US 20060195183 A1
An apparatus and method for replacing a cardiac valve includes an expandable support member having oppositely disposed first and second ends, a main body portion extending between the ends, and a prosthetic valve within the main body portion. The main body portion has an annular shape for expanding into position in the annulus of the valve. The first and second ends include a plurality of upper and lower wing members movable from a collapsed condition into an extended condition for respectively engaging a first section of cardiac tissue surrounding the valve and for engaging a portion of the native valve leaflets to pin the leaflets back against the annulus. The second end further includes at least two strut members spaced apart from each other. A respective one of the strut members is attached to at least one commissural section of the prosthetic valve to prevent prolapse of the valve leaflets.
1. An apparatus for replacing a cardiac valve having at least two native valve leaflets, said apparatus comprising:
an expandable support member having oppositely disposed first and second ends and a main body portion extending between said ends, said main body portion of said support member having an annular shape for expanding into position in the annulus of the cardiac valve;
said first end of said support member comprising a plurality of upper wing members that extend from said main body portion, each of said upper wing members being movable from a radially collapsed condition into a radially extended condition for engaging a first section of cardiac tissue surrounding one-side of the cardiac valve;
said second end of said support member comprising a plurality of lower wing members that extend from said main body portion, each of said lower wing members being movable from a radially collapsed condition into a radially extended condition for engaging a portion of the native valve leaflets to pin the leaflets back against the annulus of the native cardiac valve;
said second end of said support member further including at least two strut members that are spaced apart from each other; and
a prosthetic valve secured within said main body portion of said support member, said prosthetic valve having at least two valve leaflets that are coaptable to permit unidirectional flow of blood, each of said at least two valve leaflets being joined together at at least two commissural sections that are spaced apart from each other, each of said at least two commissural sections being attached to a respective one of said strut members to prevent prolapse of said valve leaflets.
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17. A method for replacing a cardiac valve having at least two native valve leaflets, said method comprising the steps of:
providing a prosthetic valve that includes an expandable support member having oppositely disposed first and second ends and a main body portion extending between the ends, a plurality of upper wing members that extend from a one end of the main body portion, and a plurality of lower wing members that extend from an opposite end of the main body portion, the second end of the support member further including at least two strut members, the prosthetic valve having at least two valve leaflets that are joined together at at least two commissural sections, each of the at least two commissural sections being attached to a respective one of the strut members to prevent prolapse of the valve leaflets;
placing the main body portion of the prosthetic valve within the annulus of the cardiac valve to be replaced;
expanding the main body portion into engagement with the annulus of the cardiac valve to secure the prosthetic valve in the annulus;
deploying the upper wing members from a radially collapsed condition into a radially extended condition into engagement with a first section of cardiac tissue surrounding one side of the cardiac valve; and
deploying the lower wing members from a radially collapsed condition into a radially extended condition into engagement with a portion of the native valve leaflets to pin the leaflets back against the annulus of the native cardiac valve.
18. The method of
placing the support member around an inflatable balloon in a secured manner;
inserting the balloon and support member into an atrial chamber;
advancing the balloon until the support member is positioned within the annulus of the cardiac valve to be replaced; and
expanding the support member with the balloon so that the support member engages the annulus of the cardiac valve to secure the support member in the annulus.
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This application claims priority from U.S. provisional patent application Ser. No. 60/654,725, filed on Feb. 18, 2005, the subject matter of which is incorporated herein by reference.
The present invention relates to an apparatus and methods for treating a diseased cardiac valve, and is particularly directed to an apparatus and methods for the correction of mitral valve and tricuspid valve disorders via a minimally invasive or percutaneous approach.
There are two atrio-ventricular valves in the heart; one on the left side of the heart and one on the right side of the heart. The left side atrio-ventricular valve is the mitral valve and the right side atrio-ventricular
The mitral and tricuspid valves differ significantly in anatomy. While the annulus of the mitral valve is generally D-shaped, the annulus of the tricuspid valve is more circular. The effects of the valvular dysfunction vary between the mitral valve and the tricuspid valve. Mitral valve regurgitation has more severe physiological consequences to the patient than does tricuspid valve regurgitation, a small amount of which is tolerable.
