EA040848B1 - ARTIFICIAL HEART VALVE WITH ELASTIC SUPPORT STRUCTURES AND CORRESPONDING METHOD - Google Patents

Description

Field of invention

The object of the invention described in the present description relates to artificial heart valves, and more specifically to artificial heart valves having a support structure that stores energy and actively promotes the opening and closing of the leaflets.

State of the art

The human heart has several valves to keep blood flowing through the body in the proper direction. The main valves of the heart are the atrioventricular (AV) valves, including the bicuspid (mitral) and tricuspid valves, and the semilunar valves, including the aortic and pulmonary valves. In health, each of these valves works in a similar way. The valve changes between an open state (which allows blood flow) and a closed state (which prevents blood flow) in response to pressure differences that occur on opposite sides of the valve.

The patient's health can be seriously compromised if any of these valves malfunction. Although dysfunction can be due to various causes, it usually leads to either stenosis, which restricts blood flow, or regurgitation, where blood can flow in the wrong direction. In severe failure, the heart valve may need to be replaced.

Significant efforts have been invested in the development of replacement heart valves, especially replacement aortic and mitral valves. Replacement valves can be implanted percutaneously with a transfemorally or transapically inserted catheter, or can be implanted directly through open heart surgery. Replacement valves typically comprise a valve leaflet arrangement that is made from porcine tissues. These fabric flaps are highly elastic or stretchable. Other replacement valves have been proposed where the leaflets are artificial polymeric structures. In both cases, the leaflets are often held in position by a stent or support structure that has a relatively high stiffness (in the case of open heart replacement valves) or expands into or can be fixed in a very rigid state (in the case of transcatheter valves) to provide maximum support for the sashes. However, these very rigid support structures are generally passive structures which, apart from being supported, have little or no active effect on the operation of the valve itself in controlling flow.

For these and other reasons, there is a need for improved artificial valves.

The essence of the invention

Provided herein are many exemplary embodiments of artificial heart valves having two or more artificial leaflets and a synthetic elastic support structure. In many exemplary embodiments, the flaps may have sufficient stiffness to transfer the load to the elastic support structure during closing. The support structure has elastic properties that allow the support structure to store the transferred load in the form of potential energy and then release it in the form of kinetic energy at the appropriate time to promote the movement of the flaps from closed to open. In many embodiments, this support structure transition is preliminary and occurs without the assistance of the flaps. This pre-open state can lead to a pressure wave that closely resembles that of a healthy native human heart valve. Exemplary embodiments of related methods for the use and manufacture of artificial valves are also described.

Other systems, devices, methods, features, and advantages of the subject matter described herein will or become apparent to one of ordinary skill in the art upon examination of the following figures and detailed description. All such additional systems, methods, features, and advantages are intended to be included in this specification, fall within the scope of the subject matter described herein, and are protected by the accompanying claims. In no way should the features of the exemplary embodiments be construed as limiting the appended claims, in the absence of an express enumeration of those features in the claims.

Brief description of the drawings

Details of the subject matter of the invention set forth in the present description, with respect to its structure and operation, may become apparent from the study of the accompanying drawings, in which like reference numbers refer to like parts. The components in the drawings are not necessarily to scale, but instead use visual emphasis when illustrating the principles of the subject matter of the invention. In addition, all illustrations are intended to convey ideas where relative sizes, geometric shapes, and other detailed attributes may be illustrated schematically rather than literally or accurately.

In FIG. 1A-1B are a perspective view and a top-down view, respectively, showing an exemplary embodiment of an artificial heart valve in a neutral position,

- 1 040848 in FIG. 2A-2C are perspective view, top-down view, and side view, respectively, showing an exemplary embodiment of an artificial heart valve in the open position, FIG. 3A-3C are perspective view, top-down view, and side view, respectively, showing an exemplary embodiment of an artificial heart valve in a closed position, FIG. 4A is a plot of an example of an idealized transvalvular pressure versus time, FIG. 4B is a graph of potential energy and kinetic energy versus time for an exemplary support structure embodiment, FIG. 5A-5B are a partial side view and a perspective view, respectively, of an exemplary embodiment of an artificial heart valve with instantaneous velocity vectors acting during transition to the open position.

Detailed description of the invention

Before describing this subject matter in detail, it should be understood that this disclosure is not limited to the particular embodiments described, as variations are, of course, possible. It should also be understood that the terminology used herein is only for the purpose of describing specific embodiments and is not intended to be limiting, as the scope of the present disclosure is only limited by the appended claims.

Provided herein are exemplary embodiments of systems, devices, kits, and methods that relate to valve replacement in a human or animal subject. For ease of description, these artificial heart valve embodiments are tricuspid valves implanted through open heart surgery and thus are not compressible and expandable for catheter delivery.

However, this subject matter is not limited to such embodiments, and the subject matter may be applied to catheter-implantable heart valves that have a first radially compressed state for placement in a tubular catheter and delivery from the open distal end of the catheter, and a second radially expanded state for normal operation in heart. Similarly, the object of the invention can be applied to artificial heart valves having only two leaflets or having more than three leaflets, whether they are implantable through open heart surgery or delivered through a catheter. These artificial devices can also be used to replace valves at other locations in the patient's body outside the heart.

In FIG. 1A is a perspective view and FIG. 1B is a top down view of an exemplary embodiment of an artificial heart valve 100. The support structure 102 mates with a plurality of valve flaps 110-1, 110-2, and 110-3. Each of the flaps 110 may be separate from the others (as shown here) or may be part of the same solid body with the flaps.

When implanted, the valve 100 is configured to allow or permit blood to flow in the direction indicated here along a central axis 101 that extends through the interior of the valve 100. Blood can flow from the upstream (blood inlet) end 103 of the valve towards the end 104 downstream (bleeding), but prevented (or substantially prevented) from flowing backwards by the presence of the leaflets 110.

The support structure 102, which may also be referred to as a frame, comprises an annular base portion 105, which may have a flat or flattened edge (or surface) 120 upstream in the neutral position, or which may have a curved or serrated edge upstream in the neutral position ( not shown). Examples of upstream scalloped valves are depicted and described in US Pat. No. 9,301,837, which is incorporated herein by reference and for all purposes in its entirety. Here, the upstream edge 120 also constitutes the end of the valve 100 and lies along one flange 121 that extends radially outward from the side wall of the valve 100. it together with edge 120 upstream. Flange 121 can be used to attach a sutured cuff to the outside of support structure 102. Those of ordinary skill in the art will readily understand the design and appearance of a sutured cuff and how it can mate with support structure 102. Although a plurality of flanges 121 may be included, preferably only one flange 121 is used to increase the flexibility of the base 105.

The support structure 102 also includes three raised structures 106-1, 106-2, and 106-3, which may be referred to herein as projections or extensions. Lugs 106 protrude from base annular portion 105 toward downstream end 104, and one horn 106 is present between each pair of adjacent leaflets 110 such that leaflets 110 and ledges 106 are alternately arranged around valve 100. In embodiments with only two leaflets 110 there are only two projections 106.

Each protrusion 106 tapers towards a downstream end 107. Here, each downstream end 107 also represents the top or end of the protrusion 106.

