Patent Description:
Cardiac structures such as atrial appendages can contribute to cardiac blood flow disturbance, which is associated with a number of cardiac-related pathologies. For example, complications caused by blood flow disturbance within an appendage and associated with atrial fibrillation can contribute to embolic stroke.

<CIT> discloses apparatuses, methods, and systems relating to occlusion. The apparatuses, methods, and systems include a device for placement in vessels, appendages, and openings in a body. The devices include a unitary frame having a face portion that includes a center frame portion and a plurality of elongate members.

<CIT> discloses an occlusive implant including an expandable framework including a height and a plurality of support members defining a proximal end region of the expandable framework and a central hub member attached to the plurality of support members. Additionally, the expandable framework is configured to shift between a first configuration and a second configuration, wherein the height of the expandable framework remains substantially the same in both the first configuration and the second configuration. Further, the central hub member is configured to shift relative to the proximal end region while the expandable framework shifts between the first configuration and the second configuration.

The herein claimed invention relates to a device for placement in vessels, appendages, and openings in a body, according to claim <NUM>. Optional features are defined in the dependent claims.

This disclosure is not meant to be read in a restrictive manner. For example, the terminology used in the application should be read broadly in the context of the meaning those in the field would attribute such terminology.

With respect to terminology of inexactitude, the terms "about" and "approximately" may be used, interchangeably, to refer to a measurement that includes the stated measurement and that also includes any measurements that are reasonably close to the stated measurement. Measurements that are reasonably close to the stated measurement deviate from the stated measurement by a reasonably small amount as understood and readily ascertained by individuals having ordinary skill in the relevant arts. Such deviations may be attributable to measurement error, differences in measurement and/or manufacturing equipment calibration, human error in reading and/or setting measurements, minor adjustments made to optimize performance and/or structural parameters in view of differences in measurements associated with other components, particular implementation scenarios, imprecise adjustment and/or manipulation of objects by a person or machine, and/or the like, for example. In the event it is determined that individuals having ordinary skill in the relevant arts would not readily ascertain values for such reasonably small differences, the terms "about" and "approximately" can be understood to mean plus or minus <NUM>% of the stated value.

Persons skilled in the art will readily appreciate that various aspects of the present disclosure can be realized by any number of methods and apparatuses configured to perform the intended functions. It should also be noted that the accompanying drawing figures referred to herein are not necessarily drawn to scale, but may be exaggerated to illustrate various aspects of the present disclosure, and in that regard, the drawing figures should not be construed as limiting.

<FIG> are a cross-sectional views of a human heart <NUM> in which a delivery sheath <NUM> is positioned in preparation for deployment of an implantable medical device <NUM> into an appendage <NUM> of the heart, in accordance with various aspects of the present disclosure. <FIG> show a depiction of a right atrium <NUM>, a left atrium <NUM>, a right ventricle <NUM>, and a left ventricle <NUM> of the heart <NUM>. As is shown, the appendage <NUM> is located in the left atrium <NUM> of the heart <NUM>, and thus, the appendage <NUM> may be considered the left atrial appendage <NUM>. Although the following discussion focuses on deployment of the implantable medical device <NUM> into the left atrial appendage <NUM>, the implantable medical device <NUM> may be deployed in other appendages or openings within the human heart <NUM> or in other locations of the human body.

The left atrial appendage <NUM> may be considered a muscular pouch extending from the anterolateral wall <NUM> of the left atrium <NUM> of the heart <NUM>, which serves as a reservoir for the left atrium <NUM>. In a normal cardiac cycle, the left atrial appendage <NUM> may contract rhythmically with the rest of the left atrium <NUM> during contraction of the heart <NUM>. Thus, during a normal cardiac cycle, the left atrial appendage <NUM> contracts with the left atrium <NUM> and pumps blood that may gather or collect within the left atrial appendage <NUM> to circulate therefrom. However, during cardiac cycles characterized by arrhythmias (e.g., atrial fibrillation), the left atrial appendage <NUM> may fail to sufficiently contract along with the left atrium <NUM>, which can allow blood to stagnate within the left atrial appendage <NUM>. Stagnant blood within the atrial appendage <NUM> is susceptible to coagulating and forming a thrombus, which can dislodge from the atrial appendage <NUM> and ultimately result in an embolic stroke. The implantable medical device <NUM>, consistent with various aspects of the present disclosure, may be delivered to the left atrial appendage <NUM> to help prevent and militate against blood stagnation within the left atrial appendage <NUM>.

In certain instances and as is shown in <FIG>, the implantable medical device <NUM> may be delivered to the left atrial appendage <NUM> by way of a minimally invasive transcatheter procedure. More specifically, the delivery sheath <NUM> may be navigated through a vena cava <NUM>, into the right atrium <NUM>, through an atrial septum <NUM>, and into the left atrium <NUM> towards the appendage <NUM>. In some implementations, the percutaneous access to the patient's vasculature can be at the patient's femoral vein, for example. It should be understood that this example technique is merely one example, and many other access techniques can also be performed to deploy the occlusive devices provided herein. At this point of the deployment process, the occlusive device is contained within a lumen of the delivery sheath <NUM>, and is configured in a collapsed low-profile delivery configuration. Although transcatheter systems are generally shown and described, other delivery systems (e.g., thoracoscopic) are also contemplated.

<FIG> shows the configuration of <FIG> with the implantable medical device <NUM> deployed from the delivery sheath <NUM> and positioned within the left atrial appendage <NUM>, in accordance with various aspects of the present disclosure. As shown, an inner catheter <NUM> may releasably couple to the implantable medical device <NUM>, and is slidably disposed within the lumen of the delivery sheath <NUM>. The inner catheter <NUM> can be used by a clinician operator to make the implantable medical device <NUM> deploy from the delivery sheath <NUM>. For example, after positioning the implantable medical device <NUM> through an ostium <NUM> of the left atrial appendage <NUM>, the clinician operator can retract the delivery sheath <NUM> in relation to the inner catheter <NUM> to unsheath and deploy the implantable medical device <NUM>. The ostium <NUM> may be considered a portion of the anterolateral wall <NUM> of the left atrium <NUM> from which a taper originates to form the pouch-like structure of the left atrial appendage <NUM>. The implantable medical device <NUM> may include an occlusive face <NUM> that is arranged near the ostium <NUM> of the left atrial appendage <NUM>. The inner catheter <NUM> may releasably couple to the implantable medical device <NUM> via a hub or center frame portion arranged centrally within the occlusive face <NUM> of the implantable medical device <NUM>.

After emerging from the constraining confines of the delivery sheath <NUM>, the implantable medical device <NUM> can reconfigure to an expanded configuration. The implantable medical device <NUM> may expand to conform to the contours of the space defined within the left atrial appendage <NUM>. The devices provided herein can be used in many different areas of the body, and that deployment of the implantable medical device <NUM> into the left atrial appendage <NUM> is merely one example implementation. More specifically, <FIG> shows the configuration of <FIG> with the implantable medical device <NUM> deployed from the delivery system and positioned within a vessel between the vessel walls <NUM>, in accordance with various aspects of the present disclosure. At each implant location, forces (such as blood pumping or muscles contracting) acting on the implantable medical device <NUM> may threaten to dislodge the implantable medical device <NUM> from the implant location.

