EP4701574A1

EP4701574A1 - A compliant stent graft

Info

Publication number: EP4701574A1
Application number: EP24759235.5A
Authority: EP
Inventors: Michael Moore
Original assignee: Ascense Medical GmbH
Current assignee: Ascense Medical GmbH
Priority date: 2023-07-26
Filing date: 2024-07-25
Publication date: 2026-03-04
Also published as: CN121729200A; WO2025022343A1

Abstract

The invention provides a compliant stent graft for deployment in the descending aorta to reduce the clinical impact of a stiffened aorta. The compliant stent graft includes a tubular body which extends between a proximal end and a distal end and comprises a proximal anchor section ending at the proximal end and a distal anchor section ending at the distal end. Each section is adapted to move from a constricted state to a dilated state. A treatment section is interposed between the proximal and the distal anchor sections, which is adapted to move from an unexpanded state, having a first volume to an expanded state, having a second volume, wherein, in the unexpanded state, the treatment section has an unexpanded diameter which is less than a constricted diameter of the distal and proximal anchor sections in the constricted state and wherein the difference between the first volume and the second volume is sufficient to retain between 20% and 70 % of the volume of blood ejected during systole.

Description

A COMPLIANT STENT GRAFT

FIELD OF THE INVENTION

[0001] This invention relates to a compliant stent graft for deployment in the descending aorta to improve aortic compliance in patients with increased stiffness, such as heart failure.

BACKGROUND OF THE INVENTION

[0002] The prevalence of heart failure in the general population is approximately 4.8%. Approximately 55% of those patients have heart failure with reduced (HFrEF) or moderately reduced (HFmrEF) ejection fraction, also known as systolic heart failure, and 45% of those patients have heart failure with preserved ejection fraction (HFpEF), also known as diastolic heart failure.

[0003] Heart failure with preserved ejection fraction (HFpEF) is a form of heart failure in which the heart muscle contracts typically (preserved systolic function), but the ventricles do not relax as they should (impaired diastolic function). Ejection fraction (EF) measures the percentage of blood pumped out of the heart’s left ventricle each time it beats. In HFpEF, the ejection fraction is average, defined as greater than 50%, but the ventricles are stiff and cannot fill correctly.

[0004] There is strong evidence linking vascular stiffness, particularly in the aorta, with the development of this disease. [0005] The current solutions for preventing HFpEF are: a) lifestyle modifications: recommendations include adopting a healthy diet low in sodium, saturated fats, and refined sugars, regular physical exercise, weight management, and cessation of smoking and excessive alcohol consumption; b) pharmacological interventions: various medications and therapeutic agents, such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), beta-blockers, diuretics, and statins can help prevent, can help prevent HFpEF; c) comorbid condition management: as HFpEF often coexists with comorbidities like hypertension, diabetes, and obesity, managing these underlying conditions through appropriate medications and lifestyle modifications, are known to reduce the risk of developing HFpEF.

[0006] Each of these solutions and interventions comes with associated problems. With lifestyle modifications, changing a person’s lifestyle that has been entrenched over a lifetime is very difficult to achieve. As for pharmacological interventions, with chronic therapeutic application of these medications, tolerance to the medication often ensues.

[0007] Future directions in pharmacology for treating heart failure with preserved ejection fraction (HFpEF) are focused on developing targeted therapies that address the underlying pathophysiology of the condition, primarily aortic stiffness. As mentioned, the current treatment options for HFpEF are limited and mainly focus on symptom management. However, some of the potential future directions in pharmacology for the treatment of HFpEF include i) myocardial stiffness modulation, ii) nitric oxide pathway enhancement, iii) mitochondrial function modulation, iv) inflammation and immune modulation, v) exercise-mimetic drugs, vi) MMP9 inhibitors and vii) STAT3 inhibitors.

[0008] Most of these treatments are in early-stage development and do not currently provide treatment options.

[0009] The present invention at least partially addresses the problems and shortcomings mentioned above.

SUMMARY OF INVENTION

[0010] Hereinafter, the terms “proximal” and “distal” refer to proximity relative to the arch of the aorta.

[0011] Hereinafter, the terms “proximal landing zone” and “distal landing zone” refer to the zones or areas within the aorta to which a graft engages to anchor the graft.

[0012] Hereinafter, the term “pre-formed” refers to a forming step made on the tubular body before stents are engaged with the body.