- 2 040848

The support structure 102 includes curved connection zones 108 that are located where the support structure 102 meets the base of the sash 110. The base of each sash 110 may be a physical edge, which would be present if the sash 110 were manufactured separately from the support structure 102, and then later joined together. In the embodiments described herein, the valve 100 is fabricated with synthetic or artificial (i.e., non-fabric) flaps 110, and the curved connection zone 108 can demarcate a seamless or continuous boundary between the support structure 102 and the flap 110, which would be the case if the support structure 102 and the flaps 110 are formed in a monolithic or semi-monolithic manner, for example, using different casting procedures (eg, dip casting, etc.) and molding. Exemplary embodiments of methods for manufacturing valve 100 are described elsewhere in this specification.

In operation, valve 100 cycles between an open position, which allows blood flow through the inside of the valve, and a closed position, in which leaflets 110 prevent blood flow through the inside of the valve. Each of these flaps 110 has a free edge 111 that moves radially inward (toward a closed position) and radially outward (toward an open position). Each flap 110 also has an upstream end 112 (or upstream location), which in this embodiment is also the upstream tip or end of flap 110.

In FIG. 1A and 1B show the valve 100 with the flaps 110 in a neutral position, which may be adopted during casting or other formation of the valve 100. The neutral position is the same or similar to the rest position of the valve 100. In FIG. 2A-2C are perspective, top-down, and side views, respectively, showing an exemplary embodiment of valve 100 in an open position. Here it can be seen, in particular, in the top-down view of FIG. 2B that the free edges 111 of the leaflets 110 have moved radially outward from the central axis 101 and created a relatively large opening to allow blood flow. As further discussed herein, the movement of the leaflets 110 towards this open position is due not only to the pressure exerted by the blood, but also to the active movement of the support structure 102 at the beginning of the cycle.

In FIG. 3A-3C are perspective, top-down and side views, respectively, depicting an exemplary embodiment of valve 100 in the closed position, where the projections 106 (eg, ends 107) are radially closer together as opposed to the open position. Here, the free edges 111 of the flaps 110 have moved radially inward in the direction of the central axis 101 (not shown) and are in contact with each other. In other words, free end 111-1 is in contact with free ends 111-2 and 111-3, free end 111-2 is in contact with free ends 111-1 and 111-3, and free end 111-3 is in contact with free edges 111-1 and 111-2. This position is referred to herein as the close state of the leaflets 110. This state prevents (at least substantially) the flow of blood in the reverse wrong direction (ie, downstream to upstream). Certain embodiments of the valve 100 may be configured with a convex junction between the leaflets and the support structure, as described in incorporated US Pat. No. 9,301,837.

Those of ordinary skill in the art will appreciate that although the leaflets are referred to as being in a converging state (or fully converging state) that prevents blood flow, this does not require either absolute rendezvous or absolute prevention of blood flow, as there may be limited cases in which there is a minimal slight gap between the leaflets when the valve 100 is in the closed position. Thus, when the valve 100 is in the closed position, at least a major portion of the free edges 112 are in contact with each other, and in many embodiments, all of the free edges 112 are in contact with each other. In addition, in a short time interval, immediately before full convergence, the edges of the flaps can begin to touch without full convergence. Such a state can be referred to as partially contiguous. Likewise, the flaps may be in a partially retracted state for a short time interval after the flaps exit the fully retracted state and enter the open state.

In FIG. 4A is a graph showing an exemplary representation of the idealized transvalvular pressure of blood (or other fluid, for example, when tested) on leaflets 110 during part of the cardiac cycle. This graph represents a simulation or model of transvalvular pressure for the mitral valve and is described in this context, although the pressure on the graph can also be applied to the aortic valve. For the mitral valve, transvalvular pressure is generally left atrial pressure minus left ventricular pressure. For the aortic valve, transvalvular pressure is generally aortic pressure minus left ventricular pressure.

Area 402 shows the period of time when positive pressure is present on the leaflets 110 and generally corresponds to the period when the mitral valve is open (leaflets 110 are not close together). IN

- 3 040848 region 402 the left ventricle relaxes, and left atrial systole sets in, which additionally fills the left ventricle with blood. This time period is generally relatively long, but is condensed here for ease of illustration. Region 402 continues to point A where transvalvular pressure goes from positive to zero and blood stops moving in the proper direction from upstream to downstream (left atrium to left ventricle).

Area 404 generally shows the time period starting at point A when the transvalvular pressure is zero and then becomes negative and continues to decrease (become more negative). Negative pressure pushes the blood to move in the opposite direction (from downstream to upstream). As pressure changes from zero to negative, the mitral valve begins to close. Region 404 ends at point B, which indicates the point in time when peak negative pressure is applied to the flaps 110. At 404, the aortic valve opens and isovolumic contraction of the left ventricle occurs.

Region 406 generally reflects the period of time from point B to point C where the peak negative pressure remains generally constant. At point B, the leaflets of the mitral valve are completely brought together. Those skilled in the art will appreciate that since FIG. 4A is a graph of idealized transvalvular pressure, the pressure curve in regions 402-410 has generally constant slopes (or no slope, as in the case of region 404). In the real heart, this transvalvular pressure will exhibit greater variability, as would be expected in a complex natural environment. Thus, in direct practice, pressure in region 406 and others will vary, and region 406 can be considered a transitional region where blood pressure exhibits either a discrete peak or peak curve before becoming less negative.

Region 408 represents a period of time starting at point C, where pressure steadily increases (becomes less negative) until it reaches zero at point D. In region 408, isovolumic relaxation of the left ventricle occurs and the aortic valve closes, while the native mitral valve remains closed.

Region 410 generally reflects the period of time starting at point D where the pressure rises from zero and becomes more positive. Positive pressure moves the blood in the proper direction (from upstream to downstream). As the pressure changes from zero to positive, the native mitral valve begins to move out of its close position. Region 410 generally corresponds to the start of a new cardiac cycle and is essentially a repetition of region 402.

In FIG. 4B is a graph plotting potential energy and kinetic energy versus time for the support structure 102 itself during the idealized transvalvular pressure cycle of FIG. 4A. Potential energy is shown in curve 420 and kinetic energy is shown in curve 440. The positions of points A-D in FIG. 4A are labeled along the timeline.

In FIG. 4B is a feature of certain exemplary valve 100 embodiments where the artificial leaflets 110, as they move radially inward in a rendezvous state, transfer or release a load to an elastic support structure 102, which then stores this transferred load as potential energy. Fabric (i.e. non-artificial) sashes are too tensile to carry the load in the same way. The potential energy stored in the support structure 102 in the closed position can then be released in the form of kinetic energy, such as when the transvalvular pressure becomes less negative.

Thus, embodiments of the support structure 102 are capable of transitioning from a closed position to an open position long before the transvalvular pressure becomes positive, as is the case with a native valve. This can be referred to as the rebound or active rebound characteristic of the support structure 102, where the support structure 102 returns from the closed position back to the open position before (or earlier than the native valve), and in many cases well before, the transvalvular pressure becomes positive ( before normal blood flow). Thus, the pre-transition occurs without the leaflets initiating movement of the support structure (eg, without pulling or dragging the support structure with the leaflets) and without initially forcing the support structure to open with positive back pressure or blood flow through the valve.

