WO2025194251A1

WO2025194251A1 - Systems and methods for treating stenotic and non-stenotic vascular disease

Info

Publication number: WO2025194251A1
Application number: PCT/CA2025/050362
Authority: WO
Inventors: Mayank GOYAL; Johanna Ospel
Original assignee: Mg Mma Inc
Current assignee: Mg Mma Inc
Priority date: 2024-03-18
Filing date: 2025-03-17
Publication date: 2025-09-25
Anticipated expiration: 2026-09-18

Abstract

Plaque covering stents configured for placement within a primary vessel over a plaque adjacent a vessel bifurcation having a branch vessel are described. The plaque covering devices are configured for placement within the primary vessel over the plaque without covering the branch vessel opening while extending proximally and distally within the primary vessel, the plaque covering device configured for deployment from a stent delivery system via a stent delivery catheter and retraction into the stent delivery system wherein the plaque covering stent is detachable from the stent delivery catheter.

Description

SYSTEMS AND METHODS FOR TREATING STENOTIC AND NON-STENOTIC

VASCULAR DISEASE

FIELD

[0001] Systems and methods for targeted endovascular treatment of stenotic and symptomatic non-stenotic vascular disease (SyNC) are described.

BACKGROUND

[0002] The formation of plaques in blood vessels can lead to a range of conditions.

[0003] For example, acute ischemic stroke, that is, blockage of an arterial blood vessel in the brain, is one of the most common causes of disability and mortality worldwide. Many of the blood clots that block arteries come from the heart or plaque in arteries close to the heart, such as the carotid arteries that supply the brain. Plaques are wall-adherent accumulations of lipids and calcium that can get carried forth with the blood stream. If such plaques occur in the carotid arteries and get carried in the brain with the blood stream, ischemic strokes can result.

[0004] Plaque formations in other vessels, for example in the common femoral artery can lead to limb ischemia leading to claudication. Plaque formation in vessels of the heart can lead to myocardial infarction

[0005] As is known, stenting is a medical procedure used to open narrowed or blocked blood vessels, ducts, or other tubular structures in the body, typically to restore normal flow. Stenting involves placing a stent (a small, mesh-like tube) into the affected area, which helps keep the vessel open. Stents are most commonly used in cardiovascular medicine, particularly for coronary artery disease (CAD), where they help prevent heart attacks by maintaining blood flow to the heart. They are also used in peripheral artery disease (PAD), carotid artery disease, and even in non-vascular applications such as bile duct obstructions or esophageal strictures. However, stenting has limitations as discussed below.

[0006] For example, in-stent restenosis (ISR) can occur, where scar tissue or re-narrowing of the vessel compromises blood flow again.

[0007] Stents carry risks such as thrombosis (blood clot formation), which requires patients to take long-term antiplatelet therapy.

[0008] Some complex lesions, such as heavily calcified arteries or very small vessels, may not be ideal for stenting and may require alternative treatments like bypass surgery or newer interventional techniques.

[0009] Further, during and post-procedures, there is a risk of distal embolization, where fragments of plaque or thrombus dislodge and travel downstream. This can occur due to plaque extrusion through the stent struts, particularly in soft, lipid-rich plaques. In the case of carotid artery stenting (CAS), such embolization can lead to stroke if debris enters the cerebral circulation. To mitigate this risk, distal embolic protection devices (EPDs) such as filters or balloon occlusion systems are often used during carotid stenting.

[00010] Another risk is side branch occlusion or injury to vessels originating from the stented segment. Stents, particularly those with rigid structures, can jail side branches, restricting blood flow or even completely occluding smaller arteries that arise from the stented region. This is a major concern in bifurcation lesions, such as when treating blockages at branch points in the coronary arteries (e.g., the left main coronary artery bifurcation) or in peripheral vascular beds. In these cases, specialized techniques such as provisional side branch stenting, double stent strategies (e.g., culotte or T-stenting), or the use of drug-eluting balloons for side branches may be required. Additionally, iatrogenic vessel injury, including dissection, perforation, or thrombosis at the edges of the stent, can also compromise outcomes, requiring further intervention.

[00011] Generally, in addition to the continued development of new techniques and devices, risks are addressed and managed by careful patient selection, optimal stent placement techniques, and post-procedural monitoring to minimize complications and improve long-term vessel patency.

[00012] In the particular case of preventing restenosis, drug eluting balloons and drug eluting stents have been used. Both have advantages and disadvantages

[00013] Drug-eluting balloons (DEBs) deliver an antiproliferative drug (often paclitaxel) across the entire surface of the inflated balloon, coating the treated vessel segment uniformly. This yields a homogenous circumferential drug distribution along the lesion during the 30-60 second inflation

[00014] In contrast, drug-eluting stents (DES) release drug from polymer coatings on spaced strut surfaces. Drug diffuses outward from these discrete struts, leading to non-uniform, focal drug delivery where areas near stent struts get high drug concentration, while gaps between struts receive less [00015] In short, DEBs bathe the vessel wall evenly in drug, whereas DES create a patchier distribution corresponding to strut placement.

[00016] The collective evidence suggests that the more even drug distribution of DEBs can translate into clinical results on par with DES in many scenarios, without the downsides of a permanent implant. The homogeneous drug delivery ensures no segment of the treated artery is under-dosed, which is especially advantageous in long or diffuse lesions. Clinically, this manifests as equivalent restenosis prevention in small vessels and ISR, and it may offer advantages like quicker healing and less need for prolonged DAPT.