In mitral valve insufficiency, the valve leaflets do not fully close and a certain amount of blood leaks back into the left atrium when the left ventricle contracts. As a result, the heart has to work harder by pumping not only the regular volume of the blood, but also the extra volume of blood that regurgitated back into the left atrium. The added workload creates an undue strain on the left ventricle. This strain can eventually wear out of the heart and result in morbidity when the conditions are prolonged and severe enough. Consequently, proper function of the mitral valve is critical to the pumping efficiency of the heart.
Mitral and tricuspid valve disease is traditionally treated by either surgical repair with an annuloplasty ring or surgical replacement with a valve prosthesis. However, surgical valve replacement or repair is often an exacting operation that is done through a surgical technique where the thoracic cavity is opened. The operation requires use of a heart-lung machine for external circulation of the blood as the heart is stopped and opened during the surgical intervention and the artificial cardiac valves and/or annuloplasty rings are sewed in under direct vision. This operation exposes the patient to many risks especially in the elderly population. A percutaneous procedure that can be performed under local anesthesia in the cardiac catherization lab, rather than in cardiac surgery, could therefore offer tremendous benefits for these patients, many of whom have no options today. Consequently, an apparatus for replacing a diseased atrioventricular valve using a minimally invasive, percutaneous approach would be very helpful to provide additional opportunities to treat patients with severe valvular insufficiency, end stage heart failure, atrial fibrillation, and/or other associated arrhythmias.
In one aspect of the present invention, an apparatus for replacing a cardiac valve having at least two native valve leaflets is provided. The apparatus comprises an expandable support member having oppositely disposed first and second ends and a main body portion extending between the ends. The main body portion of the support member has an annular shape for expanding into position in the annulus of the cardiac valve. The first end comprises a plurality of upper wing members that extend from the main body portion. Each of the upper wing members is movable from a radially collapsed condition into a radially extended condition for engaging a first section of cardiac tissue surrounding one side of the cardiac valve. The second end comprises a plurality of lower wing members that extend from the main body portion. Each of the lower wing members is movable from a radially collapsed condition into a radially extended condition for engaging a portion of the native valve leaflets to pin the leaflets back against the annulus of the native cardiac valve. The second end of the support member further includes at least two strut members that are spaced apart from each other. The at least two valve leaflets are joined at at least two commissural sections that are spaced apart from each other. Each of the at least two commissural sections are attached to a respective one of the strut members to prevent prolapse of the valve leaflets. A prosthetic valve is secured within the main body portion of the support member. The prosthetic valve has at least two valve leaflets that are coaptable to permit unidirectional flow of blood.
In another aspect of the present invention, at least a portion of the support member is treated with at least one therapeutic agent for eluting into cardiac tissue.
In yet another aspect of the present invention, a method for replacing a cardiac valve having at least two native valve leaflets is provided. According to the inventive method, a prosthetic valve having at least two valve leaflets that are coaptable to permit unidirectional flow of blood is provided. The prosthetic valve includes an expandable support member having oppositely disposed first and second ends and a main body portion extending between the ends. The expandable support member further includes a plurality of upper wing members that extend from one end of the main body portion, and a plurality of lower wing members that extend from an opposite end of the main body portion. The second end of the support member further includes at least two strut members. The prosthetic valve includes at least two valve leaflets that are joined together at at least two commissural sections. Each of the at least two commissural sections are attached to a respective one of the strut members to prevent prolapse of the valve leaflets. The main body portion of the prosthetic valve is placed within the annulus of the cardiac valve to be replaced, and is then expanded into engagement with the annulus of the cardiac valve to secure the prosthetic valve in the annulus. The upper wing members are deployed from a radially collapsed condition into a radially extended condition into engagement with a first section of cardiac tissue surrounding one side of the cardiac valve. The lower wing members are deployed from a radially collapsed condition into a radially extended condition into engagement with a portion of the native valve leaflets to pin the leaflets back against the annulus of the native cardiac valve.
