid is proximally disc-shaped such that a closure disc is provided proximally, which conforms in shape to the anatomy of the ostium in the target LAA true to scale. The braid is distally connected to a tension spring, which has distally at least one fixation element. [0152] 2. The closure device according to item 1 formed of Nitinol. [0153] 3. The closure device according to item 1 or 2, wherein the braid is completely or partially covered with a plastic membrane on the outside or the inside. [0154] 4. The closure device of item 1, wherein the tension spring is made of Nitinol. [0155] 5. The closure device of item 1, wherein the fixation element is made of a Nitinol wire and formed hook-shaped at its distal end. [0156] 6. The closure device of item 1 or 5, wherein 3-10 fixation elements are provided which are grouped radially about the virtually extended central axis of the tension spring. [0157] 7. The closure device of item 6, wherein 4 Nitinol wires are provided having a distance of about 90 degrees from each other. [0158] 8. The closure device according to any one of items 1 to 7 having a central lumen and a self-sealing valve sealing the lumen to the outside. [0159] 9. A method of manufacturing a closure device that is configured to be inserted into a patient's LAA (left atrial appendage) cavity, the method comprising the following steps: [0160] a) providing a computer generated three-dimensional model of the LAA based on medical images of the LAA, [0161] b) transferring the data of the computer generated model to a 3-D printer device, [0162] c) manufacturing a real model by selective laser sintering, [0163] d) manufacturing a braid of a shape memory material and shaping the braid by pressing the braid into the model obtained in step c) or a subsequent model, wherein a braid is created by the pressing, which is formed proximally disc-shaped, such that a closure disc is created, which conforms in shape to the anatomy of the ostium in the target LAA true to scale; [0164] e) tempering the braid for fixation of the shape change; [0165] f) capturing the ends of the braid in a sleeve and connecting the braid with the tension spring, which has distally at least one fixation element. [0166] 10. A closure device manufactured according to a method described in item 9. [0167] 11. A braid of a shape memory material that is formed proximally disc-shaped so that a closure disc is provided, which conforms in shape to the anatomy of the ostium in the target atrial appendage true to scale. [0168] 12. An insertion catheter consisting of an insertion catheter, into which the closure device of the items 1 to 8 is inserted in a compressed configuration.

[0169] Further preferred embodiments are described in the enumerated following items 13 to 36, wherein the closure device as defined in the following items does not comprise at least one, any, various or all of the features of the closure device as defined in any one of the above items 1 to 8, 10 and 11. In a particularly preferred embodiment, the closure device defined in the following items does not comprise a tension spring. Likewise, the method as defined in the following items does not comprise at least one, any, various or all of the features of the method as defined in the aforementioned item 9. In a particularly preferred embodiment, in the method defined in the following items the LAA model is not manufactured by selective laser sintering. [0170] 13. A medical closure device that configured to be inserted into a patient's LAA (left atrial appendage) cavity, comprising a closure member and at least one fixing member. The closure member comprises a lid part and a body part one following the other in a proximal-distal direction. The lid part comprises a cover portion and a ring portion, the ring portion being configured to be circumferentially disposed along the rim of an individual LAA ostium, thus sealing the LAA ostium completely. [0171] 14. The closure device according to item 13, wherein the closure device is formed of metal or biocompatible polymer or a combination thereof. [0172] 15. The closure device according to item 13 or 14, wherein the closure device is formed of shape memory material. [0173] 16. The closure device according to any one of items 13 to 15, wherein the closure device is formed of Nitinol. [0174] 17. The closure device according to any one of items 13 to 16, wherein the body part of the closure member is configured to adjoin the tissue of an individual LAA cavity. [0175] 18. The closure device according to any one of items 13 to 17, wherein the closure member is a metal braid. [0176] 19. The closure device according to any one of items 13 to 18, wherein the closure member comprises a body part in the form of a polymer balloon and a lid part made of a polymer or of a metal braid. [0177] 20. The closure device according to item 18 or 19, wherein the braid comprises at least one layer of occluding material in the form of a coating or a patch. [0178] 21. The closure device according to any one of items 13 to 20, wherein the fixing member is hook-shaped and comprises at least one wire element or tape element made of shape memory material. [0179] 22. The closure device according to any one of items 13 to 21, wherein the fixing member comprises 2 to 10 wire elements, preferably 3 to 6 wire elements, connected to and grouped evenly around the distal end of the body part of the closure member. [0180] 23. The closure device according to item 22, wherein the wire elements of the