Delivery assemblies with everting sleeves

Abstract

The present disclosure relates to delivery assemblies comprising inverting sleeves. In an example, a delivery assembly comprises a delivery apparatus comprising an inverting sleeve. The inverting sleeve comprises a first portion extending from a proximal end thereof, and a second portion continuously extending from the first portion and terminating at a second end of the inverting sleeve. The inverting sleeve is configured to transition between an inverted state, in which the sleeve is folded over itself such that the second portion is surrounded by the first portion, and an at least partially everted state, in which the at least part of the second portion is turned radially outwards relative to the inverted state. The delivery assembly further comprises a prosthetic valve, configured to be distally advanced by the delivery apparatus during eversion of the inverting sleeve. The prosthetic valve comprises a frame movable between radially compressed and expanded configurations.

Description

DELIVERY ASSEMBLIES WITH EVERTING SLEEVESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 669,594, filed July 10, 2024, which is incorporated by reference herein.FIELD

[0002] The present disclosure relates to delivery systems, and in particular, to delivery systems of prosthetic valves designed to reduce the risk of damage to the blood vessels during advancing of the delivery apparatus therein.BACKGROUND

[0003] Native heart valves, such as the aortic, pulmonary and mitral valves, function to assure adequate directional flow from and to the heart, and between the heart's chambers, to supply blood to the whole cardiovascular system. Various valvular diseases can render the valves ineffective and require replacement with artificial valves. Traditionally, defective heart valves were treated by open-heart surgery, which is highly invasive, prone to complications, and requires extended recovery periods for patients. In recent years, there has been a surge in the popularity of prosthetic heart valves, which can be delivered with significantly less invasiveness than open-heart surgery. The popularity of prosthetic heart valves has led to accelerated research and development in this field.

[0004] To evade surgical interventions, alternative techniques based on delivering a prosthetic heart valve over a catheter and implanting it over the native malfunctioning valve, have been developed over the years. Delivery apparatuses are used to implant prosthetic devices, such as a prosthetic heart valve, at locations inside the body that are not readily accessible by surgery or where access without invasive surgery is desirable. For example, aortic, mitral, tricuspid, and / or pulmonary prosthetic heart valves can be delivered to a treatment site using minimally invasive surgical techniques. The delivery apparatus, carrying a prosthetic valve, can be introduced into the body through a small incision, and advanced to the location of treatment by an external operator.

[0005] Various catheters and sheaths are used in transcatheter procedures to aid in valve delivery. An introducer sheath may be used to introduce a delivery apparatus into a patient's vasculature (e.g., the femoral artery). Expandable introducer sheaths have been developed to accommodate larger prostheses and delivery systems, providing protection to blood vesselsfrom damage during passage. These expandable sheaths can locally expand to accommodate relatively large features passing through them, potentially reducing trauma to blood vessel walls. Consequently, there is a shift towards using expandable sheaths as delivery systems instead of traditional stiff tube sheaths.SUMMARY

[0006] When a delivery apparatus carries a prosthetic valve to replace a malfunctioning native valve, the introducer sheath and delivery catheter move in an axial direction relative to the wall of the blood vessel, running a relatively high risk of injuring or otherwise producing trauma to the blood vessel wall. This risk is severely increased when delivering the valve involves advancing through sensitive, narrow or complex blood vessels. In addition, navigating the delivery apparatus towards the target site of the prosthetic valve requires constant surveillance and optional intervention, and / or insertion of a guidewire which further clutters the already crowded blood vessel. The present disclosure is directed towards a delivery apparatus comprising an inverting sleeve, which significantly reduces the risk of harming the blood vessel during advancement therein. The presently disclosed apparatus may also improve the navigation of the delivery apparatus within the vasculature, optionally allowing self-navigation thereof, and may further eliminate the need for an introducer sheath.

[0007] In one of its basic configurations, a delivery assembly comprises a prosthetic valve and a delivery apparatus comprising an inverting sleeve, wherein the inverting sleeve is configured to transition between an inverted state, in which the inverting sleeve is folded over itself, and an at least partially everted state, and wherein the prosthetic valve is configured to be distally advanced by the delivery apparatus during eversion of the inverting sleeve. This basic configuration can preferably be provided with any one or more of the features described elsewhere herein, in particular with those of the examples described hereafter. However, it should be understood that the basic configuration can preferably also be provided with any one or more of the features shown in the figures and / or described in conjunction with the figures, either in addition to or alternatively to the features of the examples described hereafter.

[0008] In some examples, the inverting sleeve can optionally comprise a first portion and a second portion, wherein the first portion of the inverting sleeve extends from a proximal end of the inverting sleeve.

[0009] In some examples, the second portion of the inverting sleeve can optionally continuously extend from the first portion of the inverting sleeve.

[0010] In some examples, the second portion can terminate at a second end of the inverting sleeve.

[0011] In some examples, in the inverted state, the inverting sleeve can be folded over itself such that the second portion is surrounded by at least a part of the first portion.

[0012] In some examples, in the at least partially everted state, at least part of the second portion can optionally be turned radially outwards relative to the inverted state.

[0013] In some examples, the prosthetic valve can optionally comprise a frame movable between a radially compressed configuration and a radially expanded configuration.

[0014] In some examples, the prosthetic valve can optionally be coupled to the second portion of the inverting sleeve.

[0015] In some examples, the prosthetic valve can be crimped over a bulge formed by the second portion of the inverting sleeve.

[0016] In some examples, the delivery assembly can optionally further comprise a balloon catheter having a proximal end and a distal end and comprising a balloon at the distal end, wherein the balloon catheter extends longitudinally through the inverting sleeve.

[0017] In some examples, the balloon catheter can optionally be coupled to the inverting sleeve.

[0018] In some examples, the second end of the inverting sleeve can be attached to the balloon catheter.

[0019] In some examples, the delivery assembly can optionally further comprise a push- member that extends radially outwards, positioned distally to the inverting sleeve, and configured to be contacted by and advanced distally by the inverting sleeve when the inverting sleeve is being everted.

[0020] In some examples, the delivery apparatus can be liquid- tight.

[0021] In some examples, the delivery apparatus can be air-tight.

[0022] In some examples, the inverting sleeve, when in the inverted state, can optionally define a cavity between the first portion and the second portion.

[0023] In some examples, the delivery assembly can optionally further comprise a fluid inlet in fluid communication with the cavity defined by the inverting sleeve, wherein introduction of fluid through the fluid inlet into the cavity is configured to induce eversion of the inverting sleeve.

[0024] In some examples, the delivery assembly can optionally further comprise a biasing member having a proximal end and a distal end, wherein the biasing member is configured tocontrollably transition between at least two of a compressed state, a relaxed state, and a stretched state.

[0025] In some examples, the proximal end of the biasing member can be axially fixed relative to the proximal end of the inverting sleeve.

[0026] In some examples, the biasing member can be a spring.

[0027] In some examples, the delivery assembly can optionally further comprise a sleeve housing configured to contain at least part of the inverting sleeve when in the inverted state, wherein the sleeve housing comprises, at a distal end thereof, a sleeve-passage sized to allow passage of the inverting sleeve therethrough.

[0028] In some examples, the delivery assembly can optionally further comprise a funnel crimper distally extending from the sleeve-passage, wherein the funnel crimper extends from a narrow opening which is closer to the sleeve passage, to a wide opening which is farther from the sleeve passage.

[0029] In some examples, the narrow opening of the funnel crimper can optionally be sized to allow passage of the prosthetic valve when in the radially compressed configuration.

[0030] In some examples, the wide opening of the funnel crimper can optionally be sized to allow insertion of the prosthetic valve, when in the expanded configuration, into the funnel crimper.

[0031] In some examples, the diameter of the second end of the inverting sleeve, when in the everted state, can optionally be larger than the diameter of the proximal end of the inverting sleeve.

[0032] In one of its basic configurations, an introducer device assembly comprises an introducer sheath and a distal end portion comprising an inverting sleeve, wherein the inverting sleeve is configured to transition between an inverted state and an everted state. This basic configuration can preferably be provided with any one or more of the features described elsewhere herein, in particular with those of the examples described hereafter. However, it should be understood that the basic configuration can preferably also be provided with any one or more of the features shown in the figures and / or described in conjunction with the figures, either in addition to or alternatively to the features of the examples described hereafter.

[0033] In some examples, the introducer sheath can define a lumen and extend between a proximal end and a distal end of the introducer sheath.

[0034] In some examples, a proximal end of the inverting sleeve can optionally be coupled to the distal end of the introducer sheath.

[0035] In some examples, the inverting sleeve can optionally comprise a first portion and a second portion, wherein the first portion extends from the proximal end of the inverting sleeve.

[0036] In some examples, the second portion can optionally continuously extend from the first portion.

[0037] In some examples, the second portion can terminate at a second end of the inverting sleeve.

[0038] In some examples, in the inverted state the inverting sleeve can optionally be folded over itself such that the second portion is surrounded by at least a part of the first portion.

[0039] In some examples, in the everted state at least part of the second portion of the inverting sleeve can be turned radially outwards relative to the inverted state.

[0040] In some examples, the distal end portion can optionally define a distal opening which is in fluid communication with the lumen of the introducer sheath.

[0041] In some examples, when the inverting sleeve is in the inverted state, the distal end portion can be configured to be in an inverted collapsed state, such that the distal opening is smaller than the diameter of the sheath.

[0042] In some examples, the inverting sleeve, when in the inverted state, can optionally define a cavity between the first portion and the second portion.

[0043] In some examples, the introducer device assembly can further comprise a fluid inlet in fluid communication with the cavity defined by the inverting sleeve, wherein introduction of fluid through the fluid inlet into the cavity is configured to induce eversion of the inverting sleeve.

[0044] In one of its basic configurations, a delivery apparatus comprises an inverting sleeve, wherein the inverting sleeve is configured to transition between an inverted state, in which the inverting sleeve is folded over itself, and an at least partially everted state. This basic configuration can preferably be provided with any one or more of the features described elsewhere herein, in particular with those of the examples described hereafter. However, it should be understood that the basic configuration can preferably also be provided with any one or more of the features shown in the figures and / or described in conjunction with the figures, either in addition to or alternatively to the features of the examples described hereafter.

[0045] In some examples, the inverting sleeve can optionally be sized to be advanced within vasculature of a subject.

[0046] In some examples, the inverting sleeve can optionally comprise a first portion and a second portion, wherein the first portion of the inverting sleeve extends from a proximal end of the inverting sleeve.

[0047] In some examples, the second portion of the inverting sleeve can optionally continuously extend from the first portion of the inverting sleeve.

[0048] In some examples, the second portion can terminate at a second end of the inverting sleeve.

[0049] In some examples, in the inverted state, the inverting sleeve can be folded over itself such that the second portion is surrounded by at least a part of the first portion.

[0050] In some examples, in the at least partially everted state, at least part of the second portion can optionally be turned radially outwards relative to the inverted state.

[0051] In some examples, the delivery apparatus can be liquid- tight.

[0052] In some examples, the delivery apparatus can be air-tight.

[0053] In some examples, the second end of the inverting sleeve can optionally be a closed end.

[0054] In some examples, the inverting sleeve, when in the inverted state, can optionally define a cavity between the first portion and the second portion.

[0055] In some examples, the delivery assembly can optionally further comprise a fluid inlet in fluid communication with the cavity defined by the inverting sleeve, wherein introduction of fluid through the fluid inlet into the cavity is configured to induce eversion of the inverting sleeve.

[0056] In some examples, the delivery apparatus can optionally further comprise a biasing member having a proximal end and a distal end, wherein the biasing member is configured to controllably transition between at least two of a compressed state, a relaxed state, and a stretched state.

[0057] In some examples, the proximal end of the biasing member can be axially fixed relative to the proximal end of the inverting sleeve.

[0058] In some examples, the delivery apparatus can optionally further comprise a tissue engagement sleeve releasably disposed over an outer surface of at least part of the inverting sleeve.

[0059] In some examples, at least a portion of the inverting sleeve can optionally be a stretchable portion.

[0060] The aspects of this disclosure can be used in combination or separately. This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter. The foregoing and other objects, features, and advantages of theinvention will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.BRIEF DESCRIPTION OF THE FIGURES

[0061] Some examples of the invention are described herein with reference to the accompanying figures. The description, together with the figures, makes apparent to a person having ordinary skill in the art how some examples may be practiced. The figures are for the purpose of illustrative description and no attempt is made to show structural details of an example in more detail than is necessary for a fundamental understanding of the invention. For the sake of clarity, some objects depicted in the figures are not to scale.In the Figures:

[0062] Fig. 1 illustrates an exemplary delivery apparatus for a cardiovascular prosthetic device.

[0063] Fig. 2 illustrates an exemplary introducer device assembly.

[0064] Fig. 3 illustrates an exemplary prosthetic valve.

[0065] Fig. 4A illustrates a cross-sectional view of a delivery apparatus comprising an inverting sleeve coupled to a balloon catheter.

[0066] Fig. 4B illustrates the delivery apparatus of Fig. 4A inserted within a blood vessel.

[0067] Fig. 4C is a view of the delivery apparatus of Fig. 4B, with the balloon catheter advanced into a target site.

[0068] Fig. 5A illustrates a cross-sectional view of a delivery apparatus comprising an inverting sleeve with a prosthetic valve crimped on the second portion thereof.

[0069] Fig. 5B is a view of the delivery apparatus of Fig.5 A, in an almost fully everted state.

[0070] Fig. 5C is a view of the delivery apparatus of Fig.5B, in a fully everted state.

[0071] Fig. 6A illustrates a cross-sectional view of a delivery apparatus comprising an inverting sleeve coupled to a balloon catheter, comprising a push member attached to the balloon catheter.

[0072] Fig. 6B illustrates a cross-sectional view of a delivery apparatus comprising an inverting sleeve coupled to a balloon catheter, comprising a push member having a pushmember shaft.

[0073] Fig. 6C is a view of the delivery apparatus of Fig. 6C, with the balloon catheter extended distally.

[0074] Fig. 7A illustrates a cross-sectional view of a delivery apparatus comprising an inverting sleeve, contained within a sleeve housing having a funnel shaped element.

[0075] Fig. 7B is a view of the delivery apparatus of Fig. 7A, showing a prosthetic valve which has been retracted through the funnel shaped element.

[0076] Fig. 7C illustrates a delivery apparatus similar to Figs. 7A-7B, in which the funnel- shaped element is releasably coupled to the sleeve housing.

[0077] Fig. 8 illustrates a cross-sectional view of a delivery apparatus comprising an inverting sleeve and further comprising an introducer ring.

[0078] Fig. 9A illustrates an inverting sleeve in a fully everted state, having a different diameter for the proximal and distal portions thereof.

[0079] Fig. 9B is a view of the inverting sleeve of Fig. 9A, in which the inverting sleeve has been inverted.

[0080] Fig. 9C is a view of the inverting sleeve of Fig. 9B, being introduced into a blood vessel.

[0081] Fig. 9D is a view of the inverting sleeve of Fig. 9C, being everted within the blood vessel.

[0082] Fig. 10A illustrates a cross-sectional view of a delivery apparatus comprising an inverting sleeve within a cardiovascular system, performing pre-ballooning at a target site.

[0083] Fig. 10B is a view of the delivery apparatus of Fig. 10A, in which the inverting sleeve is retracted from the target site and the prosthetic valve is expanded therein.

[0084] Fig. 11 illustrates a cross-sectional view of a delivery apparatus comprising an inverting sleeve and a spring everting element.

[0085] Fig. 12A illustrates a cross-sectional view of a delivery apparatus comprising an inverting sleeve having an implantable member disposed on the outer surface thereof.

[0086] Fig. 12B is a view of the delivery apparatus of Fig. 12A, being retracted following implanting of the implantable member.

[0087] Fig. 13 illustrates a side view of an expandable sheath that can be used in combination with the introducer device assembly of Fig. 2.

[0088] Fig. 14 is a side cross-sectional view of a portion of the expandable sheath of Fig. 13.

[0089] Fig. 15 is a magnified view of a portion of the expandable sheath of Fig. 13.

[0090] Fig. 16A is a magnified view of a portion of the expandable sheath of Fig. 13 with the outer layer removed for purposes of illustration.

[0091] Fig. 16B is a magnified view of a portion of the braided layer of the sheath of Fig. 13.

[0092] Fig. 17 is a magnified view of a portion of the expandable sheath of Fig. 13, illustrating expansion of the sheath as a prosthetic device is advanced through the sheath.

[0093] Fig. 18A shows a distal portion of an exemplary introducer device assembly with a sheath having a distal end portion comprising an inverting sleeve and defining a tapering tip portion.

[0094] Fig. 18B shows a sectional view across line 18B-18B of Fig. 18A.DETAILED DESCRIPTION

[0095] For purposes of this description, certain aspects, advantages, and novel features of the examples of this disclosure are described herein. The disclosed methods, apparatus, and systems should not be construed as being limiting in any way. Instead, the present disclosure is directed toward all novel and nonobvious features and aspects of the various disclosed examples, alone and in various combinations and sub-combinations with one another. The methods, apparatus, and systems are not limited to any specific aspect or feature or combination thereof, nor do the disclosed examples require that any one or more specific advantages be present, or problems be solved. The technologies from any example can be combined with the technologies described in any one or more of the other examples. In view of the many possible examples to which the principles of the disclosed technology may be applied, it should be recognized that the illustrated examples are only preferred examples and should not be taken as limiting the scope of the disclosed technology.

[0096] Although the operations of some of the disclosed examples are described in a particular, sequential order for convenient presentation, it should be understood that this manner of description encompasses rearrangement, unless a particular ordering is required by specific language set forth below. For example, operations described sequentially may in some cases be rearranged or performed concurrently. Moreover, for the sake of simplicity, the attached figures may not show the various ways in which the disclosed methods can be used in conjunction with other methods. Additionally, the description sometimes uses terms like "provide" or "achieve" to describe the disclosed methods. These terms are high-level abstractions of the actual operations that are performed. The actual operations that correspond to these terms may vary depending on the particular implementation and are readily discernible by one of ordinary skill in the art.

