DESC:FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(Section 10 and Rule 13)

1. TITLE OF THE INVENTION:
PROSTHETIC VALVE

2. APPLICANT:
Meril Life Sciences Pvt. Ltd., an Indian company of the address Survey No. 135/139, Bilakhia House Muktanand Marg, Chala, Vapi, Gujarat 396191, India

3. PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention and the manner in which it is to be performed:

FIELD OF INVENTION
[001] The present invention relates to a prosthetic system. More specifically, the present invention relates to a prosthetic trans-catheter heart valve system.
BACKGROUND OF INVENTION
[002] The function of a prosthetic heart valve is to replace a diseased native heart valve. The replacement procedure may be surgical (using open heart surgery) or percutaneous. While the surgical aortic valve replacement (SAVR) procedure continues to be performed in low surgical risk population, percutaneous catheterization technique viz. Transcatheter Aortic Valve Replacement (TAVR) has become a promising therapy in cases of symptomatic, severe aortic valve stenosis over a Surgical Aortic Valve Replacement (SAVR). Since then, two THV genres are known viz. balloon expandable and self-expandable. A skilled person is well aware of the THV of both genres.
[003] Some of the important pre-requisites for a transcatheter heart valve are as follows:
1. The THV should have the ability to be implanted via a transcatheter delivery route. Hence, it should have a low entry profile.
2. It should be available in a size range (diameters) to match patient anatomical requirements.
3. It should have the ability to be deployed with precision without geographical misplacement.
4. It should have sufficient radial strength to resist dislodgement due to systolic and diastolic pressures after deployment.
5. It should not have excessive outward expansion force to avoid damage to the implantation site e.g. aortic root complex.
6. It should ensure continuous unrestricted blood flow to the coronary perfusion and allow for easy access to coronary arteries (both right and left coronary circulation) for future PCI requirements.
[004] In a self-expanding THV frame, the stent frame must have sufficient radial strength to resist dislodgement due to systolic and diastolic pressures. Conventionally, a self-expanding frame has a high axial length (taller frames) and a cell structure with multiple rows of cells, say up to 9 rows. The stent frame of a self-expanding valve, on expansion, may tend to exhibit large foreshortening (sometimes up to 50%) of its constrained axial length. The foreshortening to such an extent may result in a geographical misplacement or even valve embolization as the operating surgeon cannot accurately control the placement of the valve.
[005] As per the second genre of the THV technology, the balloon expandable THV frame is normally composed of fewer number of rows of cells viz. 2 – 4 rows. Hence, on expansion, the frame foreshortens 15-20% which is significantly less than the self-expanding THV stent frames which have up to 9 rows of cells. Thus, the balloon expandable THV frame can be deployed with high degree of precision and accuracy of placement.
[006] Further, the frame of a balloon expandable THV has relatively higher radial strength as compared to a self-expanding THV. Hence, it offers lower paravalvular leak (PVL) and the frame does not require post dilatation which happens frequently with a self-expanding THV. Additionally, this also reduces chance of an iatrogenic damage to the conduction system thereby, reducing the incidence of a new heart block necessitating a new permanent pacemaker.
[007] The frame of a balloon expandable THV is shorter in height compared to the frame of a self-expanding THV (due to lower number of cell rows). This lowers the risk of jailing coronary ostia.
[008] However, what works as advantages in balloon expandable THV also becomes a relative dis-advantage to an extent as described below.
1. The leaflets in a balloon expandable THV are sutured at the inflow zone of the valve and the THV is implanted with precision, superimposing on the diseased native aortic annulus which has diseased (thickened/calcified) native leaflets. This, obviously, lowers the EOA.
2. This intra-annular deployment of balloon expandable THV is associated with relatively higher valve gradients especially pronounced in small annuli and thus relatively higher patient prosthetic mismatch (PPM) compared to a self-expanding THV in comparable annulus diameter.
[009] There exists a strong unmet clinical need to provide a THV that achieves higher EOA which results in lower PPM.
SUMMARY OF INVENTION
[0010] This invention describes a novel concept of a balloon expandable THV with supra-annular (SA) positioning of the leaflets. This leads to larger EOA and thus lower PPM. Additionally, the novel frame design exhibits reduced fore-shortening which makes it easy to position the THV precisely at a desired implantation site. In an embodiment, the frame attains a tapered configuration post expansion of the balloon. The THV disclosed in the present invention is also suitable for Valve-in-Valve implantation.
[0011] In an embodiment, a prosthetic valve includes a radially collapsible and expandable support frame having an inflow end, an outflow end and a plurality of rows of cells extending axially between the inflow end and the outflow end. The plurality of rows of cells includes at least an upper row of cells and a lower row of cells. The upper row of cells is provided at the outflow end and includes interlaced first polygonal cells, wherein two consecutive first polygonal cells include one of a common diamond shaped cell or a rhombus body. The lower row of cells is provided at the inflow end and includes interlaced chevron shaped second polygonal cells, wherein two consecutive second polygonal cells include one of a common link or a common axially extending strut. The link includes a straight strut portion followed by a diamond shaped cell. The frame includes a valve-free zone disposed towards the inflow end, enabling supra-annular deployment of the valve, thereby, providing a higher effective orifice area (EOA).
[0012] The foregoing features and other features as well as the advantages of the invention will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] The summary above, as well as the following detailed description of illustrative embodiments, is better understood when read in conjunction with the appended figures. For the purpose of illustrating the present disclosure, various exemplary embodiments are shown in the figures. However, the disclosure is not limited to the description and figures disclosed herein. Moreover, those familiar with the art will understand that the figures are not to scale. Wherever possible, like elements have been indicated by identical numbers.
[0014] Fig. 1 depicts a perspective view of a support frame 101 of a transcatheter prosthetic heart valve (THV) 100, according to an embodiment of the present disclosure.
[0015] Fig. 1a depicts a rhombus body 101d with at least one hole 101d’ of the support frame 101, according to an embodiment of the present disclosure.
[0016] Fig. 1b depicts a planar view of the support frame 101, according to an embodiment of the present disclosure.
[0017] Fig. 1c depicts schematic view of the support frame 101, according to an embodiment of the present disclosure.
[0018] Fig. 2 depicts a perspective view of a support frame 201 of a THV 200, according to an embodiment of the present disclosure.
[0019] Fig. 2a depicts a rhombus body 201d with at least one hole 201d’ of the support frame 201, according to an embodiment of the present disclosure.
[0020] Fig. 2b depicts a planar view of the support frame 201, according to an embodiment of the present disclosure.
[0021] Fig. 2c depicts schematic view of the support frame 201, according to an embodiment of the present disclosure.
[0022] Fig. 3 depicts the THV 100 with an internal skirt 105, according to an embodiment of the present disclosure.
[0023] Fig. 3a depicts the THV 100 with an external skirt 107, according to an embodiment of the present disclosure.
[0024] Fig. 4 depicts the THV 200 with an internal skirt 205, according to an embodiment of the present disclosure.
[0025] Fig. 4a depicts the THV 200 with an external skirt 207, according to an embodiment of the present disclosure.
[0026] Fig. 5 depicts a leaflet 103, according to an embodiment of the present disclosure.
[0027] Fig. 5a depicts a leaflet 103x, according to an embodiment of the present disclosure.
[0028] Fig. 6 depicts a delivery catheter 300, according to an embodiment of the present disclosure.
[0029] Fig. 6a depicts a cross-sectional view of a distal portion of the delivery catheter 300, according to an embodiment of the present disclosure.
[0030] Fig. 6b depicts a schematic representation of a balloon 301 of the delivery catheter 300, according to an embodiment of the present disclosure.
[0031] Fig. 7 depicts an aortic root complex 1, according to an embodiment of the present disclosure.
[0032] Fig. 8 depicts an enlarged view of the aortic root complex 1, according to an embodiment of the present disclosure.
[0033] Fig. 9 depicts the THV 100 deployed at an aortic annulus, according to an embodiment of the present disclosure.
[0034] Fig. 9a depicts the THV 200 deployed at the aortic annulus, according to an embodiment of the present disclosure.
[0035] Fig. 10 depicts the support frame 101 crimped and mounted over the balloon 301 of the delivery catheter 300, according to an embodiment of the present disclosure.
[0036] Fig. 10a depicts the support frame 201 crimped and mounted over the balloon 301 of the delivery catheter 300, according to an embodiment of the present disclosure.
[0037] Figs. 11 – 11b depict various alignment of the support frame 101 at the aortic annulus 1, according to an embodiment of the present disclosure.
[0038] Figs. 12 – 12b depict various alignment of the support frame 201 at the aortic annulus 1, according to an embodiment of the present disclosure.
[0039] Fig. 13 depicts anatomy of the human heart H schematically in a simplified manner.
[0040] Fig. 14 is a schematic simplified representation of the human heart H (like Figs. 16, 16a) for illustrating the transeptal procedure, according to an embodiment of the present disclosure.
[0041] Fig. 15 depicts a delivery catheter 300’, according to an embodiment of the present disclosure.
[0042] Fig. 15a depicts a cross-sectional view of a distal portion of the delivery catheter 300’, according to an embodiment of the present disclosure.
[0043] Fig. 15b depicts a schematic representation of a balloon 301’ of the delivery catheter 300’, according to an embodiment of the present disclosure.
[0044] Fig. 16 depicts a schematic representation showing left atrium LA with the THV 100 implanted at within a degenerated surgical bioprosthetic valve 1601, according to an embodiment of the present disclosure.
[0045] Fig. 16a depicts a schematic representation of left atrium LA with the THV 200 implanted at within the degenerated surgical bioprosthetic valve 1601, according to an embodiment of the present disclosure.
[0046] Fig. 17 depicts a schematic representation of left atrium LA with the THV 100 implanted at within a damaged/degenerated annuloplasty ring 1700, according to an embodiment of the present disclosure.
[0047] Fig. 17a depicts a schematic representation of left atrium LA with the THV 200 implanted at within a damaged/degenerated annuloplasty ring 1700, according to an embodiment of the present disclosure.
[0048] Fig. 18 depicts the support frame 101 crimped and mounted over the balloon 301’ of the delivery catheter 300’, according to an embodiment of the present disclosure.
[0049] Fig. 18a depicts the support frame 201 crimped and mounted over the balloon 301’ of the delivery catheter 300’, according to an embodiment of the present disclosure.
[0050] Figs. 19, 20, 21 depict various alignment of a landing zone marker M4 with a suture ring 1602 of the degenerated surgical bioprosthetic mitral valve 1601 for the THV 100, according to an embodiment of the present disclosure.
[0051] Figs. 19a, 20a, 21a depict various alignment of the landing zone marker M4 with the suture ring 1602 of the degenerated surgical bioprosthetic mitral valve 1601 for the THV 200, according to an embodiment of the present disclosure.
[0052] Figs. 22, 23, 24 depict various alignment of the landing zone marker M4 with the damaged/degenerated annuloplasty ring 1700 for the THV 100, according to an embodiment of the present disclosure.
[0053] Figs. 22a, 23a, 24a depict various alignment of the landing zone marker M4 with the damaged/degenerated annuloplasty ring 1700 for the THV 200, according to an embodiment of the present disclosure.
DETAILED DESCRIPTION OF ACCOMPANYING DRAWINGS
[0054] Prior to describing the invention in detail, definitions of certain words or phrases used throughout this patent document will be defined: the terms "include" and "comprise", as well as derivatives thereof, mean inclusion without limitation; the term "or" is inclusive, meaning and/or; the phrases "coupled with" and "associated therewith", as well as derivatives thereof, may mean to include, be included within, interconnect with, contain, be contained within, connect to or with, couple to or with, be communicable with, cooperate with, interleave, juxtapose, be proximate to, be bound to or with, have a property of, or the like; Definitions of certain words and phrases are provided throughout this patent document, and those of ordinary skill in the art will understand that such definitions apply in many, if not most, instances to prior as well as future uses of such defined words and phrases.
[0055] Reference throughout this specification to “one embodiment,” “an embodiment,” or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, appearances of the phrases “in one embodiment,” “in an embodiment,” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment, but mean “one or more but not all embodiments” unless expressly specified otherwise. The terms “including,” “comprising,” “having,” and variations thereof mean “including but not limited to” unless expressly specified otherwise. An enumerated listing of items does not imply that any or all of the items are mutually exclusive and/or mutually inclusive, unless expressly specified otherwise. The terms “a,” “an,” and “the” also refer to “one or more” unless expressly specified otherwise.
