Claims:WE CLAIM:
1. An occlusion device (100) comprising:
a. a frame (1) including an upper disc (5), a lower disc (7) and a waist (9), the upper disc (5) having a primary top portion (5a) and a primary bottom portion (5b), the lower disc (7) having a secondary top portion (7a) and a secondary bottom portion (7b), the waist (9) extending between the primary bottom portion (5b) of the upper disc (5) and the secondary bottom portion (7b) of the lower disc (7); and
b. a jacket (3) provided at a center of the upper disc (5) or the lower disc (7);
wherein the upper disc (5) includes a convex elliptical shape;
wherein the lower disc (7) includes a concave elliptical shape;
wherein the length of the upper disc (5) is greater than the length of the lower disc (7).
2. The occlusion device (100) as claimed in claim 1 wherein, the frame (1) comprises a plurality of monofilament strands of a biodegradable material and/or metal wires.
3. The occlusion device (100) as claimed in claim 2 wherein, the metal wires comprises a plurality of nitinol wires.
4. The occlusion device (100) as claimed in claim 1 wherein, the frame (1) includes a breadth and a height (H) ranging between 06- 22mm and 5- 7mm respectively.
5. The occlusion device (100) as claimed in claim 1 wherein, the frame (1) is covered with one or more layers of fabric.
6. The occlusion device (100) as claimed in claim 1 wherein, the jacket (3) is made from one of, a biodegradable polymer, a metal or a radiopaque material.
7. The occlusion device (100) as claimed in claim 1 wherein, the length of the upper disc (5) ranges between 08mm to 26 mm and the length of the lower disc (7) ranges between 06 mm to 26mm.
8. The occlusion device (100) as claimed in claim 1 wherein, the waist (9) includes a diameter ranging between 02mm to 16mm.
9. The occlusion device (100) as claimed in claim 1 wherein, the said device is self-expandable in a radial direction.
10. The occlusion device (100) as claimed in claim 1 wherein, the device comprises a coating of a coating solution, the coating solution including poly-caprolactone with dichloromethane.
, Description:FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(Section 10 and Rule 13)

1. TITLE OF THE INVENTION:
OCCLUSION DEVICE AND METHOD OF MANUFACTURING THEREOF

2. APPLICANTS:
Meril Life Sciences Pvt Ltd, an Indian company, of the address Survey No. 135/139 Bilakhia House Muktanand Marg, Chala, Vapi-Gujarat 396191

3. The following specification particularly describes the invention and the manner in which it is to be performed:

FIELD OF INVENTION
[001] The present invention relates to a medical device, more specifically, the present invention relates to an occlusion device for a para-valvular leak.
BACKGROUND
[002] Para-valvular leak (PVL) is a medical complication related to surgical replacement of an aortic and/or mitral valve. The PVL refers to a medical condition in which blood flows through a micro-hole created between an implanted valve and a cardiac tissue due to lack of appropriate sealing. The para valvular leaks may result in abnormal pressure or traction forces on the prosthesis valve which may lead to damage to the tissue growth around the valve. Further, PVL may cause uneven blood distribution in the heart chamber, and even a minuscule of regurgitation can significantly increase left atrial pressure. The elevation of pulmonary arterial pressures may lead to right-sided heart failure. The factors which are known to increase the risk of para-valvular leak may be for example, calcification of the implanted valve, infection, suturing technique and size and shape of the prosthetic valve implant.
[003] PVL can be treated surgically via suturing and/or transcatheter deployment of an occlusion device. The suturing may not be very beneficial as it may get damaged over time and may further cause an undesired leak or blood flow. Therefore, the para-valvular leak may be sealed by means of an occlusion device. The occlusion device may be placed along with the artificial valve to occlude or seal the micro-holes created during the valve replacement procedure and block the blood flow.
[004] Conventional occlusion devices for treatment of PVL are circular, square, and/or rectangular shaped. The said shapes of the device may cause difficulty when two or more implants are required for sealing the leakages at a close distance. The said shapes of the device cover less area of the para-valvular leaks longitudinally. Moreover, the conventional occlusion devices do not cover the small hole and/or leaks which maybe present near the PVL. Therefore, there exists a need for an improved occlusion device for the treatment of a para-valvular leak (PVL) in a patient.
