WO1997024083A1 - Remplacement de valvule cardiaque a l'aide de tubes souples - Google Patents

Remplacement de valvule cardiaque a l'aide de tubes souples Download PDF

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Publication number
WO1997024083A1
WO1997024083A1 PCT/US1996/020871 US9620871W WO9724083A1 WO 1997024083 A1 WO1997024083 A1 WO 1997024083A1 US 9620871 W US9620871 W US 9620871W WO 9724083 A1 WO9724083 A1 WO 9724083A1
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Prior art keywords
valve
tissue
segment
valves
heart
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PCT/US1996/020871
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English (en)
Inventor
James L. Cox
Original Assignee
Cox James L
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Publication date
Priority claimed from US08/146,938 external-priority patent/US5480424A/en
Priority claimed from PCT/US1995/016871 external-priority patent/WO1997023640A1/fr
Application filed by Cox James L filed Critical Cox James L
Publication of WO1997024083A1 publication Critical patent/WO1997024083A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/0095—Packages or dispensers for prostheses or other implants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/24—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2412—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body with soft flexible valve members, e.g. tissue valves shaped like natural valves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3629—Intestinal tissue, e.g. small intestinal submucosa
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
    • A61L27/3645—Connective tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves

Definitions

  • This invention is in the field of heart surgery and relates to replacement of diseased or injured heart valves.
  • valves in the heart that serve to direct the flow of blood through the two sides of the heart in a forward direction.
  • On the left (systemic) side of the heart are: 1) the mitral valve, located between the left atrium and the left ventricle, and 2) the aortic valve, located between the left ventricle and the aorta. These two valves direct oxygenated blood coming from the lungs, through the left side of the heart, into the aorta for distribution to the body.
  • the right (pulmonary) side of the heart are: 1) the tricuspid valve, located between the right atrium and the right ventricle, and 2) the pulmonary valve, located between the right ventricle and the pulmonary artery. These two valves direct de-oxygenated blood coming from the body, through the right side of the heart, into the pulmonary artery for distribution to the lungs, where it again becomes re-oxygenated to begin the circuit anew.
  • All four of these heart valves are passive structures in that they do not themselves expend any energy and do not perform any active contractile function. They consist of moveable “leaflets” that are designed simply to open and close in response to differential pressures on either side of the valve.
  • the mitral and tricuspid valves are referred to as “atrioventricular valves” because of their being situated between an atrium and ventricle on each side of the heart.
  • the mitral valve has two leaflets and the tricuspid valve has three.
  • the aortic and pulmonary valves are referred to as “semilunar valves" because of the unique appearance of their leaflets, which are more aptly termed "cusps" and are shaped somewhat like a half-moon.
  • the aortic and pulmonary valves each have three cusps.
  • Figure 1 contains a cross-sectional cutaway depiction of a normal human heart 100 (shown next to heart 100 is a segment of tubular tissue 200 which will be used to replace the mitral valve, as described below) .
  • the left side of heart 100 contains left atrium 110, left ventricular chamber 112 positioned between left ventricular wall 114 and septum 116, aortic valve 118, and mitral valve assembly 120.
  • the components of the mitral valve assembly 120 include the mitral valve annulus 121, which will remain as a roughly circular open ring after the leaflets of a diseased or damaged valve have been removed; anterior leaflet 122 (sometimes called the aortic leaflet, since it is adjacent to the aortic region); posterior leaflet 124; two papillary muscles 126 and 128 which are attached at their bases to the interior surface of the left ventricular wall 114; and multiple chordae tendineae 132, which couple the mitral valve leaflets 122 and 124 to the papillary muscles 126 and 128. There is no one-to-one chordal connection between the leaflets and the papillary muscles; instead, numerous chordae are present, and chordae from each papillary muscle 126 and 128 attach to both of the valve leaflets 122 and 124.
  • the other side of the heart contains the right atrium 150, a right ventricular chamber 152 bounded by right ventricular wall 154 and septum 116, and a tricuspid valve assembly 160.
  • the tricuspid valve assembly 160 comprises a valve annulus 162, three leaflets 164, papillary muscles 170 attached to the interior surface of the right ventricular wall 154, and multiple chordae tendineae 180 which couple the tricuspid valve leaflets 164 to the papillary muscles 170-174.
  • the mitral valve leaflets 122 and 124, and tricuspid valve leaflets 164 are all passive structures; they do not themselves expend any energy and do not perform any active contractile function. They are designed to simply open and close in response to differential pressures on either side of the leaflet tissue.
  • the mitral valve 120 opens (i.e., the leaflets 122 and 124 separate). Oxygenated blood flows in a downward direction through the valve 120, to fill the expanding ventricular cavity. Once the left ventricular cavity has filled, the left ventricle contracts, causing a rapid rise in the left ventricular cavitary pressure.
  • the mitral valve 120 This causes the mitral valve 120 to close (i.e., the leaflets 122 and 124 re-approximate) while the aortic valve 118 opens, allowing the oxygenated blood to be ejected from the left ventricle into the aorta.
  • the chordae tendineae 132 of the mitral valve prevent the mitral leaflets 122 and 124 from prolapsing back into the left atrium 110 when the left ventricular chamber 114 contracts.
  • the three leaflets, chordae tendineae, and papillary muscles of the tricuspid valve function in a similar manner, in response to the filling of the right ventricle and its subsequent contraction.
  • the cusps of the aortic valve also respond passively to pressure differentials between the left ventricle and the aorta.
  • the aortic valve cusps open to allow the flow of oxygenated blood from the left ventricle into the aorta.
  • the aortic valve cusps reapproximate to prevent the blood which has entered the aorta from leaking (regurgitating) back into the left ventricle.
  • the pulmonary valve cusps respond passively in the same manner in response to relaxation and contraction of the right ventricle in moving de-oxygenated blood into the pulmonary artery and thence to the lungs for re-oxygenation. Neither of these semilunar valves has associated chordae tendineae or papillary muscles.
  • Heart valves may exhibit abnormal anatomy and function as a result of congenital or acquired valve disease.
  • Congenital valve abnormalities may be so severe that emergency surgery is required within the first few hours of life, or they may be well-tolerated for many years only to develop a life-threatening problem in an elderly patient.
  • Acquired valve disease may result from causes such as rheumatic fever, degenerative disorders of the valve tissue, bacterial or fungal infections, and trauma.
  • Heart valves are passive structures that simply open and close in response to differential pressures on either side of the particular valve
  • problems that can develop with valves can be classified into two categories: 1) stenosis, in which a valve does not open properly, or 2) insufficiency (also called regurgitation) , in which a valve does not close properly.
  • stenosis in which a valve does not open properly
  • insufficiency also called regurgitation
  • Stenosis and insufficiency may occur concomitantly in the same valve or in different valves. Both of these abnormalities increase the workload placed on the heart, and the severity of this increased stress on the heart and the patient, and the heart's ability to adapt to it, determine whether the abnormal valve will have to be surgically replaced (or, in some cases, repaired) or not.
  • CURRENT OPTIONS FOR HEART VALVE REPLACEMENT If a heart valve must be replaced, there are currently several options available, and the choice of a particular type of prosthesis (i.e., artificial valve) depends on factors such as the location of the valve, the age and other specifics of the patient, and the surgeon's experiences and preferences. Available prostheses include three categories of valves or materials: mechanical valves, tissue valves, and aortic homograft valves. These are briefly discussed below; they are illustrated and described in detail in texts such as Replacement Cardiac Valves, edited by E. Bodnar and R. Frater (Pergamon Press, New York, 1991).