[0056] Although the operations of exemplary embodiments of the disclosed method may be described in a particular, sequential order for convenient presentation, it should be understood that the disclosed embodiments can encompass an order of operations other than the particular, sequential order disclosed. For example, operations described sequentially may in some cases be rearranged or performed concurrently. Further, descriptions and disclosures provided in association with one particular embodiment are not limited to that embodiment, and may be applied to any embodiment disclosed herein. Moreover, for the sake of simplicity, the attached figures may not show the various ways in which the disclosed system, method, and apparatus can be used in combination with other systems, methods, and apparatuses.
[0057] Furthermore, the described features, advantages, and characteristics of the embodiments may be combined in any suitable manner. One skilled in the relevant art will recognize that the embodiments may be practiced without one or more of the specific features or advantages of a particular embodiment. In other instances, additional features and advantages may be recognized in certain embodiments that may not be present in all embodiments. These features and advantages of the embodiments will become more fully apparent from the following description and apportioned claims, or may be learned by the practice of embodiments as set forth hereinafter.
[0058] It should be noted that in the figures and the description to follow, the terms “frame” or “stent” or “frame” or “scaffold structure” or “support frame” or “scaffold” refer to the metallic frame of this invention. These terms are used interchangeably but carry the same meaning. The term “valve” or “prosthetic valve” refer to the prosthetic valve of the present invention assembled prosthetic valve using a support frame and other components like leaflets of animal tissue, skirt, etc. These terms are also used interchangeably. The term “native valve” is used for the natural valve in human heart.
[0059] Likewise, the terms ‘delivery system’, ‘delivery catheter’, ‘catheter’, ‘balloon catheter’, ‘delivery balloon catheter’ refer to the delivery apparatus used in the present invention. These terms are used interchangeably but carry the same meaning.
[0060] The present invention discloses a balloon expandable prosthetic heart valve system (or system). The system of the present invention includes a trans-catheter prosthetic heart valve (THV) (also, referred to as a prosthetic valve) and a THV delivery system (also referred to as a delivery system). The THV of the present invention may be implanted via a catheterization technique in a human stenosed aortic orifice using the THV delivery system. The THV and the THV delivery system work in unison to achieve an improved performance of the system.
[0061] The THV includes a flexible frame which can expand and collapse, a plurality of leaflets (say, three leaflets) formed from animal tissue or synthetic material, and optionally, at least one of an internal skirt and an external skirt that are attached to the frame. In various embodiment, the frame of the THV (also referred to as the support frame or the frame) includes at least an upper row of cells having interlaced first polygonal cells at an outflow end and a lower row of cells having interlaced chevron shaped second polygonal cells at an inflow end. In an embodiment, the chevron shaped second polygonal cells are formed by connecting valleys formed by consecutive angled struts of adjacent rows of angled struts at an inflow end, wherein peaks forms by consecutive angled struts of these adjacent rows of angled struts face each other.
[0062] The frame of the THV in the present invention offers several structural and clinical advantages over the conventional frames and mitigates the disadvantages offered by the same. The frame of the THV of the present invention includes interlaced decagonal and/or octagonal and/or hexagonal cells which incorporate a rhombus body (with holes) or a diamond shaped cell at each intersection. Such a structure enhances columnar strength thereby, resulting in improved radial strength and fatigue resistance.
[0063] The frame of a THV of a preferred embodiment includes at least two rows of tessellating decagonal, and/or octagonal and /or hexagonal cells placed one above the other as opposed to a traditional trans-catheter self-expanding prosthetic valve having a frame with more rows of cells (typically 7 – 9). The reduction in number of rows and the specific shape of the cells result in reduced foreshortening of the frame on radial expansion which makes it easier for the operator to implant the prosthetic heart valve accurately. Various designs of the frames disclosed herein, for example, chevron-shaped cells in the lower row of cells and/or short angled struts, ensure reduced foreshortening even when the frame has more than two rows of cells.
[0064] The THV frame is unique as the outflow zone diameter of the THV frame is larger than the inflow zone diameter of the THV frame upon deployment of the frame in the native annulus. The THV frame thus attains a tapered configuration post deployment. That is, when expanded in the native annulus, the frame takes a tapered shape due to the tapered balloon which inflates the frame in that shape. Along with other features mentioned below, this facilitates supra-annular deployment of the THV of the present invention thereby achieving higher EOA.
[0065] Further, the delivery system incorporates a tapered balloon that helps in maintaining differential diameter of the THV frame such that the outflow zone diameter is larger than the inflow zone diameter. Frame achieves tapered expanded diameter due to the tapered balloon. The delivery system and the frame structure further help in accurate placement and precise deployment of the THV of the present invention as described further.
[0066] In an embodiment, the first polygonal cells are octagonal cells and the chevron shaped second polygonal cells are chevron shaped decagonal cells or chevron shaped hexagonal cells. In an embodiment, the first polygonal cells are hexagonal or decagonal cells. In an embodiment, the chevron shaped second polygonal cells are chevron shaped octagonal cells.
[0067] Two exemplary embodiments of the THV of the instant invention (viz. THV 100 and THV 200) are described to illustrate the concept of the instant invention.
[0068] Perspective view of a support frame 101 (or frame 101) of THV 100 is shown in Fig. 1. The frame 101 is a radially collapsible and radially expandable having a cylindrical shape with an inflow end 100a and an outflow end 100b. The frame 101 of the exemplary embodiment is a balloon-expandable frame. Alternately, the frame 101 may be a self-expandable frame.
[0069] The structure of the frame 101 of an exemplary embodiment is shown in Figs. 1, 1a and 1b. Fig. 1 shows prospective view of the frame 101. Fig 1b depicts the cylindrical frame structure when the cylindrical portion of the frame 101 is cut vertically along its axial length and flattened. It should be noted in relation to Fig. 1b that the frame scaffold design is shown laid flat for convenience purpose only and the frame 101 may not be created from a flat metal sheet.
[0070] As evident from the Figs. 1 and 1b, the frame 101 includes the inflow end 100a, the outflow end 100b and a plurality of rows of cells (e.g., two rows of polygonal cells) including at least a lower row of cells 101b1 (towards the inflow end 100a) and an upper row of cells 101b2 (towards the outflow end 100b) of tessellating polygonal cells. In an embodiment shown in Figs. 1 and 1b, the upper and lower rows of cells 101b2, 101b1 are placed one above the other. The rows of cells are thus adjacently placed. Further, the plurality of rows of cells extends between the distal end 100a (inflow end 100a) and the proximal end 100b (outflow end 100b) of the frame 101. The cells in the upper row may be referred as first polygonal cells while the cells in the lower row may be referred as second polygonal cells. The second polygonal cells are chevron-shaped. In an embodiment, the first polygonal cells are octagonal and the second polygonal cells are decagonal.
[0071] Referring to Fig. 1b, the frame 101 has three circumferentially extending rows of angled struts having an upper row 10a at the proximal end 100b of the frame 101, a lower row 10c at the distal end 100a of the frame 101 and an intermediate row 10b located between the upper row 10a and the lower row 10c. The distal position refers to a position away from the operator. The lower row 10c is towards the inflow end 100a of the support frame 101 and the upper row 10a is towards the outflow end 100b of the support frame 101. Any two consecutive angled struts of a circumferentially extending row of angled struts form a peak or a valley giving an undulating shape to each row of angled struts. The peaks P1 of the upper row 10a of angled struts (also referred to as upper row of angled struts 10a) face the valleys V2 of the intermediate row 10b of angled struts (also referred to as intermediate row of angled struts 10b), and the peaks P2 of the intermediate row 10b of angled struts face the peaks P3 of the lower row 10c of angled struts. In other words, the valleys V1 of the upper row 10a of angled struts face the peaks P2 of the intermediate row 10b of angled struts, and the valleys V2 of the intermediate row 10b of angled struts face the valleys V3 of the lower row 10c of angled struts (also referred to as lower row of angled struts 10a).
[0072] In an embodiment, the angle (‘A’) between two adjacent angled struts in FIG. 1b is around 116°. However, it should be noted that the said angle may be less than or more than 116°.
[0073] The rows of angled struts 10a and 10b are connected to each other to form the upper row of cells 101b2. Referring to Fig. 1b and the blown-up views – ‘View Y’ and ‘View Z’, the valleys V1 of the upper row of angled struts 10a are connected to the corresponding peaks P2 of the intermediate row of angled struts 10b by diamond shaped cells 101c1 (with open structure), or a rhombus body 101d which may have at least one hole 101d’, thereby forming an upper row of cells 101b2 having interlaced octagonal cells creating a sequence of diamond shaped cells 101c1 or a rhombus body 101d at each junction. Thus, two consecutive first polygonal cells include one of a common diamond shaped cell 101c1 or a rhombus body 101d.
[0074] Referring to Fig. 1b, the rows of angled struts 10b and 10c are connected to each other to form the lower row of cells 101b1. Referring to Fig. 1b and the blown-up views – ‘View Y’ and ‘View Z’, the valleys V2 of the intermediate row of angled struts 10b are connected to the corresponding valleys V3 of the lower row of angled struts 10c by links L. As shown in View Y and View Z, a link L comprises a straight portion S and a diamond shaped cell 101c2, thereby forming a lower row of cells 101b1 that includes interlaced decagonal cells with chevron shape. The diamond shaped cells 101c2 have open structure. The position of the straight portion S and the diamond shaped cells 101c2 within the link L may be reversed according to one embodiment. Thus, two consecutive second polygonal cells include a common link L including a straight strut portion S followed by a diamond shaped cell 101c2.
[0075] This unique scaffold design geometry of the frame 101 profoundly influences its foreshortening characteristics. The foreshortening is virtually eliminated from the inflow zone (usually the ventricular end) due to the chevron shape of cells, with a marginal foreshortening of 10-12% at its outflow zone (usually the aortic end). The % foreshortening of a frame scaffold is influenced by several design characteristics of the frame scaffold structure. % foreshortening is directly proportional to the number of rows of cells that make up the THV frame; meaning more the number of rows, the more the frame foreshortens. Further, the % foreshortening is directly proportional to the heterogeneity of the rows i.e. the frame includes a mix of cells of different shapes; meaning more heterogenous the frame (e.g. the cells in a frame are a mix of diamond and hexagonal shapes), more is the foreshortening since different geometrical shapes tend to foreshorten differently.
[0076] Due to this unique characteristic, the operator has high comfort knowing that ventricular end of the THV frame 101 will deploy precisely where intended during THV expansion. The foreshortening of the frame 101 at the outflow zone of this THV frame 101 is mediated only by opening of nested inverted “V-struts” at outflow edge and the “V-struts” at the intermediate-row (if present) forming the junction of inflow-outflow zone rows. Thus, there is only 10-12% foreshortening at this junction. This purposeful outflow zone foreshortening results in reducing the fully expanded THV frame height; further reducing the risk of coronary artery obstruction and facilitating access to coronary ostia.
[0077] This offers the operator total control of the frame 101 under expansion leading to accurate deployment which further leads to predictable procedural and clinical outcomes such as Lower MACCE (Major Adverse Cardiac and Cerebrovascular Events), lower PVL, lower new permanent pacemaker implantation (PPI), possibility of shallow or deep THV frame deployment depending upon patient’s anatomic and/or clinical presentation such as bicuspids aortic valves; previously deployed bioprosthetic valve, narrow or wide left ventricular outflow tract (LVOT); presence of septal bulge; concomitant presence of surgical/mechanical valve in mitral position; narrow or calcified sino-tubular junction (STJ) etc.
[0078] The decagonal cell in the lower row of cells 101b1 is shown schematically in Fig. 1c with all ten sides and angles marked sequentially as A to J and A’ to J’ respectively. Similarly, the octagonal cell in the upper row of cells 101b2 is shown in Fig. 1c with all eight sides and angles marked sequentially as 1 to 8 and 1’ to 8’ respectively.
[0079] The sum of the angles formed by a polygon is (n-2)*180° where n denotes the number of sides. Hence, for a decagon (with 10 sides), the sum of the angles would be 1440° and an octagon (with 8 sides), the sum of the angles would be 1080°. Accordingly, sum of all angles (A’ to J’) of any of the decagonal cells is 1440°. Similarly, sum of all angles (1’ to 8’) of the octagonal cells is 1080°.