SUMMARY
[005] An occlusion device of the present invention is disclosed. The occlusion device incudes a frame which may be manufactured by braiding of a plurality of monofilaments strands of biodegradable material and/or metal wires. The frame further includes an upper disc, a lower disc and a waist.
[006] The upper disc includes a primary top portion and a primary bottom portion. In an embodiment, the upper disc includes a convex elliptical shape.
[007] The lower disc includes a secondary top portion and a secondary bottom portion. In an embodiment, the lower disc includes a concave elliptical shape. The length of the upper disc may be greater than the length of the lower disc.
[008] In an embodiment, the waist extends between the primary bottom portion of the upper disc and the secondary bottom portion of the lower disc.
[009] A jacket is provided at a center of the upper disc or the lower disc. In an embodiment the jacket is disposed on the lower disc of the frame.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The summary above, as well as the following detailed description of illustrative embodiments, is better understood when read in conjunction with the appended drawings. For the purpose of illustrating the present disclosure, exemplary constructions of the disclosure are shown in the drawings. However, the disclosure is not limited to specific methods and instrumentalities disclosed herein. Moreover, those in the art will understand that the drawings are not to scale.
[0011] FIG. 1 depicts a three-dimensional view of the occlusion device in accordance with an embodiment of the present invention.
[0012] FIG. 2 illustrates a flow-chart depicting the manufacturing process of the occlusion device in accordance with an embodiment of the present invention.
DETAILED DESCRIPTION OF THE DRAWINGS
[0013] Prior to describing the invention in detail, definitions of certain words or phrases used throughout this patent document will be defined: the terms "include" and "comprise", as well as derivatives thereof, mean inclusion without limitation; the term "or" is inclusive, meaning and/or; the phrases "coupled with" and "associated therewith", as well as derivatives thereof, may mean to include, be included within, interconnect with, contain, be contained within, connect to or with, couple to or with, be communicable with, cooperate with, interleave, juxtapose, be proximate to, be bound to or with, have a property of, or the like; Definitions of certain words and phrases are provided throughout this patent document, and those of ordinary skill in the art will understand that such definitions apply in many, if not most, instances to prior as well as future uses of such defined words and phrases.
[0014] Particular embodiments of the present disclosure are described herein below with reference to the accompanying drawings, however, it is to be understood that the disclosed embodiments are merely examples of the disclosure, which may be embodied in various forms. Well-known functions or constructions are not described in detail to avoid obscuring the present disclosure in unnecessary detail. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed structure.
[0015] In accordance with the present disclosure, an occlusion device for sealing a para-valvular leak and a method of manufacturing thereof is disclosed. The occlusion device may be made of a bioresorbable polymer or a metal. In various embodiments, the occlusion device may be manufactured in various shapes and sizes in order to properly fit at a treatment site. In an embodiment, the occlusion device is manufactured in an elliptical shape. The elliptical shape of the occlusion device may seal multiple leaks eliminating the need of deploying multiple devices at the treatment site. The occlusion device may help to reduce and/or stop the blood leakage at the valvular region. As the elliptical shape of the said device covers more area longitudinally between the implant and the valvular region, less number of implants may serve the purpose at the treatment site. The occlusion device of the present invention may be deployed at the treatment site with the help of a catheter assembly.
[0016] The occlusion device of the present invention may include a waist and at least two discs (upper and lower). The waist of the occlusion device may be circular in shape with a twisted design which helps the device of the present invention to adjust within any size of the para-valvular leak to enhance complete occlusion within a period of time.
[0017] The at least two discs (upper and lower) of the occlusion device are attached with the waist. The at least two discs may vary from each other in diameter and length which helps in providing a better grip and impressive sealing to the occlusion device when the at least two discs are being passed towards each other.
[0018] A jacket may be provided on an end of the at least two discs. The jacket is provided in order to facilitate easy deployment of the occlusion device. The jacket also helps for better entrapment of the said device. Further, the jacket reduces the risk of detachment of the occlusion device.
[0019] The occlusion device of the present invention may also include one or more layers of fabric provided at the at least two discs and the waist of the said device. The one or layers of fabric enhances the tissue growth on the said device without causing any interruptions to the artificial heart valve. The occlusion device of the present invention may also include a jacket which is provided to facilitate easy and better deployment of the device.