The foregoing and other features of the present invention will become apparent to those skilled in the art to which the present invention relates upon reading the following description with reference to the accompanying drawings, in which:
The present invention relates to an apparatus and methods for treating a diseased cardiac valve, and is particularly directed to an apparatus and methods for the correction of mitral valve and tricuspid valve disorders via a minimally invasive and/or percutaneous approach. As representative of the present invention,
As shown in
The apparatus 10 for replacing the dysfunctional mitral valve 14 includes an expandable support member 40 (
The support member 40 is annular in shape and includes oppositely disposed first and second ends 42 and 44 with a main body portion 46 extending between the ends. As shown in
The apparatus 10 may further include a layer 50 (
The first end 42 of the support member 40 comprises a plurality of upper wing members 60 that extend integrally from the main body portion 46. In the embodiment illustrated in
The second end 44 of the support member 40 comprises a plurality of lower wing members 70 that extend integrally from the main body portion 46. In the embodiment illustrated in
Each of the lower wing members 70 is movable from the radially collapsed condition of
The second end 44 of the support member 40 additionally includes at least two strut members 45. As shown in
The prosthetic valve 12 of the present invention may comprise a stentless prosthetic valve. By “stentless” it is meant that the valve components including the leaflets of the prosthetic valve 12 are not reinforced with a support structure, such as a stent or other similar structure. The prosthetic valve 12 is secured, for example, by sutures or other suitable means within the main body portion 46 of the support member 40.
The prosthetic valve 12 may be fixed and preserved using a variety of known methods. The use of chemical processes for the fixation and preservation of biological tissues have been described and are readily available in the art. For example, glutaraldehyde, and other related aldehydes have seen widespread use in preparing cross-linked biological tissues.
Glutaraldehyde is a five carbon aliphatic molecule with an aldehyde at each end of the chain, rendering it bifunctional. These aldehyde groups react under physiological conditions with primary amine groups on collagen molecules resulting in the cross-linking of collagen containing tissues. Methods for glutaraldehyde fixation of biological tissues have been extensively described and are well known in the art. In general, a tissue sample to be cross-linked is simply contacted with a glutaraldeyde solution for a duration effective to cause the desired degree of cross-linking within the biological tissue being treated.
Many variations and conditions have been applied to optimize glutaraldehyde fixation procedures. For example, lower concentrations have been found to be better in bulk tissue cross-linking compared to higher concentrations. It has been proposed that higher concentrations of glutaraldehyde may promote rapid surface cross-linking of the tissue, generating a barrier that impedes or prevents the further diffusion of glutaraldehdye into the tissue bulk. For most bioprosthesis applications, the tissue is treated with a relatively low concentration glutaraldehyde solution, e.g., typically between 0.1%-5%, for 24 hours or more to ensure optimum fixation. Various other combinations of glutaraldehyde concentrations and treatment times will also be suitable depending on the objectives for a given application. Examples of such other combinations include, but are not limited to, U.S. Pat. Nos. 6,547,827, 6,561,970, and 6,878,168, all of which are hereby incorporated by reference in their entirety.
In addition to bifunctional aldehydes, many other chemical fixation procedures have been described. For example, some such methods have employed polyethers, polyepoxy compounds, diisocyanates, and azides. These and other approaches available to the skilled individual in the art for treating biological tissues are suitable for cross-linking vascular graft tissue according to the present invention.
The prosthetic valve 12 may also be treated and preserved with a dry tissue valve procedure as described in U.S. Pat. No. 6,534,004, the entire contents of which are hereby incorporated by reference. Furthermore, the prosthetic valve 12 may be treated with anti-calcification solutions, such as XenoLogiX® treatment (Edwards Lifesciences, Irvine, Calif.) or the SynerGraft® (CryoLife, Inc., Kennesaw, Ga.) treatment process, and/or anti-calcification agents, such as alfa-amino oleic acid.
The prosthetic valve 12 can be made with only one piece of pericardial tissue, for example, as shown in
As shown in
The first and second ends 42 and 44 of the support member 40 respectively comprises a plurality of upper and lower wing members 60 and 70 that extend integrally from the main body portion 46. The upper and lower wing members 60 and 70 are movable from the radially collapsed condition of
The prosthetic valve 12 a of the apparatus 10 a (and also the previously described valve 12) may comprise a stentless prosthetic valve, for example, having dimensions that correspond to the dimensions of the native mitral valve 14. Where the prosthetic valve 12 a is comprised of biological material, the biological material can include a harvested biological material such as bovine pericardial tissue, equine pericardial tissue, porcine pericardial tissue, animal or human peritoneal tissue, or mitral, aortic, and pulmonary xenograft or homograft. The biocompatible material may also include a suitable synthetic material such as polyurethane, expanded PTFE, woven velour, Dacron®, heparin-coated fabric, or Gore-Tex®.
