Flow-reducing stent grafts

Abstract

Various aspects of the present invention are devices, systems and methods for modifying blood flow in a patient's blood vessel. These devices, systems and methods may include restricting blood flow in a first side branch vessel to reduce blood flow into the first side branch and increase blood flow into one or more arteries located distal to the first side branch vessel.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of Provisional Patent Application No. 62 / 702,717, filed on July 24, 2018, which is incorporated herein by reference in its entirety for all purposes. Technical Field

[0003] The present disclosure relates to systems, medical devices and methods for treating heart failure and / or other cardiovascular diseases. More specifically, the present disclosure relates to removing the accumulation of excess fluid that is often caused by poorly perfused kidneys. Background Art

[0004] Patients experiencing heart failure may accumulate excess fluid in their bodies. Excessive fluid accumulation may increase fluid accumulation in the interstitial spaces and worsen the patient's symptoms and quality of life. Excess fluid (or hypervolemia) is the leading cause of hospitalization for heart failure patients (approximately 1,000,000 cases per year in the United States).

[0005] Treatment of excess fluid accumulation can be treated pharmaceutically with diuretics (or other agents). However, patients may develop drug resistance, undesirable side effects, inappropriate dosages, or other problems such as failure to follow drug instructions. Non-drug options such as implantable device solutions that provide replacement or enhanced efficacy by affecting renal function can be beneficial to avoid these and other problems in treating excessive fluid accumulation in the body. Similarly, chronic hypertension (high blood pressure) can also be managed pharmaceutically with diuretics (or other antihypertensive agents). In addition, other disease states may lead to hypotension, reduced cardiac output, and poor renal function. As long as the kidneys play a central role in regulating systemic blood pressure and fluid homeostasis, non-drug options such as implantable device solutions that provide replacement or enhanced efficacy by affecting renal function can provide alternative methods to manage fluid imbalances caused by chronic disease states such as heart failure, hypertension, and other disease states. Summary of the invention

[0006] In one example ("Example 1"), a method of altering blood flow in a patient's blood vessel includes: delivering an implantable medical device within the blood vessel, the implantable medical device comprising a stent element and a graft component attached to at least a portion of the stent element; and setting the implantable medical device to restrict blood flow within a first side branch vessel to reduce flow into the first side branch vessel and increase flow into one or more arteries distal to the first side branch vessel and supplying an organ of the patient.

[0007] In another example ("Example 2") further than the method of Example 1, the organ is one of a kidney, a brain, a pancreas, or a liver.

[0008] In another example ("Example 3") that is further relative to the method of Example 1, the method also includes: setting an implantable medical device to limit blood flow within a first side branch vessel includes reducing blood flow into the first side branch to increase blood flow into one or both renal arteries of the patient to improve renal perfusion.

[0009] In another example ("Example 4") further relative to the method of Example 3, the method also includes: setting an implantable medical device to restrict blood flow in the first side branch vessel includes covering the first side branch vessel set proximal to the ostium of the renal artery.

[0010] In another example ("Example 5") further than the method of any of Examples 1-4, the method includes: positioning the implantable medical device includes positioning a perfusable portion of the implantable medical device adjacent to the first side-branch vessel.

[0011] In another example ("Example 6") further relative to the method of Example 5, the method also includes: setting the perfusable portion adjacent to the first side branch vessel to reduce the blood flow (flow) entering the first side branch vessel by about 20% to about 30%.

[0012] In another example ("Example 7") further to the method of any of Examples 5-6, the perfusable portion of the implantable medical device is one or both of a stent element and a graft component.

[0013] In another example ("Example 8") further than the method of Example 7, the method includes: disposing the perfusable portion includes disposing the perfusable portion of the graft component adjacent to the first side-branch vessel.

[0014] In another example ("Example 9") further than the method of Example 7, the method includes: disposing the perfusable portion includes disposing the perfusable portion of the stent component adjacent to the first side-branch vessel.

[0015] In another example ("Example 10") that is further relative to the method of any one of Examples 1-9, the method also includes: setting an implantable medical device to limit blood flow within a first side branch vessel includes: covering the first side branch vessel, which is set proximal to one or more arteries supplying an organ of the patient.

[0016] In one example ("Example 11"), an implantable medical device for modifying blood flow within a patient's blood vessel includes: a stent element; and a graft component attached to at least a portion of the stent element, the graft component having a porosity configured to reduce flow into a first side branch disposed adjacent to the graft component by between about 10% and about 30% to increase flow or pressure at a renal artery of the patient to improve renal perfusion and diuresis.

[0017] In another example ("Example 12") further than the apparatus of Example 11, the graft component includes a porous membrane configured to allow blood to flow through the membrane with minimal pressure drop such that flow within the blood vessel is reduced by between about 10% and about 30%.

[0018] In another example ("Example 13") further than the apparatus of Example 11, the graft component includes pores configured to allow blood to flow through the membrane.

[0019] In another example ("Example 14") further than the apparatus of Example 11, the hole is a laser drilled hole in the graft component.

[0020] In one example ("Example 15"), an implantable medical device for altering blood flow within a patient's blood vessel includes a stent element configured to impose an amount of restriction within the stent element to alter blood flow within the vessel to increase blood flow into one or more branch vessels extending from the vessel, and to vary the amount of restriction in response to pulsatile flow; and an anchoring portion configured to engage a vessel wall of the vessel and position the stent element within the vessel.

[0021] In another example ("Example 16") further than the apparatus of Example 15, the anchoring portion includes a membranous member disposed around a portion of the stent element.

[0022] In another example ("Example 17") that is further than the device of any of Examples 15-16, the device also includes a restriction portion, which includes a restriction diaphragm component surrounding a portion of the stent element, and the restriction diaphragm component is configured to restrict a portion of the stent element and cause the stent element to taper and reduce the diameter of the stent element from the proximal end to the distal end.

