Europäisches Patentamt
`
`European Patent Office
`
`Office européen des brevets
`
`Printed by Xerox (UK) Business Services
`2.16.7 (HRS)/3.6
`
`EP 1 088 529 A2
`
`

`

`1
`
`EP 1 088 529 A2
`
`2
`
`Description
`
`[0001]
`The present invention relates to a device for
`cardiac valve replacement or repair operations.
`[0002]
`In more detail, repair operations are under-
`taken by introduction into a valve site of an annuloplasty
`ring so as to renew the original geometry of the annulus
`and permit reinstatement of the correct function of the
`natural valve.
`[0003]
`Implant devices used for repair operations
`are constituted by a closed or partially open annular
`structure reproducing the geometry of the inlet edge of
`the mitral valve. They comprise a more or less flexible
`inner core and an outer cladding of polyester or poly-
`tetrafluoroethylene (PTFE) fabric which allows surgical
`suture.
`[0004]
`In the case of replacement operations, on
`the other hand, the entire natural valve is removed and
`replaced with a cardiac valve prosthesis.
`[0005]
`As is known to those skilled in the art cardiac
`valve prostheses can be classified into two fundamental
`categories: mechanical prostheses and biological pros-
`theses.
`[0006]
`Mechanical valve prostheses are usually
`constituted by an annular frame of generally rigid mate-
`rial intended to be connected by a ring of suture to the
`annulus of the natural valve which is removed. In the
`annular frame are mounted one or more valve obturator
`members which move under the action of the blood.
`Biological valves are usually formed starting from
`sheets of suitably treated biological tissue of animal ori-
`gin.
`[0007]
`Whatever the nature of the operation per-
`formed and, in the case of replacement operations, the
`type of prosthesis used, the implantation technique
`essentially used until now was a surgical technique by
`sternotomy. Although by now well consolidated the con-
`ventional surgery is, however, very traumatic and not
`free from complications for the patient, above all in the
`presence of concomitant risk factors (for example
`advanced age, other pathologies and the like).
`[0008]
`For this reason, and also taking into consid-
`eration the significant development which has occurred
`in the last years in adjacent fields with various operating
`techniques involving percutaneous access, such as
`angioplasty of coronary vessels, mapping of the walls of
`the cardiac cavity with a view to ablation of arrhythmia
`etc., there is an increasing interest in producing devices
`such as rings for annuloplasty and cardiac valve pros-
`theses, capable of being introduced with low-invasive
`surgery techniques. Such techniques, as far the cardiac
`sector is concerned, include both surgical access via
`minithoracotomy with direct or assisted vision in the
`operating field, and endoluminal percutaneous access.
`[0009]
`There is therefore a need to provide rings for
`annuloplasty and cardiac valve prostheses which lend
`themselves to application with the above mentioned
`low-invasive surgery techniques in order to be then
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`2
`
`unfolded in the valve site of interest and fixed in position.
`[0010]
`This choice presupposes an almost obliga-
`tory recourse to devices which have characteristics of
`flexibility so that they can be folded into compact dimen-
`sions during introduction in order subsequently to
`become unfolded in the implant position. Biological
`valves, for example of the types described in European
`Patent EP-B-0 155 245 in which the biological tissue
`used to form the valve membrane is a different biologi-
`cal tissue from the valve tissue (for example bovine peri-
`cardium) has shown itself to be particularly suitable in
`this respect, at least potentially.
`[0011]
`In particular, it is known (see for example
`document EP-A-0 515 324) that biological valves of the
`above-specified type lend themselves to being pro-
`duced in the form of valves free from rigid or substan-
`tially rigid annular support frames.
`[0012]
`The object of the present invention is that of
`providing a device for cardiac valve replacement or
`repair operations which can be unfolded in situ so as to
`allow them to be introduced by low-invasive surgery
`techniques.
`[0013]
`According to the present invention this
`object is achieved by a device having the characteristics
`specifically set out in the following Claims.
`[0014]
`The invention will now be described purely
`by way of non-limitative example, with reference to the
`annexed drawings, in which:
`
`Figure 1 illustrates in plan a first embodiment of a
`device according to the invention;
`Figure 2 is a section view taken on the line II-II of
`figure 1;
`Figure 3 illustrates in plan another embodiment of
`the device according to the invention; and
`Figure 4 is a perspective illustration of a further
`embodiment of a device according to the invention.
`
`[0015]
`In Figures 1 and 2 the reference 10 indicates
`a ring for annuloplasty comprising, as a central core, an
`annular support formation 12 of a shape-memory mate-
`rial such as, for example, the metal material known as
`nitinol (an alloy based on Ti-Ni).
`[0016]
`The support formation 12 is embedded in an
`annular casing 14 of biocompatible material such as, for
`example, polyester or PTFE textile.
`[0017]
`The support formation 12 is moreover pro-
`vided with a plurality of spaced projections 16 which
`extend transversely with respect to the general plane of
`the ring 10 and are formed of a shape-memory material,
`preferably having different properties from those of the
`material used for the support formation 12.
`[0018]
`The ring 10 can be introduced at a valve site,
`the original geometry of the annulus of which needs
`reinstatement, using low-invasive surgery techniques
`by means of suitable manipulating instruments.
`[0019]
`In both cases the support formation 12 and
`therefore the ring 10 as a whole is first caused to
`
`NORRED EXHIBIT 2221 - Page 2
`
`