[0020] The occlusion device of the present invention may further be coated with a coating solution. The coating provides excellent grip to the occlusion device and also enhances the strength of the said device in order to provide an excellent grip to the said device. The coating disposed on the surface of the occlusion device further enhances the shape memory property of the said device.
[0021] Now referring specifically to the drawings, FIG. 1 depicts a three-dimensional view of the occlusion device 100. The occlusion device 100 may include a frame 1, a jacket 3, an outer surface (not shown) and an inner surface (not shown). The occlusion device 100 may be self-expandable in radial direction and may be delivered with the help of a catheter assembly. The profile of the catheter may be in a range of 6 French to 10 French. The occlusion device 100 may have a controlled degradation rate inside the body. For example, the occlusion device 100 may degrade completely over a period of 1 to 2 years following the treatment of the targeted defect.
[0022] The frame 1 of the occlusion device 100 may be manufactured by braiding of a plurality of monofilaments strands of biodegradable material and/or metal wires. The biodegradable material may include without limitation, poly-L-lactic acid (PLLA), poly lactic-co-glycolic acid (PLGA), poly-D,L-lactic acid (PDLA), polydioxanone (PDO) or combination thereof. The metals may include without limitation, nitinol, elgiloy, stainless steel (SS) etc. In an embodiment, the frame 1 is made of nitinol wires. Nitinol is utilized for making the frame 1 due to its excellent biocompatibility, kink resistance, physiological compatibility, shape-memory deployment, dynamic interference, and fatigue resistance.
[0023] The thickness of the nitinol wires may be in the range of 50- 300 µm, preferably 60-200 µm, more preferably 70-170 µm. In an embodiment, the thickness of the nitinol wire is 70 µm.
[0024] Optionally/additionally, if the frame 1 is made of a biodegradable material, the frame 1 may include a locking system (not shown). The locking system may help to keep the occlusion device 100 effectively anchored to the tissue wall containing an opening and/or defect.
[0025] The breadth of the frame 1 may range between 06mm to 22mm. In an embodiment, the breadth of the frame 1 is 08 mm.
[0026] In an exemplary embodiment, the frame 1 of the occlusion device 100 includes a plurality of portions. The plurality of portions includes at least two discs- an upper disc 5, a lower disc 7 and a waist 9 extending between the upper disc 5 and the lower disc 7. The upper disc 5 and the lower disc 7 of the frame 1 cover and/or occlude a defect at a treatment site. The height of the frame 1 (including the upper disc 5, the lower disc 7 and the waist portion 9) may be in the range of 5- 7mm. In an embodiment, the height H of the frame 1 is 06mm.
[0027] The upper and the lower disc (5 and 7) may be of any shape known in the art depending upon the type of defect. In an embodiment, the upper disc 5 includes a primary top portion 5a and a primary bottom portion 5b. The lower disc 7 includes a secondary top portion 7a and a secondary bottom portion 7b. The shape of the upper disc 5 and the lower disc 7 may be same and/or different. In an embodiment, the upper and the lower discs (5 and 7) are elliptical in shape. The upper disc 5 may have a convex elliptical shape and the lower disc 7 may have a concave elliptical shape.
[0028] The elliptical shape of the upper and lower discs (5 and 7) may reduce and/or stop blood leakage of multiple leaks at a valvular region in a patient. The elliptical shape of the upper and lower discs (5 and 7) covers a large longitudinal area, therefore can easily occlude a greater number of leaks present at the treatment site within a short distance. The elliptical shape of the at least two discs also helps the occlusion device 100 to fit properly at a defect site.
[0029] The upper disc 5 and the lower disc 7 may have a same and/or different value of length. In an embodiment, the length of the upper disc 5 is greater than the lower disc 7. The length of the upper disc 5 ranges between 08mm to 26 mm and the length of the lower disc 7 ranges between 06 mm to 26mm. In an embodiment, the length of the upper disc 5 is 12mm and the length of the lower disc is 10mm. The thickness of the upper disc 5 and the lower disc 7 may be same and/or different. The thickness of the upper disc 5 may be in a range of 01mm - 02mm and the thickness of the lower disc 7 may be in a range of 01mm - 02mm. In an embodiment, the thickness of the upper disc 5 is 01mm and the thickness of the lower disc 7 is 01mm.
