Optimized device for modifying flow in body lumen

Abstract

Optimized acute and chronic devices and methods described herein include a body cavity fluid flow regulator including an upstream nozzle and a downstream diffuser. The fluid flow regulator preferably includes one or more openings that define an entrainment region that provides a path through which additional fluid from the branch chamber (s) can be entrained into a fluid flow flowing from the upstream nozzle to the downstream diffuser. The one or more openings may extend across at least a portion of both a first diverging portion and a second diverging portion of the downstream component, wherein an average diverging angle of the first diverging portion is greater than an average diverging angle of the second diverging portion.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 491,235, filed on March 20, 2023, and U.S. Provisional Patent Application No. 63 / 383,884, filed on November 15, 2022, the entire contents of each of which are incorporated herein by reference. Technical Field

[0002] The present invention generally relates to acute and chronic devices and methods for modifying flow in body lumens, such as optimized devices and methods for creating pressure differentials and / or entraining fluids at lumens that branch from other lumens for enhancing fluid flow to treat various disorders or diseases. Background Art

[0003] Heart failure is a physiological condition in which cardiac output is insufficient to meet the needs of the body and lungs. Patients with any of the various forms of heart failure are prone to an increase in body fluids. Congestive heart failure (CHF) occurs when cardiac output is relatively low and the body becomes saturated with fluid. CHF has many possible underlying causes, including myocardial infarction, coronary artery disease, valvular disease, and myocarditis. Chronic heart failure is associated with changes in neurohormonal activation and autonomic control. Although these compensatory neurohormonal mechanisms provide valuable support to the heart under normal physiological conditions, they also play an important role in the development and subsequent progression of CHF. For example, one of the body's main compensatory mechanisms for reduced blood flow in CHF is to increase the amount of salt and water retained by the kidneys. Retaining salt and water, rather than excreting them in the urine, increases the amount of blood in the bloodstream and helps maintain blood pressure. However, an increased amount of blood also stretches the myocardium, causing the heart chambers, particularly the ventricles, to enlarge. Under a certain amount of stretch, the heart's contractions weaken, and heart failure worsens. Another compensatory mechanism is vasoconstriction of the arterial system. This mechanism, like salt and water retention, increases blood pressure to help maintain adequate perfusion.

[0004] Glomerular filtration rate (GFR), the rate at which the kidneys filter blood, is commonly used to quantify kidney function, and therefore the extent of a patient's kidney disease. Individuals with normal kidney function exhibit a GFR of at least 90 mL / min with no evidence of kidney damage. Progression of kidney disease is indicated by a decrease in GFR, with a GFR below 15 mL / min typically indicating that a patient has end-stage renal disease (ESRD), a complete inability of the kidneys to remove waste products or concentrate urine.

[0005] In addition to the increase in systemic salt and water, it has also been found that the altered capacity of the splanchnic venous vessels changes the blood volume distribution. Reduced venous capacity can cause fluid to be diverted from the venous reservoir to the effective circulating volume / splanchnic circulation, thereby increasing filling pressure. This can lead to clinical cardiac congestion.

[0006] Cardiovascular problems, such as, but not limited to, insufficient blood flow or chronic high blood pressure, can lead to fluid retention in the kidneys, chronic kidney disease, decreased GFR, renal failure, or even ESRD. For example, high blood pressure is considered the second most common cause of renal failure (after diabetes). It is estimated that high blood pressure leads to kidney damage and reduces GFR.

[0007] A transjugular intrahepatic portosystemic shunt (TIPS or TIPSS) is an artificial channel in the liver that creates a connection between the inflowing portal vein and the outflowing hepatic vein. Typically, under imaging guidance, a small metal stent is placed to keep the channel open and allow it to carry blood draining from the intestine back to the heart, while avoiding the liver. TIPS can be used to treat conditions such as portal hypertension (often caused by cirrhosis of the liver), which often leads to intestinal bleeding, life-threatening esophageal bleeding (esophageal varices), and a buildup of fluid in the abdomen (ascites), and has shown promise in treating hepatorenal syndrome. A disadvantage of TIPS is that blood that should be filtered by the liver bypasses the liver via the artificial channel, which can lead to complications.

[0008] Therefore, it is desirable to provide acute and / or chronic devices and methods to improve blood flow to prevent disease, improve body function, and / or treat conditions that would benefit from modified body fluid flow. For example, it is desirable to treat heart failure, treat high blood pressure, prevent kidney disease, improve kidney function, restore normal values of splanchnic circulation, improve liver function, enhance or replace TIPS, and / or prevent blood clots from traveling through the vasculature to sensitive areas of the body (such as the brain) to prevent stroke.

[0009] It would also be desirable to provide a flow regulator device that is effective over a wide range of blood flows. Summary of the Invention

[0010] The present invention seeks to provide acute and chronic devices and methods for modifying flow in body cavities. For example, devices and methods are provided for creating pressure differentials and / or fluid entrainment in cavities branching from other cavities to enhance or modify fluid flow for treating various disorders or diseases. For positioning, the devices can be acutely or chronically implanted in a body cavity.

[0011] The devices and methods of the present invention have a variety of applications. For example, the device can be used to reduce pressure and improve flow, thereby improving flow in narrow body cavities. It can also be used in the aortic arch to reduce peak systolic pressure in the brain or to divert emboli to other parts of the body (e.g., the legs), thereby reducing the risk of stroke. The device can also be installed in a bifurcation (e.g., in the brachiocephalic vessels) to reduce the peak pressure gradient or divert emboli with very little energy loss.

[0012] The devices and methods of the present invention have particular applications in treating blood flow to and from the kidneys. According to one embodiment, the device is configured to be installed near one of the renal arteries or in the inferior vena cava near a branch that branches to the renal veins or in one of the renal veins. When installed in the inferior vena cava or renal veins, the device can (due to the Bernoulli effect or other factors) create an area with increased blood velocity and reduced pressure in the inferior vena cava or renal veins. In this way, blood can be drawn from the kidneys into the renal veins and then into the inferior vena cava, thereby improving renal function and reducing necrotic damage to the kidneys.

[0013] When installed in or near the renal vein, the device of the present invention can improve renal function by improving the net filtration pressure, which is the glomerular capillary blood pressure minus (plasma colloid osmotic pressure + Bowman's capsule hydrostatic pressure), for example, 55 mm Hg minus (30 mm Hg + 15 mm Hg) = 10 mm Hg. Thus, the device and method of the present invention provide an improvement over existing therapies such as diuretics (although the present invention can use substances other than diuretics), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), which can have deleterious effects on renal function. When used in combination with current treatment modalities such as diuretics, the device and method of the present invention are expected to improve the response to diuretics and reduce the dose required to obtain the therapeutic benefits of such previously known therapies without the disadvantages of these existing therapies.