[0023] In another example ("Example 18") further than the apparatus of Example 17, the restricting membrane component is disposed at a distal end of the stent element and the anchoring portion is at a proximal end of the stent element.

[0024] In another example ("Example 19") that is further than the device of any of Examples 15-18, the stent element is configured to expand in response to pressure from the pulsating flow and to contract in response to a lack of pressure, thereby ensuring increased blood flow and pressure to the side branches throughout the cardiac cycle.

[0025] In another example ("Example 20") further than the apparatus of any of Examples 15-19, the blood vessel is the aorta and the stent element is configured to increase flow into the patient's renal artery (blood flow into the patient's renal artery) to improve renal perfusion and diuresis.

[0026] In another example ("Example 21") that is further than the device of any of Examples 15-19, the anchoring portion is configured to relatively abut against a vessel wall in the aorta and form a narrow flow lumen of between about 40% and about 80% in a catheter in the aorta distal to one or both renal arteries to alter blood flow into at least one branch vessel of the aorta.

[0027] In another example ("Example 22") that is further than the device of any of Examples 15-19, the anchoring portion is configured to relative to a vessel wall in the vena cava and form a narrow flow lumen of between about 40% and about 90% in a catheter in the vena cava distal to one or both renal veins and alter blood flow through one or both of the renal veins.

[0028] In another example ("Example 23") that is further related to the apparatus of Example 22, the stent element is configured to reduce blood pressure exiting one or both of the renal veins to promote blood flow through the kidney.

[0029] In another example ("Example 24") further than the apparatus of any of Examples 15-23, the stent element is configured to increase positive pressure on one or more branch vessels throughout the cardiac cycle.

[0030] In another example ("Example 25") further than the apparatus of any of Examples 15-24, the stent element and the anchoring portion are capturable and configured to be retrieved.

[0031] The foregoing examples are merely, and should not be construed as limiting or otherwise narrowing the scope of any inventive concept provided by the present disclosure. Although a number of examples are disclosed, other examples will become apparent to those skilled in the art from the following detailed description, which illustrates and describes illustrative examples of the present invention. Therefore, the drawings and detailed description should be considered to be illustrative in nature and not restrictive in nature. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] The accompanying drawings are used to provide a further understanding of the present disclosure, and are incorporated in and constitute a part of this specification, illustrate embodiments, and together with the description serve to explain the principles of the present disclosure.

[0033] Figure 1 Exemplary implantable medical devices according to various aspects of the present disclosure are shown.

[0034] Figure 2 Exemplary implantable medical devices according to various aspects of the present disclosure are shown.

[0035] Figure 3 An exemplary implantable medical device according to various aspects of the present disclosure is shown implanted in a patient's blood vessel.

[0036] Figure 4 A close-up view of a portion of an exemplary implantable medical device according to various aspects of the present disclosure is shown.

[0037] Figure 5 Exemplary implantable medical devices with varying limitations in accordance with various aspects of the present disclosure are shown.

[0038] Figure 6 An exemplary implantable medical device that changes in response to pulsatile flow according to various aspects of the present disclosure is shown. DETAILED DESCRIPTION

[0039] Definitions and terminology

[0040] This disclosure is not intended to be read in a limiting manner. For example, the terms used in this application should be read broadly in the context of the meanings that those skilled in the art would attribute to such terms.

[0041] With respect to imprecise terms, the terms "about" and "approximately" are used interchangeably to refer to a measurement value that includes the measurement value and also includes any measurement value that is reasonably close to the measurement value. As understood and easily determined by a person of ordinary skill in the relevant art, a measurement value that is reasonably close to the measurement value deviates from the measurement value by a relatively small amount. Such deviations may be attributed to, for example, measurement errors, differences in the measurement values ​​and / or calibration of manufacturing equipment, human errors in reading and / or setting the measurement values, fine-tuning to optimize performance and / or structural parameters in view of differences in the measurement values ​​associated with other components, specific implementation scenarios, imprecise adjustment and / or manipulation of the object by a person or machine, and / or the like. If it is determined that a person of ordinary skill in the relevant art would not easily determine the value of such a reasonable small difference, the terms "about" and "approximately" may be understood to be plus or minus 10% of the value.

[0042] Description of various embodiments

[0043] Those skilled in the art will readily appreciate that various aspects of the present invention may be implemented by any number of methods and devices configured to perform the intended functions. It should also be noted that the drawings referenced herein are not necessarily drawn to scale, but may be exaggerated to illustrate various aspects of the present disclosure, and in this regard, the drawings should not be construed as limiting.

[0044] Various aspects of the present disclosure relate to treating heart failure and / or other cardiovascular diseases such as hypertension and hypotension in patients. In some cases, the patient's condition may worsen due to the accumulation of excessive fluid (e.g., hypervolemia) in the body. The accumulation of fluid may mainly increase fluid accumulation in tissues and increase fluid and pressure in various circulations and organs. The increased fluid and pressure in the tissues and themselves or in combination with the already failing heart may further harm the patient. As discussed in further detail below, various aspects of the present disclosure relate to reducing the accumulation of excess fluid by using an implantable medical device.

[0045] Various aspects of the present disclosure relate to implantable medical devices configured to manipulate renal blood flow hemodynamics to cause a physiologically mediated therapeutic response. In some cases, the implantable medical devices discussed herein are intended to increase natural diuresis and reduce the accumulation of excess fluid by increasing blood flow to the kidneys. Through this action, the device is configured to redirect blood flow to the kidneys to reperfuse the kidneys, improve diuresis (increase fluid removal) and minimize / eliminate the effects of excessive fluid on the heart. Renal health can include the amount of damage maintained, maintained, or reduced in function by the kidney relative to the baseline renal function of the patient when healthy. In some cases, renal injury can be quantified by measuring neutrophil gelatinase-associated lipocalin (NGAL).

