Coated flow correction device

Abstract

To provide a suitable coated flow correction device. [Solution] A flow modification device may include a plurality of struts joined together to form a radially expandable frame having a proximal end and a distal end. The proximal and distal ends may be radially expandable to the expanded proximal and distal ends. A reduced diameter portion of the expandable frame may be disposed between the expanded proximal and distal ends, the reduced diameter portion providing a fluid flow passageway therethrough. A cover may be disposed over at least a portion of the radially expandable frame. The reduced diameter portion modifies fluid flow therethrough immediately after implantation, creating a pressure gradient between the inflow end and the reduced diameter portion.

Description

Background Art

[0001] (Claiming Priority) This application claims the benefit of priority of U.S. Provisional Patent Application No. 62 / 795,836, filed on Jan. 23, 2019 (Attorney Docket No. 5130.020PRV), and U.S. Provisional Patent Application No. 62 / 868,356, filed on Jun. 28, 2019 (Attorney Docket No. 5130.020PV2), each of which is incorporated herein by reference in its entirety.

[0002] (Cross - Reference to Related Applications) This application relates to U.S. Patent No. 9,364,354, the entire content of which is incorporated herein by reference.

[0003] (Background) Obstruction and / or stenosis of the coronary artery can result in chronic pain known as angina pectoris. While not life - threatening, angina pectoris can cause a change in the quality of life. Various treatments exist to address angina pectoris, such as drug therapy, stent implantation, balloon angioplasty, coronary artery bypass grafting (CABG), etc. Angina pectoris, where medical and interventional therapies are ineffective, is a common and everyday - life - disrupting medical condition and a major public health problem affecting millions of patients worldwide. This is common not only in patients who are not good candidates for revascularization but also in patients after successful revascularization. The prevalence of angina pectoris is as high as 25% one year after revascularization and can reach up to 45% three years later. Various treatments for angina pectoris are currently available. Each treatment is promising but may be limited to certain indications for use, and thus, new treatments are desirable.

Summary of the Invention

Means for Solving the Problems

[0004] Example 1 is a plurality of struts that are coupled together to form a radially expandable frame having proximal and distal ends, wherein the proximal and distal ends are radially expandable to the expanded proximal and distal ends, a plurality of struts; a reduced diameter portion of the expandable frame disposed between the expanded proximal and distal ends, the reduced diameter portion comprising a fluid flow through a passageway, the reduced diameter portion; and a cover disposed over at least a portion of the radially expandable frame, the reduced diameter portion being a flow modifying device that modifies the fluid flow therethrough immediately after its implantation and forms a pressure gradient between the inlet end and the reduced diameter portion.

[0005] For example, the present invention provides the following items. (Item 1) A flow modifying device, a plurality of struts that are coupled together to form a radially expandable frame having proximal and distal ends, the proximal and distal ends being radially expandable to the expanded proximal and distal ends, a plurality of struts; a reduced diameter portion of the expandable frame disposed between the expanded proximal and distal ends, the reduced diameter portion comprising a fluid flow through a passageway, the reduced diameter portion; and a cover disposed over at least a portion of the radially expandable frame comprising, wherein the reduced diameter portion is a flow modifying device that modifies the fluid flow therethrough immediately after its implantation and forms a pressure gradient between the inlet end and the reduced diameter portion. (Item 2) The device according to item 1, wherein the pressure gradient is greatest between the inlet end of the device and the reduced diameter portion. (Item 3) The device according to item 1, wherein the velocity of the fluid flow is greatest within the reduced diameter portion. (Item 4) The device according to item 1, wherein the expanded proximal and distal ends are flared ends. (Item 5) The device according to item 1, wherein the radially expandable frame has an outer surface and the cover is disposed over only a portion of the outer surface. (Item 6) The radially expandable frame has an outer surface, and the cover is disposed over all of the outer surface, the apparatus according to item 1. (Item 7) The cover is disposed only over the reduced diameter portion, the apparatus according to item 1. (Item 8) The expanded proximal and distal ends remain at least partially uncovered, the apparatus according to item 1. (Item 9) The cover includes a polymer, fabric, synthetic material, tissue, or a combination thereof, the apparatus according to item 1. (Item 10) The cover is centered over at least 2 / 3 of the expandable frame, the apparatus according to item 1. (Item 11) The cover is positioned over the reduced diameter portion such that when the flow modifying implant is radially expanded to engage the blood vessel, the cover does not contact the blood vessel directly, thereby modifying or preventing an inflammatory response, the apparatus according to item 1. (Item 12) The cover is configured to prevent or minimize an inflammatory response by the blood vessel wall, the apparatus according to item 1. (Item 13) The reduced diameter portion has a diameter of 2 to 4 mm, the apparatus according to item 1. (Item 14) The plurality of struts form a plurality of rectangular slots when the expandable frame is in a collapsed configuration, and the plurality of rectangular slots expand into a rhombus shape when the expandable frame is in a radially expanded configuration, the rhombus shape having a height and a length, the height decreasing from the proximal and distal ends toward a center point disposed therebetween, the apparatus according to item 1. (Item 15) The length decreases from the proximal and distal ends toward the center point, the apparatus according to item 14. (Item 16) The flow modification device according to item 1, which is self-expanding or balloon-expandable. (Item 17) The device according to item 1, further comprising an inflow end and an outflow end, wherein the cover is disposed only on the inflow end or only on the outflow end. (Item 18) A system for delivering a flow modification implant, the system comprising: The flow modification implant according to item 1; and A delivery catheter and comprising a system. (Item 19) A method for modifying flow within a blood vessel, the method comprising: Providing a flow modification device having a proximal end and a distal end; Delivering the flow modification device to a target treatment region within the blood vessel; Radially expanding the flow modification device such that the proximal end and the distal end are larger in diameter than a reduced diameter portion disposed therebetween; Immediately modifying blood flow through the flow modification device in response to delivery of the flow modification device, thereby forming a pressure gradient between an inflow end of the flow modification device and the reduced diameter portion, wherein a cover disposed across the flow modification device facilitates the modification of the blood flow; and including a method. (Item 20) The method according to item 19, wherein the velocity of the fluid flow is maximized within the reduced diameter portion. (Item 21) The method according to item 19, wherein radially expanding the flow modification device includes forming flare regions at the proximal end and the distal end. (Item 22) The method according to item 19, wherein radially expanding the flow modification device includes expanding a cover disposed only over a portion of the outer surface of the flow modification device. (Item 23) Expanding the flow modification device radially includes expanding the cover, the cover being disposed over all of the outer surface of the flow modification device, the method of item 19. (Item 24) Expanding the flow modification device radially includes expanding the cover, the cover being disposed only over the reduced diameter region, the method of item 19. (Item 25) Expanding the flow modification device radially includes expanding the cover, the proximal and distal ends remaining at least partially uncovered, the method of item 19. (Item 26) Expanding the flow modification device radially includes expanding the cover without direct contact with the blood vessel, thereby modifying or preventing an inflammatory response, the method of item 19. (Item 27) Expanding the flow modification device radially includes forming rhomboid-shaped cells from rectangular-shaped cells, the height of the rhomboid-shaped cells decreasing from the proximal and distal ends towards a central point disposed therebetween, the method of item 19. (Item 28) The rhomboid-shaped cells have a length, the length decreasing from the proximal and distal ends towards the reduced diameter region, the method of item 27. In drawings that are not necessarily drawn to scale, like numbers may identify similar components in different figures. Like numbers with different letter suffixes may represent different instances of similar components. The drawings, generally as examples and not by way of limitation, illustrate various embodiments discussed in this document.

Brief Description of the Drawings

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DETAILED DESCRIPTION OF THE INVENTION

[0026] In drawings that are not necessarily drawn to scale, like numbers may identify similar components in different figures. Like numbers with different letter suffixes may represent different instances of similar components. The drawings generally, as examples and not limitations, illustrate various embodiments discussed in this document.

[0027] Figure 1 is a schematic view showing a flow modification implant 100 disposed within a coronary sinus 102. The coronary sinus 102 communicates a plurality of cardiac veins 106 into the right atrium 104. The cardiovascular system is generally hierarchical and comprises stages of blood vessels of decreasing (or increasing) diameter. Thus, the veins 106 in turn communicate with a plurality of thin venules 108, which after several stages communicate with a plurality of capillaries 110. The capillaries 110 are fed by a plurality of arterioles 112, which after several stages are fed by a plurality of coronary arteries 114 and 120. A stenosis 116 is shown within the coronary artery 114. The cardiovascular system is generally hierarchical, but there are some connections that exist between different branches. Occasionally, the presence of the stenosis 116 will cause a collateral connection 118 to form naturally (or widen an existing connection) between the coronary arteries 114 and 120 that bypasses the stenosis 116.