[0014] The devices and methods of the present invention can be used to divert blood flow from the kidneys to the inferior vena cava with minimal energy loss. For example, with minimal energy loss due to pressure drop and other fluid factors, a significantly greater increase in blood flow can be achieved. This diversion of flow from the kidneys to increase blood flow with minimal energy loss is expected to treat conditions such as heart failure and / or hypertension.

[0015] It should be noted that there is a significant difference between using an upstream nozzle without a downstream flow decelerator (such as a diffuser). If only the upstream nozzle is placed in the flow path, there is a significant energy loss downstream of the nozzle due to the sudden expansion of the flow. However, by using a downstream flow decelerator (such as a diffuser), the energy loss is significantly reduced. This brings another advantage: because the energy loss is significantly reduced, the additional flow flowing through the entrainment zone is effectively added to the flow from the upstream flow accelerator.

[0016] Furthermore, the present invention contemplates providing an optimal structure for an upstream flow accelerator when used with a downstream flow decelerator. For example, the length of the entrainment region between the upstream flow accelerator and the downstream flow decelerator should be less than a predetermined length to reduce the pressure at the entrainment region between the outlet and the inlet.

[0017] When installed in the renal artery, the device reduces the pressure applied to the kidneys. Without being bound by theory, high blood pressure can damage the blood vessels and filters in the kidneys, making it difficult to remove waste from the body. By reducing pressure in the renal artery, filtration rates improve. Although perfusion pressure may be lowered, filtration rates will increase because the kidneys function more efficiently overall.

[0018] It should be noted that the fluid flow regulator of the present invention can regulate fluid flow without any input from an external energy source (such as a fan, motor, etc.) and without any moving parts. The structure of the device of the present invention transfers energy from one cavity flow to another different cavity flow with minimal flow energy loss. Some energy loss (in the form of pressure loss and / or volume reduction) can beneficially reduce cardiac preload (i.e., filling pressure). For example, in healthy patients, the Frank-Starling mechanism stipulates that an increase in preload will increase cardiac output; however, in cases of impaired contractility (such as the case of many chronic and acute heart failure patients), this relationship is reversed so that an increase in preload can lead to a decrease in cardiac output. Therefore, it is expected to reduce the preload of heart failure patients to improve cardiac function. It is particularly expected to reduce preload in heart failure patients with reduced renal blood flow, because reduced renal blood flow can lead to fluid accumulation, thereby increasing both filling pressure and renal congestion.

[0019] According to one aspect of the present invention, a flow modulator device is provided for changing the flow of fluid through a body cavity connected to a branch cavity. The flow modulator may include an upstream component, a downstream component, and an entrainment region between the inlet of the upstream component and the outlet of the downstream component. The upstream component may have an inlet, an outlet, and a cross-sectional flow area that converges from the inlet toward the outlet to form a nozzle. The downstream component may have an entry, an exit, and a cross-sectional flow area that diverges from the inlet toward the exit to form a diffuser. In addition, the downstream component also includes a first diverging portion and a second diverging portion downstream of the first diverging portion, so that the average divergence angle of the first diverging portion is greater than the average divergence angle of the second diverging portion. The entrainment region may include one or more openings that extend across at least a portion of both the first diverging portion and the second diverging portion of the downstream component. Thus, the flow conditioner device can be configured to be positioned within a body cavity such that the nozzle accelerates a fluid stream passing through an upstream component toward a downstream component to generate a low pressure region near the entrainment region, and when the fluid stream enters the downstream component, the low pressure region entrains additional fluid into the fluid stream via the one or more openings.

[0020] The upstream component and the downstream component may be formed by a frame, and the flow conditioner device may include a coating on at least a portion of the upstream component and the downstream component, such that the one or more openings may be defined by one or more uncoated portions of the frame. The frame may define a plurality of cells. At least a portion of a distal portion of the downstream component may be uncoated, the distal portion being configured to conform to a body lumen to prevent migration of the flow conditioner device within the body lumen.

[0021] In some embodiments, the coating can be configured to tear upon application of a force to the coating to cause the flow regulator device to transition from an operable state to an inoperable state, wherein in the operable state, the nozzle accelerates the fluid flow passing through the upstream component toward the downstream component to generate a low pressure region near the entrainment region, the low pressure region entraining additional fluid into the fluid flow, and in the inoperable state, the hemodynamic effect of the flow regulator device is effectively eliminated. For example, the coating can be configured to tear upon application of a force via at least one of a cutting tool, a puncturing tool, or an energy-driven tool. Thus, the frame can be configured to transition between a contracted hourglass configuration and an expanded cylindrical configuration, wherein the contracted hourglass configuration includes the nozzle and diffuser in an operable state, and in the expanded cylindrical configuration, the fluid flow is no longer regulated by the flow regulator device in the inoperable state. The coating can include one or more weak lines, wherein the one or more weak lines are configured to promote tearing of the coating upon application of a force to the one or more weak lines, thereby promoting the transition of the frame from the contracted hourglass configuration to the expanded cylindrical configuration. In some embodiments, the frame is distorted between the sealing areas of the flow conditioner device to form a collapsed hourglass configuration, and wherein the one or more lines of weakness are disposed along the distorted portion between the sealing areas.

[0022] The frame may include a first frame forming an upstream component and a second frame forming a downstream component, such that the first frame can be coupled to the second frame via a coating. The first frame and the second frame may be biased toward an expanded cylindrical configuration. Furthermore, the coating may include one or more lines of weakness configured to facilitate tearing of the coating upon application of force to the one or more lines of weakness, thereby facilitating the transition of the first and second frames from the collapsed hourglass configuration to the expanded cylindrical configuration. The flow conditioner device may further include one or more fasteners configured to maintain the first and second frames in the collapsed hourglass configuration. The one or more fasteners may be configured to break upon application of force to the one or more fasteners, thereby facilitating the transition of the first and second frames from the collapsed hourglass configuration to the expanded cylindrical configuration. For example, the one or more fasteners may be configured to break via at least one of cutting, ablation, degradation, or balloon expansion. The distal end of the first frame may include a first set of rings configured to receive the one or more fasteners therethrough, and the proximal end of the second frame may include a second set of rings configured to receive the one or more fasteners therethrough. Furthermore, the one or more fasteners may include a first fastener configured to couple to a distal end of the first frame and a second fastener configured to couple to a proximal end of the second frame, thereby maintaining the first frame and the second frame in a collapsed hourglass configuration. Upon breaking of the one or more fasteners, the one or more fasteners may be configured to remain coupled to the first frame and / or the second frame to prevent emboli from flowing downstream of the one or more fasteners toward the flow conditioner device.

