CA2297777A1

CA2297777A1 - Intravascular dilatation implant with a deflector

Info

Publication number: CA2297777A1
Application number: CA002297777A
Authority: CA
Inventors: Nikolaos Stergiopulos
Original assignee: Individual
Current assignee: Ecole Polytechnique Federale de Lausanne EPFL
Priority date: 1997-06-20
Filing date: 1998-06-19
Publication date: 1998-12-30
Also published as: CN1261261A; EP0989830B1; DE69825162D1; JP2002506367A; RU2211006C2; AU730691B2; DE69825162T2; AU7669498A; CH691846A5; ID25838A; IL133463A0; US7094254B2; ES2222594T3; BR9810208A; US20020198591A1; WO1998058599A1; ATE271358T1; US6641605B1; EP0989830A1

Abstract

The invention concerns an intravascular dilator comprising a central body (3) acting as deflector of the blood flow and thereby increasing the value of shear stress to the artery wall. Flexible spires (4) soldered to the deflector (3) are radially extensible from a first diameter substantially equal to the deflector diameter (3) to a second diameter greater than the artery diameter. Said spires (4) rest against the artery internal wall (2) in operative position.

Description

Intravascular Dilatation Implant with a Deflector The present invention relates to an intravascular implant permitting radial dilatation of the arterial walls.
These implants or dilatators are known as "stems" in the field of transluminal angioplasty. Transluminal angioplasty consists in treating diseased regions of the arterial system by the introduction of apparatus, particularly catheters, along natural routes. This permits localized intervention without having to have recourse to conventional surgical interventions which have, because of their seriousness, numerous drawbacks for the patients. This technique is particularly used when a constric-tion or stenosis of the arteries is diagnosed. There is then introduced through the femoral artery a catheter provided at its distal end with an inflatable angioplasty balloon. This catheter is then pushed and guided, with radioscopic monitoring, through the arterial system to the diseased region of the artery. Once this region is reached, the balloon is inflated to dilate the constricted region of the artery. This operation is repeated until it is determined, with the help of the radioscopic monitoring means, that the artery again has a diameter sufficient to ensure an acceptable blood flow. These interventions however have certain drawbacks. Thus, clinical observations show that in about a third of the cases treated, the artery again retracts over a period of time comprised between several days and several months. This phenomenon, which is called "restenosis", requires S a new intervention in the diseased artery either by the same method, or by more serious surgical techniques.
In an effort to solve this problem, it has been proposed to implant permanently in the artery dilatators or "stems" to avoid repeated contraction. These implants usually have a tubular structure open at its ends so as not to disturb the blood flow. These devices, independently of their particular structures, generally have the following characteristics: they are radially extensible from a first diameter, permitting their introduction into the artery with the help of a catheter, to a second larger diameter corresponding substantially to the diameter of the artery. After dilatation of the artery, they are implanted in this latter and bear against the internal wall of the artery, thereby preventing, by a mechanical action, a new constriction of the artery. Once implanted, these stem s have a certain resistance to radial compression and thus maintain the artery open whilst permitting blood flow. In practice, stents of two different types are used at present. The first are deformed by inflation of a balloon during their emplacement; the second stems are so-called auto-extensible. The auto-extensible stems do not require external mechanical action to pass from a first diameter during introduction, to a second larger diameter in the service position. This effect is obtained either by the use of material having a shape memory, such as Nitinol (trade-mark), or by a spring effect. There has also been proposed, for example by European patent EP-433 011 B1, a stmt which comprises a radioactive isotope which tends to decrease the phenomenon of restenosis by radiotherapy. In other embodiments, the surface of the stmt, in contact with the internal wall of the artery or the vessel, has a suitable surface treatment permitting the local distribution of antithrombogenetic chemical substances.
These devices, although having contributed to the decrease in the rate of restenosis, have nevertheless not totally solved the problem. Thus there is seen, in about 22% of the cases treated by angioplasty and the implantation of a stmt, a tissue reaction which leads to increase the thickness of the internal layer of the artery. If this phenomenon is not stabilized and continues to increase, the artery becomes plugged again.
The present invention has for its object to overcome the drawbacks mentioned above, by providing a dilatation implant promoting the decrease in the rate of restenosis, in particular by its action on the internal wall of artery. Another object of the invention consists in the use of such a device to increase the shear stress at the blood/wall interface in an artery or a blood vessel. Finally, the invention also has for its object a process permitting the increase of shear stress at the level of the arterial wall. The stmt according to the present invention is distinguished for this purpose by the characteristics defined in claim 1. Other advantages will appear from the description which follows and from the dependent claims.
The invention will now be described with reference to the accompanying drawings, which show schematically and by way of non-limiting example, one embodiment of an intravascular stmt according to the invention.
Figure 1 is a schematic view showing the profile of the speeds in an artery without an implant.
Figure 2 is a schematic view showing the profile of speeds in an artery having at its center a flow deflector.
Figure 3 is a graph illustrating the relative intimal shear as a function of the dimensions of the deflector relative to the dimensions of the artery.
Figure 4 is a side view of a stmt according to the present invention.
Figure 5 is an end view of the stmt shown -in Figure 4.
Scientific studies, confirmed by critical observations, have shown that restenosis is attributed to a cellular proliferation of the intimal tissue, called -ntimal hyperplasia. The mechanisms of this reaction are not e-!tirely understood at present. However, it is certain that the ~reven-tion or reduction of intimal hyperplasia constitutes a key element in the success of the treatment of stenosis or arterial occlusions. It has been determined in animals that intimal hyperplasia is reduced when the blood flow is high in the vessel in question. On the other hand, when this flow rate is low, the intimal layer increases. The same determination has been made by cardiologists and radiologists, who have observed that following an angioplasty, the stems remain open if the flow rate is high and that they have the tendency to plug in the presence of a low blood flow rate. There exists as a result a certain relationship between the blood flow rate and intimal hyperplasia.
This fact is confirmed by several medical studies which tend to show that intimal hyperplasia is not a pathological process, but rather an adaptive response of the artery or the vessel which remodels itself so as to maintain or to restore the optimum level of shear stress at the wall.
The passage of blood in an artery creates by friction forces on the internal wall of the artery. When the flow rate is high, the shear stresses are high on the endothelial cells of the artery wall. These forces are on the contrary low in the presence of an insufficient flow. It is moreover known that the shear stress at the internal wall is directly propor-tional ~o the flow (Q) and inversely proportional to the cube of the arterial diameter. It results from this that when the perfusion flow rate is low, intimal hyperplasia reduces the diameter of the artery so as to restore the normal value of the stress. If a low flow rate persists, or if progressively diminishes, the normal shear stress cannot be reestablished and intimal hyperplasia continues, leading finally to restenosis.