[0028] However, in some cases, this natural formation does not occur. In any embodiment, the flow-modifying implant 100 is placed within the coronary sinus 102 and has a sufficiently significant narrowing to promote the formation of collateral connections 118. Without being bound by any theory, it is hypothesized that the collateral connection 118 is caused by an increase in venous blood pressure, which in turn increases the pressure within the capillaries and / or causes retrograde flow within the capillaries and / or causes a direct capillary connection to the heart. However, even if this hypothesis is incorrect, several studies, including numerous experiments and actual procedures, have shown that constriction of the coronary sinus 102 will generally cause the formation of collateral circulation and / or improve the condition of patients with otherwise occluded coronary arteries. Optionally, alternative or additional hypotheses used to select the constriction effect of the flow-modifying implant 100 include the following. (a) The flow-modifying implant 100 increases the pressure upstream of the implant within the coronary capillaries and thus increases the perfusion duration. (b) An increase in venous system resistance causes a redistribution of blood flow within the coronary arteries. (c) An increase in venous system resistance increases the myocardial perfusion pressure and / or the intramyocardial pressure. (d) Increasing the arterial diastolic pressure (by restricting venous drainage), such as through autoregulation as described in, for example, Braunwald "Heart Disease: A Textbook of Cardiovascular Medicine", 5th Edition, 1997, W.B. Saunders Company, Chapter 36, pages 1168 - 1169, causes the arterial autoregulation to begin to function again.

[0029] Note that the selection of the flow-modifying implant 100 can be made optionally, to achieve one or more of the effects suggested above, to the extent desired, such as allowing a certain degree of drainage and maximum pressure enabled by the coronary venous drainage system, and / or taking into account safety issues.

[0030] Figure 2 is a schematic side view of a flow-modifying implant 100 that can be used in any of the embodiments herein. The flow-modifying implant 100 includes a narrowing section 204 and at least one flared section 200 (and optionally, the opposing end 202 is also flared) that connects to the narrowing section 204. The sections 200 (and optionally, 202) include sections 210 and 206 that are inclined with respect to the wall of the coronary sinus 102 and sections 212 and 208 that are substantially parallel to the vessel wall.

[0031] In the embodiments and measurements shown or in any embodiment of this specification, the flow modification implant 100 is radially expandable and may be slightly shortened during expansion, and the implant may have a length of 20 mm before expansion and about 18.8 mm after expansion. Optionally, in any embodiment, a non-shortening design, such as a mesh as in a creep stent as described in U.S. Patent No. 5,662,713, the disclosure of which is incorporated herein by reference, may be used. An example of the material thickness that can be used is 0.15 mm, however, thinner or thicker materials may be used. Other examples of implant lengths are 5 mm, 12 mm, 24 mm, 35 mm, 45 mm, and any smaller, intermediate, or larger size may be used. The length is optionally selected to match the physiological size (e.g., length and curvature) of the target vein and / or to ensure good contact with the vein wall. The length of the narrowing section 204 may be, for example, 0.5 mm, 1 mm, 2 mm, 3 mm, 5 mm, or any shorter, intermediate, or longer length may be used to achieve the desired flow dynamics. Exemplary inner diameters of the flare section are 2 mm to 30 mm, e.g., 5 mm, 10 mm, 15 mm, 20 mm, or any larger, smaller, or intermediate diameter may be used in any embodiment to match the vein or blood vessel diameter. The inner diameter of the narrowing section may be, for example, 1 mm, 2 mm, 3 mm, 5 mm, 10 mm, or any smaller, larger, or intermediate diameter may be used in any embodiment to achieve the desired flow dynamics and / or the desired pressure difference across the flow modification implant.

[0032] In any embodiment of the flow modification implant, the ratio between the cross-section of the narrowing section 204 and the flare of the flow modification implant 100 may be 0.9, 0.8, 0.6, 0.4, 0.2, or any larger, smaller, or intermediate ratio may be used to achieve the desired flow dynamics and / or the desired pressure difference across the flow modification implant.

[0033] A circular cross-section is shown, but any other cross-section, such as polygonal, oval, and elliptical, may be used. A potential advantage of a non-circular cross-section is that the implant is less likely to move axially and / or rotate. Alternatively, or in addition, in any embodiment, the outside of the flow-modifying implant is roughened and / or otherwise adapted to adhere to the vein wall. The cross-sectional shape and / or orientation in any embodiment may optionally vary along the length of the flow-modifying implant 100.

[0034] FIG. 3A is a flat layout of the cut pattern of the slit-type flow-modifying implant, and FIG. 3B is a detail of FIG. 3A. In this planar layout, the ends of sections 200 and 202 are made to be parallel to the blood vessel wall when the flow-modifying implant 100 is expanded.

[0035] In any embodiment, the outer flare of the flow-modifying implant 100 is defined by sections 340 and 342 shown in FIG. 3B. Optionally, in any embodiment, the total length of these sections defines the maximum flare length. Alternatively, or in addition, in any embodiment, the flexure areas within and between these sections define the relative forces required to expand the flare region relative to the area near the periphery. If the peripheral region is more difficult to expand than, and / or expands less than, the adjacent regions, the expansion of the flow-modifying implant 100 will tend to bend the periphery inward or at least not flare it outward. Alternatively, in a self-expanding flow-modifying implant, the presence of sections 340 and 342 can be used to determine the final shape of the flare. Optionally, in any embodiment, an additional section 346 is provided around the circumference of the flow-modifying implant 100, which defines an outer slit within the flow-modifying implant 100, and the outer slit may have the same or a smaller maximum expansion than the adjacent (axially inward) slit. This design can also be used to control the shape of the flare.

[0036] The implant may be cut from a hypodermic cannula using a laser or by electrical discharge machining so as to have a plurality of longitudinally oriented slots substantially parallel to the longitudinal axis of the device. Each slot is defined by a plurality of struts that are axially oriented struts and are connected with circumferentially oriented connector elements, thereby forming a series of rectangular slots in a collapsed configuration. The slots are present on both sides of the flat layout of the cutting pattern 100, and an intermediate portion 204, with or without slots, may be present. Opposing ends of the device may have smooth edges formed from connector elements that join the elongate struts. The connector elements may have arcuate regions that form enlarged head regions at the ends. When a radial force, such as from a balloon, is applied to the inner diameter of the device, the device radially expands outwardly into an expanded configuration that forms a flare.

[0037] In any embodiment of the flow modification implant, the implant may be characterized by this maximum diameter, which may be used, for example, to select a particular flow modification implant to match a patient. Optionally, in any embodiment of the implant, during expansion, the balloon is aligned with the flow modification implant 100 such that it contacts only the flare region or only the non-flare region of the flow modification implant 100.

[0038] Figure 3C is an isometric view of a flow modification implant 100 (Figure 3A) mounted on a balloon catheter delivery system 302, according to an embodiment of the present invention.

[0039] In any embodiment of the implant, the flow modification implant 100 is formed by cutting from a sheet or tube of metal, for example, using a laser, waterjet cutting, chemical etching, or metal stamping (e.g., the result is welded to form a tube). Alternatively, the flow modification implant 100 is woven (e.g., from metal or plastic fibers), for example, using methods similarly known in the art. Optionally, in any embodiment, the narrowing section 204 is made using a different method than the flare sections 200 and 202. For example, the flare sections are woven and the narrowing section is cut from sheet metal. In any embodiment, the flow modification implant may include a clamping ring that prevents expansion of the narrowing section 204. Optionally, in any embodiment, the restraint ring is plastically deformable, or self-expanding, or plastically expandable under higher pressure than the rest of the flow modification implant 100, which may potentially be plastically deformable. Alternatively, or in addition, in any embodiment, the restraint ring is selected to set the desired degree of narrowing and is then mounted on the flow modification implant, stent, or stent graft for implantation. In a sleeve flow modification implant (FIG. 7G), a similar effect can be achieved by suturing the stent graft.

[0040] In response to delivery of the implant to the target treatment site, a standard balloon catheter with a single expansion area, e.g., the Fox Catheter by Jomed, Inc. TM may be used to urge the implant to achieve its contour shape. When the balloon presses against the lumen of the implant, the narrowing section is prevented from expanding while the flare sections 200 and 202 expand under pressure. Various methods for preventing the narrowing section from expanding, e.g., providing the narrowing section with different mechanical properties, different designs, or additional elements relative to the non-narrowing sections, are described below.

[0041] In any embodiment of the implant, the flow modification implant 100 may be cut from a sheet and then twisted spirally around a mandrel to form the shape of the flow modification implant 100. Alternatively, the flow modification implant 100 may be cut from a tube, with the flared portion being a spiral cut and the narrowed portion being a ring cut. Alternatively, the flow modification implant 100 is formed as a coil spring with axially varying relaxation positions.