`

`3
`
`EP 1 088 529 A2
`
`4
`
`assume a contracted form of reduced dimensions,
`which considerably facilitates and shortens the intro-
`duction operation.
`[0020]
`Then, having reached the implant valve site,
`the ring 10 is unfolded, for example by heating it to a
`temperature greater than that of the body during operat-
`ing conditions, preferably of the order of 50°C so that
`the support formation 12 reassumes the substantially
`circular shape illustrated in Figure 1. The methods by
`which this heating is achieved are conventional and
`some of these will be described in more detail hereinaf-
`ter with reference to another embodiment of the inven-
`tion.
`[0021]
`Subsequently, by further heating to a higher
`temperature, for example of the order of 60°C, the pro-
`jections 16 pass from the substantially rectilinear shape
`illustrated in the drawing to a hook shape projecting out-
`wardly from the ring 10, which thus grip onto the natural
`tissue of
`the
`implant site and become securely
`anchored to it.
`[0022]
`In this way the expansion of the ring 10 and
`its anchorage system are achieved independently from
`one another. This makes it possible for the surgeon to
`effect first of all optimum orientation of the ring 10 in
`relation to the surrounding anatomical structures upon
`expansion, and subsequently to anchor it to the implant
`site by means of expansion of the projections 14. The
`original geometry of the annulus is thus reinstated and
`the associated valve can again function in a correct
`manner.
`[0023]
`Figure 3 illustrates a variant embodiment
`10a of a ring for annuloplasty which differs from that
`described with reference to the preceding Figures only
`by the fact that it has an open rather than a closed loop
`structure, the method of introduction and unfolding in
`situ remaining unchanged.
`[0024]
`Figure 4 illustrates a device according to the
`invention formed as a cardiac valve prosthesis, gener-
`ally indicated with the reference 88.
`[0025]
`As already previously indicated, this type of
`prosthesis constitutes a development of the arrange-
`ment described in prior art documents EP-B-0 155 245
`and EP-A-0 515 324.
`[0026]
`For a complete description of the manufac-
`turing details of the prosthesis (also as far as the proc-
`esses and apparatus usable to produce the shaping of
`the component parts are concerned) reference can in
`general be made to the description in the two preceding
`documents: solely all the elements characteristic of the
`arrangement according
`to
`the
`invention will be
`described explicitly in the present description. Other
`elements not specifically illustrated must, however, be
`considered to be known to the man skilled in the art (for
`example through the knowledge of the two documents
`to which reference has been made several times) and in
`any event are not, per se, relevant for the purposes of
`understanding the invention.
`[0027]
`The prosthesis 88 is essentially constituted
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`3
`
`by a sleeve comprising two sheets 90 and 92 of biologi-