[0097] All features described herein are independent of one another and, except where structurally impossible, can be used in combination with any other feature described herein.

[0098] As used in this application and in the claims, the singular forms "a," "an," and "the" include the plural forms unless the context clearly dictates otherwise. Additionally, the terms "have" or "includes" means "comprises". Further, the terms "coupled", "connected", and"attached", as used herein, are interchangeable and generally mean physically, mechanically, chemically, magnetically, and / or electrically coupled or linked and does not exclude the presence of intermediate elements between the coupled or associated items absent specific contrary language. As used herein, "and / or" means "and" or "or", as well as "and" and "or".

[0099] Directions and other relative references may be used to facilitate discussion of the drawings and principles herein, but are not intended to be limiting. For example, certain terms may be used such as "inner," "outer," "upper," "lower," "inside," "outside,", "top," "bottom," "interior," "exterior," "left," right," and the like. Such terms are used, where applicable, to provide some clarity of description when dealing with relative relationships, particularly with respect to the illustrated examples. Such terms are not, however, intended to imply absolute relationships, positions, and / or orientations. For example, with respect to an object, an "upper" part can become a "lower" part simply by turning the object over. Nevertheless, it is still the same part and the object remains the same.

[0100] The term "plurality" or "plural" when used together with an element means two or more of the element. Directions and other relative references (e.g., inner and outer, upper and lower, above and below, left and right, and proximal and distal) may be used to facilitate discussion of the drawings and principles herein but are not intended to be limiting.

[0101] The terms "proximal" and "distal" are defined relative to the use position of a delivery apparatus. In general, the end of the delivery apparatus closest to the user of the apparatus is the proximal end, and the end of the delivery apparatus farthest from the user (e.g., the end that is inserted into a patient’s body) is the distal end. The term "proximal" when used with two spatially separated positions or parts of an object can be understood to mean closer to or oriented towards the proximal end of the delivery apparatus. The term "distal" when used with two spatially separated positions or parts of an object can be understood to mean closer to or oriented towards the distal end of the delivery apparatus. The terms "longitudinal" and "axial" are interchangeable, and refer to an axis extending in the proximal and distal directions, unless otherwise expressly defined.

[0102] It should be understood that the disclosed examples can be adapted to deliver and implant prosthetic devices in any of the native annuluses of the heart (e.g., the aortic, pulmonary, mitral, and tricuspid annuluses), and can be used with any of various delivery approaches (e.g., retrograde, antegrade, transseptal, transventricular, transatrial, etc.).

[0103] Throughout the figures of the drawings, different superscripts for the same reference numerals are used to denote different examples of the same elements. Examples of the disclosed devices and systems may include any combination of different examples of the sameelements. Specifically, any reference to an element without a superscript may refer to any alternative example of the same element denoted with a superscript. In order to avoid undue clutter from having too many reference numbers and lead lines on a particular drawing, some components will be introduced via one or more drawings and not explicitly identified in every subsequent drawing that contains that component.

[0104] Fig. 1 illustrates an exemplary sheath 40 in use with a representative delivery apparatus 10, for the delivering of an implant such as a prosthetic heart valve or other prosthetic implant, to a patient. The delivery apparatus 10 illustrated can generally include a steerable guide catheter 14 and a balloon catheter 16 extending through the guide catheter 14. A prosthetic device, such as a prosthetic valve 50, can be positioned on the distal end of the balloon catheter 16. The guide catheter 14 and the balloon catheter 16 can be adapted to slide longitudinally relative to each other to facilitate delivery and positioning of a prosthetic valve 50 at an implantation site in a patient's body. The sheath 40 is an elongate tube that can include a hemostasis valve at the proximal end of the sheath to stop blood leakage. The guide catheter 14 includes a handle portion 18 and an elongated guide tube or shaft extending from the handle portion 18.

[0105] The prosthetic valve 50 can be delivered into a patient’ s body in a radially compressed configuration, and radially expanded to a radially expanded configuration at the desired deployment site. In the illustrated example, the prosthetic valve 50 is a plastically expandable prosthetic valve that is delivered into the patient’s body in a radially compressed configuration on a balloon of the balloon catheter 16 (as shown in Fig. 1) and then radially expanded to a radially expanded configuration at the deployment site by inflating the balloon (or by actuating another type of expansion device of the delivery apparatus). Further details regarding a plastically expandable heart valve that can be implanted using the devices disclosed herein are disclosed in U.S. Publication No. 2012 / 0123529, which is incorporated herein by reference. In other examples, the prosthetic valve 50 can be a self-expandable heart valve that is restrained in a radially compressed configuration by a sheath or other component of the delivery apparatus and self-expands to a radially expanded configuration when released by the sheath or other component of the delivery apparatus. Further details regarding a self-expandable heart valve that can be implanted using the devices disclosed herein are disclosed in U.S. Publication No. 2012 / 0239142, which is incorporated herein by reference. In still other examples, the prosthetic valve 50 can be a mechanically expandable heart valve that comprises a plurality of struts connected by hinges or pivot joints and is expandable from a radially compressed configurationto a radially expanded configuration by actuating an expansion mechanism that applies an expansion force to the prosthetic valve.

[0106] Further details regarding a mechanically expandable heart valve that can be implanted using the devices disclosed herein are disclosed in U.S. Publication No. 2018 / 0153689, which is incorporated herein by reference. In still other examples, a prosthetic valve can incorporate two or more of the above-described technologies. For example, a self-expandable heart valve can be used in combination with an expansion device to assist expansion of the prosthetic heart valve.

[0107] FIG. 2 illustrates an example of an introducer device assembly 20. The assembly 20 may include the sheath 40 and an introducer 30. The introducer 30 may be positioned within a lumen of the sheath 40, as shown in Fig. 2. A control housing 22 may be positioned at a proximal end of the assembly and may include a sheath housing 24 and an introducer housing 34. The sheath housing 24 and introducer housing 34 may couple together, as shown in Fig. 2.

[0108] The sheath 40 and introducer 30 are shown in an insertion configuration, for insertion together into the patient’s vasculature. Upon insertion into the patient’s vasculature, the introducer 30 may be withdrawn longitudinally from the sheath 40, leaving the sheath 40 within the patient's vasculature.

[0109] The sheath 40 comprises an elongate body that may have a cylindrical shape. The sheath 40 has a sheath distal end 42 and a sheath proximal end 44. The sheath 40 is configured to be inserted into a patient's vasculature. The sheath 40 may further comprise an introducer sheath that is used to introduce a delivery apparatus into the patient's vasculature.

[0110] The vasculature may comprise the blood vessels of the patient's body which may include the femoral artery or other vessels of the patient's body. The vasculature, such as the femoral artery, may be narrow or stiff, and may be difficult to easily insert a delivery apparatus therein. For example, the delivery apparatus may be larger than the vasculature, or may be unwieldy to penetrate through the skin or vasculature of the patient to pass therethrough by itself. Also, the vasculature may be fragile, such that direct insertion of the delivery apparatus may have a risk of causing a tear in the blood vessel.

[0111] The sheath 40 accordingly may be inserted into the patient's vasculature prior to the delivery apparatus being introduced, to provide an entryway or guide path for the delivery apparatus 10 to introduce the delivery apparatus into the patient's vasculature. After the sheath 40 is inserted, the sheath 40 may remain positioned within and surrounded by the patient's vasculature. The delivery apparatus 10 may then be passed through the lumen of the sheath 40for introduction into the patient’s body. The sheath 40 may remain in the vasculature until a desired time to remove the sheath 40.

[0112] The sheath 40 may be inserted into the vasculature percutaneously or a portion of the patient's body may be surgically opened for the sheath 40 to access the vasculature. The delivery apparatus 10 passes through the lumen of the sheath 40 to reach a desired position in the patient’s body. As shown in Fig. 1, the delivery apparatus 10 may pass through an opening at the proximal end of the sheath 40 (the control housing 22 is not shown in Fig. 1) for passage through the lumen of the sheath 40 and the vasculature of the patient.

[0113] The delivery apparatus and the assemblies disclosed herein may be used in transcatheter aortic valve implantation (TAVI). The delivery apparatus and the systems disclosed herein may be utilized for transarterial access, including transfemoral access, to a patient’s heart.

[0114] The sheath 40 may include a strain relief portion 46 at the sheath proximal end 44. The strain relief portion 46 may be sized larger than a proximate portion of the sheath 40 and may seal the entry point of the vasculature, to reduce the possibility of blood or other fluid being released between the exterior surface of the sheath 40 and the vasculature. A seal 48 may be positioned along the length of the sheath 40 to further prevent blood or other fluid flow from passing around the sheath 40 toward and out of the sheath proximal end 44.

[0115] Fig. 3 illustrates a prosthetic valve 50, according to one example. Fig. 3 shows a view in perspective on an exemplary prosthetic valve 50 that can be expanded by a balloon assembly, illustrated in an expanded configuration. The prosthetic valve 50 can comprise an outflow end 301 and an inflow end 302, wherein the height of the valve is defined as the distance between the inflow and outflow ends 302, 301. In some instances, the outflow end 301 is the proximal end of the prosthetic valve 50, and the inflow end 302 is the distal end of the prosthetic valve 50. In some examples, depending for example on the delivery approach of the valve, the outflow end can be the distal end of the prosthetic heart valve, and the inflow end can be the distal end of the prosthetic heart valve. The term "outflow", as used herein, refers to a region of the prosthetic heart valve through which the blood flows through and out of the prosthetic valve 50. The term "inflow", as used herein, refers to a region of the prosthetic heart valve through which the blood flows into the prosthetic valve 50.

[0116] The prosthetic valve 50 comprises an annular frame 310 movable between a radially compressed configuration and a radially expanded configuration, and a valvular structure 360 mounted within the frame 310. The frame 310 can be made of various suitable materials, including plastically-deformable materials such as, but not limited to, stainless steel, a nickel based alloy (e.g., a cobalt-chromium or a nickel-cobalt-chromium alloy such as MP35N alloy),polymers, or combinations thereof. When constructed of a plastically-deformable materials, the frame 310 can be crimped to a radially compressed configuration on the balloon assembly, and then expanded inside a patient by the balloon assembly.

[0117] In the example illustrated in Fig. 3, the frame 310 is an annular, stent- like structure comprising a plurality of intersecting struts 314. A strut 314 may be any elongated member or portion of the frame 310. The frame 310 can include a plurality of strut rungs that can collectively define one or more rows of cells 330. The frame 310 can have a cylindrical or substantially cylindrical shape having a constant diameter from the inflow end 302 to the outflow end 301 as shown, or the frame can vary in diameter along the height of the frame, as disclosed in US Pat. No. 9,155,619, which is incorporated herein by reference.

[0118] The end portions of the struts 314 are forming apices 328 at the outflow end 301 and apices 329 at the inflow end 302. The struts 314 can intersect at additional junctions 327 formed between the outflow apices 328 and the inflow apices 329. The junctions 327 can be equally or unequally spaced apart from each other, and / or from the apices 328, 329, between the outflow end 301 and the inflow end 302.

[0119] At least some of the struts can be pivotable or bendable relative to each other, so as to permit frame expansion or compression. For example, the frame 310 can be formed from a single piece of material, such as a metal tube, via various processes such as, but not limited to, laser cutting, electroforming, and / or physical vapor deposition, while retaining the ability to collapse / expand radially in the absence of hinges and like.

[0120] A valvular structure 360 can include a plurality of leaflets 362 (e.g., three leaflets), positioned at least partially within the frame 310, and configured to regulate flow of blood through the prosthetic valve 50 from the inflow end 302 to the outflow end 301. While three leaflets 362 arranged to collapse in a tricuspid arrangement are shown in the illustrated example, it will be clear that a prosthetic valve 50 can include any other number of leaflets 362. The leaflets 362 can be made from, in whole or part, biological material (e.g., pericardium), bio-compatible synthetic materials, or other such materials. Further details regarding transcatheter prosthetic heart valves, including the manner in which the valvular structures 360 can be coupled to the frame 310 of the prosthetic valve 50, can be found, for example, in U.S. Patent Nos. 6,730,118, 7,393,360, 7,510,575, 7,993,394, 8,652,202, and 11,135,056, all of which are incorporated herein by reference in their entireties.

[0121] The leaflets 362 define a non-planar coaptation plane (not annotated) when free outflow edges thereof co-apt with each other to seal blood flow through the prosthetic valve 50. Adjacent leaflets 362 can be secured to one another to form commissures 380 of the valvularstructure 360, which can be secured, directly or indirectly, to structural elements connected to the frame 310 or integrally formed as portions thereof, such as commissure posts, commissure windows, and the like. When the leaflets 362 are coupled to the frame and to each other, the lower edge of the resulting valvular structure 360 desirably has an undulating, curved scalloped shape. By forming the leaflets with this scalloped geometry, stresses on the leaflets 362 are reduced which, in turn, improves durability of the prosthetic valve. Moreover, by virtue of the scalloped shape, folds and ripples at the belly of each leaflet, which can cause early calcification in those areas, can be eliminated or at least minimized. The scalloped geometry also reduces the amount of tissue material used to form the valvular structure, thereby allowing a smaller, more even crimped profile at the inflow end of the valve.

[0122] In some examples, the prosthetic valve can further comprise at least one skirt or sealing member. Fig. 3 shows an example of a prosthetic valve 50 that includes an inner skirt 306, which can be secured to the inner surface of the frame 310. Such an inner skirt 306 can be configured to function, for example, as a sealing member to prevent or decrease perivalvular leakage. An inner skirt 306 can further function as an anchoring region for valvular structure 360 to the frame 310, and / or function to protect the leaflets 362 against damage which may be caused by contact with the frame 310, for example during valve crimping or during working cycles of the prosthetic valve 50. In some examples, the prosthetic valve 50 can comprise an outer skirt 307 mounted on the outer surface of frame 310, configure to function, for example, as a sealing member retained between the frame 310 and the surrounding tissue of the native annulus against which the prosthetic valve is mounted, thereby reducing risk of paravalvular leakage past the prosthetic valve 50.

[0123] Any of the inner skirt 306 and / or outer skirt 307 can be made of various suitable biocompatible materials, such as, but not limited to, various synthetic materials (e.g., PET) or natural tissue (e.g., pericardial tissue). In some cases, the inner skirt 306 can be formed of a single sheet of material that extends continuously around the inner surface of frame 310. In some cases, the outer skirt 307 can be formed of a single sheet of material that extends continuously around the outer surface of frame 310.

[0124] In some examples, a delivery apparatus 10 comprising a balloon assembly 100 and a prosthetic heart valve assembled thereon, can be packaged in a sterile package that can be supplied to end users for storage and eventual use. In some examples, the leaflets of the prosthetic heart valve (typically made from bovine pericardium tissue or other natural or synthetic tissues) are treated during the manufacturing process so that they are completely or substantially dehydrated and can be stored in a partially or fully crimped state without ahydrating fluid. In this manner, the package containing the prosthetic valve 50 and the delivery apparatus 10 can be free of any liquid. Methods for treating tissue leaflets for dry storage are disclosed in U.S. Pat. Nos. 8,007,992 and 8,357,387, both of which documents are incorporated herein by reference.

[0125] The term "prosthetic valve", as used herein, refers to any type of a prosthetic valve deliverable to a patient's target site over a catheter, which is radially expandable and compressible between a radially compressed, or crimped, state, and a radially expanded state. Thus, the prosthetic valves can optionally he crimped on or retained by an implant delivery apparatus in the radially compressed state during delivery, and then expanded to the radially expanded state once the prosthetic valve reaches the implantation site. The expanded state may include a range of diameters to which the valve may expand, between the compressed state and a maximal diameter reached at a fully expanded state. Thus, a plurality of partially expanded states may relate to any expansion diameter between radially compressed or crimped state, and maximally expanded state.

[0126] A prosthetic valve of the current disclosure (e.g., prosthetic valve 50) may include any prosthetic valve configured to be mounted within the native aortic valve, the native mitral valve, the native pulmonary valve, and the native tricuspid valve. The disclosed prosthetic valves also can be implanted within vessels communicating with the heart, including a pulmonary artery (for replacing the function of a diseased pulmonary valve), or the superior vena cava or the inferior vena cava (for replacing the function of a diseased tricuspid valve) or various other veins, arteries and vessels of a patient. The disclosed prosthetic valves also can be implanted within a previously implanted prosthetic valve (which can be a prosthetic surgical valve or a prosthetic transcatheter heart valve) in a valve-in-valve procedure.

[0127] In some examples, the disclosed prosthetic valves can be implanted within a docking or anchoring device that is implanted within a native heart valve or a vessel. In some examples, the disclosed prosthetic valves can be implanted within a docking device implanted within the pulmonary artery for replacing the function of a diseased pulmonary valve, such as disclosed in U.S. Patent No. 10,363,130, which is incorporated by reference herein. In some examples, the disclosed prosthetic valves can be implanted within a docking device implanted within or at the native mitral valve, such as disclosed in US Publication No. 2022 / 0079749, which is incorporated herein by reference. In some examples, the disclosed prosthetic valves can be implanted within a docking device implanted within the superior or inferior vena cava for replacing the function of a diseased tricuspid valve, such as disclosed in U.S. Patent No. 11,291,540, which is incorporated herein by reference.

[0128] It is to be understood that any prosthetic valves disclosed herein may be used with a variety of implant delivery apparatuses. Balloon expandable valves generally involve a procedure of inflating a balloon within a prosthetic valve, thereby expanding the prosthetic valve within the desired implantation site. Once the valve is sufficiently expanded, the balloon is deflated and retrieved along with a delivery apparatus 10 (see Fig. 2). Self-expandable valves include a frame that is shape-set to automatically expand as soon an outer retaining shaft or capsule (not shown) is withdrawn proximally relative to the prosthetic valve. Mechanically expandable valves are a category of prosthetic valves that rely on a mechanical actuation mechanism for expansion. The mechanical actuation mechanism usually includes a plurality of expansion and locking assemblies (such as the prosthetic valves described in U.S. Patent No. 10,603,165, International Application No. PCT / US2021 / 052745, and U.S. Provisional Application Nos. 63 / 085,947 and 63 / 209904, each of which is incorporated herein by reference in its entirety), releasably coupled to respective actuation assemblies of a delivery apparatus, controlled via a handle (not shown) for actuating the expansion and locking assemblies to expand the prosthetic valve to a desired diameter. The expansion and locking assemblies may optionally lock the valve's diameter to prevent undesired recompression thereof, and disconnection of the actuation assemblies from the expansion and locking assemblies, to enable retrieval of the delivery apparatus once the prosthetic valve is properly positioned at the desired site of implantation.