[0042] In any embodiment of the implant, the flow modification implant 100 may be adapted for use in the coronary sinus or other coronary veins or other veins having a non-muscular wall. The veins exhibit the characteristic of having a low elasticity (compared to arteries) and being relatively sensitive to tearing. In any embodiment, the edge of the flow modification implant 100 curves inwardly, or is bent, as shown, for example, by reference numeral 130 in FIG. 1. Alternatively, or in addition, in any embodiment, the edge is folded and / or smoothed to remove sharp edges. Alternatively, the parallel segments 208 and 212 (FIG. 2) are made long enough to support the flow modification implant 100 without harming the coronary sinus 102. Alternatively, or in addition, in any embodiment, the flow modification implant 100 or at least its larger diameter portion is made sufficiently soft and / or with a low spring constant to prevent the flow modification implant 100 from applying excessive pressure against the coronary artery flow modification implant wall. Alternatively, or in addition, in any embodiment, the flare of the flow modification implant 100 is coated with a biologically inert flexible coating, such as a soft silicone elastomer or latex, Teflon®, and / or another soft plastic or rubber material such as polyurethane (e.g., Angioflex, a biologically inert polyurethane plastic).

[0043] Figures 4A-4B are the planar layouts of the slit type flow modifying implant 100. In Figure 4B, the periphery 402 is defined by sections 440 and 446. As shown, these sections are designed to provide a relatively smooth periphery, possibly with a small amount of distortion at the locations where the sections connect to sections 442 and 444 (thus, the periphery 402 remains smooth). Together, sections 442, 444, and 446 define an outer slit for the periphery 402. The structure of the implant, such as struts, slots, and connector elements, generally takes the same form as that previously described in Figures 3A-3C. Optionally, or in addition, in any embodiment, a connector 446, which may be in a "V" shape in a crimped configuration, may be present. When expanded, the "V" shape may become linear and circumferentially oriented struts that define the periphery, as most clearly seen in Figure 4C.

[0044] A patient who is a candidate for an angiogenesis promoting technique may have a significant vascular disorder of the coronary circulation with constriction and / or lack of flow in one or more coronary arteries supplying blood to the coronary artery tissue. Invasive surgical techniques, even for percutaneous introduction and / or positioning of the reduction implant 100 into the coronary sinus, can induce cardiovascular accidents with unfavorable sequelae. Thus, for example, in some individuals, it is desirable to avoid and / or limit the amount of time the vasculature is invaded during the use of, for example, a balloon catheter.

[0045] Figures 4C-4D are, respectively, the planar layout and isometric view of a slit type flow modifying implant 1100 with a smooth periphery.

[0046] In any embodiment, the slit type flow modification implant 1100 automatically achieves its final configured state, for example, in response to exiting a delivery catheter or sheath, thereby obviating the use of a balloon catheter for initial deployment and implantation of the slit type flow modification implant 1100, and includes a shape memory material (e.g., nitinol). Alternatively, a balloon-expandable material, e.g., one that plastically deforms upon expansion, may be used.

[0047] In any embodiment, the slit type coronary flow modification implant 1100, shown in plan view in FIG. 4C, contains pre-formed slits 1102. The slits 1102 (and optionally, a set of slits 1104 in a second or further row) define rows 1122 (and row 1124) along the outer edge 1132 of the slit type flow modification implant 1100, with at least one edge 1132 having a wavy configuration in the non-expanded state. For example, in response to expansion as shown in FIG. 4D, the edge 1132 becomes smooth and linear while the slit 1102 takes on a rectangular appearance, and the edge 1132 is, for example, transverse to the slit 1126. In any embodiment of the present invention, the peripheral slits are wider than the slits in the remainder of the implant 1100, thereby affecting its final expanded configuration.

[0048] In any embodiment, the slit type coronary flow modification implant 1100 is delivered to its deployment site within the coronary sinus using a guide sheath, without the accompaniment of a balloon catheter. When the slit type coronary flow modification implant 1100 reaches its destination and exits its guide sheath, the coronary flow modification implant 1100 automatically expands to its final shape as shown in FIG. 4D. Thus, the slit type coronary flow modification implant 1100 does not require, for example, the operations and / or expansions associated with using a balloon catheter.

[0049] Alternatively, or in addition, in any embodiment, a balloon catheter may be used to facilitate expansion of the slit type flow modification implant 1100, for example when it is made of a material that does not automatically achieve its memorized shape. In any embodiment, the rows of slits 1122 and / or 1124 have a length and / or orientation that promotes the flow modification implant 1100 being formed into its final shape under the pressure of the balloon catheter, and thus being deployed with a minimum amount of time and / or stress to the surrounding tissue.

[0050] In any embodiment, the implant may have an hourglass-shaped body with enlarged opposing ends and a constricted intermediate section. The enlarged ends may include a flared section and a peripheral section. The flared section is a monotonically increasing flared section and a peripheral section of a constant diameter. The intermediate section may be substantially cylindrical. In the flared section, there are a plurality of axially oriented slots that are substantially parallel to the longitudinal axis of the device. Each slot is surrounded by several struts that include a plurality of axially oriented struts that are substantially parallel to the longitudinal axis, and is connected with one or more circumferentially oriented connector elements, thereby defining a rectangular slot. In the peripheral section, there are a plurality of circumferentially oriented slots that are substantially transverse to the longitudinal axis of the device. For example, the circumferentially oriented slots may be perpendicular to the longitudinal axis of the device. Each slot is surrounded by several struts that include a plurality of circumferentially oriented struts that are substantially transverse to the longitudinal axis, and is connected with one or more axially oriented connector elements that are substantially parallel to the longitudinal axis of the device, thereby defining a rectangular slot. In the intermediate section, there are a plurality of axially oriented slots that are substantially parallel to the longitudinal axis of the device. Each slot is surrounded by several struts that include a plurality of axially oriented struts that are substantially parallel to the longitudinal axis, and is connected with one or more circumferentially oriented connector elements, thereby defining a rectangular slot. The struts in the intermediate region may be wider than the struts in either, or both, of the flared region or the peripheral region to create a more rigid region that does not expand radially as much as the flared region. Similarly, the length of the struts may be longer, or shorter, or adjusted to the struts in the flared region to control the radial expansion. Optionally, or in addition, in the flared region, the slots may be of a plurality of sizes with various lengths and widths, and thus the slots may be the same or different.

[0051] In any embodiment, the slit-type coronary flow modification implant 1100 is designed to modify its shape in response to subsequent manipulation and / or expansion during deployment. In any embodiment, the slit 1138 expands such that the narrow passage 1168 automatically achieves a first diameter during deployment. In any embodiment, following the deployment of the slit-type coronary flow modification implant 1100, a balloon catheter is introduced into the narrow passage 1168 and inflated to press radially outwardly against the narrow passage 1168. In any embodiment, depending on the stiffness of the component material, a pressure of 7 to 8 atmospheres, or less than 7 atmospheres, or greater than 8 atmospheres, expands the expansion slit 1138 to a larger cross-section. Thereby, the narrow section 1168 has a larger diameter than it had immediately after its deployment.

[0052] Although not shown, some of the slits, for example, the slit 1138, are angled with respect to the longitudinal axis of the implant and thus may potentially require different amounts of force to expand and / or provide a twist to the deployed implant. Providing opposing angled slits may be used in any embodiment to control shortening of the implant. The angled slits may be used to bias the implant to shorten in response to expansion.

[0053] In any embodiment, when the flow modification implant 1100 is deployed, blood moves little or not at all through the walls of the narrow passage 1168 and / or the flare 1160 so as to contact the wall of the coronary sinus. This can be achieved by the narrow configuration of the slit. Alternatively or in addition, the length of the slit decreases in the vicinity of the narrowing 1168.

[0054] In any of the embodiments discussed herein, the constriction 1168 remains unexpanded or is only partially expanded while one or more flares 1160 at the ends are expanded to engage the vessel wall to anchor the device. A typical coronary sinus can be 4 mm to 16 mm in diameter, and thus the flared end of the implant may be expanded to about 4 mm to 16 mm in diameter, although this is not intended to be limiting. The flared end may be expanded to any size for engaging and anchoring the implant into the treatment area tissue. Similarly, the constriction 1168 may have a diameter of about 2 mm to 4 mm in order to provide desired flow characteristics, although this is not intended to be limiting. Thus, depending on the expansion, the constriction 1168 may have a diameter that is 10% to 50%, or 15% to 45%, or 20% to 40%, or 25% to 35% of the flare diameter, although this is not intended to be limiting. In any of the embodiments, the constricted section may be 15%, 20%, 25%, 30%, 35%, 40%, or 45% of the flare diameter, although this is not intended to be limiting.

[0055] In any of the embodiments, to achieve a limitation and / or interruption of blood flow through the implant wall, slits (e.g., not only slits 1102 and 1104 at the periphery) are increased in number while their width is modified. The viscosity of the blood impedes its flow through the reduced width of the slits, while the increased number of slits may facilitate the expansion of the implant 1100. This can result in a net reduction of blood flow through the implant wall.

[0056] Alternatively, or in addition, in any of the embodiments, the slit width may be used to help define the device geometry. For example, slit (actually space) 1104 is wider than the other slits. If slit 1104 is made wider than slit 1102, a curvature at the periphery can be brought about.