[0023] In some embodiments wherein the coating comprises one or more lines of weakness, the one or more lines of weakness are configured to facilitate tearing of the coating upon application of a force to the one or more lines of weakness, the one or more lines of weakness being disposed on the coating in such a manner that, in an inoperable state, the torn coating along the one or more lines of weakness forms one or more flap openings configured to effectively eliminate the hemodynamic effects of the flow regulating device. For example, the one or more lines of weakness may be disposed within one or more cells defined by the frame. Alternatively, the one or more lines of weakness may extend across one or more cells defined by the frame.

[0024] The one or more openings may include a plurality of openings spaced circumferentially around the entrainment region. The downstream component may include a third diverging portion downstream of the second diverging portion, such that an average divergence angle of the third diverging portion may be greater than an average divergence angle of the second diverging portion. The flow conditioner device may be configured to transition from a collapsed delivery state to an expanded deployment state within a body cavity. In the expanded deployment state, the proximal portion of the upstream component and the distal portion of the downstream component may be configured to conform to the body cavity. In some embodiments in which the upstream component and the downstream component may be formed by a frame, the flow conditioner device may include an anchor. For example, the anchor may include: a frame portion configured to couple to the frame; a pair of struts including a downstream portion extending from the frame portion and away from each other in an upstream direction and an upstream portion extending from the downstream portion and toward each other in the upstream direction; and a collar portion extending axially and radially outwardly from the frame portion in an upstream direction between the pair of struts. The collar portion may be configured to engage the body cavity in the expanded deployment state to secure the flow conditioner device within the body cavity. Thus, when the flow conditioner device transitions from the expanded deployed state to the collapsed delivery state, the pair of struts can be configured to move toward each other to collapse the loop portion radially inwardly such that the loop portion does not extend radially beyond the pair of struts.

[0025] The flow conditioner device may further include a retraction portion extending from the inlet of the upstream component and converging in an upstream direction toward the upstream end of the flow conditioner device. The retraction portion may be configured to facilitate retraction of the flow conditioner device. For example, the retraction portion may include a hook at the upstream end of the flow conditioner device, the hook being configured to be pulled to cause the upstream component to collapse. The diffuser may decelerate the fluid flow with the entrained additional fluid passing through the downstream component. Furthermore, the length of the downstream component may also be greater than the length of the upstream component. Furthermore, the average convergence angle of the upstream portion may also be greater than the average divergence angle of the downstream portion. The one or more openings may extend into the narrowest portion of the flow conditioner device.

[0026] The flow regulator device may further include an adjustment device disposed around a circumference of the upstream component adjacent to the outlet of the upstream component, such that the adjustment device can be configured to be actuated to adjust the inner diameter of the outlet in vivo. For example, the adjustment device may include an annular balloon disposed around a circumference of the upstream component adjacent to the outlet of the upstream component, and an access port fluidically coupled to the annular balloon via an inflation line. Thus, the access port can be configured to receive and discharge fluid, thereby inflating and deflating the annular balloon to adjust the inner diameter of the outlet in vivo. Alternatively, the adjustment device may include: a band disposed around a circumference of the upstream component adjacent to the outlet of the upstream component; a motor operably coupled to the band; and an external control unit operably coupled to the motor. Thus, the external control unit can be configured to actuate the motor to adjust the diameter of the band, thereby adjusting the inner diameter of the outlet in vivo.

[0027] According to another aspect of the present invention, a method for modifying fluid flow through a body lumen coupled to a branch lumen is provided. The method may include providing a flow conditioner device configured to be positioned within the body lumen such that an upstream component of the flow conditioner device is positioned in a first portion of the body lumen upstream of the branch lumen, a downstream component of the flow conditioner device is positioned in a second portion of the body lumen downstream of the branch lumen, and an entrainment region of the flow conditioner device is positioned adjacent the branch lumen, the upstream component having an inlet, an outlet, and a cross-sectional flow area converging from the inlet toward the outlet, the downstream component having an inlet, an outlet, and a cross-sectional flow area diverging from the inlet toward the outlet, and the entrainment region comprising one or more openings extending across at least a portion of both a first diverging portion of the downstream component and a second diverging portion of the downstream component, the first diverging portion having an average divergence angle greater than an average divergence angle of the second diverging portion; receiving a fluid flow through the inlet of the upstream component; and accelerating the fluid flow passing through the upstream component toward the downstream component to generate a low pressure region adjacent the entrainment region and to entrain additional fluid from the branch lumen into the fluid flow as the fluid flow enters a downstream diffuser.

[0028] For example, the upstream component can be configured to be positioned in the inferior vena cava upstream of a branch that branches to the renal vein, and the downstream component can be configured to be positioned in the inferior vena cava downstream of a branch that branches to the renal vein, so that the entrainment region is near the branch that branches to the renal vein, thereby drawing blood from the renal vein and improving renal function. In addition, drawing blood from the renal vein to improve renal function can further reduce excess fluid to treat heart failure. The flow regulator device can be configured to be delivered to the body cavity in a collapsed delivery state, and to transition from the collapsed delivery state to an expanded deployment state within the body cavity such that a proximal portion of the upstream component adapts to a first portion of the body cavity and a distal portion of the downstream component adapts to a second portion of the body cavity. The method can further include pulling a retraction portion to transition the flow regulator device to the collapsed delivery state, the retraction portion extending from an inlet of the upstream component in an upstream direction toward an upstream end of the flow regulator device.

[0029] According to another aspect of the present invention, another flow conditioner device for modifying fluid flow through a body lumen is provided, the body lumen being coupled to a branch lumen. The flow conditioner device may include: an upstream component having an inlet, an outlet, and a cross-sectional flow area converging from the inlet toward the outlet to form a nozzle; a downstream component having an inlet, an outlet, and a cross-sectional flow area diverging from the inlet toward the outlet to form a diffuser, the upstream component and the downstream component being formed by a frame; a coating disposed on at least a portion of the upstream component and the downstream component; and an entrainment region between the inlet of the upstream component and the outlet of the downstream component. The entrainment region may include one or more openings defined by one or more uncoated portions of the frame. Furthermore, the coating may be configured to tear upon application of a force to the coating, thereby transitioning the flow conditioner device from an operable state to an inoperable state. In the operable state, the nozzle accelerates a fluid flow passing through the upstream component toward the downstream component to generate a low-pressure region near the entrainment region. When the fluid flow enters the downstream component, the low-pressure region entrains additional fluid into the fluid flow through the one or more openings. In the inoperable state, the hemodynamic effect of the flow conditioner device is effectively eliminated.