In certain instances, positioning of the implantable medical device <NUM> relative to the ostium <NUM> of the left atrial appendage <NUM> may be enhanced and ensures that the implantable medical device <NUM> prevents thrombus from embolizing from the left atrial appendage <NUM>. More specifically, the occlusive face <NUM> may be arranged within the left atrial appendage <NUM> such that the occlusive face <NUM> connects portions of the anterolateral wall <NUM> on opposite sides of the ostium <NUM> to form a substantially uniform surface. In certain instances, blood may collect or stagnate along the face of a device implanted therein if the occlusive face <NUM> is non-uniform (e.g., a device having a hub that protrudes beyond other portions of the occlusive face; a device having an occlusive face that is concave, partially concave, or includes depressions, or a device having an occlusive face that is concave, partially concave) relative to the ostium <NUM> of the left atrial appendage <NUM> or the occlusive face includes protuberances. In these instances, thrombus may occur along the face of the implantable medical device <NUM> as a non-uniform surface may alter/disrupt the blood flow within the left atrium <NUM>. Thus, a patient may remain susceptible to blood coagulation and thrombus formation if an implantable medical device <NUM> includes a non-uniform surface as the result of improper positioning or the design of the device.

After proper positioning and delivery of the implantable medical device <NUM>, the inner catheter <NUM> can be decoupled from the implantable medical device <NUM>, and the delivery sheath <NUM> and inner catheter <NUM> can be removed from the patient. With the implantable medical device <NUM> deployed as shown, the space defined within the left atrial appendage <NUM> is essentially separated from the left atrium <NUM> by virtue of the physical barrier provided by the implantable medical device <NUM>. In this manner, stagnant blood within the LAA <NUM> that is susceptible to coagulating and forming thrombi may be prevented from entering the left atrium <NUM>, and thereby prevented from potentially causing an embolic stroke. In addition, positioning of the occlusive face <NUM> of the implantable medical device <NUM> relative to the ostium <NUM> of the left atrial appendage <NUM> may help prevent blood collecting or stagnating along the face of the implantable medical device <NUM>.

The implantable medical device <NUM> may include a frame element and a membrane coupled or attached to at least a portion of the frame. As discussed in further detail below, the membrane is configured to allow the inner catheter <NUM> to interface with the implantable medical device <NUM> during positioning. In addition, the membrane is also configured to maintain a uniform occlusive face <NUM>. Thrombus may occur along the occlusive face <NUM> of the implantable medical device <NUM> as a non-uniform surface may alter/disrupt the blood flow within the left atrium <NUM>. Thus, the implantable medical device <NUM>, and system for deployment of the device <NUM>, may be configured to maintain a uniform face <NUM> to lessen the opportunity for blood coagulation and thrombus formation.

<FIG> shows an example frame <NUM> for an implantable medical device, in accordance with various aspects of the present disclosure. The implantable medical device may be a device for placement in vessels, appendages, and openings in a body. The frame <NUM> may be a unitary frame formed of a plurality of elongate members <NUM>. In certain embodiments, the frame <NUM> may be unitary and self-expanding. The frame <NUM> may include body portions that have different shapes, angles, or other features (as explained in further detail with reference to <FIG>) or may be another shape such as cylindrical, conical, frustoconical, hemispherical, a spherical cap, pyramidal, truncated pyramidal, and the like, and combinations thereof. Any and all combinations and sub-combinations of such varying shapes and varying geometries of shapes are envisioned and within the scope of this disclosure.

The frame <NUM> may include any number of rows and cells formed by the elongate members <NUM> within a body portion <NUM>. The elongate members <NUM> within the body portion <NUM> may form multiple cells in a row. A single cell <NUM> is highlighted (as shown, the frame <NUM> includes multiple similar cells). The cell(s) <NUM> may be formed of a five-sided shape, a six-sided shape, or other shapes such as, but not limited to, polygonal, square, rectangular, parallelogram-shaped, rhomboidal, trapezoidal, diamond-shaped, chevron-shaped, octagonal, triangular, and the like. As shown in <FIG>, the frame <NUM> tapers inwardly relative to a longitudinal axis <NUM> of the frame <NUM> from the body portion <NUM>. The point at which the frame <NUM> transitions to the taper is a waist portion <NUM> of the frame <NUM> with an end portion <NUM> of the frame <NUM> being distal to the waist portion <NUM>. The elongate members <NUM> also form the end portion <NUM>. In certain instances, the elongate members <NUM> converge at the waist portion <NUM> of the frame <NUM> and diverge or bifurcate within the end portion <NUM> of the frame <NUM>.

In addition to transitioning the frame <NUM> to a tapered portion, one or more anchors <NUM> may also be located at the waist portion <NUM>. The one or more anchors <NUM> may be located at a portion of the cell <NUM> near or at which members <NUM> converge. The one or more anchors <NUM>, arranged along the waist portion <NUM> configured to move inwardly (e.g., rotate) relative to and toward the longitudinal axis in response to the frame <NUM> being arranged in a delivery configuration. The one or more anchors <NUM> may retract, move or rotate inwardly such that when the frame <NUM> is loaded into a delivery catheter and into the delivery configuration (e.g., collapsed for transcatheter delivery). The frame <NUM> also includes a distal opening <NUM> at a distal end of the frame. The elongate members <NUM> taper inwardly within the end portion <NUM> of the frame and terminate or end at the distal opening <NUM>. In certain instances, the distal opening <NUM> may include a diameter that is about between <NUM>% and <NUM>% of a diameter of the body portion <NUM>. The distal opening <NUM> may be approximately about <NUM> and about <NUM> or more specifically about <NUM> in certain instances. Sizing of the distal opening <NUM> may facilitate uniform collapsing of a frame to a delivery configuration when arranged with a delivery sheath.

The frame <NUM> also includes a proximal end portion <NUM> formed by the elongate members <NUM> extending from a center frame portion (as shown in further detail in <FIG>). In certain instances, the elongate members <NUM> bifurcate after transitioning from the proximal end portion <NUM> to the body portion <NUM> of the frame <NUM>. In addition and as shown, the proximal end portion <NUM> of the frame <NUM> is uniform. In certain instances, the proximal end portion <NUM> of the frame <NUM> being uniform may include a substantially uniform surface. In addition, the proximal end portion <NUM> of the frame <NUM> being uniform may include instances where the elongate members <NUM> may form a unitary surface (e.g., within a common plane) across the proximal end portion <NUM> of the frame <NUM>. In certain instances, the elongate members <NUM> are within the proximal end portion <NUM> of the frame <NUM> are arranged perpendicular to the waist portion <NUM>. In certain instances, the proximal end portion <NUM> of the frame <NUM> may be without protrusions or without abrupt changes in shape. For example, the proximal end portion <NUM> of the frame <NUM> may include a gradual upward or downward slope increase in height relative to the longitudinal axis <NUM> of the frame <NUM> (e.g., about between <NUM> and about <NUM> increase or decrease) while maintaining a substantially uniform surface.

In addition, the elongate members <NUM> may transition from a plane perpendicular to the longitudinal axis <NUM> of the frame <NUM> into a plane that is parallel with the longitudinal axis <NUM> of the frame <NUM> in the body portion <NUM>. When covered with a membrane (e.g., as shown in <FIG>), the proximal end <NUM> of the frame <NUM> form an occlusive face. In addition, the proximal end <NUM> of the frame <NUM> may be configured to maintain a substantially uniform occlusive face in response to compressive forces acting on the body portion <NUM> and/or the end portion <NUM> of the frame <NUM>. As described in further detail below, the elongate members <NUM> and the center frame portion (not shown).

<FIG> shows a perspective view of an example frame <NUM> for an implantable medical device, in accordance with various aspects of the present disclosure. The frame <NUM> may be used as a device for placement in vessels, appendages, and openings in a body. The frame <NUM> includes a substantially uniform proximal end <NUM> forming a face portion that includes a center frame portion <NUM> arranged at or within the proximal end <NUM> of the frame <NUM> and a plurality of elongate members <NUM> extending from the center frame portion <NUM>.