  • Mechanical valves include caged-ball valves (such as Starr- Edwards valves), bi-leaflet valves (such as St. Jude valves), and tilting disk valves (such as Medtronic-Hall or Omniscience valves). Caged ball valves usually are made with a ball made of
  • TM a silicone rubber (Silastic ) inside a titanium cage
  • bi- leaflet and tilting disk valves are made of various combinations of pyrolytic carbon and titanium. All of these valves are
  • TM attached to a cloth (usually Dacron ) sewing ring so that the valve prosthesis can be sutured to the patient's native tissue to hold the artificial valve in place postoperatively. All of these mechanical valves can be used to replace any of the heart's four valves. No other mechanical valves are currently approved for use by the FDA in the U.S.A.
  • the main advantage of mechanical valves is their long-term durability. Their main disadvantage is that they require the patient to take systemic anticoagulation drugs for the rest of his or her life, because of the propensity of mechanical valves to cause blood clots to form on them. If such blood clots form on the valve, they may preclude the valve from opening or closing correctly or, more importantly, the blood clots may disengage from the valve and embolize to the brain, causing a stroke.
  • the anticoagulant drugs that are necessary to prevent this are expensive and potentially dangerous in that they may cause abnormal bleeding which, in itself, can cause a stroke if the bleeding occurs within the brain.
  • tissue valves are constructed by sewing the leaflets of pig aortic valves to a stent (to hold the leaflets in proper position), or by constructing valve leaflets from the pericardial sac (which surrounds the heart) of cows or pigs and sewing them to a stent.
  • the stents may be rigid or slightly flexible and are covered with cloth (usually a synthetic
  • TM material sold under the trademark Dacron TM material sold under the trademark Dacron
  • the porcine or bovine tissue is chemically treated to alleviate any antigenicity (i.e., to reduce the risk that the patient's body will reject the foreign tissue).
  • These tri-leaflet valves may be used to replace any of the heart's four valves.
  • tissue valves do not cause blood clots to form as readily as do the mechanical valves, and therefore, they do not absolutely require systemic anticoagulation. Nevertheless, many surgeons do anticoagulate patients who have any type of artificial mitral valve, including tissue valves.
  • tissue valves lack the long-term durability of mechanical valves. Tissue valves have a significant failure rate, usually appearing at approximately 8 years following implantation, although preliminary results with the new commercial pericardial valves suggest that they may last longer. One cause of these failures is believed to be the chemical treatment of the animal tissue that prevents it from being antigenic to the patient. In addition, the presence of the stent and sewing ring prevents the artificial tissue valve from being anatomically accurate in comparison to a normal heart valve, even in the aortic valve position.
  • Homograft valves are harvested from human cadavers . They are most commonly aortic valves but also occasionally include pulmonic valves. These valves are specially prepared and frozen in liquid nitrogen, where they are stored for later use in adults for aortic valve replacement, or in children for pulmonary valve replacement.
  • a variant occasionally employed for aortic valve replacement is to use the patient's own pulmonary valve (an autograft) to replace a diseased aortic valve, combined with insertion of an aortic (or pulmonary) homograft from a cadaver to replace the excised pulmonary valve (this is commonly called a "Ross procedure").
  • aortic homograft valves appear to be as durable as mechanical valves and yet they do not promote blood clot formation and therefore, do not require anticoagulation.
  • the main disadvantage of these valves is that they are not available in sufficient numbers to satisfy the needs of patients who need new aortic or pulmonary valves. They also cannot be used to replace either the mitral valve or tricuspid valve. In addition, they are extremely expensive and much more difficult to implant than either mechanical or tissue valves.
  • the difficulty in implantation means that the operative risk with a homograft valve is greater in a given patient than it is with either a mechanical or tissue valve.
  • An additional problem is that in June 1992, the FDA re-classified homograft valves as an experimental device, so they are no longer available on a routine basis.
  • All artificial heart valves are designed to optimize three major physiologic characteristics and one practical consideration.
  • the three major physiologic characteristics are (1) hemodynamic performance, (2) thrombogenicity, and (3) durability.
  • the practical consideration involves ease of surgical implantation.
  • the Omniscience valve has the partially opened disk itself in the valve orifice when open, and the Starr-Edwards caged-ball valve has both the ball and the cage within the flow orifice of the valve in the open position. All of these structures decrease the hemodynamic performance of the mechanical valves.
  • the construction of artificial tissue valves has been based on the concept that if the artificial valve can be made to approximate the anatomy (form) of the native valve, then the physiology (function) of the artificial valve will also approximate that of the native valve.
  • This is the concept that "Function Follows Form.”
  • the manufacturers of all artificial porcine valves first re-create the form of a native human aortic valve by: 1) harvesting a porcine aortic valve, 2) fixing it in glutaraldehyde to eliminate antigenicity, and 3) suturing the porcine valve to a stent to hold the three leaflets in place.
  • the primary goal in the construction of these artificial valves is to reproduce the form of the human aortic valve as closely as possible.
  • the assumption is made that if the artificial valve can be made to look like the human aortic valve, it will function like the human aortic valve (i.e., proper function will follow proper form).
  • the same assumption is also followed for commercially available pericardial valves.
  • Porcine and bovine pericardial valves not only require chemical preparation (usually involving fixation with glutaraldehyde), but the leaflets must be sutured to cloth-covered stents in order to hold the leaflets in position for proper opening and closing of the valve.
  • a recent advance has been made in this regard by using "stentless" porcine valves that are sutured directly to the patient's native tissues for aortic valve replacement, but the problem of chemical fixation remains.
  • these stentless artificial valves cannot be used for mitral or tricuspid valve replacement.
  • the major limitation of the "Function Follows Form" concept is that no efforts have been made previously to approximate the form of either the mitral valve or the tricuspid valve.
  • a longitudinal suture line was used to convert the flat sheet of tissue into a cylinder, then two triangular regions were removed from one end of the cylinder, to generate two flaps.
  • the inlet end was sutured to the mitral valve annulus, while the two tissue flaps at the carved outlet end were sutured to the papillary muscles.
  • the mitral valve disclosed by Mickleborough et al suffers from a drawback which is believed to be important and perhaps even crucial to proper valve functioning.
  • the anterior leaflet does not have its center portion directly attached to the anterior papillary muscle via chordae. Instead, the anterior leaflet is attached to both the anterior and posterior papillary muscles, via chordae that are predominantly attached to the peripheral edges of the leaflet.
  • a native posterior leaflet is attached to both the anterior and posterior papillary muscles, via chordae that are predominantly attached to the peripheral edges of the leaflet.
  • the line of commissure (closure) between the two mitral leaflets when the valve is closed during systole is oriented in roughly the same direction as an imaginary line that crosses the tips of both papillary muscles.
  • This orientation of the leaflets and papillary muscles ' is shown in illustrations such as page 11 of Netter 1969. This natural orientation can be achieved in the valve of the subject invention as depicted in FIGS. 2 and 3, discussed below.
  • the replacement valve described by Mickleborough et al alters and distorts the proper orientation of the replacement leaflets.
  • Mickleborough ' s approach requires each sculpted leaflet to be trimmed in a way that forms an extended flap, which becomes a relatively narrow strand of tissue near its tip.
  • the tip of each pericardial tissue strand is sutured directly to a papillary muscle, causing the strand to mimic a chordae tendineae.
  • Each strand extends from the center of a leaflet in the Mickleborough et al valve, and each strand is sutured directly to either an anterior and posterior papillary muscle. This requires each leaflet to be positioned directly over a papillary muscle. This effectively rotates the leaflets of the Mickleborough valve about 90° compared to the leaflets of a native valve.
  • pericardial tissue from the same animal that was to receive the artificial valve.
  • tissue if harvested from the same human body that will receive the implant, is referred to as autologous or autogenous (the terms are used interchangeably, by different researchers).
  • the pericardial tissue was cut into a carefully defined geometric shape, treated with glutaraldehyde, then clamped in a sandwich-fashion between two stent components. This created a tri-leaflet valve that again resembles an aortic or pulmonary valve, having semilunar-type cusps rather than atrioventricular-type leaflets. These valves were then tested in the mitral (or occasionally tricuspid) valve position, using sheep.