The prosthetic valve 12 a further includes first and second leaflets 90 and 92 that mimic the three-dimensional anatomical shape of the anterior and posterior leaflets 22 and 24, respectively, of the mitral valve 14. The valve leaflets of the prosthetic valve 12 a are joined together at at least two commissural sections 47 that are spaced apart from each other. The prosthetic valve 12 a also includes a distal end 86 that defines a first annulus 94 at which the first and second leaflets 90 and 92 terminate.
Additionally, the prosthetic valve 12 a includes first and second pairs 102 and 104, respectively, of prosthetic chordae 106 that project from the first and second leaflets 90 and 92 at the first annulus 94. Each of the prosthetic chordae 106 comprises a solid uninterrupted extension of biocompatible material. Each of the first pair 102 of prosthetic chordae 106 has a distal end 108 and each of the second pair 104 of prosthetic chordae has a distal end 110.
As shown in
The present invention may be treated with at least one therapeutic agent capable of preventing a variety of pathological conditions including, but not limited to, thrombosis, restenosis and inflammation. Accordingly, the therapeutic agent may include at least one of an anticoagulant, an antioxidant, a fibrinolytic, a steroid, an anti-apoptotic agent, and/or an anti-inflammatory agent.
Optionally or additionally, the therapeutic agent may be capable of. treating or preventing other diseases or disease processes such as microbial infections, arrhythmias, and/or heart failure. In these instances, the therapeutic agent may include an antiarrhythmic agent, an inotropic agent, a chronotropic agent, and/or a biological agent such as a cell or protein. More specific types of these therapeutic agents are listed below, including other types of therapeutic agents not discussed above.
Examples of acceptable therapuetic agents include Coumadin, heparin, synthetic heparin analogues (e.g., fondaparinux), G(GP) IIb/IIIa inhibitors, vitronectin receptor antagonists, hirudin, antithrombin III, drotrecogin alpha; fibrinolytics such as alteplase, plasmin, lysokinase, factor XIIa, factor VIIa, prourokinase, urokinase, streptokinase; thrombocyte aggregation inhibitors such as ticlopidine, clopidogrel, abciximab, dextrans; corticosteroids such as aldlometasones, amcinonides, augmented betamethasones, beclomethasones, betamethasones, budesonides, cortisones, clobetasol, clocortolones, desonides, desoximetasones, dexamethasones, flucinolones, fluocinonides, flurandrenolides, flunisolides, fluticasones, halcinonides, halobetasol, hydrocortisones, methylprednisolones, mometasones, prednicarbates, prednisones, prednisolones, triamcinolones; fibrinolytic agents such as tissue plasminogen activator, streptokinase, dipyridamole, ticlopidine, clopidine, and abciximab; non-steroidal anti-inflammatory drugs such as salicyclic acid and salicyclic acid derivatives, para-aminophenol derivatives, indole and indene acetic acids (e.g., etodolac, indomethacin, and sulindac), heteroaryl acetic acids (e.g., ketorolac, diclofenac, and tolmetin), arylpropionic acids (e.g., ibuprofen and derivatives thereof), anthranilic acids (e.g., meclofenamates and mefenamic acid), enolic acids (e.g., piroxicam, tenoxicam, phenylbutazone, and oxyphenthatrazone), gold compounds (e.g., auranofin, aurothioglucose, and gold sodium thiomalate), diflunisal, meloxicam, nabumetones, naproxen, oxaprozin, salsalate, celecoxib, rofecoxib; cytostatics such as alkaloids and podophyllum toxins such as vinblastin, vincristin; alkylants such as nitrosoureas and nitrogen lost analogues; cytotoxic antibiotics such as daunorubicin, doxorubicin, and other anthracyclins and related substances, bleomycin, and mitomycin; antimetabolites such as folic acid analogues, purine analogues