[0129] Fig. 4A is a cross-sectional illustration of an exemplary delivery assembly 100, comprising delivery apparatus 110. Delivery apparatus 110 comprises inverting sleeve 120 defining a cavity 122, the inverting sleeve including a first portion 124, and a second portion 128 which is shown in an inverted configuration when the sleeve 120 is folded within itself. Folds 132 represent the folded material of second portion 128 of inverting sleeve 120. The term "inverted state", as used herein, refers to a state in which the inverting sleeve 120 is at least partially folded within itself, such that its second end 130 is retracted in a proximal direction and is surrounded by at least part of the first portion 124 of the inverting sleeve.

[0130] As the second end 130 of the inverting sleeve 120 is retracted further in a proximal direction, the second portion 128 of the inverting sleeve is turned inwards and retracted in the wake of the second end 130, such that the second end 130 is at the proximal end of the second portion 128 in the inverted state. When the inverting sleeve 120 is turned back outward, i.e., everted, from an inverted state towards an "everted state", the process is reversed, such the second portion 128 of the inverting sleeve gradually turns outward followed by the second end 130, which in the everted state is at the distal end of the second portion 128 (and of the invertingsleeve as a whole). Further illustration and exemplification of transition of the inverting sleeve from an everted state to an inverted state, and vice versa, is presented, for example, with relation to Figs. 9A to 9D. The terms "inverting sleeve 120" and "sleeve 120", as used herein, are interchangeable. The terms "delivery assembly 100" and "assembly 100", as used herein, are interchangeable. The terms "delivery apparatus 110" and " apparatus 110", as used herein, are interchangeable.

[0131] The term "folded state", as used herein, refers to a state of the sleeve in which the second portion 128, which is inverted such that it is surrounded by the first portion 124 of the sleeve, has a lager length L2 (indicated, for example, in Fig. 9A) than the length LI of the first portion 124 into which it is inverted. The excess length of the inverted second portion 128 requires folding thereof, so as to be confined by the sleeve first portion 124. The excess material may be folded, for example, in a corrugated formation (e.g., accordion shape). It is to be understood that the excess material of the inverted second portion 128 may be folded in any other suitable folded formations. The excess material in the folded formation is referred to herein as "folds". As the sleeve 120 is everted and the second portion 128 is reversely advanced outward (i.e., the part of the second portion 128 most proximate to the first portion 124 is extracted first, and the second end 130 extracted last), the second portion 128 gradually unfolds, until the folds 132 are straightened out. This situation is referred to herein as an "unfolded state". It is noted, in continuation to the definitions above, that the inverting sleeve 120, when in an inverted state, may be folded or unfolded, and when in an everted state is essentially unfolded.

[0132] Various exemplary implementations for delivery assemblies and components thereof, such as a delivery apparatus, can be referred to, throughout the specification, with superscripts, for ease of explanation of features that refer to such exemplary implementations. It is to be understood, however, that any reference to structural or functional features of any delivery assembly, delivery apparatus, or components thereof, without a superscript, refers to these features being commonly shared by all specific exemplary implementations that can be also indicated by superscripts. In contrast, features emphasized with respect to an exemplary implementation of any delivery assembly, delivery apparatus, or components thereof, referred to with a superscript, may be optionally shared by some but not necessarily all other exemplary implementations. For example, a delivery assembly 100aillustrated in Figs. 4A-4C is an exemplary implementation of delivery assembly 100, and thus can include any of the features described for delivery assembly 100 throughout the current disclosure, except that a shaft or catheter carrying the prosthetic valve 50, such as a balloon catheter 116a, is coupled to theinverting sleeve 120aof delivery apparatus 110“, and can extend through an aperture 134 formed in the inverting sleeve 120a, as described in greater detail below.

[0133] As shown in Fig. 4A, balloon catheter 116aextends longitudinally along and through the inverting sleeve 120a. According to some examples, the balloon catheter 116 can optionally extend, at least partially, through the cavity 122 of the inverting sleeve 120a. Balloon catheter 116aextends between a proximal end 106 and a distal end 108 thereof, and comprises an inflatable balloon 118 at distal end 108. According to some examples, the proximal end 106 of the balloon catheter 1 16aextends proximally to the proximal end 126 of the inverting sleeve, exposing a portion of the balloon catheter 116aexternally to inverting sleeve 120ato allow maneuverability of the balloon catheter 116arelative to the inverting sleeve 120a. The portion of the balloon catheter 116aextending proximally from the inverting sleeve 120acan be utilized, for example, for axially maneuvering balloon catheter 116“, for inflating and / or deflating balloon 118 (for example, via dedicated ports coupled to a proximal end of the balloon catheter), and the like.

[0134] According to some examples, the distal end 108 of the balloon catheter 116 can optionally extend distally past the second end 130aof the inverting sleeve through catheteraperture 134. According to some examples, the distal end 108 of the balloon catheter 116 extends distally to second end 130aof the inverting sleeve both when the inverting sleeve 120ais in an inverted state and when it is in an everted state (or in any state therebetween). This may be achieved, for example, by coupling second end 130“ of the inverting sleeve 120ato the balloon catheter at a connection-point (e.g., point 136) on balloon catheter 116a, proximal to the distal end 108 of the balloon catheter 116a. According to some examples, the connectionpoint 136 may be proximally adjacent to balloon 118. According to some examples, said coupling can optionally comprise fixedly adhering or attaching the second end 130aof inverting sleeve 120“ to the balloon catheter 116 at said connection point, e.g., by gluing or suturing the sleeve portion which forms catheter-aperture 134 to balloon catheter 116. Other attachment means known in the art may also be used.

[0135] According to some examples, said coupling may comprise tightly gripping balloon catheter 116“ by second end 130“, e.g., by a sealing member such as a rubber band disposed at catheter-aperture 134 which can enclose balloon catheter 116 at said connection-point. Any other tight stretchable materials may also be used. According to some examples, balloon catheter 116“ can optionally be at least somewhat axially slidable in relation to second end 130a, such that said connection-point 136 moves proximally or distally along balloon catheter 116a. According to some examples, the coupling of the second end 130“ of inverting sleeve120awith balloon catheter 116ais substantially liquid-tight (i.e., such that no type of liquid can pass between sleeve 120aand catheter 116a).

[0136] According to some examples, the coupling of the second end 130aof inverting sleeve 120awith balloon catheter 116ais substantially air-tight (i.e., such that air cannot pass between sleeve 120aand catheter 116a). The level of permeability, or lack thereof, in the coupling between the sleeve 120aand the balloon catheter 116amay optionally correspond to the permeability of the material from which the inverting sleeve 120“ is composed; the permeability at other connecting points of the sleeve with additional features, e.g., with an everting mechanism; and / or may correspond to the type of fluid which is used to evert the sleeve under pressure, when such fluids are utilized as further described herein. It is noted that inverting sleeve 120amay be coupled to balloon catheter 116 at regions other than second end 130a(or aperture 134) of inverting sleeve 120a, or connection-point 136 on balloon catheter 116a.

[0137] According to some examples, and as shown in Fig. 4A, when inverting sleeve 120ais in an inverted state, the distal end 108 of the balloon catheter 116ais located within a pocket 12 laformed by the sleeve 120a, surrounded by the inverted second portion 128a. According to some examples, the distal end 108 of the balloon catheter 116amay optionally extend distally beyond the pocket 12 laof the inverting sleeve 120a.

[0138] It is noted that as inverting sleeve 120atransitions from an inverted and fully unfolded state to an everted state, pocket 121a, which is defined by the inverted second portion 128, gradually diminishes in length and volume as second portion 128ais everted, and cavity 122 correspondingly increases in volume to include the space which was occupied by pocket 12 la. When inverting sleeve 120ais in a substantially fully everted state, pocket 12 lais substantially non-existent, and cavity 122ais defined by substantially the whole of inverting sleeve 120a. Stated otherwise, a distal end 130aof a second portion 128aof exemplary inverting sleeve 120ais configured to move distally as the sleeve 120ais everted, and the pocket 121adefined by the inverting sleeve 120ain its inverted state, shortens in length, optionally such that no pocket 12 lais present in a fully everted state of the sleeve 120a.

[0139] According to some examples, the distal end 108 of the balloon catheter 116 may not necessarily extend distally to the distal end of the inverting sleeve 120awhen in an inverted state, and may rather be located within the cavity 122 of the inverting sleeve 120a, proximally to the second end 130.

[0140] Fig. 4B is an illustration of delivery assembly 100aof Fig. 4A, advanced through a patient's vasculature towards a target site of implantation. The delivery apparatus 110 is shownin an advanced position, such that the second portion 128aof the inverting sleeve 120ais in an unfolded state (i.e., folds 132 shown in Fig. 4A are illustrated in Fig. 4B to have been straightened out) and is almost entirely everted. Balloon catheter 116ais advanced correspondingly to second end 130aof inverting sleeve 120a, for example by virtue of the coupling of catheter 116ato second end 130asuch that advancement of second end 130a, achieved by further eversion of inverting sleeve 120a, causes advancement of balloon catheter 116atherewith.

[0141] Balloon catheter 1 16ais shown in Fig. 4B to still reside within the pocket 121aof inverting sleeve 120a. The distal portion of apparatus 110ais shown in Fig. 4B to be positioned proximate to a target site of treatment within a patient's body, which can be, for example, a native heart valve (e.g., the aortic valve 152) in which a prosthetic valve, such as prosthetic valve 50 described above with respect to Fig. 3, should be implanted. As shown in the example illustrated in Fig. 4B, the distal end portion of delivery apparatus 110 can optionally terminate proximal to the aortic valve 152.

[0142] According to some examples, eversion of inverting sleeve 120 can be optionally actively halted prior to reaching the annulus of aortic valve 152. According to some examples, the length of the inverting sleeve 120, when fully everted, is designed to be extended up to a position proximal to the aortic valve 152 without extending through aortic valve 152. According to the example illustrated in Fig. 4B, in order for prosthetic valve 50, shown to be crimped over balloon 118, to extend into the aortic valve 152 and be expanded thereagainst, balloon catheter 116 must be advanced beyond inverting sleeve 120 towards aortic valve 152 (for example, towards an annulus of the aortic valve 152, and in some examples, having the inflow end of the prosthetic valve even positioned inside of the left ventricle, distal to the native annulus). In such an example, at least some volume of fluid can be optionally withdrawn in the direction of arrow 252 from the inverting sleeve 120 via its proximal end 126, which fluid was used for everting and thereby advancing inverting sleeve 120 through the patient's vasculature. Withdrawal of the fluid reduces the volume of inverting sleeve 120. Eversion of sleeve 120 by introduction of fluid into cavity 122 will be described in greater detail below with reference to Figs. 6A-6C.

[0143] Fig. 4C is an illustration of the delivery apparatus 110aof Figs. 4A-4B after fluid has been withdrawn from the cavity 122aand the pressure within inverting sleeve 120ahas been somewhat reduced. The pressure reduction (which can be also referred to herein as deflation) within inverting sleeve 120areduces the radial force applied by the inverting sleeve 120aagainst prosthetic valve 50 and / or any other component of the apparatus 110aresiding inside the pocket121a, thereby allowing for axial movement of the balloon catheter 116arelative to the sleeve 120a. It is to be understood that a limited volume of fluid can be withdrawn from cavity 122, sufficient to reduce the pressure applied against the prosthetic valve and allow undisturbed axial movement thereof relative to the sleeve.

[0144] Following pressure reduction in the sleeve 120a, the balloon catheter 116acan be distally advanced, optionally by being actively pushed, towards the aortic valve 152. Upon proper positioning of the prosthetic valve 50 within the aortic valve 152, the balloon 118 can be inflated via balloon catheter 1 16a, as described herein, such that balloon inflation expands the prosthetic valve 50 against the native anatomy. Following implantation of prosthetic valve 50 within aortic valve 152, the balloon 118 can be deflated and optionally retracted from prosthetic valve 50 and / or aortic valve 152, optionally back into pocket 121 of inverting sleeve 120. Inverting sleeve 120 may then be retrieved from the patient's body. In some examples, inverting sleeve 120 can be retracted by further withdrawal of fluid therefrom, optionally accompanied by retraction of balloon catheter 116. In some examples, inverting sleeve 120 can be retracted by being proximally pulled in a fully or partially deflated state thereof.

[0145] In some examples, a method of delivering a prosthetic valve 50 can include introducing a delivery apparatus 110 comprising an inverting sleeve 120 into a blood vessel, everting the inverting sleeve 120 and thereby advancing a balloon catheter 116 coupled thereto through the vasculature of a patient towards a target site of treatment, optionally reducing pressure within cavity 122 of inverting sleeve 120, and advancing balloon catheter 116 into the target site of treatment.

[0146] It is noted that delivery apparatus 110 may be used in conjunction with any of the elements described with relation to delivery apparatus 10 of Figs. 1 and 2. Delivery apparatus 110 may also be used in conjunction with sheath 40, introducer 30, and / or any elements related thereto, which are described in more detail with relation to Figs. 13-17. As further disclosed herein, delivery apparatus 110 may also be utilized substantially independently, without requiring the use of an introducer sheath, thereby simplifying the implantation procedure.

[0147] It is to be understood that implantation of a prosthetic valve 50 inside an aortic valve 152 is described herein and shown, for example, in Figs 4B-4C, by way of illustration and not limitation, and that a prosthetic valve 50 can be implanted in any other native heart valve, such as the mitral valve, the tricuspid valve, or the pulmonary valve. Moreover, a prosthetic valve can be similarly implanted inside a previously implanted prosthetic device, such as inside a docking device configured to facilitate anchoring of a prosthetic valve inside an anatomicalregion of interest, or a previously implanted valve, such as in Valve- in- Valve (ViV) implantation procedures.

[0148] It is to be understood that an apparatus 110 equipped with a balloon catheter carrying a balloon-expandable valve is described and illustrated herein by way of illustration and not limitation, and that the delivery apparatus can include any other catheter adapted for use with any other type of valve, such as self-expandable valves or mechanically-expandable valves. For example, when used to deploy a self-expandable prosthetic valve, the balloon catheter can be replaced with a delivery catheter configured to retain the prosthetic valve in a crimped state inside a distal end portion of the catheter or a capsule attached to a distal end portion of the catheter. Upon reaching a target site of treatment, such as an aortic valve 152, the distal end portion of the catheter (or capsule) can be similarly advanced out of the pocket of the inverting sleeve, and the prosthetic valve can be exposed out of the catheter or a capsule thereof, so as to allow it to self-expand inside the aortic valve.

[0149] Fig. 5 A shows a distal portion of an exemplary delivery apparatus 110bof an exemplary delivery assembly 100bcomprising an exemplary inverting sleeve 120band a prosthetic valve 50 crimped over part of the second portion 128bof the inverting sleeve 120b. Delivery assembly 100bis an exemplary implementation of delivery assembly 100, and thus can include any of the features described for delivery assembly 100 throughout the current disclosure, except that the delivery apparatus 110bof delivery assembly 100bcan be devoid of a separate shaft carrying prosthetic valve, such as by being devoid of a balloon catheter 116, wherein the inverting sleeve 120bcan be configured to carry a prosthetic valve 50 disposed directly over a portion of the 120bin a crimped state thereof, and further configured to facilitate expansion of the prosthetic valve 50.

[0150] Inverting sleeve 120bis shown in Fig. 5A in a delivery configuration in which second portion 128bis inverted, forming pocket 12 lb, and is in a folded state. Second end 130bis a closed end, i.e., does not include any aperture. Prosthetic valve 50 is crimped over a bulge 138 formed from the material of the inverting sleeve at its second end 130b, and thus is positioned within pocket 121b. Reference numerals 129 indicate an exemplary portion of the inverting sleeve 120bmarked for illustrative purpose only, to represent the transition from an inverted state to an everted state, as will be further described with respect to Fig. 5B. As shown in Fig. 5 A, the portion marked by indicators 129 is within pocket 12 lbat a position axially aligned with the bulge 138, wherein a portion of the sleeve 120bis shown to extend proximally from the markings 129 and then folded over itself to form the bulge 138 extending distally from the proximal fold.

[0151] Fig. 5B is an illustration of inverting sleeve 120bof Fig. 5A, in an almost fully everted state thereof. The second portion 128bis turned inside out together with second end 130band extracted from being surrounded by first portion 124b, now forming an axial continuation of first portion 124b(and extending cavity 122b), such that bulge 138 with prosthetic valve 50 crimped thereover is distally advanced at the end of inverting sleeve 120b. Indicators 129 are now in a proximal position relative to bulge 138, wherein a sleeve portion extending therebetween is distal to indicators 129.

[0152] The mode of advancement of inverting sleeve 120b, based on eversion as represented, for example, by the change in position of indicators 129 between Fig. 5A and Fig. 5B, may be highly advantageous for use in body lumens of a patient, particularly in relatively delicate body lumens such as blood vessels. During eversion and advancement of inverting sleeve 120b, the portion of inverting sleeve 120bwhich is not inverted, referred to also as the externalized sleeve portion, which can include the first portion 124 along with sections of second portion 128 which have been everted, remains substantially stationary relative to the walls of the body lumen in which the inverting sleeve is being applied. Substantially no axial push force is applied to the externalized sleeve portion, which is at least partially in direct contact with the body lumen wall. Only the portion of the inverting sleeve which is in an inverted state is distally pushed by the everting mechanism (e.g., streaming of fluid into the lumen), and is mobile relative to the body lumen wall. However, this inverted portion (e.g., second portion 128) has no direct contact with the body lumen wall as it is surrounded by first portion 124 of inverting sleeve 120.