In FIG. 4B, potential energy 420 and kinetic energy 440 of support structure 102 are generally minimal, while transvalvular pressure occurs in region 402. As transvalvular pressure shifts away from zero and becomes more negative in region 404, potential energy 420 begins to increase with a comparable but with an inverse slope relative to pressure reduction (FIG. 4A). As the pressure becomes more negative, the flaps 110 carry a higher fluid load and accelerate radially inward towards the approached position. The increase in potential energy 420 in region 404 is primarily due to the transfer or release of this load from the flaps 110 to the support structure 102, which stores the potential

- 4 040848 energy in the form of elastic deformation of the physical body of the support structure 102.

As the transvalvular pressure continues from zero and becomes more negative in region 404, kinetic energy 440 exhibits a spike 442 corresponding to the initial rapid movement of support structure 102 from an open position to a closed position. At 444, potential energy 420 increases from zero and kinetic energy 440 decreases at a variable rate of decrease as support structure 102 elastically deforms towards the closed position.

At point B, the flaps 110 touch and move into a fully contiguous state. This corresponds to a steep drop 446 in the kinetic energy 440 indicating that the support structure 102 has essentially reached the closed position. Some continuous decrease in kinetic energy occurs in the region 406 until point C, when the support structure 102 assumes the closed position. Potential energy 420 reaches its maximum at 406 and remains generally constant, corresponding to a generally constant negative transvalvular pressure peak.

At point C, the transvalvular pressure equals its peak negative pressure, and immediately thereafter, the transvalvular pressure becomes less negative (increases). In this embodiment, stored potential energy 420 begins to be released from support structure 102 in the form of kinetic energy 440. Thus, a steep increase 448 in kinetic energy 440 occurs just after point C or as transvalvular pressure decreases from peak negative pressure. The kinetic energy 440 reaches a transition energy 450 where the kinetic energy initially plateaus and then gradually increases as the potential energy 420 continues to decrease in region 408. In this embodiment, the kinetic energy 440 can be described as behaving essentially like a step function and at point B and at point C.

The decrease 448 of the kinetic energy 440 corresponds to the preliminary movement of the support structure back to the open position (more details about this movement are described below). At point C, the leaflets 110 are still fully approached. Leaflets 110 leave the fully retracted state as the pressure becomes less negative towards point D. In some embodiments, valve 100 may be 20% or more open at point D (i.e., valve 100 allows 20% or more of its flow in a normally open state), in other embodiments, valve 100 may be fully open at or before point D, and in other embodiments, valve 100 is fully open upon reaching the next cycle's peak positive pressure. This increase 448 in kinetic energy is caused by the unloading of potential energy 420 stored as elastic deformation of the support structure 102. Thus, the support structure 102 has the advantage of pre-or actively transitioning (eg, recoil or rebound) to or from its open position before the flaps 110 fully exit the confinement state, and before blood begins to flow through the interior of the valve 100. The effects of this pre-transition 448 may include a significantly reduced pressure gradient or opening resistance, which in turn may lead to a smaller effective orifice area (EOA) and increased effective direct blood flow.

As noted above, during actual operation of the valve 100, the transvalve pressure may not exhibit a constant peak negative pressure, as shown at region 406 in FIG. 4A. Instead, the transvalvular pressure may exhibit a curvilinear or parabolic character, with a peak negative pressure at the apex. In some embodiments, the peak negative transvalvular pressure is approximately 120 mm Hg, although it is emphasized that this is only an example and other peak negative pressures may occur. In the embodiment described with respect to FIG. 4B, the pre-pass 448 begins immediately when the transvalvular pressure becomes less negative after the peak negative pressure.

However, in other embodiments, the implementation of the support structure 102 can be configured such that this preliminary transition begins at a later time. In some exemplary embodiments, pre-transition may occur when the transvalvular pressure is 90-99.9% of peak transvalvular pressure, when the transvalvular pressure is 85-95% of peak transvalvular pressure, when the transvalvular pressure is 7590% of peak transvalvular pressure, when the transvalvular pressure is 50-75% of the peak transvalvular pressure, or when the transvalvular pressure is 25-50% of the peak transvalvular pressure.

In FIG. 5A is a partial side view showing an exemplary embodiment of support structure 102 with vectors simulating relative velocities on the surface of elastic support structure 102 as structure 102 transitions from a closed to an open position. In this example, the velocity vectors reflect the point at which the pre-transition was initiated (eg, just after point C in FIG. 4B). Only the front half of the support structure 102 is shown here, with the flaps 110 (although present) omitted for ease of illustration. The position in which the end 112-1 will lie upstream of the flap 110-1 is indicated by the arrow.

The support structure 102 has a plurality of first locations 501 and second locations

- 5 040848

502 aligned with the downstream ends 107 of the projections 106 and the upstream ends 112 of the flaps 110. In FIG. 5A, the position of the first locations 501-1 and 501-3 is indicated immediately upstream of the downstream ends 107-1 and 107-3, respectively. The position of the second location 502-1 is indicated immediately upstream of the upstream end 112-1 of the flap. The first location 501-1 is immediately upstream of end 107-1 downstream under the side wall of projection 106-1 and along flange 121 as it continues radially outward aligned with end 107-1. While some asymmetry may be present in various embodiments, during normal operation, embodiments of valve 100 operate symmetrically, with each leaflet 110 and lip 106 as a whole moving back and forth in a similar manner between open and closed positions.

The longer the velocity vector, the greater the instantaneous velocity. As can be seen here, the relatively largest instantaneous velocities occur along the projections 106, in particular at and near the downstream ends 107, as these are the areas with the most elastic strain in the closed position.

In many embodiments, the upstream elastic edge 120 also exhibits movement when the support structure 102 begins a preliminary transition from a closed to an open position. In the embodiment of FIG. 5A, the upstream edge 120 moves in the upstream direction at each of the first locations 501 and the upstream edge 120 simultaneously moves in the downstream direction at each of the second locations 502.

This feature is shown in Fig. 5B, which shows the flange 121 with the corresponding velocity vectors increased in magnitude compared to FIG. 5A for ease of illustration. The remainder of the support structure 102 is shown in outline without the rest of the velocity vectors (see FIG. 5A) and the flaps 110 are also omitted for clarity.

In FIG. 5B, the velocity vectors have a generally sinusoidal distribution along the upstream edge 120 over the entire periphery of the valve 100, which translates into a sinusoidal displacement. For example, the area surrounding each first location 501 has downstream velocity vectors with the greatest magnitude at or near the very first location 501, and generally decreasing or coning with increasing distance to the first location 501 on either side. Conversely, the area surrounding every second location 502 has upstream velocity vectors with greatest magnitude at or near the second location 502 itself, and generally decreasing or coning with increasing distance to the second location 502 on either side. Approximately midway between each first location 501 and its immediately adjacent second location 502 is a third location 503 at which the velocity vectors reach zero, reflecting no movement at that location and at that point in time. Locations 503 are pivot points located between the oscillating cross sections. For each location near the periphery of the upstream edge 120, the velocity vectors become relatively large as they move radially outward from the inner edge of the flange 121 to the outer edge of the flange 121 (shown in three concentric rows of vectors in FIG. 5B).