and related inhibitors (e.g., mercaptopurine, thioguanine, pentostatin, and 2-chlorodeoxyadenosine), pyrimidine analogues (e.g., fluorouracil, floxuridine, and cytarabine), and platinum coordination complexes (e.g., cisplatinum, carboplatinum and oxaliplatinum); tacrolimus, azathioprine, cyclosporine, paclitaxel, docetaxel, sirolimus; amsacrin, irinotecan, imatinib, topotecan, interferon-alpha 2a, interferon-alpha 2b, hydroxycarbamide, miltefosin, pentostatin, porfimer, aldesleukin, bexarotene, and tretinoin; antiandrogens and antiestrogens; antiarrythmics, in particular antiarrhythmics of class I such as antiarrhythmics of the quinidine type (e.g., quinidine, dysopyramide, ajmaline, prajmalium bitartrate, and detajmium bitartrate); antiarrhythmics of the lidocaine type, (e.g., lidocaine, mexiletin, phenyloin, and tocainid); antiarrhythmics of class I C (e.g., propafenone, flecainide (acetate)); antiarrhythmics of class II, including betareceptor blockers such as metoprolol, esmolol, propranolol, metoprolol, atenolol, and oxprenolol; antiarrhythmics of class III such as amiodaron and sotalol; antiarrhythmics of class IV such as diltiazem, and verapamil; and other antiarrhythmics such as adenosine, orciprenaline, and ipratropium bromide.
Other types of therapeutic agents may include digitalis glycosides such as acetyl digoxin/methyldigoxin, digitoxin, and digoxin; heart glycosides such as ouabain and proscillaridin; antihypertensives such as centrally effective antiadrenergic substances (e.g., methyldopa and imidazoline receptor agonists); calcium channel blockers of the dihydropyridine type, such as nifedipine and nitrendipine; ACE inhibitors (e.g., quinaprilate, cilazapril, moexipril, trandolapril, spirapril, imidapril, and trandolapril); angiotensin-II-antagonists (e.g., candesartancilexetil, valsartan, telmisartan, olmesartan medoxomil, and eprosartan); peripherally effective alpha-receptor blockers such as prazosin, urapidil, doxazosin, bunazosin, terazosin, and indoramin; vasodilators such as dihydralazine, diisopropyl amine dichloroacetate, minoxidil, and nitropiusside-sodium; other antihypertonics such as indapamide, codergocrin mesilate, dihydroergotoxin methane sulphonate, cicletanin, bosentan, and fludrocortisone; phosphodiesterase inhibitors, such as milrinone and enoximone, as well as antihypotonics (e.g., adrenergics and dopaminergic substances such as dobutamine, epinephrine, etilefrine, norfenefrine, norepinephrine, oxilofrine, dopamine, midodrine, pholedrine, and amezinium methyl) and partial adrenoceptor agonists (e.g., dihydroergotamine); fibronectin, polylysines and ethylene vinyl acetates; and adhesive substances such as cyanoacrylates, beryllium, and silica.
Additional therapeutic agents may also include antibiotics and antiinfectives such as β-lactam antibiotics (e.g., β-lactamase-sensitive penicillins, including benzyl penicillins (penicillin G) and phenoxymethylpenicillin (penicillin V)); β-lactamase-resistant penicillins, such as aminopenicillins, which include amoxicillin, ampicillin, and bacampicillin; acylaminopenicillins such as mezlocillin and piperacillin; carboxypenicillines and cephalosporins (e.g., cefazolin, cefuroxim, cefoxitin, cefotiam, cefaclor, cefadroxil, cefalexin, loracarbef, cefixim, cefuroximaxetil, ceftibuten, cefpodoximproxetil, and cefpodoximproxetil); aztreonam, ertapenem, and meropenem; β-lactamase inhibitors such as sulbactam and sultamicillintosilates; tetracyclines such as doxycycline, minocycline, tetracycline, chlorotetracycline, oxytetracycline; aminoglycosides such as gentamicin, neomycin, streptomycin, tobramycin, amikasin, netilmicin, paromomycin, framycetin, and spectinomycin; makrolide antibiotics such as azithromycin, clarithromycin, erythromycin, roxithromycin, spiramycin, and josamycin; lincosamides