[0013] Hereinafter, when used to describe a structure, the term “compliance” refers to the ability of a structure to expand from a native state and then to recoil back to the native state, i.e., the ability of the structure to mimic the elasticity and distensibility of a healthy aorta, allowing it to accommodate and regulate blood flow effectively. [0014] The invention provides a compliant stent graft for deployment in the descending aorta to reduce the clinical impact of a stiffened aorta, the compliant stent graft including: a tubular body which extends between a proximal end and a distal end, and which comprises: a proximal anchor section ending at the proximal end and a distal anchor section ending at the distal end, each section adapted to move from a constricted state to a dilated state, a treatment section which is interposed between the proximal and the distal anchor sections, which is adapted to move from an unexpanded state, having a first volume, to an expanded state, having a second volume, wherein, in the unexpanded state, the treatment section has an unexpanded diameter which is less than a constricted diameter of the distal and proximal anchor sections in the constricted state, and wherein the difference between the first volume and the second volume is sufficient to retain between 20% and 70% of the volume of blood ejected during systole.

[0015] The compliant graft may be adapted to provide a distensibility between 2 and 8 x 10-³ mm Hg-¹ in a physiological blood pressure range of 50 to 200 mmHg. Aortic distensibility is calculated as: (Area max - Area min) I (Area min x pulse pressure). [0016] The expanded state may occur when the heart's left ventricle contracts, creating a rise in blood pressure (pulse pressure of 40 to 60 mmHg) within the blood pressure range of 50 to 200 mmHg.

[0017] The tubular body may be made of a composite material which allows:

(a) the treatment section to expand from the unexpanded state to the expanded state during systole and to elastically recoil from the expanded state to the unexpanded state during diastole,

(b) the proximal and the distal anchor sections to expand from the constricted state to the dilated state.

[0018] The composite material may comprise a mechanical component and a compliant component.

[0019] The mechanical component may be a knitted or a woven fabric.

[0020] The knitted or woven fabric may comprise elastic, non-elastic, or composite yarns.

[0021] The elastic yarns may be made of TPU or polyurethane-polyurea copolymer. The inelastic yarns are polyethene terephthalate (PET) or Nylon 6,6.

[0022]The compliant component may be a liquid-tight material elastomeric polymeric material such as for example, polyurethane (TPU) or a polyurethane silicone copolymer (TPU-Silicone). [0023] The compliant component may be present in the tubular body in one or more layers. The compliant material may cover, coat, or encapsulate the mechanical component.

[0024] The first and second anchor sections may be adapted to engage the aorta in the dilated state, securing the tubular body to proximal and distal landing zones, respectively.

[0025] The first and second anchor sections may be pre-formed with the constricted diameter to conform, in use, to a diameter of the native aorta along a proximal and a distal landing zone, respectively.

[0026] The first and second anchor sections may each have at least one stent of a first set that is adapted to bias the respective anchor section from the constricted state, in which the at least one stent is strained, to the dilated state, in which the at least one stent is expanded and at least partially relaxed.

[0027] The at least one stent of the first set may be adapted to impose a radial force on the aorta when biasing the respective anchor section from the constricted state to the dilated state.

[0028] The constricted state refers to a condition where the anchor sections have a diameter equivalent to the minimal aortic diameter.

[0029] The first and second anchor sections may have a dilated diameter in the dilated state.

[0030] The dilated diameter may exceed the constricted diameter by up to 20%, preferably between 9% and 11%. [0031] The difference between the first volume (unexpanded state) and the second volume (expanded state) of the treatment section may be from 20 to 60 cc. Preferably, the difference between the first and second volumes is from 25 cc to 45 cc.

[0032] In use, the treatment section in the expanded state may either be radially spaced from the aorta or partially engaged with the aorta.

[0033] In use, the treatment section in the expanded state has an expanded diameter smaller than the diameter of the native aorta.

[0034] The treatment section may have at least one stent of a second set.

[0035] The at least one stent may be adapted to maintain the unexpanded state of the treatment segment, in which the at least one stent is relaxed, but allow the treatment segment to move to the expanded state, in which the at least one stent is strained.

[0036] The stents of the first and second sets may be fixed to the anchor sections and the treatment sections, respectively, by being sandwiched between the first and second layers. Alternatively, the stents of the first and second sets may be fixed to the anchor sections and the treatment sections, respectively, embedded within the second layer.

[0037] Each stent of the first and second sets may be a circumferential selfexpanding stent.

[0038] Each stent of the first and second sets may be a helical self-expanding stent. [0039] Each stent of the first and the second sets may be made of a suitable super-elastic alloy such as nitinol.

[0040] Each stent of the first and second sets may have a waveform wire body configuration or an expanded slotted tube configuration.