[0080] Each link L connecting the two adjacent rows of angled struts 10b and 10c has a diamond shaped cell 101c2 which is defined by two pairs of crooked struts (s1’/s2’ and s3’/s4’ as shown in exploded view Y in Fig. 1b) which form the diamond shaped cells 101c2. Similarly, the diamond shaped cell 101c1 connecting the two adjacent rows of angled struts 10a and 10b is defined by two pairs of crooked struts (s1/s2 and s3/s4 as shown in exploded view Y in Fig. 1b) which form the diamond shaped cells 101c1. This means that any diamond shaped cell 101c1 or 101c2 includes an opening enclosed within the pairs of crooked struts s1/s2 and s3/s4 or s1’/s2’ and s3’/s4’. The interconnection of the one row and the adjacent row of angled struts 10a/10b/10c thus results in a cell structure having interlaced decagonal and octagonal cells and diamond shaped cells 101c1/101c2 or solid rhombus bodies 101d with holes. This structure enhances columnar strength of the frame 101 resulting in improved radial strength and fatigue resistance of the frame 101.
[0081] In an embodiment, the first polygonal cells in the upper row of cells 101b2 are larger than the second polygonal cells in the lower row of cells 101b1. In a preferred embodiment and as shown in Fig. 1b, the upper row of cells 101b2 occupy around 55% of the total height H of the frame; while the lower row of cells 101b1 occupy around 45% of the total height H of the frame. The larger cells in the upper (outflow) part of the frame 101 keeps coronary ostia unjailed to allow unrestricted flow of blood from the aorta to the coronary arteries. However, the size of the cells in the upper and lower rows of cells 101b2, 101b1 may be equal or the cells in the lower row of cells 101b1 may be marginally larger than the cells in the upper row of cells 101b2.
[0082] Though the frame 101 shows two rows of polygonal cells, it is possible that the frame 101 of the THV 100 may have more than two rows of polygonal cells with the upper row of cells 101b2 having interlaced octagonal cells and the lower row of cells 101b1 having interlaced chevron-shaped decagonal cells.
[0083] The frame 101 depicted in Figs. 1 and 1b is for a THV with three leaflets 103/103x (refer to Figs. 5 and 5a). There are three rhombus bodies 101d spaced uniformly at 120° with respect to each other. In a preferred exemplary embodiment, each rhombus body 101d has four holes 101d’. Fig. 1a shows the details of the rhombus body 101d of this embodiment with four holes 101d’ which are provided for suturing the commissural tabs of two adjacent leaflets 103/103x to form commissures. It may be noted that the number of holes 101d’ may be less than or more than four. Similarly, the number of rhombus bodies 101d with holes 101d’ may be more or less than three depending on the number of leaflets in the THV for which the frame is made.
[0084] The frame 101 of the THV 100 has an anchoring zone at the inflow portion of the frame 101 (lower row of cells 101b1). Various embodiments of the frame of the THVs of the instant invention are expected to be anchored at the annular level and the leaflets are sutured a little higher within the frame (above the anchoring zone), keeping the anchoring zone of the inflow zone free of leaflets (termed as a valve-free zone). The leaflets are positioned preferably at the end of the first 30%-50% portion of the frame from the inflow zone. Thus, the inflow zone of the valve frame will have no leaflets. Thus, the valve-free zone, in other words, extends from below a suturing line of the leaflets (or leaflet suturing line) till the inflow end. The deployment of the THV with its valve-free zone at the aortic level results in the prosthetic leaflets being located above the native aortic annulus achieving supra-annular deployment where the diameter of the frame is higher due to tapered shape of the expanded THV. The supra-annular deployment, hence, provides higher effective orifice area (EOA) compared to the EOA of the native valve.
[0085] In an embodiment, at least one radiopaque marker (not shown) may be provided on the frame 101 on any of the struts preferably on the crooked struts (s1’, s2’, s3’, s4’) forming the diamond shaped cells 101c2 (located in the lower row of cells 101b1) for easy visualization under fluoroscopy. However, the radiopaque markers may be provided on other struts.
[0086] Perspective view of a support frame 201 (or frame 201) of a THV 200 of another embodiment is shown in Fig. 2. The frame 201 is a radially collapsible and radially expandable having a cylindrical shape with an inflow end 200a and an outflow end 200b. The frame 201 of the exemplary embodiment is a balloon-expandable frame. Alternately, the frame 201 may be a self-expandable frame.
[0087] The structure of the frame 201 of this exemplary embodiment is shown in Figs. 2, 2a and 2b. Fig. 2 shows prospective view of the frame 201. Fig 2b depicts the cylindrical frame structure when the cylindrical portion of the frame is cut vertically along its axial length and flattened. It should be noted in relation to Fig. 2b that the frame scaffold design is shown laid flat for convenience purpose only and the frame 201 may not be created from a flat metal sheet.
[0088] As evident from the Figs. 2 and 2b, the frame 201 includes an inflow end 200a, an outflow end 200b and a plurality of rows of cells (e.g., two rows of cells) including at least a lower row of cells 201b1 (towards the inflow end 200a) and an upper row of cells 201b2 (towards the outflow end 200b) of tessellating polygonal cells. In an embodiment shown in Figs. 2 and 2b, the upper and lower rows of cells 201b2, 201b1 other placed one above the other. The rows of cells are thus adjacently placed. Further, the plurality of rows of cells extend between the distal end (inflow end 200a) and the proximal end (outflow end 200b) of the frame 201. The cells in the upper row may be referred as first polygonal cells while the cells in the lower row may be referred as second polygonal cells. The second polygonal cells are chevron-shaped. In an embodiment, the first polygonal cells are octagonal and the second polygonal cells are hexagonal.
[0089] Referring to Fig. 2b, the frame 201 has three circumferentially extending rows of angled struts having an upper row 20a at the proximal end 200b of the frame 201, a lower row 20c at the distal end 200a of the frame 201 and an intermediate row 20b located between the upper row 20a and the lower row 20c. The distal position refers to a position away from the operator. The lower row 20c is towards the inflow end 200a of the support frame 201 and the upper row 20a is towards the outflow end 200b of the support frame 201. Any two consecutive angled struts of a circumferentially extending row of angled struts form a peak or a valley giving an undulating shape to each row of angled struts. The peaks P1’ of the upper row 20a of angled struts (also referred to as upper row of angled struts 20a) face the valleys V2’ of the intermediate row 20b of angled struts (also referred to as intermediate row of angled struts 20b), and the peaks P2’ of the intermediate row 20b of angled struts face the peaks P3’ of the lower row 20c of angled struts. In other words, the valleys V1’ of the upper row 10a of angled struts face the peaks P2’ of the intermediate row 10b of angled struts, and the valleys V2’ of the intermediate row 10b of angled struts face the valleys V3’ of the lower row 10c of angled struts (also referred to as lower row of angled struts (20c).
[0090] In an embodiment, the angle (‘A’) between two angled struts in FIG. 2b is around 116°. However, it should be noted that the said angle may be less than or more than 116°.
[0091] The rows of angled struts 20a and 20b are connected to each other to form an upper row of cells 201b2. Referring to Fig. 2b and the blown-up views - View Y’ and View Z’, the valleys V1’ of the upper row 20a of angled struts are connected to the corresponding peaks P2’ of the intermediate row 20b of angled struts by diamond shaped cells 201c (with open structure), or a rhombus body 201d which may have at least one hole 201d’, thereby forming an upper row of cells 201b2 having interlaced octagonal cells creating a sequence of diamond shaped cells 201c or a rhombus body 201d at each junction. Thus, two consecutive first polygonal cells include one of a common diamond shaped cell 201c or a rhombus body 201d.
[0092] The frame 201 depicted in Figs. 2 and 2b is for a THV with three leaflets 103/103x (refer to Figs. 5 and 5a). There are three rhombus bodies 201d spaced uniformly at 120° with respect to each other. In a preferred exemplary embodiment, each rhombus body 201d has four holes 201d’. Fig. 2a shows the details of the rhombus body 201d of this embodiment with four holes 201d’ which are provided for suturing the commissural tabs of two adjacent leaflets 103/103x to form commissures. It may be noted that the number of holes 201d’ may be less than or more than four. Similarly, the number of rhombus bodies 201d with holes 201d’ may be more or less than three depending on the number of leaflets in the THV for which the frame is made.
[0093] Again referring to Fig. 2b, the rows of angled struts 20b and 20c are connected to each other to form the lower row of cells 201b1. Referring to Fig. 2b and the blown-up views View Y’ and View Z’, the valleys V2’ of the intermediate row 20b of angled struts are connected to the corresponding valleys V3’ of the lower row 20c of angled struts by axially extending strut L’. As shown in View Y’ and View Z’, the lower row of cells 201b1 includes hexagonal cells with chevron shape. Thus, two consecutive second polygonal cells include a common axially extending strut L’.
[0094] The hexagonal cell in the lower row of cells 201b1 is shown schematically in Fig. 2c with all six sides and angles marked sequentially as A to F and A’ to F’ respectively. Similarly, the octagonal cell in the upper row of cells 201b2 is shown in Fig. 2c with all eight sides and angles marked sequentially as 1 to 8 and 1’ to 8’ respectively.
[0095] The sum of the angles formed by a polygon is (n-2)*180° where n denotes the number of sides. Hence, for an octagon (with 8 sides), the sum of the angles would be 1080° and a hexagon (with 6 sides), the sum of the angles would be 720°. Accordingly, sum of all angles (1’ to 8’) of any of the octagonal cells is 1080°. Similarly, sum of all angles (A’ to F’) of the hexagonal cells is 720°.
[0096] The interconnection of the one row and the adjacent row of angled struts 20a/20b/20c thus results in a cell structure having hexagonal cells (with chevron shape) and interlaced octagonal cells and diamond shaped cells 201c or solid rhombus bodies 201d with holes 201d’. This structure enhances columnar strength of the frame 201 resulting in improved radial strength and fatigue resistance of the frame 201.
[0097] In an embodiment, the first polygonal cells in the upper row of cells 201b2 are larger than the second polygonal cells in the lower row of cells 201b1. In a preferred embodiment and as shown in Fig. 2b, the upper row of cells 201b2 occupy around 70% of the total height H’ of the frame 201; while the lower row of cells 201b1 occupy around 30% of the total height H’ of the frame 201. The larger cells in the upper (outflow) part of the frame 201 keeps coronary ostia unjailed to allow unrestricted flow of blood from the aorta to the coronary arteries. However, the size of the cells in the upper row of cells 201b2 may occupy 50%-70% and the cells in the lower rows of cells 201b1 may occupy 30%-50% of the total height H’. It is possible that the size of the cells in the upper and lower rows of cells 201b2, 201b1 may be equal or the cells in the lower row of cells 201b1 may be marginally larger than the cells in the upper row of cells 201b2.
[0098] In an embodiment, at least one (not shown) radiopaque marker may be provided for easy visualization under fluoroscopy. In THV 200, the radiopaque marker may be provided on the frame 201 on any of the struts preferably on the axially extending strut L’ forming the hexagonal shaped cells located in the lower row of cells 201b1. However, the radiopaque markers may be provided at any of the struts.
[0099] In one embodiment, the frame 101/201 includes at least one intermediate row of cells between the upper row of cells 101b2/201b2 and the lower row of cells 101b1/201b1. The at least one intermediate row of cells includes interlaced polygonal (e.g., hexagonal, octagonal and/or decagonal) formed in a similar manner as described herein.
[00100] The THV 100 in accordance with an embodiment of the present invention is represented in Figs. 3 & 3a. Fig. 3 shows THV 100 without an external skirt 107, while Fig. 3a shows THV 100 with the external skirt 107. If the THV 100 is implanted in a human stenosed aortic orifice, the THV 100 may also be referred as a ‘prosthetic aortic valve’.
[00101] As shown in Figs. 3 and 3a, the THV 100 includes an inflow end 100a (lower end) and an outflow end 100b (upper end). Blood enters the THV 100 at the inflow end 100a and leaves at the outflow end 100b. The leaflets 103/103x prevent the blood flow in reverse direction. The THV 100 includes a frame 101 (or support frame 101), a plurality of leaflets 103/103x, an internal skirt 105 (as shown in FIG. 3) and an external skirt 107 (as shown in FIG. 3a).