[00017] On the other hand, DES with their focal drug release remain extremely effective, particularly in very high-risk lesions or when mechanical scaffolding is needed to prevent recoil or dissection. In those cases, the concentrated and prolonged drug release from DES can slightly outperform a balloon if uniform drug application alone cannot overcome aggressive biology. Overall, uniform drug distribution is a key strength of DEBs, contributing to their success in many applications

[00018] Overall, DEB with antiproliferative therapy that, when combined with proper lesion preparation and patient selection, achieves outcomes comparable to the gold-standard DES while also offering benefits in vessel healing and flexibility for future interventions. The choice between DEB and DES thus comes down to clinical context - balancing the value of even drug coverage and no implant (DEB) versus the need for sustained drug release and scaffolding (DES) for optimal patient outcomes.

[00019] Thus, there is a need for drug eluting covered stents that takes into account advantages of both techniques.

[00020] Further, covered stents, namely those that have a polymeric mesh over an expandable metal frame are generally disadvantaged as being more thrombogenic.

SUMMARY

[00021] In accordance with the disclosure, a plaque covering stent configured for placement within a primary vessel over a plaque adjacent a bifurcation is described, the bifurcation defining a branch vessel off the primary vessel and a branch vessel opening, the plaque covering device configured for placement within the primary vessel over the plaque without covering the branch vessel opening while extending proximally and distally within the primary vessel, the plaque covering device configured for deployment from a stent delivery system via a stent delivery catheter and retraction into the stent delivery system and wherein the plaque covering stent is detachable from the stent delivery catheter.

[00022] In various embodiments:

• the plaque covering stent is a truncated tube.

• the truncated tube is bioabsorbable.

• the truncated tube is configured with a minimal metal wire frame to expand the plaque covering surface.

• the plaque covering surface is a tensionable partial tube surface configured to an expandable metal frame, the expandable metal frame configured to the expand the partial tube surface into a partial tube.

• the expandable metal frame includes a first elliptical metal hoop having first and second apexes and a second elliptical metal hoop having third and fourth apexes and where the first and second elliptical metal hoops are configured to expand and bias each of the first, second, third and fourth apexes away from each other.

• a delivery catheter is configured with T and L radio markers for alignment of the plaque covering surface over the plaque.

• the plaque covering surface is a half-tube configured with a minimal wire stent to provide an outward radial force to the plaque covering surface.

• the plaque covering stent is a tube having an elliptical tube opening.

• the tube has a tube longitudinal axis and the elliptical opening has a major axis aligned with the tube longitudinal axis.

• the tube includes first and second radio markers adjacent the elliptical tube opening and aligned with the major axis. the first and second radio markers include at least one lateral band extending a partial circumferential distance around the tube for determining rotational alignment of the tube within a vessel. • the tube includes a distal and a proximal edge each having at least one radio marker adjacent the proximal and distal edge.

• the tube is configured with a minimal metal wire frame having a polymer stent covering.

• the minimal metal frame is a woven mesh.

• the woven mesh is 1-5% of the surface area of the stent.

• the polymer stent covering is configured with 30-100 micron endothelization pores.

• the minimal metal frame is a laser cut tube having a plurality of openings.

• the system includes a stent delivery device and wherein the tube is compressed within the stent delivery device as a compressed stent and the stent is configured to a stent delivery catheter.

• the first and second radio markers are configured to the stent delivery device at positions that overlay proximal and distal edges of the elliptical tube opening of the compressed stent.

• the system includes an inflatable balloon configured to the stent delivery catheter.

• the inflatable balloon is configured over the compressed stent and within the stent delivery device.

• the inflatable balloon is configured to the stent delivery catheter distal to the compressed stent.

• the tube includes a plaque burden zone and a non-plaque burden zone and the endothelization pores are formed in the covering in the non-plaque burden zone.

• the covering is configured to the tube via electro-spinning.

• the covering is configured with a drug eluting coating selected from any one or a combination of Sirolimus, Everolimus, Zotarolimus, Biolimus or Paclitaxel.

• the covering is configured with a Heparin coating.

• the covering is configured with a Nitric Oxide (NO)-Releasing coating. the covering is configured with a Polymer-Free Drug coating. • the covering is configured with a Platelet-Inhibiting coating.

• the covering is configured with a Endothelial Cell-Promoting coating.

• the covering is configured with a Passive Surface coating.

• the covering has inner and outer surfaces and different drugs are configured to the inner and outer surfaces.

• the system includes a proximal torquing arm configured to the stent delivery catheter.

In another aspect a method of configuring a stent for a specific patient is described comprising the steps of:

• Conduct diagnostic imaging of affected vessel(s) in patient including a primary vessel and at least one secondary vessel branching off the primary vessel;

• Forward imaging data to a processing computer;

• Analyze imaging data to determine 3D dimensions and configuration of affected vessel(s);

• Using dimensions and configuration data from c., forward dimensions and configuration data to stent construction device to configure stent having minimal metal tube and tube openings and adapted for placement within the primary vessel and over the at least one secondary vessel;

• Construct a stent using the stent construction device, the stent having a polymer covering;

• Apply radio markers to the stent and/or on a stent delivery device;

• Install stent delivery catheter on stent and install stent delivery catheter and stent within a stent delivery device;

• Forward stent assembly to a treating medical team.