  • glutaraldehyde fixation as a treatment to reduce shrinkage or other physical distortion (as distinct from using it as a method of reducing tissue antigenicity) is an old and well-established technique for treating non-autologous tissue, but whether it is also beneficial for treating autologous tissue has not yet been extensively evaluated.
  • the effects of chemical fixation of intestinal or other tubular tissue used to create heart valves as described herein can be evaluated by routine experimentation.
  • the subject invention relates to a method of using tubular starting material to replace any of the four heart valves during cardiac surgery.
  • This approach is supported by and consistent with a fundamental principle of native heart valve function. which either went unrecognized in previous efforts to develop replacement valves, or which was sacrificed and lost when compromises were required to adapt available materials to surgical requirements.
  • the basic principle which deserves repeated emphasis because it has been so widely disregarded by other efforts in this field, is that Form Follows Function. In one manifestation of this principle, if an artificial valve can be created that can truly function like a native valve, its resultant form will be similar to that of the native valve.
  • the entire cardiovascular system begins in utero as a single, relatively straight tube of tissue.
  • Anatomical drawings depicting the in utero development of the heart are available in numerous scientific publications and books, including Netter 1969.
  • the so-called "heart tube” is readily discernible by the 23rd day of gestation. This tube will eventually develop into the entire cardiovascular system of the body.
  • the tissue that exists between the portion of the tube destined to become the ventricles, and the portion that will become the atria, is where the mitral and tricuspid valves will ultimately form. This region of tissue is in a tubular form.
  • the heart tube undergoes a process of convolution beginning at approximately 25 days gestation. This convolution of the heart tube forms what is called the "heart loop" and is responsible for the aortic valve ultimately coming to lie adjacent to the mitral valve.
  • the anterior portion of the mitral valve annulus is relatively flat. This distortion of the original roundness of the mitral annulus is caused by the presence of the aorta against the anterior mitral valve. It is also the reason that the anterior leaflet of the mitral valve is contiguous with the aortic valve annulus.
  • the tissues that are to eventually become the heart valves maintain their tubular structure.
  • portions of the walls of these tubular structures undergo a process of dissolution, leaving behind only those portions of the original tubes that are necessary for the proper functioning of the heart.
  • This dissolution also affects the ventricular walls as they rapidly enlarge in size; if it did not, the walls would become prohibitively thick as the physical size of the heart increased, and the heart could not function effectively as a pump since it would become simply a large mass of ventricular muscle.
  • the dissolution process also operates on the tubular constrictions that will become the four heart valves.
  • the thickened tissue that is commonly referred to as the "annulus" of these valves is simply the flexion point of the three cusps, the remnants of a simple tube that is fixed at three points distally and subjected to uniform pressure on its outside, resulting in collapse of the tube on the three sides between the points of distal fixation, which in turn, results in three nearly identical cusps. All tissue other than these moveable and functional cusps has undergone the normal process of dissolution as the aorta and pulmonary artery have enlarged, leaving behind only that tissue recognized as the cusps of these semilunar valves.
  • valve leaflets are tube remnants, which are attached circumferentially to the fibrous annulus of the heart at their base and attached by chordae tendineae (additional tube remnants) at their free edges to papillary muscles (still more tube remnants) inside the ventricles.
  • chordae tendineae additional tube remnants
  • papillary muscles of each the two A-V valves represent the necessary functional remnants of the original in utero tubular structures of the heart.
  • the present invention is based on the realization that a tubular structure having proper size and suitable material characteristics, if placed inside a mitral or tricuspid valve annulus after excision of the native valve (or inside an aorta or pulmonary artery, as described below) will function exactly like the normal valve in that position, assuming proper fixation of the inlet and outlet ends of the tube.
  • the "Form Follows Function” principle predicts that if the intended function of a replacement valve is to emulate the performance and function of a native mitral or tricuspid valve, then the form of a replacement valve—the structure and appearance of the replacement valve—should resemble the form of a native mitral or tricuspid valve. Since the native valves are generated from tubular starting material during fetal development, this principle further suggests that replacement valves should also be generated from tubular material.
  • the artificial valve had to be removed because its leaflets had become calcified and immobile, resulting in both mitral stenosis and mitral insufficiency.
  • the surgeon was struck by the similarity in shape and appearance of the diseased trileaflet valve to a normal mitral valve.
  • the commissures of the three leaflet artificial tissue valve had fused in a manner so that two leaflets had been formed: one large anterior leaflet, and one smaller posterior leaflet, as seen in a native mitral valve.
  • the commissure between the two leaflets when the patent's valve was closed by back pressure closely resembled the semi-circular commissure formed by leaflets in a native mitral valve.
  • This form then creates a function: the new valve allows flow in only one direction, from the atrium to the ventricle.
  • This function creates another form: the leaflets of the new mitral valve will close in a "smile" configuration resembling a native mitral valve during closure.
  • This secondary form then creates a secondary function: the new valve will provide good long-term use and low levels of turbulence, hemolysis, calcification, and leaflet stress.
  • Form and function form a cycle, and this cycle cannot be disrupted by injecting and imposing an artificial, unnatural form in the heart without impeding the ability of proper form and proper function to interact with, support, and enhance each other.
  • one object of this invention is to provide a method of surgically replacing heart valves using natural autologous tubular tissue (i.e., the patient's own tissue) as the starting material.
  • natural autologous tubular tissue i.e., the patient's own tissue
  • Use of the patient's own tissue can completely avoid the need for chemical processing, freezing, or other treatment, which are required to reduce the antigenicity of tissue obtained from animals or cadavers.
  • Another object of this invention is to provide a method of surgically replacing heart valves using innately tubular material (i.e., tissue or synthetic material which is harvested or synthesized in tubular form) as the starting material, to increase the long-term durability of replacement heart valves.
  • Another object of this invention is to provide a method of using tubular starting material to create a replacement heart valve without requiring the use of a foreign object such as a stent to secure the replacement valve in position.
  • This invention comprises a method of using tubular material to replace a heart valve during cardiac surgery.
  • the tube inlet is sutured to the mitral or tricuspid valve annulus, and the outlet end of the tube is sutured to papillary muscles in the ventricle.
  • the tube inlet is sutured to the aortic or pulmonary valve annulus, and the tube is either "tacked" at three points distally, or sutured longitudinally along three lines; either method will allow the flaps of tissue between the suture lines to function as movable cusps.
  • a preferred non-antigenic material comprises a segment of submucosal tissue from the small intestine of the same patient who is undergoing the cardiac operation.
  • tissue from the same patient the risk of immune rejection and the need to use fixation treatment to reduce the antigenicity of animal or cadaver tissue are eliminated.
  • animal or human cadaver intestinal tissue can be used if desired, if properly treated (such as by glutaraldehyde fixation) to reduce antigenicity, or biocompatible synthetic materials can be used.
  • This invention also discloses a prepared, chemically treated intestinal tissue segment suitable for implantation as a replacement heart valve, with or without an annuloplasty ring attached to the tissue segment, enclosed in a sealed sterile package.
  • FIGURE 1 is a cutaway depiction showing the mitral valve on the left (systemic) side of the heart and the tricuspid valve on the right (pulmonary) side of the heart, showing a piece of small intestinal submucosal (SIS) tissue adjacent to the heart, having a size and configuration that will render the SIS tissue suitable for implantation as a replacement mitral valve.
  • FIGURE 2 depicts a top view (from the left atrium) of a tubular tissue valve sutured into the mitral position, showing the orientation of the anterior and posterior leaflets in relation to the anterior and posterior papillary muscles.
  • FIGURE 3 shows a top view of the tubular mitral valve during systolic contraction of the ventricle. The two leaflets are pressed against each other in a natural "smile” configuration; this closure (approximation) of the leaflets prevents blood from flowing back into the atrium.
  • FIGURE 4 depicts a tubular segment of small intestine submucosal (SIS) tissue that has been inserted into an aorta or pulmonary artery, to create a semilunar valve with cusps.
