Patent Application
20220233338
Stenosis is a narrowing or partial occlusion of a lumen, such us in the arterial or venous system. A local stenosis is characterized by a rapid change in lumen cross-sectional area that occurs over a very short segment length of the vessel, typically over a length of about 1 to 2 cm. Diffuse stenosis is stenosis that is not focal and is characterized by a narrowing of the lumen which occurs over greater vessel segment length, typically lengths greater than 2 cm. Stenosis is accompanied by changes in velocity of blood flow through the narrowed lumen.
A stenosis is often treated with a stent. Stents are generally cylindrically shaped devices which function to expand when deployed. Stents may be balloon expandable or self-expanding. The balloon expandable stent is a stent that is usually made of a coil, mesh or zigzag design. The stent is pro-mounted on a balloon and the inflation of the balloon plastically expands the stent with respect to the balloon diameter. Self-expanding stents are tubular devices stored in an elongated configuration in what is called a delivers system or applicator. The applicator is introduced percutaneously into the body into a vessel at a suitable location and guided through the vessel lumen to the location where the stent is to be released. The delivery system and the stent are often provided with radiological markers with which the positioning and the release of the stent can be monitored in situ under fluoroscopy. Upon release, the stent material auto expands to a predetermined size. Auto expansion is rather weak in many self-expanding stents. This may require pre-dilatation of the stenotic lesion with a balloon of appropriate size before the stent is deployed to enable it to expand to its intended size. In some stents, auto expansion must be assisted with ‘post—dilatation’ for full expansion of the stent to occur.
Commonly used self-expanding stents are braided stents, or laser cut stents. A braided stent is a metal stent that is produced by what is called a plain weaving technique. It is composed of a hollow body, which can stretch in the longitudinal direction and whose jacket is a braid made up of a multiplicity of filament-like elements which, in the expanded state of the braided stent intersects a plane, perpendicular to the longitudinal direction, at a braid angle. Laser cut stents are constructed from a tube of material (most frequently, nitinol, a nickel titanium alloy), and stainless steel, cobalt. etc. that is laser-cut during production to create a meshed device. The tube is comprised of sequential aligned annular rings that are interconnected in a helical fashion. The tube is compressed and loaded into the delivery device and expands to original size when released. Nitinol, which has thermal memory, may help stents made of this material expand into position when exposed to body temperature after delivery. Compared with self-expanding braided stents, laser cut stents provide more accurate stent deployment with less foreshortening. Laser cut stents are much less subject to foreshortening but are probably less rigid than braided stents. The stent, after expansion, is intended to restore the occluded vessel to normal or near normal flow conditions in the stented area. In the arterial and venous system, the stented area should have smooth laminar blood flow of uniform velocity. To help avoid restenosis, or the depositing of material in the stented vein, and the resultant re-occurrence of an occlusion, maintaining adequate flow through the stent is desirable. Unfortunately, existing stents do not provide such. A better stent product is needed.
A stent that contains a portion of the stent that has increased flow or “unitary,” or constant conductance flow, where the radius r of the portion expands with the length l so that so that r4/l remains constant in the portion. or near constant conductance flow. where the radius expands with the length of the portion of the stent so that rn/l, remains constant, where n>4. in the near constant conductance portion.
Venous system blood flow is normally modeled with Poiseuille law, and hydrodynamic relationships, including the expression between flow, pressure and resistance. The unitary conduit, or increased flow conduit, or constant conductance flow conduit concept described here and in
Poiseuille equation, Volumetric Fluid flow, Q=ΔP/R where I/R is known as the conductance
and where R=8 μL/πr4 and where μ is the fluid viscosity
Rearranging, and combining the two equations
Q=ΔP*(π/8)*(r4/L)*(1/μ).
where L represents the length of the cylinder (stent) (measured from the start of the stent), the last three terms represent the numeric, geometric or growth and viscosity factors respectively. Q, or volumetric fluid flow (m3/sec) or flow, in the venous system, is generally measured in ml/sec or liters/min. In low pressure areas of the arterial system, these relationships can also be used for modeling flow. For instance, we constructed a “unitary” conduit with an initial diameter of 11.2 mm with an initial section of 1 cm of constant radius and expanding to an end diameter of 17.7 mm at a length of 6 cm. The radius expanded with length l so that r4/l=(0.56)4. We compared fluid flow through the unitary conduit to a second uniform diameter or non-unitary conduit. A total of 4.5 liters was run through each conduit with a head pressure of 25 mm Hg. The time taken to empty the 4.5 l from the reservoir is shown in Table 1 below.
Thus, the flow rate for the increased flow or unitary conduit was 103 mL/sec and was 68 mL/sec (averaged) for the non-unitary or uniform conduit (constant diameter). As can be seen, errors in the stent radius can have significant consequences on blood flow.