[0030] The frame may define a plurality of cells, such that the frame may further include one or more connectors at one or more joints between adjacent cells of the plurality of cells. The one or more connectors may be configured to facilitate the transition of the frame from a contracted hourglass configuration to an expanded cylindrical configuration, such that a section of the frame adjacent to the one or more connectors may maintain its total length when the frame transitions from the contracted hourglass configuration to the expanded cylindrical configuration. In addition, the flow regulator device may include a retraction portion extending from the inlet of the upstream component, and a hook coupled to the retraction portion. Thus, the hook may be configured to be pulled to cause the upstream component to collapse, thereby facilitating the retraction of the flow regulator device. In addition, the downstream component may further include a first diverging portion and a second diverging portion downstream of the first diverging portion, the average divergence angle of the first diverging portion being greater than the average divergence angle of the second diverging portion, and the one or more openings may extend across at least a portion of both the first diverging portion and the second diverging portion of the downstream component.

[0031] According to another aspect of the present invention, another method for modifying fluid flow through a body lumen coupled to a branch lumen is provided. The method may include: providing a flow conditioner device configured to be positioned within the body lumen such that an upstream component of the flow conditioner device having an inlet, an outlet, and a cross-sectional flow area converging from the inlet toward the outlet is positioned in a first portion of the body lumen upstream of the branch lumen, a downstream component of the flow conditioner device having an inlet, an outlet, and a cross-sectional flow area diverging from the inlet toward the outlet is positioned in a second portion of the body lumen downstream of the branch lumen, and an entrainment region of the flow conditioner device including one or more openings is positioned adjacent to the branch lumen, the upstream component and the downstream component being formed by a frame, and at least a portion of the upstream component and the downstream component including a coating such that the one or more openings are defined by one or more uncoated portions of the frame; receiving a fluid flow through the inlet of the upstream component; and, when the flow conditioner device is in an operable state, accelerating the fluid flow passing through the upstream component toward the downstream component to generate a low pressure region adjacent to the entrainment region and entrain additional fluid from the branch lumen into the fluid flow as the fluid flow enters a downstream diffuser. Furthermore, the coating may be configured to tear upon application of a force to the coating to transition the flow regulator device from an operable state to an inoperable state, wherein the hemodynamic effects of the flow regulator device are effectively eliminated.

[0032] The method may further include applying a force to the coating to tear the coating and transition the flow conditioner device from an operable state to an inoperable state. The frame may include a collapsed hourglass configuration, the collapsed hourglass configuration including a nozzle and a diffuser in an operable state; and an expanded cylindrical configuration in an inoperable state. Thus, applying a force to the coating to tear the coating and transition the flow conditioner device from an operable state to an inoperable state may include applying a force to one or more fasteners that maintain the frame in the collapsed hourglass configuration to break the one or more fasteners. Additionally, applying a force to the one or more fasteners to break the one or more fasteners may include applying a force via at least one of cutting, ablation, degradation, or balloon expansion. In some embodiments, the frame may be twisted between one or more sealing areas to form a collapsed hourglass configuration. Thus, applying a force to the coating to tear the coating and transition the flow conditioner device from an operable state to an inoperable state may include applying a force to the coating to tear the coating along one or more lines of weakness provided on the one or more sealing areas.

[0033] In addition, applying a force to the coating to tear the coating and transition the flow regulator device from an operable state to an inoperable state may include applying a force to the coating to tear the coating along one or more lines of weakness disposed on the coating to form one or more valves configured to eliminate the hemodynamic effects of the flow regulator device. In addition, applying a force to the coating to tear the coating may include applying the force via at least one of a cutting tool, a puncturing tool, or an energy-driven tool. The method may further include adjusting the inner diameter of the outlet of the upstream component in vivo. For example, adjusting the inner diameter of the outlet of the upstream component in vivo may include inflating or deflating an annular balloon via an inlet port fluidically coupled to the annular balloon via an inflation line, the annular balloon being disposed around a circumference of the outlet of the upstream component adjacent to the upstream component. Alternatively, adjusting the inner diameter of the outlet of the upstream component in vivo may include actuating a motor operably coupled to a band to adjust the diameter of the band, the band being disposed around a circumference of the outlet of the upstream component adjacent to the upstream component. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 is a side view of a fluid flow regulator.

[0035] Figure 2A and Figure 2B is a side view of an exemplary fluid flow regulator constructed in accordance with the principles of the present invention.

[0036] Figure 2C Showing the principle of the present disclosure Figure 2B The divergence angles of the first diverging portion and the second diverging portion of the fluid flow conditioner.

[0037] Figure 3 A device according to the principles of the present disclosure is shown disposed within a body cavity coupled to a branch lumen. Figure 2A Fluid flow regulator.

[0038] Figure 4A Show and pass Figure 1 The entrained fluid flow of the fluid flow conditioner is compared to the Figure 2A Entrained fluid flow of the fluid flow conditioner.

[0039] Figure 4B yes Figure 4A Cross-sectional diagram of entrained fluid flow.

[0040] Figure 5 Show Figure 2A Frame structure of a fluid flow regulator.

[0041] Figure 6 is a graph illustrating renal function versus renal blood flow according to principles of the present disclosure.

[0042] Figure 7 is a graph showing population survival rates for patients with various glomerular filtration rates.

[0043] Figure 8A is a graph showing the effect of a flow regulator on urine output before, during, and after treatment.

[0044] Figure 8B is a graph showing the effect of a flow regulator on total urinary sodium excretion before, during, and after treatment.

[0045] Figure 9A and Figure 9B is a side view of an alternative exemplary fluid flow regulator constructed according to the principles of the present disclosure.

[0046] Figures 10A to 10C is a side view of another alternative exemplary fluid flow regulator constructed according to the principles of the present disclosure.

[0047] Figures 11A to 11C is a side view of another alternative exemplary fluid flow regulator constructed according to the principles of the present disclosure.

[0048] Figure 12A is a side view of another alternative exemplary fluid flow regulator constructed according to the principles of the present disclosure.

[0049] Figure 12B Show Figure 12A The frame structure of the fluid flow regulator before expansion.

[0050] Figure 12C Show Figure 12A The frame structure of the fluid flow regulator after expansion.

[0051] Figure 13Ais a perspective view of an unextended hook assembly for a fluid flow regulator constructed according to the principles of the present disclosure in an unassembled configuration.

[0052] Figure 13B yes Figure 13A A perspective view of the unextended hook assembly in the assembled configuration.

[0053] Figure 13C yes Figure 13A and Figure 13B Side view of the unextended hook assembly in a radially compressed configuration.

[0054] Figure 13D yes Figure 13A Upstream view of the unextended hook assembly in an unassembled configuration.

[0055] Figure 13E and Figure 13F According to the principles of this disclosure Figure 13B and Figure 13D Upstream view of the unextended hook assembly as the flow conditioner sealing area diameter changes.