The frame <NUM> may also include a body portion <NUM> that is also formed by the elongate members <NUM>. At least a portion of the body portion <NUM> extends substantially perpendicular to the proximal end <NUM> of the frame <NUM>. The portions of the elongate members <NUM> within the proximal end <NUM> and the center frame portion <NUM> form the face portion of the frame <NUM>. When covered with a membrane (a shown in <FIG>) the elongate members <NUM> within the proximal end <NUM> and the center frame portion <NUM> form an occlusive face of an implantable medical device.

In certain instances, face portions of the plurality of elongate members <NUM> (within the proximal end portion <NUM>) are configured to angularly displace the center frame portion <NUM> in response to a compressive force applied to the body portion <NUM> of the frame <NUM> as is explained in greater detail with reference to <FIG>. The face portions of the plurality of elongate members <NUM> may be configured to angularly displace the center frame portion <NUM> to maintain the proximal end <NUM> of the frame <NUM> within a common plane. In certain instances, the proximal end <NUM> is substantially uniform in the absence of forces acting on the body portion <NUM> and/or edges or a perimeter of the proximal end <NUM> of the frame <NUM> and when forces are acting on the body portion <NUM> and/or edges or a perimeter of the proximal end <NUM> of the frame <NUM>.

The face portions of the plurality of elongate members <NUM> are configured to absorb one or more forces from a location of implantation such as the left atrial appendage. The face portions of the plurality of elongate members <NUM> angularly displace the center frame portion in response the forces acting on the body portion of the frame <NUM>. Absorbing one or more forces from the left atrial appendage includes mitigating thrombosis formation by maintaining a substantially uniform occlusive face. Maintaining the proximal end <NUM> as substantially uniform by way of the angular displacement of the center frame portion <NUM> lessens the opportunity for blood coagulation and thrombus formation. In certain instances, substantially uniform can include a surface that is without abrupt or random deviations along the surface of the proximal end <NUM>.

<FIG> shows a top down view of a proximal end portion <NUM> of an example frame <NUM> for an implantable medical device, in accordance with various aspects of the present disclosure. Face portions <NUM> of the elongate members <NUM>, as noted above, may be configured to maintain a substantially uniform shape of the proximal end <NUM> of the frame <NUM>. For ease of illustration, one of the face portions <NUM> of the elongate members <NUM> are shown highlighted in <FIG>.

Each of the face portions <NUM> of the elongate members <NUM> may include a first curved section <NUM>, a second curved section <NUM>, and an inflection point <NUM> between the first curved section <NUM> and the second curved section <NUM> within the proximal end <NUM> of the frame <NUM>. According to the invention, face portions <NUM> of the elongate members <NUM> include a starting point <NUM> at the center frame portion <NUM> and an end point <NUM> at a perimeter of the proximal end <NUM>. The starting point <NUM> and the ending point <NUM> are radially offset relative to a tangent between the starting point <NUM> and the ending point <NUM>. In certain instances, the tangent, as shown, is perpendicular to the starting point <NUM> at the center frame portion <NUM> and the tangent intersects the perimeter of the proximal end <NUM> between adjacent ones of the face portions <NUM> of the elongate members <NUM>.

In certain instances, the first curved section <NUM> includes a first radius of curvature and the second curved section <NUM> includes a second radius of curvature. The first radius of curvature and the second radius curvature of may be approximately equal. In addition and as shown, the first curved section <NUM> and the second curved section <NUM> may be in opposite directions. In addition, the radiuses of curvature may distribute strain across the face portions <NUM> of the elongate members <NUM>. The strains that occur on the proximal end <NUM> may distribute evenly across the face portions <NUM> of the elongate members <NUM> in certain instances.

In certain instances, the starting point <NUM> of the face portions <NUM> of the elongate members <NUM> and the ending point <NUM> of the face portions <NUM> of the elongate members <NUM> are offset by between about <NUM> degrees and about <NUM> degrees. As shown, the starting point <NUM> of the face portions <NUM> of the elongate members <NUM> and the ending point <NUM> of the face portions <NUM> of the elongate members <NUM> are offset by about <NUM> degrees (with about including +/- <NUM>%). In addition, the starting point <NUM> of the face portions <NUM> of the elongate members <NUM> and the ending port <NUM> of the face portions <NUM> of the elongate members <NUM> are offset by about <NUM> degrees (with about including +/- <NUM>%).

<FIG> shows side and top views, respectively, of example frame <NUM> for an implantable medical device in response to a compressive force, in accordance with various aspects of the present disclosure. The implantable medical device may be a device for placement in vessels, appendages, and openings in a body. The frame <NUM> may be a unitary frame formed of a plurality of elongate members <NUM>. In certain embodiments, the frame <NUM> may be unitary and self-expanding. As discussed in detail above, the frame <NUM> includes a body portion <NUM> and tapers inwardly relative to a longitudinal axis <NUM> of the frame <NUM> from the body portion <NUM>. The point at which the frame <NUM> transitions to the taper is a waist portion <NUM> of the frame <NUM> with an end portion <NUM> of the frame <NUM> being distal to the waist portion <NUM>. The frame <NUM> also includes a distal opening <NUM> at a distal end of the frame. The elongate members <NUM> taper inwardly within the end portion <NUM> of the frame and terminate or end at the distal opening <NUM>. The frame <NUM> also includes a proximal end portion <NUM> formed by the elongate members <NUM> extending from a center frame portion <NUM> (shown in <FIG>).

Forces may act on the frame <NUM> when implanted in a patient. The frame <NUM> may alter in shape or configuration in response to compressive forces acting on the frame <NUM>, an example of which is shown in <FIG>. In certain instances and as shown, the frame <NUM>, the plurality of elongate members <NUM> are configured to angularly displace the center frame portion <NUM> in response to a compressive force applied to the body portion <NUM> of the frame <NUM>. By angularly displacing the center frame portion <NUM>, face portions <NUM> of the elongate members <NUM> may be configured to maintain a substantially uniform shape of the proximal end <NUM> of the frame <NUM>. For ease of illustration, one of the face portions <NUM> of the elongate members <NUM> are shown highlighted in <FIG>.

In certain instances and as shown in <FIG>, the proximal end portion <NUM> of the frame <NUM> maintains a uniform surface may include instances across the proximal end portion <NUM> of the frame <NUM> in response to the compressive forces as a result of the angular displacement by the elongate members <NUM>. In certain instances, the elongate members <NUM> may angularly displace the center frame portion <NUM> by between about <NUM> degrees and about <NUM> degrees. The amount of angular displacement may be determined by viewing a starting point <NUM> at the center frame portion <NUM> of the face portions <NUM> of the elongate members <NUM>. The starting point <NUM> (e.g., a peak or outwardly extending undulation of the center frame portion <NUM>) may rotate about the longitudinal axis <NUM> in response to the compressive forces. In certain instances, the proximal end portion <NUM> of the frame <NUM> maintains a uniform surface with an outward or inward movement, relatively to the longitudinal axis <NUM>, of less than <NUM> - <NUM>. For example, in some instances, upon a <NUM>% radial compression of implantable device body, the proximal end portion <NUM> maintains uniformity without extending inward or outward, greater than about <NUM>. The inward our outward movement of the proximal end portion <NUM> may result in a curvature from perimeter (e.g., end point <NUM> shown in <FIG>) of the proximal end portion <NUM>. In these instances, the curvature of the proximal end portion <NUM> of the frame <NUM> is constant and without additional protrusions such that the proximal end portion <NUM> of the frame <NUM> maintains a uniform surface. Absorbing one or more forces from the left atrial appendage includes mitigating thrombosis formation by maintaining a substantially uniform occlusive face.