[00023] In one embodiment, the stent includes a plaque burden zone and a non-plaque burden zone and the method further comprises the step of configuring endothelization pores to the non-plaque burden zone. DESCRIPTION OF THE DRAWINGS

[00024] Devices for treatment of non-stenotic artery disease in accordance with the disclosure are described with reference to the drawings in which:

Figures 1A-1 D are images showing representative high-risk features of SyNC lesionsthat often cause strokes. (A) and (B) show exclusively non-calcified, irregular plaques on CTA. Both features are associated with high risk of future stroke due to plaque embolization. (C) shows an ulcerated plaque on CT angiography, indicative of a very high future stroke risk. (D) shows intraplaque hemorrhage (seen as a bright component in the vessel wall) on non-contrast fat saturated T1 MRI, indicating a very high future stroke risk. Note that the plaque shown in C is an ulcerated plaque and extends relatively far inferiorly, far below the level of the external carotid artery origin. Therefore, this plaque will be challenging to treat with an asymmetric SyNC plaque stabilizer device. However, most plaques, eg, those shown in A, B and D, extend only minimally or not at all below the level of the external carotid artery origin and therefore would be well suited for treatment with the proposed SyNC plaque stabilizer device.

Figures 2A-2C are images showing a typical SyNC patient. This 65-year old patient presented to the emergency department because of left-sided hemiplegia and aphasia with onset 2 days before. She had suffered similar episodes in the past. The noncontrast CT scan (A) showed numerous subacute and old infarcts in the right-sided internal carotid artery territory. CT angiography revealed a long-segment non-stenotic, irregular-appearing plaque of the proximal right internal carotid artery (B), magnification of the plaque shown on the right. The left-sided internal carotid artery was unremarkable (C).

Figure 3 are images of current commercially available stents. All available stents are characterized by a 360° wire mesh to generate the high radial force that is necessary when stenting stenotic carotid lesions. As can be seen in the figure, except for the CASPER stent, the pores are relatively large, allowing small plaque fragments to migrate through the stent struts into the vessel lumen.

Figure 4 is a sketch of SyNC plaques and representative locations and morphologies at different locations at an ICA/ECA bifurcation in the CCA.

Figures 5A-5D are sketches of how a completely (fig 5B) or partially (fig 5C) bioabsorbable stent can lead to stent fragmentation.

Figures 6A-6C are sketches showing how a potential completely or partially bioabsorbable stent would be placed in the carotid covering the origin of the ECA.

Figures 7A-7D are sketches of SyNC plaque stabilizer devices (SSDs) as truncated tubes configured to cover a plaque at a bifurcation without covering the branch vessel opening and placement of markers that allows proper alignment prior to deployment (fig 7D).

Figures 8A and 8B are sketches showing different degree of difference of length from one side to the other of a truncated tube SSD. This difference in length would allow for treatment of different SyNC lesions depending on degree of extension into the CCA.

Figures 9A and 9B are sketches of a partial tube SSD having expandable hoops that may be positioned at a branch vessel opening without occlusion of the branch vessel opening.

Figure 10 are sketches of a main vessel and branch vessel from a direct front view A and side view B with a deployed stent having an elliptical opening showing the appearance of markers based on view in accordance with one embodiment.

Figures 11A and 11B are sketches of covered stents. Figure 11A illustrates a laser-cut metal stent and Figure 11 B illustrates a a woven stent.

Figures 12A and 12B are sketches of a process of deploying a stent in accordance with one embodiment.

Figure 13 is sketches of a proximal end of a stent delivery system with a torque handle.

DESCRIPTION

[00025] Plaque stabilizer devices (PSDs) are described that may be configured within vessels over a plaque at a vessel bifurcation. The PSDs are described for general application in vessels where a plaque may have formed adjacent a vessel bifurcation as well as PSDs optimized for SyNC treatment. [00026] The inventors, who are experienced in the treatment of vascular disorders recognized the need for procedures for treatment of vascular plaque as an embolic source while minimizing the undesirable side-effects of currently available stents such as carotid stents. In particular, PSDs for endovascular use are described with reduced metal coverage.

[00027] By way of background, until recently, it was thought that only carotid plaques that cause a “stenosis”, that is, a significant narrowing of the vessel diameter, are responsible for strokes. However, there is increasing evidence for non-stenosing carotid plaques, that is plaques that cause only minimal vessel diameter narrowing, as underlying cause of stroke. Recent studies show that such non-stenotic carotid plaques may constitute sources of stroke in up to 20% of patients with undetermined stroke of source. Annual stroke recurrence rates in these so-called symptomatic non-stenotic carotid plaque (SyNC) patients are high. Those SyNC patients in whom carotid plaques with so-called “high-risk features” are present, have high recurrence rates between 25% and 44%.

[00028] The two procedures used to treat stenotic carotid plaques are 1) endovascular carotid artery stenting (CAS), that is, insertion of a laser-cut or woven metal tube into the artery, and 2) surgical carotid endarterectomy (CEA), that is open surgical removal of the plaque. Early randomized controlled trials in the 1990’s and 2000’s investigating the benefit of CEA and CAS only included patients with carotid plaques >50% stenosis. Thus, treatment guidelines adopted CEA and CAS as standard of care only for patients with >50% stenosis and devices were optimized to treat these patients with severe stenosis.

[00029] In the last several years, both CT and MRI imaging have shown routine ability to identify numerous potentially “high risk” features within the carotid artery wall itself that identify non-stenotic plaques at high risk of causing strokes. Specifically, intraplaque hemorrhage within lipid-rich and necrotic plaques, has correlated strongly with stroke risk (Figure 1).

[00030] The combination of clinical and imaging findings of stroke in the territory of a carotid artery without stenosis but with complex, “high risk” plaques, led to the syndrome now widely accepted as Symptomatic Non-Stenotic Carotid Artery Disease (SyNC) (Figure 2).

[00031] Currently, the biggest problem in interventional/surgical SyNC treatment is the lack of appropriate treatment tools and techniques: CEA and CAS have been optimized to treat patients with carotid stenosis but not SyNC.

