DEVICES FOR REDUCING LEFT ATRIAL PRESSURE HAVING BIODEGRADABLE CONSTRICTION, AND METHODS OF MAKING AND USING SAME

• US 20130030521A1
• Filed: 07/28/2011
• Published: 01/31/2013
• Est. Priority Date: 07/28/2011
• Status: Active Grant

• Current Assignee: V-Wave Ltd.
• Original Assignee: V-Wave Ltd.
• Inventors: NITZAN, Yaacov, Yacoby, Menashe
• Granted Patent: US 9,629,715 B2
• Time in Patent Office: Days
• US Class Current: 623/2.13
• CPC Class Codes: A61B 17/0057 Implements for plugging an opening in the wall of a hollow or tubular organ, e.g. for sealing a vessel puncture or closing a cardiac septal defect sutures A61B17/04; closing rectum or urethra near body surface A61F2/0009
• CPC Class Codes: A61B 2017/00004 (bio)absorbable, (bio)resorbable, resorptive for implantable prostheses A61F2210/0004
• CPC Class Codes: A61B 2017/00243 cardiac
• CPC Class Codes: A61B 2017/00252 for by-pass connections, i.e. connections from heart chamber to blood vessel or from blood vessel to blood vessel
• CPC Class Codes: A61B 2017/00592 Elastic or resilient implements
• CPC Class Codes: A61B 2017/00606 Implements H-shaped in cross-section, i.e. with occluders on both sides of the opening
• CPC Class Codes: A61B 2017/00623 Introducing or retrieving devices therefor
• CPC Class Codes: A61F 2/2412 with soft flexible valve members, e.g. tissue valves shaped like natural valves check valves with flexible valve members in general F16K15/14
• CPC Class Codes: A61F 2/2418 Scaffolds therefor, e.g. support stents
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2230/001 Figure-8-shaped, e.g. hourglass-shaped
• CPC Class Codes: A61F 2250/0039 differing in diameter

Abstract

A device for regulating blood pressure between a patient'"'"'s left atrium and right atrium comprises an hourglass-shaped stent comprising a neck region and first and second flared end regions, the neck region disposed between the first and second end regions and configured to engage the fossa ovalis of the patient'"'"'s atrial septum; and a one-way tissue valve coupled to the first flared end region and configured to shunt blood from the left atrium to the right atrium when blood pressure in the left atrium exceeds blood pressure in the right atrium. The inventive device may include a biodegradable material that biodegrades to offset flow changes caused by tissue ingrowth. The inventive device may reduce left atrial pressure and left ventricular end diastolic pressure, and may increase cardiac output, increase ejection fraction, relieve pulmonary congestion, and lower pulmonary artery pressure, among other benefits.

Claims

1. A device for regulating blood pressure between a patient'"'"'s left atrium and right atrium, the device comprising:

a stent comprising a neck region and first and second flared end regions, the neck region disposed between the first and second end regions and configured to engage the fossa ovalis of the patient'"'"'s atrial septum;

a one-way tissue valve having an outlet coupled to a first portion of the first flared end region and an inlet coupled to a second portion of the first flared end region proximal to the neck region, the valve configured to shunt blood from the left atrium to the right atrium when blood pressure in the left atrium exceeds blood pressure in the right atrium; and

a biodegradable material disposed in the neck region and the second flared end region and configured to biodegrade to offset changes in flow caused by tissue ingrowth.

2. The device of claim 1, wherein the biodegradable material comprises collagen-terpolymer, polylactic acid (PLA), poly L-lactic acid (PLLA), polyglycolic acid (PGA), poly(lactic-co-glycolic) acid copolymer (PLGA), poly(ε

-caprolactone), methacrylated dextran-aminoethyl methacrylate copolymer (Dex-MA/AEMA), polydiaxanone, poly(glycerol sebacate) (PGS), polysialic acid (PSA), collagen type I/III, chitosan, or chitin.

3. The device of claim 1, wherein the biodegradable material has a thickness of 0.10 to 0.50 mm.

4. The device of claim 1, wherein the first and second flared end regions each flare by about 50 to 120 degrees.

5. The device of claim 1, wherein the stent comprises a plurality of sinusoidal rings interconnected by longitudinally extending struts.