The flow equations can be simplified further by inserting known values for π and μ (the viscosity of blood). As shown in
The preferred constant value will be ri4/(Leff) where ri is the starting radius of the unitary section near the beginning of the stent. Leff is described above., or as used herein, is set as 1 cm. If the expanding portion of the stent starts at length LSO, with radius ri at this length, the constant K will he ri4/(LSO). A conduit extending from the common femoral vein to the inferior vena cava was modeled in
When shorter length balloons and stents are used, there should be some provision for overlap if the segment to be treated is longer than the length of a chosen balloon or stent. For instance, a 2.0 cm length stent overlap is shown in the
The R4 geometric scaling factor can be illustrated in the following example: a parent vein receiving two tributaries, each 10 mm in diameter, will need to be only 12 mm in diameter (20% larger than each tributary) to maintain pressure unchanged even though the flow has doubled (
The unitary or constant conductance flow stent concept is applicable in the venous system, and in some circumstances, the arterial system. The concept is to keep the conductance or flow constant in the stent, or portions of the stent, which can be achieved by maintaining the geometric factor (r4/L) as a constant K in the growth portion of the stent. All examples used herein will have the stent grow after the first cm of length, with constant radius for that first cm, thus avoiding the ambiguity of examining r4/L as L→0.
As an example, consider a stent having a diameter of 18 mm (9 mm radius) (a common stent diameter used in the common iliac vein) at the end of a 1 cm length of constant radius, then r4/L=(1.8/2)4/l=0.6561, the constant K used for the remainder of this stent. Consequently, for a 2 cm long stent, the terminating radius would be (0.6561*2) 025=1.070 or a diameter of 2.14 mm. A 3 cm long stent would have a terminating radius of (0.6561*3)−025=1.18, or diameter of 2.36 mm; a 4 cm long stent would have radius of 12.7 mm, or a diameter of 25.4 mm; and for a stent length of 5 cm, the terminating radius would be 13.45 mm, or a diameter of 25.7 mm (an overall increase in cross-sectional area of about 123.3% (1.34/0.9)**2 (the iliac vein has been shown to tolerate as large as 24 mm diameter stent sizes).
As used, the “downstream” end of the constant conductance flow stent is larger. In the venous system, “downstream” is closer to the heart than the upstream end of the stent. This increase in diameter with length will assist to help offset flow reduction in the stent, to prevent stent malfunctions like in-stent restenosis caused by ingrowth of clot/tissue which accumulates and lines the wall of the stent. We have calculated the length necessary for various diameters in stents up to 5 cm length, in Table 2 for typical diameter stents used in the iliac system. The first cm in length is of constant diameter.
As described, for a lengthwise cross section though a stent, the outer envelope preferably creases as a 4the order polynomial, or r4 with length. Such an increase is not required but is preferred. Slower growth and slower flows, achieved with r5/l, r6/l or r7/l being constant with length can also provide benefits similar to constant conductance flow. Faster growth, and faster flow, such a linear growth, or growth by x2 or x3 or a combination such as a second order polynomial or a third order polynomial can also provide a benefit, as flow is further increased with R1, R2 or R3 growth, which can be useful in areas of the stent where restenosis or growth might accumulate from deposits with slower flow.
Stent Growth with Length
As long as the stent radius grows with length over portions of the stent (preferably consistent growth over each portion and preferably monotonic growth overall in the stent), such increased RN growth e.g., 1<n<4, or n>4, is considered “unitary like” growth or “near constant conductance flow herein, and within the scope of the invention. Flow as used herein is volumetric fluid velocity. Additionally, the stent's outer envelope may linearly increase between fixed stent radii at specific lengths, where those radii represent r4 or RN growth at those radii/length combinations. Connecting the RN radii with linear radius therebetween approximates RN growth in piecewise steps. Such a step wise construction is suitable for Z stents, such as the five Z stent 300, 3001, 3002, 3003, 3005 stacks shown in
Radius growth with length is so that rn/l remain a constant, in all or a portion of the stent, where n>1, is within the scope of the invention. All segmented stents with segments or portions that are unitary or unitary-like growth, are within the scope of the invention. However, it is preferred that the growth of the stent in each segment or portion increases uniformly up to the ending segment radius. Stent growth overall is preferred to be monotonic growth, but is not required.
An expanding or increasing dimeter stent is suitable for all stent types, braided, woven, laser cut mesh. and either self-expanding or balloon expandable for the venous system. While a 4th order polynomial increase is preferred for the outer envelope of all or portions of the stent (excluding for instance, constant diameter starting and possibly ending sections).