`cal material such as, for example, bovine pericardium
`subject to a fixation process in glutaraldehyde.
`[0028]
`The first sheet 90 is intended to constitute
`the outer portion of the valve sleeve of the prosthesis
`88. The other sheet 92, constitutes the inner or func-
`tional part of the valve sleeve (that is to say, in practice,
`the valve lips) has been preliminarily subject to a shap-
`ing process. This process is intended to give the sheet
`92 three shaped portions 94 of semi-circular or crescent
`shape with arcuate edges and with a generally cup or
`claw like configuration in such a way that, when the
`valve sleeve is closed in a tube, the flaps 94 project in a
`convergent manner towards the internal orifice of the
`prosthesis 88. A detailed description of a process and
`apparatus usable for performing this shaping operation
`is provided in European Patent EP-B-0 133 420.
`[0029]
`The two sheets 90 and 92 are then con-
`nected together by a line of suture stitching (for example
`of spun polyester thread covered in biocompatible car-
`bonaceous material) which extends closely adjacent to
`the outer outline of the crescent portions forming the
`valve membranes 94 and therefore has a festoon
`shape.
`[0030]
`More precisely, the two sheets 90 and 92
`connected together by the festoon line of stitching 96,
`are closed in a tube and connected together at their fac-
`ing ends by means of a further line of stitching 98. This
`is done in such a way as to give rise to a structure in
`which the three valve membranes 94 can, alternatively,
`move away from one another so as to allow the flow of
`blood in one direction (from below upwardly with refer-
`ence to the drawing) and to move together again
`against one another under the act of the blood pressure
`so as to prevent the flow of blood in the opposite direc-
`tion. All this according to criteria widely known in the art,
`which do not require to be further explained here.
`[0031]
`Preferably, the stitch line 98 is located at one
`of the so-called commissures that is to say in the region
`of maximum axial extent of the sheets 90 and 92.
`[0032]
`As well as this, the edge 99 of the outer
`sheet 90 intended to be situated down stream in the
`implant position of the valve (that is to say the edge
`intended to face towards the output side of the valve -
`orientated upwardly when the prosthesis is located as
`illustrated in Figure 4) is cut off in close proximity to the
`festoon line of stitching 96, and therefore in close prox-
`imity to the arcuate edges of the valve flaps 94.
`[0033]
`It will be appreciated that this choice (the dis-
`tance between edge 99 and the stitch line of the order,
`for example, of 2mm) is closer to the arrangement
`described
`in document EP-B-0 155 245 (which
`describes a valve provided with a reinforcement or
`frame), than to the arrangement described in document
`EP-A-0 515 324 which relates to a valve without rein-
`forcement or frame.
`[0034]
`However, in the prosthesis 88 according to
`the invention it is preferential that the outer sheet has a
`
`NORRED EXHIBIT 2221 - Page 3
`
`