[00032] CEA is an invasive surgical procedure which requires general anesthesia and temporary ligation of the carotid artery, and as such, carries substantial peri-operative risks. CAS seems therefore the preferred treatment option for many patients.

[00033] Generally, there are two types of stents: self-expanding and balloon-mounted stents. Balloon mounted stents are packaged with a balloon inside the stent and once the collapsed stent with the deflated balloon inside the stent have been navigated to the targeted vessel segment, the balloon is inflated and thereby expands the stent and models the stent to fit the vessel wall. The advantage of this technique is that it allows for very precise and controlled deployment and expansion of the stent. The disadvantages are that a) the combination of the collapsed stent and balloon is very stiff, and thus, it is hard to navigate the devices to the target occlusion site, particularly when the vessels are tortuous, and b) balloon mounted stents do not have “shape memory”, i.e., when they are expanded, they stay in the same shape, but theoretically, if they get compressed again, they will not “re-expand”. Therefore, balloon mounted stents are generally not used for superficial locations close to the skin (e.g., the carotid artery, where compression could easily occur e.g., by a seatbelt or during sports or even accidentally by manual pressure) or in locations with high mobility (e.g. neck motion may damage the stent).

[00034] The second type of stents are self-expanding stents. These are typically made out of Nitinol, and do not need to be delivered with a balloon. They self-expand once the catheter is pulled back, and even when compressed from the outside, regain their expanded shape (“shape memory”).

[00035] The disadvantages of these stents is that they cannot be deployed as precisely as balloon mounted stents. Generally, self-expanding stents are overall better suited to treat carotid stenosis because of the superficial location of the carotid artery, and because precise deployment is not a big problem (most stents are long enough to have some redundancy proximal and distal to the stenosis).

[00036] Currently available stents used for CAS are either laser cut, self-expanding stents with relatively large, open cells between stent struts, or self-expanding high mesh density devices. Both these stent types are not well-suited for SyNC. Figure 3 shows a number of commercially available stents.

[00037] These available stents exhibit high radial force, since they are intended for narrowed (“stenotic”) vessel segments, intended to widen a severely narrowed lumen and keep it open. This however comes at the cost of vessel wall stretching and resultant micro-injuries, which predisposes the patient to complications such as in-stent stenosis or thrombosis (narrowing or complete blockage of the vessel segment that has been stented). Additionally, to achieve this high radial force, their metal coverage encompasses the full stent circumference (360°), which increases thrombogenicity (propensity for blood clots to form at the metal wires) and mandates dual antiplatelet therapy to prevent these blood clots from forming. These stents are typically deployed across the carotid bifurcation, where the internal and external carotid arteries bifurcate, and therefore cover and block the external carotid artery orifice, which prohibits endovascular access to the vessel for future procedures, increases the risk of jaw claudication and hemifacial ischemia (because the external carotid artery supplies the face and jaw muscles). It also renders subsequent CEA impossible because the dense wire mesh cannot be cut by a surgical scalpel.

[00038] This high radial force, which comes at a high cost, is not needed in SyNC treatment, since SyNC is, per definition, non-stenotic. Clot formation on the metal surface remains a major risk that mandates use of dual antiplatelet therapy. That is, and as shown in Figure 4, because SyNC plaques preferentially form in one specific area opposite of the external carotid artery orifice, and do not affect the entire vessel circumference, in the case of SyNC, focal coverage by the stent material at the site of plaque would be sufficient and preferred over circumferential metal coverage.

[00039] As shown, the SyNC plaque is typically located at the and/or slightly above the level of the common carotid artery (CCA) bifurcation, where the CCA bifurcates into the internal carotid artery (ICA) and external carotid artery (ECA). The left sketch shows the CCA bifurcation in longitudinal view, and right sketch shows different levels of the bifurcation/ slightly above and below the bifurcation in cross-sectional view (levels indicated by the dotted lines in the left sketch). It is seen on the right sketch that SyNC plaques typically are located at the opposite side of the ECA orifice and usually affect <40 percent of the vessel circumference. Therefore, circumferential coverage is not needed to exclude the plaque surface from the blood flow.

[00040] Bioabsorbable materials such as PGI_A or PLI_A are available, which resorb after 1- 2 years. The bioabsorbable stent is placed, and endothelized n over time, i.e. incorporated into the vessel wall and covered by a thin layer of blood vessel cells. Then, the bioabsorbable material is resorbed over the course of months to years. There are some bioabsorbable stents available for aneurysm treatment, whereby the aneurysm is excluded from the circulation by placing the stent, leading to aneurysm thrombosis, and the stent is then endothelized and resorbed. However, one problem when placing such a stent in the common carotid artery bifurcation is that the stent covers the ECA orifice as shown in Figure 5. Thus, there will be constant blood flow through the stent struts at the ECA orifice to supply the ECA branches, and endothelization does not occur. When the bioabsorbable material gets resorbed, fragments of the material will be carried into the ECA branches, and, due to turbulent flow at the CCA bifurcation, may also get carried into the ICA branches, which could lead to blockage of blood vessels supplying the brain and devastating brain infarcts.

[00041] Figure 5 shows endothelization of a bio-absorbable stent over time when a stent is placed in a vessel segment without bifurcation (top row) and at the carotid bifurcation (bottom row). ICA = internal carotid artery, ECA = external carotid artery. Top row: A bioabsorbable stent is placed in a vessel segment without branches (A). Over time, partial (B) and eventually, complete (C) endothelization occurs. After a period of time, the bio-absorbable stent, which is covered by endothelium starts to get resorbed (D) and will eventually resorb fully (not shown). Bottom row: A bio-absorbable stent is placed at the level of the carotid bifurcation (A). Over time, partial (B) and eventually, complete (C) endothelization occurs, except for the ECA orifice, where constant blood flow prevents endothelization. Therefore, the part of the bio-absorbable stent covering the ECA orifice does not get incorporated into the vessel wall. When the bioabsorbable stent eventually starts to get resorbed, fragmentation of the uncovered stent parts at the ECA orifice occurs, and the fragments get carried into the brain vessels (via the ICA) and the face/ neck vessels (via the ECA) (D).