[0046] In some cases, an implantable medical device can achieve continuous and controlled fluid removal. As described below, the blood vessels near a patient's renal arteries are complex. More specifically, the patient's blood vessels may include side branches of the aorta in addition to the renal arteries. The implantable medical device may include a porous portion of the device or a portion that is perfusable for blood flow. In some cases, the entire device is porous or perfusable for blood flow. In addition, various portions of the implantable medical device may have a different porosity or perfusability than other portions of the implantable medical device. In each of these cases, the implantable medical device is implanted in the main vessel and is configured to change blood flow from the main vessel into the side branches.

[0047] In some cases, the implantable medical devices discussed herein can be implanted in other blood vessels. The implantable medical device can promote an increase in peripheral resistance to treat a decrease in blood pressure or resistance within the vasculature. As discussed further below, this can include implantation of an implantable medical device for treating an arteriovenous (AV) fistula.

[0048] Figure 1 An exemplary implantable medical device 100 is shown in accordance with various aspects of the present disclosure. Implantable medical device 100 is shown disposed within the vasculature of a patient. Figure 1 The vasculature of the patient shown in FIG. 1 includes the patient's heart 102, aortic root 104, superior vena cava 106, aortic arch 108, pulmonary trunk 110, descending aorta 112, celiac artery 114, superior mesenteric artery 116, renal arteries 118, 120, inferior mesenteric artery 122, abdominal aorta 124, and iliac arteries 126, 128. As shown, the implantable medical device 100 can be disposed within the aorta proximal to the renal arteries 118, 120. In addition, the implantable medical device 100 can be configured to increase blood flow into at least one of the renal arteries 118, 120 while maintaining substantially unrestricted blood flow within the aorta proximal to the renal arteries 118, 120. As shown, the implantable medical device 100 covers the superior mesenteric artery 116 while allowing less blood flow to enter the superior mesenteric artery 116 to increase blood flow into the renal arteries 118, 120. In some cases, implantable medical device 100 may be configured to restrict blood flow into an artery that is proximal to an artery targeted for increased blood flow.

[0049] In some cases, the implantable medical device 100 can be used to enhance perfusion of branch vessels from the aorta (e.g., the renal arteries 118, 120 or the iliac arteries 126, 128). The implantable medical device 100 can be adjusted to increase pressure within the aorta to increase blood flow into the branch vessels by increasing resistance to blood flow through the implantable medical device 100. In addition, the implantable medical device 100 can be configured to remain in the aorta to continuously increase perfusion.

[0050] An implantable medical device 100 configured to increase blood flow into at least one of the renal arteries 118, 120 can reduce fluid accumulation by increasing the amount of blood filtered by the kidneys. In patients with heart failure, insufficient blood flow through the kidneys due to impaired cardiac output and venous congestion can (at least in part) cause fluid overload. Using an implantable medical device 100 to increase blood flow into at least one renal artery 118, 120 can increase renal perfusion hemodynamically rather than pharmaceutically. Increased renal perfusion enhances renal filtration and thus removes fluid volume. In addition, the implantable medical device 100 can be used to enhance the performance of pharmacological treatments associated therewith. For example, pharmacological treatments (e.g., diuretics and / or hypertension medications) can be enhanced by additionally enhancing the patient's renal function.

[0051] In some cases, an implantable medical device 100 configured to increase blood flow into at least one of the renal arteries 118, 120 while maintaining substantially unrestricted blood flow in the aorta proximal to the renal arteries 118, 120 can focus blood flow into one or both of the renal arteries 118, 120. The restriction proximal to the renal arteries 118, 120 can direct blood flow to other areas supplied by the aorta, such as the celiac artery 114, the superior mesenteric artery 116, or the brain. Thus, in some cases, the implantable medical device 100 can be disposed in the patient's aorta proximal to (or overlapping with) an artery proximal to the renal arteries 118, 120. The result can be increased blood flow to at least one kidney by increasing blood flow to one or both of the renal arteries 118, 120, which can increase fluid removal from the circulation, which can alleviate fluid and pressure accumulation in various circulations and organs.

[0052] The implantable medical device 100 provides a non-drug method to increase urine production (diuresis) and / or change systemic blood pressure. Patients may experience drug resistance, inaccurate dosage or undesirable side effects. When drugs fail, water separation or hemodialysis can be used to filter fluid directly from the blood, however, these solutions are relatively invasive and disruptive to the patient's lifestyle and mobility. In addition, water separation or hemodialysis may also produce hemodynamic instability, with associated cardiovascular complications, renal injury, infection and / or the need for capital equipment.

[0053] The implantable medical device 100 can change the peripheral resistance when implanted percutaneously or surgically, temporarily or permanently, and can be adjustable to meet the needs of the patient. The implantable medical device 100 can remain in the body after implantation as long as the patient requires intervention. The implantable medical device 100 can be implanted for hours, days, or even years.

[0054] The paired branch vessels that separate from the aorta (leave the aorta) can be at an angle to the aorta, or may not be perpendicular to the aorta. In addition, the unpaired branch vessels originating from the aorta do not always branch at the same angle (e.g., the blood vessels extending away from the aorta are specific to the patient's anatomical structure). As discussed in further detail below, the implantable medical device discussed can be configured to at least partially overlap the arteries located near the renal arteries 118, 120. The implantable medical device discussed herein allows lateral blood flow to the arteries where the implantable medical device overlaps to reduce the blood flow entering these arteries. The result may be to increase the blood flow to at least one kidney by increasing the blood flow to one or both of the renal arteries 118, 120, which can increase the removal of fluid from the circulation, and this fluid removal will alleviate the fluid and pressure accumulation in various circulations and organs. The implantable medical device allows lateral blood perfusion over the length of the device to address the implantation difficulties caused by the geometry of the branch vessels in the specific patient's anatomical structure.