6. The device of claim 1, wherein the stent comprises a shape memory material, and wherein the shape memory material is coated with a biocompatible material from the neck region to the second flared end region.

7. The device of claim 6, wherein the shape memory material comprises a shape memory metal.

8. The device of claim 6, wherein the tissue valve extends between the first flared end region and the biocompatible material.

9. The device of claim 1, wherein the inlet of the tissue valve is about 1-3 mm from a narrowest portion of the neck region, and the outlet of the tissue valve is about 5-8 mm from the narrowest portion of the neck region.

10. The device of claim 9, wherein the tissue valve comprises a sheet of tissue having a flattened length of about 10-16 mm, and the sheet of tissue is folded and sutured to define two or more leaflets each having a length of about 5-8 mm.

11. The device of claim 1, wherein the tissue valve has a flattened length no greater than 18 mm, a flattened height no greater than 10 mm, and a flattened area no greater than 150 square mm.

12. The device of claim 1, wherein the device is configured so that, when the shunt is deployed across the patient'"'"'s atrial septum, the first flared end region protrudes 5.5 to 7.5 mm into the right atrium.

13. The device of claim 12, wherein the device is configured so that, when the shunt is deployed across the patient'"'"'s atrial septum, the second flared end region protrudes 2.5 to 7 mm into the left atrium.

14. The device of claim 13, wherein the neck has a diameter of 4.5 to 5.5 mm.

15. The device of claim 14, wherein the first flared end region has a diameter between 9 and 13 mm, and wherein the second flared end region has a diameter between 8 and 15 mm.

16. The device of claim 1, wherein the stent is configured to transition between a collapsed state suitable for percutaneous delivery and an expanded state when deployed across the patient'"'"'s fossa ovalis.

17. The device of claim 1, wherein the stent has an hourglass configuration in the expanded state.

18. The device of claim 1, wherein the one-way tissue valve comprises pericardial tissue of bovine, porcine, or equine origin.

19. The device of claim 18, wherein the pericardial tissue consists primarily of mesothelial and connective tissue layers and substantially no dense fibrous layer.

20. The device of claim 1, wherein the one-valve tissue valve comprises two or more leaflets.

21. The device of claim 1, wherein the stent is configured for implantation through the middle of the fossa ovalis, away from a surrounding limbus, inferior vena cava, and atrial wall.

22. The device of claim 1, wherein the biocompatible material comprises expanded-polytetrafluoroethylene, polyurethane, DACRON (polyethylene terephthalate), silicone, polycarbonate urethane, or pericardial tissue from an equine, bovine, or porcine source.

23. The device of claim 1, including means for measuring cardiac output of the subject, wherein shunting blood from the left atrium to the right atrium increases the cardiac output of the subject.

24. The device of claim 1, including means for measuring pulmonary congestion of the subject, wherein shunting blood from the left atrium to the right atrium decreases pulmonary congestion of the subject.

25. The device of claim 1, including means for measuring pulmonary artery pressure of the subject, wherein shunting blood from the left atrium to the right atrium decreases the pulmonary artery pressure of the subject.

26. The device of claim 1, including means for measuring ejection fraction of the subject, wherein shunting blood from the left atrium to the right atrium increases the ejection fraction of the subject.

27. The device of claim 1, including means for measuring fractional shortening of the subject, wherein shunting blood from the left atrium to the right atrium increases the fractional shortening of the subject.

28. The device of claim 1, including means for measuring fractional shortening of the subject, wherein shunting blood from the left atrium to the right atrium decreases the left ventricle internal diameter in systole of the subject.

29. A device for regulating blood pressure between a patient'"'"'s left atrium and right atrium, the device comprising:

a stent comprising a neck region and first and second flared end regions, the neck region disposed between the first and second end regions and configured to engage the fossa ovalis of the patient'"'"'s atrial septum;

a biocompatible material disposed on the stent in the neck and the second flared end region and a portion of the first flared end region;

a one-way tissue valve configured to shunt blood from the left atrium to the right atrium when blood pressure in the left atrium exceeds blood pressure in the right atrium, the valve having an outlet coupled to the first flared end region and an inlet coupled to an edge of the biocompatible material, the valve and the biocompatible material defining a continuous sheath that inhibits excessive tissue ingrowth into the valve and channels blood flow through the valve; and

a biodegradable material disposed in the neck region and the second flared end region and configured to biodegrade to offset changes in flow caused by tissue ingrowth.