`

`5
`
`EP 1 088 529 A2
`
`6
`
`very reduced axial dimension at its margin on the output
`side for the purposes of production of a valve prosthesis
`intended to be introduced with low-invasive surgery
`techniques, above all when the operation is performed
`for the purpose of replacing an aortic valve so as not to
`obstruct the coronary ostia.
`[0035]
`The prosthesis 88 can to some extent be
`comparable to a valve provided with a reinforcement
`frame due to the presence, preferably at the base
`perimeter of the prosthesis itself, of an annular support
`formation 100 (preferably continuous, although a dis-
`continuous structure formed from several arcuate seg-
`ments is possible) made of a shape memory material
`such as, for example, the above mentioned nitinol.
`[0036]
`The connection of the annular formation 100
`to the sheets of biological material 90, 92 is usually
`achieved by stitching, for example in a manner substan-
`tially similar to that described in document EP-B-0 155
`245 for the connection of the base region of the rein-
`forcement frame or stent to the sheets of biological or
`other material again in a manner similar to that adopted
`for the connection of the same sheet together in the
`base region (ingress or inflow side of the prosthesis) in
`the arrangement described in document EP-A-0 515
`324.
`[0037]
`It will be appreciated that, in general, the
`support formation 100 is preferably located in direct
`connection, or at least in close proximity, to the base
`region (inflow side) of both sheets of biological material.
`[0038]
`As will be seen better hereinafter, the forma-
`tion 100 has in fact the purpose of ensuring the unfold-
`ing of the prosthesis in the implant position: it is
`therefore important that both the outer sleeve 90 and
`the inner sleeve 92 which carries the valve membranes
`94 are accurately unfolded in a closely contiguous rela-
`tionship with the annulus defining the implant site.
`[0039]
`It will also be appreciated from observation
`of Figure 4 that the annular formation 100 preferably
`does not have a flat but rather a slightly undulating form
`with crests located in correspondence with the commis-
`sures of the valve membranes 94. It is in fact estab-
`lished that such a configuration allows, on one hand,
`further to reduce the axial dimension of the prosthesis
`and, on the other hand, to obtain an even better adapta-
`tion of the prosthesis to the physiology of the implant
`site.
`[0040]
`A substantially similar support formation,
`indicated 102, also made of shape memory material
`such as nitinol, which can also be made in the shape of
`a continuous or substantially continuous body both by
`juxtaposition of several arcuate segments, is applied (by
`stitching) to the output edge (outflow side) of the outer
`sleeve 90 of the prosthesis.
`[0041]
`Both the annular formations 100 and 102
`have characteristics of flexibilty (due both to the flexibil-
`ity of the constitutent material and to their thin section:
`in fact very thin wire-like elements are used, for example
`with circular section and a diameter of the order of
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`4
`
`tenths of mm) which makes it possible to mount the
`prosthesis on a catheter or other suitable instrument for
`introduction into the implant.
`[0042]
`It will be appreciated however that, although
`less preferred, the prosthesis 88 could be also provided
`with only one of the formations 100 and 102.
`[0043]
`In any case, the prosthesis 88 lends itself, in
`an arrangement that has been found to be preferential,
`to be folded into a generally lobed configuration (for
`example by forming three lobes the radially outer verti-
`ces of which correspond to the commissures of the
`valve) and then rolled by acting tangentally in a manner
`entirely similar to that adopted for the folds of the cover
`of a closed umbrella for folding it around the umbrella
`frame itself. In these conditions the prostheses 88 is
`reduced to a cylinder having a length of the order of 1.5-
`2.5 cm (depending on the overall dimensions of the
`prostheses, which in turn depends on the type of valve
`replaced and the anthropometric characteristics of the
`patient) and a diameter of the order of several millime-
`tres so as to allow its positioning on a suitable instru-
`ment for low invasive surgery techniques.
`[0044]
`Having reached the implant site the prosthe-
`sis 88 can be unfolded by making it re-acquire the func-
`tional shape illustrated in Figure 1 by heating to
`moderate temperature. For example, with reference to
`the choice of a material such as nitinol, for producing
`the formations 100 and 102, this unfolding temperature
`can be greater than that of the body in the operating
`conditions, and preferably of the order of 50°C so as not
`to create detrimental effects on the prostheses, the sur-
`rounding tissue or the organism of the patient in gen-
`eral.
`[0045]
`The heating can easily be caused for exam-
`ple by utilising a transport catheter provided, at its distal
`end, with an expandable balloon situated in correspond-
`ence with the region intended to receive the valve and
`retain it in position. By introducing hot water through the
`catheter into the balloon it is possible to induce the
`recovery of the shape memory metal into the definitive
`shape.
`[0046]
`Alternatively it is possible to effect heating of
`the support formations 100, 102 by the Joule effect by
`means of an induced electric current by electromagnetic
`coupling via a suitable device located in proximity
`thereof.
`[0047]
`In order to anchor the prostheses 88 in situ it
`is possible to utilise various arrangements, for example
`that already described with reference to the rings of the
`preceding Figures 1 to 3, which envisages the use of
`projections 104 of shape memory material, preferably
`having different thermal properties from those of the
`material utilised for the support formations 100 and 102.
`[0048]
`In the retracted condition of the prosthesis
`88 the projections 104 are collapsed upon themselves
`in a strongly curved shape, which they also maintain
`during the heating phase which allows unfolding of the
`support formations 100, 102.
`
`NORRED EXHIBIT 2221 - Page 4
`
`