such as clindamycin and lincomycin; gyrase inhibitors, such as fluoroquinolones, which include ciprofloxacin, ofloxacin, moxifloxacin, norfloxacin, gatifloxacin, enoxacin, fleroxacin, and levofloxacin; quinolones such as pipemidic acid; sulphonamides such as trimethoprim, sulphadiazin, and sulphalene; glycopeptide antibiotics such as vancomycin and teicoplanin; polypeptide antibiotics, such as polymyxins, which include colistin, polymyxin-b, and nitroimidazol derivatives (e.g., metronidazol and tinidazol); aminoquinolones such as chloroquin, mefloquin, and hydroxychloroquin; biguanides such as proguanil; quinine alkaloids and diaminopyrimidines such as pyrimethamine; amphenicols such as chloramphenicol; rifabutin, dapsone, fusidinic acid, fosfomycin, nifuratel, telithromycin, fusafungin, fosfomycin, pentamidindiisethionate, rifampicin, taurolidine, atovaquone, and linezolid; virostatics such as aciclovir, ganciclovir, famciclovir, foscamet, inosine (dimepranol-4-acetamidobenzoate), valganciclovir, valaciclovir, cidofovir, and brivudin; tyrosine kinase inhibitors; anti-apoptotic agents such as caspase inhibitors (e.g., fluoromethylketone peptide derivatives), calpain inhibitors, cathepsin inhibitors, nitric oxide synthase inhibitors, flavonoids, vitamin A, vitamin C, vitamin E, vitamin D, pycnogenol, super oxidedismutase, N-acetyl cysteine, selenium, catechins, alpha lipoic acid, melatonin, glutathione, zinc chelators, calcium chelators, and L-arginine; warfarin; beta-blockers; diuretics; spirolactone; and natural products such as vinca alkaloids (e.g., vinblastine, vincristine and vinorelbine).
As noted above, the therapeutic agent may also include a biological agent. The biological agent may include organic substances such as peptides, proteins, enzymes, carbohydrates (e.g., monosaccharides, oligosaccharides and polysacchardies), lipids, phospholipids, steroids, lipoproteins, glycoproteins, glycolipids, proteoglycans, polynucleotides (e.g., DNA and RNA), antisense polynucleotides (e.g., c-myc antisense), antibodies (e.g., monoclonal or polycolonal) and/or antibody fragments (e.g., anti-CD34 antibody), bioabsorbable polymers (e.g., polylactonic acid), chitosan, extracellular matrix modulators, such as matrix metalloproteinases (MMP), which include MMP-2, MMP-9 and Batimastat; and protease inhibitors.
Biological agents may include, for example, agents capable of stimulating angiogenesis in the myocardium. Such agents may include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), non-viral DNA, viral DNA, and endothelial growth factors (e.g., FGF-1, FGF-2, VEGF, TGF). Other growth factors may include erythropoietin and/or various hormones such as corticotropins, gonadotropins, sonlatropin, thyrotrophin, desmopressin, terlipressin, oxytocin, cetrorelix, corticorelin, leuprorelin, triptorelin, gonadorelin, ganirelix, buserelin, nafarelin, and goserelin. Additional growth factors may also include cytokines, epidermal growth factors (EGF), platelet derived growth factor (PDGF), transforming growth factors-β (TGF-β), transforming growth factor-α (TGF-α), insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), tumour necrosis factor-β (TNF-β), interferon-γ (INF-γ), colony stimulating factors (CSFs); monocyte chemotactic protein, and fibroblast stimulating factor 1.
Still other biological agents may include regulatory peptides such as somatostatin and octreotide; bisphosphonates (e.g., risedronates, pamidronates, ibandronates, zoledronic acid, clodronic acid, etidronic acid, alendronic acid, and tiludronic acid); fluorides such as disodium fluorophosphate and sodium fluoride; calcitonin and dihydrotachystyrene; histamine; fibrin or fibrinogen; endothelin-1; angiotensin II; collagens; bromocriptin; methylsergide; methotrexate; carbontetrachloride and thioacetamide.