  • SIS small intestine submucosal
  • FIGURE 5 depicts a semilunar valve as described herein, in a closed position.
  • FIGURE 6 depicts a configuration that can be used if desired to secure tubular tissue inside an aorta in a configuration in which the cusps of the valve are pinched together adjacent to the arterial wall.
  • FIGURE 7 depicts a tubular segment of intestinal or synthetic material, enclosed within a sealed pouch that maintains sterility of the tubular segment.
  • FIGURE 8 depicts a tubular tissue segment of intestinal or synthetic material which has been attached to an annuloplasty ring, enclosed within a sealed sterile pouch.
  • This invention comprises a method of using tubular material to replace heart valves during cardiac surgery.
  • a segment of small intestinal submucosal (SIS) tissue is used.
  • the SIS tissue can be harvested from the body of the same patient who is receiving the replacement valve. This eliminates the risk of immune rejection and the need to use fixation treatment to reduce the antigenicity of tissue from animals or cadavers.
  • tubular starting material refers to material that is harvested from a human or animal body in tubular form (such as intestinal tissue), and to synthetic material that is synthesized, molded, woven, or otherwise created in tubular form.
  • Tubular starting material is distinct from flat starting material that has been secured by means such as suturing into a tubular intermediate form.
  • a flexible tubular segment was created in a three-dimensional CAD-CAM program, which was run on a computer in the Applicant's research laboratory.
  • the tube segment was affixed, at certain designated points, to the interior wall of a cylindrical flow conduit.
  • One end (corresponding to the inlet) of the flow conduit and flexible tube were flattened on one side, and the flexible tube inlet was fixed around the entire inner circumference of the flow conduit.
  • the other end (the "outlet”) of the flexible tube was fixed at only two opposed points inside the flow conduit.
  • a similar CAD-CAM analysis was performed for an aortic (or pulmonary) valve in which the inlet end of the flexible tube was fixed circumferentially around the inlet of the flow conduit, and the other end of the flexible tube was fixed at 3 equidistant points around the circumference of the conduit.
  • the external pressure applied to the outside of the tube was 80 mm Hg, corresponding to the arterial pressure exerted on normal aortic valve leaflets during diastole.
  • the resultant shape of the tube after 12 hours of mathematical deformation appeared to exactly mimic a natural aortic valve.
  • tubular starting material such as intestinal tissue
  • flat starting material is advantageous, provided that the intestinal tissue segment has a diameter compatible with the valve being created.
  • a pre-treated packaged segment of SIS tissue having the desired diameter from an animal (such as a pig) or a human cadaver can be used to avoid the need for using a longitudinal suture line to convert flat material into tubular material.
  • an animal such as a pig
  • a human cadaver can be used to avoid the need for using a longitudinal suture line to convert flat material into tubular material.
  • the approach used by Mickleborough et al caused the anterior and posterior leaflets of their replacement valve to be rotated roughly 90° compared to the native leaflets in a native mitral valve.
  • the subject invention allows the creation of mitral leaflets having a natural orientation. This factor was discussed in the Background section and is depicted in FIGS. 2 and 3.
  • This invention teaches a method for replacing heart valves using tissue from the body of the same patient who receives the replacement valve.
  • a segment of tissue several inches long is removed from the jejunal or ileal region of the small intestine.
  • item 200 in Figure 1 refers to a cylindrical (tubular) segment of tissue that has been surgically removed from the jejunal portion of the small intestine (i.e., the extended segment between the duodenal region near the stomach, and the ilial region).
  • the jejunal region of the small intestine is approximately 6 meters (20 feet) long in an adult, and the removal of a short segment (such as about 15 cm, or 6 inches, which would provide more than enough SIS tissue to create a replacement valve) will not significantly affect the digestive capabilities of the patient.
  • This segment of intestinal tissue can be removed from the patient's abdomen during the same surgical operation used to replace the heart valve. Therefore, only one operation under general anesthesia is required, and the intestinal tissue is fresh and unaltered by storage and/or fixation when it is harvested for immediate use.
  • the small intestine segments on each side of the removed portion are anastomosed (sutured together) using standard techniques, and the abdomen is closed. This entire abdominal portion of the operation can usually be performed in the time it takes to open the chest and cannulate the heart and great vessels in preparation for valve replacement.
  • the intestinal segment is wiped with a sterile cloth on the outside, to remove two outer layers of tissue known as the serosa and the muscularis (smooth muscle).
  • the segment is then turned inside out and wiped again to remove the mucosal layer that lines the inside of the intestinal segment.
  • Tests using animals have indicated that all three of these layers of the intestinal wall can be wiped off easily and without damaging the basement membrane or submucosa, by a simple wiping procedure. In tests on dogs, the wiping and cleaning procedure has taken only a few minutes. After the serosa, muscularis, and mucosal layers have been removed, two layers remain in the tissue segment.
  • tissue segment If the tissue segment is returned to its original orientation, these two layers are the basement membrane (on the outside of the tube) and the submucosa (inside the tube). These two layers form a tough, durable, highly flexible tissue segment, referred to herein as "Small Intestine Submucosa” (SIS) tissue.
  • SIS Standard Intestine Submucosa
  • tissue if desired can also be used to treat the tissue if desired, such as glutaraldehyde or other crosslinking treatment.
  • glutaraldehyde or other crosslinking treatment.
  • Such treatment is not necessary to reduce the antigenicity of the tissue, if the tissue comes from the same body that will be receiving the valve; however, as mentioned in the Background section, some reports suggest that treatment with a crosslinking agent such as glutaraldehyde can provide a useful degree of crosslinking between adjacent collagen fibers, which can reduce the tendency of certain types of tissue to shrink or thicken over prolonged periods of time.
  • the SIS tissue segment can be implanted in a mitral valve position using any of several methods. In one method, it can be initially implanted as an unsculpted tube, then trimmed as necessary to preclude redundancy of the leaflets. This method can be performed as follows. The patient or animal is placed on total cardiopulmonary bypass so that the heart can be opened safely. The heart is either arrested or fibrillated and the mitral valve is exposed through an incision in the left atrium. The leaflets and chordae tendineae of the native mitral valve are surgically removed, leaving behind a mitral valve annulus 121. This annulus 121 has a roughly circular shape; however, as shown in FIG.
  • annulus 2 there is a somewhat “flattened” area 123 in the annulus, on the side closest to the aortic valve
  • the base of the anterior leaflet is attached to this "flattened” region of the mitral valve annulus.
  • the inlet (proximal) 202 end of the tubular segment 200 is sutured into the mitral valve annulus 121, using a suture line 204 which travels around the entire circumference of the annulus 121 and the tubular segment 200.
  • an annuloplasty ring (such as illustrated in FIG. 8) can be used to create a bridge between the valve annulus 121 and the SIS tissue inlet 202.
  • the length of the SIS segment can be trimmed to eliminate most of the excess length while retaining adequate tissue for the surgeon to work with.
  • Sutures are then used to temporarily secure the outlet (distal) end of the tube to the papillary muscles at a distance from the mitral annulus compatible with the desired degree of "closure" of the tubular valve. This can be done by placing a tacking suture through the appropriate side of the tube distally and then passing it through the tip of the anterior papillary muscle 126. The same procedure is performed on the opposite side of the tube, temporarily attaching it to the posterior papillary muscle 128.
  • Saline is then injected into the left ventricular chamber 112, which will remain capable of sustaining fluid pressure inside a closed chamber if access to the mitral valve is obtained via an incision through the left atrial wall.
  • the saline flush generates fluid pressure in ventricle 112, which causes the sides of the tube to be forced into approximation. In other words, the saline flush closes the newly-created valve.
  • the tube 200 can permanently attached to the tips of the papillary muscles 126 and 128. This can be done in any of several ways. If the distal end of the SIS tissue has been carved, trimmed, or sculpted to create elongated wedges or strands of tissue which will serve as substitute chordae tendineae for attachment purposes, the distal ends of the sculpted tissue segments can be sutured to the papillary muscles.