[00102] The THV 200 in accordance with an embodiment of the present invention is represented in Figs. 4 & 4a. Fig. 4 shows THV 200 without an external skirt 207, while Fig. 4a shows THV 200 with the external skirt 207. If the THV 200 is implanted in a human stenosed aortic orifice, the THV 200 may also be referred as a ‘prosthetic aortic valve’.
[00103] As shown in Figs. 4 and 4a, the THV 200 includes an inflow end 200a (lower end) and an outflow end 200b (upper end). Blood enters the THV 200 at the inflow end 200a and leaves at the outflow end 200b. The leaflets 103/103x prevent the blood flow in reverse direction. The THV 200 includes a frame 201 (or support frame 201), a plurality of leaflets 103/103x, an internal skirt 205 (as shown in FIG. 4) and an external skirt 207 (as shown in FIG. 4a).
[00104] Referring to Figs. 3 and 3a/4 and 4a, the blood enters the THV 100/200 at the inflow end 100a/200a (also referred to as “lower end” or “distal end”) and leaves at the outflow end 100b/200b (also referred to as “upper end” or “proximal end”).
[00105] The frame 101/201 may be formed by following any pre-defined methodology known in the art. For example, the frame 101/201 of the THV 100/200 may be formed by laser cutting a metal tube. The metal tube may be made from a metal or a metal alloy, including but not limited to, stainless steel, cobalt-chromium alloy, cobalt-chromium-nickel alloy, cobalt-chromium-nickel-molybdenum alloy such as MP35N, Nitinol, titanium etc. The material used for the frame 101/201 may be fluoroscopic. In a preferred embodiment of the present invention, the frame 101/201 is balloon expandable and is made from a tube of cobalt-chromium-nickel-molybdenum alloy viz. MP35N which ensures optimal radial strength, radiopacity and prompt MRI compatibility of the frame 101/201.
[00106] The THV 100/200 of the present invention further includes a plurality of leaflets 103/103x. In an embodiment, the THV 100/200 includes three leaflets 103/103x. The leaflets 103/103x may be made from any bio-compatible material with sufficient flexibility to allow movement of the leaflets 103/103x. For example, in the present invention, the leaflets 103/103x of a preferred embodiment are made from an animal tissue such as bovine pericardial tissue. Alternately, the leaflets 103/103x may be formed from any other tissue material or a synthetic polymeric material.
[00107] The leaflets 103/103x allow unidirectional flow of blood from inflow end 100a/200a of THV 100/200 to the outflow end 100b/200b and prevent the flow of blood in the reverse direction. This is achieved by opening and closing the leaflets during systolic and diastolic cycles.
[00108] An exemplary embodiment of the structure of the leaflet 103 is shown in FIG. 5. As depicted, each leaflet 103 of this embodiment may include a body 103’ having a relatively straight upper edge 103a. The upper edge 103a in the embodiment shown in FIG. 5 has an apex 103a1. However, alternately, the apex 103a1 may be absent. The upper edge 103a is kept free for coaptation with the corresponding free edges of the other leaflets 103.
[00109] The upper edge 103a of each leaflet 103 may extend into oppositely disposed side tabs (or commissure tabs) marked as 103b1, 103b2 at either side of the leaflet 103. A plurality of holes may be disposed at both the side tabs 103b1, 103b2 for ease of suturing. In the embodiment shown in FIG. 5, two vertical rows of holes marked as Y, Z are provided near the portion of each side tab 103b1, 103b2 near the body 103’ of the leaflet 103. In an embodiment, each row of holes Y, Z may include four holes (marked as 1, 2, 3, 4). The number of holes may be more than or less than four. The number of holes in a row is same as the number of holes 101d’/201d’ in the rhombus body 101d/201d. Similarly, the number of vertical rows of holes may be one or more than two. The said holes are utilized for attachment of the leaflets 103 to the connecting fabric and/or frame 101/201 by suturing.
[00110] Each leaflet 103 may further include a lower edge 103c. As shown in the embodiment of Fig. 5, the lower edge 103c may include a scalloped shape with optional small straight portions 103c1 and 103c2 located at the junction of the lower edge103c and the side tabs 103b1, 103b2. The scalloped lower edge 103c of the leaflet 103 of a preferred embodiment may include a constant radius R. However, the scalloped lower edge 103c of the leaflet 103 may have varying radius. The scalloped lower edge 103c of each of the leaflets 103 may be attached to the internal skirt 105/205 by any known method such as suturing.
[00111] Alternately, the THV 100/200 may include a leaflet 103x as shown in embodiment of FIG. 5a, which is similar to the embodiment shown in FIG. 5, except that it has a straight lower edge 103c’ and the sides 103c” which are vertically oriented (unlike scalloped lower edge 103c as in the embodiment of FIG. 5). The sides 103c” may be vertical or at an angle to the straight lower edge 103c’. Fig. 5a shows an embodiment where the sides 103c” are not exactly vertical but are at an angle with respect to the lower edge 103c’. The straight lower edge 103c’ and the sides 103c’’ of the leaflet 103x may be attached to the internal skirt 105/205 by any known method such as suturing.
[00112] The above defined leaflets 103 or 103x may be attached to the frame 101/201 using a pre-defined method. A skilled person is well aware of various methods known in the art of attaching leaflet tabs to the commissure areas defined by the rhombus body 101d/201d of the frame 101/201 using one or more supporting fabrics. Hereinafter, the commissure areas are interchangeably referred by 101d/201d. One of the side tabs 103b1/103b2 of a given leaflet 103 or 103x is paired with one side tab 103b1/103b2 of another adjacent leaflet 103 or 103x to form a leaflet-commissure. The leaflet-commissures may then be attached to the commissure areas 101d/201d of the frame 101/201 using supporting fabric so as to avoid direct contact of the tissue with metal of the frame 101/201.
[00113] The internal skirt 105/205 is attached to the inner (or internal) surface of the frame 101/201 and in a preferred embodiment, covers the internal surface of the lower row of cells 101b1 (the decagonal cells) or 201b1 (the hexagonal cells) at least partially as shown in FIGs. 3 and 4. The scalloped lower edge 103c or the straight lower edge 103c’of the leaflets 103 or 103x is attached to the inner surface of the internal skirt 105/205. The vertically oriented edges 103c” of the leaflets 103x are also attached to the inner surface of the internal skirt 105/205. The internal skirt 105/205 of a preferred embodiment may be made from a fabric such as PET. However, any other biocompatible fabric or animal tissue with required flexibility, strength and porosity can be used for making the internal skirt 105/205. The internal skirt 105/205 prevents leakage of blood from the openings of the cells of the frame 101/201 in the lower row of cells 101b1/201b1 and also prevents inadvertent damage of the leaflets 103/103x by calcium spicules present in diseased native valve.
[00114] The external skirt 107/207 of an exemplary embodiment is shown in Fig. 3a/4a. The external skirt 107/207 includes an upper end 107b/207b and a lower end 107a/207a. In an embodiment, the upper end 107b/207b (towards the outflow end) of the external skirt 107/207 may be attached to the internal skirt 105/205 and the frame 101/201 via suturing at an intermediate portion of the frame 101/201 as shown in Fig. 3a/4a. The lower end 107a/207a (towards the inflow end 100a/200a) of the external skirt 107/207 is attached to the lower end 105a/205a of the internal skirt 105/205 by suturing. The function of the external skirt 107/207 is to plug microchannels between THV 100/200 and the inner surface of the vasculature and prevent or minimize paravalvular leakage.
[00115] Fig. 3a/4a show an exemplary embodiment in which the external skirt 107/207 is attached to the outer (or external) surface of the frame 101/201 and it covers the external surface of the lower row of cells 101b1 (the decagonal cells) or 201b1 (the hexagonal cells) at least partially. The extent of this covering further assists in placing the THV 100/200 with minimal error across asymmetric cusp geometry, cusp with severe calcification, anatomically challenging aorta like horizontal aorta and reduces the operator learning curve during placement and deployment.
[00116] The external skirt 107/207 of the present invention may be made from a fabric such as PET. However, any other biocompatible fabric or material like animal tissue with required flexibility, strength and porosity can be used.
[00117] The delivery system i.e. a delivery catheter 300 for implantation of the THV 100/200 in aortic position will now be described. Fig. 6 depicts an exemplary delivery catheter 300. The delivery catheter 300 is utilized for deploying the THV 100/200 within a diseased native aortic valve at a target location. The frame structure of THV 100/200 and the delivery catheter 300 of the instant invention provide an easy and accurate method for supra-annular deployment of the THV 100/200 at the target location.
[00118] The delivery catheter 300 as shown in FIG. 6 is a balloon catheter. A skilled person is well aware of the construction of a conventional balloon catheter used for radially expanding a balloon expandable device such as a stent or a prosthetic valve. The exemplary delivery catheter 300 includes a proximal end A and a distal end B. The delivery catheter 300 further includes a balloon 301 at its distal end B (shown in detail in Fig. 6a), an outer shaft 303, an inner shaft 305, an optional support tube 307, one or more stoppers 309, a handle 311 and a connector 313 at the proximal end. The distal end refers to the end away from the operator as mentioned earlier.
[00119] The outer shaft 303 is in the form of an elongated external tube referred also as ‘elongated shaft’. The outer shaft 303 defines an outer lumen through which the inner shaft 305 extends coaxially. The inner shaft 305 defines an inner lumen. A guidewire passes through the inner lumen.
[00120] The outer shaft 303 and the inner shaft 305 (also referred to as “inner lumen”) have respective proximal and distal ends (A and B respectively). Proximal end is towards the handle 311 i.e. towards the operator. The opposite end towards the balloon 301 is the distal end which is away from the operator. The proximal ends of the outer shaft 303 and the inner shaft 305 may pass through the handle 311 and may be attached to the connector 313. The connector 313 may be a Y-shaped connector having a port 313a (also referred to as a guidewire port 313a) for exit of a guidewire and a port 313b for injecting inflation fluid into the delivery catheter 300. The guidewire port 313a is in communication with the inner lumen 305. The port 313b for inflation fluid is in communication with the annular space between the two shafts 303 and 305. This arrangement is normally provided in a conventional balloon catheter.
[00121] An exemplary embodiment of the balloon 301 of the delivery system 300 of the instant invention is shown in Fig. 6a. The balloon 301 is attached to the distal end of the outer shaft 303. The inner lumen 305 extends through the balloon 301 and it ends into a soft tip 315 at a distal most end of the delivery catheter 300. The guidewire (not shown) enters the guidewire lumen at the distal end B of the soft tip 315 of the catheter 300, passes through the inner lumen, passes through the balloon 301 and exits from the connector 313 at guidewire port 313a.
[00122] The balloon 301 is an inflatable balloon that is radially expanded by injecting pressurised inflation fluid into the balloon 301 through the annular space between the outer shaft 303 and the inner shaft 305.
[00123] In a preferred embodiment, a support tube 307 is attached to the distal end of the outer shaft 303. The support tube 307 extends within the balloon 301 and the inner shaft 305 passes through the support tube 307 coaxially as more clearly shown in the FIG. 6a. As shown in FIG. 6a, the support tube 307 includes a proximal end 307a and a distal end 307b. The proximal end 307a is attached to the outer shaft 303. The distal end 307b is a free end and overhangs within the balloon 301. At least one stopper made from a resilient and biocompatible material is attached to the outer surface of the support tube 307. A preferred embodiment of the balloon 301 shown in Fig. 6a is provided with two stoppers; a proximal stopper 309a and a distal stopper 309b attached to the outer surface of the support tube 307.
[00124] The proximal stopper 309a and the distal stopper 309b may be spaced apart at a pre-defined distance. In the preferred embodiment, the clear gap between the distal end of the proximal stopper 309a and the proximal end of the distal stopper 309b is little more than the length of the crimped THV 100/200. The THV 100/200 is crimped on the balloon 301 within this gap. The clear gap as defined above may vary depending upon the length of the crimped THV 100/200.