`

`7
`
`EP 1 088 529 A2
`
`8
`
`[0049]
`Subsequently, by the effect of a further heat-
`ing to a higher temperature than that necessary to
`cause unfolding of the support formations 100, 102, the
`projections 104 extend in a hook like form, opening out-
`wardly, and penetrate into the vasal wall or into the
`implanted valve annulus so as to anchor the prostheses
`88 in situ.
`[0050]
`Naturally, it is possible to use other anchor-
`age arrangements, for example arrangements such as
`those currently adopted for anchorage in situ of vascular
`(graft) prostheses introduced endoluminally. By the way,
`these other arrangements could be utilised, at least in
`principle, also for the anchorage of a ring for annulo-
`plasty of the type described with reference to the pre-
`ceding Figures from 1 to 3. By way of example one may
`cite the arrangements described in US Patents US-A-4
`787 899, US-A-5 104 399, US-A-5 256 150 and US-A-5
`275 622 or else by having recourse to an endoluminal
`stent of the type known as a Palmaz stent stitched to the
`inlet edge of the valve prosthesis which in this case is
`made with a slightly longer shape (this arrangement
`appears to be preferable for use in replacement of the
`pulmonary valve).
`[0051]
`In the case of use for replacement of the aor-
`tic valve it can be advantageous to provide the inlet
`edge of the prosthesis 88 with a strip of biological or pol-
`ymeric tissue (schematically shown with the broken line
`and indicated 106 in Figure 4) for the purpose of acting
`as a seal.
`[0052]
`It is also possible to consider duplicating the
`function of the projections 104 with respect to that of the
`formation 100 by arranging them on another ring ele-
`ment (not shown in Figure 4) formed with material hav-
`ing a shape memory and possibly disposed in a
`marginal position with respect to the edge 106.
`[0053]
`for
`Again, another arrangement usable
`anchoring the prostheses 88 in situ is that based on the
`use of helices which can be controlled to rotate remotely
`by means of catheters as described in Italian Patent
`application BO94A000552.
`[0054]
`Again, since it can be critical to facilitate the
`orientation of the valve by the surgeon during the oper-
`ation, it is preferable that in correspondence with the
`commissural supports there be located radio opaque
`markers connected to the introduction instrument and
`capable of being removed after positioning of the pros-
`thesis.
`[0055]
`Naturally, the principle of the invention
`remaining the same, the details of construction and the
`embodiments can be widely varied with respect to what
`has been described and illustrated, without by this
`departing from the ambit of the present invention: this
`relates in particular to the choice of shape-memory
`material usable for the support formations.
`
`Claims
`
`1. A device (10, 10a, 88) for cardiac valve replace-
`
`ment or repair operations, characterised in that it
`comprises at least one support formation (12, 100,
`102) of shape-memory material which can adopt:
`
`-
`
`-
`
`a first, generally contracted shape, in which the
`said formation (12, 100, 102) can be wound on
`itself or folded for the purpose of location in the
`implant position, for example with low-invasive
`surgical techniques, and
`a second, generally unfolded shape, to which
`the said shape memory material is brought
`after positioning of the support formation (12,
`100, 102) in the implant position.
`
`2. A device (10, 10a, 88) according to Claim 1, char-
`acterised in that the said shape memory material is
`a metal and the passage from the said first to the
`said second shape is achieved by heating.
`
`5
`
`10
`
`15
`
`20
`
`3. A device (10, 10a, 88) according to Claim 2, char-
`acterised in that the said metal is nitinol.
`
`4. A device (10, 10a, 88) according to Claim 2 or
`Claim 3, characterised in that the said shape mem-
`ory material passes from the said first to the said
`second shape by the effect of heating to a tempera-
`ture of the order of about 50°C.
`
`5. A device (10, 10a, 88) according to any preceding
`claim, characterised in that the said at least one
`support formation (12, 100, 102) is of generally
`annular shape.
`
`6. A device (10, 88) according to Claim 5, character-
`ised in that the said at least one support formation
`(12, 100, 102) is formed in the shape of a continu-
`ous annular body.
`
`7. A device (10, 10a, 88) according to any preceding
`claim, characterised in that it includes anchorage
`means for fixing it in the implant position.
`
`8. A device (10, 10a, 88) according to Claim 7, char-
`acterised in that the said anchorage means com-
`prise formations capable of extending outwardly
`from the said support formation (12, 100, 102).
`
`9. A device (10, 10a, 88) according to Claim 8, char-
`acterised in that the said formations are projections
`(16, 104) of the said at least one support formation
`(12, 100, 102).
`
`10. A device (10, 10a, 88) according to Claim 9, char-
`acterised in that the said projections (16, 104) are
`made of a shape-memory material different from
`that utilised for the said support formation and
`which can adopt:
`
`NORRED EXHIBIT 2221 - Page 5
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`5
`
`