[0055] Figure 1 The illustrative implantable medical device 100 shown in is not intended to suggest any limitation as to the scope of use or functionality of the embodiments of the present disclosure disclosed in this document. Nor should the illustrative implantable medical device 100 be interpreted as having any dependency or requirement relating to any single component or combination of components shown therein. Furthermore, in various embodiments, Figure 1 Any one or more of the components depicted in the figures may be integrated with various other components depicted in the figures (and / or components not shown).

[0056] Figure 2 An exemplary implantable medical device 200 is shown in accordance with various aspects of the present disclosure. The implantable medical device 200 is configured to alter blood flow in a patient's blood vessel as described above. The implantable medical device 200 includes a stent element 202 and a graft component 204 attached to at least a portion of the stent element 202.

[0057] In some cases, the graft component 204 can be at least partially perfused to allow flow into the side branch while maintaining flow through the vessel. Figure 4 As described in further detail, graft component 204 can include pores configured to allow blood to flow through graft component 204. In some cases, graft component 204 includes a porous membrane configured to allow blood to flow through the membrane within a blood vessel with minimal pressure drop.

[0058] As mentioned above and referenced below Figure 3In further detail, implantable medical device 200 can be configured to be implanted in a patient's aorta and restrict or increase flow into at least one of the celiac artery, the hepatic artery, and the mesenteric artery. In certain examples, implantable medical device 200 can increase or decrease flow into branch vessels (or vessel pairs), which can include gastric arteries, splenic arteries, adrenal arteries (paired), phrenic arteries (paired), gonadal arteries (paired), lumbar arteries (paired), and sacral arteries (unpaired).

[0059] When implanted in the aorta, the device 200 is configured to redirect (redirect) blood flow to at least one of the renal arteries by diverting the fluid in the aorta. In order to achieve increased renal perfusion, the resistance to blood flow distal to the renal artery can be increased, which reduces distal perfusion. Increased renal perfusion enhances renal production and thus removes fluid volume. In some cases, the device 200 is configured to produce a fluid lumen of about 40% to about 80% stenosis (narrowing) in a catheter in the patient's aorta at least partially distal to the renal artery, and changes the blood flow (blood flow) in the branch vessels (e.g., one or both of the renal arteries) flowing to at least one aorta. In some cases, the restriction caused is between about 50% to about 70% of the nominal flow.

[0060] When implanted in the vena cava, the device 200 can increase perfusion from a branch vessel (e.g., a renal vein) that terminates in the vena cava by changing the pressure within the vena cava to change the blood flow from the branch vessel of the vena cava. In some cases, the device 200 can be configured to create a narrow flow lumen of between about 40% and about 90% in a catheter in the vena cava distal to at least one branch vessel. The use of a flow restriction device by reducing pressure in the renal vein, which will be discussed in further detail below, can increase renal perfusion hemodynamically rather than pharmacologically.

[0061] In some cases, the device 200 is disposed in a blood vessel other than the aorta or venules. In these cases, the device 200 can be configured to alter blood flow (blood flow) through the lumen to restrict blood flow in the vessel and induce a physiologically mediated therapeutic response in the patient. In some cases, the device 200 is configured to induce a physiologically mediated therapeutic response to include increasing peripheral resistance within the vessel. The device 200 can be configured to treat fistulas within the vessel, as well as increase peripheral resistance within the vessel as described in further detail below.

[0062] Figure 3 An exemplary implantable medical device 200 is shown implanted in a patient's blood vessel 300 according to various aspects of the present disclosure. In some cases, the implantable medical device 200 can be used in a method of altering blood flow 314 in a patient's blood vessel. Figure 3As shown, an implantable medical device 200 is implanted in the aorta. The implantable medical device 200, which includes a stent element 202 and a graft component 204 attached to at least a portion of the stent element 202, can be delivered to a target location in a blood vessel (e.g., the aorta). The implantable medical device 200 is configured to at least partially direct blood flow into one or more side branches 308, 310, 312 that exit (branch off) a blood vessel (aorta) 300.

[0063] In altering blood flow in a blood vessel 300, an implantable medical device 200 is delivered into the blood vessel and configured to restrict blood flow in one or more first branches 308, 310 to reduce blood flow into one or both of the first branches 308, 310, thereby increasing blood flow into one or more arteries (such as blood vessel 312) supplying an organ of the patient. In some cases, the organ is one of the patient's adrenal glands, testicles or ovaries, pancreas, intestines, appendix, liver, stomach, gallbladder, duodenum, spleen, spine, bladder, or muscle. As described in detail below, the implantable medical device 200 is configured to restrict blood flow into (one or more) first side branch vessels 308, 310, which are proximal to one or more arteries 312 supplying an organ of the patient.

[0064] In the case where the organ is a kidney, the branch into which the greater flow (more blood flow) is intended to flow is one or more renal arteries. By configuring the implantable medical device 200 in this manner, the graft component 204 and / or the stent component 202 restricts blood flow within one or more branches 308, 310 to increase blood flow into one or more arteries (such as blood vessel 312). In some cases, the blood vessel 312 can be a renal artery, wherein the flow into one or both renal arteries of the patient is increased to improve renal perfusion. In some cases, the graft component 204 and / or the stent component 202 is configured to restrict blood flow to the first side branch blood vessels 308, 310 by covering the first side branch blood vessels 308, 310 disposed proximal to the ostium of the renal artery.