fixing member have different lengths with respect to one another. [0181] 24. The closure device according to any one of items 13 to 23, further comprising a tension member placed between the closure member and the fixing member. [0182] 25. The closure device according to item 24, wherein the fixing member comprises two to ten wire elements, preferably three to six wire elements, connected to and grouped evenly around the distal end of the tension member. [0183] 26. The closure device according to item 24 or 25, wherein the tension member is a coil spring. [0184] 27. The closure device according to any one of items 13 to 26, further comprising a thread or double thread at the proximal end of the closure member. [0185] 28. The closure device according to any one of items 1 to 27, wherein the closure member has a central lumen extending through the lid part and the body part with a valve placed therein, said valve sealing the lumen. [0186] 29. The closure device according to item 13, wherein the whole closure device is made of Nitinol, including the closure member, the fixing member and a tension member, wherein the closure member is a braid comprising at least 30 wire elements having a diameter of about 0.03 to 0.15 mm, said braid defining the lid part and the body part; wherein the fixing member comprises two to ten wire elements grouped evenly around a distal end of the tension member; wherein the tension member is a coil spring, said coil spring being attached to the distal end of the body part of the closure member. [0187] 30. A method of manufacturing a closure device that is configured to be inserted into a patient's LAA (left atrial appendage) cavity, preferably the closure device of any one of items 13 to 29, the method comprising the following steps: [0188] a) generating a three-dimensional computer graphic of the patient's left atrial appendage (LAA) based on medical images of the LAA, [0189] b) transferring the data of the computer graphic to a 3-D printer device, [0190] c) forming an LAA model by 3-D printing, said model being an exact reproduction of the patient's LAA, [0191] d) manufacturing the closure device by pre-fabricating a closure member comprising a lid part and a body part one following the other in a proximal-distal direction and pre-fabricating a fixing member and forming at least the lid part of the closure member according to the LAA model obtained in step c) to obtain a pre-formed closure device with at least the lid part of the closure member conforming in size and shape to the patient's LAA ostium; and attaching the fixing member to the closure member either before forming the closure member or thereafter. [0192] 31. A method of manufacturing a closure device that is configured to be inserted into a patient's LAA (left atrial appendage) cavity, preferably the closure device of any one of items 13 to 29, the method comprising the following steps: [0193] a) generating a three-dimensional computer graphic of the patient's left atrial appendage (LAA) based on medical images of the LAA, [0194] b) transferring the data of the computer graphic to a 3-D printer device, [0195] c) forming an LAA model by 3-D printing, said model being an exact reproduction of the patient's LAA, [0196] d) manufacturing the closure device by pre-fabricating a closure member comprising a lid part and a body part one following the other in a proximal-distal direction, and pre-fabricating a fixing member, filling the closure member with a heat-resistant material and forming the closure member by placing it into the LAA model obtained in step c) to obtain a pre-formed closure device which conforms in size and shape to the patient's LAA ostium and the LAA cavity; and attaching the fixing member to the closure member either before forming the closure member or thereafter. [0197] 32. A method of manufacturing a closure device that is configured to be inserted into a patient's LAA (left atrial appendage) cavity, preferably the closure device of any one of items 13 to 29, the method comprising the following steps: [0198] a) generating a three-dimensional computer graphic of the patient's left atrial appendage (LAA) based on medical images of the LAA, [0199] b) transferring the data of the computer graphic to a 3-D printer device, [0200] c) forming an LAA model by 3-D printing, said model being an exact reproduction of the patient's LAA, [0201] d) manufacturing the closure member and forming the closure member by first forming a metal ring according to the opening of the LAA model and fixing the closure member to the metal ring to shape it. [0202] 33. The method according to any one of items 30 to 32, wherein the medical image is an X-ray image, a CT scan, an MRI scan, or an ultrasound image. [0203] 34. The method according to any one of items 30 to 33, wherein 3-D printing is 3-D laser printing and the LAA model is made of metal. [0204] 35. The method according to any one of items 30 to 33, wherein 3-D printing is 3-D polymer printing and the LAA model is made of polymer. [0205] 36. The method according to any one of items 30 to 35, wherein the closure device is made of a shape memory alloy, the method further comprising the following step e): [0206] e) heat-treating the LAA model together with the closure member or closure device placed therein to the transformation temperature of the shape memory alloy to obtain a pre-formed closure device with at least the lid part of the closure member conforming in size and shape to the patient's LAA ostium.