In certain instances, plurality of elongate members <NUM> (e.g., face portions <NUM> of the elongate members <NUM>) are configured to angularly displace the center frame portion <NUM> by between about <NUM> degrees and about <NUM> degrees in response to the compressive force reducing the circumference of the body portion <NUM> of the frame <NUM> by between about <NUM>% and about <NUM>%. For example, in some instances, the center frame portion <NUM> has an angular displacement of between about <NUM> degrees and about <NUM> degrees in response to a compressive force reducing the circumference by about <NUM>%. In addition, the plurality of elongate members <NUM> may be configured to angularly displace the center frame portion <NUM> and maintain the center frame portion approximately aligned with a longitudinal axis <NUM> of the frame <NUM> in response to the compressive force. Further, the face portions <NUM> of the elongate members <NUM> may be configured to maintain spacing at the center frame portion <NUM> in response to the compressive force as shown in <FIG>.

In addition, the frame <NUM> may be configured to substantially maintain a length <NUM> of the frame <NUM> in response to compressive forces. As the face portions <NUM> of the elongate members <NUM> may be configured to absorb forces acting on the body to maintain the uniformity of the proximal end <NUM>, the body portion <NUM>, in certain instances, maintains the length <NUM> of the frame <NUM> within a percentage of the original length <NUM>. In certain instances, the length <NUM> of the frame <NUM> is maintained between about <NUM>%, about <NUM>%, about <NUM>%, about <NUM>%, about <NUM>%, about <NUM>%, about <NUM>%, or about <NUM>% of the original length <NUM> in response to compressive forces.

<FIG> shows another example frame <NUM> for an implantable medical device, in accordance with various aspects of the present disclosure. The implantable medical device may be a device for placement in vessels, appendages, and openings in a body. The frame <NUM> may be a unitary frame formed of a plurality of elongate members <NUM>. The frame <NUM> may include body portions (e.g., body portion <NUM> and end portion <NUM>) that have different shapes, angles, or other features or may be another shape such as cylindrical, conical, frustoconical, hemispherical, a spherical cap, pyramidal, truncated pyramidal, and the like, and combinations thereof. Any and all combinations and sub-combinations of such varying shapes and varying geometries of shapes are envisioned and within the scope of this disclosure.

The frame <NUM> also includes a proximal end portion <NUM> formed by the elongate members <NUM> extending from a center frame portion as explained in detail above. In certain instances, the elongate members <NUM> bifurcate after transitioning from the proximal end <NUM> to the body portion <NUM> of the frame <NUM>. In addition and as shown, the proximal end portion <NUM> of the frame <NUM> is substantially uniform. The elongate members <NUM> may form a unitary surface (e.g., within a common plane) across the proximal end portion <NUM> of the frame <NUM>. In certain instances, the elongate members <NUM> are within the proximal end portion <NUM> of the frame <NUM> are arranged perpendicular to the longitudinal axis <NUM>. In addition, the elongate members <NUM> may transition from a plane perpendicular to the longitudinal axis <NUM> of the frame <NUM> into a plane that is parallel with the longitudinal axis <NUM> of the frame <NUM> in the body portion <NUM>.

The frame <NUM> tapers inwardly relative to a longitudinal axis <NUM> of the frame <NUM> from the body portion <NUM>. The point at which the frame <NUM> transitions to the taper is a waist portion <NUM> of the frame <NUM> with an end portion <NUM> of the frame <NUM> being distal to the waist portion <NUM>. The elongate members <NUM> also form the end portion <NUM>. In certain instances, the elongate members <NUM> converge at the waist portion <NUM> of the frame <NUM> and diverge or bifurcate within the end portion <NUM> of the frame <NUM>.

In addition, the elongate members <NUM> may include portions of greater width and less width than other portions of the elongate members <NUM>. The elongate members <NUM> may include varying width depending on the location within the frame <NUM>. For example, the elongate members <NUM> within the proximal end <NUM>, the body portion <NUM>, and/or the end portion <NUM> may have areas of differing widths as discussed in further detail and highlighted in <FIG>. The end portion <NUM> may be shorter in length relative to the body portion <NUM>.

The frame <NUM> also includes a distal opening <NUM> at a distal end of the frame. The elongate members <NUM> taper inwardly within the end portion <NUM> of the frame and terminate or end at the distal opening <NUM>. The distal opening <NUM> may be sized, as explained in further detail below, relative to an outer diameter of the body portion <NUM> to facilitate deployment of the frame <NUM> as discussed in further detail and highlighted in <FIG>.

<FIG> shows a close-up view of a portion of an example frame <NUM> for an implantable medical device, in accordance with various aspects of the present disclosure. The portion of the body portion <NUM> of the frame <NUM> shown in <FIG> is immediately adjacent or below the proximal end <NUM> of the frame <NUM>. As noted above with reference to <FIG>, the elongate members <NUM> within the proximal end <NUM> may transition from a plane perpendicular to the longitudinal axis of the frame <NUM> to a plane that is parallel with the longitudinal axis <NUM> of the frame <NUM> in the body portion <NUM>. At the perimeter of the proximal end <NUM> is a shoulder <NUM> of the device that is curved to transition the elongate members <NUM>. For ease of illustration, the shoulder <NUM> of the frame <NUM> is highlighted once on <FIG>, however, each elongate member <NUM> may include the shoulder <NUM> to transition the proximal end <NUM> to the body portion <NUM>.

In certain instances, the elongate members <NUM> bifurcate within the body portion <NUM> immediately adjacent to or distal of the shoulder <NUM>. The sections of the elongate members <NUM> immediately adjacent to or distal of the shoulder <NUM> may include sections of lesser width within the body portion <NUM>. Other sections of the elongate members <NUM> may also include or alternatively include sections of lesser width.

As shown in <FIG>, a first section <NUM> of the elongate members <NUM> has a less width than a second section <NUM> of the elongate members <NUM>. The differing widths in this area of the body portion <NUM> may facilitate fatigue resistance of the frame <NUM>. Forces acting on the body portion <NUM> may collect or be distributed toward the shoulder <NUM> of the frame <NUM>. The differing widths in this area of the body portion <NUM> may facilitate fatigue resistance through absorption and distribution of forces through the elongate members <NUM>.

<FIG> shows a close-up view of another portion of an example frame <NUM> for an implantable medical device, in accordance with various aspects of the present disclosure. Similar to the body portion <NUM>, the end portion <NUM> of the frame <NUM> includes cells <NUM>.

As shown, the frame <NUM> tapers inwardly toward an end portion <NUM> starting at the waist portion <NUM> with the elongate members <NUM> originating at adjacent anchors <NUM> converging at the distal opening <NUM>. The frame <NUM> shown in <FIG> includes circumferential members <NUM> between the elongate members <NUM> originating at adjacent anchors <NUM> converge at the distal opening <NUM> within the cells <NUM>. In certain instances, the circumferential members <NUM> facilitate uniform compression of the frame <NUM>. In certain instances, the frame <NUM> may pleat when compressed in the absence of the circumferential members <NUM>. The circumferential members <NUM> lessen the chance that the frame <NUM> pleats or non-uniformly reduces in diameter during device deployment, device loading, and device re-loading.