[0153] Once a portion of inverting sleeve 120 is extracted therefrom, i.e., becomes everted, it is not influenced any longer by the everting mechanism, and thus remains substantially stationary relative to the body lumen wall. Thus, inverting sleeve 120 may extend along a body lumen with a minimal amount of friction between the sleeve 120 and the surrounding lumen wall, thereby substantially lowering the risk of injury to the surrounding lumen wall. This may be particularly useful in cases of the inverting sleeve being passed through hyper-sensitive blood vessels, such as calcified blood vessels, and the like.

[0154] In the almost fully everted state shown in Fig. 5B, prosthetic valve 50 can remain in a crimped configuration after exiting pocket 12 lb, according to examples in which prosthetic valve 50 is not self-expandable. According to some examples, in which prosthetic valve 50 is self-expandable, upon exiting pocket 121bby virtue of eversion of second portion 128b, prosthetic valve 50 can self-expand within a target site of treatment. According to someexamples, prosthetic valve 50 can comprises a plastically-deformable material and requires a radial force to be applied thereto in order to assume it’s expanded configuration.

[0155] Fig. 5C is an illustration of inverting sleeve 120bof Figs. 5A and 5B when in a fully inverted state thereof. According to some examples, when eversion of inverting sleeve 120bis achieved by streaming fluid into cavity 122bof inverting sleeve 120b, additional fluid is introduced into inverting sleeve 120bin its almost fully everted state (as shown in Fig. 5B), which additional fluid raises the pressure within inverting sleeve 120band radially expands the distal end of second portion 128b, to assume a maximal-volume conformation of inverting sleeve 120b. The radial expansion of second portion 128bserves, in turn, to expand the prosthetic valve 50. According to some examples, prosthetic valve 50 may be expanded by other means, including self-expansion, mechanical expansion, or other mechanisms for expanding prosthetic valves as described hereinabove.

[0156] According to some examples, the total length of inverting sleeve 120 when in a fully everted state, or optionally the length of a portion thereof which is intended to be introduced into the vasculature of a subject, may correspond to a length of the vascular path of a patient up to the target site of implantation. The “length of the vascular path”, as used herein, refers to the distance of the path within the patient's body which leads from the point of introduction of the delivery apparatus into the vasculature to the target site of implantation. According to some examples, the length of the inverting sleeve may be substantially the same, somewhat longer, or somewhat shorter than the length of the vascular path of a patient. According to some examples, the length of the vascular path to which the inverting sleeve corresponds may be tailored to a specific patient. According to some examples, the length of the vascular path to which the inverting sleeve corresponds may be an average length of the vascular path of a plurality of subjects.

[0157] According to some examples, the length of the vascular path to which the inverting sleeve corresponds may be an average length of a plurality of subjects sharing a common profile, such as male subjects, female subjects, subjects of a certain age range, height range, weight range, and the like. According to some examples, the length of the vascular path to which the inverting sleeve corresponds may be based on an average length adapted for various different treatment procedures. According to some examples, the length of inverting sleeve 120, when fully everted, may be in the range of between 40-50 cm, between 50-60 cm, between 60-70 cm, between 70-80 cm, between 80-90 cm, between 80-100 cm, between 90-100 cm, between 100-110 cm, between 100-120 cm, between 110-120 cm, between 120-130 cm,between 130-140 cm, between 130-150 cm, between 140-150 cm, between 150-160 cm, between 160-170 cm, or between 170-180 cm.

[0158] In some examples, inverting sleeve 120 may be composed of a relatively flexible material, allowing inverting, everting, folding and unfolding thereof. According to some examples, the material from which inverting sleeve 120 is formed may be substantially non- stretchable, in a radial and / or in an axial direction. This may be conducive to the advancement of inverting sleeve by everting as the pushing and / or pressure forces which are applied upon the inverting sleeve, for example by fluid streamed thereinto, will have a limited or null effect in the radial direction and will therefore be utilized mostly for advancement in an axial direction. According to some examples, as demonstrated for example with relation to Figs. 10A-10B, inverting sleeve 120 may be somewhat stretchable, at least in a portion thereof. The term "somewhat stretchable", as used herein, means that the diameter of the cavity 222 increases by up to 5%, by up to 10%, by up to 15%, by up to 20%, by up to 25%, by up to 50%, by up to 75%, and / or by up to 100%.

[0159] In some examples, inverting sleeve 120 may comprise a relatively non-stretchable material, such as a polymeric material having a modulus of elasticity of 400 MPa or greater. Exemplary materials can include ultra-high- molecular- weight polyethylene (UHMWPE), high-molecular- weight polyethylene (HMWPE), or polyether ether ketone (PEEK).

[0160] In some examples, the inverting sleeve 120 can include an exterior hydrophilic coating on an outer surface thereof. Such a hydrophilic coating can further facilitate insertion of inverting sleeve 120 into a patient’s vessel, reducing potential damage. Examples of suitable hydrophilic coatings can optionally include PTFE, polyethylene, polyvinylidine fluoride, and the like. In some examples, a hydrophobic coating, such as Perylene, may be used on an outer surface of the inverting sleeve in order to reduce friction.

[0161] According to some examples, the thickness of inverting sleeve can be from 0.1 mm to 0.5 mm, 0.1 mm to 1 mm, 0.1 mm to 2 mm, 0.1 mm to 5 mm, 0.5 mm to 1 mm, 0.5 mm to 2 mm, 0.5 mm to 4 mm, 0.5 mm to 5 mm, 1 mm to 2.5 mm, 1 mm to 5 mm, or 1 mm to 10 mm. As described in more detail with relation to Fig. 9A, the thickness of inverting sleeve 120 may be uniform along the length and / or along the circumference of inverting sleeve, or the thickness (and other traits, including composition) may vary, optionally to assist progression and / or navigation of the inverting sleeve within the vasculature of a subject.

[0162] According to some examples, first portion 124 and second portion 128 of inverting sleeve 120 may be composed of the same material. According to some examples, first portion 124 and second portion 128 may be composed of different materials. According to someexamples, first portion 124 may be more rigid, and / or thicker, than second portion 128, as first portion 124 generally does not require the ability to invert.

[0163] Figure 6A illustrates delivery assembly 100ccomprising delivery apparatus 110c. Delivery assembly 100cis an exemplary implementation of delivery assembly 100, and thus can include any of the features described for delivery assembly 100 throughout the current disclosure, except that the delivery apparatus 110cfurther comprises a push- member 160 extending radially outwards around the balloon catheter 116cand axially disposed between the balloon 118 and a distal fold 140 of the inverting sleeve 120c. Delivery apparatus 1 10ccomprises inverting sleeve 120cincluding a first portion 124c, and a second portion 128cshown in an inverted state, and in a folded state indicated by folds 132. According to some examples, proximal end 126cof inverting sleeve 120cis in fluid communication with fluid inlet 102, optionally via fluid compartment 104, to which the proximal end 126cmay be coupled.

[0164] According to some examples, proximal end 126cis sealably coupled to fluid compartment 104. According to some examples, proximal end 126cis fixedly attached to fluid compartment 104. According to some examples, proximal end 126cis directly coupled with fluid inlet 102, optionally sealably coupled therewith, without requiring fluid compartment 104 as an intermediate. According to some examples, first portion 124cis in fluid communication with fluid inlet 102, and optionally directly coupled thereto, at a side of first portion 124c, i.e., at a location upon first portion 124cwhich is not at proximal end 126c.

[0165] According to some examples, eversion of inverting sleeve 120 is performed by an everting mechanism which includes streaming of fluid into a cavity 122 enclosed by sleeve 120, having a volume represented as VI. As mentioned above, inverting sleeve 120 comprises a first portion 124, which is essentially in a spread out non-inverted state, which can be referred to as an externalized state, optionally devoid of folds (such as folds 132). Inverting sleeve 120 further comprises a second portion 128, which continuously extends from the distal end of first portion 124 (as further exemplified in relation to Fig. 9 A) but is inverted in the delivery configuration of the sleeve 120, such that it is surrounded by first portion 124.

[0166] According to some examples, the second end 130 of second portion 128 is substantially sealed, optionally by simply not containing any holes in the sleeve material, or, when containing an aperture, by the aperture being sealably coupled to a catheter or other component, such as balloon catheter 116, fluid compartment 104, and the like. According to some examples, proximal end 126 of inverting sleeve is similarly substantially sealed, optionally apart from an opening configured to allow introduction of fluid into cavity 122 of invertingsleeve 120. The opening for introduction of fluid may also have a sealed state, and may be selectively opened when needed.

[0167] When the second end 130 and the proximal end 126 are substantially sealed, volume VI is sealably enclosed within the material of inverting sleeve 120. As second portion 128 is inverted and pulled inwards towards the proximal end of inverting sleeve 120, volume VI is reduced. When the material of second portion 128 is also folded, volume VI becomes even smaller (as illustrated by a transition from Fig. 9A to Fig. 9B). Without wishing to be bound by any theory or mode of action, it is suggested that when fluid is introduced into a cavity 122 enclosed by inverting sleeve 120, pressure is built up within inverting sleeve 120 which exerts a push force on inverting sleeve 120, and particularly on its inverted second portion 128. The increasing pressure drives towards increase of the enclosed volume V 1 , which can be achieved especially by eversion of second portion 128. Optionally, according to some examples, eversion of second portion 128 may be driven by a push force which the momentum of the streamed fluid applies to second portion 128, optionally against second end 130 and / or a part of second portion 128 which is closest to being everted, referred to herein also as distal fold 140.

[0168] According to some examples, the fluid introduced into inverting sleeve 120 to induce eversion thereof may be selected from at least one of: inert gas, air, water, saline, or any other suitable fluid.

[0169] According to some examples, second end 130cof inverting sleeve 120cis axially- anchored, optionally to fluid compartment 104, such that when inverting sleeve 120cis being everted, for example by fluid being streamed thereinto, second end 130cremains substantially stationary, at least axially, and does not advance distally. In some examples, the inverting sleeve 120ccan extend into a compartment 104 and the second end 130ccan be axially affixed inside of the compartment 104. While folds 132 are illustrated in Figs. 6A-6C to extend along a length of the sleeve 120cextending distally from the fluid compartment 104, it is to be understood that this is shown by way of illustration and not limitation, and that a portion of the inverting sleeve 120 that includes folds 132 can be situated inside the compartment 104. According to some examples, folds 132 of an inverting sleeve 120 disclosed herein are configured to be situated inside the patient's body upon insertion of the inverting sleeve 120 into the patient's body. According to some examples, folds 132 of an inverting sleeve 120 disclosed herein are configured to remain outside the patient's body.

[0170] When second end 130cis anchored and inverting sleeve 120ccannot be fully everted, advancement of inverting sleeve 120c, for example within the vasculature of a subject, may beachieved by the part of second portion 128cwhich is in the form of folds 132 being advanced distally, unfolding, and at least partially everting when inverting sleeve 120cis being everted. In addition, a part of second portion 128cwhich is distal to folds 132 when in an inverted state (i.e., extending between first portion 124cand folds 132) can also be distally advanced and at least partially everted. A pocket 121cenclosed by the second portion 128cof sleeve 120ccan be defined by the second portion 128cand the enclosed end at second end 130c, such that the pocket 12 lcin this configuration can be also referred to as a lumen of the inverting sleeve 120c.

[0171] Delivery apparatus 1 10cfurther comprises a shaft carrying a crimped prosthetic valve, which can optionally be, in some examples, a balloon catheter 116C. The balloon catheter 116Cextends longitudinally along and through the lumen or pocket 121cof inverting sleeve 120c, such that proximal end 106cof balloon catheter 116cextends proximally out of pocket 12 lc(and optionally also out of cavity 122), and the distal end 108cof balloon catheter 116cextends through and distally to the lumen or pocket 121c. According to some examples, inverting sleeve 120cincludes a catheter passage 107 at a first portion 124cthereof, through which the balloon catheter 116ccan extend, optionally such that the balloon catheter can be externally in a similar manner to that described herein with respect to delivery assembly 100aof Figs. 4A-4C.

[0172] According to some examples, catheter passage 107 may be at the proximal end 126cof inverting sleeve 120c. According to some examples, catheter passage 107 is configured to enclose balloon catheter 116cin a substantially liquid- tight manner. According to some examples, catheter passage 107 is configured to enclose balloon catheter 116cin a substantially air-tight manner. According to some examples, catheter passage 107 may have an adjustable diameter, and may be configured to transition between tightly enclosing balloon catheter 116c, for example during streaming of fluid into cavity 122cof inverting sleeve 120c, and more loosely surrounding balloon catheter 116c, for example when balloon catheter 116cis being independently advanced to a target site of treatment or is being retracted such as be being proximally pulled. According to some examples, catheter passage 107 may pass through fluid inlet 102.

[0173] According to some examples and as shown in Fig. 6A, balloon 118 is located distally and adjacently to inverting sleeve 120c, at least in an initial position, such as during delivery. A push-member 160, which can optionally be cap-shaped as illustrated in Figs. 6A-6C, is axially disposed between balloon 118 and inverting sleeve 120c, and is coupled to balloon catheter 116c. Push- member 160 is sized to extend radially beyond pocket distal opening 123 of pocket 12 lc, such that it radially covers at least a part of the width of distal fold 140 which surrounds pocket distal opening 123. When distal fold 140 is advanced by virtue of invertingsleeve 120cbeing everted, distal fold 140 pushes against push-member 160 and advances it correspondingly. Push-member 160, in turn, advances balloon catheter 116c, as will be described in greater detail herein below, thereby advancing balloon 118 by virtue of the advancement of distal fold 140.

[0174] According to some examples, push-member 160 surrounds balloon catheter 116cwithout being attached thereto. According to some examples, push-member 160 is coupled to ballon catheter 116c. According to some examples, push-member 160 is fixedly attached to balloon catheter 116C, optionally at a location proximally adjacent to balloon 1 18, or at any other suitable position along catheter 116c. Push-member 160 can cause balloon catheter 116cto advance by virtue of its attachment thereto, when they are attached, and / or can advance balloon catheter 116cby pushing against an element of the balloon catheter which is distal to push-member 160. For example, push- member 160 may advance balloon catheter 116cby pushing against balloon 118, which can radially extend beyond the diameter of the balloon catheter even in a deflated state thereof, and / or against an outflow end of the prosthetic valve 50 crimped around the balloon 118. In some examples, push-member 160 can advance the balloon catheter by pushing against a protrusion (not shown) extending radially outwards from the balloon catheter at a position distal to the push-member 160.

[0175] In some examples, push-member 160 is formed from a relatively rigid material. According to some examples, push-member 160 can be collapsible in a proximal direction, collapsible in a distal direction, or collapsible in both directions (depending on the direction of force applied to it). In an example where push member 160 is collapsible in a distal direction, push-member 160 should be sufficiently stable to remain in a radially expanded state when being pushed against by the advancing distal fold 140 of inverting sleeve 120c. Push-member 160 may optionally have a radially extending formation, such as a proximally tapering cone, a distally tapering cone, a spindle, a plate-like shape, and the like.

[0176] According to some examples, push-member 160 can extend radially outwards in a non- uniform manner around the circumference of the balloon catheter. That is to say, the pushmember can optionally extend radially outwards from one side of the balloon catheter without radially extending from another side (or radially extending to a smaller degree from the other side), for example by having a semi-circular shape, or any other non-uniform radial extension along the circumference of the balloon catheter. This may be advantageous in guiding the advance of a delivery apparatus 110 within a vasculature of a subject, such as to navigate tight turns, or steer towards a selected branching of the vasculature.

[0177] In some examples, the push-member 160 is connected to a push-member shaft 162, as shown for example in Fig. 6B. The push-member shaft 162 may optionally allow rotating of push-member 160, thereby selectively angularly orienting the portion of push-member 160 which is radially extended to a greater extent. This can allow alignment of the inverting sleeve or the balloon with the radially extended portion of the push-member 160, or with a portion which is not radially extended, or extended to a smaller degree, depending on angular manipulation of the push-member shaft 162.

[0178] Fig. 6B is an illustration of a delivery assembly similar to the delivery assembly 100cshown in Fig. 6A, except that instead of being shown as a radial extension which is directly coupled to the balloon catheter in Fig. 6A, the push- member 160cis shown in Fig. 6B to be attached to a push-member shaft 162 extending proximally therefrom. The distal end of push- member shaft 162 can optionally extend proximally to proximal end 126cof inverting sleeve 120c, allowing control and maneuvering thereof, optionally by an external operator. According to some examples, push-member shaft 162 extends along and through pocket 12 lc, optionally alongside balloon catheter 116. According to some examples, push-member shaft 162 can optionally define a lumen through which balloon catheter 116 may extend longitudinally, and the proximal end 106 of balloon catheter 116 may extend beyond the proximal end of pushmember shaft 162, to allow control and maneuvering of ballon catheter 116 independently of push-member shaft 162.