The present invention may also be treated (i.e., seeded) with other biological agents, such as cells. Suitable cells may include any one or combination of eukaryotic cells. Additionally or optionally, the cells may be capable of producing therapeutic agents and/or genetically engineered to produce therapeutic agents. Suitable cells for use in the present invention include, for example, progentior cells such as adult stem cells, embryonic stem cells, and umbilical cord blood stem cells. The cells may be autologous or allogenic, genetically engineered or non-engineered, and may include, for example, mesenchymal or mesodermal cells, including, but not limited to, endothelial progenitor cells, endothelial cells, and fibroblasts. Mixtures of such cells can also be used.
A variety of ex vivo or in vivo methods can be used to deliver a nucleic acid molecule or molecules, such as a gene or genes, to the cells. For example, the cells can be modified (i.e., genetically engineered) to produce or secrete any one or combination of the aforementioned therapeutic agents, including, but not limited to, anticoagulant agents, antiplatelet agents, antifibrinolytic agents, angiogenesis factors, and the like. Ex vivo gene transfer is a process by which cells are removed from the body using well known techniques, genetically manipulated, usually through transduction or transfection of a nucleic acid molecule into the cells in vitro, and the returned to the body for therapeutic purposes. This contrasts with in vivo genetic engineering where a gene transfer vector is administered to a patient resulting in genetic transfer into cells and tissues in the intact patient. Ex vivo and in vivo gene transfer techniques are well known to one of skill in the art.
To treat the present invention with at least one therapeutic agent, a variety of methods, agents, and compositions may be used. For example, the therapeutic agent can be simply linked to the stent surface, embedded and released from within polymer materials, such as a polymer matrix, or surrounded by and released through a carrier. Several approaches to treating medical devices with therapeutic agents exist. Some therapeutic agents can be loaded directly onto metallic surfaces; however, a coating composition, typically comprised of at least one polymer and at least one therapeutic agent, is usually used to treat drug-eluting devices. The coating composition ensures retention of the therapeutic agent during deployment and modulates elution kinetics of the therapeutic agent. By altering the release kinetics of different therapeutic agents in the same coating composition, distinct phases of a given disease process may be targeted.
The present invention may be treated with a coating composition comprising at least one therapeutic agent and at least one polymer or oligomer material. The polymer(s) and/or oligomer(s) may be of various types and from various sources, including natural or synthetic polymers, which are biocompatible, biodegradable, bioabsorbable and useful for controlled release of the therapeutic agent. For example, synthetic polymers can include polyesters, such as polylactic acid, polyglycolic acid, and/or combinations thereof, polyanhydrides, polycaprolactones, polyhydroxybutyrate valerates, and other biodegradable polymers or mixtures of copolymers thereof. Natural polymeric materials can include proteins such as collagen, fibrin, elastin, extracellular matrix components, other biologic agents, and/or mixtures thereof.
The polymer material or mixture thereof of the coating composition can be applied with the therapeutic agent on the surface of the present invention and can comprise a single layer. Optionally, multiple layers of the polymer material can be applied to form the coating composition. Multiple layers of the polymer material can also be applied between layers of the therapeutic agent. For example, the polymeric layers may be applied sequentially, with the first layer directly in contact with the uncoated surface of the apparatus and a second layer comprising the therapeutic agent and having one surface in contact with the first layer and the opposite surface in contact with a third layer of polymeric material which is in contact with the surrounding tissue. Additional layers of the polymeric material and therapeutic agent can be added as required.
Alternatively, the coating composition can be applied as multiple layers comprising one or more therapeutic agents surrounded by polymer material. For instance, the coating composition can comprise multiple layers of a single therapeutic agent, one or more therapeutic agents in each layer, and/or differing therapeutic agents in alternating layers. Alternatively, the layers comprising the therapeutic agent can be separated from one another by a layer of polymer material.
The coating composition may further comprise at least one pharmaceutically acceptable polymers and/or pharmaceutically acceptable carriers, for example, non-absorbable polymers, such as ethylene vinyl acetate and methylmethacrylate. The non-absorbable polymer, for example, can aid in further controlling release of the therapeutic agent by increasing the molecular weight of the coating composition and thereby delaying or slowing the rate of release of the therapeutic agent.