[00125] Crimping THV 100/200 between the proximal stopper 309a and the distal stopper 309b as described above, prevents the THV 100/200 from shifting on or dislodging from the balloon 301 during insertion of the crimped THV 100/200 into the patient’s vasculature and while manoeuvring the THV 100/200 through tortuous vascular pathway to reach implantation site. The stoppers 309a and 309b also prevent inadvertent valve embolization during balloon inflation. The stoppers 309a and 309b create a lower entry profile at their respective ends due to their resilient nature which assists the smooth exit of the THV 100/200 from an introducer sheath into the patient’s vasculature and also for easy retrieval of an undeployed THV 100/200. The inflation fluid enters into the balloon 301 through holes 307c in the support tube 307 at its proximal end 307a and also from its free and open distal end 307b. This feature ensures uniform filling of the balloon 301 and facilitate its steady expansion simultaneously from the distal and proximal end creating a dog bone which stabilizes the THV 100/200 during expansion and prevents inadvertent valve embolization.
[00126] The support tube 307 described above is to ease the accurate attachment of the stoppers 309a, 309b and for providing free passage to the inflation fluid into the balloon 301. A delivery system without the support tube 307 would also function. In this case, the stoppers may be located on the inner shaft 305 and the inflation fluid will enter the balloon 301 at its proximal end from the annular space between the inner shaft 305 and the outer shaft 303 at the proximal end A of the balloon 301.
[00127] The support tube 307 of the present invention may include a plurality of radiopaque marker bands (or markers). The markers include at least a landing zone marker M4. In a preferred embodiment, the support tube 307 includes four radiopaque marker bands including a proximal marker band M1, a distal marker band M2, a middle marker band M3 and a landing zone marker band M4. If the delivery system 300 does not have a support tube 307, these markers may be provided on the inner shaft 305 on the portion located within the balloon 301. The marker bands may be made of any biocompatible radiopaque material known in the art such as platinum, platinum-iridium alloy, tantalum, gold etc. Radiopaque markers in a preferred embodiment of the delivery catheter 300 of the instant invention are made from platinum-iridium alloy.
[00128] The above description refers to a specific THV frame scaffold structure of the frame 101/201 with two rows of cells each with specific cell structure as described above. The concept of providing radiopaque markers (viz. M1, M2, M3 and M4) for accurate placement of a THV at desired position can be applied to a frame scaffold structure with cells of any polygonal shape (e.g. diamond shape etc.).
[00129] As the name suggests, the proximal marker band M1 and the distal marker band M2 are disposed towards the proximal end 307a and the distal end 307b of the support tube 307 respectively. The middle marker band M3 is located between M1 and M2, equidistant from M1 and M2. The placement of the landing zone marker M4 is calculated on the basis of one or more parameters including without limitation the length of a frame, foreshortening properties of the frame, number of rows of cells, shape of cells, position of the leaflets, anchoring zone of the frame (that is, position where the frame is anchored to the native annulus or annulus of previously implanted THV or annuloplasty ring), etc. The placement of the landing zone marker M4 thus calculated, helps an operator in accurate placement of the THV 100/200 as described later.
[00130] In an exemplary embodiment of the frame 101/201 depicted in Figs. 1b and 2b, the landing zone marker M4 is placed between the distal and mid marker bands M2, M3 at a distance of around 32-34% of the distance between proximal and distal markers M1, M2 from the distal end marker M2 i.e. dimension B is 32-34% of dimension A as shown in FIG. 6a. This distance is for the specific frame structures as depicted in Figs. 1b/2b and described above. The landing zone marker M4 helps the operator in accurate placement of the THV 100/200 as described later. For any other frame with a different scaffold structure and shape of cells, etc., the placement of the landing zone marker M4 can be predetermined on the basis of aforesaid parameters.
[00131] As shown in Fig. 6a, the distal edge of the proximal marker M1 is in line with the distal edge of the proximal stopper 309a as shown by the broken line L1. Similarly, the proximal edge of the distal marker M2 is in line with the proximal edge of the distal stopper 309b as shown by the broken line L2. This feature fixes exact location of all the radiopaque markers. Again, as mentioned above, this feature is applicable to the embodiment of THV with the frame 101/201 depicted in Figs. 1b/2b.
[00132] The delivery catheter 300 of the instant invention involves a differential diameter tapered balloon such that when expanded at its nominal pressure, it inflates (expands) attaining varying diameter across its axial length. These diameters are referred to as nominal diameters. Fig. 6b shows the balloon 301 schematically with proximal end A and distal end B. The balloon 301 is attached to the distal end of the outer shaft 303. The stoppers 309a and 309b are also shown. Radiopaque markers and other details are not shown for clarity. The shoulders (conical end portions) of the balloon 301 are marked as E1 (proximal end) and E2 (distal end). The middle portion, where the THV 100/200 is located in crimped configuration is tapered and is marked as E3. As shown in Fig. 6b, the nominal diameter D1 at the proximal end A of the balloon 301 in expanded configuration is larger than the nominal diameter D2 at its distal end B. The difference between the largest diameter D1 and the smallest diameter D2 in a preferred embodiment may be between 1 and 2.5 mm. However, this difference may be more than 2.5 mm.
[00133] This configuration of the balloon 301 is suitable for implantation of THV 100/200 in the aortic position. Thus, the balloon diameter tapers proximally (towards the operator) to distally (away from the operator) with lower diameter at the inflow zone (distal zone). The nominal expansion diameter D2 of the balloon 301 at its distal end may preferably be matched to the nominal diameter of the prosthetic valve crimped over it which closely approximates to the diseased native annulus diameter. The balloon 301 has a higher diameter D1 towards the outflow zone (proximal zone). The balloon 301 shown in Fig. 6b has a uniform taper from distal to proximal ends of the balloon 301 i.e. the balloon 301 has a conical shape when expanded. Alternately, the balloon 301 may have a stepped construction i.e. it has a lower diameter in the inflow zone (distal zone, which is, for example, about 1/3 of the total active length of the balloon 301) and a larger diameter in the outflow zone (proximal zone, which is, for example, about 2/3 of the total active length of the balloon 301).
[00134] When the balloon 301 with the THV 100/200 mounted on it is expanded, the THV 100/200 will expand and attain a tapered shape which will be nearly same as that of the expanded balloon 301. Thus, in an embodiment, the frame 101, 201 attains a tapered configuration upon expansion via the balloon 301, 301’ having tapered profile. For treating a diseased native aortic valve, the operator chooses a THV 100/200 of appropriate size (e.g. its nominal diameter) which corresponds to the aortic annulus. The lower row of cells 101b1/201b1 (at the distal end of the frame 101/201) would be anchored to the diseased native aortic valve. The cells in the lower row of cells 101b1/201b1 at the inflow zone of the frame 101/201 are covered at least partially with the fabric skirt 105/107 or 205/207 both from inside (to prevent any calcium spicules on native diseased valve from damaging the bioprosthetic tissue leaflets 103/103x and also to minimize paravalvular leaks) and from outside (to block micro-channels formed between the THV 100/200 and the native diseased aortic valve annulus and reduce paravalvular leaks). The cells in the upper row of cells 101b2/201b2 at the outflow zone of the frame 101/201 are kept open in order to keep the coronary ostia unobstructed (un-jailed). The leaflets 103/103x are positioned at the end of the first 30%-50% portion of the frame 101/201 from the inflow zone. Thus, the inflow zone of the valve frame 101/201 will have cells in the lower row of cells 101b1/201b1 covered at least partially with the internal skirt (105/205) and external skirt (107/207), but no leaflets. Additionally, the inflow zone may be provided with radiopaque markers to assist the operator in precise positioning and placement of the THV 100/200. Additional radiopaque marker/s may be placed in the outflow zone of the THV 100/200 to facilitate commissural/coronary alignment.
[00135] As described above, the frame of the THV 100/200 has an anchoring zone at the inflow portion of the frame 101/201 (e.g., the lower row of cells 101b1/201b1) which is expected to be anchored at the annular level. The leaflets 103/103x are sutured higher (above the anchoring zone) and placed preferably at the end of first 30% - 50% portion of the frame 101/201 from the inflow zone, keeping the inflow zone (anchoring zone) free of leaflets (termed as a valve-free zone). The valve-free zone is provided towards the inflow end 100a, 200a and extends from a leaflet suturing line till the inflow end 100a, 200a. Thus, on deployment, the THV 100/200 with its valve-free zone at the aortic level, results in the prosthetic leaflets 103/103x being located above the level of native aortic annulus enabling or achieving supra-annular deployment i.e. above aortic annulus where the diameter of the frame 101/201 is higher due to tapered shape of the expanded THV 100/200. The supra-annular deployment, hence, provides higher effective orifice area (EOA) compared to the EOA of the native valve.
[00136] The landing zone marker M4 plays a guiding role in accurate positioning of the THV 100/200 at the implantation site to achieve implantation at the most preferred location such that only the valve free zone of THV 100/200 is anchored to the aortic annulus and the leaflets 103/103x are located above the anchored zone.
[00137] The distal end of the outer shaft 303 of the exemplary delivery catheter 300 may be configured to be flexed in a controlled manner for easy passage through aortic arch. In an alternate embodiment, the distal end of the outer shaft 303 of the delivery catheter 300 may not be configured to be flexed. In yet another alternate embodiment, the distal end of the outer shaft 303 of the delivery catheter 300 may be pre-shaped with a fixed radius for easy passage through aortic arc. The pre-shaping of the outer shaft 303 can be achieved by known methods such as thermal treatment.
[00138] FIG. 7 depicts the aortic root complex 1. The anatomical representation of the aortic root is only schematic and not drawn with precision. Aortic root is the dilated first part of aorta attached to the heart at its end. It is a part of the ascending aorta (AA) 2 containing the native aortic valve. There are generally three cusps of the native aortic valve. The coronary arteries usually originate from the vicinity of the aortic bulb from two of the three cusps. The Right Coronary Artery (RCA) 3 usually originates from Right Coronary Cusp (RCC) and the Left Coronary Artery (LCA) 4 usually originates from Left Coronary Cusp (LCC). The remaining cusp is termed Non-Coronary Cusp (NCC) as no coronary artery originates in the vicinity of this cusp. There are two distinct demarcation planes, one is the Virtual Annular Plane (VAP) 6 and the second is Sino tubular Junction (SJ) 7. In a standard procedure under fluoroscopic guidance, the native coronary cusps are made co-planar wherein the hinge point of each cusp is in a straight line and all the three cusps are well separated. The VAP 6 thus achieved can be visible under fluoroscopy and is a guiding feature to position the prosthetic valve at the optimal location for implantation.
[00139] During THV replacement procedure, under fluoroscopic guidance, the three native coronary cusps (sinuses) NCC, RCC, LCC are visually aligned in a co-planar view wherein non-coronary cusp (NCC) appears to the right of the patient and the left coronary cusp (LCC) appears to the left of the patient with the RCC lying in the center. This is shown schematically in Fig. 8. It may be noted that the fluoroscopic view is a mirror image of the true anatomical/AP view. Hence, in the schematic image of Figs. 7 and 8, NCC appears to the right of the patient and the LCC appears to the left of the patient.
[00140] As mentioned above, accurate placement and precise deployment of a prosthetic valve in aorta is very important to achieve optimal performance i.e. reduced valve gradients (sustained hemodynamics), increased EOA, absence of paravalvular regurgitation, uncompromised access to coronary ostia and avoiding any iatrogenic damage to conduction system that necessitates a new permanent pacemaker implantation. The traditional location of implantation of a prosthetic valve in aorta is preferably the orthotopic position wherein the attempt is to superimpose the prosthetic annulus (neo-annulus) to the native annulus ring.
[00141] The THV 100/200 of the instant invention has a valve free zone at its inflow end 100a/200a which anchors at the native aortic annulus while the bioprosthetic valve within the THV 100/200 is situated above the valve free anchoring zone where the diameter is larger than the native aortic annulus. Implanting the prosthetic valve 100/200 at this supra annular location has four important advantages, viz. (a) better anatomical placement of the prosthetic valve whereby the frame is held firmly within the stenosed annulus, thereby offering geographical fix, (b) minimal protrusion of the valve in left ventricle, thereby not disturbing cardiac conduction system, (c) minimizing obstruction to ostia of coronary arteries located along the coronary sinus of valsalva or may be above the sino-tubular junction and (d) achieving larger EOA and thus improved hemodynamics.