  • the tips of the tissue segments can be inserted into small incisions in the tips of the papillary muscles; these can then be reinforced using reinforcing devices on the out ⁇ ides of papillary muscles, to reduce the risk of tearing the tissue segments or the tips of the papillary muscles.
  • a sculpting or trimming step which physically divides the replacement leaflets into an anterior leaflet that has been partially divided from the posterior leaflet is presumed to be preferable, because it can help the valve leaflets more closely emulate the physical shape of the leaflets in a native mitral valve. If such a sculpting or trimming step is desired, it can be carried out at any suitable time during the operation, such as immediately after a temporary suturing step followed by a saline flush have confirmed that a certain attachment configuration will function in the desired manner.
  • the left atrium is closed and the heart is restarted.
  • the leaflets will be forced open.
  • this tubular valve when open during the systolic phase of each heartbeat, has no obstructions in its flow path.
  • various devices must be positioned in the flow path of the blood. These hinder blood flow, leading to pressure gradients across the valve, especially at high flow rates and with small sized valves, and they also generate turbulence that can damage blood cells.
  • previous artificial tissue valves require stents and do not mimic the function of native valves, they also cause turbulence in blood flow, which is believed to be a potentially important factor in the production of calcification in the leaflets of the artificial tissue valve.
  • FIG. 3 shows a top view (from the left atrium) of the closed valve during contraction of the ventricle.
  • the two sides of the tube effectively create a new anterior leaflet 122A and a new posterior leaflet 124A, which closely emulate the shapes and orientations of the native anterior leaflet 122 and the native posterior leaflet 124.
  • the commissure between the two natural leaflets is curved, in a manner that resembles a smile. This occurs because: 1) the mitral valve annulus 121 is not completely round, and has a "flattened" region 123 on the side closest to the aortic valve, and 2) pressure on the outside of any tube that has one flat side and is attached at two points distally (in line with the two ends of the flat side) will result in apposition of the two sides of that tube in a manner that resembles a smile.
  • HOCM Hypertrophic Obstructive Cardiomyopathy
  • Tricuspid valve replacement in humans is especially problematic because tissue valves tend to fail earlier and mechanical valves tend to form clots at a much higher rate than either do in the mitral or aortic position.
  • tissue valves tend to fail earlier and mechanical valves tend to form clots at a much higher rate than either do in the mitral or aortic position.
  • re-infection of the new artificial valve is so common that some authors have actually advocated removal of an infected native valve without replacement with a new artificial one!
  • the need for a satisfactory artificial valve for tricuspid valve replacement is especially acute.
  • Tricuspid valve replacement can be created in essentially the same manner as mitral valve replacement, described above.
  • Preliminary studies on animals indicate that the natural shape of the tricuspid annulus at the proximal end of a tube valve and three points of fixation distally to the normal papillary muscles in the right ventricle will result in an anatomically correct trileaflet tricuspid valve.
  • papillary muscles are more variable and unpredictable in their placement than in the left ventricle; accordingly, tricuspid valves tend to be more difficult to replace than any of the other three valves, and successful replacement depends even more heavily upon the experience and expertise of the surgeon in tricuspid valve repair than in other valves.
  • annuloplasty Ring for Replacement of Atrio-ventricular Heart Valves
  • a preferred mode for surgical insertion of the valves described herein completely avoids the use of an annuloplasty ring.
  • annuloplasty rings in the mitral or tricuspid position pose a theoretical problem in regard to the threat of thrombosis. Accordingly, by disclosing replacement valves that can be created without using annuloplasty rings, this invention offers an advance over prior art replacement valves currently in use.
  • annuloplasty rings are widely used without severe adverse effects, and in many patients suffering from heart disease or congenital abnormalities, they can be advantageous or even necessary.
  • this invention discloses (1) replacement valves made of tubular tissue (or suitable synthetic material) coupled to annuloplasty rings, and (2) a method of surgically implanting such replacement valves.
  • the tubular tissue will work in the same manner as described above, while the annuloplasty ring will help create a bridge between the inlet end of the tubular tissue segment, and a valve annulus in a patient (such as a patient whose native mitral valve annulus is weak, dilated, and/or "rounded" out of its normal shape.
  • the implantation of the annuloplasty ring can be carried out using the same techniques that are currently used for mitral and tricuspid valve reparative techniques.
  • the inlet rim of the SIS tissue is sutured to an annuloplasty ring.
  • the annuloplasty ring has been sutured to an atrioventricular valve annulus, the distal end of the SIS tissue is sutured to the papillary muscles as described above.
  • the annuloplasty ring can be coupled to the tube and both can be packaged together in a sealed package which maintains their sterility.
  • This article of manufacture is described in more detail below and is shown in FIG. 8, in which a tubular segment 500 has been attached to an annuloplasty ring 502.
  • the subject invention discloses a method of using small intestinal submucosal (SIS) tissue in conjunction with an annuloplasty ring to create a heart valve replacement.
  • SIS small intestinal submucosal
  • tubular valves of this invention do not require stents.
  • stent includes any man-made device (other than a suture, annuloplasty ring, or leaflet material) which is surgically implanted in a patient's heart (or aorta or pulmonary artery) as part of a replacement valve, and which is contacted by blood which flows through the heart (or aorta or pulmonary artery).
  • Stents are major components in all mechanical replacement valves, since they must securely hold the ball, flapper, or other movable elements of the valve in proper position; they are also used in nearly every type of artificial tissue valve, to secure the tissue flaps in the proper configuration.
  • stent does not include reinforcing pledgets placed on the outside of an aorta or pulmonary artery, since such pledgets would not be contacted by blood flowing through the artery. Stents are known to increase turbulence and thrombosis. Since the valves disclosed herein are stentless, this invention offers an important advance over prior art replacement valves which are currently approved by the FDA.
  • atrioventricular (mitral or tricuspid) replacement valve can be described as follows:
  • a tubular segment is obtained, consisting of thin and flexible tubular tissue or synthetic material, having an inlet end and an outlet end.
  • the damaged or deformed leaflets of the native diseased valve are surgically removed from the heart of the patient, to generate an open valve annulus.
  • the chordae tendineae are also removed, while the papillary muscles in the ventricular chamber are left intact.
  • the inlet end of the tube is sutured to the valve annulus, or to an annuloplasty ring if necessary for a specific patient.
  • the outlet end of the tube is sutured to the papillary muscles, in a manner which will allow the outlet flaps to function as valve leaflets that will open during ventricular diastole, when blood flows from the atrium into the ventricle.
  • the valve leaflets will approximate and close the valve during ventricular systole, to prevent backflow when fluid pressure in the ventricle exceeds fluid pressure in the atrium.
  • the specific sites of attachment of the tubular material to the papillary muscles should allow the resulting leaflets to approximate in a manner that emulates the shape and angular orientation of the leaflets in a properly functioning native valve.
  • a segment of intestinal tissue several inches long is removed from the patient and treated to remove the serosa, smooth muscle, and mucosal layers in the same manner described above.
  • SIS small intestinal submucosal
  • the tubular material may be obtained from other animals or from human cadavers, or it may be manufactured from a suitable synthetic material.
  • an SIS segment is used.
  • the desired length can range from about 2 cm for neonates to about 6 cm for adults.
  • an aortic wall is opened by an incision above the level of the commissural posts of the aortic valve, and the cusps of the native aortic valve are removed, leaving behind a valve annulus.
  • the tubular SIS segment 200 is then inserted, and as shown in FIGS. 4 and 5, the inlet end 202 is secured to the interior surface of the aortic wall 250 by means of a circumferential suture line 210; this step can utilize an annuloplasty ring if desired.
  • the SIS segment can then be secured by means of three longitudinal suture lines 220 spaced at one-third intervals (120° apart from each other) around the internal periphery of the aortic wall 250.