[0065] To reduce blood flow into the (one or more) side branch vessels 308, 310, the perfusable portion of the implantable medical device 200 is disposed adjacent to the (one or more) first side branch vessels 308, 310. In some cases, the entire implantable device 200 is perfusable and allows blood to flow laterally. Because the implantable device 200 is in contact with the wall of the vessel 300, blood flow does not flow laterally from the implantable device 200 in each portion. The perfusable portion, i.e., the portion disposed adjacent to the first side branch vessel 308, 310, reduces the flow into the first side vessel 308, 310 by about 10%-about 20%, about 20%-about 30%, about 30%-about 40%, or any amount therebetween. In some cases, the graft component 204 is perfusable and thus controls the blood flow into the branch vessels 308, 310. The porosity of the graft component 204 can be tailored to achieve the desired flow reduction into the (one or more) vessels 308, 310. In other cases, the stent component 202 is perfusable and controls blood flow into the vessel(s) 308, 310. The stent component 202 can be braided or configured to achieve a desired flow reduction into the vessel(s) 308, 310. Further, in other cases, the combination of the graft component 204 and the stent element 202 can control flow into the vessel 308, 310. In some cases, the porosity of the graft component 204 and the braiding or configuration of the stent component 202 are tailored to achieve a desired flow reduction into the vessel(s) 308, 310. The stent component 202 can be a wire wound structure or laser cut from a tube.

[0066] In some cases, the graft component 204 of the implantable medical device 200 includes one or more porous or perfusable portions. The implantable medical device 200 can be configured such that the porous or perfusable portion of the graft component 204 of the implantable medical device 200 is disposed adjacent to one or more side branches 308, 310, 312 to direct blood flow into one or more side branches 308, 310, 312 that are distal to the branch vessels 308, 310, 312 in which the implantable medical device 200 is disposed. The implantable medical device 200 can change the pressure within the aorta to increase or decrease blood flow 314 into the side branches 308, 310, 312 (such as the renal arteries). Figure 1 120 or distal to the renal arteries 118, 120 or distal to a target branch(es) such as the iliac arteries 126, 128) may increase blood flow 314 into distal regions thereof (e.g., into the renal arteries 118, 120 and / or the iliac arteries 126, 128, depending on the placement of the implantable medical device 200).

[0067] In some cases, the implantable medical device 200 can produce long-term or chronic physiological changes in the patient. The implantable medical device 200 changes the flow into the kidneys and can produce a neurohormonal response that causes changes in the patient to move toward normal kidney function. The kidneys are feedback regulators of systemic pressure through the patient's body. The implantable medical device 200 changes the flow into the kidneys and provides a non-pharmacological means of affecting the kidneys' natural feedback mechanism to regulate systemic pressure.

[0068] By adjusting the degree of hemodynamic change in renal perfusion, patient-specific adjustments can be made to regulate blood pressure. Adjusting the aortic fluid flow rate imparted by the implantable medical device 200 can affect the renal artery pressure and / or flow rate, which in turn can manifest as a transient or persistent change in systemic blood pressure. The changes in kidney-mediated blood pressure levels caused by the implantable medical device 200 can themselves have therapeutic benefits. Likewise, the changes in kidney-mediated blood pressure levels caused by the implantable medical device 200 can be used in combination with various blood pressure medications to optimize blood pressure management on an individualized basis.

[0069] The implantable medical device 200 can block the branch proximal to the side branches 308, 310 (e.g., the renal artery) by between about 5% and about 30% to increase blood flow 314 into the kidney. The porosity of the implantable medical device 200 can be customized to achieve an increase of between about 5% and about 30% in blood flow 314 into the kidney. Figure 4 As explained in further detail, the size, location, number, and perfusability of the pores can be varied to achieve a desired blood flow.

[0070] Figure 4 2 shows a close-up view of a portion of an exemplary implantable medical device 200 according to various aspects of the present disclosure. Figure 4 As shown, the graft component 204 coupled to the stent component 202 can include pores 414 configured to allow blood to flow through the membrane. The pores 414 can be perforations or laser drilled holes in the graft component 204. The openings or pores 414 in the graft component 204 can further provide perfusion to the side branch vessels. For example, the graft component 204 can have a perfusion area with pores 414 and an exclusion area that is substantially free of pores 414.

[0071] like Figure 4As shown, graft component 204 may include additional pores 416 having a different porosity than pores 414. Additional pores 416 and pores 414 may have different sizes, shapes, and / or locations. As a result, and in some cases, graft component 404 includes a first portion having a porosity configured to direct fluid into one or more side branches exiting a blood vessel (branching from a blood vessel) of about 10%-about 20%, about 20%-about 30%, about 30%-about 40%, or any amount therebetween to improve renal perfusion and diuresis, and a second portion that is non-porous and configured to inhibit radial blood flow through the second portion. Furthermore, graft component 204 may include multiple layers having different porosities.

[0072] Figure 5 An exemplary implantable medical device 500 with varying limitations in accordance with various aspects of the present disclosure is shown. Implantable medical device 500 includes a stent element 506 and an anchoring portion 502. Implantable medical device 500 is shown disposed within a blood vessel 300 of a patient.

[0073] The stent element 506 is configured to apply an amount of restriction to alter blood flow within the vessel, thereby increasing blood flow into one or more branch vessels 308, 310 extending from the vessel 300, and in response to the Figure 6 The amount of restriction is modified by the pulsatile flow shown and discussed in further detail. The support element 506 is configured to extend in response to pressure from the pulsatile flow and to contract in response to a lack of pressure. In addition, the blood vessel 300 is the aorta, and the support element 506 is configured to increase the flow into the patient's renal artery to improve renal perfusion and diuresis. In some cases, the support element 506 is configured to extend in response to pressure from the pulsatile flow and to contract in response to a lack of pressure, thereby ensuring increased blood flow and pressure to the side branches throughout the cardiac cycle.