[0056] Figure 14 is a side view of an elongated hook assembly constructed according to the principles of the present disclosure.

[0057] Figure 15A is a perspective view of a collapsible anchoring feature for a fluid flow regulator constructed according to the principles of the present disclosure.

[0058] Figure 15B For use with a fluid flow regulator constructed according to the principles of the present disclosure Figure 15A Side view of the foldable crepe anchoring feature.

[0059] Figure 15C For use with fluid flow regulator and retrieval tool Figure 15A and Figure 15B Side view of the foldable crepe anchoring feature.

[0060] Figure 16A is a cross-sectional view of a delivery system sheath with a fluid flow regulator retracted, constructed according to the principles of the present disclosure.

[0061] Figure 16B is deployed in the fluid flow regulator section Figure 16A Cross-sectional view of the delivery system sheath.

[0062] Figure 17A is a side view of an adjustable nozzle balloon for a fluid flow regulator constructed according to the principles of the present disclosure.

[0063] Figure 17B It is used with a fluid flow regulator placed in a body cavity Figure 17ASide view of the adjustable nozzle balloon operably coupled to a control unit.

[0064] Figure 18A is a perspective view of an adjustable nozzle strip for a fluid flow conditioner constructed according to the principles of the present disclosure.

[0065] Figure 18B For use with fluid flow regulators Figure 18A Perspective view of the adjustable nozzle strip.

[0066] Figure 18C yes Figure 18B Side view of a fluid flow regulator with an adjustable nozzle strip positioned within a body cavity, wherein the adjustable nozzle strip is operably coupled to a control unit.

[0067] Figure 19A A frame structure constructed according to the principles of the present disclosure utilizing exemplary connectors is shown in a compact configuration.

[0068] Figure 19B Show the use Figure 19A The frame structure of the connector in the expanded configuration. DETAILED DESCRIPTION

[0069] Devices and methods are provided for modifying flow in body lumens for creating pressure differentials and / or inducing entrainment of fluid from branch lumens to enhance or modify fluid flow to treat various disorders or diseases.

[0070] refer to Figure 1 , a flow conditioner 10 constructed and operated according to the principles of the present invention is provided. The flow conditioner 10 can be constructed similarly to the flow conditioners described in, for example, PCT International Patent Application Publications WO 2016 / 128983, WO 2018 / 029688, WO 2018 / 220589, WO 2019 / 097424, and WO 2020 / 109979, PCT / IB2022 / 060573, U.S. Patent Nos. 10,195,406 and 11,324,619, and U.S. Patent Application Publication No. 2022 / 0039938 (each of which is incorporated herein by reference in its entirety). For example, Figure 1 As shown, the flow regulator 10 can have an upstream component 12, a downstream component 16, and an entrainment region 14 disposed between the upstream component 12 and the downstream component 16. The flow regulator 10 is sized and shaped for implantation in a body lumen and can be compressed for delivery (e.g., percutaneously within a delivery sheath) and expanded upon deployment (e.g., self-expanding or balloon-expandable upon release from one end of a delivery sheath).

[0071] The entrainment zone 14 may be as follows Figure 1The entrainment region 14 is shown integrally formed in the downstream component 16, or optionally formed in the upstream component 12, or both. The entrainment region 14 may include one or more openings 18 that are designed to entrain fluid into the fluid flow flowing from the upstream component 12 to the downstream component 16. The upstream component 12 and the downstream component 16 create a low pressure area near the entrainment region 14 that preferably entrains fluid into the fluid flow flowing across the entrainment region 14. Fluid entrainment is caused by shear-induced turbulent flux. In accordance with the principles of the present invention, such entrainment is expected to transport blood or other body fluids to or from an area to improve organ function (e.g., from the renal vein(s) to the inferior vena cava to promote better kidney(s) function and / or from the hepatic vein(s) to the inferior vena cava to improve liver function, thereby treating disorders and / or diseases such as heart failure).

[0072] The upstream component 12 has an inlet 11 and an outlet 13, and has a cross-sectional flow area that converges in the downstream direction (e.g., from the upstream component 12 toward the downstream component 16) along part or all of the length of the upstream component 12 to form a nozzle. In this manner, the upstream component 12 accelerates the flow of fluid through the upstream component 12. The downstream component 16 has an inlet 15 and an outlet 17, and has a cross-sectional flow area that diverges in the downstream direction along part or all of the length of the downstream component 16 to form a diffuser.

[0073] like Figure 1 As shown, the downstream component 16 may include a first diverging portion 16a, a second diverging portion 16b downstream of the first diverging portion 16a, and a portion 16c downstream of the second diverging portion 16b. The average diverging angle of the second diverging portion 16b is preferably greater than the average diverging angle of the first diverging portion 16a. Figure 1 As shown, the opening 18 can extend longitudinally along a proximal portion of the first diverging portion 16a, e.g., adjacent the narrowest portion of the downstream component 16, such that the divergence angle of the entrainment zone 14 is constant along the opening 18. Portion 16c can include a proximal sealing zone that contacts the wall of the body lumen in its expanded, deployed state, and a distal portion downstream of the sealing zone that can conform to the vessel without damaging the vessel to prevent migration of the flow conditioner 10. The downstream component 16 thus decelerates fluid flow through the downstream component 16. The length of the entrainment zone 14 can be selected to create a low-pressure region adjacent to the entrainment zone 14 while minimizing pressure losses and reducing resistance to fluid flow (e.g., renal flow) from the branch lumen(s).

[0074] Now refer to Figures 2A to 2C , provides an optimized flow conditioner constructed and operated according to the principles of the present invention. Flow conditioner 100 can be constructed similarly to flow conditioner 10. For example, Figure 2Aand Figure 2B As shown, the flow regulator 100 can have an upstream component 102, a downstream component 106, and an entrainment region 104 disposed between the upstream component 102 and the downstream component 106 (e.g., disposed on at least a proximal portion of the downstream component 106). Similar to the flow regulator 10, the flow regulator 100 is sized and shaped for implantation in a body lumen and can be compressed for delivery (e.g., percutaneously delivered within a delivery sheath) and expanded upon deployment (e.g., self-expanding or balloon-expandable upon release from one end of a delivery sheath).

[0075] The entrainment region 104 may be as follows Figures 2A to 2C 104 is shown integrally formed in the downstream component 106, or optionally in the upstream component 102, or both. The entrainment region 104 may include one or more openings 108 designed to entrain fluid into the fluid flow flowing from the upstream component 102 to the downstream component 106. The upstream component 102 and the downstream component 106 create a low pressure region near the entrainment region 104, which preferably entrains fluid into the fluid flow flowing across the entrainment region 104. Fluid entrainment is caused by shear-induced turbulent flux. In accordance with the principles of the present invention, such entrainment is expected to transport blood or other body fluids to or from an area to improve organ function (e.g., from the renal vein(s) to the inferior vena cava to promote better kidney(s) function and / or from the hepatic vein(s) to the inferior vena cava to improve liver function, thereby treating disorders and / or diseases such as heart failure).