[00142] Fig. 9 depicts the aortic root complex 1 schematically with THV 100 implanted such that the valve free zone at its inflow end 100a is anchored at the native aortic annulus. As mentioned above, the anatomical representation of the aortic root is only schematic and not drawn with precision. The THV 100 shown in Fig. 9 is not to scale and all features of the THV 100 are not shown in the drawing e.g. THV 100 is shown without internal skirt 105, external skirt 107 and other components for clarity. LCA is left coronary artery. RCA is right coronary artery. 8 is pig tail catheter. THV 100 is shown with leaflets 103x sutured above the anchoring zone i.e. in the supra-annular position. It may be noted that the leaflets 103 may also be sutured in a similar manner. In an embodiment, as shown in Fig. 9, 80%-95% of the length of the expanded THV 100 remains above the virtual annular plane 6 while, the residual 5%-20% of the length of the expanded THV 100 dwells in the sub-valvular space i.e. below the virtual annular plane 6. This 80-20 to 95-5 aorta to ventricle position can be controlled by the operator is possible due to reduced foreshortening of the frame 101 of the THV 100 of the instant invention.
[00143] Fig. 9a depicts the aortic root complex 1 schematically with THV 200 implanted such that the valve free zone at its inflow end 200a is anchored at the native aortic annulus. As mentioned above, the anatomical representation of the aortic root is only schematic and not drawn with precision. The THV 200 shown in Fig. 9a is not to scale and all features of the THV 200 are not shown in the drawing e.g. THV 200 is shown without internal skirt 205, external skirt 207 and other components for clarity. LCA is left coronary artery. RCA is right coronary artery. 8 is pig tail catheter. THV 200 is shown with leaflets 103x sutured above the anchoring zone i.e. in supra-annular position. It may be noted that leaflets 103 may also be sutured in a similar manner. In an embodiment, as shown in Fig. 9a, 80%-95% of the length of the expanded THV 200 remains above the virtual annular plane 6 while, the residual 5%-20% of the length of the expanded THV 200 dwells in the sub-valvular space i.e. below the virtual annular plane 6. This 80-20 to 95-5 aorta to ventricle position is possible due to reduced foreshortening of the frame 201 of the THV 200 of the instant invention.
[00144] As shown in Fig. 1b, the frame 101 of the THV 100 has three circumferentially extending rows of angled struts 10a, 10b, 10c; wherein, the rows of angled struts 10a and 10b are connected to each other by diamond shaped cells 101c1 (with open structure), or a rhombus body 101d which may have holes 101d’, thereby forming an upper row of cells 101b2 as described earlier. The THV 100 is crimped on the balloon 301 between the two stoppers 309a, 309b and two extreme radiopaque markers M1, M2. Fig. 10 depicts schematically the frame 101 of the THV 100 (as depicted in FIGs. 1 and 1b) mounted on the balloon 301 under collapsed condition as visible under fluoroscopy. A and B indicate proximal and distal ends respectively. The other components of the THV 100 are not shown for clarity and only the frame 101 would be visible clearly under fluoroscopy as it is made from radiopaque material.
[00145] The angled struts (also referred to as ‘V-struts’) of the lower row 10c of angled struts on the inflow end 100a of the frame 101 (refer to Fig. 1b) play an important role in accurate placement of the THV 100 such that the valve free zone at its inflow end 100a is anchored at the native aortic annulus. Fig. 10 depicts the lower row 10c at the distal end B where the V-struts’ Vs are seen nested close to each other in the exploded View X. The converging of these V-struts Vs commences at the distal edge (the edge towards the inflow end 100a of the frame 101) of the landing zone marker M4 and the apex Ax of a V-strut Vs is visibly away from the distal edge of the landing zone marker M4 towards the distal direction B.
[00146] As shown in Fig. 2b, the frame 201 of the THV 200 has three circumferentially extending rows of angled struts 20a, 20b, 20c; wherein, the rows of angled struts 20a and 20b are connected to each other by diamond shaped cells 201c (with open structure), or a rhombus body 201d which may have holes 201d’, thereby forming an upper row of cells 201b2 as described earlier. The THV 200 is crimped on the balloon 301 between the two stoppers 309a, 309b and two extreme radiopaque markers M1, M2. Fig. 10a depicts schematically the frame 201 of the THV 200 (as depicted in FIGs. 2 and 2b) mounted on the balloon 301 under collapsed condition as visible under fluoroscopy. A and B indicate proximal and distal ends respectively. The other components of the THV 200 are not shown for clarity and only the frame 201 would be visible clearly under fluoroscopy as it is made from radiopaque material.
[00147] The angled struts (also referred to as ‘V-struts’) of the row of angled struts on the inflow end 200a of the frame 201 (lower row 20c, refer to Fig. 2b) play an important role in accurate placement of the THV 200 such that the valve free zone at its inflow end 200a is anchored at the native aortic annulus. Fig. 10a depicts the lower row 20c at the distal end B where the V-struts’ Vs are seen nested close to each other in the exploded View X’. The converging of these V-struts’ Vs commences at the distal edge (the edge towards the inflow end 200a of the frame 201) of the landing zone marker M4 and the apex Ax’ of a V-strut Vs’ is visibly away from the distal edge of the landing zone marker M4 towards the distal direction B. In other words, a peak of two consecutive angled struts in the lower row 10c/20c of angled struts coincides with the edge of the landing zone marker M4 disposed towards the inflow end 200a (in this case, the distal edge), when the THV 100/200 is crimped on the delivery catheter 300.
[00148] As mentioned above, during implantation of a prosthetic heart valve, a pigtail catheter 8 is introduced into the vasculature of the patient. Reference is made to Figs. 7 and 8. The pigtail catheter 8 is shown in Fig. 8. The curved distal end 8a of the pigtail catheter 8 is ideally placed at the base of the non-coronary cusp NCC of the aortic annulus. Alternately, the curved distal end 8a of the pigtail catheter 8 may be placed at the base of right or left coronary cusps i.e. RCC or LCC (though not ideal) and also at the sino tubular junction 7 (SJ). The decision of the location of this placement is usually taken by the operator based on aortic root anatomy. The curved distal end 8a of the pigtail catheter 8 can be used as landmark for accurate placement of the prosthetic heart valve in aorta. For this, the curved distal end 8a of the pigtail catheter 8 is made to rest on the base of a cusp (NCC, RCC or LCC) at the aortic root; preferably on the base of the non-coronary cusp NCC.
[00149] For accurate placement, the THV 100/200 crimped on the balloon 301 of the delivery catheter 300 is advanced across the aortic annulus till the distal edge (inflow edge) of the landing zone marker M4 comes in line i.e. matches with the curved distal end 8a of the pigtail catheter 8 as visible under fluoroscopic guidance. This scenario is depicted in Fig. 11 and exploded View A for THV 100 and Fig. 12 for THV 200. Under fluoroscopy, the frame 101/201 of the THV 100/200 is visible with clarity. A brief angiogram with a small volume of diluted contrast helps opacify and locates the annular plane 6. This helps the operator to ensure precise positioning of THV 100/200 prior to its deployment. Under rapid pacing of the heart, due to its aforementioned foreshortening characteristics, when expanded to its nominal diameter at this location, the THV 100/200 is deployed at optimal position in the aortic annulus such that the valve free zone at its inflow end 100a/200a is anchored at the native aortic annulus with leaflets 103/103x sutured above the anchoring zone i.e. in supra annular position. This is made possible because the foreshortening of the frame 101/201 of THV 100/200 is absent at the inflow zone due to chevron shape cells. Hence, to an operator, THV deployment is totally predictable when the THV 100/200 is expanded to its nominal diameter.
[00150] As mentioned above, the curved distal end 8a of the pigtail catheter 8 is made to rest on the base of a cusp (ideally NCC or even RCC or LCC) at the aortic root and hence, the distal edge (inflow edge) of the landing zone marker M4 is brought in line with the base of the cusp at the aortic root; in other words, in line with the virtual annular plane 6 as the native coronary cusps are made co-planar wherein the hinge point of each cusp is in a straight line and all the three cusps are well separated (refer to Fig. 8). The virtual annular plane 6 can be visible under fluoroscopy and hence, it also acts as an alternate guiding feature to position the THV 100/200 at the optimal location for implantation. Placing a radiopaque marker in the frame 101/201 of THV 100/200 in the valve free zone helps the operator during implantation.
[00151] As described above, the positioning is achievable when the THV 100/200 is expanded to its nominal diameter which is an ideal situation. In a real case, the operator may be required to over-expand or in some cases, under-expand the THV 100/200 for proper deployment. In such a situation, the operator may have to make little adjustment in locating the landing zone marker M4 relative to the curved distal end 8a of the pigtail catheter 8 i.e. the base of the cusp at the aortic root and the virtual annular plane 6. This adjustment is, however, very small i.e. to the extent of maximum 3 mm. The length of the landing zone marker M4 is preferably kept 3 mm which the operator may use as an indicator for adjusting the position of the crimped THV 100/200 to arrive at desired placement location. The operator may, for example, match the center of the landing zone marker M4 with the curved distal end 8a of the pigtail catheter 8 or the annular plane 6. This situation is shown in Fig. 11a and exploded View B for THV 100 and in Fig. 12a and exploded View B’ for THV 200. In another situation, the operator may, for example, match the proximal edge of the landing zone marker M4 with the curved distal end 8a of the pigtail catheter 8 or the annular plane 6. This situation is shown in Fig. 11b and exploded View C for THV 100 and in Fig. 12b and exploded View C’ for THV 200.
[00152] In some situations, based on the anatomy of the aortic root of the patient, the operator may decide to place the curved distal end 8a of the pigtail catheter 8 at another location, for example at the sinotubular junction 7 (refer to Fig. 7). In such a situation, the operator would have to determine the location of the virtual annular plane 6 with the help of fluoroscopy as detailed above and position the THV 100/200 such that appropriate location of the landing zone marker M4 (e.g. the distal edge, the center, or the proximal edge) is in line with the virtual annular plane 6.
[00153] In any situation, the virtual annular plane 6 which is visible under fluoroscopy is a guiding feature to position the THV 100/200 at the optimal location for implantation. As mentioned above, this is made possible because in the frame 101/201 of THV 100/200, the foreshortening of the frame 101/201 of THV 100/200 is absent at the inflow zone due to chevron shape cells. Hence, to an operator, THV deployment is totally predictable when the THV 100/200 is expanded to its nominal diameter. Once the landing zone marker M4 is aligned as described herein, the balloon 301 is inflated to inflate the THV 100/200, thereby resulting in supra-annular deployment of the THV 100/200 in the native annulus.
[00154] In the above description, the THV 100/200 of the instant invention is presented as an aortic prosthetic valve. The description includes details related to its implantation to replace degenerated native aortic valve. However, the THV 100/200 of the instant invention is suitable for implantation in mitral and tricuspid positions also.
[00155] Mitral and Tricuspid heart valve replacement is usually done with a bioprosthetic surgical tissue valve in case there is a degeneration of native valve. Annular repair of mitral and tricuspid heart valve is done in situations where the valve leaflets and apparatus (chordae and papillary muscles) are undamaged. In such situations the repair device is called annuloplasty ring (also referred to as ‘ring’). In case the surgically implanted bioprosthetic valve or surgically implanted annuloplasty ring fails or gets degenerated, surgical redo of degenerated bioprosthetic heart valve or annuloplasty ring is often associated with higher operative risk of surgical mortality. In such cases, transcatheter mitral/tricuspid valve-in-valve or valve-in-ring interventions are known to be safe and offer lower procedural risks allowing for successful clinical outcomes.
[00156] In case of a mitral procedure, in order to access the mitral valve, one must cross the septal wall that divides right and left atria (interatrial septum) via the thin fossa ovalis (described below). The common route to mitral valve is normally through common femoral vein to inferior vena cava to right atrium (alternately, one may also reach right atrium via superior vana cava) where the interatrial septum (IS) is crossed by puncturing the wall at fossa ovalis to left atrium and across the mitral valve.
[00157] Interatrial septal wall is marked by a small oval shaped (or round shaped in a few cases) depression called fossa ovalis. Fossa ovalis (FO) is a preferred site for transseptal puncture as it offers a safe and effective entry point for transseptal puncture because of the following advantages: (a) FO is relatively easy to access, (b) the tissues covering FO is thinner compared to other parts of the IS, (c) FO is away from the tricuspid and mitral valves as well as other critical structures.