[0074] Anchoring portion 502 of implantable medical device 500 is configured to engage the vessel wall of blood vessel 300 and position stent element 500 within blood vessel 300. Anchoring portion 502 may include a membrane or graft component 508 that reduces the likelihood of thrombosis. The membrane or graft component 508 of anchoring portion 520 may contact the vessel wall.

[0075] In some cases, the implantable medical device 500 includes a constraining portion 504 that includes a constraining membrane component 510 disposed around a portion of the stent element 506. The constraining membrane component 510 is configured to constrain a portion of the stent element 506 and to taper the stent element and reduce the diameter of the stent element 506 from the proximal end to the distal end. As shown, the constraining membrane component 510 is disposed at the distal end of the stent element 506, and the anchoring portion 502 is disposed at the proximal end of the stent element 506.

[0076] In some cases and as shown, the stent element 506 can partially block the side branches (e.g., branches located proximal to the renal artery) 308, 310 by between about 5% and about 30% to increase blood flow into the kidney. The implantable medical device 500 can be implanted to have lateral perfusion and restrict blood flow into one or more arteries 308, 310 located proximal to the renal artery (or other arteries supplying the organ) to increase blood flow into the renal artery (or other arteries supplying the organ) that is distal to the location of the implantable medical device 500. In these cases, the stent element 506 is perfusable, as discussed in detail above.

[0077] In some cases, the anchoring portion 502 is positioned upstream of the renal artery to prevent obstruction of the "landing zone," i.e., the portion of the stent element 506 between the anchoring portion 502 and the limiting membrane member 510. In other cases, the anchoring portion 502 may be positioned below the kidney, which has the same clinical effect. The implantable medical device 500 is configured for a variety of placements that are often plagued by disease or acute arterial angulation. In addition, the limiting membrane member 510 facilitates expansion and contraction of the stent element 506.

[0078] In some cases, when the increased blood flow encounters the implantable medical device 500, there is more blood flow to the upstream side vessels due to the obstruction of blood flow by the implantable medical device 500. As the implantable medical device 500 extends, blood flow to the kidney (or other branch vessels) increases due to the restrictive diaphragm component 510 that restricts blood flow. When the implantable medical device 500 contracts and returns quickly upstream, the implantable medical device 500 also forces blood into the kidney (or other side branches) because the implantable medical device 500 directs a small amount of blood back upstream of the implantable medical device 500. As a result, the implantable medical device 500 increases the positive pressure on the kidney (or side branches) throughout the cardiac cycle. In some cases, the implantable medical device 500 can be captured or retrieved by the clinician during the procedure or at a later time.

[0079] In other cases, the stent element 506 is not perfusable and the implantable medical device 500 is not arranged as shown. In these cases, the stent element 506 can increase or decrease the fluid flow rate in the blood vessel (aorta) 300 located distal to the side branches (e.g., renal arteries) 308, 310 by between about 5% and about 30% compared to normal flow. In some cases, the stent element 506 is configured to cause a stenosis of between about 40% and about 80% of the patient's aorta at least partially distal to the side branches (e.g., renal arteries) 308, 310, and change the blood flow into one or more of the side branches (e.g., renal arteries) 308, 310, while maintaining substantially unrestricted blood flow in the blood vessel (aorta) 300 located proximal to one or more of the side branches (e.g., renal arteries) 308, 310. In some cases, the stenosis caused is between about 50% and about 70%. Clinically, measurements of ankle joint pressures, Doppler ultrasound velocities, ankle-brachial index, or other hemodynamic parameters in the lower extremity may be used to optimize the magnitude of induced stenosis while ensuring adequate limb perfusion.

[0080] When implanted in the aorta, the device 500 is configured to redirect blood flow to at least one of the renal arteries by diverting the fluid in the aorta. In order to achieve increased renal perfusion, the resistance to blood flow distal to the renal artery can be increased, which reduces distal perfusion. Increased renal perfusion enhances renal production and thus removes fluid volume. In some cases, the device 500 is configured to produce a narrow fluid lumen between about 40% and about 80% in a catheter in the patient's aorta at least partially distal to the renal artery, and changes the blood flow in the branch vessels (e.g., one or both of the renal arteries) of at least one aorta. In some cases, the restriction caused is between about 50% and about 70% of the nominal flow.

[0081] When implanted in the vena cava, the device 500 can increase perfusion from a branch vessel (e.g., a renal vein) that terminates in the vena cava by changing the pressure within the vena cava to change the blood flow from the branch vessel of the vena cava. In some cases, the device 500 can be configured to create a narrow flow lumen of between about 40% and about 90% in a catheter in the vena cava distal to at least one branch vessel. The use of a flow restriction device by reducing pressure in the renal vein, which will be discussed in further detail below, can increase renal perfusion hemodynamically rather than pharmacologically.

[0082] Figure 6 An exemplary implantable medical device 500 is shown that changes in response to pulsatile flow according to various aspects of the present disclosure. The pulsatile flow represented by the R wave in the EKG is shown adjacent to the contracting and extending implantable medical device 500. Figure 6As shown, stent element 506 of implantable medical device 500 is configured to extend in response to pressure from pulsatile flow and to contract in response to a lack of pressure. Stent element 506 applies further restriction in the extended configuration to restrict blood flow into side branch vessels proximal to the artery where increased blood flow is desired.

[0083] In some cases, patients with heart failure (such as advanced heart failure) may have an elevated sympathetic nervous system state, in part because of reduced cardiac output (blood pressure and flow in one of the two kidneys). A compensatory output of this state is to generate a signal to try to maintain cardiac output, which puts further pressure on the heart (myocardial oxygen demand). The implantable medical devices and methods including implantable medical devices discussed herein involve increasing pressure in the kidneys (mean or peak systolic pressure) to reduce stimulation of neurohormonal responses (e.g., reduction in sympathetic activation of the nervous system). The result of reducing the activation of the sympathetic nervous system by means of an implantable medical device or a method including an implantable medical device can reduce resting heart rate and blood pressure.