[0057] Also shown is an optional design where the slits are arranged in an alternating pattern of long and short slits. Alternatively, or in addition, in any embodiment, as shown, the size and / or density of the slits may be greater near the periphery than near the center of the implant 1100. Alternatively, or in addition, in any embodiment, as shown, the length of the slits increases as a function of the distance from the narrowing 1168.

[0058] As shown in FIG. 4D, the material of the implant 1168 is distorted by the expansion. Alternatively, or in addition, in any embodiment, the slits are distorted and the material is distorted to conform to these distortions. For example, the short axial slits nearest the periphery achieve a trapezoidal shape rather than a rectangular shape. Generally, the expanded configuration is idealized and the actual expanded shape may potentially include stepped distortions caused by the discrete pattern of slits within the implant.

[0059] FIG. 5 shows a vascular pathway to the coronary sinus 102 that may be used in conjunction with any embodiment of the flow modification implant. The flow modification implant 100 may be implanted using a transvascular approach, for example, by traversing from the venous system or through the intraventricular wall within the heart. In any embodiment of the method, the delivery system is inserted into the right atrium 506 of the heart 500 via the superior vena cava 508 and / or the inferior vena cava 504 via the jugular vein 510 or the subclavian vein 512 and via the femoral vein 502. Once in the right atrium 506, the delivery system is directed (e.g., through a sharp bend) into the opening 514 into the coronary sinus 102. In some patients, a valve is present at the entrance to the coronary sinus 102.

[0060] FIG. 6 is an isometric view of the dual-layer flow modification implant 1400. In this embodiment, the dual-layer flow modification implant 1400 includes a first flare section 1450 and / or a second flare section 1460. For purposes of clarity, the components of the flare 1460 will be focused on individually, but similar features can be applied to the flare section 1450.

[0061] In any embodiment, the dual-layer flow modification implant 1400 includes a flare section 1460 that includes an outer cone 1420 and an inner cone 1410. For example, the dual-layer flow modification implant may be formed by disposing any of the flow modification implants disclosed herein inside a second flow modification implant, which may be any of the embodiments disclosed herein. The inner cone 1420 includes, for example, slits 1422 and 1426, and the outer cone 1410 includes slits 1412 and 1416 such that the cones 1410 and 1420 can be delivered to the implantation site in a non-expanded state and expanded at the implantation site. The flare portion of any of the embodiments disclosed herein may increase linearly and monotonically, with or without a flat linear plateau section, or it may be a curved flare with a linear plateau section. The struts, slots, and cross-sections generally take the same form as those in FIG. 4D.

[0062] Further expansion of the cones 1410 and / or 1420 may be desirable, and it can be incorporated into their individual designs such that when the cones 1410 and / or 1420 are radially outwardly pressed by a balloon catheter at a first expansion pressure, they expand to a first diameter. The cones 1410 and / or 1420 can then expand to a second larger diameter when radially outwardly pressed by a balloon catheter at a second larger expansion pressure.

[0063] In any embodiment, when slits 1422 and 1426 are circumferentially aligned with slits 1412 and 1416 respectively, blood flows in direction 1454 (e.g., within space 132 shown in FIG. 1) through slits 1432 and 1436. With the alignment of slit 1412 with 1422 and / or the alignment of slit 1416 with 1426, the flow modification implant 1400 can be implanted into the blood vessel with a relatively slow flow rate and / or low pressure. For example, in an implantation within the coronary sinus, the narrow area 1440 can be filled with tissue (e.g., endothelialization) that helps to tether the implant 1400 without the risk of embolism.

[0064] Alternatively, or in addition, due to the limitation or interruption of flow into space 132 (most clearly seen in FIG. 1), a blood clot can form within area 1440 and stabilize at that location. The stabilized blood clot within area 1440 becomes incorporated into the surrounding tissue and with respect to the double-cone flow modification implant 1400, and thus it is further stabilized at that location.

[0065] In any embodiment, slits 1422 and 1426 can be rotated prior to implantation in relation to slits 1412 and 1416 such that blood flow in direction 1451 is substantially stopped to various degrees. With the misalignment of slits 1422 and 1426, the reduced implant 1400 is implanted into a blood vessel with a relatively higher flow rate and / or higher pressure, such as the main trunk of an artery, thereby protecting the patient against the risk of embolism migration.

[0066] In any of the embodiments described herein, the flow-modifying implant has a flared end with a cross-sectional area larger than the middle portion. Due to the continuity of the flow, the flow rate must be the same across the entire flow-modifying implant discussed herein. Thus, due to the smaller cross-sectional area of the middle portion, a higher fluid velocity and a lower pressure exist within the middle portion, thereby resulting in a lower velocity and a higher pressure within the inflow and outflow regions of the flared end.

[0067] The alignment of slits 1422 and 1426 is optionally set in relation to slits 1412 and 1416 prior to implantation within a blood vessel to establish a predetermined blood flow pattern, and both layers are either expanded or enabled to expand. To ensure that cones 1410 and 1420 remain fixed in position relative to each other, cones 1410 and / or 1420 have a friction surface interface and / or fit in any embodiment, for example, and may include it. Alternatively, or in addition, in any embodiment, the two layers may be deployed in different ways, for example, the inner layer may be plastically deployed and the outer layer may be self-deployed. Possibly, the outer shapes of the two layers do not match along their entire length. Alternatively, or in addition, in any embodiment, the outer layer is plastically deformed by a self-deploying inner layer (whose self-deployment may also provide friction for locking). Alternatively, or in addition, in any embodiment, cone 1420 may be rotated, for example, using a suitable internal engagement catheter after implantation.

[0068] The flared sections 1450 and 1460 may be symmetric or they need not be symmetric. For example, the implant may also be selected between flow interruption in one section, the other section, and optionally both. Flow only into space 132 may assist in clot formation. Flow only out of space 132 may assist in collapsing the peripheral blood vessels.

[0069] Figures 7A - 7G illustrate various flow - modifying implant variations. A sigmoid - shaped flare is shown, although linear or other flare - shaped designs may also be provided.

[0070] Figure 7A shows a flow - modifying implant 900 having a narrowing section 902 and a single flare - shaped section 904. The narrowing section 902 may face upstream or downstream. One potential advantage of this design is that the delivery system is less likely to snag inside the narrowing section 902. Another potential advantage is that an implant that completely occludes may be provided. However, in any embodiment, even such a completely occluding implant has a smooth side surface to prevent damage to the coronary sinus. Optionally, the outer diameter of a completely occluding implant or a nearly complete flow - modifying implant is increased beyond that of the coronary sinus to prevent implant dislodgment. Alternatively, or in addition, in any embodiment, one or more returns (not shown) on the outside of the implant may be provided. Optionally, a conical flow - modifying implant is provided with one or more openings for blood flow on the surface of the cone rather than at its apex as shown. For example, one or more openings may be present on the sidewall of the device.

[0071] As an alternative to a simple flow - modifying implant, the narrowing may be a valve, e.g., a valve that opens to its full or partial diameter after a suitable pressure is achieved within the coronary sinus distal to the right atrium. For example, a leaflet valve or other type of vascular valve known in the heart may be provided.

[0072] Figure 7B shows an alternative flow - modifying implant 910 in which two narrowing sections 912 and 916 sandwich a flare - shaped section 914 therebetween. Optionally, the different narrowing sections have different inner diameters and thus one may be larger than the other. Optionally, the narrowing sections are selectively expanded using a balloon to achieve a desired pressure profile.

[0073] FIG. 7C shows an alternative flow modification implant 920 with three constricted sections 922, 926, and 929 and two flared sections 924 and 928 between the constricted sections.

[0074] A blood vessel can be tapered along its length and can form an angle 1310, as shown, for example, in FIG. 7D. A blood vessel that varies in size along its length can occur, for example, within the coronary sinus when it anastomoses into the right atrium. In a tapered blood vessel, it may be desirable to utilize a tapered type flow modification implant 930 (FIG. 7E), as seen in detail in FIG. 7D, according to an embodiment of the implant.

[0075] FIG. 7D is an isometric view of an embodiment of a tapered flow modification implant 1300 (with a configuration similar to implant 930). The tapered flow modification implant includes a smaller flared section 1330, a constricted section 1340, and a larger flared section 1320. The size of the smaller flared section 1330 is controlled, for example, by one or more slits 1342 that are transverse to the axis of the constricted section 1340 and one or more slits 1346 that are generally parallel to the longitudinal axis.

[0076] The size of the larger section 1320 is controlled, for example, by two or more slits 1322 that are transverse to the axis of the constricted section 1340 and / or two or more slits 1320 that are generally parallel to the longitudinal axis.

[0077] Optionally, the slits 1342, 1346, 1322, and / or 1326 may be varied in size and / or geometric configuration to control the shape of the flared sections 1320 and / or 1330. Alternatively, or in addition, in any embodiment, the slits 1342, 1346, 1322, and / or 1326 may have various arrangements to provide different contours to the flared sections 1320 and / or 1330 and / or the constricted section 1340.