[0030] The upper disc 5 may perfectly overlap on the lower disc 7 when the occlusion device 100 is implanted at the defect site. The complete overlapping between the upper disc 5 and the lower disc 7 lead to adequate occlusion of the leak at the treatment site. The difference in diameters of the two discs (the upper disc 5 and the lower disc 7) may provide excellent grip and/or sealing, when the upper disc 5 and the lower disc 7 are pressed against each other at the treatment site.
[0031] The waist 9 may extend between the upper disc 5 and the lower disc 7. In an embodiment, the waist 9 extends between the primary bottom portion 5b of the upper disc 5 and the secondary bottom portion 7b of the lower disc 7. The waist 9 may have any shape known in the art. In an embodiment, the waist 9 has a cylindrical shape with a slightly narrow diameter at one of the ends (not shown). The wire used to make the waist 9 may be twisted when the diameter of the waist 9 is narrowed or reduced. The said shape of the waist 9 may help the occlusion device 100 to adjust within any size of the para-valvular leak in order to provide complete occlusion within a predefined period of time. In cases where high pressure para-valvular leaks are present, the narrow diameter of the waist 9 provides excellent occlusion. The waist 9 along with the upper disc 5 and the lower disc 7 provides excellent grip to the defected area in order to reduce blood leakage.
[0032] The waist 9 is placed in the defect when the occlusion device 100 is implanted at the treatment site. The diameter of the waist 9 may vary depending upon the size of targeted defect. The diameter of the waist 9 may be in a range of 02mm to 16mm. In an embodiment, the diameter of the waist 9 is 6mm. In an embodiment, the upper disc 5 and the lower disc 7 have a diameter distinctly larger compared to the waist 9 in order to enable the occlusion device 100 to be efficiently seated in the defect.
[0033] In an embodiment, the occlusion device 100 is provided with a jacket 3. The jacket 3 may be provided on one of, the two upper disc 5 and the lower disc 7. In an embodiment, the jacket 3 is provided at a center of the lower disc 7 of the frame 1. The jacket 3 may be made of without limitation, a biodegradable polymer, a metal or a radiopaque material. The biodegradable material may include without limitation PLGA, PLA, PDO. The metal may include without limitation stainless steel, CoCr, magnesium, nitinol, or any radiopaque material. In an embodiment, the jacket 3 is made of stainless steel.
[0034] The jacket 3 may be of any shape such as a conical-shaped jacket or a ball-shaped jacket. In an embodiment, if the frame 1 is made of a metal, the jacket 3 is a conical shaped jacket. In another embodiment, if the frame 1 is made of a bioresorbable material, the jacket 3 is a ball-shaped jacket which includes one or more barbs and/or hook like extensions.
[0035] The jacket 3 may be mounted on the lower disc 7 by any method such as crimping, laser welding. In an embodiment, the jacket 3 is crimped on the lower disc 7 of the frame 1 of the occlusion device 100. Post crimping, the jacket 3 may be subjected to heat treatment such that the jacket 3 is properly attached on the lower disc 7 of the frame 1. The jacket 3 may act as a housing for a bunch of free ends of the strands as well as facilitate effective deployment of the occlusion device 100.
[0036] Additionally, the plurality of portions of the frame 1 (i.e. the upper disc 5, the lower disc 7 and the waist 9) may be covered with one or more layers of fabric (not shown). In an embodiment, three layers of fabric are disposed on the surface of the frame 1. The one or more fabric layers are porous and may play a vital role as an appendage in the occlusion process and/or provide enhanced occlusion at the treatment site. Further, the one or more fabric layers do not rupture or destroy the red blood cells when the occlusion device 100 is deployed at the treatment site.
[0037] The one or more fabric layers may be stitched on the surface of the frame 1 with the help of a curved needle (elaborated below in FIG. 2). The fabric may help in promoting tissue growth over the occlusion device 100, thereby blocking the blood flow at the defect site.
[0038] The fabric may include a plurality of monofilaments and/or multifilament strands of bioresorbable material. The bioresorbable material may include without limitation PLGA, PLLA, PDLA, PDO, or combination thereof. In an embodiment, the bioresorbable material is poly L- lactide (PLA). In another embodiment, if the frame 1 is made of metal, the one or more layers of fabric are made of polyethylene terephthalate (PET). The thickness of the strands of the fabric material may be in range of 10-30 GSM (grams per square meter), more preferably 15-25 GSM.