[0179] Fig. 6C is an illustration of the delivery assembly of Fig. 6B, where inverting sleeve 120cis in an everted state represented by the disappearance of folds 132 (as second end 130cis axially-anchored and does not advance along cavity 122c). Push-member 160cis positioned distally and adjacently to inverting sleeve 120c, (i.e., adjacently to distal fold 140 and pocket opening 123), and the distal end 108 of balloon catheter 116 is extended distally therefrom, at a distance L3 from push-member 160c. This distancing of the distal portion of balloon catheter 116 from inverting sleeve 120cand push-member 160cmay represent, for example, a process of insertion of balloon 118 and prosthetic valve 50 into a target site for treatment, such as aortic valve 152. The relative freedom of movement of balloon catheter 116 in relation to inverting sleeve 120c(and push member 160c) may be advantageous, for example, for fine tuning of the position of balloon catheter 116 during placement of a prosthetic valve, or for advancement of balloon catheter 116 into anatomical regions which may be too narrow for safe advancement of inverting sleeve 120 thereinto. While no folds 132 are shown in Fig. 6C, it is to be understood that an everted state of the sleeve 120, placing a distal end thereof, such as distal fold 140, ator proximate to a target site of implantation, can be achieved with some but not necessarily all folds 132 being straightened,

[0180] Fig. 7A shows an exemplary delivery assembly 100d. Delivery assembly 100dis an exemplary implementation of delivery assembly 100, and thus can include any of the features described for delivery assembly 100 throughout the current disclosure, except that the delivery apparatus 110dfurther comprises a sleeve housing 180. Sleeve housing 180 is configured to contain inverting sleeve 120dwhen in an inverted state prior to insertion into a patient’s body, and comprises, at a distal end thereof, a sleeve-passage 182 which is sized to allow passage of inverting sleeve 120dtherethrough, optionally when inverting sleeve 120dis being everted. According to some examples, sleeve housing 180 may be shaped such that distal fold 140d, surrounding pocket opening 123d, is positioned adjacently to sleeve-passage 182, or can conveniently be brought to be positioned adjacently thereto.

[0181] According to some examples, distal fold 140dmay be positioned slightly proximally to sleeve-passage 182, within sleeve-passage 182, or slightly distally to sleeve-passage 182. Sleeve-passage 182 may have a diameter similar to the diameter of, for example, a blood vessel into which inverting sleeve 120dis intended to be introduced, or to the diameter of the incision in a patient's skin through which inverting sleeve 120dis introduced. The incision (referred to herein also as "point of entry", or "entry-point") through which inverting sleeve 120 is introduced will be discussed in more detail with reference to Fig. 8.

[0182] According to some examples, sleeve housing 180 may be configured to contain at least a portion of inverting sleeve 120din a tight or compressed state. According to some examples, the tight or compressed state is a radially tight or compressed state, i.e., a state in which the externalized portion of inverting sleeve 120dis radially confined or pushed against towards a central longitudinal axis thereof. According to some examples, the tight or compressed state of inverting sleeve 120din sleeve housing 180 is similar to the state of radial tightness or compression of inverting sleeve 120dwhen present within at least a portion of the vasculature of a patient. According to some examples the tight or compressed state of inverting sleeve 120din sleeve housing 180 imitates the state of radial tightness or compression of inverting sleeve 120dwhen present within at least a portion of the vasculature of a patient, is somewhat more tight or compressed, or is somewhat less tight or compressed. According to some examples, only the portion of inverting sleeve 120dwhich is adjacent to, or within, sleeve-passage 182 is in a tight or compressed state.

[0183] According to some examples, sleeve housing 180 further comprises a funnel-shaped crimper 184 (referred to herein also as "funnel crimper 184"), tapering between a distal wideopening 186 to a narrow opening 185 thereof. Funnel crimper 184 can extend distally from the sleeve-passage 182, and can be coupled to sleeve-passage 182 at narrow opening 185. According to some examples, narrow opening 185 is essentially a direct distal continuation of sleeve-passage 182. According to some examples, narrow opening 185 can be narrower or may have a smaller diameter than sleeve-passage 182, such that funnel crimper 184 can optionally protrude proximally into sleeve-passage 182.

[0184] According to some examples, narrow opening 185 is oriented toward, and can optionally protrude into, pocket 121dof inverting sleeve 120d, when inverting sleeve 120dis positioned adjacently to sleeve-passage 182. According to some examples, narrow opening 185 is sized to allow passage of a prosthetic valve 50 therethrough, when prosthetic valve 50 is in a crimped state. According to some examples, funnel crimper 184, or at least narrow opening 185 thereof, comprises a non-flexible and optionally rigid material. The non-flexible and optionally rigid material can exert an inward radial pushing force on an element, e.g., prosthetic valve 50, which is passed (e.g., proximally pulled) therethrough, the prosthetic valve having a diameter which is larger than the diameter of the narrow opening 185 of funnel crimper 184 (but not larger than the diameter of the wide opening 186).

[0185] When an element which is proximally pulled through funnel crimper 184 is radially collapsible or compressible, passage of the element through funnel crimper 184, from wide opening 186 to narrow opening 185, can gradually compress the element. An example of this process is depicted in Figs. 7A and 7B. As shown in Fig. 7A, balloon catheter 116, in a first position, extends longitudinally through cavity 122dand pocket 121dof inverting sleeve 120d, such that proximal end 106 of balloon catheter 116 extends proximally to sleeve proximal end 126dand to housing 180, and distal end 108 extends distally beyond funnel crimper 184.

[0186] The balloon 118 at the distal end 108 of the balloon catheter 116 is illustrated in Fig. 7A to be in an inflated state thereof, with the expanded prosthetic valve 50 disposed thereover. According to some examples, balloon catheter 116 is slidably disposed within inverting sleeve 120d, such that catheter 116 may be axially advanced or retracted relative to inverting sleeve 120d(and optionally also relative to sleeve-housing 180). Balloon catheter 116 may pass through a catheter passage (such as but not limited to catheter passage 107 mentioned above), the passage passing through at least one of the proximal end 126dof inverting sleeve 120d, the second end 130dof inverting sleeve 120d, the sleeve housing 180, and / or the fluid compartment 104, which can optionally be coupled to the sleeve housing 180. The catheter passage 107 can optionally be configured to transition between a relatively open state, which allows sliding ofballoon catheter 116 therethrough, and a relatively tight or sealed state, in which axial movement of balloon catheter 116 is limited.

[0187] In some examples, the sleeve housing 180 is attached to a fluid compartment 104. In some examples, the sleeve housing 180 comprises a fluid compartment which can be optionally situated therein. While the sleeve 120dis shown in Figs. 7A-7B to have an axially movable second end 130 through which the balloon catheter 116 extends, in a manner that can be somewhat similar to that described above for delivery apparatus 110awith respect to Figs. 4A- 4C, it is to be understood that this is shown by way of illustration and not limitation. For example, a second end 130 of the sleeve 120dcan be axially affixed in position, in a manner similar to that described above for delivery apparatus 110cwith respect to Figs. 6A-6C.

[0188] Fig. 7B shows the balloon catheter 116 in a second position, after balloon catheter 116 has been retracted such that distal end 108 is pulled through funnel crimper 184 into pocket 121dof inverting sleeve 120d. The inward radial pushing force applied to prosthetic valve 50 as it is pulled through funnel crimper 184 serves to compress or crimped the prosthetic valve 50, allowing it to be further pulled into pocket 12 ldof inverting sleeve 120d. The balloon 118 can be optionally deflated prior to and / or during crimping of the valve, either by actively draining inflation fluid from balloon 118, or by allowing it to be passively compresses and deflated as it is passed through the funnel crimper 184 along with the prosthetic valve 50.

[0189] In some examples, once positioned within pocket 121d, balloon catheter 116 can optionally be advanced by the everting of inverting sleeve 120d, as described in relation to Figs. 4A-4C. Pulling of prosthetic valve 50 through funnel crimper 184 can serve as an effective crimping mechanism for prosthetic valve 50, optionally obviating the need for using a separate conventional crimper. This may simplify the process of preparing a prosthetic valve for delivery to a patient, and optionally also reduce costs.

[0190] In some examples, funnel crimper 184 is affixed to the remainder of the sleeve housing 180. In some examples, funnel crimper 184 can be releasably attached to the sleeve housing. Fig. 7C illustrates an exemplary delivery assembly 100e, which is similar to any example described herein for delivery assembly 100d, except that the funnel crimper 184eof delivery assembly 100cis configured to be releasably attached to sleeve housing 180c. According to some examples, narrow opening 185eof funnel crimper 184emay be configured to be releasably coupled to sleeve-passage 182e, such as by being threadedly engaged, by a groove and tongue mechanism, or any other suitable releasable attachment mechanism.

[0191] Removal of funnel crimper 184efrom sleeve-passage 182emay be conducive to insertion of inverting sleeve 120einto a patient. For example, sleeve-passage 182ecansubstantially correspond in size to an opening at an entry point, as mentioned above, whereas the wide opening 186eof funnel crimper 184ecan be wider than sleeve-passage 182eand incision through which the assembly 100 should be inserted into a patient's body, which may therefore hinder introduction of inverting sleeve 120 into body.

[0192] Fig. 8 shows an exemplary delivery assembly 100f, which is similar to any example described herein for delivery assemblies 100dor 100e, except that the delivery assembly 100ffurther comprises an introducer tube 188 extending distally from the sleeve housing 180f, and is either devoid of a funnel crimper 184, or can be provided with a removable funnel crimper releasably connectable to the sleeve housing in a similar to that described with respect to delivery assembly 100e. When delivery assembly 100fis devoid of a funnel crimper, the prosthetic valve 50 can be crimped by using a separate conventional crimper as known in the art, after which the crimped valve 50 can be optionally retracted into the sleeve housing 180f. When delivery assembly 100fincludes a releasably attachable funnel crimper 184, the funnel crimper can be removed prior to insertion of a rigid introducer tube 188, through the entrypoint, into a patient's body, wherein a lumen of the introducer tube 188 is sized to allow advancement of inverting sleeve 120f, with the crimped valve 50, therethrough.

[0193] As mentioned above in relation to Figs. 1 and 2, a delivery apparatus may be introduced into a blood vessel through an introducer sheath (such as an expandable introducer sheath). One of the roles of the introducer sheath is to protect the blood vessel during advancement of a delivery catheter, which advancement may be relatively forceful, producing potentially harmful friction levels between the catheter and the blood vessel. Delivery assemblies 100 disclosed herein, comprising an inverting sleeve 120 which progresses within the vasculature by eversion thereof, may obviate the need of an introducer sheath. As mentioned above, during eversion of an inverting sleeve 120, there is substantially no movement of the externalized sleeve portion relative to the surrounding vessel wall against which it is pressed, and the risk of harming the vasculature is therefore significantly reduced.

[0194] According to some examples, inverting sleeve 120 is introduced directly into the patient at the entry point, optionally without the use of a pre-inserted introducer sheath. According to some examples, first portion 124 of inverting sleeve 120 can comprise a rigid material, which rigidity of first portion 124 may be advantageous in penetrating through the entry-point, and optionally in keeping the entry-point open for the duration of the procedure. Inverting sleeve 120 can be advanced along the vascular path of the patient from the entry point to the target site for delivery of the prosthetic valve to the target site of implantation, thus essentially functioning both as an introducer sheath and as a delivery apparatus.

[0195] According to some examples, the introducer tube 188 is affixed to the sleeve housing 180f, and distally extends from the sleeve passage 182f. According to some examples, the introducer tube 188 is integrally formed with the sleeve housing 180f. According to some examples, the introducer tube 188 can be releasably attached to the sleeve housing 180f. For example, if a delivery apparatus 110fincludes a funnel crimper that is releasably attachable to the sleeve housing 180f, the funnel crimper can be released and removed from the sleeve housing 180fsubsequent to crimping the prosthetic valve 50 and placing it inside the sleeve housing 180f, after which the introducer tube 188 can be connected to the sleeve housing 180f, optionally having a releasably engagement mechanism similar to that of the releasable funnel crimper 184.

[0196] According to some examples (not shown), a funnel crimper 184 can be releasably attached to a distal end of the introducer tube 188 instead of being attached directly to the sleeve housing 180. For example, an introducer tube 188 can be either affixed to, or releasably attached to, the sleeve housing 180f, and a funnel crimper 184 can be releasably attached to a distal end of the introducer tube 188 in a similar manner to that described for releasable attachment of a funnel crimper 184eto a sleeve housing 180eof delivery assembly 100e, mutatis mutandis. The prosthetic valve 50 can be similarly crimped by being proximally pulled through such a funnel crimper 184, and optionally further pulled, through the introducer tube 188, to position the prosthetic valve 50 inside the sleeve housing 180f, optionally inside a pocket 121 of the sleeve 120. The funnel crimper 184 can be released in such examples from the distal end of the introducer tube 188, prior to insertion of the introducer tube 188 into a patient's body.

[0197] According to some examples, introducer tube 188 is inserted into the patient's body through the entry-point 240 prior to advancement of inverting sleeve thereinto. Introducer tube 188 can comprise a rigid material, which may be advantageous in penetrating entry-point 240 and in keeping entry-point 240 open, to allow introduction of inverting sleeve 120fthrough introducer tube 188. According to some examples, introducer tube 188 may extend into a blood vessel of the patient (e.g., the femoral artery), though the entry-point 240, to a depth of up to 1 cm, 1.5 cm, 2 cm, 3 cm, 4 cm, 5 cm, 6 cm, 7 cm, 8 cm, 9 cm, 10 cm, or 15 cm from the external side of the entry-point. Each possibility consists of a separate example. According to some examples, introducer tube may extend into a blood vessel of the patient to a depth in the range of 1-2 mm, 1-3 mm, 2-4 mm, 1-5 mm, 2-6 mm, 3-7 mm, 4-8 mm, 5-9 mm, 1-10 mm, 0.5-1 cm, 0.5-1.5 cm, 1-2 cm, 1-3 cm, 1-4 cm, 1-5 cm, 0.5-5 cm, 2.5-7.5 cm, 2-8 cm, 0.5-10 cm, 1-10 cm, 1-15 cm, or 5-15 cm. Each possibility consists of a separate example.

[0198] According to some examples, introducer tube 188 may be used to introduce an inverting sleeve 120 which is not necessarily contained within a sleeve housing 180. According to some examples, introducer tube 188 may be coupled to inverting sleeve 120, such as to the first portion 124.

[0199] Fig. 9A shows an isolated view of an exemplary inverting sleeve 120g, in a fully everted state. Inverting sleeve 1208is an exemplary implementation of inverting sleeve 120, and thus can include any of the features described for inverting sleeve 120 throughout the current disclosure, except that the inverting sleeve 120sis configured to assume a non-uniform diameter along a length thereof as it everts. First portion 124gis substantially open at proximal end 126s, and second portion 128sis sealed at second end 130s. In the fully everted state of inverting sleeve 1208shown in Fig. 9A, first portion 124sis essentially the proximal portion of the inverting sleeve, and second portion 128sis essentially the distal portion of inverting sleeve 120s, second end 130sbeing the distal end thereof. As shown in Fig. 9A, the inverting sleeve can have a non-uniform diameter in the everted state, having a diameter DI at the distal end 130 that is larger than the diameter D2 at the proximal end 126s. According to some examples, the diameter of the inverting sleeve can be substantially uniform along its length. According to some examples, the diameter of the inverting sleeve may be non-uniform, for example as shown in Fig. 9A.

[0200] Non-uniform diameter of the inverting sleeve can assist progression of the sleeve within the vasculature, during eversion thereof. For example, since the blood vessels expand in size between the point of entry (e.g., at a femoral artery) towards the target site of implantation (e.g., the aortic arch leading to the aortic valve), the inverting sleeve may be predesigned to assume a similarly expanding profile in the distal direction.

[0201] It is noted that any exemplary inverting sleeve 120 disclosed herein can comprise a relatively soft and flexible material, suitable for advancement by eversion. Therefore, the inverting sleeve can optionally adapt to the shape and directionality of the blood vessel in which it is progressing, without requiring any further steering mechanism. This may be highly advantageous, for example, in substantially reducing the risk of the inverting sleeve 120 being forcefully pushed against the surrounding anatomical walls and causing trauma thereto. It is further advantageous in reducing the intervention required for navigating and / or steering the delivery apparatus through the vasculature of the patient, as the everting sleeve 120 can naturally advance along the course of a lumen in which it is being everted. These advantages are in addition to the advantages of eversion mentioned above, including having substantially no movement of the externalized surface of the inverting sleeve 120 relative to the surroundinganatomical walls, which significantly reduces or even eliminates potentially harmful friction that may be otherwise developed therebetween.

[0202] Non-uniform diameter of the type illustrated, for example, in Fig. 9A, as well as other adjustments to the dimensions and composition of the sleeve material, can further assist the advancement of the inverting sleeve within the vasculature of the subject. Dimensional adjustments can include, for example, forming the sleeve wall to have a non-uniform wall thickness along its length; shortening the material at particular locations or along regions of the sleeve on one side (for example by pinching, gluing, and the like) while leaving the longitudinally opposing side without such intervention; and the like. Any other modification design parameters related to the dimensions or materials are similarly contemplated.

[0203] According to some examples, adjustments to design parameters of the inverting sleeve 120 can assist the navigation of the inverting sleeve within the vasculature. According to some examples, the inverting sleeve 120 may be self-steerable, meaning that the inverting sleeve 120 is advanced by eversion thereof, and that it progresses within the vasculature towards the target site of treatment without requiring active manipulation of dedicated steering mechanisms. According to some examples, tailored adjustments of such design parameters may be made to inverting sleeve 120 which are suited to the pathway which the inverting sleeve is intended to take within the vasculature.

[0204] According to some examples, the inverting sleeve 120 can comprise a remotely controlled element, which allows directing the course in which the inverting sleeve progresses. According to some examples, delivery apparatus 110 can be advanced over, and guided by, a guidewire (not shown). The guide wire may extend, for example, through cavity 122 and / or pocket 121 of the inverting sleeve, or through balloon catheter 116, when utilized.

[0205] The example shown in Fig. 9A, in which first portion 1248has a relatively narrow diameter and second portion 128sis configured to assume a relatively wider diameter when everted, can be advantageous during insertion of inverting sleeve 120gthrough the entry-point, as the entry-point and the blood vessel extending in close proximity therefrom, is generally of narrow dimensions relative to the blood the more distal portions of the vascular path of advancement.

[0206] Fig. 9B shows inverting sleeve 120sin an inverted state. Second portion 128shas been turned inwards and retracted towards proximal end 126sof first portion 124suntil it is fully surrounded by the first portion 124s. Second portion 128gis shown to have an axially longer length L2 than the length LI of first portion 124s, such that folds 132sare formed from the material of second portion 128sallowing it to fit within first portion 124sin an inverted andfolded state. As mentioned above, according to some examples, the second portion 128 can optionally extend in the proximal direction past the proximal end 126, such that the second send 130, and is some cases, at least some of the folds 132, can be proximal to the proximal end 126 of the first portion 124 in the inverted state.