[00158] In case of a tricuspid procedure, in order to get access to the tricuspid Valve, one simply goes from right atrium to right ventricle via the tricuspid valve. In this case, transseptal puncture is not required. The route to tricuspid valve is normally through common femoral vein to inferior vena cava to right atrium and across the tricuspid valve to right ventricle (alternatively via superior vena cava as mentioned above).
[00159] If transcatheter mitral/tricuspid valve-in-valve intervention procedure is done in an existing failed bioprosthetic valve in mitral position, it is called Transcatheter Mitral Valve-in-Valve (V-i-V) Replacement (TMVR). If this procedure is done in an existing failed annuloplasty ring in mitral position, it is called Transcatheter Mitral Valve-in-Ring (V-i-R) Replacement. If this procedure is done in an existing failed bioprosthetic valve in tricuspid position, it is called Transcatheter Tricuspid Valve-in-Valve (V-i-V) Replacement (TTVR). If this procedure is done in an existing failed annuloplasty ring in tricuspid position, it is called Transcatheter Tricuspid Valve in Ring (V-i-R) Replacement. The THV 100/200 of the instant invention is suitable for mitral/tricuspid implantation using V-i-V (TMVR/TTVR) and V-i-R procedures. The THV 100/200 of the instant invention is also suitable for replacing degenerated previously implanted prosthetic valve in aortic position.
[00160] The native mitral valve is anatomically connected to the aortic valve and posteriorly placed. The anterior leaflet of the mitral valve towards the aortic side creates the left ventricular outflow tract (LVOT). During TMVR, especially V-i-V procedure, it is common practice to measure neo-LVOT to ensure that the THV device within the failed surgical valve does not cause neo-LVOT Obstruction (Neo-LVOTO). This is done using CT measurement and is known to the experts in the field.
[00161] The native tricuspid valve is located between the right atrium (RA) and the right ventricle (RV). The blood flows from RA across the tricuspid valve towards the RV and then into the pulmonary artery. Like there is LVOT, there is also a right ventricular outflow tract RVOT. Unlike the potential for anterior mitral valve leaflet to cause neo-LVOTO, the chances of neo-RVOTO obstructing flow to pulmonary valve is unlikely due to its anatomical location.
[00162] Short frame balloon expandable valves are a treatment of choice due to their lower foot-print and ability to be negotiated easily across the fossa ovalis. Further, short frame height prevents neo-left ventricular outflow tract obstruction (neo-LVOTO). Fig. 13 depicts anatomy of the human heart H schematically in a simplified manner as anatomical vertical section which is not drawn with precision. A skilled person is well familiar with function and anatomy of human heart. The four chambers of heart are shown in Fig. 13 as left atrium LA, left ventricle LV, right atrium RA and right ventricle RV. LA and RA are separated by a wall of muscular tissue viz. interatrial septum IS. LV and RV are separated by a wall viz. ventricular septum Vs. LA and LV are in communication through mitral valve MV. RA and RV are in communication through tricuspid valve TV.
[00163] Normally, the access to the mitral valve is achieved by transseptal approach through right atrium as mentioned above. The procedure involves access first to RA via common femoral vein and inferior vena cava VC as depicted in Fig. 14 showing human heart H depicted in Fig. 13. The alternate route through superior vena cava is not shown. RA and LA are separated by the interatrial septum IS which is a solid muscular wall. IS wall is marked by a small oval shaped (or round shaped in a few cases) depression called fossa ovalis. Fossa ovalis (FO) is a preferred site for transseptal puncture as mentioned above.
[00164] Using routine trans-esophageal echo-based (TEE) imaging, a guide wire (GW) is placed across the fossa-ovalis FO using trans-septal puncture techniques into LA crossing mitral annulus. Fig. 14 is a schematic simplified schematic representation of the human heart H (like Fig. 13) for illustrating the transeptal procedure. As shown in Fig. 14, the balloon expandable THV system BS with THV 100/200 mounted on the balloon under collapsed condition is introduced over the guide wire GW.
[00165] A skilled person would readily realize that for approach to the tricuspid valve TV, it is not necessary to cross the IA wall and hence, transseptal puncture is not required.
[00166] The delivery system i.e. an exemplary delivery catheter 300’ for implantation of the THV 100/200 in mitral/tricuspid is depicted in Fig. 15. The delivery catheter 300’ is similar to the delivery catheter 300 depicted in Fig. 6 except the position of radiopaque landing zone marker M4 as described below. The frame structure of THV 100/200 and the delivery catheter 300’ of the instant invention provide an easy and accurate method for supra-annular deployment of the THV 100/200 at the target location in mitral/tricuspid position. Fig. 15a shows the details of the balloon 301’ which is similar to the balloon 301 depicted in Fig. 6. Hence, the nomenclature of other components in Fig. 15 and 15a is same as that in Fig. 6. However, the location of the radiopaque landing zone marker band M4 is changed compared to that shown in Fig. 6. As shown in Fig. 15a, the landing zone marker M4 is placed between the proximal and mid marker bands M1, M3 at a distance of around 32-34% of the distance between proximal and distal markers M1, M2 from the proximal end marker M1 i.e. dimension B is 32-34% of dimension A as shown in FIG. 15a.
[00167] The distal edge of the proximal marker M1 is in line with the distal edge of the proximal stopper 309a as shown by the broken line L1. Similarly, the proximal edge of the distal marker M2 is in line with the proximal edge of the distal stopper 309b as shown by the broken line L2. This feature fixes exact location of all the radiopaque markers.
[00168] The balloon catheter 300’ of the instant invention involves a differential diameter tapered balloon such that when expanded at its nominal pressure, it inflates (expands) attaining varying diameter across its axial length. These diameters are referred to as nominal diameters. Fig. 15b shows the balloon 301’ schematically with the proximal end A and distal end B. The balloon 301’ is attached to the distal end of the outer shaft 303. The stoppers 309a and 309b are also shown. Radiopaque markers and other details are not shown for clarity. The shoulders (conical end portions) of the balloon 301’ are marked as E1 (proximal end) and E2 (distal end). The middle portion, where the THV 100/200 is located in crimped configuration is tapered and is marked as E3. As shown in Fig. 15b, the nominal diameter D1’ at the proximal end A of the balloon 301’ in expanded configuration is smaller than the nominal diameter D2’ at its distal end B. The difference between the largest diameter D2’ and the smallest diameter D1’ may be between 1 and 2.5 mm. In other embodiment, this difference may be more than 2.5 mm.
[00169] The nominal expansion diameter D1’ of the balloon 301’ at its proximal end A may preferably be matched to the nominal diameter of the prosthetic valve crimped over it which closely approximates to the annulus diameter of the degenerated bioprosthetic valve or damaged/degenerated annuloplasty ring. The balloon 301’ has a higher diameter D2’ towards the outflow zone (distal zone). The balloon 301’ shown in Fig. 15b has a uniform taper from proximal to distal ends of the balloon 301’ i.e. the balloon 301’ has a conical shape when expanded. Alternately, the balloon 301’ may have a stepped construction i.e. it has a lower diameter in the inflow zone (proximal zone, which is, for example, about 1/3 of the total active length of the balloon 301’) and a larger diameter in the outflow zone (distal zone, which is, for example, about 2/3 of the total active length of the balloon 301’).
[00170] Accurate placement and precise deployment of a prosthetic valve in mitral/tricuspid position is very important to achieve optimal performance; implanting the prosthetic valve at optimal location achieves better anatomical placement of the THV 100/200 whereby the inflow end 100a/200a of the frame 101/201 (valve free zone) is held firmly within the degenerated bioprosthetic valve annulus or annulus of the previously implanted annuloplasty ring, thereby offering geographical fix. In other words, the valve free zone at its inflow end 100a/200a is anchored at the degenerated bioprosthetic valve annulus or annulus of the previously implanted annuloplasty ring with leaflets sutured above the anchoring zone i.e. in supra annular position and the distal (outflow) zone which houses the prosthetic leaflets has higher diameter due to tapered shape and hence offers higher EOA.
[00171] When THV 100/200 is crimped on the balloon 301’ (with changed location of radiopaque landing zone marker M4) of the delivery system 300’, the in-flow zone of the THV 100/200 is towards the proximal end and the out-flow zone is towards distal end (towards the soft tip 315). This positioning is technically reverse crimping to that done in the case of THV 100/200 for aortic implantation described above. The THV system is maneuvered across the fossa ovalis FO and further advanced towards neo mitral annulus to cross the degenerated bioprosthetic valve or the previously implanted annuloplasty ring. Depending on (a) the anatomical presentation of the failed bioprosthetic valve/annuloplasty ring in mitral position, (b) the neo-LVOT area available (calculated during pre-procedure planning), (c) the foreshortening characteristics of THV frame of the prosthetic valve to be implanted (THV 100/200) and (d) the nominally expanded THV frame height, the THV 100/200 is positioned across the in-flow zone of the bioprosthetic valve/annuloplasty ring in most balanced footprint of the THV 100/200 in the left ventricle. The description below is provided in the context of implanting the THV 100/200 at the mitral position by way of example. A person skilled in the art will appreciate that a similar procedure is applicable, mutatis mutandis, for implanting the THV 100/200 at the tricuspid position without deviating from the scope of the present disclosure.
[00172] Fig. 16 depicts a schematic representation of view J (refer to Fig. 13) showing left atrium LA with THV 100 implanted at within the degenerated surgical bioprosthetic valve 1601 (also referred to as degenerated bioprosthetic valve 1601). The anatomical representation of LA is only schematic and not drawn with precision. THV frame 101 in any situation - either implanted in degenerated prosthetic valve or in degenerated/damaged annuloplasty ring is not to scale. Only the frame 101 of THV 100 (without leaflets/skirts etc.) is shown for clarity. The inflow end 100a of the THV 100 is towards LA and the outflow end 100b is towards LV. Left ventricle LV and right atrium RA are marked for reference. Virtual annular plane 6 (refer to Fig. 7) is also marked. The native leaflets of the mitral valve are marked as Lf. The suture ring of the bioprosthetic valve 1601 is marked as 1602. In an embodiment, as shown in Fig. 16, 80%-95% of the length of the expanded THV 100 remains below the virtual annular plane 6 (deployment zone) while, the residual 5%-20% of the length of the expanded THV 100 dwells above the virtual annular plane 6. This 80-20 to 95-5 ventricle to atrium positioning is possible due to reduced foreshortening of the frame 101 of the THV 100 of the instant invention.
[00173] Fig. 16a depicts a schematic representation of view J (refer to Fig. 13) similar to that shown in Fig. 16 with THV 200 implanted at within the degenerated surgical bioprosthetic valve 1601. In an embodiment, as shown in Fig. 16a, 80%-95% of the length of the expanded THV 200 remains above virtual annular plane 6 while, the residual 5%-20% of the length of the expanded THV 200 dwells below the virtual annular plane 6. This 80-20 to 95-5 atrium to ventricle position is possible due to reduced foreshortening of the frame 201 of the THV 200 of the instant invention.
[00174] Fig. 17 depicts a schematic representation of view J similar to Fig. 16, showing left atrium LA with THV 100 implanted at within the damaged/degenerated annuloplasty ring 1700. Only the frame of THV 100 (without leaflets/skirts etc.) is shown for clarity. The inflow end 100a of the THV 100 is towards RA and the outflow end 100b is towards LV. All other nomenclatures are same as described in Fig. 16. Like in Fig. 16 and as shown in Fig. 17, 80%-95% of the length of the expanded THV 100 remains below the virtual annular plane 6 (deployment zone) while, the residual 5%-20% of the length of the expanded THV 100 dwells above the virtual annular plane 6. This 80-20 to 95-5 ventricle to atrium positioning is possible due to reduced foreshortening of the frame 101 of the THV 100 of the instant invention.
[00175] Fig. 17a depicts a schematic representation of view J similar to Fig. 16, showing left atrium LA with THV 200 implanted at within the damaged/degenerated annuloplasty ring 1700. Like in Fig. 17 and as shown in Fig. 17a, for an exemplary embodiment, 80%-95% of the length of the expanded THV 200 remains below the virtual annular plane 6 (deployment zone) while, the residual 5%-20% of the length of the expanded THV 200 dwells above the virtual annular plane 6. This 80-20 or 95-5 ventricle to atrium positioning is possible due to reduced foreshortening of the frame 201 of the THV 200 of the instant invention.
[00176] The frames 101/201 of THV 100 and THV 200 are described earlier and are depicted in Figs. 1b and 2b. The description is not repeated here for brevity and the reader is directed to appropriate sections above.