[0084] In addition, in some cases, patients with heart failure (such as advanced heart failure) may activate the renin-angiotensin-aldosterone system (RAAS), in part because of reduced cardiac output leading to impaired blood flow to the kidneys. The result of elevated RAAS is the generation of signals that stimulate adverse myocardial structural changes. The implantable medical devices discussed herein and methods including implantable medical devices involve increasing the pressure (mean or peak systolic pressure) in the kidneys to reduce stimulation of RAAS. The result of reducing the activation of RAAS by means of an implantable medical device or a method including an implantable medical device can be reduced sympathetic nervous system activation and weakening of adverse cardiac remodeling.

[0085] Previous studies on implantable medical devices implanted in the aorta have been used to evaluate the response of canines to induced heart failure (coronary microembolism resulting in an ejection fraction of approximately 30%). Hemodynamic conditions were observed in the test group relative to the control group, indicating improved cardiac function and reduced sympathetic nervous system tone. For example, heart rate and mean arterial pressure decreased, while contractility increased relative to the control. These comparative results were supported by positive changes in biomarkers such as pro-BNP (B-type natriuretic peptide) and NGAL compared to the control. As an example, animals with implants produced approximately 35% more urine, creatinine levels increased by approximately 21%, and serum creatinine increased by approximately 52% due to diuretic stimulation. These results indicate that implantable medical devices placed in the aorta, such as implantable medical devices that direct blood to the kidneys or restrict blood flow in the aorta distal to the renal arteries, can help reduce fluid overload and cardiac stress symptoms associated with heart failure. The device is shown to increase blood pressure proximal to the stenosis, and in doing so, increase renal perfusion pressure, thereby increasing renal perfusion. The secondary effect of the device is to reduce activation of the RAAS system. The effectiveness of the device is based on the assessment of central hemodynamics, left ventricular (LV) function, and renal function.

[0086] Furthermore, previous studies have found that induced stenosis has little effect on flow or pressure until it reaches about 40%, after which the effect is dependent on arterial diameter and blood flow rate (blood flow). However, based on the above-mentioned animal studies, it has been found that there is a threshold above which the effect increases dramatically. Based on these results, the stenosis protocol is between about 40% to about 80%, and more specifically between about 50% to about 70%. Clinically, measurements of ankle joint pressures, Doppler ultrasound velocities, or other hemodynamic parameters in the lower extremities may be used to optimize the magnitude of the induced stenosis while ensuring adequate limb perfusion.

[0087] Furthermore, in some cases, the above devices describe a restriction of the diameter of the aorta or vena cava, however, the length of the restriction portion may also affect the amount of restriction in the aorta or vena cava. Thus, the length of the restriction portion and the diameter or circumference of the restriction portion may be varied to achieve a desired stenosis or restriction percentage.

[0088] Further, the devices discussed herein can be implanted intravascularly to treat arteriovenous (AV) fistulas. The formation of AV fistulas may result in a decrease in peripheral resistance within the vascular system. Implantation of the devices discussed herein at or adjacent to the AV fistula may increase flow resistance to nominal levels and offset the decrease in peripheral resistance caused by the AV fistula. In some cases, the device is implanted distal to the AV fistula, proximal to the AV fistula, or across the AV fistula.

[0089] Examples of synthetic polymers (which can be used as graft components) include, but are not limited to, nylon, polyacrylamide, polycarbonate, polyoxymethylene, polymethyl methacrylate, polytetrafluoroethylene, polychlorotrifluoroethylene, polyvinyl chloride, polyurethane, elastomeric silicone polymers, polyethylene, polypropylene, polyurethane, polyglycolic acids, polyesters, polyamides, and mixtures, blends, and copolymers thereof are suitable for use as graft materials. In one embodiment, the graft is made of (a class of) polyesters, polyfluorocarbons, and porous or non-porous polyurethanes, such as polyethylene terephthalate, including and and polyaramids, such as The above-mentioned polyfluorocarbons are hexafluoropropylene ( or ) of polytetrafluoroethylene (PTFE). In some cases, the graft includes expanded fluorocarbon polymer (particularly PTFE) materials described in British Patent Nos. 1,355,373, 1,506,432, or 1,506,432, or in U.S. Patent Nos. 3,953,566, 4,187,390, or 5,276,276, all of which are incorporated herein by reference. Included in this class of preferred fluoropolymers are polytetrafluoroethylene (PTFE), fluorinated ethylene propylene (FEP), copolymers of tetrafluoroethylene (TFE) and perfluoro(propyl vinyl ether) (PFA), homopolymers of polytrifluorochloroethylene (PCTFE), and copolymers thereof with TFE, ethylene-chlorotrifluoroethylene (ECTFE), copolymers of ethylene-tetrafluoroethylene (ETFE), polyvinylidene fluoride (PVDF), and polyvinyl fluoride (PVF). ePTFE is particularly preferred because it is widely used in vascular prostheses. In certain embodiments, the graft includes a combination of the materials listed above. In some cases, the graft is substantially impermeable to body fluids. The substantially impermeable graft can be made of a material that is substantially impermeable to body fluids, or can be made of a permeable material that is treated or manufactured (e.g., by laminating different types of materials as described above or known in the art) to be substantially impermeable to body fluids.