[0207] Fig. 9C is shows the inverting sleeve 120gof Fig. 9B as part of an exemplary delivery assembly 100s, being introduced via entry-point 240 into the patient's vasculature. Inverting sleeve 120sis in a substantially inverted state during insertion, and a distal part of the sleeve 120g, including a distal fold 140 thereof, has been inserted through entry -point 240. As can be seen, entry-point 240 is shown to have a relatively narrow diameter, while blood vessel(s) 242 can increase in profile in a distal direction therefrom.

[0208] Fig. 9D shows delivery assembly 100sof Fig. 9C, where inverting sleeve 120sis illustrated to be at least partially everted. At least a portion of second portion 128shas been turned inside out and spread out along the walls of blood vessel(s) 242. As the second portion 128geverts out of first portion 124g, it can gradually widen in the distal direction. As shown in Fig. 9D, gradual widening of inverting sleeve 1208can improve the fitting of inverting sleeve 120swithin the blood vessel(s) 242 along the vascular path of advancement, which can be advantageous to the progression of inverting sleeve 120g. According to some examples, widening of inverting sleeve 120gcan be relatively abrupt instead of gradual, such that different portions of the sleeve 120 can have different diameters, each portion optionally being uniform in diameter along its length, wherein the diameters are configured to be larger for portions which are more distal in the everted state, In such examples, one or more neck portions can be defined at the transition(s) between a smaller-diameter to a larger-diameter region of the sleeve.

[0209] Fig. 10A is an illustration of delivery assembly 100, where inverting sleeve 120 is introduced at entry-point 240 and advanced along the vascular path of the patient until reaching target site of treatment, e.g., aortic valve 152. Balloon catheter 116 is advanced together with inverting sleeve 120, optionally by virtue of an attachment thereof to inverting sleeve 120, such that balloon 118 with prosthetic valve 50 crimped thereover is positioned substantially within aortic valve 152 in a deflated state of the balloon 118 and crimped configuration of the prosthetic valve 50.

[0210] Fluid compartment 104bis sealably attached to proximal end 126 of inverting sleeve 120 and comprises fluid inlet 102bon a side thereof. Arrows 254 represent fluid being streamed from fluid inlet 102binto fluid compartment 104b, and from fluid compartment travelling distally within cavity 122 towards the distal end of inverting sleeve 120, such as towards distal fold 140.

[0211] In some cases, an initial procedure of widening the native annulus may be performed prior to prosthetic valve implantation therein. Such procedures, often referred to as 'preballooning', conventionally involve inflation of a balloon that does not have a prosthetic valve disposed thereover, inside of the annulus. According to some examples, a delivery assembly 100 that includes an inverting sleeve 120 can be utilized for performing pre-expansion of the native annulus, prior to prosthetic valve implantation therein, without the need for inflating a separate balloon.

[0212] When the sleeve 120 is everted and the distal portion of the sleeve is positioned inside the native heart valve, for example such that the distal fold 140 is axially aligned with, or is distal to, the annulus of the aortic valve 152, continued streaming of an increased quantity of fluid can optionally increase pressure at the distal portion of the sleeve 120, which can radially inflate and push against aortic valve 152. Arrows 256 represent widening of the aortic valve 152, by virtue of the increased fluid pressure at the distal end of inverting sleeve 120. Widening of a target site of treatment, e.g., the annulus of an aortic valve 152, is referred to as prestretching. This can be performed prior to implantation of a prosthetic device at the expanded or stretched anatomical site, such as prior to implantation of a prosthetic valve 50 inside a preexpanded aortic valve 152, or as a stand-alone procedure that does not involve subsequent implantation of a prosthetic device, such as when used for valvuloplasty procedures, in which case a delivery apparatus 110 can be used without including a balloon catheter 116 and / or prosthetic valve 50.

[0213] According to some examples, inverting sleeve 120 can perform pre- stretching at an entry-point 240, at a target site of implantation of a prosthetic valve 50, or at any other location along the cardiovascular system of the patient, optionally by virtue of increasing fluid pressure within a distal end portion of inverting sleeve 120. According to some examples, the material of inverting sleeve may be substantially non-stretchable. According to some examples, the material of inverting sleeve may be somewhat stretchable, allowing for some radial expansion when pressure or mechanical force is exerted thereupon. According to some examples, one or more portions of inverting sleeve may be somewhat stretchable, and other portion(s) may be substantially non-stretchable. In some examples, a portion of the inverting sleeve 120 which is at a distal end thereof when in an everted state can be stretchable. In some examples, a portion of inverting sleeve 120 which is adjacent to proximal end 126 and / or a portion which is adjacent to second end 130 can be stretchable.

[0214] According to some examples, when pre-stretching is performed or intended to be performed, inverting sleeve 120 may be designed to have at least a portion thereof which issomewhat stretchable. The stretchable portion of inverting sleeve 120 can comprise or substantially be made from, for example, any of a variety of natural or synthetic elastomers, including silicone rubber, natural rubber, any of various thermoplastic elastomers, polyurethanes such as polyurethane siloxane copolymers, urethane, plasticized polyvinyl chloride (PVC), styrenic block copolymers, polyolefin elastomers, etc. In some examples, the stretchable portion can comprise an elastomeric material having a modulus of elasticity of 200 MPa or less. In some examples, the stretchable portion can comprise a material exhibiting an elongation to tear of 200% or greater, 300% or greater, or an elongation to tear of 400% or greater.

[0215] Fig. 10B illustrates the delivery assembly of Fig. 10A, in which the target site for treatment has undergone pre-stretching. Arrows 258 represent withdrawal of at least some volume of fluid from inverting sleeve 120, to optionally reduce the force with which the distal portion of the inverting sleeve 120 pushes against the annulus of aortic valve 152. Arrows 260 represent a partial withdrawal of fluid from fluid compartment 104b, and proximal end 126 attached thereto, through entry-point 240, which withdrawal facilitates proximal retraction of distal fold 140 from aortic valve 152. Balloon catheter 116 can be either kept in place or even distally advanced, optionally by virtue of being actively pushed, such that balloon 118 remains within, or advanced to be positioned in, aortic valve 152, without being surrounded by any portion of inverting sleeve 120. Balloon 118 can then be inflated, e.g., by inflation fluid being streamed through balloon catheter 116, so as to expand prosthetic valve 50 against the aortic valve 152. Optionally, following implantation of prosthetic valve 50, balloon 118 may be deflated and retracted together with inverting sleeve 120 out of the patient's body.

[0216] Fig. 11 is an illustration of an exemplary delivery assembly 100h. Delivery assembly 100his an exemplary implementation of delivery assembly 100, and thus can include any of the features described for delivery assembly 100 throughout the current disclosure, except that delivery assembly 100hfurther comprises a biasing member 190 configured to bias the inverting sleeve 120hto the everted state, in lieu of, or in addition to, streaming fluid into the cavity 122h. According to some examples, the biasing member 190 comprises a compression spring 190 configured facilitate eversion of the sleeve 120h. Biasing member 190 extends from a proximal end 192 to a distal end 194 thereof. According to some examples, the distal end 194 can be optionally coupled to a second end 130hor a bulge 138hof inverting sleeve 120h, optionally via intermediate connector 196, which can be a relatively rigid connector, optionally attached to a proximal side of bulgel38h(for example, to a proximal fold 142).

[0217] According to some examples, second end 130 comprises a rigid material that can perform the function of intermediate connector 196. According to some examples, distal end 194 of biasing member 190 is coupled to second end 130 without an intermediate rigid connector. Proximal end 192 of the biasing member 190 can be axially fixed in position relative to proximal end 126hof the sleeve 120h, such that when the second portion 128his everted and distally advanced, or inverted and proximally retracted, the proximal end 192 of the biasing member 190 remains substantially stationary. Compressing, releasing, and / or stretching of biasing member 190, such as a spring 190, is configured to induce corresponding eversion or inversion of inverting sleeve 120h.

[0218] According to some examples, when a biasing member that can be implemented as a spring 190 is in a compressed state, the second portion 128his at a most retracted position and the inverting sleeve 120his in a fully inverted state thereof, and as the spring 190 is gradually released and / or axially expanded, the second end 130his distally advanced and the inverting sleeve 120his gradually everted. According to some examples, when a biasing member that can be implemented as a spring 190 is in a relaxed state thereof, the second portion 128his retracted, and when the spring 190 is distally expanded, inverting sleeve 120his everted. The state of compression, relaxation, and / or stretching or axial expansion of spring 190 may be controlled by an external control mechanism (not shown) coupled thereto.

[0219] According to some examples, second end 130his a closed end, and a prosthetic valve 50 may be crimped over a bulge thereof, in a manner that can be similar to that described above for delivery assembly 100b, mutatis mutandis. According to some examples, second end 130 is open ended by including an aperture 134, and can optionally be coupled to a balloon catheter 116, in a manner that can be similar to that described above for delivery assembly 100a, mutatis mutandis.

[0220] According to some examples, the distal end 194 of biasing member 190 can be coupled to any other location on sleeve second portion 128h. For example, the distal end 194 of the biasing member can be coupled to a location on sleeve second portion 128h, which location is the most distally advanced when inverting sleeve 12011is everted. Thus, full opening, relaxing, and / or stretching of the spring can evert second portion 128hto its most distally advanced state.

[0221] According to some examples, the biasing member 190 can be disposed around the sleeve second portion 128h, for example by having the second portion 128hproximally extended, in the inverted state, through coils of a spring 190. The distal end 194 of the biasing member can abut, in such example, the distal fold 140 of the sleeve, without being attachedthereto, such that upon release of the biasing member, it can impinge against the distal fold 140 and facilitate axial advancement and eversion of the inverting sleeve 120h.

[0222] According to some examples, eversion of an inverting sleeve may be achieved by streaming fluid into the inverting sleeve via at least one fluid inlet, and / or a biasing member, such as, but not limited to, a spring.

[0223] Fig. 12A is an illustration of an exemplary delivery apparatus 1101. Delivery apparatus HO1is an exemplary implementation of delivery apparatus 110, and thus can include any of the features described for delivery apparatus 1 10 throughout the current disclosure, except that delivery apparatus 1101further comprises a tissue engagement sleeve 170 configured to engage with, and / or anchor to, tissue walls surrounding the inverting sleeve 1201of the delivery apparatus 1101. The tissue engagement sleeve 170 can be optionally disposed over at least a portion of an outer surface of inverting sleeve 1201.

[0224] As used herein, for example in the context of the inverting sleeve, the term "outer surface" refers to a side or surface of the sleeve 120 configured to face radially outwards when the inverting sleeve 120 is in a fully everted state (e.g., the state shown in Fig. 9A). When the inverting sleeve 120 is inserted into, and everts along, a blood vessel, the outer surface faces, and optionally contacts (in the absence of any other component disposed over the outer surface), the surrounding wall of the blood vessel. When a second portion 128 of the inverting sleeve is in an inverted state and a balloon catheter is passed though pocket 121, the outer surface of the second portion, prior to eversion thereof, is the surface which faces the balloon catheter, while the outer surface of the first portion 124 can dace radially outwards, and optionally contact the surrounding blood vessel wall, when the inverting sleeve is either in an inverted or an everted state thereof.

[0225] According to some examples, a tissue engagement sleeve 170 is disposed over at least a portion of the outer surface of inverting sleeve 1201, and can optionally be releasable from the inverting sleeve upon contacting the surrounding wall tissue. For example, when inverting sleeve 1201is inserted and everted within a blood vessel, tissue engagement sleeve 170 can be optionally correspondingly everted and sandwiched between the outer surface of the inverting sleeve 120 and the surrounding blood vessel. When tissue engagement sleeve 170 is pressed radially outwards against the surrounding blood vessel wall, it can be attached to the tissue wall and remain implanted thereagainst.

[0226] According to some examples, tissue engagement sleeve 170 further comprises a plurality of anchoring elements 172 on an outer surface thereof, configured to engage with. And couple or attach the tissue engagement sleeve 170, to the surrounding wall of a bloodvessel when the tissue engagement sleeve 170 is everted and / or radially pressed thereagainst by the inverting sleeve 1201. According to some examples, the anchoring elements 172 can comprise spikes, barbs, tines, and the like, optionally configured to penetrate into the surrounding tissue. According to some examples, the anchoring elements 172 can be made of a biodegradable material.

[0227] After eversion of the inverting sleeve 1201and attachment of the tissue engagement sleeve 170 to the surrounding wall tissue, the inverting sleeve 1201can be optionally removed from the patient's body, while the tissue engagement sleeve 170 remains in position, attached to the blood vessel wall. According to some examples, the tissue engagement sleeve 170 can be configured to deliver an active ingredient to the surrounding tissue. In some examples, the tissue engagement sleeve 170 comprises patches 174 containing the active ingredient (as shown, for example, in Figs. 12A-12B), configured to release the active ingredient to the surrounding tissue after attachment of the tissue engagement sleeve 170 to the surrounding tissue wall. In some examples, the active ingredient is embedded, contained in, and / or spread over the tissue engagement sleeve 170.

[0228] According to some examples, the active ingredient may be a therapeutic ingredient, such as a drug releasable from the tissue engagement sleeve 170. According to some examples, the active ingredient may be contained within the implantable member such that it is released substantially immediately, gradually (i.e., extended release), and / or following a particular time period (e.g., delayed release).

[0229] Fig. 13 illustrates a side view of an exemplary introducer sheath 40 that can be used in the introducer device assembly 20 of Fig. 2. As shown, the sheath housing 24 may be positioned at the sheath proximal end 44. The sheath housing 24 may include an internal chamber (not shown) for the delivery apparatus 10 to be passed through to be delivered to the patient's vasculature. The sheath housing 24 may be configured to remain external to the patient's vasculature when the sheath 40 is inserted therein and may be configured to remain external to the patient's skin for a percutaneous implantation of the sheath 40. The sheath housing 24 may be configured for a user (such as a surgeon) to grip to manipulate the sheath 40.

[0230] The sheath housing 24 may comprise a cylindrical body and may include a coupler 29 for coupling to another housing or component of the system. The sheath housing 24 may include a fluid port 26 for passing fluid such as blood to or from the patient's vasculature. Tubing 27 with a valve 28 may be coupled to the fluid port 26, for passing fluid through the fluid port 26 and for sealing flow of the fluid through the fluid port 26.

[0231] In some examples, the introducer sheath need not include a sheath housing 24. For example, the sheath 40 can be an integral part of a component of the delivery apparatus 10, such as the guide catheter. For example, the sheath can extend from the handle portion 18 of the guide catheter. Additional examples of introducer devices and expandable sheaths can be found in U.S. Patent No. 11,273,062, which is incorporated by reference in its entirety.

[0232] Figs. 14 and 15 illustrate a cross-sectional view and a side view, respectively, of a portion of the introducer sheath 40. In some examples, introducer sheath may be an expandable sheath. As shown in Fig. 15, the sheath 40 can have a natural, unexpanded outer diameter D3. In certain examples, the expandable sheath 40 can comprise a plurality of co-axial layers extending along at least a portion of the length of the sheath (Fig. 13). For example, with reference to Fig. 14, the expandable sheath 40 can include a first layer 52 (also referred to as an inner layer), a second layer 54 disposed around and radially outward of the first layer 52, a third layer 56 disposed around and radially outward of the second layer 54, and a fourth layer 58 (also referred to as an outer layer) disposed around and radially outward of the third layer 56. In the illustrated configuration, the inner layer 52 can define the sheath lumen 68 extending along a central axis Cl.

[0233] Referring to Fig. 15, when the sheath 40 is in an unexpanded state, the inner layer 52 and / or the outer layer 58 can form longitudinally-extending folds or creases such that the surface of the sheath comprises a plurality of ridges 62. The ridges 62 can be circumferentially spaced apart from each other by longitudinally-extending valleys 64. When the sheath expands beyond its natural diameter D3, the ridges 62 and the valleys 64 can level out or be taken up as the surface radially expands and the circumference increases. When the sheath collapses back to its natural diameter, the ridges 62 and valleys 64 can reform.

[0234] In certain examples, the second layer 54 can be a braided layer. Figs. 16A and 16B illustrate the sheath 40 with the outer layer 58 removed to expose the elastic layer 56. With reference to Figs. 16A and 16B, the braided layer 54 can comprise a plurality of members or filaments 60 (e.g., metallic or synthetic wires or fibers) braided together. The braided layer 54 can have any desired number of filaments 60, which can be oriented and braided together along any suitable number of axes. For example, with reference to Fig. 16B, the filaments 60 can include a first set of filaments 60A oriented parallel to a first axis A, and a second set of filaments 60B oriented parallel to a second axis B. The filaments 60A and 60B can be braided together in a biaxial braid such that filaments 60A oriented along axis A form an angle theta (0) with the filaments 60B oriented along axis B. In certain examples, the angle theta (0) can be from 5° to 70°, 10° to 60°, 10° to 50°, or 10° to 45°. In the illustrated example, the angletheta (0) is 45°. In other examples, the filaments 60 can also be oriented along three axes and braided in a triaxial braid, or oriented along any number of axes and braided in any suitable braid pattern. The braided layer 54 can extend along substantially the entire length of the sheath 40, or alternatively, can extend only along a portion of the length of the sheath.

[0235] The third layer 56 can be a resilient, elastic layer (also referred to as an elastic material layer). In certain examples, the elastic layer 56 can be configured to apply force to the underlying layers 52 and 54 in a radial direction (e.g., toward the central axis Cl of the sheath) when the sheath expands beyond its natural diameter by passage of the delivery apparatus through the sheath. Stated differently, the elastic layer 56 can be configured to apply encircling pressure to the layers of the sheath beneath the elastic layer 56 to counteract expansion of the sheath. The radially inwardly directed force is sufficient to cause the sheath to collapse radially back to its unexpanded state after the delivery apparatus is passed through the sheath.