On the contrary, if the flow is sufficient to reestablish a stress level equal or even superior to the normal stress, intimal hyperplasia stops and the artery remains permanently open.
It results from the above determinations that to stop and block intimal hyperplasia, it is necessary to increase locally the shear stress at the wall, particularly when the flow rate is low. The object of the invention is particularly to permit a substantial local increase of the shear stress at the wall.
lb Given that the blood flow rate cannot be ir_creased locally, because it is automatically controlled by the organism through resistances which constitute the peripheral vessels, it is necessary as a result to decrease locally the open cross-section of the artery such that the value of the shear stress on the arterial wall increases. To this end, it is proposed to position and to maintain in position, preferably at the center of the artery, at least one body which will act as a deflector of the blood flow on the arterial wall. This flow deflector will thus permit substantially increasing locally the shear stresses on the endophilial cells. Figure 1 shows schematically the profile of speeds in an artery of radius ro. Figure 2 shows the same profile of speeds when a flow detector 1 of cylindrical shape is disposed at the center of the artery. The deflector 1 deflects the lines of flow in the radial direction in the direction of the arterial walls 2 and leads to a greater radial gradient of speed adjacent the walls 2 of the artery. Because of this, the shear stress at the blood/wall interface is increased. With reference to Figure 2, and given the hypothesis that the flow is evolute, the Navier-Stokes equation along the longitudinal axis of symmetry is:
1 a au x aP (~~
-.(r-) = .r where r'a~- a~- '~. aX
S a is the axial speed, P the pressure and ~C the blood viscosity.
By double integration, there is obtained u(r) - 4 aPr~ -ct ln(r) +cz _ (2) a By applying the limit conditions a (r=r~) - a (r=ro) - 0, then by deriving, there is obtained the final expression for the speed distribution i z a (r) - x aP ~_Z _ oz y; - ro ln~ r (3) 4 a ax In ro r,.
rr The flow rate Q can then be calculated by simple integration z ~c aP , -r ,J = a (r) (2nr)dr = _.~- rQ _ t~4 -. ~ °
8u ax r°
in --rr The shear stresses acting on the arterial wall z are given by _ _~u "E-lar which by using equation 3 for a (r) becomes (5) r=r, IaP 1rz-oz .r..._. Zro ; ~ (6) y4 ax ~~ In ~i Equation 6 can also be expressed as a function of the flow rate Q by using equation 4 for the pressure gradient Q 2r-rrr2--oz lz z~
lrQ - rr ~ r° In r-o~ ~7t< - T
In r°
r, S So as better to appreciate the effect of the deflector 1 on the magnitude of shear, this latter is normalized by shear stresses under laminal flow of the Poiseuille type for the same flow as in an open artery. For a flow of the Poiseuille type, it is known that:
'~ rov - °rr' ~ . ~8) .. a There is also obtained the following expression:
3 2 _ 2 T' 2ro + ~~ rr T° (9) Z 2 )' 'C 2 A 4 ~, o " r r ~ In r.~.
Polt o To ... Tf ~ r r In -°
Tj 9 ' PCT/IB98/00948 It is thus possible to define the ratio of the deflector/artery radii as a parameter ~ - r , to reformulate equation 9 in a non-ro dimensional form:

z _ I ~ 21n(y ) (I O) Zao;s ~1-yx~x 1~ 1 Y
The dependence of shear relative to the parameter D is shoran in Figure 3, in which there is shown on the ordinate the relative intimal shear and on the abscissa the ratio between the radius of the deflector and the radius of the artery. Taking for example a cylindrical deflector whose radius corresponds to about one-third the radius of the artery, the intimal shear is increased at the wall by a factor of 2. If as in the example mentioned above, the ratio between the radius of the deflector and that of the artery is one-third, the surface occupied by the deflector represents only about 11% of the cross-section of the artery and hence constitutes only a negligible resistance to blood flow, according to fluid mechanics.
Thanks to the presence of a cylindrical body at the center of the artery, giving rise to a deflection of the blood flow, the shear stress at the wall is significantly 1 orally increased. This body, by reason of its dimensions, does not greatly decrease the blood flow.
Figure 4 shows a possible embodiment from among numerous variants, of a stmt according to the present invention.

This stmt is in place in an artery or a vessel whose wall 2 has been schematically shown. It comprises a central portion 3 which fulfills the function of a flow deflector. This deflector 3 is made of a coil spring whose turns touch, in which each turn is connected to the adjacent turn for example by laser soldering.
The solder points 6 are distributed along a spiral extending over all the length of the spring. Because of this, the deflector cannot deform along the longitudinal axis but nevertheless retains a certain flexibility, which facilitates its travel toward the region to be treated. At the two ends of the deflector 3, as well as at one or several points di stributed over its length, small spirals 4 are soldered to the central deflector 3. These spirals 4 are radially expansible from a first diameter corresponding approximately to the diameter of the deflector 3, to a second larger diameter corresponding to the diameter of the artery. The spirals 4 bear, in the service position, on the internal walls 2 of the artery and have the same mechanical action on the wall as conventional auto-extensible stems . These spirals 4, once in contact with the arterial wall, maintain the deflector 3 in a centered position in the artery and avoid the latter from coming into contact with the annular wall of the artery. With reference to Figure 5, there will be seen a passage 5 at the center of the deflector 3. This longitudinal passage 5, which extends over all the length of the deflector 3, permits mounting the stmt at the end of an angioplasty catheter on a wire guide to facilitate its emplacement in the treated vessel.