[0078] The openings 1330 and 1320 are shown as being circular, but they may have various configurations in order to conform to different vascular configurations as described above. Further, the ratio between the openings 1330 and 1320 may be varied to conform to any vascular diameter into which the flow modification implant 1300 is implanted. As in other figures, the material of the implant is shown as being distorted, while in some embodiments, possibly in addition to the material, what is distorted may be a slit.

[0079] FIG. 7E is a tapered flow modification implant 930 in which one flared section 932 has a smaller diameter than a second flared section 936 but larger than an intermediate narrowing section 934.

[0080] FIG. 7F is a flow modification implant 940 that is not axially symmetric and / or rotationally symmetric about its axis. In any embodiment, a first flared section 946 is distorted with respect to the axis defined by a second flared section 942 and a narrowing section 944.

[0081] Optionally, the flow modification implant 940 is curved. Here, an asymmetric or curved flow modification implant includes special markings, such as radiopaque or radiolucent areas, to assist in the correct orientation of the flow modification implant 940 within the blood vessel.

[0082] Figure 7G shows a flow modification implant 950 where the narrowing section 954 is a sleeve 954. For example, the sleeve 954 is formed from a flexible graft material, such as DACRON or GORTEX. The flow modification implant 950 further includes at least one of two outer rings 952 and 956 that serves to anchor the flow modification implant 950 within a blood vessel. A potential advantage of using a sleeve is that it can bend to conform to the vein geometry and / or dynamics. Other flow modification implant designs can also bend. Optionally, the graft material is elastic and thus can serve as a pressure limiting valve to better control the coronary sinus pressure. Optionally, a clamping ring is provided on the outside of section 954 to limit the lumen of the flow modification implant 950. Optionally, the ring is placed on the flow modification implant 950 during the procedure to achieve the desired narrowing effect. Alternatively, or in addition, in any embodiment, the ring is expandable, for example, using a balloon, to enable control of the narrowing section of the flow modification implant 950. Optionally, the ring is sutured to the narrowing section 954. Optionally, section 954 is stiffened using wires, as is known in the technical field of stent-grafts, for example. The flow modification implant can be any of the implants disclosed herein with a cover disposed thereover. In any embodiment, the cover can be porous, semi-porous, or non-porous.

[0083] In any embodiment, the flow modification implant 100 is potentially provided in kit form with a delivery system, a flow modification implant diameter control system, additional flow modification implants, external bands, and / or other means for including instructions for reducing its inner diameter, for use and / or size marking. Optionally, the flow modification implant 940 is inserted into or packaged with the delivery system for provision.

[0084] As described above, in any embodiment, the flow modification implant may be tightened by providing a band on the outside of the implant.

[0085] Figures 8A-8B are, respectively, an isometric view and details of an annular mesh type flow modification implant embodiment. In any embodiment, the mesh type flow modification implant 1500 (Figure 8A) includes relatively long flare shoulders 1502 and / or flare shoulders 1504, for example, to increase the area of contact between the flow modification implant 1500 and the peripheral blood vessel wall. Alternatively, or in addition, in any embodiment, tissue may grow through the mesh of the flare shoulders 1502 and / or 1504 to provide good anchoring of the mesh type flow modification implant 1500. Optionally, the mesh type flow modification implant 1500 includes and / or is coated with a material that promotes in-growth into tissue. For example, a periphery 1620, which may be serrated (e.g., a wavy edge) or smooth, is also optionally provided on each shoulder.

[0086] Optionally, the initial shape of the mesh type flow modification implant 1500 is controlled by one or more bands 1522 and / or 1524 that contract the area 1528 of the mesh type flow modification implant 1500. In any embodiment, the peripheral tissue crushes onto the mesh type flow modification implant 1500 to modify blood flow through the wall of the contracted area 1528. Two bands 1522 and 1524 are shown, but a single band, e.g., band 1522, may be used alone to create the contracted area 1528.

[0087] In any embodiment, prior to implantation, an operator who manually binds their ends together adjusts, for example, the ring formed by bands 1522 and / or 1524 at the circumference. Adjustment of bands 1522 and / or 1524 prior to implantation enables the operator to establish a constricted area 1528 with a specific size in order to modify blood flow, thereby promoting angiogenesis or otherwise redirecting blood flow. Alternatively, or in addition, in any embodiment, for example, a balloon catheter is expanded within area 1562, causing expansion of bands 1522 and / or 1524, thereby expanding area 1562 and increasing blood flow therethrough. In this manner, blood modification through the flow modification implant 1500 can be adjusted prior to and / or subsequent to the placement of the flow modification implant 1500 within a blood vessel.

[0088] In any embodiment, band 1524 may be frangible and break when a large expansion force is applied thereto. To adjust the diameter of area 1528 subsequent to implantation, a balloon catheter is positioned inside area 1562 and expanded until the pressure exceeds that required to break band 1524. When band 1524 is broken, the area of mesh area 1562 directly below it expands such that area 1562 expands in diameter and has the diameter of ring 1522.

[0089] Optionally, in any embodiment, band 1524 has a smaller diameter than band 1522 and provides two levels of expansion. For example, as the balloon catheter expands to a first diameter, it expands to a diameter smaller than band 1524, increasing the diameter of constricted area 1528 to the first expansion diameter. If a further increase in flow is desired, the balloon catheter is expanded to a second diameter, expanding the larger diameter band 1524 and / or the smaller diameter band 1524 and increasing the diameter of constricted area 1528 to the second expansion diameter.

[0090] The area 1562 has a flow passage of 6 millimeters. The ring 1524 has a diameter of, for example, 6 millimeters, while the ring 1522 has a diameter of 8 millimeters. By expanding the balloon inside the area 1562 and rupturing the ring 1524, the area under the ring 1524 expands. However, the ring 1522 with its 8 - millimeter diameter maintains its integrity. Thus, the area 1562 now has a flow passage of 8 millimeters (less than the thickness of the mesh or other material from which the implant is formed).

[0091] FIG. 8B details an embodiment of the ring 1522 with an adjustable band 1540 that forms the ring 1522 and is held at a specific diameter by the fastener 1544. Alternatively, or in addition, in any embodiment, the adjustable band 1540 is maintained at a specific diameter by the fastener 1546. In any embodiment, the fasteners 1544 and / or 1546 hold the adjustable band 1540 such that during implantation, the ring 1522 remains at a specific diameter until, for example, an expandable balloon catheter is expanded against the adjustable band 1540 and the diameter of the ring 1522 is expanded. In any embodiment, the clips 1544 and 1546 include, for example, a nylon material that holds the band 1522 at a specific diameter and allows diameter expansion only under the expansion pressure from the balloon catheter. Optionally, two fasteners are provided such that no portion of the band 1540 protrudes from the ring. In any embodiment of the present invention, the fastener is in a "C" shape and the band 1540 optionally includes a ridge that prevents sliding of the band through the fastener. Alternatively, or in addition, in any embodiment, friction prevents such sliding.

[0092] In any embodiment, the flare shoulders 1504 and / or 1502 are 0.5 centimeters to 1 centimeter in length, but they can be less than 0.5 centimeters or greater than 1 centimeter in length, for example, depending on the vascular configuration.

[0093] In any embodiment, the mesh type flow modification implant 1500 includes strands that form its mesh, including GORTEX, DACRON, and / or steel. Further, the material that makes up the mesh can be configured to be flexible or rigid, for example, based on the desired fluid dynamics, such as depending on the material and its thickness.

[0094] Figure 9 is an isometric view of a partially coated mesh type flow modification implant 1600. The mesh type flow modification implant 1600 includes a coating 1614 over or within a narrow section 1624 that is implanted within a blood vessel 1680 as shown in cross-section. In any embodiment, the mesh type flow modification implant 1600 includes one or more flare shoulders 1602 that contact the blood vessel 1680 to provide anchoring. For example, a periphery 1620, which can be serrated or smooth, is also optionally provided on each shoulder.

[0095] Alternatively, or in addition, in any embodiment, the mesh type flow modification implant 1600 includes a coating 1614 that limits blood flow through the wall of the flow modification implant 1600 and / or blood turbulence within the area of constriction 1624, thereby reducing the risk of embolism migration problems.

[0096] In any embodiment, the covering 1614 comprises a separate flexible layer that is attached to the flow modification implant 1600 at several points (e.g., at the constricted area 1624 and / or the flare shoulder 1602) to prevent tearing as the implant 1600 expands. Prior to expansion, for example, the covering 1614 is folded and / or pleated. Alternatively, or in addition, in any embodiment, the covering 1614 has a low bulk and is, for example, integrated into the flow modification implant 1600 structure such that it substantially covers the open area of the mesh. Examples of materials that make up the covering 1614 include GORTEX, latex, and / or silicone on the inside and / or outside of the flow modification implant 1600. Additional details regarding the various configurations of the cover that can be applied to any embodiment of the flow modification implant disclosed herein are disclosed later in this application.