BRIEF DESCRIPTION OF THE DRAWINGS

[0041] The invention is further described by way of an example with reference to the accompanying drawings in which:

Figure 1 diagrammatically illustrates a compliant stent graft in accordance with the invention with a middle treatment section in a relaxed, unexpanded state,

Figure 2 diagrammatically illustrates the compliant stent graft with a middle treatment section in a strained expanded state;

Figure 3 diagrammatically illustrates a compliant aorta in an expanded state during systole,

Figure 4 diagrammatically illustrates a compliant aorta in a retracted state during diastole;

Figure 5 diagrammatically illustrates a compliant stent graft deployed in an aorta with the treatment section in the strained expanded state; and

Figure 6 diagrammatically illustrates a compliant stent graft deployed in an aorta with the treatment section in the relaxed, unexpanded state. DESCRIPTION OF PREFERRED EMBODIMENTS

[0042] Figure 1 of the accompanying drawings illustrates a compliant stent graft 10, designed and configured for deployment in a descending aorta 12 to reduce the clinical impact of a stiffening or stiffened aorta.

[0043] The stent graft 10 has a generally tubular body 14 having a tubular wall 16, within which a lumen 18 is defined. In a longitudinal direction, the body extends between a proximal end 20 and a distal end 22.

[0044] For example, wall 16 of the stent graft body 14 has a first or support layer of a mechanical component and a second or coating layer of a compliant component. This layered wall configuration is not illustrated as a configuration and is just one of many possible ways of combining the components.

[0045] The first layer of the tubular wall 16 is a knitted fabric made of polyester, such as PET. A knitted mesh of a nonabsorbable, biocompatible material, such as PET, provides a supportive frame onto which the coating layer can be applied whilst being compliant and stretchable.

[0046] The tubular wall 16 is blood-tight to prevent or limit blood leakage from the lumen 18. This is done by providing the second layer, which is comprised of a layer or coating of TPU. The polyurethane is applied by any suitable means to adhere to the first layer.

[0047] The tubular body 14 is functionally segmented into relatively short proximal and distal anchor sections (respectively designated 24.1 and 24.2) of cylindrical form and a relatively long treatment section 26, interposed between the two anchor sections. As an example, each anchor section will be from 10 to 30mm in length, whilst the treatment section will be from 100 to 250mm in length

[0048] The first and the second anchor sections (24.1 , 24.2) have a relaxed dilated state (shown in the Figures) and a strained constricted state. Movement between the dilated and the constricted state is enabled with a plurality of stents of a first set (respectively designated 28.1, 28.2...28.N), each engaged to either the first or the second section.

[0049] Conversely, the treatment section 26 exhibits a relaxed unexpanded state, shown in Figure 1 , and a strained expanded state, shown in Figure 2. Movement between the unexpanded and the expanded state is enabled via the tubular polymer composite wall, which may or may not be aided with a plurality of stents of a second set (respectively designated 30.1 , 30.2...30.N), each of which is engaged to this section, spaced at regular intervals.

[0050] The compliant property of wall 16 of the stent graft body 14 is achieved through the interaction between the mechanical and compliant components, enabling this movement.

[0051] The first and the second anchor sections (24.1, 24.2) are adapted to partially engage an internal surface of an aorta, in which stent graft 10 is deployed, to fix the stent graft in a secure position at a proximal and distal landing zone, respectively (designated 32.1 , 32.2). [0052] The first and the second anchor sections (24.1, 24.2) are so adapted by being pre-formed with a constricted diameter (designated X in Figure 1), which is the diameter of each of these sections when in the constricted state, to conform to the minimal diameter of the native aorta 12. The stents 28 are oversized and therefore adapted to bias the anchor sections from constricted to dilated states. In the dilated state, a dilated diameter (designated Y in Figure 2) is up to 20% larger than the constricted diameter and, for that matter, the aortic diameter.

[0053] The anchor sections are pre-formed to avoid pleating or infolding when these sections are moved to the constricted state after being in the dilated state.

[0054] The treatment section remains in the (relaxed) unexpanded state unless deployed within an aorta 12, and blood pressure rises during systole. In this unexpanded state, the treatment section has a uniform cylindrical shape with an unexpanded diameter (designated Z in Figure 1), which is structurally maintained by the stents 30 of the second set. This unexpanded diameter is smaller than the constricted diameter of the distal and proximal anchor sections and the aortic diameter. This configuration allows room for the treatment section to expand when the graft is placed in the vessel without being restricted by the vessel walls.

[0055] In deploying the stent graft, the stents 28 of the first set compress towards the constricted diameter to allow passage within the aorta. Once the graft is in position, these stents are allowed to expand with inherent spring bias towards the dilated diameter and, in so doing, push into the aortic walls with a radial force, which will resist the longitudinal movement of the stentgraft.