The coating composition can be applied to the present invention using standard techniques to cover the entire surface of the apparatus, or partially, as a single layer in a dot matrix pattern, for example. The coating composition can be applied using various techniques available in the art, such as dipping, spraying, vapor deposition, an injection-like and/or a dot matrix-like approach. Upon contact of the coating composition with adjacent tissue where implanted, the coating composition can begin to degrade in a controlled manner. As the coating composition degrades, the therapeutic agent is slowly released into adjacent tissue and the therapeutic agent is eluted so that the therapeutic agent can have its effect locally.
Where the therapeutic agent comprises a biological agent, such as cells, the biological agent can be coated directly onto the surface of the present invention or, alternatively, they can be incorporated into the polymeric material (e.g., into a polymer matrix). Such biological agents may also be included within at least one microscopic containment vehicle (e.g., a liposome, nanocapsule, nanoparticle, micelle, synthetic phospholipid, gas-dispersion, emulsion, microemulsion, nanosphere, and the like) that can be stimulated to release the biological agent(s) and/or that release the biological agent(s) in a controlled manner. The microscopic containment vehicle can be coated onto the surface of the present invention or incorporated into the polymeric material. Where the biological agent comprises cells, for example, the cells can be induced to produce, activate, and/or release their cellular products (including one or more therapeutic agents) by an external stimulation device (e.g., an electrical impulse). Alternatively, cells can constitutively release one or more therapeutic agents at a desired level.
To enable delivery and deployment of the apparatus 10, the apparatus is positioned about a balloon 120 (
In addition, releasable constraining wires (not shown) are used to temporarily hold the upper wing members 60 and the lower wing members 70 in the radially collapsed conditions shown in
To replace the mitral valve 14 with the apparatus 10 using a percutaneous (or intravascular) approach, the apparatus is first sized for the particular mitral valve using fluoroscopic and/or echocardiographic data. The catheter 128 is then introduced into either the right or left jugular vein (not shown), a femoral vein (not shown), or the subclavian vein (not shown) using a known percutaneous technique, such as the Seldinger technique, and is advanced through the superior or inferior vena cava (not shown) to approach the right atrium (not shown). The catheter 128 is passed through the interatrial septum (not shown) to reach the left atrium 16. From inside the left atrium 16, the apparatus 10 is then positioned within the annulus 20 of the mitral valve 14 as is shown in
Next, the catheter 128 is pulled back so that the support member 40 can expand to the condition shown in
The constraining wires are then released, which allows the upper wing members 60 and the lower wing members 70 of the support member 40 to spring radially outward toward their expanded conditions illustrated in
As the lower wing members 70 move from their radially collapsed condition to their radially extended condition, each of the lower wing members engages a portion of the native valve leaflets 22 and 24. The first and second lower wing members 72 and 74 engage the commissures of the native mitral valve 14 (
It should be noted that the engagement of the main body portion body 46 with the valve annulus 20, the engagement of the upper wing members 60 with the wall of the left atrium 16, and the engagement of the lower wing members 70 that pins the native valve leaflets 22 and 24 back against the valve annulus provides a unique three-way locking mechanism for securing the apparatus 10 in the valve annulus.
It is contemplated that the apparatus 10 according to the present invention could alternatively be placed by a retrograde, percutaneous approach. For example, the apparatus 10 may be urged in a retrograde fashion through a femoral artery (not shown), across the aortic arch (not shown), through the aortic valve (not shown), and into the left ventricle 18 where the apparatus may then be appropriate positioned in the native mitral valve 14.
As shown in
As may be seen in
The present invention thus allows for the apparatus 10 to be delivered in a cardiac catheterization laboratory with a percutaneous approach under local anesthesia using fluoroscopic as well as echocardiographic guidance, thereby avoiding general anesthesia and highly invasive open heart surgery techniques. This approach offers tremendous advantages for high risk patients with severe valvular disease. It should be understood, however, that the present invention contemplates. various other approaches, including standard open heart surgeries as well as minimally invasive surgical techniques. Because the present invention omits stitching of the apparatus 10 in the valve annulus 20, surgical time is reduced regardless of whether an open, minimally invasive or percutaneous approach is used.
From the above description of the invention, those skilled in the art will perceive improvements, changes and modifications. For example, it should be understood by those skilled in the art that the various portions of the support member 40 could be self-expanding or expanded by a change in temperature (because they are made from a shape memory material). Such improvements, changes and modifications within the skill of the art are intended to be covered by the appended claims.