[0076] The upstream component 102 has an inlet 101 and an outlet 103, and has a cross-sectional flow area that converges in the downstream direction (e.g., from the upstream component 102 toward the downstream component 106) along part or all of the length of the upstream component 102 to form a nozzle. In this manner, the upstream component 102 accelerates the flow of fluid through the upstream component 102. The downstream component 106 has an inlet 105 and an outlet 107, and has a cross-sectional flow area that diverges in the downstream direction along part or all of the length of the downstream component 106 to form a diffuser.

[0077] like Figure 2A and Figure 2B As shown, the downstream component 106 may include a first diverging portion 106a, a second diverging portion 160b downstream of the first diverging portion 106a, a third diverging portion 106c downstream of the second diverging portion 106b, and a portion 106d downstream of the third diverging portion 106c. The average diverging angle of the first diverging portion 106a is preferably greater than the average diverging angle of the second diverging portion 106b, and the average diverging angle of the third diverging portion 106c is preferably greater than the average diverging angle of the second diverging portion 106b. For example, as shown in FIG. Figure 2CAs shown, the first diverging portion 106a has an average diverging angle α, and the second diverging portion 106b has an average diverging angle β that is smaller than the average diverging angle α. The average diverging angle α of the first diverging portion 106a may be, for example, in the range of 10-75 degrees, and the average diverging angle β of the second diverging portion 106b of the downstream component 106 may be, for example, in the range of 2-30 degrees (e.g., 3-10 degrees). Figure 2C , α is about 25 degrees and β is about 4 degrees.

[0078] like Figure 2C As shown, the openings 108 can extend longitudinally along at least a portion of the first diverging portion 106a (e.g., adjacent the narrowest portion of the downstream component 106) and at least a portion of the second diverging portion 106b such that the divergence angle of the entrainment region 104 transitions from an average divergence angle α to an average divergence angle β in the downstream direction. For example, the upstream end of the openings 108 can be positioned immediately downstream of the outlet 103 of the upstream component 102, such as at the inlet 105 of the downstream component 106. Alternatively, the upstream end of the openings 108 can be positioned, for example, 0-5 mm downstream of the outlet 103 of the upstream component 102. As described in further detail below, the average divergence angle α of the openings 108 extending along the first diverging portion 106a allows for an additional amount of entrained fluid to pass through the openings 108 as the fluid flow accelerates from the upstream component 102, through the flow conditioner 100, and through the downstream component 106.

[0079] Portion 106d may include a proximal sealing region that contacts the wall of the body lumen in its expanded, deployed state, and a distal portion downstream of the sealing region that can conform to the vessel without damaging the vessel to prevent migration of the flow conditioner 100 during, for example, a cough or other event that can cause a dramatic change in vessel diameter. Downstream component 106 thus decelerates fluid flow through downstream component 106. The length of entrainment region 104, e.g., the length of opening 108 extending along first diverging portion 106a and the length of opening 108 extending along second diverging portion 106b, can be selected to create a low-pressure region near entrainment region 104 while minimizing pressure loss and reducing resistance to fluid flow (e.g., renal flow) from the branch lumen(s). Other converging and diverging configurations suitable for use in accordance with the principles of the present invention are described herein. In addition, the present invention can also be implemented using other types of converging and diverging structures, such as Stratford slope nozzles (e.g., where the flow through the nozzle is at the edge of separation, which gives the diffuser an optimal length-to-efficiency ratio), de Laval nozzles (e.g., asymmetric hourglass shape), variable cross-sectional area nozzles and venturis, slope nozzles and venturis, etc.

[0080] The central axis of the diverging portion may be arranged to be in line with or offset from the central axis of the converging portion. Figure 2A and Figure 2B As shown, the upstream component 102 and the downstream component 106 share a common, collinear flow axis. Alternatively, the upstream component 102 may be angled relative to the downstream component 106. The upstream component 102 and the downstream component 106 may also be positioned along a continuously curved path.

[0081] The upstream component 102 and the downstream component 106 can be configured as a graft, a stent (coated or uncoated), a stent-graft (coated or uncoated), etc., and formed from a biocompatible material (such as stainless steel or nitinol). The outer contour of either the upstream component 102 or the downstream component 106 can be sealed against the inner wall of the body lumen (such as by expanding against it), or alternatively, can be non-sealing, depending on the specific application. This can be referred to as the fixation region(s).

[0082] The flow regulator 100 can be inserted into a body cavity in an antegrade or retrograde manner and can similarly be removed in an antegrade or retrograde manner. The flow regulator 100 can be used as an acute device that is removed after a few hours / days or as a chronic permanent device, or as a device that can be retracted after long-term implantation. In addition, the flow regulator 100 can also be decoupled from the delivery device and left in the patient's body for, for example, 1-5 days or preferably 3 days, after which it is retracted and removed from the patient's body. When used as an acute device, the flow regulator 100 can remain connected to the delivery / retrieval device (e.g., a sheath and / or wire / shaft) throughout the short-term implantation period to facilitate device delivery and retrieval. The flow regulator 100 can be compressible when disposed in a body cavity to allow periodic flushing of stagnant flow zones created adjacent to the flow regulator 100. For example, the diameter of the flow regulator 100 within the body cavity can be partially or completely reduced to allow blood to flow through the stagnant flow zones.

[0083] Preferably, when expanded, the flow modulator 100 is sized to contact the inner wall of the body lumen to anchor the flow modulator 100 within the lumen. Specifically, the upstream component 102 may have a fixation region sized to anchor the upstream component 102 in its expanded, deployed state within the body lumen. For example, the fixation region of the upstream component 102 may be sized to contact the inner wall of the body lumen and preferably have a diameter that is the same size as or slightly larger than the diameter of the body lumen. The fixation region of the upstream component 102 may have a constant diameter and a length suitable for anchoring the upstream component 102 within the body lumen. Similarly, the downstream component 106 may have a fixation region sized to anchor the downstream component 106 within another portion of the body lumen. For example, the fixation region of the downstream component 106 may include at least a portion of the third diverging portion 106c and / or the uncovered portion 106d of the downstream component 106. The securing region of the downstream component 106 can be sized to contact the inner wall of another portion of the body lumen and preferably has a diameter that is the same size as or slightly larger than the diameter of the portion of the body lumen. The securing region of the downstream component 106 can have a constant diameter and a length suitable for anchoring the downstream component 106 within the body lumen. Preferably, the securing regions of the upstream component 102 and the downstream component 106 are configured to seal the fluid regulator 100 within the body lumen so that fluid flows only into the fluid passage created by the fluid regulator 100 and does not flow between the securing regions of the upstream component 102 and the downstream component 106 and the vessel wall.