Thus, in many embodiments, when edge 120 is considered as a whole, the velocity and motion profile as a whole is sinusoidal, where a particular point along upstream edge 120 can range from full upstream displacement, to neutral displacement, to full downstream displacement. downstream, back to neutral offset, and so on, depending on the location of the point along the upstream edge 120 of interest. In the closed position, the upstream edge 120 has a sinusoidal surface with locations 501 offset relatively downstream and locations 502 offset relatively upstream. In the open position, upstream edge 120 also has a sinusoidal surface, but with a complementary or inverted profile, with locations 501 offset relatively upstream and locations 502 offset relatively downstream. In the embodiment shown here, pivot locations 503 are not subject to relative displacement as valve 100 transitions between open and closed positions.

Also in this embodiment, the warp edge 120 does not have a sinusoidal geometry in the neutral position, but is flat or flattened. In alternative embodiments where warp edge 120 is not flat in the neutral position, such as aortic configurations where warp edge 120 is serrated, the sinusoidal displacement occurs from a serrated neutral position as opposed to a flat neutral position. Although the velocities and displacements are described in sinusoidal form, these velocities and displacements can also be essentially sinusoidal, and those of ordinary skill in the art, after reading this description, will easily understand what geometric shapes are essentially , sinusoidal. In any case, those skilled in the art will appreciate that sinusoidal functions can vary in amplitude and frequency. They will also understand that the manufacture and use of artificial valves can lead to deviations due to manufacturing variations, variations due to

- 6 040848 implantation, variations due to the length of valve implantation time (for example, accumulation of material such as calcification, etc.) and / or noise, and the effects that these deviations have on sinusoidal functions, are included in the scope of the term sinusoidal, as used in the present description.

In FIG. 5A-5B depict the instantaneous velocities on the support structure 102 at the time the pre-transition begins, which may be just after point C in FIG. 4B, or other times as noted elsewhere in this specification. Movement in these directions continues eventually at decreasing speeds until the support structure 102 reaches its open position (see FIGS. 2A-2C), which can occur any number of times. For example, if the support structure 102 reaches its open position when the transvalvular pressure becomes positive, then movement in the directions indicated by these vectors may continue from the start of the pre-transition (for example, just after point C in FIG. 4A when the pressure is 90-99 .9% of peak, 85-95% of peak, 75-90% of peak, 50-75% of peak or 25-50% of peak, etc.) until the moment when the transvalvular pressure becomes positive. Similarly, if support structure 102 reaches its fully open position when maximum downstream fluid flow occurs (e.g., peak positive pressure), then movement in the directions indicated by these vectors may continue from the start of the pre-transition until the time when transvalvular pressure becomes positive.

In FIG. 5A-5B depict the velocities as support structure 102 moves from a closed position (see, for example, FIGS. 3A-C) to an open position (see, for example, FIGS. 2A-2C). In these embodiments, a similar but opposite movement (not illustrated) occurs as the support structure 102 moves from the open position to the closed position. Thus, for example, each of the directions of the velocity vectors in FIG. 5A can be reversed to show the direction of movement as support structure 102 moves from open to closed position (e.g., projections 106 move radially inward, first locations 501 move in an upstream direction, second locations 502 move in a downstream direction, and etc). The value of the instantaneous velocities will be relatively less than what is shown in Fig. 5A-5B because the peak positive transvalvular pressure (eg, about 20 mmHg) is generally significantly less than the peak negative transvalvular pressure (eg, about 120 mmHg).

In many embodiments, the downstream ends 107 of support structure 102 show the most displacement when structure 102 transitions between closed and open positions. The downstream ends 107 of the support structure also exhibit relatively high instantaneous velocities when the support structure 102 is released from the open or closed position.

Embodiments of the valve 100 may have different maximum displacements, as measured from the valve's neutral position (see, for example, FIGS. 1A-1B), to the open position, or the closed position, depending on the size of the valve. The following paragraphs describe embodiments having various displacements and velocities that were obtained from exemplary mitral and aortic configurations. The exemplary mitral configuration had a diameter of 27 mm and a protrusion length 510 of 13.5 mm, which was measured along the central longitudinal axis of the protrusion from a position in line with the edges 112 of the leaflet base (see FIG. 5A). The exemplary aortic configuration had a diameter of 23 mm and a protrusion length 510 of 12.5 mm. The speeds and displacements described herein scale in a substantially linear manner between dimensions. Various sizes of mitral and aortic embodiments are described in more detail below.

For a neutral to closed mitral valve configuration, in some embodiments, the maximum radial inward displacement (DMRI) for the downstream ends 107 is 0.45 mm or more, in some embodiments, the DMRI is 0.50 mm or more , in some embodiments the D _MRI is 0.55 mm or more, in some embodiments the D _MRI is 0.60 mm or more, in some embodiments the D _MRI is 0.65 mm or more, and in some embodiments the D _MRI is 0.70 mm or more. Although dependent on actual implementation, in certain exemplary embodiments, D _MRI does not exceed 1.50 mm and in other embodiments, D _MRI does not exceed 0.90 mm.

For a mitral valve configuration that transitions from a neutral position to an open position, in some embodiments the maximum radial outward displacement (DMRO) of the downstream ends 107 is 0.020 mm or more, in some embodiments the DMRO is 0.021 mm or more, and in some embodiments DMRO is 0.022 mm or more. Although it depends on the actual implementation, in certain exemplary embodiments the DMRO does not exceed 0.060 mm and in other exemplary embodiments the DMRO does not exceed 0.030 mm.

For an aortic valve configuration that transitions from a neutral to a closed position, in some embodiments, the maximum radial inward displacement (DMRI) at the downstream ends 107 is 0.31 mm or more, in some embodiments, the DMRI is 0, 35 mm or more, in some embodiments the DMRI is 0.38 mm or more, in some embodiments the DMRI is 0.40 mm or more, in some embodiments the DMRI is 0.45 mm or more, and in some embodiments the DMRI is 0.50 mm or more. Although it depends on the actual implementation, in certain exemplary embodiments the DMRI does not exceed 1.20 mm and in other exemplary embodiments the DMRI does not exceed 0.60 mm.

In many embodiments, downstream ends 107 of support structure 102 also exhibit particular instantaneous velocities when structure 102 begins a pre-transition from a closed position to an open position. For a mitral valve configuration transitioning from a closed position to an open position, in some embodiments, the instantaneous velocity of each downstream end 107 at pre-transition initiation (V _ICO ) is 5.10 mm/s or more, in some embodiments, V _ICO is 5.20 mm/s or more, in some embodiments V _ICO is 5.30 mm/s or more, in some embodiments V _ICO is 5.40 mm/s or more, in some embodiments V _ICO is 5, 50 mm/s or more, in some embodiments V _ICO is 5.60 mm/s or more, in some embodiments V _ICO is 5.80 mm/s or more, in some embodiments V _ICO is 6.00 mm /s or more, in some embodiments, V _ICO is 6.20 mm/s or more, in some embodiments, V _ICO is 6.40 mm/s or more, in some embodiments, VICO is 6.60 mm/s, or bol ee, in some embodiments the VICO is 6.80 mm/s or more, in some embodiments the V _ICO is 7.00 mm/s or more, and in some embodiments the VICO is 7.10 mm/s or more. Although dependent on actual implementation, in certain exemplary embodiments, VICO does not exceed 14.50 mm/s and in other exemplary embodiments, _VICO does not exceed 7.8 mm/s.