  • tissue segment 200 Suturing the tissue segment 200 to the inside of the aortic (or pulmonary artery) wall 250 by means of three longitudinal suture lines 220 will leave three tissue regions 222 which will function as cusps during operation of the valve.
  • tissue cylinder 220 After the tissue cylinder 220 is properly secured and the patient's heart is closed by the surgeons and restarted, the three cusp regions 222 will go through a cyclical movement with each heartbeat.
  • the cusps 222 be held open by blood entering inlet end 202 and exiting outlet end 204.
  • the three longitudinal suture lines 220 can be reinforced by strips (often called pledgets) placed on the exterior of the aortic wall. These reinforcing strips can be made of autologous tissue, materials sold under trademarks such as TEFLON, GORETEX, SILASTIC, or any other suitable material.
  • these strips would be positioned outside the aorta or pulmonary artery, they would not come into contact with blood flowing through the artery. Therefore, they can reinforce the arterial wall, distribute any tensile stresses more evenly across a wider area of the arterial wall, and reduce the risk of tearing the arterial wall, without increasing the risk of thrombosis inside the artery.
  • reinforcing strips can also be positioned inside an aorta or pulmonary artery, and a stent can be used to reinforce the inlet attachment.
  • a stent can be used to reinforce the inlet attachment.
  • any reinforcing component which is exposed to blood inside the artery would increase the risk of thrombosis and probably would suggest to the surgeon that the patient would need to be placed on anticoagulant drugs to reduce the risk of clot formation.
  • the subject invention discloses a method of replacing the aortic and pulmonary valves in which a round annuloplasty ring is used in conjunction with the artificial tubular tissue or mechanical valve. After obtaining a tubular segment of tissue or synthetic material, the tubular segment is sutured at its inlet end to a round annuloplasty ring which is then sutured into the aorta (or pulmonary artery) at the level of the lowest point of the excised native semilunar valve. The distal end of the tubular segment for both aortic valves and pulmonary valves is then handled in the same manner as described above for these valves without annuloplasty rings.
  • non-planar cuts such as a mildly sinusoidal cut
  • non-planar outlets can be tested using any of several techniques (computerized CAD-CAM analysis, in vitro testing using a closed mechanical pumping circuit, or in vivo using animals such as dogs or sheep) to determine whether they are preferable to a square-end outlet, either for particular patients or as a general approach.
  • a semilunar replacement valve i.e., an aortic or pulmonary valve
  • a tubular segment is obtained, consisting of thin and flexible tissue or synthetic material having an inlet end and an outlet end.
  • the damaged or deformed leaflets of the native valve are surgically removed, to generate an open valve annulus.
  • the outlet end of the tube is sutured to the aorta or pulmonary artery at three equidistant points around the circumference. This creates three outlet flaps between the three points of attachment, and the outlet flaps will function as valve cusps that will open during ventricular systole, when blood flows from the ventricle into the aorta or pulmonary artery.
  • the valve cusps will approximate and close the valve during ventricular diastole, to prevent backflow when fluid pressure in the aorta or pulmonary artery exceeds fluid pressure in the respective ventricle.
  • the first method involves creating a partial closure of adjacent cusps at their outer periphery. This can be done by gently pinching the walls of the inserted SIS cylinder 200 together at the outlet end of each of the three longitudinal suture lines 220 (or outlet attachment points), as shown in FIG. 6.
  • the pinched SIS junctures can then be held in place by one or more suture stitches 240.
  • the suture stitches 240 can be reinforced to prevent tearing of the SIS segment 200 by placing small reinforcing pieces 242, made of a flexible, soft, blood-compatible material such as GoreTex or Silastic, on the outside surfaces of the SIS wall 200, as shown in FIG. 6.
  • An alternate potential method for ensuring that the three cusps will not become flattened against the inside of the aorta involves a stent device that could be secured within the aortic wall 250, outside the SIS segment 200.
  • This type of stent if used, would containing projections which extend in an inward radial direction, toward the central axis of the aorta. These projections, which would be positioned at midpoints between the three attachment points at the outlet end, would prevent any flattening of the cusp regions 222 against the interior of aortic wall 250. This would ensure that back pressure in the aorta would force each cusp in an inward direction, to ensure closure, rather than pressing the cusps in an outward direction which would cause them to flatten against the interior of the arterial wall and allow regurgitation.
  • certain types of chemical treatment of intestinal or other tubular tissue may be able to further reduce the calcification potential of a replacement valve that is created as described herein.
  • autologous human intestinal tissue specifically the submucosa of the small intestine (SIS)
  • SIS small intestine
  • an important aspect of this invention is the disclosure, in broad terms, that intestinal tissue harvested from the body of the same patient who is receiving a new heart valve can be used in the replacement valve.
  • this invention discloses a method of surgically replacing a heart valve in a human patient in need thereof, comprising the steps of (a) extracting a segment of intestinal tissue from the patient's abdomen, and (b) using the intestinal tissue to form at least one component of a replacement valve for the patient's heart. It also discloses certain articles of manufacture comprising previously prepared intestinal segments, from animals or human cadavers, which have been treated to render them suitable for use in creating replacement valves, and which are contained in sealed packages that maintain their sterility. These articles of manufacture are discussed in more detail below.
  • tissue from the body of the patient receiving the heart valve replacement can be used if desired, rather than intestinal tissue.
  • the pericardial sac which encloses the heart has enough tissue so that a segment can be removed and used as a heart valve. This would allow a surgeon to conduct the entire operation without having to make an additional incision in the patient's abdomen.
  • recent studies by others have indicated the feasibility of using freshly harvested autologous pericardial tissue to create artificial cusps that can then be sutured inside the aorta to serve as an artificial aortic valve. That technique, however, differs in several ways from the current invention, and those investigators apparently have not recognized the importance of the principal that Form Follows Function.
  • pericardial tissue which is essentially flat
  • the subject invention states that pericardial tissue (which is essentially flat) can be used to replace an aortic valve if desired, but the pericardium should first be fashioned into a tube, and that tube should be fixed inside the aorta in the manner described above.
  • Form follows Function By fixing the inlet end of the tube circumferentially and the outlet end of the tube at 3 points (or along three longitudinal lines from the inlet), the external diastolic pressure in the aorta will cause the non-fixed sides of the tube to collapse against one another and the pericardial tube will be forced into the shape of a normal aortic valve.
  • Form follows Function The principle that Form follows Function will be operative in all artificial tubular valves used to replace any of the four native valves regardless of the specific type of tissue used to create the tubes.
  • a potential source of tissue is the "fascia lata," a membranous layer which lies on the surface of certain skeletal muscles.
  • Another potential source of autologous tissue is suggested by a known phenomenon involving mechanical objects that are implanted in the body, such as heart pacemakers. When such objects remain in the body for several months, they become encapsulated by a layer of smooth, rather homogeneous tissue. This phenomenon is described in articles such as Jansen et al 1989. The cellular growth process can also be controlled by manipulating the surface characteristics of the implanted device; see Chehroudi et al 1990. Based upon those observations and research, it is possible that mandrill implantation in the body of a patient who will need a heart valve replacement might become a potentially feasible technique for generating the cylindrical tissue.
  • "homograft" tissue can be harvested from the bodies of human cadavers for later use in artificial tubular heart valves.
  • a very long segment of intestinal tissue comprising all or a major portion of the jejunal region of the small intestine can be resected from the body of someone who has recently died, such as an accident victim. This harvesting operation would be comparable to harvesting a heart, kidney, or other internal organ from a deceased organ donor.
  • the intestinal tissue is then cut into segments of roughly 10 to 20 cm (four to eight inches) each, which would then be prepared (by removing the serosa, smooth muscle, and submucosal layers), treated to reduce its antigenicity, and stored (at either refrigerated or frozen temperature) in a sterile preservation solution until use. When needed as a heart valve replacement, the tissue would be warmed and treated as necessary, and cut into the precise size and configuration needed.