These growth factors, e.g., rn/L where n<4 will grow faster than a constant conductance flow stent, and hence provide increasing flow rates., which can be a benefit in areas where deposits may accumulate causing restenosis, Slower growth rates, e.g., where rn/L is constant, where n>4, such as n=5, 6, or 7 will be beneficial where long length stents or long stent stacks (e.g., multiple overlapping stents) are contemplated. While such growth is slower that R4 growth and hence the volumetric flows is less than R4 growth, the added benefit is that the ending radius size will be smaller than that in R4 growth, and hence is more likely to be acceptable in a biological conduit systems, such as a vein or artery. All such RN growth still provides increased flow over constant diameter stents.
For instance, fabrication of a stent with r4 growth will yield a gradually expanding tube that will double its radius at 16 cm length. In many applications, this growth is too quick, resulting in an ending radius that is too large for the application. A more practical formulation is to keep r5/l or even r6/l or r7/l or larger, constant over the length of the stent or portions thereof. This will yield longer tube lengths before the radius doubles (Table 3); the conductive performance (volumetric flow) will be less than the constant r4/l formulation but still better (greater than) than that of a uniform cylinder. The ending diameters for various lengths with initial diameters of, 6, 8, and 10 mm is shown in Table 4.
To demonstrate performance of slower growth stents, the following experiment was done.
To test less aggressive growth stent designs, rn growth conduits with n>4. were designed using engineering software (Autodesk, Inc.; San Rafael, Calif.) and fabricated in a commercial 3D printer (Stratasys; Eden Prairie, Minn.).
The basic flow model consisted is of a header tank 10 with outflow controlled by a calibrated ball valve 20 (
The flow rates of expanding caliber conduits (r4-6) compared to traditional constant radius cylindrical conduits are shown in Table 5 and
In closed flows where the fluid completely fills the conduit and the flow is driven by a pressure gradient, the incidence of transition to non-laminar flow should be reduced, in an expanding conduit, as in an expanding conduit, where rn/l is constant, the fluid velocity still declines with length.
aFlow separation did not occur in the constant radius conduits; Penrose air-traps did not affect these flows
Accretive manufacturing (3-D printing) makes it much easier to fabricate expanding caliber stents for biological use. 3D printing with Nitinol is possible for stents, but traditional stent manufacturing techniques could also be used for these expanding stents.
There is a practical limit to the length of the stent depending upon location and use. Examination of Table 3 (length of conduit when initial radius doubles) and Table 5 (measured flow rated for the conduits tested without an air trap) suggests that up to X16 cm is practical for stent designs keeping r4/L constant. As shown in table 7, for common iliac vein stents of 14 mm diameter, the ending radius is calculated for various length conduits for different rN N=4, 5, or 6. with all conduits having an initial starting length (1 cm) of constant radius. As shown, combinations up to 64 cm length appear practical for stents keeping r5/L constant. Longer lengths may be required for particular applications and are possible keeping r6/L or r7/L or higher r values constant. Fabrication techniques described above or known to those of ordinary skill in the art may be used to construct the rN expanding sent/conduit.
The expanding caliber stents may have an advantage over the traditional cylindrical prosthetics in the following areas of vascular surgery.
Venous caliber naturally scales up as tributaries coalesce. The iliac veins are the most common site for stent placement. Common femoral vein is 12 mm in diameter. The external iliac vein is ≈14 mm in diameter; the common iliac vein is slightly larger at ≈16 mm diameter. A gradual configuration as shown in Table 7 starting at 14 mm diameter may provide greater flow than current cylindrical designs. In-stent restenosis is a substantial problem in iliac vein stents and correlates with low inflow. It is believed that the expanding stent will ameliorate these problems of legacy design. The most frequent cause of stent thrombosis is poor inflow; outflow problems are less frequent causes. In either case, the pressure gradient (ΔP) is reduced causing flow decrease. A greater flow rate may be possible with the reduced gradient if the expanded configuration stent is used. Hence, a stent stack can be designed starting at 12 cm diameter in the common femoral, growing at RN until it reaches 14 mm diameter at the external iliac, then growing at RM until it reaches 16 mm diameter at the common iliac and then growing, for instance, at R4 to the end of the stack. Her N and M can be solved for given the respective lengths in each vein segment to be stented. Alternatively, a single RN growth can be chosen, to best fit the circumstances.
These composite stent/sleeved or grafts are used in specific anatomic locations where the prosthetic is subject to external compression/stress. Flow characteristics of the expanded configuration may function better where both the stent and graft (a non-elastic sleeve on the exterior of the sent) expands equally. Indeed, the stent expansion may be greater, but the sleeve will control/limit the expansion of the stent.
As will be understood by one of skill in the art, the length l used in (r=kn√l ), is measured from the start of the conduit, not the start of the expanding section) for standalone stents. Long “stents” can be constructed in steps or segments, by overlapping adjacent stents (such as 2 cm) to create longer stent stacks that emulates a single long stent. Overlapping stent diameters preferably match, by choosing the overlapped segment starting diameters to match, and selecting the geometric expansion of growth factor to match. However, as the stack of stents is used to emulate a single stent, the length used in RN growth is measured from the beginning of the first stent in the stack.