<FIG> shows a close-up view of a cut pattern for an example frame <NUM> for an implantable medical device, in accordance with various aspects of the present disclosure. The frame <NUM> adjacent the anchors <NUM> includes a radius <NUM> that separates the anchors <NUM> from the elongate members <NUM> adjacent either side of the anchors <NUM>. The radius <NUM> may be semi-circular and configured to distribute strains or forces acting on the frame <NUM> adjacent the anchors <NUM>.

<FIG> shows an example delivery sheath <NUM>, collet <NUM> and a portion of an example frame <NUM> for an implantable medical device, in accordance with various aspects of the present disclosure. The portion of the frame <NUM> shown in <FIG> is a center frame portion <NUM> and portions of elongate members <NUM> described in detail above.

The collet <NUM> may form a portion of a delivery catheter and may interface with the center frame portion <NUM>. The collet <NUM> may be integrally formed or attached to a distal end of the delivery catheter (as shown in <FIG>) arranged through the delivery sheath <NUM>. The collet <NUM> may be configured to pass at least partially through and engage the center frame portion <NUM> to enable movement of the frame <NUM>. The collet <NUM> may be frictionally engaged with the center frame portion <NUM> and release in response to rotational movement of the delivery catheter. Movement of the collet <NUM> moves the frame <NUM> into and out of the delivery sheath <NUM>. The collet <NUM> may be configured to releasable couple to the frame <NUM> without use of a screw or other mechanical engagement to facilitate maintaining a substantially uniform proximal end portion as described in detail above.

<FIG> is a first perspective view of an example implantable medical device <NUM>, <FIG> is a side view of the implantable medical device <NUM> and <FIG> is a second perspective view of the implantable medical device <NUM>, in accordance with various aspects of the present disclosure. The implantable medical device <NUM> includes a membrane <NUM> and a frame <NUM> (partially obscured by the membrane <NUM>). The frame <NUM> may be formed by a plurality of elongate members <NUM>. A proximal end <NUM> of the frame <NUM> includes a center frame portion <NUM>. In addition, the proximal end <NUM> of the frame <NUM> may be hubless. The center frame portion <NUM> may may be configured to releasable couple to a delivery system (e.g., a collet <NUM>) without use of a screw or other mechanical engagement to facilitate maintaining a substantially uniform proximal end portion.

The proximal end <NUM> of the frame <NUM> may lack a feature that extends outwardly or inwardly relative to the proximal end <NUM> of the frame <NUM>. Face portions <NUM> of the plurality of elongate members <NUM> may extend from the enter frame portion <NUM> as a substantially uniform surface (e.g., within a common plane) and form the occlusive face <NUM> along with the frame <NUM>. As shown above, for example, with reference to <FIG>, the face portions <NUM> of the plurality of elongate members <NUM> may include a curved pattern within a plane that includes the proximal end <NUM> of the frame <NUM>. In certain instances, the proximal end <NUM> of the frame <NUM> may be within a common plane or include approximately between a <NUM>% and <NUM>% deviation inwardly or outwardly from the plane. In certain instances, the frame <NUM> may be formed of a metal or metallic material such as nitinol (NiTi). In certain more specific embodiments, the frame <NUM> may be formed from a single unitary piece of nitinol. The curved pattern of the face portions <NUM> of the plurality of elongate members <NUM> may facilitate conformability of the proximal end <NUM> of the frame (e.g., occlusive face <NUM> of the device <NUM>). The face portions <NUM> of the plurality of elongate members <NUM> may absorb forces when the device is deployed within a patient such that the proximal end <NUM> is compliant to forces (e.g., soft) and conformable (e.g., responds and adapts to forces within the patient).

The implantable medical device <NUM>, as shown in <FIG>, may also include a first body portion <NUM> extending substantially parallel to the longitudinal axis <NUM> of the implantable medical device <NUM>. A shoulder portion <NUM> of the frame <NUM> may transition the elongate members <NUM> from the plane of the proximal end <NUM> of the frame <NUM> to be aligned substantially parallel (e.g., within approximately between a <NUM>% and <NUM>% deviation from) the longitudinal axis <NUM> of the implantable medical device <NUM> (or frame <NUM>). First body portions <NUM> of the elongate members <NUM> form the body portion <NUM>.

The implantable medical device <NUM> may also include a waist portion <NUM> angled relative to the longitudinal axis <NUM>. The waist portion <NUM> may transition the frame <NUM> to a second body portion <NUM> (or end portion of the frame <NUM> as discussed in detail above). The second body portion <NUM> converges the frame <NUM> inwardly toward the longitudinal axis <NUM>. Each of the first body portion <NUM> and the second body portion <NUM> include a plurality of cells extending above the circumference of the frame <NUM> as shown and discussed above relative to in <FIG>, for example. Second body portions <NUM> of the elongate members <NUM> form the second body portion <NUM>.

The frame <NUM> also includes a distal opening <NUM> at a distal end of the frame. The elongate members <NUM> taper inwardly within the end portion <NUM> of the frame and terminate or end at the distal opening <NUM>. In certain instances, the distal opening <NUM> may include a diameter that is about between <NUM>% and <NUM>% of a diameter of the body portion <NUM>.

As noted above, the implantable medical device <NUM> may be a device for placement in vessels, appendages, and openings in a body. The implantable medical device <NUM> may have a shape that mirrors or conforms to a target location into which it is implanted. For example and as shown in <FIG>, the implantable medical device <NUM> includes an acorn-like shape when the implantable medical device <NUM> is configured for implantation into a patient's left atrial appendage. The implantable medical device <NUM> may have a tubular shape, a circular shape, or other shapes that are consistent with the target location into which the implantable medical device <NUM> is implanted.

In certain instances, the membrane <NUM>, may be coupled or attached to at least a portion of the frame <NUM>. In certain instances, the membrane <NUM> may be coupled to only or at least and the proximal end <NUM> of the frame <NUM>. The membrane <NUM> and the face portion <NUM> of the frame <NUM> form a substantially uniform occlusive face <NUM> with the membrane <NUM> extending across and covering the center frame portion <NUM>. The proximal end <NUM> of the frame <NUM> may be disposed across an ostium of a target portion of a patient (such as the left atrial appendage as shown in <FIG>) and rapidly occlude and block the target portion behind the membrane <NUM>. In addition, the membrane <NUM> may substantially or fully cover the proximal end <NUM> of the frame <NUM> such that there is no or minimal exposure to the frame <NUM>. In certain instances and as discussed in further detail below, at least the membrane <NUM> that is in contact or coupled to the proximal end <NUM> of the frame <NUM> may include a coating that is configured to minimize a thrombogenic response that may occur due to exposure of the membrane <NUM> to blood contact.

The face portions <NUM> of the elongate members <NUM>, as discussed in detail above, may be configured to deflect and maintain a substantially uniform shape or surface of the proximal end <NUM> of the frame <NUM>. For ease of illustration, one of the face portions <NUM> of the elongate members <NUM> are shown highlighted in <FIG>. The face portions <NUM> of the plurality of elongate members <NUM> are configured to absorb one or more forces from a location of implantation such as the left atrial appendage. The face portions <NUM> of the plurality of elongate members <NUM> angularly displace the center frame portion <NUM> in response the forces acting on the body portions <NUM>, <NUM> of the frame <NUM>. Absorbing one or more forces from the left atrial appendage may include mitigating thrombosis formation by maintaining a substantially uniform occlusive face and conforming the device to the left atrial appendage.