  • One advantage of this approach is that it would spare the cardiac patient from any additional pain or surgical stress that might result from having a surgical incision made in the abdomen to harvest autologous SIS tissue as described above.
  • the additional stress or pain of obtaining a segment of intestinal tissue through a small abdominal incision is quite small compared to open-heart surgery, where the chest and rib cage must be opened.
  • several of the newest approaches to coronary artery bypass surgery (the most frequently performed cardiac operation) require much larger abdominal incisions to harvest abdominal arteries that are now used as bypass conduits.
  • Another alternate embodiment is to use "heterograft" tissue from other animal species.
  • This embodiment probably would require chemical fixation of the heterograft tissue (which presumably would comprise intestinal segments) by techniques such as glutaraldehyde crosslinking, as currently used to fix porcine or bovine pericardial tissue for conventional heart valve replacements.
  • glutaraldehyde crosslinking as currently used to fix porcine or bovine pericardial tissue for conventional heart valve replacements.
  • any pig which has descended from a genetically-engineered hypoallergenic pig is itself considered to be a genetically-engineered hypoallergenic pig, since the genetically-engineered hypoallergenic traits are inheritable).
  • Tubular "Mechanical” Non-Tissue Valves
  • this invention also suggests the use of tubular synthetic material as a starting material for such valves.
  • Various types of highly durable and flexible synthetic materials have been developed and are continuing to be developed, and some of these materials are promising candidates which can be evaluated for possible use as described herein.
  • One such material is sold under the trademark "GoreTex.” It is, in essence, a polymerized layer of PTFE which is rendered flexible by coating it onto a flexible woven or knitted substrate material, such as nylon fabric. By coating PTFE onto a tubular substrate, it is possible to create tubular forms of such coated materials.
  • Such materials are highly durable inside the body, they can occasionally causes problems of blood clotting, apparently due in part to their rough surface textures, and possibly due also to plasticizers and other chemicals used to control the polymerization, thickness, and flexibility of the PTFE coating material.
  • Perfluorinated elastomers a different class of synthetic materials that have recently been developed, also offer promise as potential artificial tubular valves as described herein. These elastomers are described in patents such as U.S. patent 4,900,793 (Lagow and Chester, 1990). Essentially, they contain only carbon and fluorine atoms, which are bonded together in highly stable polymeric configurations. Perfluorinated elastomers contain very little oxygen, hydrogen, nitrogen, sulfur, or other substances that might chemically react with physiological fluids to degrade the elastomer or cause leaching of constituent ions into the blood.
  • elastomers can provide very smooth surfaces, and since they are elastomeric in their own right, it is unnecessary to coat them onto the rough surface of a second material such as woven or knitted nylon in order to provide flexibility. They can be molded or otherwise synthesized directly into tubular form.
  • An additional advantage that can be obtained by using synthetic materials in the manner disclosed herein is that an essentially tubular configuration can be provided which has a gradually varying diameter. For example, a relatively long tubular device can be created from synthetic material, having a diameter at the inlet end of up to about 5 cm and a diameter at the outlet end of about 2 cm.
  • a surgeon can simply cut the piece of tubing at any appropriate location along its length, to provide an inlet diameter corresponding to the diameter of a patient's valve annulus, which can be measured after the heart has been opened and the damaged or defective leaflets have been removed.
  • a single tubing size can be adapted to accommodate various different patients; this will reduce the costs that would be required to manufacture or stock tubes having multiple different sizes.
  • this invention discloses an article of manufacture depicted in FIG. 7.
  • This item comprises a tubular segment 500, made of tissue from the small intestine, or synthetic material having suitable overall dimensions and walls sufficiently thin and flexible to allow them to function as leaflets in a heart replacement valve. Since autologous tissue would not require storage for later use, this portion of the disclosure relates to the use of non-autologous (homograft or heterograft) tissue.
  • This tubular segment 500 is enclosed within a sealed container 510 that maintains sterility of the segment 500.
  • a sterile container 510 can comprise a plastic pouch, as shown in FIG. 7, having a transparent front layer 512 to allow visual inspection (this layer is shown folded up at one corner, for depiction purposes only). The front layer 512 is sealed around its periphery to a back layer 514.
  • tubular segment 500 is attached to an annuloplasty ring 502 before both are sealed inside package 510.
  • the tube-to-ring attachment can be done by suturing in the case of tubular tissue segments, or by any suitable synthetic method (such as molding) if a synthetic tube is attached to a synthetic annuloplasty ring.
  • intestinal tissue If intestinal tissue is used, it should be packaged in hydrated form, in a suitable liquid (such as phosphate-buffered saline with one or more preservative agents, such as glutaraldehyde, if desired) contained within the pouch.
  • a suitable liquid such as phosphate-buffered saline with one or more preservative agents, such as glutaraldehyde, if desired
  • Such pouches can be shipped and stored in stiff-walled boxes for protection; alternately, instead of using a flexible pouch as the container, a plastic box with a transparent closure layer sealed around its rim can be used as the container itself.
  • a segment of intestinal tissue is contained in such a sterile container, it preferably should be treated before being sealed within the pouch, to remove the exterior serosa and muscularis layers and the interior mucosal layer, leaving only the desirable submucosal and basement layers.
  • a synthetic tube as described herein can have a diameter that varies gradually over its length. Such a tube can be transsected at a location having the desired diameter. This would allow a tube with a single size to accommodate patients who have valve annulus diameters with varying sizes.
  • different sizes of synthetic tubes can be packaged separately. This raises an important issue. In most cases, it will probably be possible to directly insert an SIS intestinal segment harvested from a patient directly into the mitral or tricuspid valve location in that patient, since the diameters of an SIS segment and a mitral or tricuspid valve annulus in most humans is believed to be comparable or at least compatible.
  • an SIS segment can be cut longitudinally, to convert it into a flat segment that can be trimmed to any desired size before creation of the replacement valve.
  • three longitudinal suture lines can be used to create a replacement aortic or pulmonary valve, as part of the surgical procedure. Therefore, one of these suture lines can be used to re-size the SIS segment into a different diameter while retaining its tubular form.
  • a prepackaged intestinal tissue segment can be used which has the desired diameter, harvested from a human cadaver or animal. This would avoid the need for a longitudinal cut, and it would preserve the tubular form of the intestinal segment throughout the entire procedure. Tissue from cadavers or animals would need to be treated by fixation (using glutaraldehyde crosslinking or another suitable method) to reduce its antigenicity before implantation.
  • one of the preferred embodiments of this invention comprises an array of sealed sterile packages containing intestinal tissue segments from cadavers or animals for use in creating replacement valves.
  • Each separate container would hold an intestinal segment having a known diameter or circumference (presumably measured in millimeters), which would be indicated on the label of the container.
  • the tissue segments Before being packaged, the tissue segments would be cleaned to remove the undesired tissue layers and fixed to reduce antigenicity.
  • a surgeon opens a patient's chest and excises the cusps or leaflets from a diseased or damaged valve, he or she can directly measure the valve annulus. This measurement will indicate the exact diameter or circumference of the intestinal segment that should be used.
  • a sealed package containing an intestinal tissue segment having the desired diameter or circumference can be selected and opened, and the segment will be immediately available. If desired, the tissue segment in the sterile package can already be attached to an annuloplasty ring, which would also be contained in the package. Accordingly, this invention discloses an article of manufacture comprising a sealed sterile package containing a tubular intestinal tissue segment which has been treated to render it suitable for implantation as a heart valve.
  • the diameter or circumference of the intestinal segment preferably should be indicated on the label of the package, and if desired, the intestinal tissue can be affixed at one end to an annuloplasty ring.
  • these prepackaged intestinal segments can be sold and stored in groups of packages containing tissue segments having various sizes, so that a package containing an intestinal segment having an exact desired diameter or circumference will be available to a surgeon during a cardiac operation even if he cannot specify the exact size before the operation begins.