[0097] FIG. 10 illustrates a flow modification device 2000 known in the art. This is a radially expandable implantable device. In some embodiments, the device is formed from a plurality of interconnected struts 2040 and 2030. The struts are generally axially oriented and parallel to the longitudinal axis of the device. When the device is in its radially collapsed configuration, it is thin and may be delivered to a target treatment site using a catheter. The interconnected struts generally form a plurality of rectangular-shaped cells 2040 through which rectangular windows pass. When the device is expanded radially, the rectangular cells expand radially into diamond-shaped cells 2030 at the proximal end 2010 and distal end 2020 of the device. In the intermediate section 2050 therebetween, the rectangular cells 2040 may remain substantially rectangular, or they may form small diamond-shaped cells depending on the amount by which the intermediate section expands. The expanded diameter of the intermediate section 2050 may be any diameter, but may be between 2 mm and 4 mm in diameter. Also, in any embodiment, the cells at the proximal end 2010 and distal end 2020 have a certain length and a certain height. The height generally decreases inwards from the proximal end 2010 and distal end 2020 towards the intermediate section 2050. Additionally, the length of the cells may decrease inwards from the proximal end 2010 and distal end 2020 towards the intermediate section 2050 due to shortening of the cells during radial expansion. Thus, the proximal end 2010 and distal end 2020 are generally flared to form trumpet-shaped ends and may increase monotonically in diameter outwards from the intermediate section 2050 towards the proximal or distal sections. The intermediate section 2050 has a diameter significantly modified with respect to the expanded proximal and distal flared ends. Also, over the entire length of the device, the proximal end 2010 or downstream end may have a larger diameter than that of the distal end 2020 or upstream end, assuming placement within the coronary sinus in a retrograde manner via the right atrium. In another embodiment, the proximal end 2010 or downstream end may possibly have a smaller diameter than that of the distal end 2020 or upstream end if delivered in the anterograde direction.The proximal end with a larger diameter tapers to a modified diameter towards the central region, where the diameter can be minimized and then increases towards the distal end with a smaller diameter. Or, put another way, the diameter tapers downward from both ends of the device towards the intermediate section. The diameter of the proximal end 2010 or the distal end 2020 can be either of a predetermined size or made to expand to a variable size.

[0098] The flow modification device may be balloon-expandable or it may self-expand. Once deployed within a body lumen, the larger diameter flared end engages adjacent tissue to anchor the device to the vessel wall. The frame may be expanded 10% to 20%, or 10% to 15%, or 15% to 20% in size over the vessel diameter to help ensure proper engagement and implantation within adjacent tissue. Fluid flows into the device and due to the smaller diameter intermediate region, the cross-sectional area decreases, the flow velocity is accelerated, creating a pressure gradient across the device. Also, over time, the device becomes endothelialized and tissue grows inwardly into or onto the metal struts of the device, thereby further helping to anchor the device and modify flow through it and establish a pressure gradient across the device. High backpressure can actually drive blood flow into other vessels, which is supplied to the myocardium that requires more blood supply, thereby helping to relieve ischemia and angina. In addition, the pressure gradient creates backpressure, which can also help with neovascularization due to collateral opening, collateral formation, angiogenesis, and vasculogenesis. In any embodiment, the proximal end 2010 of the device closer to the right atrium has a larger diameter than the distal end of the device to accommodate the natural tapering of the lumen, such as in a vessel like the coronary sinus. However, one of ordinary skill in the art will understand that the proximal end 2010 may have the same diameter as the distal end 2020 or the distal end 2020 may have a larger diameter than the proximal end 2010. Further details regarding the pressure and flow modification device are disclosed in U.S. Patent No. 9,364,354, the entire contents of which are incorporated herein by reference. Any aspect of the expandable frame of FIG. 10 of the present application may be applied to any embodiment of the flow modification implant described herein.

[0099] Figures 11A1, 11A2, and 11A3 illustrate some embodiments of the covered flow modification device. The covering enables immediate flow modification in response to implantation, unlike the uncovered embodiment of FIG. 10 where in-growth of tissue is time-consuming and thus complete modification of flow is not seen for weeks until in-growth of tissue occurs. FIG. 11A1 includes a completely covered flow modification device. The radially expandable frame may be the same frame as disclosed in FIG. 10 above, the frame in U.S. Pat. No. 9,364,354 (incorporated by reference), or any other frame disclosed herein or known in the art. In this embodiment, the cover 2060 may be any material such as a synthetic material such as a fabric, PTFE, ePTFE, DACRON, or any other polymer, or it may be any tissue such as a pericardium or other biological tissue. The cover 2060 may be attached to the frame using sutures, adhesives, or any other technique known in the art. The cover 2060 may be disposed on the outer surface, inner surface, only within the open cell region, or any combination thereof of the frame. Having a completely covered device can modify flow immediately after implantation and relieve angina promptly.

[0100] The intermediate embodiment shown in FIG. 11A2 illustrates a partially covered flow modification device. In this embodiment, the intermediate section 2095 of the flow modification device remains uncovered, while the flared ends have a proximal cover 2065 and a distal cover 2070. The ends of the frame within the flared region may be fully covered or, as shown, remain partially uncovered. The ends of the proximal flared end may remain uncovered (2090), or the ends of the distal flared end may remain uncovered (2080). This may have clinical advantages as a pressure gradient across the device will occur immediately after implantation and thus the anti-anginal and anti-ischemic effects that will commence immediately after implantation of the device. In some cases, leaving the flared ends at least partially uncovered may be advantageous as having the bare metal struts of the device in direct contact with the vessel wall may have less of an inflammatory response than engaging the covered material with the tissue.

[0101] The lower illustration of FIG. 11A3 shows an embodiment where the covered portion of the frame is only within the intermediate section 2100 and the upstream end 2120 and downstream end 2110, such as the flared trumpet ends, remain uncovered so that the bare metal engages the adjacent tissue. One of ordinary skill in the art will understand that the amount of coverage can be adjusted to provide the desired flow rate, pressure gradient, or backpressure. In any embodiment, the cover may cover 1 / 3, 1 / 2, or 2 / 3 of the center of the device. Other aspects of the embodiment shown in FIG. 11A may generally take the same form as those disclosed elsewhere in this specification.

[0102] The sequence of sketches in FIGS. 11B1 - 11B3 illustrates a delivery system for a flow modification device. The upper sketch in FIG. 11B1 shows a delivery catheter that may include an outer sheath 2130 and an inner shaft. The flow modification device may be crimped or otherwise loaded onto the inner shaft, and then the outer sheath is advanced over the flow modification device and tightened around it. In FIG. 11B2, the sheath 2130 is retracted once the device has been delivered to the desired target treatment site. This removes the tightening from the flow modification device, allowing it to self - expand within the treatment site. The flared end helps to anchor the device in place. In FIG. 11B3, the sheath 2130 is fully retracted, allowing for full radial expansion of the flow modification device 2140 in its fixed position. The catheter may then be removed from the patient, leaving the flow modification implant 2140 within the treatment area. The method of delivering the flow modification implant may be used in combination with any of the flow modification devices disclosed herein. In other embodiments of the delivery system, the delivery system may include an expandable member such as a balloon configured to balloon - expand the flow modification implant instead of self - expanding.

[0103] FIG. 11C illustrates another embodiment of a flow modification implant where, instead of a plurality of interconnected struts, the implant is formed from a plurality of interwoven filaments that form a mesh, which is then formed into the flow modification device and generally takes the same form as that described previously in FIG. 10, except that it is generally the same as that in FIG. 10 except that the implant is formed from a plurality of interwoven filaments that form a mesh instead of a plurality of interconnected struts. The mesh may include a narrow middle region 2050 and two flared regions, namely, a proximal flared region 2010 and a distal flared region 2020. This may be delivered using any of the methods disclosed herein and, as previously disclosed, modifies flow and has similar results in treating angina.

[0104] FIG. 11D illustrates a flow modification device implanted within blood vessel 2150. The flow modification device may be any of those disclosed herein, and the blood vessel is the coronary sinus, a large vein that drains deoxygenated blood from the heart. As shown, the device modifies flow through the device by utilizing an intermediate region 2165 of smaller diameter, thereby creating a pressure gradient with a higher pressure upstream than downstream. As discussed previously, this can create a backpressure that helps redistribute blood to more needy areas of the myocardium, or stimulate collateral vessel formation, i.e., angiogenesis, thereby alleviating angina. The proximal flared end 2160 may have a larger diameter than the distal flared end 2155, or the distal flared end 2155 may have a larger diameter than the proximal flared end 2160, or the proximal flared end 2160 and the distal flared end 2155 may have the same diameter. The device may be delivered using any of the delivery systems and methods disclosed herein.