[00042] In the inventors’ own large stroke dataset, 72% of SyNC-type plaques encompassed <180° of the vessel circumference and only 6% encompassed >270°, i.e., focal coverage is feasible due to the limited circumferential extension of SyNC lesions, and it would greatly reduce attendant thrombogenic risks and allow for subsequent CEA because the device could be cut at the site of minimal metal coverage. Furthermore, the pores in the wire mesh of currently used stents are relatively large (as shown in Figure 3) and allow small plaque fragments to migrate between the stent struts into the vessel lumen, particularly when manipulating the plaque while initially deploying the stent. This may result in embolic strokes during deployment. In the context of this description, the term “minimal metal” is understood to be a fractional weight and/or volume of metal relative to an existing metal stent where the fractional weight is in the range of about 5-20% of the amount of metal in an existing stent. That is, existing stents, due to their metal volume, mass and wire diameters cannot be cut by scalpels during surgery (using normal surgical movements); hence, by reducing metal volume/mass by 80-95% can be sufficient to enable a scalpel to effectively cut through these structures. Such “minimal metal” stents can be achieved by effectively reducing the number of wires in a stent (e.g. conceptually removing 4 out of 5 wires) and/or reducing wire diameter or a combination of both.

[00043] There are some metal stents with very small pores, however, the higher smaller pore size results in higher metal density and thus increased thrombogenicity. In theory, fully covered stents would also minimize the risk of embolization during deployment; however, no fully covered carotid stents are currently available, and full circumferential coverage would have similar disadvantages compared to high-metal density stents (increased thrombogenicity, prohibiting future CEA). Focal complete coverage would minimize this risk.

[00044] Figure 6A shows a SyNC plaque 8 at the carotid bifurcation. In the past, a fully bioabsorbable stent 6 (having a bioabsorbable body 6a) as shown in Figure 6B or a partially bioabsorbable stent 7 (having wires 7a and bioabsorbable body 7b) as shown in Figure 6C could be placed proximally to the ECA origin with the result being coverage of the ECA. The risk of these stents is that fragments of the bioabsorbable material may embolize into the ECA and ICA.

[00045] From the foregoing, the inventors recognized a need for a SyNC plaque stabilizer device (SSD) (Figures 7-9; Table 1) that selectively covers the non-stenotic plaque to minimize the risk of embolic strokes, while at the same time minimizing a) thrombogenic surface area and the resulting stroke risk & need for antiplatelet therapy, b) vessel wall injury and the subsequent risk of in-stent stenosis and thrombosis, c) risk of peri-procedural strokes caused by migration of plaque fragments through the stent pores during deployment, and d) avoiding external carotid artery coverage and the resulting complications and e) leave the option of CEA at a later date still available. A comparison of features of the SyNC stabilizer devices (SSDs) and existing devices is shown in Table 1.

Table 1. Comparison of Features of Existing and SyNC Stabilizer Devices (SSDs).

[00046] The key features of the SSDs are: la. Endoluminal patch (having substantially no pores) (bioabsorbable or permanent material) that can be aligned with the SyNC lesion prior to device deployment, with minimal metal wireframe.

OR lb. Circumferential bioabsorbable stent with or without minimal metal wireframe that is designed to not cover the origin of the external carotid artery.

2. Minimal thrombogenicity.

3. Radio-opaque markers for device alignment and deployment

4. Compatibility with current commercially-available embolic protection devices

5. Diameters, shapes and lengths compatible with typical common and internal carotid artery anatomies

[00047] Various embodiments of SSDs are described with reference to Figures 7-9.

[00048] In embodiments as shown in Figures 7 (A-D) and 8, the SSD is a truncated tube 13 having a truncated/trapezoid profile. This embodiment is particularly useful for shorter plaques (i.e. , shorter cranio-caudal extension, as shown in Figure 7A). The trapezoid profile covers the plaque fully but does not cover the ECA orifice, because it is longer on the side opposite to the ECA orifice and shorter at the side of the ECA orifice. The SSD could either be fully bioabsorbable (Figure 7B) or a hybrid design (Figure 7C), comprised of bioabsorbable material 13a and a metal wire frame 13b consisting of only few wires with minimal thrombogenicity that can be cut by a scalpel (should carotid endarterectomy become necessary) and allow continued flow into the ECA. [00049] Note that, depending on the slope/angle, at the inferior end of the trapezoid embodiment, balloon angioplasty may be necessary and can be performed to model the longer inferior side of the device to the vessel wall in order to achieve optimal wall apposition.

[00050] Figure 7D shows an example of a delivery system for the SSD. The appearance of the L and T marker bands 15a, 15b of the delivery catheter depending on their orientation can be used to ensure that the longer side of the trapezoid as seen in Figure 7D is aligned with the plaque and covering the plaque. The distal marker band 15c indicates where the superior end of the stent is.

[00051] Figures 8A and 8B show a plan view of the inferior end 13d of the trapezoid SSD 13 shown in Figure 7. Different embodiments of the SSD may have different slopes/angles at the inferior end 13d of the SSD, resulting in a smaller 13a (Figure 8A) or larger 13b (Figure 8B) discrepancy in length in the device at opposite sides which may be selected based on the relative position of the plaque and the relative bifurcation angles of the CCA, ICA and ECA. Generally, after an SSD is selected, the short side of the SSD will be placed at the site of the external carotid artery origin, so that the ECA origin is not covered. Depending on where the plaque is located in relation to the external carotid artery origin, the slope/angle needs to be steeper or shallower.