For an open-to-closed mitral valve configuration, in some embodiments, the instantaneous velocity of each downstream end 107 at initiation of the pre-transition (V _IOC ) is 4.10 mm/s or more, in some embodiments, V _IOC is 4.20 mm/s or more, in some embodiments, V _IOC is 4.30 mm/s or more, in some embodiments, V _IOC is 4.40 mm/s or more, and in some embodiments, V _IOC is 4, 50 mm/s or more. Although it depends on the actual implementation, in certain exemplary embodiments the VIOC does not exceed 10.00 mm/s and in other exemplary embodiments the VIOC does not exceed 5.00 mm/s.

For an aortic valve configuration that transitions from closed to open position, in some embodiments, VICO is 14.60 mm/s or more, in some embodiments, VICO is 14.75 mm/s or more, in some embodiments, VICO is 15 .00 mm/s or more, in some embodiments V _ICO is 16.00 mm/s or more, in some embodiments V _ICO is 17.00 mm/s or more, in some embodiments V _ICO is 18.00 mm/s or more and in some embodiments, the V _ICO is 18.50 mm/s or more. Although dependent on actual implementation, in certain exemplary embodiments, V _ICO does not exceed 40.00 mm/s and in other exemplary embodiments, V _ICO does not exceed 21.00 mm/s.

For an aortic valve configuration that transitions from open to closed, in some embodiments the VIOC is 6.10 mm/s or more, in some embodiments the VIOC is 6.20 mm/s or more, in some embodiments the VIOC is 6 .50 mm/s or more, in some embodiments the VIOC is 7.00 mm/s or more, and in some embodiments the V _IOC is 7.50 mm/s or more. Although dependent on actual implementation, in certain exemplary embodiments VIOC does not exceed 15.00 mm/s and in other exemplary embodiments V _IOC does not exceed 8.5 mm/s.

The characteristics of the above embodiments are achieved through a balanced use of materials, cross-sections, stiffnesses and elasticities for both the flaps 110 and the support structure 102. For example, if the support structure is made of a plastically deformable material, it does not behave in this way. Rather, the support structure will take on a deformed geometry determined by the load being shed by the sash, but gradually the material of the support structure will relax and lose its resilience to restore the nominal geometry.

On the contrary, if the flaps, where each less structurally strong flap, essentially deforms and significantly reduces the amount of load dropped on the support structure, and thus significantly reduces the potential energy stored in the support structure for the preliminary transition. Often this is true for tissue artificial heart valves, where the leaflets are made from predominantly bovine or porcine pericardial tissue, which is highly deformable with a very low modulus of elasticity. These fabric valves have support structures that are often made of relatively rigid substrates such as Elgiloy wire or thick curved sections of Delrin or acetal polymers, which are more rigid due to the inertia of the sections.

The amount of stretch in the leaf also affects the mechanism. If the support structure experiences a very small fraction of the load when fully closed, there will be no stored potential energy to actuate the pre-transition mechanism as the minimum pressure becomes less negative, the leaflets will elastically rebound but not open the valve until the pressure is positive, since the support structure does not have recovery.

In the embodiments described herein, as the flaps 110 approach each other, they release a load on the support structure 102, which in turn deforms. The amount of deformation can ensure that there is no additional stretch in the plane of the flaps 110 and allow a pre-transition mechanism to occur. Also in many embodiments, the base 105 (and upstream edge 120 of the base) is flexible and allows for significant movement. If the base is rigidly constrained or free deformation is prevented, which may be true for a substantially rigid double flange configuration, the resulting elastic strain energy in the system to promote pretransition will be reduced and the maximum stress level will be greatly increased.

The support structure 102 may be made from one or more materials (eg, a core structure of one material coated with the same or a different material). The materials are preferably polymeric materials such as polyether ether ketones (PEEK), polyurethanes, polyetherimides (PEI) such as ULTEM, any of the materials used to form flaps 110, and others. Shutters 110 are also preferably made from polymeric materials, including any biostable polyurethanes and polyurethane compositions (eg, polysiloxane-containing polyurethanes, etc.) known in the art. Examples of polyurethane-containing flaps are described in US Pat. No. 6,984,700, US Pat. No. 7,262,260, US Pat. No. 7,365,134 and Yilgor et al. Polym. sci. (2013), all of which are incorporated herein by reference in their entirety for all purposes. Materials that approach ideal isotropic low creep characteristics are particularly suitable for use in many embodiments.

Although many materials can be used, it is preferred that the selected material has a suitable elastic modulus to allow for the load shedding and elastic deformation characteristics described herein. In many exemplary embodiments, the modulus of elasticity for flaps 110 is in the range of 10-45 MPa. In certain exemplary embodiments, the modulus of elasticity for flaps 110 is in the range of 20-35 MPa, while in certain other exemplary embodiments, the modulus of elasticity for flaps 110 is in the range of 23-32 MPa, while in other exemplary embodiments, the modulus of elasticity for flaps 110 is in the range of 25-30 MPa. In many exemplary embodiments, the modulus of elasticity for the support structure 102 is in the range of 3000-5000 MPa. In certain exemplary embodiments, the modulus of elasticity for the support structure 102 is in the range of 3300-3500 MPa.

Embodiments of support structure 102 are relatively less rigid than prior art rigid valves. In many embodiments, the support structure 102 has a stiffness per unit force (RUF) (mm ² ) between 600 and 1500. In other embodiments, the support structure 102 has a RUF of 900-1400, and in other embodiments, the support structure 102 has a RUF of 110 0-1300 . The projections 106 can be modeled as an elastic beam and RUF can be calculated according to (1) R _UF =EI/P=L ³ /3δ (1) where E is Young's modulus, I is sectional inertia, P is end force 107 downstream, L is the length 510 of the protrusion 106 and δ is the offset at the end 107 downstream.

In certain embodiments, the implementation of the support structure 102 may include a rod frame. The flaps 110 can be seamlessly formed on this core frame, for example, through a casting process (eg, dip casting) or molding or other. An exemplary dip casting process that is suitable for forming flaps is described here. The rod frame can be made from a suitable material, such as that described in the present description. This can be done by machining or injection molding. The rod frame can then be placed on the dipping core, which has the geometric shape of the inner surface of the support structure and the flaps. The core can be placed in the polymer solution using molding equipment that wraps around the core frame and molds the sashes into the desired shape.

The rod frame and core can be dipped into the polymer solution at high temperature and humidity and then taken out. While the methods disclosed herein are not limited thereto, in some exemplary embodiments, the relative humidity (RH) may be in the range of 20-80% and the temperature may be in the range of 20-50°C. This stage may

- 9 040848 lead to the formation of the support structure 102 and the flaps 110 together as a whole in a formed but not unfinished state.