[0236] In certain examples, one or both of the inner layer 52 and / or the outer layer 58 can be configured to resist axial elongation of the sheath 40 when the sheath expands. For example, one or both of the inner layer 52 and / or the outer layer 58 can resist stretching against longitudinal forces caused by friction between a prosthetic device and the inner surface of the sheath such that the length if sheath 40 remains substantially constant as the sheath expands and contracts. As used herein with reference to the length of the sheath, the term “substantially constant” means that the length of the sheath increases by not more than 1%, by not more than 5%, by not more than 10%, by not more than 15%, or by not more than 20%. Meanwhile, with reference to Fig. 16B, the filaments 60 A and 60B of the braided layer can be allowed to move angularly relative to each other such that the angle theta (0) changes as the sheath expands and contracts. This, in combination with the longitudinal creases 62 in the layers 52 and 58, can allow the sheath lumen 68 to expand as a prosthetic device is advanced through it.

[0237] Fig. 17 illustrates radial expansion of the sheath 40 as a prosthetic device 50 is passed through the sheath in the direction of arrow 82 (e.g., distally). As the prosthetic device 50 is advanced through the sheath 40, the sheath can resiliently expand to a second diameter D4 that corresponds to a size or diameter of the prosthetic device. As the prosthetic device 50 is advanced through the sheath 40, the prosthetic device can apply longitudinal force to the sheath in the direction of motion by virtue of the frictional contact between the prosthetic device and the inner surface of the sheath. However, as noted above, the inner layer 52 and / or the outer layer 58 can resist axial elongation such that the length of the sheath remains constant, or substantially constant. This can reduce or prevent the braided layer 54 from lengthening, and thereby constricting the sheath lumen 68. Additional examples of introducer devices andexpandable sheaths can be found in U.S. Patent No. 11,273,062, which is incorporated by reference in its entirety.

[0238] Figs. 18A-18B shows a distal portion of an exemplary introducer device assembly 20>. Introducer device assembly 20' is an exemplary implementation of introducer device assembly 20, and thus can include any of the features described for introducer device assembly 20 throughout the current disclosure, except that the introducer sheath 40' of introducer device assembly 20' comprises an inverting sleeve 220 at a distal end portion 200 thereof. Fig. 18 A shows the distal end portion 200 folded around an introducer 30, for example around the introducer's tapered distal portion 212. Fig. 18B is a perspective sectional view of the distal end portion 200 of the sheath 401folded around the introducer 30. The terms "introducer sheath 40" and "sheath 40", as used herein, are interchangeable.

[0239] The distal end portion 200 of introducer sheath 401, which terminates at sleeve distal fold 216, comprises an inverting sleeve 220, which may be similar to inverting sleeve 120 described hereinabove, but does not necessarily form the entire body of the introducer sheath 401and does not extend to the sheath proximal end 44. Inverting sleeve 220 comprises an outer first portion 224 having a proximal end 226 which is attached to sheath distal end 421. According to some examples, the inverting sleeve 220 can be optionally coupled to the inner layer 52 or to the outer layer 58 of the sheath 401.

[0240] Inverting sleeve 220 further comprises an inverted second portion 228, which is turned inwards and proximally retracted towards inverting sleeve proximal end 226. The distal opening 218, defined at sleeve distal fold 216, can be in fluid communication with lumen 68 of sheath 40. Second end 230 of inverting sleeve 220 is coupled to the inner surface of sleeve first portion 224, or to sheath distal end 42. According to some examples, second end 230 may be movable relative to first portion 224 and / or sheath distal end 42, when transitioning from an inverted to an everted state. For example, second end 230 may advance distally when being everted. In some examples, second end 230 is advanced distally when everted by a biasing member, in a manner that can be similar to that described hereinabove in relation to Fig. 11, mutatis mutandis.

[0241] According to some examples, the second end 230 is fixedly coupled, and optionally adhered or attached to an inner surface of sleeve first portion 224, or to the sheath distal end 421, thereby forming a cavity 222 having a substantially sealed volume V2 having an inlet feed opening, the cavity 222 enclosed between the first portion 224, the inverted second portion 228, and optionally sheath distal end 421. According to some examples, second end 230 is attached or adhered to proximal end 226 of the sleeve first portion 224, or to a region on theinner surface of first portion 224. According to some examples, second end 230 is attached or adhered to sheath distal end 421, such that the circumference of sheath distal end 42 also encloses cavity 222. According to some examples, sleeve second end 230 can be optionally attached or adhered to a more inner layer of sheath distal end 421relative to the layer thereof to which sleeve proximal end 226 is attached. For example, sleeve proximal end 226 may be attached to layer 58 or an outer surface thereof, and sleeve second end 230 may be attached to layer 54 and / or 56; sleeve proximal end 226 may be attached to layer 54, and sleeve second end 230 may be attached to layer 52 or the inner face thereof; and the like.

[0242] The distal end portion 200 and inverting sleeve 220 thereof may extend distally beyond a longitudinal portion of sheath 40 that includes braided layer 54 and elastic layer 56. In some examples, the braided layer 54 may extend distally beyond the elastic layer 56, and the distal end portion 200 and inverting sleeve 220 thereof may extend distally beyond both the braided layer 54 and elastic layer 56, as shown in Figs. 18A-18B.

[0243] According to some examples, the distal end portion 200 and inverting sleeve 220 thereof may have a smaller collapsed diameter than the more proximal portions of the sheath, giving it a tapered appearance. For example, the distal opening 218 may have a smaller diameter than the diameter surrounded by sleeve proximal end 226 and / or sheath distal end 421. In some examples, the diameter of distal opening 218 can decrease from the initial diameter of the sheath 40 (e.g., 8 mm) to 3.3 mm (10F), and may decrease to the diameter of a guidewire, allowing the sheath 40 and / or the introducer 30 to run on a guidewire. This smooths the transition between the introducer 30 and the sheath 40, preventing sheath 40 from getting lodged against the tissue during insertion into the patient.

[0244] The smaller collapsed diameter can be a result of multiple folds (for example, 1, 2, 3, 4, 5, 6, 7, or 8 folds) positioned circumferentially (evenly or unevenly spaced) around the distal end portion 200. For example, a circumferential segment of inverting sleeve 220 can be brought together and then laid against the adjacent outer surface of the inverting sleeve 220 to create an overlapping fold. In the collapsed configuration, the overlapping portions of the fold extend longitudinally along the distal end portion 200. Exemplary folding methods and configurations are described in U.S. Patent Numbers 10,792,471 and 10,327,896, each of which are hereby incorporated by reference in their entireties. Folding of the inverting sleeve 220 allow for the expansion of the distal end portion 200 upon sleeve eversion, for example by streaming fluid into the cavity 222 enclosed by the inverting sleeve 220 of distal end portion 200, which may ease the passage through and retraction of a delivery apparatus back into the sheath 40 once the procedure is complete.

[0245] According to some examples, sleeve second portion 228 has a substantially equal length to sleeve first portion 224. According to some examples, sleeve second portion 228 has a longer length than sleeve first portion 224. According to some examples, sleeve second portion 228 has a shorter length than sleeve first portion 224. When sheath distal end portion 200 is in a collapsed and inverted state, second portion 228 of inverting sleeve 220 may comprise folds 232. When second end 230 is axially anchored such that inverting sleeve 220 cannot be fully everted, eversion of inverting sleeve 220 may be achieved, for example, by the folds 232 being unfolded.

[0246] According to some examples, inverting sleeve is coupled to an everting element, configured to induce eversion of inverting sleeve 220. According to some examples, the everting element can be activated by an everting-activator which is external to sheath 401and to the vasculature of the subject. According to some examples, the everting element can be activated by an everting-activator which is introduced through sheath 40 and interacts with inverting sleeve 220 to induce eversion thereof. According to some examples, the everting element comprises a fluid inlet 202, in fluid communication with cavity 222 of inverting sleeve 220, which allows streaming of fluid into inverting sleeve 220. Fluid inlet 202 can be connected or coupled to a distal end of tube 204 which extends along sheath 401, such that a proximal end of the tube 204 is proximally external to sheath 401, allowing external introduction of fluid thereinto. The tube 204 can optionally extend within the lumen of sheath 40, or along the outer surface thereof. In some examples, the sheath 401can be a multi-lumen sheath, optionally defining a lumen that can extend, for example, through a wall thickness thereof, being in fluid communication with the cavity 222 instead of a separate tube.

[0247] According to some examples, the everting element comprises a biasing element (not shown with respect to the introducer sheath, but can be similar to any example described above for biasing member 190, including such as in the form of a spring). According to some examples, a proximal end of the biasing member can be optionally fixed to sheath distal end 421. According to some examples, a distal end of the biasing member can be attached to a sleeve second portion 228. According to some examples, the biasing member may be attached to sleeve second end 230, optionally when second end 230 is not axially anchored to a proximal region, e.g., sheath distal end 421or sleeve proximal end 226, as described hereinabove. According to some examples, the biasing member can be attached to a location on sleeve second portion 228 which is the most distally advanced when inverting sleeve 220 is everted. Thus, full opening or stretching of the spring can evert second portion 228 to its most distally advanced state.

[0248] According to some examples, a distal end of the biasing member can be configured to engage and push against the sleeve distal fold 216 without being attached thereto, such that when the biasing member is released, it impinges against the distal fold 216 to facilitate eversion of the sleeve 220. According to some examples, the biasing member can be coupled to an external activator. According to some examples, the spring may be activated, for example being released form a compressed state to an axially expanded state when implemented as a spring, by an activator that is introduced through the lumen of sheath 401.

[0249] Tn some examples, a distal end portion 200 comprising inverting sleeve 220 can be added, the sheath 401and distal end portion 200 can be crimped, and the crimping of the distal end portion 200 and sheath 401can be maintained, by the following method. As mentioned above, the distal end portion 200 comprises an inverting sleeve 220, which may be heat bonded to the remainder of the sheath 401prior to the tip crimping processing steps, optionally to a distal extension of the outer layer 58 of the sheath 401, to form the distal end portion 200. For crimping of the sheath 401after distal end portion 200 attachment, the sheath 401is heated on small mandrel. Inverting sleeve 220 can be folded around the mandrel to create the folded configuration shown in Fig. 18 A. The folds can be added to the inverting sleeve 220 prior to the distal end portion 200 crimping process, or at an intermediate point during the distal end portion 200 crimping process. In some examples, the small mandrel can be from about 2 millimeters to about 4 millimeters in diameter (including about 2.2 millimeters, about 2.4 millimeters, about 2.6 millimeters, about 2.8 millimeters, about 3.0 millimeters, about 3.2 millimeters, about 3.4 millimeters, about 3.6 millimeters, about 3.8 millimeters and about 4.0 millimeters).

[0250] The heating temperature will be lower than the melting point of the material used. This can cause the material to shrink on its own to a certain extent. The bonds formed at inverting sleeve 220 induced by the high temperature melting step, will still be weak enough to be broken when the inverting sleeve is everted by the everting element, e.g., by the push force of a biasing member or by the pressure of fluid streamed through fluid inlet 202.

[0251] In some examples, a method of utilizing introducer device assembly 20 can include advancing delivery apparatus 10 within the sheath 401until a point proximal to sheath distal end 42, activating an everting element (e.g., streaming fluid through tube 204 into cavity 222), thereby everting inverting sleeve 220, and pushing the delivery apparatus 10 distally towards and past sheath distal end 200.Some Examples of the Disclosed Implementations

[0252] Some examples of above-described implementations are enumerated below. It should be noted that one feature of an example in isolation or more than one feature of the example taken in combination and, optionally, in combination with one or more features of one or more examples below are examples also falling within the disclosure of this application.

[0253] Example 1. A delivery assembly, comprising: a delivery apparatus, comprising: an inverting sleeve comprising a first portion extending from a proximal end of the inverting sleeve, and a second portion continuously extending from the first portion and terminating at a second end of the inverting sleeve, wherein the inverting sleeve is configured to transition between an inverted state, in which the inverting sleeve is folded over itself such that the second portion is surrounded by at least a part of the first portion, and an at least partially everted state, in which at least part of the second portion is turned radially outwards relative to the inverted state; and a prosthetic valve configured to be distally advanced by the delivery apparatus during eversion of the inverting sleeve, the prosthetic valve comprising a frame movable between a radially compressed configuration and a radially expanded configuration.

[0254] Example 2. The delivery assembly of any example herein, particularly of example 1, wherein the prosthetic valve is coupled to the second portion of the inverting sleeve.

[0255] Example 3. The delivery assembly of any example herein, particularly of example 2, wherein the prosthetic valve is crimped over a bulge formed by the second portion of the inverting sleeve.

[0256] Example 4. The delivery assembly of any example herein, particularly of any one of examples 1 to 3, wherein the second portion of the inverting sleeve, when in the inverted state, is in at least a partially folded state.

[0257] Example 5. The delivery assembly of any example herein, particularly of any one of examples 1 to 4, further comprising a balloon catheter having a proximal end and a distal end and comprising a balloon at the distal end, wherein the balloon catheter extends longitudinally through the inverting sleeve.

[0258] Example 6. The delivery assembly of any example herein, particularly of example 5, wherein the balloon catheter is coupled to the inverting sleeve.

[0259] Example 7. The delivery assembly of any example herein, particularly of examples 5 or 6, wherein the proximal end of the balloon catheter extends proximally to the proximal end of the inverting sleeve.

[0260] Example 8. The delivery assembly of any example herein, particularly of any one of examples 5 to 7, wherein the distal end of the balloon catheter extends distally to the second end of the inverting sleeve.

[0261] Example 9. The delivery assembly of any example herein, particularly of any one of examples 5 to 8, wherein the second end of the inverting sleeve is attached to the balloon catheter.

[0262] Example 10. The delivery assembly of any example herein, particularly of example 9, wherein the second end of the inverting sleeve is attached to the balloon catheter at a location which is proximal to the balloon.

[0263] Example 11. The delivery assembly of any example herein, particularly of example 8, further comprising a push-member that extends radially outwards, positioned distally to the inverting sleeve, and configured to be contacted by and advanced distally by the inverting sleeve when the inverting sleeve is being everted.

[0264] Example 12. The delivery assembly of any example herein, particularly of example 11, wherein the push-member is attached to the balloon catheter at a location which is proximal to the balloon.

[0265] Example 13. The delivery assembly of any example herein, particularly of example 11, further comprising a push-member shaft attached to and extending proximally from the pushmember, wherein the push-member shaft extends longitudinally through the inverting sleeve.

[0266] Example 14. The delivery assembly of any example herein, particularly of example 13, wherein a proximal end of the push member shaft extends proximally to the proximal end of the inverting sleeve.

[0267] Example 15. The delivery assembly of any example herein, particularly of examples 13 or 14, wherein the balloon catheter extends longitudinally through the push-member shaft.

[0268] Example 16. The delivery assembly of any example herein, particularly of example 15, wherein the proximal end of the balloon catheter extends proximally to the proximal end of the push-member shaft.

[0269] Example 17. The delivery assembly of any example herein, particularly of any one of examples 1 to 16, wherein the delivery apparatus is liquid- tight.

[0270] Example 18. The delivery assembly of any example herein, particularly of any one of examples 1 to 17, wherein the delivery apparatus is air-tight.

[0271] Example 19. The delivery assembly of any example herein, particularly of any one of examples 1 to 18, wherein the second end of the inverting sleeve is a closed end.

[0272] Example 20. The delivery assembly of any example herein, particularly of any one of examples 1 to 19, wherein the inverting sleeve, when in the inverted state, defines a cavity between the first portion and the second portion.

[0273] Example 21. The delivery assembly of any example herein, particularly of example 20, further comprising a fluid inlet in fluid communication with the cavity defined by the inverting sleeve, wherein introduction of fluid through the fluid inlet into the cavity is configured to induce eversion of the inverting sleeve.

[0274] Example 22. The delivery assembly of any example herein, particularly of example 21, wherein the fluid inlet is sealably coupled to the inverting sleeve.

[0275] Example 23. The delivery assembly of any example herein, particularly of examples 21 or 22, wherein the fluid inlet is located proximally to the inverting sleeve.

[0276] Example 24. The delivery assembly of any example herein, particularly of any one of examples 21 to 23, wherein at least one of the fluid inlet and the first portion of the inverting sleeve further comprises a catheter passage, configured to allow slidable movement of a catheter therethrough.

[0277] Example 25. The delivery assembly of any example herein, particularly of example 24, wherein the catheter passage is configured to enclose the catheter in a liquid-tight manner.

[0278] Example 26. The delivery assembly of any example herein, particularly of example 24, wherein the catheter passage is configured to enclose the catheter in an air-tight manner.

[0279] Example 27. The delivery assembly of any example herein, particularly of any one of examples 1 to 26, further comprising a biasing member having a proximal end and a distal end, wherein the proximal end of the biasing member is axially fixed relative to the proximal end of the inverting sleeve, and wherein the biasing member is configured to controllably transition between at least two of a compressed state, a relaxed state, and a stretched state.

[0280] Example 28. The delivery assembly of any example herein, particularly of example 27, wherein proximal end of the biasing member is coupled to the proximal end of the inverting sleeve.

[0281] Example 29. The delivery assembly of any example herein, particularly of examples 27 or 28, wherein the distal end of the biasing member is coupled to the second portion of the inverting sleeve.

[0282] Example 30. The delivery assembly of any example herein, particularly of example 29, wherein the distal end of the biasing member is coupled to the second end of the inverting sleeve.

[0283] Example 31. The delivery assembly of any example herein, particularly of any one of examples 27 to 30, wherein the distal end of the biasing member is configured to push against a distal fold of the inverting sleeve, the distal fold formed between the first portion and thesecond portion at a distal end of the inverting sleeve, at least when the inverting sleeve is in the inverted state.

[0284] Example 32. The delivery assembly of any example herein, particularly of any one of examples 27 to 31, wherein the distal end of the biasing member is coupled to a distal fold of the inverting sleeve, the distal fold formed between the first portion and the second portion at a distal end of the inverting sleeve, at least when the inverting sleeve is in the inverted state.