[0105] Figure 12 illustrates an example of a flow modification implant. The expandable frame is substantially the same as that of FIG. 10, but may be any of those disclosed herein. Covers 2185 and 2190 are then coupled to the frame at the proximal and distal ends. The covers may be of any material, including but not limited to fabric, polymer, tissue, or any other. Examples of polymers include but are not limited to PTFE, ePTFE, DACRON, polyurethane, etc. Examples of tissue include but are not limited to pericardial tissue or other tissue. The intermediate section 2200 of the frame remains uncovered, and the proximal end 2170 and distal end 2180 of the device also remain uncovered. A composite implant may also be provided and implanted. For example, a plurality of rings or tubular elements may be joined together to form a flow modification implant. Each ring or tubular element may have a different geometry or structure, or may be formed from a different material. For example, FIG. 12 may be modified such that cover 2190 may differ from that of cover 2185 in material and structure, and a tubular support ring may or may not be present disposed under the section. Additionally, covers 2190 or 2185 may not be porous, and thus there is no risk of blood flow through side openings within these sections, and thus no "cover" is actually required. Alternatively, or in addition, covers 2190 and cover 2185 may be part of the structure of the device but not a cover. For example, covers 2190 and 2180 may be a ring section that is joined together by intermediate section 2200 and also bonded to the proximal and distal rings. Covers 2190 and 2180 acting as a ring section may be fabric, metal, or a combination thereof. Alternatively, or in addition, ring components 2180, 2200, and 2170 may be fabric, metal, or a combination thereof. The implant may include different materials and sections joined together.For example, ring 2180 may be a metal ring component that is coupled together with ring 2190, which may be a fabric component, and ring 2200, which may also be a metal component. In any of the embodiments discussed herein, the material forming cover 2190, 2185, or the composite ring segment may be porous, semi-porous, or non-porous. Optionally, in any of the embodiments, cover 2190, 2185 may have discrete segments that are porous, semi-porous, or non-porous within a single ring such that the material has multiple properties. It should be understood that in any of these embodiments, the material itself forming the cover may comprise more than one material. In this embodiment, the upstream end has a flared diameter that is smaller than the downstream flared diameter to accommodate the natural vascular taper. However, this is not intended to be limiting, and the upstream end may have a diameter that is larger than or equal to the downstream end. This flow modification implant may be delivered using any of the delivery devices or methods disclosed herein, and other aspects of this device are generally the same as those described in FIG. 10.

[0106] FIGS. 15A - 15F illustrate examples of covers disposed on the inflow or outflow ends of a flow modification device that include any of those disclosed herein. In FIG. 15A, cover 602 is disposed on the inflow end 606 of device 600. Here, cover 602 extends from the edge 604 of the inflow end toward the opposing end of the device but terminates while on the tapered portion of the inflow end and does not extend past the midpoint of the device along its longitudinal axis.

[0107] In FIG. 15B, cover 602 is still disposed on the inflow end 606 of device 600. However, here, the cover does not extend to the edge of the inflow end, and thus, the edge of the inflow end remains uncovered there. The cover then extends toward the opposing end of the device but is interrupted while still on the tapered portion of the inflow end and does not extend past the midpoint of the device along its longitudinal axis.

[0108] The cover may extend from any point on the inflow end and extend towards any point along the device. FIG. 15C shows that the cover may start from the edge 604 of the inflow end of the device 600, or it may start at any location along the taper 608 and extend towards the midpoint 610 of the device along its longitudinal axis, or even beyond the midpoint (612).

[0109] In FIG. 15D, the cover 614 is disposed on the outflow portion of the device 600. This may start from the edge 616 and extend towards the opposite end of the device, but the terminating edge may still be on the tapered portion 616a of the outflow end.

[0110] In FIG. 15E, the cover 614 is disposed on the outflow end of the device 600, but the cover does not extend to the edge 616 of the outflow end. The opposite end extends towards the midpoint of the device along the longitudinal axis of the device, but ends while still on the tapered portion 616a of the outflow end.

[0111] The cover may extend from any point on the outflow end of the device 600, as shown in FIG. 15F. For example, the cover may be disposed on the edge 616 of the outflow end, or it may start while on the tapered portion 616a of the outflow end and extend towards the midpoint 618 of the device along its longitudinal axis, or extend beyond the midpoint (620).

[0112] In any of the embodiments disclosed herein, the cover may be a fabric such as DACRON or a polymer such as silicone, or it may be a tissue such as pericardial tissue. The cover may be coupled to the device using sutures, adhesives, or other techniques known in the art.

[0113] Figures 13A - 13B illustrate the basic anatomical structure of the human heart. In Figure 13A, the left atrium LA, right atrium RA, and left ventricle are shown together with the coronary sinus CS. The coronary sinus is a large vein that drains venous blood from the heart.

[0114] Figure 13B highlights the area around the left atrium LA, right atrium RA, and left ventricle LV, including the coronary sinus CS and the inferior vena cava IVC.

[0115] Figures 14A - 14C illustrate an example of a method for delivering a flow modification implant to the coronary sinus CS as a treatment for angina using any of the implants disclosed herein.

[0116] In Figure 14A, a delivery catheter 2300, such as any one of those disclosed herein, is used to advance a flow modification implant (any of those disclosed herein) into the coronary sinus CS. The delivery catheter 2300 has a crimped flow modification implant 2320 coupled to the delivery catheter. The flow modification implant may be any of those disclosed herein.

[0117] In Figure 14B, the balloon 2330 on the delivery catheter 2300 is radially expanded, thereby expanding the flow modification implant 2310. The flow modification implant 2310 assumes a size and shape similar to the balloon that expands the flow modification implant 2310.

[0118] In Figure 14C, the balloon expands the flow modification device to engage the coronary sinus vessel wall. The balloon is then deflated and removed from the vessel, thereby leaving the flow modification device 2310 at the target treatment site.

[0119] Any of the flow modification devices described herein may be balloon-expandable or self-expanding. They may be placed within any target treatment area, such as a blood vessel like the coronary sinus. Notes and Examples

[0120] The following non-limiting examples detail certain aspects of the subject matter, among other things, to solve problems and provide the benefits discussed herein.

[0121] Example 2 is the apparatus described in Example 1 where the pressure gradient is greatest between the inlet end and the reduced-diameter portion of the apparatus.

[0122] Example 3 is any of the apparatuses described in Examples 1-2 where the velocity of the fluid flow is greatest within the reduced-diameter portion.

[0123] Example 4 is any of the apparatuses described in Examples 1-3 where the expanded proximal and distal ends are flared ends.

[0124] Example 5 is any of the apparatuses described in Examples 1-4 where the radially expandable frame has an outer surface and the cover is disposed over only a portion of the outer surface.

[0125] Example 6 is any of the apparatuses described in Examples 1-5 where the radially expandable frame has an outer surface and the cover is disposed over the entire outer surface.

[0126] Example 7 is any of the apparatuses described in Examples 1-6 where the cover is disposed over only the reduced-diameter portion.

[0127] Example 8 is any of the apparatuses described in Examples 1-7 where the expanded proximal and distal ends remain at least partially uncovered.

[0128] Example 9 is any of the apparatuses described in Examples 1-8 where the cover is made of a polymer, fabric, synthetic material, tissue, or a combination thereof.

[0129] Example 10 is any of the apparatuses described in Examples 1-9 where the cover is centrally disposed over at least 2 / 3 of the expandable frame.

[0130] Example 11 is any of the devices described in Examples 1-10, wherein the cover is positioned over a reduced diameter portion such that when the flow modification implant radially expands to engage the blood vessel, the cover does not contact the blood vessel directly, thereby modifying or preventing an inflammatory response.

[0131] Example 12 is any of the devices described in Examples 1-11, wherein the cover is configured to prevent or minimize an inflammatory response by the blood vessel wall.

[0132] Example 13 is any of the devices described in Examples 1-12, wherein the reduced diameter portion has a diameter of 2-4 mm.

[0133] Example 14 is any of the devices described in Examples 1-13, wherein a plurality of struts form a plurality of rectangular slots when the expandable frame is in a crimped configuration, and the plurality of rectangular slots expand into a rhombus shape when the expandable frame is in a radially expanded configuration, the rhombus shape having a height and a length, the height decreasing from proximal and distal ends toward a central point disposed therebetween.

[0134] Example 15 is any of the devices described in Examples 1-14, wherein the length decreases from proximal and distal ends toward a central point.

[0135] Example 16 is any of the devices described in Examples 1-15, wherein the flow modification device is self-expanding or balloon-expandable.

[0136] Example 17 is any of the devices described in Examples 1-16, further comprising an inflow end and an outflow end, wherein the cover is disposed only on the inflow end or only on the outflow end.

[0137] Example 18 is a system for delivering a flow modification implant, the system comprising a flow modification implant as described in any of Examples 1-17 and a delivery catheter.

[0138] Example 19 is a method for modifying flow within a blood vessel, the method comprising the steps of providing a flow modification device having proximal and distal ends, delivering the flow modification device to a target treatment region within the blood vessel, radially expanding the flow modification device such that the proximal and distal ends are larger in diameter than a reduced diameter portion disposed therebetween, and immediately modifying blood flow through the flow modification device in response to delivery of the flow modification device, thereby creating a pressure gradient between the inflow end of the flow modification device and the reduced diameter portion, the step including a cover disposed across the flow modification device facilitating modification of the blood flow.