The dipping step may be performed only once to obtain a fully formed (but unfinished) valve, or may be performed multiple times (eg, two times, three times, or as many times as desired). In one embodiment, the core frame is made from a first material (eg, PEEK) other than the polymeric material from which the sashes are made. In this case, it may be desirable to form the flaps on the stem frame only after pre-coating the stem frame with a flap resin in order to achieve higher cohesion. The stem frame can be precoated by first dipping the stem frame in a leaf polymer having a first viscosity. This can be done with or without a core. If performed with a core, the resulting flaps can be removed. The pre-coated rod frame can then be placed on the core and dipped again, this time in leaf polymer with the same or relatively higher viscosity. This second dipping may lead to the formation of complete leaflet bodies integrally formed with the support structure. The use of a low viscosity followed by a higher viscosity may allow the formation of a thin precoat that does not significantly distort the geometry of the underlying stem frame, followed by the formation of flaps having the desired thickness.

The support structure 102 and flaps 110 can then be trimmed and otherwise finished to achieve neat and precise edges and a smooth surface. This can occur, for example, when using laser cutting, ultrasonic cutting, water knife, mechanical double-wing cutter, etc. The sutured cuff may be mated with the support structure 102 (using any flange 121 if present) and the final device may be packaged in the desired sterile container.

Those of ordinary skill in the art will readily recognize, in light of this disclosure, many variations of suitable dip casting procedures, pressures, and temperatures that are not set forth here, but are still suitable for making the artificial heart valves described herein. Likewise, those of ordinary skill in the art will also recognize, in light of this disclosure, dip casting alternatives that can be used to make the artificial heart valves described herein.

Embodiments of the valve 100 described herein are suitable for implantation in a subject (human or animal). This can be done using any number of medical procedures. Preferably, these valve 100 embodiments are intended for direct implantation, for example, in the mitral or aortic annulus using open heart surgery.

In one such exemplary open heart implantation procedure, an appropriately sized replacement valve can be determined and the surgeon then performs an open heart access procedure to gain access to the failed heart valve to be replaced. The surgeon can then place the selected artificial heart valve 100 in place over the failed valve and attach the valve 100 to the surrounding tissue. Attachment can take place, for example, by attaching the cuff to be sutured to the fabric with one or more sutures. Prior to attachment, if the surgeon determines that the valve of the selected size is not optimal, then another valve of a different size can be selected and placed in place in the heart. In some other embodiments, the failed valve may be removed before the valve 100 is placed in the intended location. When the valve 100 is attached, the open heart cavity is closed and the procedure is completed.

Embodiments of valve 100 used for open heart surgery are not radially compressible for placement in either an intravascular delivery device (eg, catheter) or a transapical delivery device. However, in other embodiments, the valve 100 may be provided with a radially compressible support structure that allows the lateral dimensions of the valve 100 to be reduced sufficiently to allow placement in an appropriately sized intravascular or transapical delivery device.

For most aortic valve replacement configurations, valve 100 can be implemented to fit the aortic tissue ring in the following sizes: 17 mm, 19 mm, 21 mm, 23 mm, 25 mm, and 27 mm. Other sizes can be implemented, including 18mm, 20mm, 22mm, 24mm, 26mm, 28mm, and 29mm, and non-integer sizes between those listed, of which there are many. These dimensions are also commonly referred to as the inside diameter or valve ID, and refer to the lateral dimensions of the valve in position corresponding to the leaflets 110. The valve may have an even larger diameter elsewhere, such as the location of the flange 121. For most mitral valve replacement configurations it is possible to implement valve 100 with any of the following IDs: 23mm, 25mm, 27mm, 29mm, and 31mm. Other sizes can be realized, including 22mm, 24mm, 26mm, 28mm, 30

- 10 040848 mm, 32 mm, and non-integer sizes between those listed, of which there are many.

Although the support structure 102 may take on various non-cylindrical shapes, in all embodiments described herein, the support structure 102 may be substantially cylindrical or cylindrical. As those of ordinary skill in the art will appreciate, cylindrical does not require the support structure 102 to be in the form of an entire geometric cylinder (e.g., vertical walls oriented at the correct angle to the circular section), but rather requires the support structure 102 to lie along a portion of the hypothetical geometric cylinder (with only a slight deviation). For example, the entire inner surface of the lumen (the surface immediately adjacent to the blood stream) of the support structure 102 may be cylindrical, as the term is used herein. Likewise, those of ordinary skill in the art will recognize that a support structure 102 that is essentially cylindrical allows for greater deviation from the mathematical cylinder than a simple cylindrical support structure, and will readily recognize those support structures that are essentially cylindrical. , cylindrical.

Although the entire support structure 102 may be cylindrical or substantially cylindrical, it is also true that only a portion of the support structure 102 may be cylindrical or substantially cylindrical, where the remainder of the support structure 102 is non-cylindrical. For example, in certain embodiments, only a portion of the support structure 102 along the curved zones of the joint 107 may be cylindrical or substantially cylindrical.

When the support structure 102 is formed from a polymer-coated bar frame, then in some embodiments, only the bar frame (in whole or in part) may be cylindrical or substantially cylindrical, while the outer surface of the polymer coating is not cylindrical or substantially cylindrical. For example, in some embodiments, the inner surface of the stem frame lumen is cylindrical and the outer surface of the polymeric coating (along the inner stem frame lumen) is substantially cylindrical (or even non-cylindrical) due to variations in coating thickness.

All valve 100 embodiments described herein can also be provided to the healthcare professional (or the healthcare professional may retain) as part of a set (or set) of artificial valves sized for various tissue ring sizes. Sizes may include any combination of two or more of the following: 17mm, 18mm, 19mm, 20mm, 21mm, 22mm, 23mm, 24mm, 25mm, 26mm, 27mm, 28mm, 29mm , 30 mm and 31 mm.

Although the embodiments described herein can actively assist in opening and closing the valve through the storage and release of energy in response to pressure differences in the bloodstream, these valve embodiments, when viewed as a whole, can be characterized as passive devices that do not actively receive power from an artificial power source. Some examples of actively powered devices include mechanisms used for cardiopulmonary bypass (eg, heart-lung machines) and an implantable artificial heart.

The behavior of the valve 100 can be evaluated in various ways. For example, the behavior of the valve 100 can be observed after the valve 100 is implanted in a subject. Transvalvular pressure can be measured directly at the subject, for example by placing catheter pressure transducers on opposite sides of the valve. Alternatively, the behavior of valve 100 can be assessed by testing valve 100 in a test apparatus that applies fluid pressure in a manner that mimics transvalvular pressure in a subject. In addition, the behavior of the valve 100 can be evaluated by computer simulation using an idealized model of transvalvular pressure in a subject, such as that described with respect to FIG. 4A-B.

Various aspects of this object of the invention are set forth below, while considering and/or supplementing the embodiments described so far, here with emphasis on the relationship and interchangeability of the following embodiments. In other words, emphasis is placed on the fact that each feature of the embodiments can be combined with each and every other feature, unless explicitly stated otherwise or logically implausible.

In many embodiments, an artificial heart valve is provided that includes a plurality of synthetic leaflets and a support structure that comprises a plurality of protrusions associated with the plurality of leaflets and a base upstream of the plurality of protrusions, where the plurality of protrusions and the base are elastic. The artificial heart valve may have a closed position and an open position, and a plurality of leaflets and a support structure move between a closed position and an open position.

In certain embodiments, the artificial heart valve can be configured to flow fluid in the proper direction from an upstream position to a downstream position when transvalvular fluid pressure is positive, and configured so that the plurality of leaflets are in a contiguous state when the transvalve pressure of the fluid is the peak negative pressure. The artificial heart valve may be configured such that when the transvalvular fluid pressure is a negative value less than the peak negative pressure, the plurality of protrusions automatically move from a closed position to an open position.