`

`9
`
`EP 1 088 529 A2
`
`10
`
`-
`
`-
`
`a first shape, usable upon implant of the
`device, in which the said projections (16, 104)
`are generally contracted, and
`a second shape, usable when the device is in
`the unfolded position, in which the said projec-
`tions (16, 104) extend outwardly from the
`device itself, the passage from the said first to
`the said second shape occurring by the effect
`of heating to a temperature greater than that at
`which the passage from one shape to the other
`of the shape memory material used for the said
`support formation (12, 100, 102) takes place.
`
`11. A device (10, 10a) according to any preceding
`claim characterised in that it is a ring for annulo-
`plasty.
`
`12. A device (88) according to any of Claims from 1 to
`10, characterised in that it is a valve prosthesis
`comprising a valve sleeve (90, 92) of generally flex-
`ible material having respective inlet and outlet
`edges (99) with respect to the direction of free flow
`of blood through the prosthesis, the said support
`formation (100, 102) of shape-memory material
`being associated with at least one of the said inlet
`and outlet edges (99).
`
`13. A device (88) according to Claim 12, characterised
`in that there are provided first (100) and second
`(102) support formations located respectively in
`correspondence with the said inlet edge and the
`said outlet edge (99) of the prosthesis.
`
`14. A device (88) according to any of Claims 12 or 13,
`characterised in that the said at least one support
`formation (100) is located in correspondence with
`the inlet edge of the prosthesis and has a generally
`festoon configuration with crests located in corre-
`spondence with the commissures of the valve
`membranes (94) of the prosthesis.
`
`15. A device (88) according to any of Claims from 12 to
`14, characterised in that the said at least one sup-
`port formation (102) is located in correspondence
`with the outlet edge of the prosthesis and has a
`generally festoon configuration with crests located
`in correspondence with the commissures of the
`valve membranes (94) of the prosthesis.
`
`16. A device (88) according to Claim 15, characterised
`in that the said valve sleeve comprises an outer
`layer (90) and an inner layer (92) carrying the valve
`membranes (94) of the prosthesis, the said outer
`layer (90) and the said inner layer (92) being con-
`nected together by a line of stitching (96) having a
`generally festoon configuration and in that a
`respective support formation (102) is located in cor-
`respondence with the said outlet edge (99) closely
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`6
`
`adjacent the said stitch line (96).
`
`17. A device (88) according to any of Claims from 12 to
`16, characterised in that it comprises, in corre-
`spondence with the said inlet edge, a seal strip of
`sheet material (106) which can be fitted in contact
`with the wall of the implant site.
`
`NORRED EXHIBIT 2221 - Page 6
`
`

`

`EP 1 088 529 A2
`EP 1 088 529 A2
`
`14
`
`14
`
`16
`
`7
`
`NORRED EXHIBIT 2221 - Page 7
`NORRED EXHIBIT 2221 - Page 7
`
`

`

`EP 1 088 529 A2
`EP 1 088 529 A2
`
` 8
`
`8
`
`NORRED EXHIBIT 2221 - Page 8
`NORRED EXHIBIT 2221 - Page 8
`
`