For the production of the spirals 4, there is preferably used a material which can be pre-stressed at a certain temperature and which resumes its original shape at a higher temperature . Nickel and titanium base alloys such as Nitinol (trademark) are perfectly adapted for the production of the spirals 4. Thus, during fabrication of the stmt, the spirals 4 are cooled and hence become very malleable. They are then wound about the deflector 3. The stmt is then emplaced in a catheter. During the emplacement of the stmt, after separating the catheter from the stmt, the spirals 4 reheat in contact with the blood and deploy radially to come into contact with the blood vessel wall.
It follows that other known techniques in the field of auto-extensible stems can be used. The central deflector 3 can also be present in the form of solid cylindrical body provided with a central longitudinal bore, or be constituted by a hollow cylindrical body which can as the case may be serve as a reservoir for a substance to be administered in situ. Other modified embodiments of the deflector 3 are possible, in particular the use of several assembled elements such as a double spring for example. It is also possible to provide several flow deflectors 3 of smaller diameter and interconnected, for example three deflectors arranged at the summits of an isosceles triangle. So as not to disturb the blood flow in the vessel or the artery, there will be selected a ratio between the radius of the deflector 3 and that of the artery, lying between 0.1 and 0.8, preferably 0.3. To produce a stmt according to the present invention, there will preferably be used biologically compatible material such as Nitinol (trademark) or stainless steel. It will be noted that certain copper alloys can also be envisaged using a suitable surface treatment, for example a polyester or TEFLON
(trademark) coating.
To minimize the phenomenon of intimal hyperplasia, as has been mentioned in the introductory portion of the description, there is envisaged a local therapeutic action either by surface treatment permitting local distribution of an anti-restenosis substance, or by radiotherapy. These techniques can easily be applied to the stent according to the present inven-tion. It thus suffices to provide a suitable surface treatment of the spirals 4 in contact with the arterial wall. The cumulative effect of an increase in shear stresses at the wall is thus combined with a radiotherapeutic or chemically therapeu-tic action. It will be noted that not only the portions directly in contact with the arterial wall can have suitable surface treatment, but also the deflector 3.
It is evident that the stmt according to the present invention can have other shapes, the essential character-istic remaining in the presence of a flow deflector increasing the shear stress at the internal wall of the artery and main-tamed in position in the artery, preferably centered in this latter. In particular, the stmt could have the form of a tubular body open at its two ends and comprising at its center a cylindrical body connected in a flexible manner to the external tubular body.
In certain cases, it is not desired to leave the stmt permanently in the artery. To this end, certain stems are made of biodegradable materials. These materials can of course be used to make a stmt according to the present invention.
The process which permits locally increasing the shear stress at the wall of a vessel or an artery comprises the following steps. There is introduced with a catheter and a wire guide an intravascular stent of the type described above to the diseased region of the artery to be treated. During the passage of the stmt through the arterial system, this latter has a diameter approximately identical to that of the catheter. The stmt is then emplaced by separating this latter from the catheter; during this operation, the spirals S of the stmt extend radially and bear against the internal wall of the artery.
Finally the catheter is withdrawn, then the wire guide.
It will further be noted that the stent which is the object of the present invention is easy to produce and can be packaged with a catheter, such that it is directly usable by the practitioner.

Claims

1. Stent adapted to be introduced into an artery or a blood vessel, characterized in that it comprises at least one flow deflector (3) permitting deflecting the lines of current radially in the direction of the arterial walls, thereby giving rise to a greater radial speed gradient adjacent the arterial walls (2) which locally increases the shear stress on the internal wall of the artery (2); and in that the flow deflector (3) is provided with holding means (4) bearing in the service position against the internal wall of the vessel (2), said means (4) preventing the deflector (3) from coming into contact with the internal wall of the vessel (2) and having a mechanical action to support the arterial wall.

2. Stent according to claim 1, characterized in that the ratio between the radius of the deflector and the radius of the artery is comprised between 0.1 and 0.8, preferably 0.3.

3. Stent according to one of the preceding claims, characterized in that the flow deflector (3) or deflectors have a generally cylindrical shape.

4. Stent according to one of the preceding claims, characterized in that the deflector (3) is constituted by a spring rolled turn by turn in which each turn is connected to the following by a solder point (6) and in that the holding means are constituted by at least two flexible radially extensible spirals (4) connected to the deflector (3) at one of their ends.

5. Stent according to claim 4, characterized in that the solder points (6) are arranged in a spiral extending over all the length of the deflector (3).

6. Stent according to one of the preceding claims, characterized in that it comprises a plurality of radially extensible spirals (4) connected to the deflector (3) and distributed at regular intervals along the longitudinal axis of the deflector (3).

7. Stent according to one of the preceding claims, characterized in that it is made of a material having shape memory.

8. Stent according to one of the preceding claims, characterized in that it comprises a radioactive isotope effective to reduce intimal hyperplasia of the arterial wall.

9. Stent according to one of claims 1 to 6, characterized by the fact that the radially extensible holding means (4) and/or the deflector 3 have a specific surface treatment or are constituted of a biologically active material permitting the diffusion of a substance having an action on the arterial wall.

10. Stent according to one of the preceding claims, characterized in that the deflector (3) has a central passage (5) extending over all its length.

11. Stent according to one of the preceding claims, characterized in that it is made of a biodegradable material.

12. Process permitting increasing locally the shear stress at the blood/wall interface in an artery or a blood vessel, characterized in that it comprises bringing by a natural route a stent according to one of claims 1 to 10 to the region to be treated, with a catheter; emplacing the stent and disconnecting the catheter, thereby giving rise to the radial extension of the holding means (4) of the deflector (3) which bear against the internal wall of the artery or the vessel, and withdrawing the catheter.

13. The use of a stent according to one of claims 1 to 10 to increase the shear stress at the blood/wall interface in an artery or a blood vessel.