30. The device of claim 29, wherein the biodegradable material comprises collagen-terpolymer, polylactic acid (PLA), poly L-lactic acid (PLLA), polyglycolic acid (PGA), poly(lactic-co-glycolic) acid copolymer (PLGA), poly(ε

-caprolactone), methacrylated dextran-aminoethyl methacrylate copolymer (Dex-MA/AEMA), polydiaxanone, poly(glycerol sebacate) (PGS), polysialic acid (PSA), collagen type chitosan, or chitin.

31. The device of claim 29, wherein the biodegradable material has a thickness of 0.10 to 0.50 mm.

32. The device of claim 29, wherein the biocompatible material promotes limited tissue ingrowth into the valve, the tissue ingrowth comprising an endothelial layer inhibiting thrombogenicity of the device.

33. The device of claim 29, wherein the edge of the biocompatible material is about 1-3 mm from a narrowest portion of the neck region.

34. A device configured for implantation in a fossa ovalis between a patient'"'"'s left atrium and right atrium without loss of patency, the device comprising:

an hourglass-shaped stent having a neck region and first and second flared end regions;

a one-way tissue valve disposed in the first flared end region;

a biocompatible material disposed on the stent, the valve and the biocompatible material defining a continuous sheath that smoothly channels blood flow from the left atrium to the right atrium through the tissue valve substantially without high shear rates, stagnation points, or turbulence,

the biocompatible material configured to promote ingrowth of a neointima layer to a thickness of less than 0.2 mm so as to render the material inert and inhibit hyperplasia; and

a biodegradable material disposed in the neck region and the second flared end region and configured to biodegrade to offset changes in flow caused by the ingrowth of the neointima layer.

35. The device of claim 34, wherein the biodegradable material comprises collagen-terpolymer, polylactic acid (PLA), poly L-lactic acid (PLLA), polyglycolic acid (PGA), poly(lactic-co-glycolic) acid copolymer (PLGA), poly(ε

-caprolactone), methacrylated dextran-aminoethyl methacrylate copolymer (Dex-MA/AEMA), polydiaxanone, poly(glycerol sebacate) (PGS), polysialic acid (PSA), collagen type I/III, chitosan, or chitin.

36. The device of claim 34, wherein the biodegradable material has a thickness of 0.10 to 0.50 mm.

37. The device of claim 34, wherein the one-way tissue valve comprises leaflets disposed completely in the first flared end region and configured to be continuously flushed by blood circulating in the right atrium so as to inhibit excessive tissue ingrowth, stiffening of the leaflets, and impairment of valve closure.

38. A method of treating a subject with heart pathology, the subject having a heart with an atrial septum having a fossa ovalis therein, the method comprising:

providing a device having first and second flared end regions and a neck region disposed therebetween, a tissue valve coupled to the first flared end region, and a biodegradable material disposed in the neck region and the second flared end region;

deploying the device across a puncture through the fossa ovalis such that the neck region is positioned in the puncture, the first flared end region is disposed in, and engages, the atrial septum, and the second flared end region is disposed in, and flanks, the atrial septum;

reducing left atrial pressure and left ventricular end diastolic pressure by shunting blood from the left atrium to the right atrium through the device when the left atrial pressure exceeds the right atrial pressure; and

biodegrading the biodegradable material to offset changes in flow caused by tissue ingrowth.

39. The method of claim 38, wherein the biodegradable material comprises collagen-terpolymer, polylactic acid (PLA), poly L-lactic acid (PLLA), polyglycolic acid (PGA), poly(lactic-co-glycolic) acid copolymer (PLGA), poly(ε

-caprolactone), methacrylated dextran-aminoethyl methacrylate copolymer (Dex-MA/AEMA), polydiaxanone, poly(glycerol sebacate) (PGS), polysialic acid (PSA), collagen type I/III, chitosan, or chitin.