In certain embodiments, the support structure has a periphery and the base includes an edge that extends around the periphery of the support structure. Each flap of the plurality of flaps may have an upstream end, and each projection of the plurality of projections may have a downstream end. In certain embodiments, the edge may comprise: a first location immediately upstream of each end downstream of a plurality of protrusions such that a plurality of first locations are present at the edge; and a second location immediately upstream from each end upstream of the plurality of flaps such that a plurality of second locations are present at the edge, where at a first time as the support structure moves from a closed position to an open position, each first location moves in an upstream direction and every second location moves downstream.

In certain embodiments, the first time is when the transvalvular fluid pressure is 90-99.9% of peak negative pressure, 85-95% of peak negative pressure, or 25-75% of peak negative pressure. The first point in time may occur when the transvalvular pressure of the fluid has a negative value. In certain embodiments, each first edge location moves in a downstream direction and every second edge location moves in an upstream direction continuously as the transvalvular fluid pressure transitions from 75% of peak negative pressure to zero. In certain embodiments, each first edge location moves in a downstream direction and every second edge location moves in an upstream direction in immediate response to the transvalvular fluid pressure transition from peak negative pressure to less negative pressure. A plurality of flaps may begin to move out of the converged state at the first moment in time. Also, at a first time, each downstream end of the plurality of protrusions can move in a radially outward direction.

In certain embodiments, the support structure comprises a sutured cuff and no more than one sutured cuff flange.

In certain embodiments, the heart valve is an aortic replacement valve or mitral replacement valve, the heart valve contains exactly three synthetic leaflets. In certain embodiments, the heart valve is a mitral replacement valve containing exactly two synthetic leaflets.

In certain embodiments, the support structure is not radially compressible for placement in an intravascular delivery device. In certain embodiments, the support structure is not radially compressible for placement in a transapical delivery device.

In certain embodiments, the support structure and the plurality of flaps are formed from the same material. In certain embodiments, the support structure comprises a cover, and the plurality of flaps is a continuation of the cover. The plurality of flaps may be polymeric.

In certain embodiments, the plurality of flaps are not sewn to the support structure. A plurality of sashes can be seamlessly mated to the support structure. The plurality of flaps and the support structure may be a monolithic body.

In many embodiments, the artificial heart valve is neither part of a cardiopulmonary bypass machine, nor an implantable artificial heart, nor an artificial heart valve powered by an artificial power source.

In certain embodiments, the support structure has an internal diameter selected from the group consisting of: 17 mm, 19 mm, 21 mm, 23 mm, 25 mm, 27 mm, 29 mm, and 31 mm.

In certain embodiments, the plurality of flaps have a first resiliency and the support structure has a second resiliency, the first resiliency may be in the range of 10-45 MPa. In certain embodiments, the implementation of the first elasticity may be in the range of 20-35 MPa. In certain embodiments, the implementation of the first elasticity may be in the range of 25-30 MPa. In certain embodiments, the implementation of the second elasticity may be in the range of 3000-5000 MPa. In certain embodiments, the implementation of the second elasticity may be in the range of 3300-3500 MPa.

In certain embodiments, the implementation of the support structure may have a rigidity per unit force between 600 and 1500 mm ² . In certain embodiments, the implementation of the support structure may have a rigidity per unit force between 900 and 1400 mm ² . In certain embodiments, the implementation of the support structure may have a stiffness per unit force between 1100 and 1300 mm ² .

Each of the plurality of protrusions may have a downstream end. In certain mitral embodiments, where each downstream end may exhibit an instantaneous velocity (V _ICO ) of 5.10 mm/s or more when moving from a closed position to an open position. IN

- 12 040848 various embodiments VIcO can be any of a variety of values and ranges between 5.10 mm/s and 14.50 mm/s. In certain embodiments, when moving from an open position to a closed position, each downstream end may exhibit an instantaneous velocity (V _IOC ) of 4.10 mm/s or more. In various embodiments, V _IOC may be any of a variety of values and ranges between 4.10 mm/s and 10.00 mm/s.

In certain aortic embodiments where each downstream end may exhibit an instantaneous velocity (V _ICO ) of 14.60 mm/s or more upon transition from a closed position to an open position. In various embodiments, V _ICO may be any of a variety of values and ranges between 14.60 mm/s and 40.00 mm/s. In certain embodiments, where each downstream end may exhibit an instantaneous velocity (VIOc) of 6.10 mm/s or more when transitioning from an open position to a closed position. In various embodiments, V _I0C may be any of a variety of values and ranges between 6.10 mm/s and 15.00 mm/s.

The artificial heart valve may have a closed position, a neutral position, and an open position, and the plurality of leaflets and support structure transition between a closed position, a neutral position, and an open position during operation of the valve. In certain mitral embodiments, each downstream end may move inward by 0.45 mm or more when moving from a neutral position to a closed position. In various embodiments, each downstream end may move inward by 0.45-1.50 mm. In certain aortic embodiments, each downstream end may move inward by 0.31 mm or more when moving from a neutral position to a closed position. In various embodiments, each downstream end may move inward by 0.31-1.20 mm.

When a range of values is provided, each intermediate value, up to a tenth of one of the lower limit, unless the context clearly dictates otherwise, between the upper and lower limits of that range and any other specified or intermediate value in that specified range, is included in the disclosure and may be claimed as a single value or as a smaller range. Where a specified range includes one or both of the limits, ranges not including either or both of those included limits are also included in the disclosure.

When a discrete value or range of values is provided, that value or range of values may be stated more broadly than the discrete number or range of numbers unless otherwise noted. For example, each value or range of values provided herein may be claimed as an approximation, and this paragraph serves as the underlying background and written justification for introducing claims, at any time, that list each such value or range of values as that approximate value, that approximate range of values, that approximate value, and/or that approximate range of values. Conversely, if a value or range of values is indicated as an approximation or generalization, such as about X or about X, then that value or range of values can be stated discretely without using such an expanding term.

However, this description should in no way be interpreted as implying that the subject matter disclosed herein is limited to a particular meaning or range of values, in the absence of that meaning or range of values being explicitly listed in the claims. Values and ranges of values are provided in the present description only as examples.

All features, elements, components, functions, and steps described in relation to any embodiment provided herein are intended to be freely combined and replaced with those of any other embodiment. If a particular feature, element, component, function, or step is described with respect to only one of the embodiments, then it should be understood that that feature, element, component, function, or step can be used with any other embodiment described herein, as long as expressly not otherwise specified. Therefore, this paragraph serves as the underlying background and written justification for the introduction of claims, at any time, that combine features, elements, components, functions, and steps from different embodiments or replace features, elements, components, functions, and steps from one from embodiments to those of others, even if the following description does not expressly indicate, in a particular case, that such combinations or substitutions are possible. It is expressly recognized that an explicit enumeration of every possible combination and substitution is too onerous, in particular, provided that the permissibility of each and every such combination and substitution is readily recognized by those of ordinary skill in the art.

As used herein and in the appended claims, singular forms include plural forms unless the context clearly dictates otherwise.