[00177] The THV 100/200 is crimped on the balloon 301’ between the two stoppers 309a, 309b and two extreme radiopaque markers M1, M2. Figs. 18 and 18a depict schematically the frames 101 and 201 respectively of the THV 100 and 200 (as depicted in FIGs. 1/1b and 2/2b) mounted on the balloon 301’ under collapsed condition as visible under fluoroscopy. A and B indicate proximal and distal ends respectively. The other components of the THV 100/200 are not shown for clarity and only the frame 101/201 would be visible clearly under fluoroscopy as it is made from radiopaque material.
[00178] The angled struts (also referred to as ‘V-struts’) of the row of angled struts on the inflow end 100a/200a of the frame 101/201 (lower row 10c/20c, refer to Fig. 1b/2b) play an important role in accurate placement of the THV. Fig. 18 depicts the lower row 10c at the proximal end A where the V-struts’ Vs are seen nested close to each other in the exploded View Z. The converging of these V-struts’ Vs commences at the proximal edge (the edge towards the inflow end 100a of the frame 101) of the landing zone marker M4 and the apex Ax of a V-struts’ Vs is visibly away from the proximal edge of the landing zone marker M4 towards the proximal direction A.
[00179] The angled struts (also referred to as ‘V-struts’) of the row of angled struts on the inflow end 200a of the frame 201 (lower row 20c, refer to Fig. 2b) similarly play an important role in accurate placement of the THV 200. Fig. 18a depicts the lower row 20c at the proximal end A where the V-struts’ Vs are seen nested close to each other in the exploded View Z’. The converging of these V-struts’ Vs commences at the proximal edge (the edge towards the inflow end 200a of the frame 201) of the landing zone marker M4 and the apex Ax’ of a V-struts’ Vs is visibly away from the proximal edge of the landing zone marker M4 towards the proximal direction A. In other words, a peak of two consecutive angled struts in the lower row 10c/20c of angled struts coincides with the edge of the landing zone marker M4 disposed towards the inflow end 200a (in this case, the proximal edge), when the THV 100/200 is crimped on the delivery catheter 300’.
[00180] For accurate placement, the THV 100/200 crimped on the balloon 301’ of the delivery catheter 300’ is advanced across the annulus of degenerated bioprosthetic valve 1601 (a degenerated bioprosthetic mitral valve in this case) till the proximal edge of the landing zone marker M4 comes in line i.e. matched with the upper (proximal) edge of the suture ring 1602 of the bioprosthetic valve 1601. This scenario is depicted in Figs. 19 (for THV 100) and 19a (for THV 200) and the exploded View A and A’ for clarity. Under fluoroscopy, the frame 101/201 of the THV 100/200 is visible with clarity. A brief angiogram with a small volume of diluted contrast helps opacify and locates the virtual annular plane 6 and the suture ring 1602 of bioprosthetic valve 1601. This helps the operator to ensure precise positioning of THV 100/200 prior to its deployment. Under rapid pacing of the heart, due to its aforementioned foreshortening characteristics, when expanded to its nominal diameter at this location, the THV 100/200 gets deployed at optimal position in the annulus of the bioprosthetic valve 1601. This is made possible because the foreshortening of the frame 101/201 of THV 100/200 is absent at the inflow zone due to chevron shape. Hence, this is totally predictable when the Valve is expanded to its nominal diameter.
[00181] As described above, the positioning is achievable when the THV 100/200 is expanded to its nominal diameter which is an ideal situation. In a real case, the operator may be required to over-expand or in some cases, under-expand the THV 100/200 for proper deployment. In such a situation, the operator may have to make little adjustment in locating the landing zone marker M4 relative to the proximal edge of the suture ring 1602 of the bioprosthetic valve 1601. This adjustment is, however, very small i.e. to the extent of maximum 3 mm. The length of the landing zone marker M4 is preferably kept 3 mm which the operator may use as an indicator for adjusting the position of the crimped THV 100/200 to arrive at desired placement location. The operator may, for example, match the center of the landing zone marker M4 with the upper (proximal) edge of the suture ring 1602. This situation is shown in Figs. 20 (for THV 100) and Fig. 20a (for THV 200) and the exploded View B and B’ for clarity. In another situation, the operator may, for example, match the distal edge of the landing zone marker M4 with the proximal edge of the suture ring 1602. This situation is shown in Fig. 21 (for THV 100) and Fig. 21a (for THV 200) and the exploded View C and C’. Once the landing zone marker M4 is aligned as described herein, the balloon 301’ is inflated to inflate the THV 100/200, thereby resulting in supra-annular deployment of the THV 100/200 in the annulus of the bioprosthetic valve 1601.
[00182] For accurate placement, the THV 100/200 in the annulus of the damaged/degenerated annuloplasty ring (or ring) 1700, THV 100/200 crimped on the balloon 301’ of the delivery catheter 300’ is advanced across the annulus of the ring 1700 till the proximal edge of the landing zone marker M4 comes in line i.e. matched with the upper (proximal) edge of the ring 1700. This scenario is depicted in Fig. 22 (for THV 100) and Fig. 22a (for THV 200) and the exploded View A” and A’’’ for clarity. Under fluoroscopy, the frame 101/201 of the THV 100/200 is visible with clarity. A brief angiogram with a small volume of diluted contrast helps opacify and locates the virtual annular plane 6 and the ring 1700. Under rapid pacing of the heart, due to its aforementioned foreshortening characteristics, when expanded to its nominal diameter at this location, the THV 100/200 gets deployed at optimal position in the annulus of the ring 1700. This is made possible because the foreshortening of the frame 101/201 of THV 100/200 is absent at the inflow zone due to chevron shape. Hence, this is totally predictable when the Valve is expanded to its nominal diameter.
[00183] As described above, the positioning is achievable when the THV 100/200 is expanded to its nominal diameter which is an ideal situation. In a real case, the operator may be required to over-expand or in some cases, under-expand the THV 100/200 for proper deployment. In such a situation, the operator may have to make little adjustment in locating the landing zone marker M4 relative to the upper (proximal) edge of the ring 1700. This adjustment is, however, very small i.e. to the extent of maximum 3 mm. The length of the landing zone marker M4 is preferably kept 3 mm which the operator may use as an indicator for adjusting the position of the crimped THV 100/200 to arrive at desired placement location. The operator may, for example, match the center of the landing zone marker M4 with the upper (proximal) edge of the ring 1700. This situation is shown in Fig. 23 (for THV 100) and Fig. 23a (for THV 200) and exploded View B” and B’’’. In another situation, the operator may, for example, match the distal edge of the landing zone marker M4 with the upper (proximal) edge of the ring 1700. This situation is shown in Fig. 24 (for THV 100) and Fig. 24a (for THV 200) and exploded View C” and C’’’. Once the landing zone marker M4 is aligned as described herein, the balloon 301’ is inflated to inflate the THV 100/200, thereby resulting in supra-annular deployment of the THV 100/200 in the annulus of the bioprosthetic valve 1601.
[00184] The scope of the invention is only limited by the appended patent claims. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used. ,CLAIMS:WE CLAIM:
1. A prosthetic valve (100, 200) comprising:
• A radially collapsible and expandable support frame (101, 201) having an inflow end (100a, 200a), an outflow end (100b, 200b) and a plurality of rows of cells extending axially between the inflow end (100a, 200a) and the outflow end (100b, 200b), wherein the plurality of rows of cells includes at least:
o an upper row of cells (101b2, 201b2) provided at the outflow end (100b, 200b) and comprising interlaced first polygonal cells, two consecutive first polygonal cells include one of a common diamond shaped cell (101c1, 201c) or a rhombus body (101d, 201d);
o a lower row of cells (101b1, 201b1) provided at the inflow end (100a, 200a) and comprising interlaced chevron shaped second polygonal cells, two consecutive second polygonal cells include one of a common link (L) or a common axially extending strut (L’), the link includes a straight strut portion (S) followed by a diamond shaped cell (101c2); and
o a valve-free zone towards the inflow end (100a, 200a) enabling supra-annular deployment of the valve, thereby, providing a higher effective orifice area (EOA).
2. The prosthetic valve (100, 200) as claimed in claim 1 wherein, the upper row of cells (101b2, 201b2) includes:
• an upper row (10a, 20a) and an intermediate row (10b, 20b) of angled struts having an undulating shape, two consecutive angled struts of the intermediate row (10b, 20b) or the upper row (10a, 20a) form a peak or a valley,
wherein the valleys (V2, V2’) of the intermediate row (10b, 20b) of angled struts face the peaks (P1, P1’) of the upper row (10a, 20a) of angled struts.
3. The prosthetic valve (100, 200) as claimed in claim 1 wherein, the lower row of cells includes:
• a lower row (10c, 20c) and an intermediate row (10b, 20b) of angled struts, two consecutive angled struts of the lower row (10c, 20c) or the intermediate row (10b, 20b) form a peak or a valley;
wherein the peaks (P3, P3’) of the lower row (10c, 20c) of angled struts face the peaks (P2, P2’) of the intermediate row (10b, 20b) of angled struts.
4. The prosthetic valve (100, 200) as claimed in claim 1 wherein, the first polygonal cells are octagonal cells.
5. The prosthetic valve (100, 200) as claimed in claim 1 wherein, the second polygonal cells are one of hexagonal or decagonal cells.
6. The prosthetic valve (100, 200) as claimed in claim 1 wherein, the first polygonal cells in the upper row of cells (101b2, 201b2) are one of larger than or equal to the second polygonal cells in the lower row of cells (101b1, 201b1), in size.
7. A prosthetic valve (100) comprising:
• a radially collapsible and expandable support frame (101) having an inflow end (100a), an outflow end (100b) and a plurality of rows of cells extending axially between the inflow end (100a) and the outflow end (100b), wherein the plurality of rows of cells include at least:
o an upper row of cells (101b2) provided at the outflow end (100b) and comprising interlaced octagonal cells;
o a lower row of cells (101b1) provided at the inflow end (100a) and comprising interlaced chevron shaped decagonal cells; and
o a valve-free zone towards the inflow end (100a).
8. The prosthetic valve (100) as claimed in claim 7, wherein the upper row of cells (101b2) comprises:
• an upper row (10a) and an intermediate row (10b) of angled struts having an undulating shape, two consecutive angled struts of the intermediate row (10b) or the upper row (10a) form a peak or a valley,
wherein the peaks (P2) of the intermediate row (10b) of angled struts face the valleys (V1) of the upper row (10a) of angled struts and are connected to each other using one of a diamond shaped cell (101c1) or a rhombus body (101d), forming interlaced octagonal cells.
9. The prosthetic valve (100) as claimed in claim 7, wherein, the lower row of cells (101b1) comprises:
• a lower row (10c) and an intermediate row (10b) of angled struts, two consecutive angled struts of the lower row (10c) or the intermediate row (10b) form a peak or a valley;
wherein the valleys (V3) of the lower row (10c) of angled struts face the valleys (v2) of the intermediate row (10b) of angled struts and are connected to each other using a link (L) comprising a straight strut portion (S) followed by a diamond shaped cell (101c2), forming interlaced chevron shaped decagonal cells.
10. The prosthetic valve (100, 200) as claimed in any of claims 1 – 9, wherein, the valve-free zone extends from a leaflet suturing line till the inflow end (100a, 200a) of the support frame (101, 201).
11. The prosthetic valve (100, 200) as claimed in any of claims 1 – 9, wherein, the support frame (101, 201) is configured to attain a tapered configuration upon expansion via a tapered balloon.
12. The prosthetic valve (100, 200) as claimed in any of claims 1 - 9, wherein the plurality of rows of cells comprises two rows of cells.
13. The prosthetic valve (100, 200) as claimed in any of claims 1 - 9, wherein the prosthetic valve (100, 200) comprises at least one intermediate row of cells disposed between the upper row of cells (101b2, 201b2) and the lower row of cells (101b1, 201b1), the at least one intermediate row of cells comprising interlaced polygonal cells.
14. The prosthetic valve (100, 200) as claimed in any of claims 1 - 9, wherein, the upper row of cells (201b2) occupies 50% - 70% of total height of the support frame (201).
15. The prosthetic valve (100, 200) as claimed in claims 14, wherein, the upper row of cells (101b2) occupies around 55% of total height of the support frame (101).