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  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Transplantation (AREA)
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  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Heart & Thoracic Surgery (AREA)
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  • Urology & Nephrology (AREA)
  • Zoology (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne un procédé d'utilisation d'un matériau tubulaire pour remplacer une valvule cardiaque lors d'une opération chirurgicale du coeur. Afin de créer une valvule auriculo-ventriculaire (mitrale ou tricuspide) de remplacement, on suture l'orifice d'entrée d'un tube à un anneau de valvule dont on a ôté les valves originelles, et on suture l'orifice de sortie du tube au pilier du coeur, dans le ventricule. Afin de créer une valvule sigmoïde (aortique ou pulmonaire), on suture l'orifice d'entrée (222) du tube à un anneau dont on a ôté les valves originelles et soit on 'agrafe' le tube au niveau de trois points situés de manière distale dans l'artère, soit on le suture longitudinalement le long de trois lignes (220), ce qui permet aux pans de tissu placés entre les trois points de fixation, au niveau de l'orifice de sortie de la valvule, de fonctionner en tant que valves mobiles. Ces conceptions permettent d'obtenir des profils d'écoulement reproduisant étroitement les profils d'écoulement des valvules originelles. Un matériau tubulaire préféré comprend un tissu sous-muqueux prélevé sur l'intestin grêle du patient subissant l'opération cardiaque. En utilisant un tissu prélevé sur le patient lui-même, on élimine le risque de rejet immun ainsi que la nécessité de traiter ou de diminuer l'antigénicité. On peut également utiliser du tissu intestinal de cadavre animal ou humain si on traite ce tissu de façon appropriée, ou bien un matériau tubulaire synthétique biocompatible. L'invention concerne également un segment de tissu intestinal traité de façon appropriée ou un segment tubulaire synthétique, lesquels sont conçus pour être implantés en tant que valvule cardiaque de remplacement et sont enfermés dans un emballage stérile scellé.
PCT/US1996/020871 1993-11-01 1996-12-27 Remplacement de valvule cardiaque a l'aide de tubes souples WO1997024083A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US08/146,938 US5480424A (en) 1993-11-01 1993-11-01 Heart valve replacement using flexible tubes
PCT/US1995/016871 WO1997023640A1 (fr) 1995-12-26 1995-12-26 Cytokine i chimiotactique de l'homme
AUPCT/US95/16872 1995-12-28

Publications (1)

Publication Number Publication Date
WO1997024083A1 true WO1997024083A1 (fr) 1997-07-10

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PCT/US1996/020871 WO1997024083A1 (fr) 1993-11-01 1996-12-27 Remplacement de valvule cardiaque a l'aide de tubes souples

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WO (1) WO1997024083A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6524339B1 (en) 1999-01-27 2003-02-25 David H. Adams Cryopreserved homografts and other stentless bioprosthetic heart valves having natural tissue sewing rings
US6616684B1 (en) 2000-10-06 2003-09-09 Myocor, Inc. Endovascular splinting devices and methods
US6802319B2 (en) 1993-02-22 2004-10-12 John H. Stevens Minimally-invasive devices and methods for treatment of congestive heart failure
US7213601B2 (en) 1993-02-22 2007-05-08 Heartport, Inc Minimally-invasive devices and methods for treatment of congestive heart failure
US7666224B2 (en) 2002-11-12 2010-02-23 Edwards Lifesciences Llc Devices and methods for heart valve treatment
US7678145B2 (en) 2002-01-09 2010-03-16 Edwards Lifesciences Llc Devices and methods for heart valve treatment
US7766812B2 (en) 2000-10-06 2010-08-03 Edwards Lifesciences Llc Methods and devices for improving mitral valve function
US7981020B2 (en) 1998-07-29 2011-07-19 Edwards Lifesciences Llc Transventricular implant tools and devices
US8092367B2 (en) 2001-09-07 2012-01-10 Mardil, Inc. Method for external stabilization of the base of the heart
US8226711B2 (en) 1997-12-17 2012-07-24 Edwards Lifesciences, Llc Valve to myocardium tension members device and method
US8579798B2 (en) 1998-09-21 2013-11-12 Edwards Lifesciences, Llc External cardiac stress reduction method
EP2714068A4 (fr) * 2011-05-27 2015-07-29 Cormatrix Cardiovascular Inc Conduits en matière de matrice extracellulaire et procédés de fabrication et d'utilisation de ces conduits
CN106668949A (zh) * 2011-04-01 2017-05-17 W.L.戈尔及同仁股份有限公司 适用于植入物的耐用高强度聚合物复合材料及其制品
US11147673B2 (en) 2018-05-22 2021-10-19 Boston Scientific Scimed, Inc. Percutaneous papillary muscle relocation

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US5344442A (en) * 1991-05-16 1994-09-06 Mures Cardiovasular Research, Inc. Cardiac valve

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US4211325A (en) * 1979-06-07 1980-07-08 Hancock Laboratories, Inc. Heart valve holder
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US4512471A (en) * 1984-04-06 1985-04-23 Angicor Limited Storage unit
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US5344442A (en) * 1991-05-16 1994-09-06 Mures Cardiovasular Research, Inc. Cardiac valve

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6802319B2 (en) 1993-02-22 2004-10-12 John H. Stevens Minimally-invasive devices and methods for treatment of congestive heart failure
US7213601B2 (en) 1993-02-22 2007-05-08 Heartport, Inc Minimally-invasive devices and methods for treatment of congestive heart failure
US8226711B2 (en) 1997-12-17 2012-07-24 Edwards Lifesciences, Llc Valve to myocardium tension members device and method
US7981020B2 (en) 1998-07-29 2011-07-19 Edwards Lifesciences Llc Transventricular implant tools and devices
US8579798B2 (en) 1998-09-21 2013-11-12 Edwards Lifesciences, Llc External cardiac stress reduction method
US6524339B1 (en) 1999-01-27 2003-02-25 David H. Adams Cryopreserved homografts and other stentless bioprosthetic heart valves having natural tissue sewing rings
US6540781B2 (en) 1999-01-27 2003-04-01 The Brigham & Women's Hospital, Inc. Cryopreserved homografts and other stentless bioprosthetic heart valves having natural tissue sewing rings
US6616684B1 (en) 2000-10-06 2003-09-09 Myocor, Inc. Endovascular splinting devices and methods
US9198757B2 (en) 2000-10-06 2015-12-01 Edwards Lifesciences, Llc Methods and devices for improving mitral valve function
US7766812B2 (en) 2000-10-06 2010-08-03 Edwards Lifesciences Llc Methods and devices for improving mitral valve function
US8092367B2 (en) 2001-09-07 2012-01-10 Mardil, Inc. Method for external stabilization of the base of the heart
US8128553B2 (en) 2001-09-07 2012-03-06 Mardil, Inc. Method and apparatus for external stabilization of the heart
US9289298B2 (en) 2001-09-07 2016-03-22 Mardil, Inc. Method and apparatus for external stabilization of the heart
US8070805B2 (en) 2002-01-09 2011-12-06 Edwards Lifesciences Llc Devices and methods for heart valve treatment
US7678145B2 (en) 2002-01-09 2010-03-16 Edwards Lifesciences Llc Devices and methods for heart valve treatment
US7666224B2 (en) 2002-11-12 2010-02-23 Edwards Lifesciences Llc Devices and methods for heart valve treatment
CN106668949A (zh) * 2011-04-01 2017-05-17 W.L.戈尔及同仁股份有限公司 适用于植入物的耐用高强度聚合物复合材料及其制品
EP2714068A4 (fr) * 2011-05-27 2015-07-29 Cormatrix Cardiovascular Inc Conduits en matière de matrice extracellulaire et procédés de fabrication et d'utilisation de ces conduits
US11147673B2 (en) 2018-05-22 2021-10-19 Boston Scientific Scimed, Inc. Percutaneous papillary muscle relocation
US11678988B2 (en) 2018-05-22 2023-06-20 Boston Scientific Scimed, Inc. Percutaneous papillary muscle relocation

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