[00052] Figure 9 shows another embodiment of the SSD 18, having a plaque patch or covering 18c configured to a metal frame that expands the patch 18c when deployed. The plaque patch 18c may be a material such as GoreTex™. In this embodiment, the SSD 18 has at least two outer hoops 18a, 18b configured to the patch 18c that cause the patch to expand to form a partial tube or “basket” that can be positioned over a plaque. The “apexes” 18d-g of the metal hoops are configured to expand away from one another so as to apply tension to the patch at its edges to form the basket or partial tube shape. Additional hoop wires 18h may be provided to provide additional expansion and/or spring pressure to the hoops 18a, 18b.

[00053] Figure 9A schematically shows the SSD 18 in a delivery catheter in a collapsed position with appropriate alignment markers shown that enable the surgeon to align the patch 18c over the plaque using T and L markers.

[00054] In another embodiment, the plaque patch 18c is a half-tube configured to a minimal metal (as defined herein) stent that is a tube (not shown). In this embodiment, minimal metal stent wires may be present over the branch vessel opening. Since there is generally no stenosis and the stent does not need much outward force, the metal structure could be minimal and made of very thin wires that could potentially be cut if there was a need for CEA at a later time point.

Balloon Angioplasty After Stent Deployment

[00055] Currently, balloon angioplasty is often performed inside the stent after stent deployment. This is done for two reasons:

• Better wall apposition of the stent

• To further expand the vessel at the point of residual narrowing after stent deployment

[00056] It is expected that similar to what is already done, balloon angioplasty would be used for SSD deployment. In patients with SyNC since there is not substantial stenosis, thus, angioplasty would allow better wall apposition.

[00057] The SSD system may be packaged as a kit with multiple SSDs having different diameters and/or truncation angles.

Other Designs

[00058] Referring to Figures 10-13, further embodiments of PSDs are described where the stent is configured with an elliptical hole 20a within a middle section 20b of the stent. The stent is configured for placement over the junction of a vessel bifurcation namely within the primary vessel 20c and the opening of the secondary vessel 20d. Figure 10A shows the junction vessel bifurcation from a top view above a plane that bisects both the primary vessel 20c and the secondary vessel 20b whereas Figure 10B is a side view looking towards the junction 20e. In these embodiments, the stent is a covered stent including both a minimal wire tube and a cover as described above. The hole 20a is preferably a few mm larger than the junction opening 20e to allow some margins for the surgeon to correctly place the stent over the opening.

[00059] Placement of the stent 20 requires correct sizing of the stent hole 20a relative to the junction opening 20e which can be measured by imaging and selection of the correctly sized stent at the time of the procedure. Placement further requires correct orientation of the stent such that the stent hole is aligned over the junction opening such that the stent does not occlude or partially occlude the junction opening.

[00060] In one embodiment, radio markers 22 are configured to the stent at particular locations around the circumference of the stent to enable the surgeon to align the stent both proximally and distally relative to the junction opening and rotationally relative to the junction opening.

[00061] In one embodiment, partial circumferential bands (e.g “T” markers) are aligned with the outer edges of the hole 20a. These markers serve to enable the surgeon to properly align the stent in the axial/proximal direction relative to the junction opening. That is, during the procedure, the surgeon is able to see the proximal 24a and distal 24b edges of the junction opening and is able to align markers 22a adjacent these edges.

[00062] In order to rotationally align the hole 20a with opening 20e, the arms of the “T” will be visible only from particular viewing angles. The imaging view angle that the surgeon typically works from is the top view as shown in Figure 10A. In this Figure, the stent has been properly placed over the junction opening such that the hole 20a aligns with the junction opening.

[00063] Figure 10B shows the correct alignment of the stent but viewed from the side.

[00064] The arms of the T are visible when looking from the side (Figure 10B) but are not visible when looking from the top where the surgeon is looking at the thickness of the T (Figure 10A). Accordingly, if the surgeon knows the viewing angle as in Figure 10A, the correct rotation of the stent can be achieved by rotation of the stent to the point where the T arms are seen as minimal.

[00065] Additional markers 22b may be configured to the stent at the proximal and distal edges of the stent to provide additional positional information to the surgeon during the procedure.

[00066] It is noted that other shaped markers can be configured the stent that provide similar alignment capabilities.

[00067] Figure 11A illustrates a stent 20 that may be configured as a laser-cut metal stent having hole 20e within a stent body mesh and with markers 22. Figure 11 B illustrates a stent 20 that may be configured as a woven stent having hole 20e within a stent body mesh, markers 22 and covering 23. Each will include a covering.

[00068] The covering is configured to the wire tube by known techniques such that the covering fully encapsulates the wire tube. Endothelization pores may be formed in particular zones of the covering to promote endothelization around the stent after placement.

[00069] For example, the stent may include a plaque burden zone Z (Figure 10A) and a nonplaque burden zone. The plaque burden zone is generally the area of the stent that covers a plaque. The remaining area of the stent covering would be considered as the non-plaque burden zone. Endothelization pores may be configured to the non-plaque burden zone by subsequent processing of the coating after adherence to the metal tube. Such pores may be formed by various techniques including laser cutting and may generally be in the size of about 30-100 microns, preferably about 50 microns.

[00070] Figures 12 and 12a illustrates an assembly and process for deploying the stent 20 from a stent delivery device 26 via a stent catheter 26a over a vessel junction 20e. Figure 13 illustrates distal components of an assembly used by the surgeon to deploy the stent.

