Methods for replacing dysfunctional heart valves

1. A method for replacing a dysfunctional atrioventricular (AV) valve in a heart of a subject, comprising the steps of:

(i) providing a prosthetic valve, said prosthetic valve comprising a base valve structure and a self-expanding stent structure,

said base valve structure comprising collagenous tissue derived from a first mammalian tissue source,

said base valve structure further comprising an internal region, an open proximal valve annulus engagement end and a distal valve structure end, said open proximal valve annulus engagement end being configured and adapted to engage an AV valve annulus, receive fluid flow therein and direct said fluid flow into said internal region of said base valve structure,

said base valve structure further comprising a plurality of elongated ribbon members that extend from said open proximal valve annulus engagement end to said distal valve structure end, each of said plurality of elongated ribbon members comprising first and second edge regions and proximal and distal ends, said plurality of elongated ribbon members being positioned circumferentially about said base valve structure, wherein said first edge regions of said plurality of elongated ribbon members are positioned proximate said second edge regions of said plurality of elongated ribbon members and form a plurality of flow modulating regions,

said distal ends of said plurality of elongated ribbon members being positioned proximate each other in a constrained relationship, wherein said fluid flow through said distal ends of said plurality of elongated ribbon members and, thereby, said base valve structure is restricted,

said plurality of elongated ribbon members being configured and adapted to deflect outwardly when said open proximal valve annulus engagement end of said base valve structure directs said fluid flow into said internal region of said base valve structure and said fluid flow comprises a positive fluid pressure, whereby a first pressure differential between first valvular pressure in said internal region of said base valve structure relative to first external pressure exerted on said base valve structure is generated, wherein each of said plurality of flow modulating regions transitions from a restricted fluid flow configuration to an open fluid flow configuration and allows said fluid flow to be transmitted through said plurality of flow modulating regions and, thereby, through and out of said base valve structure,

said plurality of elongated ribbon members being further configured and adapted to deflect inwardly when said first pressure differential transitions to a second pressure differential between second valvular pressure in said internal region of said base valve structure relative to second external pressure exerted on said base valve structure, said second pressure differential being lower than said first pressure differential, wherein each of said plurality of flow modulating regions transitions from said open fluid flow configuration to said restricted fluid flow configuration and restricts said fluid flow through said plurality of flow modulating regions and, thereby, through and out of said base valve structure,

said self-expanding stent structure being positioned in said internal region of said base valve structure,

said self-expanding stent structure comprising a shape-memory alloy,

said self-expanding stent structure comprising a plurality of tethers adapted to pierce into and engage cardiovascular tissue,

said prosthetic valve being adapted to be everted to an everted pre-deployment configuration and, thereafter, be compressed to an everted, compressed pre-deployment configuration,

said prosthetic valve being further adapted to transition from said everted, compressed pre-deployment configuration to an everted, expanded post-deployment configuration, and, thereafter, be reverted to a reverted, expanded post-deployment configuration;

(ii) providing a catheter assembly adapted to access an AV valve annulus region of said dysfunctional AV valve, said catheter assembly comprising a sheath member and a deployment member, said sheath member comprising an internal lumen and a distal opening,

said internal lumen of said sheath member being adapted to receive said prosthetic valve therein when said prosthetic valve is in said everted, compressed pre-deployment configuration,

said deployment member being adapted to be translated through said internal lumen;

(iii) everting said prosthetic valve to said everted pre-deployment configuration;

(iv) compressing said prosthetic valve in said everted pre-deployment configuration to said everted, compressed pre-deployment configuration;

(v) loading said prosthetic valve in said everted, compressed pre-deployment configuration into said internal lumen of said sheath member of said catheter assembly;

(vi) selecting a vein in communication with said heart of said subject, said vein providing access to said AV valve annulus region of said dysfunctional AV valve;

(vii) placing an incision through tissue proximate said vein and through said vein, wherein an opening is provided in said vein;

(viii) inserting said sheath member of said catheter assembly through said incision and A into and through said vein, and into said heart of said subject;

(ix) guiding said sheath member of said catheter assembly into said AV valve annulus region of said dysfunctional AV valve;

(x) slidably translating said prosthetic valve in said everted, compressed pre-deployment configuration through said internal lumen of said sheath member, out of said distal opening of said sheath member and into said AV valve annulus region of said dysfunctional AV valve with said deployment member, wherein said prosthetic valve transitions from said everted, compressed pre-deployment configuration to said everted expanded post-deployment configuration, whereby said plurality of tethers of said self-expanding stent structure pierce into said cardiovascular tissue at said AV valve of said dysfunctional AV valve and, thereby, position said prosthetic valve at said AV valve of said dysfunctional AV valve and securely engage said prosthetic valve thereto in said everted, expanded post-deployment configuration;

(xi) reverting said prosthetic valve in said everted, expanded post-deployment configuration to said reverted, expanded post-deployment configuration; and

(xii) withdrawing said sheath member of said catheter assembly out of said subject's body.

2. The method of claim 1 , wherein said first mammalian tissue source is selected from the group consisting of the heart, small intestine, large intestine, stomach, lung, liver, kidney, pancreas, peritoneum, placenta, amniotic membrane, umbilical cord, bladder, prostate, and fetal tissue from any mammalian organ.

3. The method of claim 1 , wherein said first mammalian tissue source is devoid of xenogeneic antigens.

4. The method of claim 1 , wherein said collagenous tissue comprises a first pharmacological agent.

5. The method of claim 4 , wherein said first pharmacological agent is selected from the group consisting of an antibiotic, anti-viral agent, analgesic, anti-inflammatory, anti-neoplastic, anti-spasmodic, anticoagulant and antithrombotic.

6. The method of claim 5 , wherein said antibiotic is selected from the group consisting of aminoglycosides, cephalosporins, chloramphenicol, clindamycin, erythromycins, fluoroquinolones, macrolides, azolides, metronidazole, penicillin, tetracyclines, trimethoprim-sulfamethoxazole, gentamicin and vancomycin.

7. The method of claim 5 , wherein said anti-inflammatory is selected from the group consisting of dexamethasone, betamethasone and prednisolone.

8. The method of claim 1 , wherein said shape-memory alloy comprises a nickel-titanium (Ni—Ti) alloy.

9. The method of claim 1 , wherein said self-expanding stent structure comprises an outer coating.

10. The method of claim 9 , wherein said outer coating comprises an extracellular matrix (ECM) composition comprising acellular ECM derived from a second mammalian tissue source.

11. The method of claim 10 , wherein said second mammalian tissue source is selected from the group consisting of small intestine submucosa (SIS), urinary bladder submucosa (UBS), stomach submucosa (SS), heart tissue, mesothelial tissue, placental tissue and omentum tissue.

12. The method of claim 10 , wherein said ECM composition is in the form of an expandable composition.

13. The method of claim 10 , wherein said ECM composition further comprises a second pharmacological agent selected from the group consisting of dexamethasone, betamethasone and prednisolone.