[0056] Once the stent graft is in place, treatment section 26 bridges the pair of anchor sections (24.1, 24.2), providing a conduit for blood pumped from the left ventricle during systole past the aortic valve 32. This treatment section provides an artificial aortic section to maintain the “windkessel function” of the diseased/stiff aorta section where the stent graft is deployed.

[0057]As illustrated in Figure 5, during systole, the rise of blood pressure in treatment section 26 will cause this section to expand towards the strained expanded state, illustrated in Figure 6. At the maximum extent, i.e., the strained expanded state, the walls 16 of the stent graft approach the aorta. However, any further expansion is limited at this point due to the “lock-out” effect imposed by the mechanical component of the tubular body’s composite material.

[0058] The stent graft's utile capacity lies in the volumetric difference between the treatment section in the unexpanded state and the expanded state. This volumetric difference should be enough to retain between 20% and 70% of the volume of blood ejected during systole.

[005S]Then, as the aortic valve closes, and there is a drop in blood pressure in the aorta as the heart cycle enters diastole, the treatment section will elastically recoil from the expanded state to the unexpanded state and, in so doing, eject the retained blood from the stent-graft, thus mimicking the Windkessel effect of a healthy aorta. In so doing, the stent graft assists with the maintenance of a continuous and smoother flow of blood during diastole, which leads to a rise in diastolic blood pressure, lowering of afterload and a slow down the progression of the symptoms or reversal of the symptoms of heart failure.

[0060] In mimicking, the stent graft, as an artificial section of the descending aorta, must maintain a well-functioning Windkessel effect by retaining a portion of the ejected blood volume, enabled by the compliant properties of its walls, allowing it to stretch and store some of the blood ejected from the left ventricle during systole. The stored blood volume is then displaced into the circulation during diastole.

[0061] The blood retained in the descending aorta during systole can vary depending on factors such as arterial compliance, heart rate, and blood pressure. Around 60 to 80% of the stroke volume (amount of blood ejected from the left ventricle per heartbeat) is estimated to be retained within the aorta during systole. If the stroke volume is approximately 70 ml per beat, the retained blood volume in the descending aorta during systole would be approximately 42 to 56 ml. This means that during systole, the aorta maintains a significant portion of the blood ejected by the left ventricle.

Claims

1. A compliant stent graft which includes a tubular body which extends between a proximal end and a distal end and comprises a proximal anchor section ending at the proximal end and a distal anchor section ending at the distal end, each section adapted to move from a constricted state to a dilated state, a treatment section which is interposed between the proximal and the distal anchor sections that is adapted to move from a relaxed unexpanded state having a first volume to a strained expanded state having a second volume, wherein, in the unexpanded state, the treatment section has an unexpanded diameter which is less than a constricted diameter of the distal and proximal anchor sections in the constricted state, and wherein the difference between the first volume and the second volume is sufficient to retain between 20% and 70 % of the volume of blood ejected during systole.

2. A compliant stent graft, according to claim 1 wherein the tubular body is made of a composite material which allows the treatment section to expand from the unexpanded state to the expanded state during systole and to recoil from the expanded state to the unexpanded state during diastole, and which allows the proximal and the distal anchor sections to expand from the constricted state to the dilated state.

3. A compliant stent graft according to claim 2 wherein the composite material comprises a mechanical component and a compliant component.

4. A compliant stent graft according to claim 3 wherein the mechanical component is a knitted or woven fabric comprising elastic, non-elastic or composite yarns.

5. A compliant stent graft according to anyone of claims 1 to 4 wherein the first and second anchor sections are pre-formed with the constricted diameter to conform to a diameter of the native aorta along the proximal and the distal landing zone respectively.

6. A compliant stent graft according to anyone of claims 1 to 5 wherein the first and second anchor sections have at least one stent of a first set that is adapted to bias the respective anchor section from the constricted state to the dilated state.

7. A compliant stent graft according to claim 6 wherein the at least one stent is adapted to impose a radial force on the aorta when biasing the respective anchor section from the constricted state to the dilated state.

8. A compliant stent graft according to anyone of claims 1 to 7 wherein a dilated diameter of the first and second anchor sections in the dilated state is up to 20% larger than the constricted diameter.

9. A compliant stent graft according to anyone of claims 1 to 8 wherein the difference between the first and second volume is from 20 cc to 60 cc.

10. A compliant stent graft according to anyone of claims 1 to 9 wherein the treatment section in the expanded state has an expanded diameter smaller than the diameter of the native aorta.

11. A compliant stent graft according to anyone of claims 1 to 10 wherein the treatment section has at least one stent of a second set.

12. A compliant stent graft according to claim 11 wherein the at least one stent is adapted to maintain the treatment section in the unexpanded state with the unexpanded diameter but allow the treatment segment to move to the expanded state.