[00071] An assembly of the stent delivery device, and stent wire are assembled and introduced into a vessel in accordance with standard procedures (e.g. groin or radial artery puncture). The assembly is navigated to the desired location using standard techniques including the use of guide catheters, diagnostic catheters and wires. The assembly is advanced into position upstream of the vessel junction 20e.

[00072] The stent is compressed within the stent delivery device 26 and is pushed forward over the vessel junction and aligned using markers 22a as described above. As the stent is compressed within the stent delivery device, it will be longer than the vessel junction prior to deployment. Hence, the surgeon will have to compensate for the shortening of the stent as it is deployed from the stent delivery device. The rotational orientation of the stent may be checked via markers 22a. If the stent is placed correctly, the stent catheter 26a is disconnected.

[00073] In one method, the stent delivery device and stent catheter are withdrawn and a separate balloon system is run over the microwire to the stent and inflated to apposition the stent.

[00074] In another embodiment, the stent delivery catheter 26a is configured with a balloon 30 and balloon inflation tube 27 within the stent delivery catheter 26a (Figure 12A), wherein upon stent deployment, disconnection and removal of the stent wire, the balloon, which forms part of the stent delivery catheter, is pushed forward and inflated to apposition the stent.

[00075] Figure 12A shows an embodiment where balloon 30 is configured to the stent delivery catheter proximal to the compressed stent whereas Figure 12B shows the balloon configured to the stent delivery device where it is within the compressed stent. The latter configuration is generally preferred in that after stent deployment (i.e. withdrawal of the stent delivery system), the balloon 30 is simply inflated rather than having to conduct a subsequent step of positioning the balloon. [00076] Figure 12B also shows an embodiment where all markers are on the stent delivery device.

[00077] The distal components (Figure 13) include a rotating hemostatic valve (RH V) 40 and the stent delivery system 40a having a torque arm 42 and stent delivery catheter 40a. As shown, the stent delivery catheter 40a contains balloon tube 40b and microwire 40b which collectively enable the surgeon to torque the stent using torque arm 42 and withdraw/deploy the stent by pulling back on the stent delivery system relative to the stent delivery catheter. The balloon is inflated via balloon tube 40b.

Custom stents

[00078] The clinical steps of diagnosis of stenosis in vessels may reveal patient anatomies where pre-configured stents could be problematic due to the location of vessel branches. For example, if a stenosed area has multiple branches near the stenosis, placement of a stent with a single elliptical hole may not be possible as the stent could occlude one or more of the branches. Accordingly, there is a need for systems and methods where a stent is customized to a patient’s anatomy on demand.

[00079] These steps generally include: a. Conduct diagnostic imaging of affected vessel(s) in patient; b. Forward imaging data to processing computer; c. Analyze imaging data to determine 3D dimensions and configuration of affected vessel(s); d. Using dimensions and configuration data from c., forward dimensions and configuration data to stent construction device to configure stent having minimal metal tube and tube openings; e. Construct a stent using the stent construction device; f. Design the stent to have holes appropriate for patient’s anatomy g. Apply radio markers as described above to stent and/or on stent delivery device; h. Install stent delivery catheter on stent and install stent delivery catheter and stent within a stent delivery device; i. Forward stent assembly to treating medical team. Stent Coverings and Coatings

[00080] As described above, the covering may include holes configured to promote endothelization.

[00081] In various embodiments, the inner and outer surfaces of the covering are coated with functional coatings selected from: i) Drug-Eluting Coatings

(1) These coatings release antithrombotic or antiproliferative drugs over time to prevent thrombosis and restenosis. Common drugs include:

(a) Sirolimus and its analogs (Everolimus, Zotarolimus, Biolimus): Inhibit smooth muscle cell proliferation and migration, reducing restenosis risk.

(b) Paclitaxel: Inhibits cell proliferation but has been largely replaced by sirolimus-based drugs due to safety concerns, ii) Heparin Coatings

(1) Heparin is an anticoagulant that prevents platelet aggregation and clot formation.

(a) Stents coated with heparin (e.g., Carmeda BioActive Surface) have been shown to reduce thrombotic complications, especially in high-risk patients. iii) Nitric Oxide (NO)-Releasing Coatings

(1) NO is a natural vasodilator and inhibitor of platelet aggregation.

(2) NO-releasing coatings help prevent thrombosis and inflammation while promoting endothelial healing. iv) Polymer-Free Drug Coatings

(1) Traditional drug-eluting stents (DES) use polymer carriers, which may cause inflammation and late thrombosis.

(2) Polymer-free coatings deliver drugs directly from the stent surface without a polymer carrier, reducing long-term complications. v) Platelet-Inhibiting Coatings

(1) Glycoprotein llb/llla inhibitors, such as abciximab, have been explored as stent coatings to reduce platelet adhesion.

(2) Other coatings may use peptides or biomolecules that block platelet activation. vi) Endothelial Cell-Promoting Coatings

(1) Some stents are coated with endothelial progenitor cell-capturing agents, such as antibodies against CD34+ cells, to accelerate endothelial healing and reduce thrombosis risk. vii) Passive Surface Coatings

(1) Materials like phosphorylcholine, titanium-nitride oxide, and diamond-like carbon reduce platelet adhesion and inflammation without releasing drugs.

Clinical Impact

[00082] Antithrombotic coatings have significantly improved stent safety and efficacy, reducing the need for prolonged dual antiplatelet therapy (DAPT) and lowering the risk of instent thrombosis. The choice of coating depends on patient-specific factors, including bleeding risk, restenosis risk, and comorbid conditions.