[0084] While the present invention is not bound by any theory, a simplified engineering explanation is now provided to aid in understanding how the upstream component 102 and the downstream component 106 operate to create a reduced pressure at the entrainment zone 104 .

[0085] The Bernoulli equation governs the relationship between fluid velocity and pressure (ignoring height differences): P = Pressure ρ = density V = speed 1 = Condition at the inlet (upstream component 102) 2 = Conditions at entrainment zone 104 Conservation of mass (same flow rate): V1·A1=V2·A2 A = flow cross section E 损失 =Energy loss

[0086] For example, if the flow conditioner 100 is installed near a kidney with the upstream component 102 in the inferior vena cava, then V1 and A1 are the velocity and flow area at the inferior vena cava, respectively.

[0087] The flow velocity (V2) at the entrainment region (V2) is designed to achieve the desired pressure reduction. For example, with a velocity of 0.5 m / s and an area ratio of 3, a suction force of approximately 6-8 mm Hg can be achieved. When deployed near the kidneys, this pressure differential is expected to improve renal function by improving renal perfusion pressure. This pressure will change due to the improved renal flow.

[0088] The applicant finds that, use the maximum length of opening 108, and make at least a portion of opening 108 extend along the first divergent portion 106a of the average divergent angle of the part that opening 108 extends along the second divergent portion 106b greater than the average divergent angle of the part that opening 108 extends, will improve the flow velocity in branch vessel (one or more) with relatively low pressure loss.Length is too long and will produce significant pressure loss, in fact in renal vein (one or more), sends fluid along the wrong direction.In addition, other structural features of downstream component improve kidney flow with low pressure loss, such as the internal diameter at the inlet of downstream component is greater than the internal diameter at the outlet of upstream component, the length of the divergent zone of downstream component is longer than the length of the convergence zone of upstream component and / or the average divergence angle of downstream component is less than the average convergence angle of upstream component.

[0089] In another example, the flow regulator 100 can be installed near a bifurcation to divert emboli away from the bifurcation. In yet another example, the flow regulator 100 can be deployed in the aortic arch to reduce peak systolic pressure.

[0090] Now refer to Figure 3 , shows a flow regulator 100 disposed in a body lumen coupled to a branch lumen according to a preferred embodiment, wherein each symbol depicts the size of the flow regulator 100. Figure 3 Dimensions are provided for an embodiment suitable for implantation in the inferior vena cava. Specifically, the inlet 101 of the upstream component 102 is configured to be positioned upstream of a branch branching to the renal vein(s), the downstream component 106 is configured to be positioned in the inferior vena cava such that the outlet 107 is downstream of the branch branching to the renal vein(s), and the entrainment region 104 is proximate to the branch branching to the renal vein(s). d1 is the diameter of the outlet 103 of the upstream component 102, which leads to the inlet 105 of the downstream component 106. For a given device resistance, d1 is selected to create a jet velocity. In the example of a chronic case, d1 may be in the range of 3.5-8 mm. In an acute case, d1 is preferably in the range of 3-7 mm. d2 is the diameter of the inlet 101 when in a deployed expanded state, and may be in the range of 12-45 mm. l1 is the length of the fixed area of the upstream component 102, and may be in the range of 5-30 mm. l2 is the total length of the upstream component 102 and may be in the range of 15-60 mm.

[0091] x1 is the length of the opening 108 extending along the first diverging portion 106a, and x2 is the length of the opening 108 extending along the second diverging portion 106b, such that the sum of x1 and x2 is the axial length of the entrainment region 104. Regarding the length of the entrainment region 104, a shorter length provides better performance to the downstream component 106, but results in lower renal flow due to greater resistance to flow from the renal vein(s) to the downstream component 106. Therefore, the length of the entrainment region 104 is preferably selected to provide improved renal flow rate while minimizing pressure loss. Preferably, x2 is greater than x1. For example, the ratio of x2:x1 can be 1:1 to 5:1.

[0092] Still refer to Figure 3 , L1 is the length of the stationary zone of downstream component 106 and can be in the range of 5-30 mm. L2 is the total length of downstream component 106. L2 is preferably greater than l2 because a diverging shape produces much higher pressure losses than a converging shape. The ratio of L2:l2 can be 1:1 to 3:1. D1 is the diameter of downstream component 106 at the downstream end of entrainment zone 104 and is preferably greater than d1. Therefore, the cross-sectional flow area at outlet 103 of upstream component 102 and inlet 105 of downstream component 106 is smaller than the cross-sectional flow area at the downstream end of entrainment zone 104 of downstream component 106. D1 is selected to receive all fluid ejected from outlet 103 as well as additional fluid entrained through opening 108. The ratio of D1:d1 can be 1:1 to 3.5:1. Furthermore, for longer lengths of entrainment zone 104, D1 should be larger to ensure that the ejected fluid from upstream component 102 is received. D2 is the diameter of the opening 107 in the deployed expanded state and can be in the range of 12-45 mm. The ratio of D2:d2 can be 1:1 to 1.75:1. For example, when D2 is 30 mm, d2 can be 20 mm.

[0093] Preferably, the divergence angle in the downstream component 106 is smaller than the convergence angle in the upstream component 102, and is expected to prevent pressure loss. Figure 3 In , α is the average divergence angle of the first diverging portion 106a of the downstream component 106 and may be, for example, in the range of 10-75 degrees, and β is the average divergence angle of the second diverging portion 106b of the downstream component 106 and may be, for example, in the range of 2-30 degrees (e.g., 3-10 degrees). Figure 3 As shown, the average divergence angle α is greater than the average divergence angle β. A rapid change in cross-sectional flow area across the first diverging portion 106a is preferred to maximize the amount of additional fluid entrained through the openings 108 along the first diverging portion 106a. As described above, the length of the openings 108 extending along the first diverging portion 106a can be less than or equal to the length of the openings 108 extending along the second diverging portion 106b.

[0094] In addition, the downstream component 106 should have a slowly varying angle of divergence in the region adjacent to and downstream of the first diverging portion 106a, along the second diverging portion 106b, because any additional pressure loss will reduce the flow velocity in the inferior vena cava and thus reduce the effectiveness of the device. The divergence angle in the second diverging portion 106b of the downstream component 106 can be constant or vary along the length of the downstream component 106. When the divergence angle varies along the length, it is preferably at its smallest angle (e.g., within a range of 5-30 degrees) at the downstream end adjacent to the first diverging portion 106a. A slowly varying cross-sectional flow area along the second diverging portion 106b is preferred to reduce flow separation and, therefore, pressure loss, because fluid velocity decreases with increasing cross-sectional flow area.