The membrane <NUM> may be attached to at least portions of the face portions <NUM> of the elongate members <NUM>. In certain instances, the membrane <NUM> may be attached to at least a portion of each of the face portions <NUM> of the elongate members <NUM>. The membrane <NUM> may be configured to deflect and maintain a substantially uniform surface and move along with the face portions <NUM> of the elongate members <NUM> in response to compressive forces acting on the body portion <NUM> of the frame <NUM>. The membrane <NUM> may be configured to maintain a surface smoothness and move along with the face portions <NUM> of the elongate members <NUM> in response to compressive forces acting on the body portion <NUM> of the frame <NUM>. The membrane <NUM>, in certain instances, lacks surface roughness or substantial changes in surface topography to maintain the surface smoothness of the occlusive face <NUM>. The membrane <NUM> being attached to at least a portion of each of the face portions <NUM> of the elongate members <NUM> may be configured to lessen billowing of the membrane <NUM> relative to the elongate members <NUM> and occlusive face <NUM>.

The center frame portion <NUM> of the frame is configured to interface with a delivery system as described in further detail above with reference to <FIG> delivery of the implantable medical device <NUM> to the target location. To avoid thrombus formation, it may be beneficial for the implantable medical device <NUM> maintain the uniform occlusive face after delivery. In certain instances, the membrane <NUM> is configured to stretch within the frame <NUM> in response to interaction with a delivery system. In certain instances, the membrane <NUM> may be configured to recover from being deflected into the center frame portion <NUM> to maintain a substantially uniform occlusive face <NUM> with the proximal end <NUM> of the frame <NUM>. After the delivery system has been removed from the center frame opening <NUM>, the membrane <NUM> may be configured to rebound or move back in line with the proximal end <NUM> of the frame <NUM> (either an interior surface or exterior surface of the proximal end <NUM> of the frame <NUM>) to deflect and maintain the substantially uniform occlusive face <NUM>.

The membrane <NUM> may include a first layer and a second layer. In certain instances, the second layer may be attached to a percentage of the interior surface of the frame <NUM> that is less than an entirety of the interior surface. In certain instances, the second layer may be centered relative to the center frame portion <NUM>. The second layer may be between about <NUM>% and about <NUM>% of the interior surface of the proximal end <NUM> of the frame <NUM>. In certain instances, one or both of the first layer and the second layer of the membrane <NUM> is configured to reinforce and add elastomeric properties to the membrane <NUM>. The elastomeric properties may be configured to facilitate the ability of the membrane <NUM> to stretch and rebound.

In addition to transitioning the frame <NUM> to a tapered portion, one or more anchors <NUM> may also be located at the waist portion <NUM>. The one or more anchors <NUM> may be located at a portion of the cell near or at which members <NUM> converge. The one or more anchors <NUM>, arranged along the waist portion <NUM> configured to move inwardly (e.g., rotate) relative to and toward the longitudinal axis in response to the frame <NUM> being arranged in a delivery configuration. The one or more anchors <NUM> may retract, move or rotate inwardly such that when the frame <NUM> is loaded into a delivery catheter and into the delivery configuration (e.g., collapsed for transcatheter delivery). In certain instances, the anchors <NUM> may retract, move or rotate inwardly such that when the occlusive face <NUM> is constricted.

In certain instances, the membrane <NUM> includes a plurality of openings <NUM> spaced above a circumference of the device <NUM>. The one or more anchors <NUM> may be configured to move inwardly (e.g., rotate) relative through the one or more openings <NUM> in the membrane <NUM>. The openings <NUM> in the membrane <NUM> may include a height that is approximately equal to or slightly larger than (e.g., between about <NUM>% and about <NUM>%) a height of the openings <NUM> in the membrane <NUM>. The openings <NUM> in the membrane <NUM> may enable retraction or rotation of the anchors <NUM> without catching on, encumbering, or damaging the membrane <NUM>.

<FIG> show example implantable medical devices <NUM> of varying sizes, in accordance with various aspects of the disclosure. As discussed above, the devices <NUM> may include ratios between a length of the device and an overall diameter of the devices <NUM> and/or a size of the distal opening. The four devices <NUM> shown may be configured for versatile sizing due to the conformability and adaptability of the devices <NUM> to a patient's left atrial appendage. For example, other devices may have up to eight difference diameter devices that are configured to fit the size ranges that the four devices <NUM> are intended for.

<FIG> show example implantable medical devices <NUM> having a coating after implantation, in accordance with various aspects of the disclosure. <FIG> shows an example medical device <NUM> without a coating. As shown in <FIG>, a membrane <NUM> is arranged or attached to a face portion <NUM> of face portions of elongate members <NUM> forming a substantially uniform occlusive face <NUM>. As shown in <FIG>, the occlusive face <NUM> of the device <NUM> may be disposed across an ostium of a target portion of a patient (such as the left atrial appendage) and rapidly occlude and block the target portion behind the membrane <NUM>. In addition and as is shown, the membrane <NUM> substantially or fully covers the occlusive face <NUM> that there is no or minimal exposure to the elongate members <NUM>.

The membrane <NUM> of the devices <NUM> shown in <FIG> include a coating that is configured to minimize a thrombogenic response that may occur due to exposure of the membrane <NUM> to blood contact. In certain instances, the coating may be a heparin coating. The heparin coating is utilized to bind heparin molecules to the membrane <NUM>. For further reference regarding a heparin coated membrane <NUM>, reference may be made to <CIT> ("Scholander") for the specific teachings of antithrombogenic activity of surface immobilized heparin. In certain instances, the heparin coating may be CARMEDA® BioActive Surface (CBAS® Heparin Surface). As an example, the device <NUM> shown in <FIG> includes a CBAS® Heparin Surface having been implanted in a canine for <NUM> days (and includes minimal/no thrombus on the surface of the membrane <NUM>). The device <NUM> shown in <FIG> shows a device <NUM> that includes a CBAS® Heparin Surface having been tested in the blood loop described below in the Test Methods section (and includes minimal/no thrombus on the surface of the membrane <NUM>). <FIG> shows a device without an anti-thrombogenic coating such as heparin having been tested in the blood loop described below in the Test Methods section and shows substantial thrombus coverage.

In addition, the membrane <NUM> may be configured to inhibit, filter, modulate, or substantially modulate the passage of fluids and/or materials (such as blood and/or thrombus) through the membrane <NUM>. In some embodiments, the membrane is configured to induce rapid tissue ingrowth therein. In certain instances, the membrane <NUM> provides for a blood or body fluid impermeable membrane that occludes the flow of blood or bodily fluids through the membrane <NUM> yet promotes the ingrowth and endothelialization. The membrane <NUM> can have a microporous structure that provides a tissue ingrowth scaffold for durable occlusion and supplemental anchoring strength of frames. In some embodiments, the membrane <NUM> may be a porous member. Pores of the membrane <NUM> may be sized to substantially, or in some examples completely, help prevent passage of blood, other bodily fluids, and emboli. In some implementations, the membrane prevents or substantially prevents passage of blood, other bodily fluids, thrombi, emboli, or other bodily materials through the membrane. In addition, the pores of the membrane <NUM> may facilitate attached or impregnation of heparin to lessen the opportunity for thrombus formation. Example testing parameters are set forth below that describe the methods and equipment used to show the thrombogenic responses of coated and uncoated membranes <NUM>.

In certain instances, the heparin coating may be applied to the membrane <NUM> in one or more layers. The chemical constituents of the covering material in each layer can be the same or different. In some instances, the covering material is cross-linked to itself or other covering materials in other layers. The cross-linking bonds can be covalent or ionic. The heparin covering may form at least one layer on at least a portion of the membrane <NUM> and may cross-link to itself or other layers of the covering. The cross-linking can be covalent, ionic, or both. For reference regarding the application of layers of heparin to the membrane <NUM>, reference may be made to <CIT>). The device implants with the CBAS® Heparin Surface did have evidence of non-specific entrapment of red blood cells in the film's microstructure (as discussed in further detail below with reference to <FIG>).