[0039] FIG. 2 illustrates an exemplary embodiment of the manufacturing process of the occlusion device 100 of the present invention. The process of manufacturing the occlusion device 100 commences at step 201. At this step, the strands are braided over a mandrel to form a braided structure (not shown). The braiding may be performed by means of a braiding machine. The braiding machine may include without limitation a flat braiding machine and/or a tubular braiding machine.
[0040] The braiding may be performed at a constant take-up speed of 1.0- 5.0 V/Hz, more preferably 3.0- 5.0V/Hz. The rotation of the mandrel varies between 20- 50 V/Hz, more preferably 30- 50V/Hz. The braiding angles range between 60° to 150°, preferably 80° to 130°, more preferably 90° to 120°.
[0041] At step 203, the braided structure is subjected to annealing/ heat treatment. In an embodiment, the annealing process is performed in two stages- a primary annealing stage and a secondary annealing stage/shape-setting stage (step 307). The primary annealing stage may be performed at a temperature ranging from 60- 150°C, more preferably 90- 110°C and for time duration of 1- 8 hours, more preferably 3- 4 hours. The primary annealing stage changes the mechanical properties of bioresorbable filaments and also provides shape memory to the device. The secondary annealing stage/shape-setting stage is performed after the braided occlusion device 100 is subjected to the molding process in step 205.
[001] At step 205, the braided structure is subjected to a process of molding. The process of molding is performed to yield the frame 1 having a desired anatomy (for example as depicted in FIG. 1). The molding step may be performed by means of appropriate molds which may resemble any predefined shape. In an embodiment, the mold includes two elliptical discs corresponding to the upper disc 5, the lower disc 7 respectively and a circular portion extending between the at least two discs (the upper disc 5 and the lower disc 7) corresponding to the waist 9. The material used for manufacturing of mold may include stainless steel (grade 316L). In an embodiment, the mold is made of a medical grade stainless steel.
[0042] At step 207, the frame 1 is subjected to a process of secondary annealing stage/shape-setting stage. The frame 1 may be annealed using a vacuum annealing unit. In an embodiment, if the frame 1 is made of bioresorbable material, the secondary annealing stage/shape-setting stage is performed in a vacuum annealing unit at a temperature ranging from 60- 150°C, more preferably 90- 110°C and for time duration of 1- 8 hours, more preferably 3- 4 hours at a temperature of 60°C to 150°C.
[0043] In another embodiment, if the frame 1 is made of metal, the secondary annealing stage /shape-setting stage is performed at higher temperature ranging between 500°C-520°C, preferably 505°C-510°C to achieve shape memory.
[0044] The secondary annealing process/shape-setting process is performed in order to achieve desired strength and shape memory property to the device. It also reduces the induced stress possessed inside the filament at the time of manufacturing.
[0045] At step 209, the frame 1 is subjected to welding and jacketing. The process of welding may be performed before the process of jacketing. During the process of braiding, the frame 1 may include some loose ends. The loose strands of the frame 1 are brittle in nature, consequently may pose a risk of damage to the tissue wall. Therefore, the loose ends of the frame 1 may welded in order to achieve the predefined dimensions of the occlusion device 100. The said predefined dimensions may include the diameter, shape and height of the occlusion device 100, the length of the upper disc 5 and the lower disc 7. The said predefined dimensions may depend on the size of the para-valvular leak.
[0046] In an embodiment, the loose ends (not shown) of the frame 1 are present at the lower disc 7 of the occlusion device 100. The said loose ends may be welded using a laser welding machine. The process of welding may be performed by holding together the cluster of strands at the lower disc 7 and laser welding is done over the said cluster of loose strands to form a ball shaped structure (not shown).
[0047] Post the process of welding, the frame 1 is subjected to a process of jacketing to form the occlusion device 100. The jacket 3 is mounted over the ball-shaped structure of the frame 1. The jacket 3 may be mounted by means of without limitation laser welding, crimping, etc. In an embodiment, if the occlusion device 100 is made of a bioresorbable material, the jacket 3 is crimped on the ball shaped structure provided on the lower disc 7 of the frame 1. Post crimping, the jacket 3 is subjected to heating at a high temperature such that the jacket 3 is efficiently attached with the filaments of the occlusion device 100.