[0285] Example 33. The delivery assembly of any example herein, particularly of any one of examples 27 to 32, wherein the biasing member comprises a spring.

[0286] Example 34. The delivery assembly of any example herein, particularly of any one of examples 1 to 33, further comprising a sleeve housing configured to contain at least part of the inverting sleeve when in the inverted state, wherein the sleeve housing comprises, at a distal end thereof, a sleeve-passage sized to allow passage of the inverting sleeve therethrough.

[0287] Example 35. The delivery assembly of any example herein, particularly of example 34, wherein the sleeve housing is axially fixed relative to the proximal end of the inverting sleeve.

[0288] Example 36. The delivery assembly of any example herein, particularly of examples 34 or 35, wherein the sleeve housing is coupled to the proximal end of the inverting sleeve.

[0289] Example 37. The delivery assembly of any example herein, particularly of any one of examples 34 to 36, wherein the sleeve-passage is sized to allow passage of the prosthetic valve when in the radially compressed configuration.

[0290] Example 38. The delivery assembly of any example herein, particularly of any one of examples 34 to 37, further comprising a funnel crimper distally extending from the sleevepassage, wherein the funnel crimper extends from a narrow opening which is closer to the sleeve passage, to a wide opening which is farther from the sleeve passage, wherein the narrow opening is sized to allow passage of the prosthetic valve when in the radially compressed configuration, and wherein the wide opening is sized to allow insertion of the prosthetic valve, when in the expanded configuration, into the funnel crimper.

[0291] Example 39. The delivery assembly of any example herein, particularly of example 38, wherein the funnel crimper is coupled to the sleeve housing.

[0292] Example 40. The delivery assembly of any example herein, particularly of example 39, wherein the funnel crimper is coupled to the sleeve-passage.

[0293] Example 41. The delivery assembly of any example herein, particularly of examples 38 or 39, wherein the funnel crimper is releasably attached to the sleeve housing.

[0294] Example 42. The delivery assembly of any example herein, particularly of any one of examples 1 to 41, further comprising an introducer tube configured to be inserted via an entry-point into a patient, and comprising an opening sized to allow advancement of the inverting sleeve therethrough.

[0295] Example 43. The delivery assembly of any example herein, particularly of example 42, further comprising a sleeve housing configured to contain at least part of the inverting sleeve when in the inverted state, wherein the sleeve housing comprises, at a distal end thereof, a sleeve-passage sized to allow passage of the inverting sleeve therethrough, and wherein the introducer tube extends distally from the sleeve-passage of the sleeve housing.

[0296] Example 44. The delivery assembly of any example herein, particularly of example 43, wherein the introducer tube is releasably coupled to the sleeve-passage of the sleeve housing.

[0297] Example 45. The delivery assembly of any example herein, particularly of examples 42 or 43, wherein the introducer tube is rigid.

[0298] Example 46. The delivery assembly of any example herein, particularly of any one of examples 42 to 44, wherein the opening of the introducer tube is sized to allow passage of the prosthetic valve when in the radially compressed configuration.

[0299] Example 47. The delivery assembly of any example herein, particularly of any one of examples 1 to 45, wherein the diameter of the of the inverting sleeve, in the everted state, is non-uniform at least along a length thereof.

[0300] Example 48. The delivery assembly of any example herein, particularly of example 46, wherein the diameter of the second end of the inverting sleeve, when in the everted state, is larger than the diameter of the proximal end of the inverting sleeve.

[0301] Example 49. The delivery assembly of any example herein, particularly of any one of examples 1 to 48, further comprising a tissue engagement sleeve releasably disposed over an outer surface of at least part of the inverting sleeve.

[0302] Example 50. The delivery assembly of any example herein, particularly of example 49, wherein the tissue engagement sleeve further comprises a plurality of anchoring elements on an outer surface thereof, configured to couple the tissue engagement sleeve to a tissue contacted thereby.

[0303] Example 51. The delivery assembly of any example herein, particularly of examples 49 or 50, wherein the tissue engagement sleeve further comprises an active ingredient configured to be released from the tissue engagement sleeve when the tissue engagement sleeve is implanted.

[0304] Example 52. An introducer device assembly, comprising: an introducer sheath defining a lumen and extending between a proximal end and a distal end of the introducer sheath; and a distal end portion comprising an inverting sleeve, the inverting sleeve comprising a first portionextending from a proximal end of the inverting sleeve, and a second portion continuously extending from the first portion and terminating at a second end of the inverting sleeve, wherein the proximal end of the inverting sleeve is coupled to the distal end of the introducer sheath, and wherein the inverting sleeve is configured to transition between an inverted state and an everted state.

[0305] Example 53. The introducer device assembly of any example herein, particularly of example 52, wherein when in the inverted state the inverting sleeve is folded over itself such that the second portion is surrounded by at least a part of the first portion, and when in the everted state at least part of the second portion of the inverting sleeve is turned radially outwards relative to the inverted state.

[0306] Example 54. The introducer device assembly of any example herein, particularly of examples 52 or 53, wherein the distal end portion defines a distal opening which is in fluid communication with the lumen of the introducer sheath.

[0307] Example 55. The introducer device assembly of any example herein, particularly of example 54, wherein, when the inverting sleeve is in the inverted state, the distal end portion is configured to be in an inverted collapsed state, such that the distal opening is smaller than the diameter of the sheath.

[0308] Example 56. The introducer device assembly of any example herein, particularly of any one of examples 52 to 55, wherein the inverting sleeve, when in the inverted state, defines a cavity between the first portion and the second portion.

[0309] Example 57. The introducer device assembly of any example herein, particularly of example 56, further comprising a fluid inlet in fluid communication with the cavity defined by the inverting sleeve, wherein introduction of fluid through the fluid inlet into the cavity is configured to induce eversion of the inverting sleeve.

[0310] Example 58. The introducer device assembly of any example herein, particularly of example 57, further comprising a tube extending longitudinally along the introducer sheath, the tube having a proximal end and a distal end, wherein the distal end of the tube is in fluid communication with the fluid inlet, and wherein the proximal end of the tube extends proximally to the proximal end of the sheath.

[0311] Example 59. The introducer device assembly of any example herein, particularly of example 58, wherein the tube extends through the lumen of the introducer sheath.

[0312] Example 60. The introducer device assembly of any example herein, particularly of example 58, wherein the tube extends along an outer surface of the introducer sheath.

[0313] Example 61. A delivery apparatus, comprising: an inverting sleeve comprising a first portion extending from a proximal end of the inverting sleeve, and a second portion continuously extending from the first portion and terminating at a second end of the inverting sleeve, wherein the inverting sleeve is configured to transition between an inverted state, in which the inverting sleeve is folded over itself such that the second portion is surrounded by at least a part of the first portion, and an at least partially everted state, in which at least part of the second portion is turned radially outwards relative to the inverted state; wherein the inverting sleeve is sized to be advanced within vasculature of a subject.

[0314] Example 62. The delivery apparatus of any example herein, particularly of example 61, wherein the second portion of the inverting sleeve, when in the inverted state, is in at least a partially folded state.

[0315] Example 63. The delivery apparatus of any example herein, particularly of examples 61 or 62, being liquid-tight.

[0316] Example 64. The delivery apparatus of any example herein, particularly of any one of examples 61 to 63, being air-tight.

[0317] Example 65. The delivery apparatus of any example herein, particularly of any one of examples 61 to 64, wherein the second end of the inverting sleeve is a closed end.

[0318] Example 66. The delivery apparatus of any example herein, particularly of any one of examples 61 to 65, wherein the inverting sleeve, when in the inverted state, defines a cavity between the first portion and the second portion.

[0319] Example 67. The delivery apparatus of any example herein, particularly of example 66, further comprising a fluid inlet in fluid communication with the cavity defined by the inverting sleeve, wherein introduction of fluid through the fluid inlet into the cavity is configured to induce eversion of the inverting sleeve.

[0320] Example 68. The delivery apparatus of any example herein, particularly of example 67, wherein the fluid inlet is sealably coupled to the inverting sleeve.

[0321] Example 69. The delivery apparatus of any example herein, particularly of examples 67 or 68, wherein the fluid inlet is located proximally to the inverting sleeve.

[0322] Example 70. The delivery apparatus of any example herein, particularly of any one of examples 67 to 69, wherein at least one of the fluid inlet and the first portion of the inverting sleeve further comprises a catheter passage, configured to allow slidable movement of a catheter therethrough.

[0323] Example 71. The delivery apparatus of any example herein, particularly of example 70, wherein the catheter passage is configured to enclose the catheter in a liquid-tight manner.

[0324] Example 72. The delivery apparatus of any example herein, particularly of example 70, wherein the catheter passage is configured to enclose the catheter in an air-tight manner.

[0325] Example 73. The delivery apparatus of any example herein, particularly of any one of examples 61 to 72, further comprising a biasing member having a proximal end and a distal end, wherein the proximal end of the biasing member is axially fixed relative to the proximal end of the inverting sleeve, and wherein the biasing member is configured to controllably transition between at least two of a compressed state, a relaxed state, and a stretched state.

[0326] Example 74. The delivery apparatus of any example herein, particularly of example 73, wherein proximal end of the biasing member is coupled to the proximal end of the inverting sleeve.

[0327] Example 75. The delivery apparatus of any example herein, particularly of examples 73 or 74, wherein the distal end of the biasing member is coupled to the second portion of the inverting sleeve.

[0328] Example 76. The delivery apparatus of any example herein, particularly of example 75, wherein the distal end of the biasing member is coupled to the second end of the inverting sleeve.

[0329] Example 77. The delivery apparatus of any example herein, particularly of any one of examples 73 to 76, wherein the distal end of the biasing member is configured to push against a distal fold of the inverting sleeve, the distal fold formed between the first portion and the second portion at a distal end of the inverting sleeve, at least when the inverting sleeve is in the inverted state.

[0330] Example 78. The delivery apparatus of any example herein, particularly of any one of examples 73 to 77, wherein the distal end of the biasing member is coupled to a distal fold of the inverting sleeve, the distal fold formed between the first portion and the second portion at a distal end of the inverting sleeve, at least when the inverting sleeve is in the inverted state.

[0331] Example 79. The delivery apparatus of any example herein, particularly of any one of examples 73 to 78, wherein the biasing member comprises a spring.

[0332] Example 80. The delivery apparatus of any example herein, particularly of any one of examples 61 to 79, wherein the diameter of the of the inverting sleeve, in the everted state, is non-uniform at least along a length thereof.

[0333] Example 81. The delivery apparatus of any example herein, particularly of example 80, wherein the diameter of the second end of the inverting sleeve, when in the everted state, is larger than the diameter of the proximal end of the inverting sleeve.

[0334] Example 82. The delivery apparatus of any example herein, particularly of any one of examples 61 to 81, further comprising a tissue engagement sleeve releasably disposed over an outer surface of at least part of the inverting sleeve.

[0335] Example 83. The delivery apparatus of any example herein, particularly of example 82, wherein the tissue engagement sleeve further comprises a plurality of anchoring elements on an outer surface thereof, configured to couple the tissue engagement sleeve to a tissue contacted thereby.

[0336] Example 84. The delivery apparatus of any example herein, particularly of examples 82 or 83, wherein the tissue engagement sleeve further comprises an active ingredient configured to be released from the tissue engagement sleeve when the tissue engagement sleeve is implanted.

[0337] Example 85. The delivery apparatus of any example herein, particularly of any one of examples 61 to 84, wherein at least a portion of the inverting sleeve is a stretchable portion.

[0338] Example 86. The delivery apparatus of any example herein, particularly of example 85, wherein the stretchable portion is at a distal end of the inverting sleeve when in the everted state.

[0339] It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate examples, may also be provided in combination in a single example. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single example, may also be provided separately or in any suitable sub-combination or as suitable in any other described example of the disclosure. No feature described in the context of an example is to be considered an essential feature of that example, unless explicitly specified as such.

[0340] In view of the many possible examples to which the principles of the disclosure may be applied, it should be recognized that the illustrated examples are only preferred examples and should not be taken as limiting the scope. Rather, the scope is defined by the following claims. We therefore claim all that comes within the scope and spirit of these claims.

Claims

CLAIMS1. A delivery assembly, comprising: a delivery apparatus, comprising: an inverting sleeve comprising a first portion extending from a proximal end of the inverting sleeve, and a second portion continuously extending from the first portion and terminating at a second end of the inverting sleeve, wherein the inverting sleeve is configured to transition between an inverted state, in which the inverting sleeve is folded over itself such that the second portion is surrounded by at least a part of the first portion, and an at least partially everted state, in which at least part of the second portion is turned radially outwards relative to the inverted state; and a prosthetic valve configured to be distally advanced by the delivery apparatus during eversion of the inverting sleeve, the prosthetic valve comprising a frame movable between a radially compressed configuration and a radially expanded configuration.

2. The delivery assembly of claim 1 , wherein the prosthetic valve is coupled to the second portion of the inverting sleeve.

3. The delivery assembly of claim 2, wherein the prosthetic valve is crimped over a bulge formed by the second portion of the inverting sleeve.

4. The delivery assembly of any one of claims 1 to 3, further comprising a balloon catheter having a proximal end and a distal end and comprising a balloon at the distal end, wherein the balloon catheter extends longitudinally through the inverting sleeve.

5. The delivery assembly of claim 4, wherein the balloon catheter is coupled to the inverting sleeve.

6. The delivery assembly of claim 5, further comprising a push-member that extends radially outwards, positioned distally to the inverting sleeve, and configured to be contacted by and advanced distally by the inverting sleeve when the inverting sleeve is being everted.

7. The delivery assembly of any one of claims 1 to 6, wherein the delivery apparatus is liquid-tight.

8. The delivery assembly of any one of claims 1 to 7, wherein the delivery apparatus is air-tight.

9. The delivery assembly of any one of claims 1 to 8, wherein the inverting sleeve, when in the inverted state, defines a cavity between the first portion and the second portion, and wherein the delivery assembly further comprises a fluid inlet in fluid communication with the cavity defined by the inverting sleeve, wherein introduction of fluid through the fluid inlet into the cavity is configured to induce eversion of the inverting sleeve.

10. The delivery assembly of any one of claims 1 to 9, further comprising a biasing member having a proximal end and a distal end, wherein the proximal end of the biasing member is axially fixed relative to the proximal end of the inverting sleeve, and wherein the biasing member is configured to controllably transition between at least two of a compressed state, a relaxed state, and a stretched state.

11. The delivery assembly of any one of claims 1 to 10, further comprising a sleeve housing configured to contain at least part of the inverting sleeve when in the inverted state, wherein the sleeve housing comprises, at a distal end thereof, a sleeve-passage sized to allow passage of the inverting sleeve therethrough.

12. The delivery assembly of claim 11 , further comprising a funnel crimper distally extending from the sleeve-passage, wherein the funnel crimper extends from a narrow opening which is closer to the sleeve passage, to a wide opening which is farther from the sleeve passage, wherein the narrow opening is sized to allow passage of the prosthetic valve when in the radially compressed configuration, and wherein the wide opening is sized to allow insertion of the prosthetic valve, when in the expanded configuration, into the funnel crimper.

13. The delivery assembly of any one of claims 1 to 12, wherein the diameter of the second end of the inverting sleeve, when in the everted state, is larger than the diameter of the proximal end of the inverting sleeve.

14. An introducer device assembly, comprising: an introducer sheath defining a lumen and extending between a proximal end and a distal end of the introducer sheath; and a distal end portion comprising an inverting sleeve, the inverting sleeve comprising a first portion extending from a proximal end of the inverting sleeve, and a second portion continuously extending from the first portion and terminating at a second end of the inverting sleeve, wherein the proximal end of the inverting sleeve is coupled to the distal end of the introducer sheath, andwherein the inverting sleeve is configured to transition between an inverted state and an everted state.

15. The introducer device assembly of claim 14, wherein when in the inverted state the inverting sleeve is folded over itself such that the second portion is surrounded by at least a part of the first portion, and when in the everted state at least part of the second portion of the inverting sleeve is turned radially outwards relative to the inverted state.

16. The introducer device assembly of claims 14 or 15, wherein the distal end portion defines a distal opening which is in fluid communication with the lumen of the introducer sheath.

17. The introducer device assembly of claim 16, wherein, when the inverting sleeve is in the inverted state, the distal end portion is configured to be in an inverted collapsed state, such that the distal opening is smaller than the diameter of the sheath.

18. The introducer device assembly of any one of claims 14 to 17, wherein the inverting sleeve, when in the inverted state, defines a cavity between the first portion and the second portion, and wherein the introducer device assembly further comprises a fluid inlet in fluid communication with the cavity defined by the inverting sleeve, wherein introduction of fluid through the fluid inlet into the cavity is configured to induce eversion of the inverting sleeve.

19. A delivery apparatus, comprising: an inverting sleeve comprising a first portion extending from a proximal end of the inverting sleeve, and a second portion continuously extending from the first portion and terminating at a second end of the inverting sleeve, wherein the inverting sleeve is configured to transition between an inverted state, in which the inverting sleeve is folded over itself such that the second portion is surrounded by at least a part of the first portion, and an at least partially everted state, in which at least part of the second portion is turned radially outwards relative to the inverted state; wherein the inverting sleeve is sized to be advanced within vasculature of a subject.

20. The delivery apparatus of claim 19, being liquid-tight.

21. The delivery apparatus of claims 19 or 20, wherein the inverting sleeve, when in the inverted state, defines a cavity between the first portion and the second portion, and wherein the delivery apparatus further comprises a fluid inlet in fluid communication with the cavity defined by the inverting sleeve, wherein introduction of fluid through the fluid inlet into the cavity is configured to induce eversion of the inverting sleeve.

22. The delivery apparatus of any one of claims 19 to 21 , further comprising a tissue engagement sleeve releasably disposed over an outer surface of at least part of the inverting sleeve.

23. The delivery apparatus of any one of claims 19 to 22, wherein at least a portion of the inverting sleeve is a stretchable portion.

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