<FIG> shows an example frame <NUM> and anchors <NUM> with a sheath <NUM> (or delivery device such as a delivery catheter) in a first configuration, in accordance with various aspects of the present disclosure. The first configuration shown in <FIG> may be considered a deployed configuration of the frame <NUM>. The anchors <NUM> project outwardly relative to the frame <NUM>. The deployed configuration may be prior to the frame <NUM> being loaded into the sheath <NUM> for implantation into the body, and also after the frame <NUM> is unloaded or deployed from the sheath <NUM> into the body.

<FIG> shows the frame <NUM>, anchors <NUM>, and the sheath <NUM>, as shown in <FIG>, in a second configuration, in accordance with various aspects of the present disclosure. The second configuration shows the frame <NUM> being withdrawn into or deployed from the sheath <NUM>. The frame <NUM> is not completely in a delivery configuration (e.g., within the sheath <NUM>). As shown in comparing <FIG>, the anchors <NUM>, which had been projecting outwardly the deployed configuration shown in <FIG>, have moved inwardly (e.g., rotated) relative to and toward the longitudinal axis in response to the frame <NUM> being withdrawn into the sheath <NUM>. The anchors <NUM>, in certain embodiments, are substantially aligned with the adjacent struts <NUM> in the delivery configuration.

The sheath <NUM> includes a substantially circular body portion <NUM> at a distal end of the sheath <NUM>. The substantially circular body portion <NUM> is an entry/exit point for a lumen <NUM> into which the frame <NUM> may be withdrawn for subsequent deployment or redeployment of the frame <NUM>. As shown in <FIG>, the anchors <NUM>, in response to the frame <NUM> being transitioned to the delivery configuration, the anchors <NUM> are configured to rotate inwardly such that the anchors <NUM> do not contact the substantially circular body portion <NUM> (or other portions of) the sheath <NUM>. Portions of the anchors <NUM> (such as the anchor tips) also may avoid contact with the lumen <NUM> of the sheath <NUM> when withdrawn therein. In the absence of the anchors <NUM> being configured to rotate inwardly in this manner, a user operating the sheath <NUM> would encounter a large resistance when attempting to withdraw the frame <NUM> in the sheath <NUM>. The anchors <NUM> being configured to rotate inwardly avoids unnecessary resistance in the deployment process. The unnecessary resistance could also damage the frame <NUM> itself by irreparably pleating or folding the frame <NUM>. Thus, the anchors <NUM> being configured to rotate inwardly in this manner avoids damaging the sheath <NUM>, avoids damaging the frame <NUM>, and eases delivery and deployment of the implantable medical devices that include the frame <NUM>. In certain instances, tips of the anchors <NUM> avoid contact with the sheath <NUM>. The anchors <NUM> rotating when transitioned to the delivery configuration brings a tip (which may be approximately <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>%, <NUM>% of a length of the anchor <NUM> as measured from the distal end) away from an out of contact with the sheath <NUM>. In other instances, the anchors <NUM> rotating in this manner brings the tip to the interior of the frame <NUM>.

The anchors <NUM> are also configured to move outwardly from the longitudinal axis in response to deploying the frame <NUM> from the sheath <NUM>. In addition to demonstrating the configuration or positioning changes of the anchors <NUM> when the frame transitions from the deployed configuration to the delivery configuration, the outward deflection of the anchors <NUM> is demonstrated in comparing the second configuration in <FIG> to the first configuration in <FIG>. As shown in <FIG>, the distal end <NUM> of the frame has expanded as it is retracted into the sheath <NUM>. The open distal end <NUM> facilitates transmission of the collapsing force throughout the entirety of the frame to allow the frame <NUM> to collapse into an elongated delivery configuration. In this manner, the frame <NUM> collapses by retracting into the sheath <NUM> without the need for the application of a collapsing force to the distal end <NUM>. The open distal end <NUM> lessens elongation during deployment and while the device <NUM> is arranged within a patient. In certain instances, the open distal end <NUM> may be between about <NUM> to <NUM> in diameter.

The sheath <NUM> is configured to deploy a distal end <NUM> of the frame prior <NUM> to the proximal end (shown contacting the substantially circular body portion <NUM> of the sheath <NUM> in <FIG>) of the frame <NUM>. In addition, the anchors <NUM> project outwardly (from a waist portion <NUM>) and curve upward toward the proximal end in the deployed configuration shown in <FIG>. The anchors <NUM> move outwardly in response to deploying the frame <NUM> from the sheath <NUM>.

In certain embodiments, a user of the sheath <NUM> may recapture the frame <NUM> (and implantable medical device) within the sheath <NUM>. After implanting the frame <NUM> within the body by deploying the frame <NUM> from the sheath <NUM> and expanding the frame <NUM> to the deployed configuration, placement of the frame <NUM> may not be in the intended location or at the intended angle. Thus, the user may wish to recapture and redeploy the frame <NUM>. In these embodiments, the sheath <NUM> is configured to withdraw the frame <NUM> into the sheath <NUM> (into the delivery configuration) with the anchors <NUM> being configured to rotate radially inwardly and disengage from the tissue in the body. The anchors <NUM> atraumatically disengage from the tissue due to the retracting motion.

<FIG> shows another example frame <NUM> for an implantable medical device, in accordance with various aspects of the present disclosure. In certain instances, the frame <NUM> may include a raised portion <NUM> that is an increase in height relative to a longitudinal axis <NUM> and other portions of the proximal end <NUM> of the frame <NUM>.

In certain instances, the raised portion <NUM> includes a diameter that is approximately about <NUM>%, about <NUM>%, about <NUM>% or any number therebetween of a diameter of the proximal end <NUM> of the frame <NUM>. In addition, the raised portion <NUM> may include a peak in height at the center frame portion <NUM>. The raised portion <NUM> may include a gradual increase in height relative to other portions of the proximal end <NUM> of the frame <NUM>. In certain instances, the raised portion <NUM> includes between a <NUM> degree to a <NUM> degree angle <NUM> relative to the other portions of the proximal end <NUM> of the frame <NUM>. In some embodiments, the raised portion <NUM> has about a <NUM> degree, about <NUM> degree, about <NUM> degree, about <NUM> degree, about <NUM> degree, about <NUM> degree, about <NUM> degree, about <NUM> degree, about <NUM> degree or about <NUM> degree increase relative to the other portions of the proximal end <NUM> of the frame <NUM>. The angle <NUM> being gradual facilitates the proximal end <NUM> maintaining a uniform surface by not creating a protrusion or abrupt increase in height in the proximal end <NUM> of the frame <NUM>. In some instances, the center frame portion <NUM> has a thickness equal to a thickness of at least a majority of the implantable device. In addition, the increase in height relative to other portions of the proximal end <NUM> of the frame <NUM> of the raised portion <NUM> may be between about <NUM> and about <NUM>. For example, the height relative to other portions may be about <NUM>.

In certain instances, the raised portion <NUM> may facilitate transitioning of the frame <NUM> into a collapsed configuration. The raised portion <NUM> lessen strain on the center frame portion <NUM> in transitioning to the collapsed configuration within a delivery sheath by distributing strain about the center frame portion <NUM> and/or the proximal end <NUM>.