[0048] In another embodiment, if the occlusion device 100 is made of a metal, the jacket 3 is laser welded on the ball shaped structure provided on the lower disc 7 of the frame 1.
[0049] At step 211, the occlusion device 100 is subjected to coating. The coating is done on the outer and/or inner surface of the occlusion device 100 with the help of a coating solution. The process of coating may be performed either using spray coating or dip coating method. In an embodiment, the process of coating is performed using spray coating method. In the spray coating method the primary coating solution is sprayed over the surface of the occlusion device 100. The coating parameters must be accurately controlled like the distance between the spray gun and the occlusion device 100, the mandrel rotation, the nitrogen gas pressure, the oscillation rate and the solution flow rate, etc.
[0050] In an embodiment, the distance between the spray gun and the occlusion device 100 varies from 4-6cm to achieve a smooth coating surface. The rotation of the mandrel is maintained between 10- 60rpm, preferably 20- 50rpm, and preferably 25- 45rpm. The pressure of inert nitrogen gas ranges from 6psi to 8psi. The oscillations rate ranges from 40 oscillations per minute to 50 oscillations per minute. The flow rate of the coating solution ranges 0.2ml or 0.5ml per minute. The said parameters are set to form a thin, uniform and smooth coating over the degradable occlusion device 100.
[0051] The amount of coating solution used may range from 05ml to 45ml, more preferably 10 ml to 40 ml, and preferably 15- 35ml, depending upon the size of the occlusion device 100. The coating process is performed in clean room environment (Class 10,000) to avoid the interference of temperature and moisture during the spray coating. In an embodiment, the temperature and humidity of clean room is maintained at 22°C ±3°C and 45%, respectively.
[0052] The coating solution may include without limitation, PGS (poly (glycerol sebacate), poly-L-lactide-co-caprolactone (PLCL) or poly-caprolactone (PCL) with or without cross linkers. The coating solution which includes PCL with dichloromethane improves the strength of the occlusion device 100 and bonds the cross-over points of the braided structure. The coating solution of the present invention includes PCL due to its hydrophobic, semi-crystalline nature. The crystallinity of PCL decreases with increasing molecular weight. The good solubility of PCL, its low melting point (59°C - 64°C temperature) and exceptional blend-compatibility enhances the properties of the coating solution of the present invention. The use of PCL provides advantages such as, tailor able degradation kinetics and mechanical properties, ease of shaping and manufacture enabling appropriate pore sizes conducive to tissue in-growth.
[0053] The coating solution also provides excellent grip to the occlusion device 100 and enhances the strength of the said device. The coating disposed on surface of the occlusion device 100 further enhances the shape memory property of the said device.
[0054] Due to the shape memory property, the occlusion device 100 of the present invention provides excellent grip and the ability to compress in order to be loaded inside the catheter assembly. The said device regains its original shape after releasing the said device at the defect site. The shape memory property also helps in providing the elliptical or oval shape to the occlusion device 100.
[0055] At step 213, the occlusion device 100 is stitched with one or more layers of fabric. In an embodiment, the one or more layers of fabric are stitched to the frame 1 of the occlusion device 100 by means of a curved needle in a manner where one strand of fabric passes through another strand of fabric by leaving one cross point across the outer diameter of the frame. Stitching the one or more layers of fabric with the frame 1 imparts strengths, elasticity and/or durability to the occlusion device 100 when the said device is being loaded inside the catheter or after the deployment of the said device to the treatment site.
[0056] At step 215, the occlusion device 100 is subjected to sterilization followed by packaging. Firstly, the occlusion device 100 is subjected to primary packaging. In an embodiment, the primary packaging is done with the help of a Tyvek pouch.
[0057] Secondly, the occlusion device 100 is subjected to sterilization. In an embodiment, the said device is sterilized with the help of e-beam radiation process. Post sterilization, the occlusion device 100 is subjected to final packaging. In an embodiment, the para-valvular leak 100 is packaged in a box.
[0058] The scope of the invention is only limited by the appended patent claims. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used.