[0090] Other examples of graft materials include, but are not limited to, vinylidene fluoride / hexafluoropropylene hexafluoropropylene (HFP), tetrafluoroethylene (TFE), vinylidene fluoride, 1-hydropentafluoropropylene, perfluoro(methyl vinyl ether), chlorotrifluoroethylene (CTFE), pentafluoropropylene, trifluoroethylene, hexafluoroacetone, hexafluoroisobutylene, fluorinated poly(ethylene-co-propylene) (FPEP), poly(hexafluoropropylene) (PHFP), poly(chlorotrifluoroethylene) (PCTFE), poly(vinylidene fluoride) (PVDF), poly(vinylidene fluoride-co-tetrafluoroethylene) (PVDF-TFE), poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP), poly(tetrafluoroethylene-co-hexafluoropropylene) Poly(PTFE-HFP), poly(tetrafluoroethylene-co-vinyl alcohol) (PTFE-VAL), poly(tetrafluoroethylene-co-vinyl acetate) (PTFE-VAC), poly(tetrafluoroethylene-co-propylene) (PTFEP), poly(hexafluoropropylene-co-vinyl alcohol) (PHFP-VAL), poly(ethylene-co-tetrafluoroethylene) (PETFE), poly(ethylene-co-hexafluoropropylene) (PEHFP), poly(vinylidene fluoride-co-chlorotrifluoroethylene-ethylene) (PVDF-CTFE), and combinations thereof, and other polymers and copolymers described in U.S. Publication No. 2004 / 00663805, the entire contents of which are incorporated herein by reference for all purposes. Other polyfluoropolymers include tetrafluoroethylene (TFE) / perfluoroalkyl vinyl ether (PAVE). The PAVE may be perfluoromethyl vinyl ether (PMVE), perfluoroethyl vinyl ether (PEVE), or perfluoropropyl vinyl ether (PPVE), as substantially described in U.S. Publication No. 2006 / 0198866 and U.S. Pat. No. 7,049,380, both of which are incorporated herein by reference in their entirety for all purposes. Other polymers and copolymers include: polylactides, polycaprolactone-glycolides, polyorthoesters, polyanhydrides; polyamino acids; polysaccharides; polyphosphazenes; poly(ether-ester) copolymers such as PEO-PLLA or blends thereof, polydimethylsiloxanes; poly(ethylene-vinyl acetate); acrylate-based polymers or copolymers such as poly(hydroxyethyl methyl methacrylate), polyvinyl pyrrolidone; fluorinated polymers such as polytetrafluoroethylene; cellulose esters, and any of the polymers and copolymers described in U.S. Publication No. 2004 / 0063805, the entirety of which is incorporated herein by reference.

[0091] As discussed herein, a graft component can be attached to a self-expanding stent element using a coupling member having at least one substantially flat surface, typically a flat band or strap. In some cases, the strap member is made of expanded PTFE (ePTFE) coated with an adhesive. The adhesive can be a thermoplastic adhesive. In some cases, the thermoplastic adhesive can be fluorinated ethylene propylene (FEP). More specifically, the FEP-coated side of the ePTFE can face and contact the outer surface of the self-expanding stent and the graft component, thereby attaching the self-expanding stent to the graft component. Materials and methods for attaching a stent to a graft are discussed in U.S. Patent No. 6,042,602 to Martin, which is incorporated herein by reference for all purposes.

[0092] The stent elements discussed herein can be made of a variety of biocompatible materials. These materials can include 316L stainless steel, cobalt-chromium-nickel-molybdenum-iron alloy ("cobalt-chromium"), other cobalt alloys such as L605, tantalum, nickel-titanium alloys (e.g., nitinol), or other biocompatible metals. In some cases, as discussed in detail above, the stent (and graft) can be self-expanding. The prosthesis can be capsule expandable.

[0093] Various metals, various materials such as superelastic alloys of Nitinol are suitable for these stents. The main requirement for the materials is that they are reasonably elastic even when made into very thin sheets or small diameter wires. Various stainless steels that have been physically, chemically, and otherwise treated to produce high elasticity are suitable for these stents, as are superelastic alloys such as cobalt-chromium alloys (e.g., Other metal alloys such as ), platinum / tungsten alloys, and especially nickel-titanium alloys (eg, Nitinol) are also suitable.

[0094] Various modifications and additions may be made to the exemplary embodiments discussed without departing from the scope of the present disclosure. For example, although the embodiments discussed above specify particular features, the scope of the present invention also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Therefore, the scope of the present invention is intended to cover all such substitutions, modifications and variations that fall within the scope of the claims, as well as all equivalents thereof.

Claims

1. An implantable medical device for altering blood flow in a blood vessel of a patient, the device comprising: Bracket elements; as well as and a graft component attached to at least a portion of the stent element, the graft component having a porosity configured to reduce flow into a first side branch disposed adjacent to the graft component by between 10% and 30% to increase flow or pressure at a renal artery of the patient when the implantable medical device is implanted, thereby improving renal perfusion and diuresis.

2. The device according to claim 1, characterized in that The graft component includes a porous membrane configured to allow blood to flow through the membrane with a minimal pressure drop such that flow within the blood vessel is reduced by between 10% and 30%.

3. The device according to claim 2, characterized in that The graft component includes pores configured to allow blood to flow through the porous membrane.

4. The device according to claim 3, characterized in that The holes are laser drilled holes in the graft component.

5. The device according to claim 1, characterized in that The stent elements are braided such that both the stent and the graft component reduce blood flow into the first side branch.

6. The device according to claim 1, characterized in that The graft component has a first portion that is perfused with blood flow.

7. The device according to claim 6, characterized in that The first portion includes an pore configured to allow blood to flow through the pore when the implantable medical device is implanted.

8. The device according to claim 6, characterized in that The porosity of the first portion is configured to achieve an increase in blood flow into a patient's renal artery by between 5% and 30%.

9. The device according to claim 6, characterized in that The graft component has a second portion having a different permeability to blood flow than the first portion.

10. The device according to claim 9, characterized in that The second portion is substantially non-porous.

11. The device according to claim 1, characterized in that The device is configured to be positioned proximal to a renal artery of the patient.

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