Suitable membrane materials for the membrane <NUM> include, but are not limited to, polymers such as olefin, PEEK, polyamide, polyurethane, polyester, such as polyethylene terephthalate (PET), polyethylene, polypropylene, polyurethane, silicone, fluorinated ethylene propylene (FEP), polytetrafluoroethylene (PTFE), expanded polytetrafluoroethylene (ePTFE), and fluoroelastomers, such as tetrafluoroethylene/polymethylvinylether (TFE/PMVE) copolymers. In certain instances, the second layer <NUM> of the membrane <NUM> is the elastomeric material (e.g., TFE/PMVE). The second layer <NUM> may be configured to reinforce the membrane <NUM> and facilitate deflection and rebounding of the membrane <NUM>.

In certain instances, the second layer <NUM> may be attached, adhered or coupled to the first layer <NUM>, to at least a portion of each of the face portions of the elongate members <NUM> or both the first layer <NUM> and at least a portion of each of the face portions of the elongate members <NUM>. The second layer <NUM> may be attached, adhered or coupled to the first layer <NUM> only at the perimeter of the second layer <NUM>. This may further facilitate the rebounding effect of the membrane <NUM>.

A biocompatible material for the graft components, discussed herein, may be used. In certain instances, the graft may include a fluoropolymer, such as a polytetrafluoroethylene (PTFE) polymer or an expanded polytetrafluoroethylene (ePTFE) polymer. In some instances, the graft may be formed of, such as, but not limited to, a polyester, a silicone, a urethane, a polyethylene terephthalate, or another biocompatible polymer, or combinations thereof. In some instances, bioresorbable or bioabsorbable materials may be used, for example a bioresorbable or bioabsorbable polymer. In some instances, the graft can include Dacron, polyolefins, carboxy methylcellulose fabrics, polyurethanes, or other woven, non-woven, or film elastomers.

In addition, nitinol (NiTi) may be used as the material of the frame or stent (and any of the frames discussed herein), but other materials such as, but not limited to, stainless steel, L605 steel, polymers, MP35N steel, polymeric materials, Pyhnox, Elgiloy, or any other appropriate biocompatible material, and combinations thereof, can be used as the material of the frame. The super-elastic properties and softness of NiTi may enhance the conformability of the stent. In addition, NiTi can be shape-set into a desired shape. That is, NiTi can be shape-set so that the frame tends to self-expand into a desired shape when the frame is unconstrained, such as when the frame is deployed out from a delivery system.

Several implantable occlusive device and frame embodiments have been described herein. It should be understood that one or more of the features described in the context of a particular device may be combined with one or more features of any other device or multiple devices described herein. That is, the features of the occlusive devices and frames described herein may be mixed and matched to provide hybrid occlusive device and device frame embodiments, and such hybrid occlusive device and device frame embodiments are within the scope of this disclosure. In some examples, one or more features described with respect to a particular device or frame may replace or be substituted for one or more features of another device or frame. In some examples, one or more features described with respect to a particular device or frame may be added to or included with another device or frame. Also, various combinations or sub-combinations of any of the features described herein may generally be used with any of the devices or frames described herein. It should be understood that the occlusive devices and occlusive device frames provided herein are scalable to a broad range of sizes so that the occlusive devices can be used in a variety of different anatomies, implant sites, and types of implementations.

In certain instances, the coating, as discussed in detail above, may include bio-active agents in addition to heparin or alternatively to heparin. The agents can include, but are not limited to, vasodilator, anti-coagulants, anti-platelet, anti-thrombogenic agents.

It should be understood that although certain methods and equipment are described below, other methods or equipment determined suitable by one of ordinary skill in the art may be alternatively utilized.

Evaluations of heparin coated devices were performed in an acute in vitro re-circulating blood contact model called the Chandler Loop or "blood loop". This acute blood contact model has an established history as a sensitive method for assessing thrombogenicity (Chandler AB, <NUM>, Sanchez et al, <NUM>, Andersson et al, <NUM>, Sinn et al. The method simulates the circulation of blood by rotating closed tubing loops. In vitro blood contact testing allows for determination of relative thrombogenicity of implant surfaces. The Chandler loop model utilizes direct implant contact with circulating blood. When fresh, non-anticoagulated, non-heparinized human blood is used, this model can discriminate thromboresistant from non-thrombogenic surfaces.

As one example of tested devices, control and test implants were be deployed into HeartPrint® Flex Connectors having the CBAS® Heparin Surface. The loops were completed with PVC tubing (inner diameter of <NUM>) having the CBAS® Heparin Surface which eliminated the HeartPrint® Flex and PVC surface as a trigger for any observed initiation of the clotting cascade or platelet activation. In addition, one <NUM> PVC tubing segment with the CBAS® Heparin Surface, one <NUM> dextran sulfate-coated (DS) PVC tubing segment, and one <NUM> uncoated PVC tubing segment, all without an implant, served as system controls in each experiment. The implants and system controls were then be exposed to non-anticoagulated human whole blood in a blood loop for two hours.

The PVC tubing segments coated with CBAS® Heparin Surface), with and without deployed implants, were wet out with IPA. The loops were then rinsed with water and then <NUM> NaCl (physiological saline) solution overnight to remove any residual unbound CBAS®-heparin which may be present on the surface of the implant and the tubing. Also, the tubing segments of dextran sulfate-coated and uncoated PVC (Loops <NUM> and <NUM>) were rinsed overnight with <NUM> NaCl prior to the blood contact experiments.

Following the two hour blood loop evaluation, loops were drained of the whole blood and gently flushed with saline to remove any non-adhered blood components. The drained blood (and any blood which has seeped behind the implants) was collected in a tube containing EDTA anticoagulant in order to measure platelet counts in whole blood and biomarkers in plasma. The implants were removed from the HeartPrint® Flex connectors, further rinsed, photographed, and fixed in formalin. The fixed implants and plasma aliquots were used for SEM evaluation and measurement of biomarkers, respectively.

<FIG> is a representative SEM image (1000X) of the face of a device uncoated implant. <FIG> is a representative SEM image (1000X) of the face of a device implant with the CBAS® Heparin Surface. In general, the device with the CBAS® Heparin Surface had less evidence of thrombus elements such as fibrin and activated platelets. The device implants with the CBAS® Heparin Surface did have evidence of non-specific entrapment of red blood cells in the film's microstructure (<FIG> and <FIG>). In contrast, the uncoated device implant faces showed evidence of thrombus elements (accumulation of fibrin and entrapped blood cells, including both platelets and red blood cells), both isolated and extensive as shown in <FIG> and <FIG>.

Claim 1:
A device for placement in vessels, appendages, and openings in a body, the device comprising:
a frame (<NUM>) having a plurality of elongate members (<NUM>), the frame (<NUM>) including:
a substantially uniform proximal end (<NUM>) of the frame (<NUM>) having (i) a center frame portion (<NUM>) arranged at the proximal end and (ii) face portions (<NUM>) of the plurality of elongate members (<NUM>) extending from the center frame portion (<NUM>) and including a curved pattern arranged substantially within a first plane approximately perpendicular to a longitudinal axis of the frame (<NUM>); wherein the face portions (<NUM>) of the plurality of elongate members (<NUM>) each include a starting point (<NUM>) at the center frame portion (<NUM>) and an ending point (<NUM>) at a perimeter of the proximal end (<NUM>);
a body portion (<NUM>);
a membrane (<NUM>) coupled to at least the substantially uniform proximal end (<NUM>) of the frame (<NUM>); and
a coating arranged on at least a portion of the membrane (<NUM>) configured to minimize the thrombogenic response of blood contact with the membrane (<NUM>) characterized in that the starting point (<NUM>) and the ending point (<NUM>) are radially offset relative to a tangent between the starting point (<NUM>) and the ending point (<NUM>).