Claims

1. A system comprising: a plaque covering stent configured for placement within a primary vessel over a plaque adjacent a bifurcation, the bifurcation defining a branch vessel off the primary vessel and a branch vessel opening, the plaque covering device configured for placement within the primary vessel over the plaque without covering the branch vessel opening while extending proximally and distally within the primary vessel, the plaque covering device configured for deployment from a stent delivery system via a stent delivery catheter and retraction into the stent delivery system and wherein the plaque covering stent is detachable from the stent delivery catheter.

2. The system as in claim 1 wherein the plaque covering stent is a truncated tube.

3. The system as in claim 2 where the truncated tube is bioabsorbable.

4. The system as in claim 3 wherein the truncated tube is configured with a minimal metal wire frame to expand the plaque covering surface.

5. The system as in claim 1 wherein the plaque covering surface is a tensionable partial tube surface configured to an expandable metal frame, the expandable metal frame configured to the expand the partial tube surface into a partial tube.

6. The system as in claim 5 wherein the expandable metal frame includes a first elliptical metal hoop having first and second apexes and a second elliptical metal hoop having third and fourth apexes and where the first and second elliptical metal hoops are configured to expand and bias each of the first, second, third and fourth apexes away from each other.

7. The system as in any one of claims 1-6 further comprising a delivery catheter configured with T and L radio markers for alignment of the plaque covering surface over the plaque.

8. The system as in claim 1 where the plaque covering surface is a half-tube configured with a minimal wire stent to provide an outward radial force to the plaque covering surface.

9. The system as in claim 1 where the plaque covering stent is a tube having an elliptical tube opening.

10. The system as in claim 9 where the tube has a tube longitudinal axis and the elliptical opening has a major axis aligned with the tube longitudinal axis.

11. The system as in claim 10 where the tube includes first and second radio markers adjacent the elliptical tube opening and aligned with the major axis.

12. The system as in claim 11 where the first and second radio markers include at least one lateral band extending a partial circumferential distance around the tube for determining rotational alignment of the tube within a vessel.

13. The system as in claim 11 where the tube includes a distal and a proximal edge each having at least one radio marker adjacent the proximal and distal edge.

14. The system as in any one of claims 9-12 wherein the tube is configured with a minimal metal wire frame having a polymer stent covering.

15. The system as in claim 13 wherein the minimal metal frame is a woven mesh.

16. The system as in claim 15 wherein the woven mesh is 1-5% of the surface area of the stent.

17. The system as in any one of claims 14-16 wherein the polymer stent covering is configured with 30-100 micron endothelization pores.

18. The system as in claim 14 wherein the minimal metal frame is a laser cut tube having a plurality of openings.

19. The system as in any one of claims 9-18 further comprising a stent delivery device and wherein the tube is compressed within the stent delivery device as a compressed stent and the stent is configured to a stent delivery catheter.

20. The system as in claim 19 wherein the first and second radio markers are configured to the stent delivery device at positions that overlay proximal and distal edges of the elliptical tube opening of the compressed stent.

21. The system as in any one of claims 19-20 further comprising an inflatable balloon configured to the stent delivery catheter.

22. The system as in claim 21 wherein the inflatable balloon is configured over the compressed stent and within the stent delivery device.

23. The system as in claim 21 wherein the inflatable balloon is configured to the stent delivery catheter distal to the compressed stent.

24. The system as in any one of claims 14-23 wherein the tube includes a plaque burden zone and a non-plaque burden zone and the endothelization pores are formed in the covering in the non-plaque burden zone.

25. The system as in any one of claims 14-24 wherein the covering is configured to the tube via electro-spinning.

26. The system as in any one of claims 14-25 wherein the covering is configured with a drug eluting coating selected from any one or a combination of Sirolimus, Everolimus, Zotarolimus, Biolimus or Paclitaxel.

27. The system as in any one of claims 14-25 wherein the covering is configured with a Heparin coating.

28. The system as in any one of claims 14-25 wherein the covering is configured with a Nitric Oxide (NO)-Releasing coating.

29. The system as in any one of claims 14-25 wherein the covering is configured with a Polymer-Free Drug coating.

30. The system as in any one of claims 14-25 wherein the covering is configured with a Platelet-Inhibiting coating.

31 . The system as in any one of claims 14-25 wherein the covering is configured with a Endothelial Cell-Promoting coating.

32. The system as in any one of claims 14-25 wherein the covering is configured with a Passive Surface coating.

33. The system as in any one of claims 14-26 wherein the covering has inner and outer surfaces and different drugs are configured to the inner and outer surfaces.

34. The system as in any one of claims 14-33 further comprising a proximal torquing arm configured to the stent delivery catheter.

35. A method of configuring a stent for a specific patient comprising the steps of: a. conduct diagnostic imaging of affected vessel(s) in patient including a primary vessel and at least one secondary vessel branching off the primary vessel; b. forward imaging data to a processing computer; c. analyze imaging data to determine 3d dimensions and configuration of affected vessel(s); d. using dimensions and configuration data from c., forward dimensions and configuration data to stent construction device to configure stent having minimal metal tube and tube openings and adapted for placement within the primary vessel and over the at least one secondary vessel; e. construct a stent using the stent construction device, the stent having a polymer covering; f. apply radio markers to the stent and/or on a stent delivery device; g. install stent delivery catheter on stent and install stent delivery catheter and stent within a stent delivery device; h. forward stent assembly to a treating medical team.

36. The method as in claim 35 wherein the stent includes a plaque burden zone and a nonplaque burden zone and the method further comprises the step of after step e. configuring endothelization pores to the non-plaque burden zone.