While the embodiments are susceptible to various modifications and alternative forms, specific examples thereof are shown in the drawings and are described in detail herein. However, it should be understood that these embodiments are not to be limited to the specific form disclosed,

-

Claims (36)

but, to the contrary, these embodiments are intended to cover all modifications, equivalents, and alternatives that fall within the spirit of the disclosure. In addition, any features, functions, steps, or elements of the embodiments may be listed or added in the claims, as well as negative limitations that define the patentable scope of the claims with features, functions, steps, or elements that are not included in this scope. . CLAIM 1. An artificial heart valve (100), which contains a plurality of leaflets (110), in which each leaflet (110) is synthetic; and a support structure (102) that contains a plurality of protrusions (106) coupled to a plurality of flaps (110); and a base (105) integral with a plurality of protrusions (106), where the plurality of protrusions (106) and the base (105) are elastic, where the artificial heart valve (100) has a closed position and an open position, and a plurality of leaflets (110) and the support structure (102) move between the closed position and the open position, and the base (105) is in the closed position, and the edge (120) has a sinusoidal surface in the closed position and in the open position, the edge (120) has a sinusoidal surface with a complementary or inverted profile. 2. The artificial heart valve of claim 1, wherein the support structure (102) has a periphery and the edge (120) extends around the periphery of the support structure (102). 3. The artificial heart valve of claim 1, wherein the first edge (120) location (501) is movable in the opposite direction from the second edge location as transvalvular fluid pressure changes from 75% of peak negative pressure to zero. 4. The artificial heart valve of claim 1, wherein the first location (501) of the edge (120) is movable in the opposite direction from the second edge location in immediate response to a transvalvular fluid pressure transition from a peak negative pressure to a less negative pressure. 5. The artificial heart valve of claim 1, wherein the plurality of leaflets (110) are configured to begin retracting as the fluid's transvalvular pressure transitions from a peak negative pressure to a lesser negative pressure. 6. The artificial heart valve of claim 1, wherein at the first time each end of the plurality of protrusions (107) is movable in a radially outward direction. 7. An artificial heart valve according to any one of claims 1 to 6, wherein the support structure (102) comprises a sutured cuff and no more than one sutured cuff flange. 8. The artificial heart valve according to any one of claims 1 to 7, wherein the heart valve is an aortic replacement valve or a mitral replacement valve, the heart valve comprises exactly three synthetic leaflets (110). 9. The artificial heart valve according to any one of claims 1 to 7, wherein the heart valve is a mitral replacement valve containing exactly two synthetic leaflets (110). 10. An artificial heart valve according to any one of claims 1 to 9, wherein the support structure (102) is not radially compressible for placement in an intravascular delivery device. 11. An artificial heart valve according to any one of claims 1-10, wherein the support structure (102) is not radially compressible for placement in the transapical delivery device. 12. An artificial heart valve according to any one of claims 1 to 11, wherein the support structure (102) and the plurality of leaflets (110) are formed from the same material. 13. An artificial heart valve according to any one of claims 1 to 12, wherein the support structure (102) comprises a cover, and wherein the plurality of leaflets (110) are an extension of the cover. 14. An artificial heart valve according to any one of claims 1 to 13, wherein the plurality of leaflets (110) are not stitched to the support structure. 15. An artificial heart valve according to any one of claims 1 to 14, wherein the plurality of leaflets (110) are seamlessly coupled to the support structure (102). 16. An artificial heart valve according to any one of claims 1 to 15, wherein the plurality of leaflets (110) and the support structure (102) are a monolithic body. 17. The artificial heart valve according to any one of claims 1 to 16, wherein the support structure (102) has an internal diameter selected from the group consisting of 17 mm, 19 mm, 21 mm, 23 mm, 25 mm, 27 mm, 29 mm and 31 mm. 18. An artificial heart valve according to any one of claims 1 to 17, wherein the plurality of leaflets (110) are polymeric. 19. An artificial heart valve according to any one of claims 1 to 18, wherein the plurality of leaflets (110) have a first elasticity in the range of 10-45 MPa and the support structure has a second elasticity in the range - 14 040848 3000-5000 MPa. 20. An artificial heart valve according to any one of claims 1 to 18, wherein the plurality of leaflets (110) have a first elasticity in the range of 20-35 MPa and the elasticity of the support structure (102) is in the range 3300-3500 MPa. 21. The artificial heart valve according to any one of claims 1 to 18, wherein the plurality of leaflets (110) have a first resilience and the support structure (102) has a second resiliency, the first resilience is in the range of 25-30 MPa and the second resiliency is in the range of 3300 -3500 MPa. 22. A method of using the artificial heart valve according to claims 1 to 21 inside a living subject, wherein the artificial heart valve comprises a plurality of synthetic leaflets and a support structure, the support structure comprising a plurality of protrusions associated with the plurality of leaflets; and a base integrally formed with a plurality of protrusions, where the plurality of protrusions and the base are elastic, where the artificial heart valve has a closed position and an open position, and a plurality of leaflets, and the support structure is moved between a closed position and an open position during use, where the artificial heart valve of the heart allows fluid flow when the transvalvular fluid pressure is positive and the plurality of leaflets are in contiguous state, when the transvalvular fluid pressure is peak negative pressure, and when the transvalvular fluid pressure is negative less than peak negative pressure, the plurality of protrusions automatically move from the closed position to the open position. 23. The method of claim 22, wherein the support structure has a periphery and the base comprises an edge that extends around the periphery of the support structure. 24. The method according to item 23, in which the edge contains the first location adjacent to the set of protrusions so that on the edge there are many first locations; and a second location adjacent to the plurality of flaps such that a plurality of second locations are present at the edge, where at a first time when the support structure moves from a closed position to an open position, each first location is movable in the opposite direction from each second location. 25. The method of claim 24, wherein the first time occurs when the transvalve pressure of the fluid is 90-99.9% of peak negative pressure. 26. The method of claim 24, wherein the first time occurs when the transvalve pressure of the fluid is 85-95% of peak negative pressure. 27. The method of claim 24, wherein the first time occurs when the transvalve pressure of the fluid is 25-75% of peak negative pressure. 28. The method of claim 24, wherein the first time occurs when the transvalve pressure of the fluid is negative. 29. The method of claim 24, wherein each first edge location is movable in the opposite direction from each second edge location as the transvalvular fluid pressure transitions from 75% of peak negative pressure to zero. 30. The method of claim 24, wherein each first edge location is operable to move away from each second edge location in immediate response to a transvalvular fluid pressure transition from a peak negative pressure to a less negative pressure. 31. The method of claim 24, wherein the plurality of flaps are configured to start exiting the proximity state at the first time. 32. The method of claim 24, wherein at the first time each end of the plurality of protrusions is movable in a radially outward direction. 33. A method according to any one of claims 22-32, wherein the support structure comprises a hem cuff and no more than one hem cuff flange. 34. The method of any one of claims 22-33, wherein the heart valve is an aortic replacement valve or a mitral replacement valve, the heart valve comprises exactly three synthetic leaflets. 35. The method of any one of claims 22-34, wherein the heart valve is a mitral replacement valve containing exactly two synthetic leaflets. 36. The method of any one of claims 22-35, wherein the support structure is not radially compressible for placement in an intravascular delivery device. -