40. The method of claim 38, wherein the biodegradable material has a thickness of 0.10 to 0.50 mm.

41. The method of claim 38, further comprising identifying the middle of the fossa ovalis of the atrial septum by pressing a needle against the fossa ovalis to partially tent the fossa ovalis, and puncturing the middle of the fossa ovalis with the needle.

42. The method of claim 38, wherein the puncture is through the middle of the fossa ovalis and the device is deployed away from the limbus, atrial wall, and the ridge between the inferior vena cava and coronary sinus.

43. The method of claim 38, wherein the heart pathology comprises heart failure.

44. The method of claim 38, wherein the heart pathology comprises pulmonary congestion.

45. The method of claim 38, wherein the heart pathology comprises myocardial infarction.

46. The method of claim 45, comprising deploying the device during a period immediately following the myocardial infarction.

47. The method of claim 46, wherein the period immediately following the myocardial infarction is six months after the myocardial infarction.

48. The method of claim 46, wherein the period immediately following the myocardial infarction is two weeks after the myocardial infarction.

49. The method of claim 38, wherein reducing the left atrial pressure and the left ventricular end diastolic pressure increases the cardiac output of the subject.

50. The method of claim 38, wherein shunting blood from the left atrium to the right atrium decreases pulmonary congestion of the subject.

51. The method of claim 38, wherein shunting blood from the left atrium to the right atrium decreases the pulmonary artery pressure of the subject.

52. The method of claim 38, shunting blood from the left atrium to the right atrium increases the ejection fraction of the subject.

53. The method of claim 38, wherein shunting blood from the left atrium to the right atrium increases the fractional shortening of the subject.

54. The method of claim 38, wherein shunting blood from the left atrium to the right atrium decreases the left ventricle internal diameter in systole of the subject.

55. The method of claim 38, wherein deploying the device across the puncture through the fossa ovalis comprises deploying the second flared end region by advancing the second flared end region out of a sheath and into the left atrium with a pusher, then partially retracting the sheath such that the second flared end region engages the left side of the atrial septum, and then deploying the first flared end region by fully retracting the sheath such that the first flared end region deploys in the right atrium.

56. The method of claim 55, wherein the pusher is configured to advance only the second flared end region out of the sheath.

57. A method of making a device, the method comprising:

providing a tube of shape-memory metal;

expanding the tube on a mandrel to define first and second flared end regions and a neck therebetween, and heating the expanded tube to set the shape;

coating the neck, the second flared end region, and a portion of the first flared end region with a biocompatible material;

providing a valve of animal pericardial tissue having leaflets in a normally closed position;

securing an inlet of the valve to an edge of the biocompatible material proximal to the neck region and securing an outlet of the valve proximal to an end of the first flared end region; and

disposing a biodegradable material in the neck region and the second flared end region, the biodegradable material configured to biodegrade to offset changes in flow caused by tissue ingrowth.

58. The method of claim 57, wherein the biodegradable material comprises collagen-terpolymer, polylactic acid (PLA), poly L-lactic acid (PLLA), polyglycolic acid (PGA), poly(lactic-co-glycolic) acid copolymer (PLGA), poly(ε

-caprolactone), methacrylated dextran-aminoethyl methacrylate copolymer (Dex-MA/AEMA), polydiaxanone, poly(glycerol sebacate) (PGS), polysialic acid (PSA), collagen type I/III, chitosan, or chitin.

59. The method of claim 57, wherein the biodegradable material has a thickness of 0.10 to 0.50 mm.

60. The method of claim 57, wherein the biocompatible material comprises expanded-polytetrafluoroethylene, polyurethane, DACRON (polyethylene terephthalate), silicone, polycarbonate urethane, or pericardial tissue from an equine, bovine, or porcine source.

61. The method of claim 57, wherein the inlet of the valve is secured to the edge of the biocompatible polymer at a portion of the first flared end region that is about 1-3 mm from a narrowest portion of the neck region.

62. The method of claim 57, wherein the stent comprises a plurality of sinusoidal rings and longitudinally extending struts, and wherein the valve is sutured to the longitudinally extending struts and to the biocompatible material.

63. The method of claim 57, wherein the valve comprises leaflets defined by sutures.