[0139] Example 20 is the method according to Example 19, further comprising the step of making the velocity of the fluid flow greatest within the reduced diameter portion.

[0140] Example 21 is any of the methods according to Examples 19 - 20, wherein the step of radially expanding the flow modification device includes the step of forming flare regions at the proximal and distal ends.

[0141] Example 22 is any of the methods according to Examples 19 - 21, wherein the step of radially expanding the flow modification device includes the step of expanding a cover, the cover being disposed over only a portion of the outer surface of the flow modification device.

[0142] Example 23 is any of the methods according to Examples 19 - 22, wherein the step of radially expanding the flow modification device includes the step of expanding a cover, the cover being disposed over the entire outer surface of the flow modification device.

[0143] Example 24 is any of the methods according to Examples 19 - 23, wherein the step of radially expanding the flow modification device includes the step of expanding a cover, the cover being disposed over only the central region.

[0144] Example 25 is any of the methods described in Examples 19-24, where the step of radially expanding the flow modification device includes the step of expanding the cover, and the proximal and distal ends remain at least partially uncovered.

[0145] Example 26 is any of the methods described in Examples 19-25, where the step of radially expanding the flow modification device includes the step of expanding the cover without direct contact with the blood vessel, thereby modifying or preventing an inflammatory response.

[0146] Example 27 is any of the methods described in Examples 19-26, where the step of radially expanding the flow modification device includes the step of forming rhombus-shaped cells from rectangular-shaped cells, and the height of the rhombus-shaped cells decreases from the proximal and distal ends towards a central point disposed therebetween.

[0147] Example 28 is any of the methods described in Examples 19-27, where the rhombus-shaped cells have a certain length, and the length decreases from the proximal and distal ends towards the central point.

[0148] In Example 29, any one or any combination of the devices or methods of Examples 1-28 can optionally be configured such that all elements of the recited options are available for use or selection therefrom.

[0149] The above detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention may be practiced. These embodiments are also referred to herein as "examples." Such examples can include elements in addition to those shown or described. However, the inventors also contemplate examples in which only those elements shown or described are provided. The inventors also contemplate examples that use any combination or permutation of those elements (or one or more aspects thereof) shown or described, either with respect to a particular example (or one or more aspects thereof) or with respect to one or more other examples shown or described herein.

[0150] If there is any inconsistency in the usage between this document and any document so incorporated by reference, the usage in this document shall prevail.

[0151] In this book, the terms "a" or "an" are used to include one or more, regardless of any other instance or usage of "at least one" or "one or more", as is common in patent documents. In this book, the term "or" is used to refer to non-exclusive, unless otherwise indicated, or "A or B" is used to include "A but not B", "B but not A", and "A and B". In this book, the terms "including" and "in which" are used as ordinary English synonyms for the individual terms "comprising" and "wherein". Also, in the following claims, the terms "including" and "comprising" are non-limiting, i.e., a system, device, article, composition, formulation, or process that includes elements in addition to those recited after such terms in the claims is still considered to fall within the scope of that claim. Also, in the following claims, the terms "first", "second", and "third", etc. are used merely as labels and are not intended to impose numerical requirements on those objects.

[0152] The above description is intended to be illustrative rather than restrictive. For example, the embodiments described above (or one or more aspects thereof) may be used in combination with each other. Other embodiments may be used by those skilled in the art, etc., upon review of the above description. The abstract is provided to enable the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. Also, in the above detailed description, various features may be grouped together in order to streamline the disclosure. This should not be construed as intending that the disclosed features that are not claimed are essential to any of the claims. Rather, the inventive subject matter may lie in less than all of the features of a particular disclosed embodiment. Accordingly, the following claims are incorporated herein as examples of detailed descriptions or embodiments, and each claim stands on its own as a separate embodiment, and such embodiments are contemplated to be combinable with each other in various combinations or permutations. The scope of the present invention should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

**Claim 1** A flow modification device comprising a plurality of struts coupled together to form a radially expandable frame having a proximal end portion and a distal end portion, the proximal end portion and the distal end portion being radially expandable to an expanded proximal end portion and an expanded distal end portion, the flow modification device comprising a plurality of struts extending from an inlet end of the radially expandable frame to an outlet end of the radially expandable frame; a reduced diameter portion of the expandable frame disposed between the expanded proximal end portion and the expanded distal end portion, the reduced diameter portion comprising a fluid flow through a passageway; a cover disposed over at least a portion of the radially expandable frame on the proximal end portion; and the cover comprising an upstream end and a downstream end; wherein the upstream end is downstream of the reduced diameter portion of the radially expandable frame and the downstream end is upstream of and spaced from the outlet end of the radially expandable frame such that the cover is positioned only on a flared portion of the proximal end portion; the reduced diameter portion modifying fluid flow therethrough immediately after implantation of the flow modification device and forming a pressure gradient between the inlet end and the reduced diameter portion of the device. **Claim 2** The device of claim 1, wherein the expanded proximal end portion and the expanded distal end portion are flared ends. **Claim 3** The device of claim 2, wherein the cover forms a conical shape from the upstream end to the downstream end. **Claim 4** The device of claim 1, wherein the radially expandable frame has an inner surface and the cover is disposed over only a portion of the inner surface. **Claim 5** The device of claim 1, wherein the radially expandable frame has an outer surface and the cover is disposed over only a portion of the outer surface. **Claim 6** The device of claim 1, wherein the pressure gradient is greatest between the inlet end of the device and the reduced diameter portion. **Claim 7** The device of claim 1, wherein the velocity of the fluid flow is greatest within the reduced diameter portion. **Claim 8** The device of claim 1, wherein the cover comprises a polymer, fabric, synthetic material, tissue, or a combination thereof. **Claim 9** The device of claim 1, wherein the cover is configured to prevent or minimize an inflammatory response by a blood vessel wall. **Claim 10** The device according to claim 1, wherein the reduced-diameter portion has a diameter of 2 to 4 mm.

11. The plurality of struts form a plurality of rectangular slots when the expandable frame is in a crushed configuration, and the plurality of rectangular slots expand into a rhombus shape when the expandable frame is in a radially expanded configuration, the rhombus shape having a height and a length, the height decreasing from the proximal end and the distal end toward a central point disposed therebetween, the device according to claim 1.

12. The device according to claim 11, wherein the length decreases from the proximal end portion and the distal end portion toward the central point.

13. The device according to claim 1, wherein the flow modifying device is self-expanding or balloon-expandable.

14. The flow modifying device according to claim 1, wherein the outflow end has a diameter larger than that of the inflow end.

15. A system for delivering a flow modifying implant, the system comprising the flow modifying device according to claim 1, a delivery catheter and, a system.

16. A flow modifying device, comprising a plurality of struts coupled together to form a radially expandable frame having a proximal end portion and a distal end portion, the proximal end portion and the distal end portion being radially expandable to an expanded proximal end portion and an expanded distal end portion, the flow modifying device extending from an inflow end of the radially expandable frame to an outflow end of the radially expandable frame, a plurality of struts; a reduced-diameter portion of the expandable frame disposed between the expanded proximal end portion and the expanded distal end portion, the reduced-diameter portion comprising a fluid flow through a passageway, the reduced-diameter portion; a cover having an upstream end and a downstream end located on the proximal end portion and, the cover is located only on a flared portion of the proximal end portion, the reduced-diameter portion modifies the fluid flow therethrough immediately after implantation of the flow modifying device and forms a pressure gradient between the inflow end and the reduced-diameter portion of the device, the outflow end has a diameter larger than that of the inflow end, the flow modifying device is open through the reduced-diameter portion such that the flow through the reduced-diameter portion is not blocked, a flow modifying device.

17. The flow modifying device according to claim 16, wherein the cover forms a conical shape from the upstream end to the downstream end.

18. The flow modification device according to claim 16, wherein the cover is positioned on the proximal end portion such that the cover does not contact the blood vessel wall when the radially expandable frame is expanded.

19. The flow modification device according to claim 16, wherein a part of the proximal end portion remains at least partially uncoated when the radially expandable frame is expanded.

20. The flow modification device according to claim 16, wherein a subset of the plurality of struts directly contacts the blood vessel wall when the radially expandable frame is expanded.

21. The flow modification device according to claim 16, wherein the flow modification device is self-expanding or balloon-expandable.

22. The flow modification device according to claim 16, wherein the cover is configured to prevent or minimize an inflammatory response by the blood vessel wall.

23. The flow modification device according to claim 16, wherein the frame is configured to expand 10% to 20%, 15% to 20%, or 10% to 15% larger than the blood vessel diameter into which it is inserted.

24. The flow modification device according to claim 16, wherein the reduced diameter portion has a diameter that is any of 10% to 50%, 15% to 45%, 20% to 40%, or 25% to 35% of the diameter of the flared portion of the proximal end portion.

25. The flow modification device according to claim 16, wherein the flow modification device is shorter when the radially expandable frame is expanded than when it is not expanded.

26. The flow modification device according to claim 16, wherein the expanded proximal end portion and the expanded distal end portion are symmetric.

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