Stents (r=Kn√l where n≥4) can have endless applications where the flow rate through the application is an important factor to the functioning of the system, including the arterial system. Stents are also used to correct intimal hyperplasia at the venous end of dialysis grafts and fistulas. An expanding caliber stent may function better in these locations. In biological systems, use of expanding radii stents should greatly reduce restenosis in these stents.
In one embodiment, for a stent of selected length L1, the upstream and downstream terminating diameters are chosen (for instance, the upstream diameter can be selected as the standard or minimal diameter for the particular vein segment and choosing the downstream diameter to match the desired geometric factor constant, e.g., r4/l, or rn/l for n<4 for faster growth and flows, or rn/l for n.4 for slower growth and slower flow rates then a constant conductance flow design. Alternatively, the starting and ending diameters can be chosen and then solve for the best fitting value of n in rn/l. over the selected length L1. Note that n does not have to be an integer value. and n can represent at polynomial of the chosen degree e.g. 4th order, 5th order polynomial, etc.
The stents described are for a vein or artery segment that is substantially uniform in diameter absent a stenosis. If the vein or artery segment to be stented. normally has a natural increase in size, that natural increase may be accounted for in the designed “unitary” or increased flow stent, or near constant conductance flow stents, for instance, by increasing the selected stent terminating diameter by adding an additional amount equal to the natural increase in vein size, to get a “unitary plus” sized stent. by selecting the best RN growth to get the chosen diameter.
Stents up to 15 cm long are being produced using a constant diameter stents in standard dimensions. These current stents are usually of fixed unchanging diameter. However, there are stents manufactured as expanding tapered stents, See U.S. Pat. Nos. 9,655,710: 862,3070: 7,637,939, typically chosen to fit an expanding biological conduit. The unitary or constant conductance flow stent concept can be used even in long stents, such as 15 or even 20 cm in length, such as for use in the iliac vein. Such long stents may jail the hypogastric vein, which is well tolerated. However, for long stents, the elasticity of the vein wall can be a limiting factor, and a growth factor for slower growth than the 4th power for the radius per cm length may be more practical and desirable, such as 5th, 6th or 7th power in r.
Additionally, the invention includes stents that have a portion that is increased volumetric flow such as constant conductance or near constant conductance flow. Consider a stent that has an initial radius r1 of 15 mm or 1.5 cm) and remains constant for two cm. For the next 5 cm. the stent is unitary, with the starting radius of 1.5 cm. In other words, for the next 5 cm, r4/L remains constant, where L is the distance from the starting point of the stem to the expanding section start, and at the 7th cm of the stent, L=7 cm). at the end of the growth portion. the stent may continue with a fixed radius or alternatively, the radius in the final portion may further increase with a different RN factor or remain constant or even decrease (not preferred). For instance, at the end of the unitary portion described above, the stent may continue for another 2 cm but over that 2 cm, the radius may smoothly decline, such as linearly (e.g., a first order polynomial), to end at the normal radius of the resident vein, and thus allow for a smooth flow transition from the end of the unitary portion to the end of the stent back into the vein. One design factor is to have the end of the stent designed so that the flow at the end is at least as large as that in terminating vein location.
Slower growth rates than a constant conductance flow stent (e.g., rn/l is constant) but where n>4. can be used in long stents with lesser impact on vein walls but still providing the benefit of greater flows then provided by a constant diameter stem. Note the growth exponent n does not have to be an integer and can be a polynomial.
The stems and balloons described herein may include radio markers to allow the balloons or stents to be visualized during placement for proper positioning.
The invention includes unitary or constant conductance balloons or near constant conductance balloons, where the radius of the balloon expands with length to match the growth of the stent. For instance, by varying balloon materials or by use of a balloon sleeve that assumes the desired expanded shape.
If the stent is a piece-wise growth described above, the balloon should match the growth. The balloon can be constructed of differing materials to provide such varying expansion, or the balloon can also be sleeved to control its growth into the desired shape, by having the sleeve take on the desired expanded shape.
as described, the unitary or near unitary stent can be designed to fit the vein or arterial restrictions and provide increased flows. The stents are preferable monotonic growth, but there are instances where the growth can decrease. For instance, it stent bifurcates into tow. the tow stents will start are smaller diameter than the parent, and the bifurcated stents con grow with constant or near constant conductance flow, and in these instances, the length in the bifurcated stent can start at the bifurcation.
This application is a continuation in part of PCT/US20/16895 filed on May 2, 2020, which claimed the priority benefit of U.S. provisional patent 62/801,912 filed on Feb. 6, 2019, which is incorporated by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 62801912 | Feb 2019 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/US20/16895 | Feb 2020 | US |
| Child | 17444558 | US |