[0095] Now refer to Figure 4A and Figure 4B , providing a flow of fluid through the fluid regulator 100 compared to the flow of fluid through the fluid regulator 10. Figure 4A As shown, the IVC jet F flows from the upstream nozzle through a flow conditioner (e.g., flow conditioner 10 or flow conditioner 100) through a downstream diffuser. As the IVC jet F accelerates through the upstream nozzle and decelerates through the downstream diffuser, a low-pressure region is generated near the entrainment region (e.g., entrainment region 14 or entrainment region 104), which causes additional flow (e.g., renal blood flow) to be entrained through one or more openings in the entrainment region and into the downstream diffuser. As the downstream diffuser diverges from the inlet of the downstream diffuser along its length, for example, across the entrainment region, more renal blood flow is allowed to enter the downstream diffuser without competing for space with the IVC jet F.

[0096] For example, Figure 4A As shown, the entrained renal blood flow F1 enters the downstream diffuser of the flow conditioner 10 via one or more openings at the entrainment region 14 without competing for space with the IVC jet F. Because the entrainment region 14 of the flow conditioner 10 has a constant divergence angle along its length, the entrained renal blood flow F1 can enter the downstream diffuser and surround the IVC jet F, thereby generating a jet having a certain width (e.g., Figure 4B The “annular” flow of width w1 in FIG. 1 gradually increases through the downstream diffuser corresponding to the average divergence angle of the downstream diffuser of the flow conditioner 10 .

[0097] In contrast, because the entrainment region 104 of the flow conditioner 100 has a first average divergence angle along the first diverging portion 106 a and a second average divergence angle along the second diverging portion 106 b that is smaller than the first average divergence angle, the entrained renal blood flows F1 and F2 enter the downstream diffuser of the flow conditioner 100 via one or more openings at the entrainment region 104 without competing for space with the IVC jet F. Because the upstream portion of the entrainment region 104 has a first average divergence angle that is larger than the second average divergence angle of the downstream portion of the entrainment region 104 , the diameter of the downstream diffuser of the flow conditioner 100 at the downstream end of the first diverging portion 106 a is larger than the diameter of the downstream diffuser at the same longitudinal point along the flow conditioner 100, as shown in FIG. Figure 4A Specifically, the diameter of the downstream diffuser of the flow conditioner 100 is defined by the coated portion of the downstream component 106 having an uncoated portion defining the opening 108, as shown in FIG. Figure 4B As shown. In addition, the larger divergence angle of the first diverging portion 106a also provides an increased surface area for receiving a larger volume of side flow (e.g., renal blood flow entering from the renal pocket), which creates a larger space for the renal blood flow to enter the downstream diffuser without competing for space with the IVC jet F. Therefore, during higher renal blood flow rates, there is less resistance to the renal blood flow, thereby allowing better fluid dynamics efficiency under high renal blood flow conditions. In addition, the rapid change in the cross-sectional flow area of the opening 108 across the first diverging portion 106a adjacent to the highest velocity of the IVC jet F provides more interaction between the fluid area and the high-speed IVC jet,

[0098] This rapid change is preferred to maximize the amount of additional fluid entrained through the openings 108 along the first diverging portion 106a.

[0099] Thus, the entrained renal blood flows F1 and F2 may follow both the first diverging portion 106a and the second diverging portion 106b, enter the downstream diffuser via the one or more openings 108, and surround the IVC jet F, thereby creating a jet having a width of, for example, Figure 4B The "annular" flow having the sum of widths w1 and w2 in the downstream diffuser 100 gradually increases through the downstream diffuser corresponding to a first average divergence angle of the first diverging portion 106a of the downstream diffuser of the flow conditioner 100, and then gradually increases through the downstream diffuser corresponding to a second average divergence angle of the second diverging portion 106b of the downstream diffuser of the flow conditioner 100. Because more entrained renal blood flow enters the downstream diffuser of the flow conditioner 100 over a given length of the downstream diffuser of the flow conditioner 100 than the downstream diffuser of the flow conditioner 10, the length of the downstream diffuser of the flow conditioner 100 can be shorter than that of the downstream diffuser of the flow conditioner 10 to entrain the same amount of blood therein.

[0100] The flow regulator 100 can be formed from one or more frames and can be coated with one or more biocompatible materials. For example, the frame(s) can be formed from a metal (e.g., a shape memory metal) or an alloy or a combination thereof (e.g., a stent made of stainless steel or nitinol or a cobalt-chromium alloy). For some applications, the frame(s) can include a braided stent. In the case of more than one frame, the frames can be joined together by a suitable technique (e.g., welding). For example, the upstream component 102 and the downstream component 106 can be formed from a common frame or two frames that can be joined prior to implantation.

[0101] Now refer to Figure 5 , the flow conditioner 100 may be formed from a single frame structure 120 . Figure 5 The frame 120 is shown cut and flattened to illustrate the frame cut pattern. Illustratively, the upstream component 102 and the downstream component 106 are defined by the frame 120. The frame 120 is preferably formed from a metal tube that is laser cut to define a plurality of cells and then machined (e.g., heated) to form the shape of the flow conditioner 100. The flow conditioner 100 may be at least partially coated with a biocompatible material 122. For example, the frame 120 of the flow conditioner 100 may initially be completely coated with the biocompatible material 122, and then selected portions of the coating may be removed, for example, via cutting, melting, lasering, chemically, etc. Figure 5 As shown, the flow conditioner 100 may be only partially covered with the biocompatible material 122 such that a plurality of cells upstream of the inlet 101 , a plurality of cells forming the uncovered portion 106d , and a plurality of cells at the entrainment region 104 remain uncoated.

[0102] Specifically, the upstream component 102 can be coated with a biocompatible material 122 to define a fluid flow path through the upstream component 102 such that fluid flowing through the body cavity enters the inlet 101, is accelerated through the converging portion of the upstream component 102, and exits the outlet 103 and enters the inlet 105 of the downstream component 106, passing through the entrainment region 104 of the fluid regulator 100 having an opening 108 (e.g., an uncoated portion of the frame 120 at the entrainment region 104). A low pressure region is formed at the entrainment region 104 by the shape of the upstream component 102 and the downstream component 106. Additional fluid from the branch lumen(s) at the entrainment region 104 is entrained into the fluid flow traveling from the upstream component 102 to the downstream component 106 via the plurality of openings 108 formed by the uncoated portion at the entrainment region 104. Figure 5As shown, the frame 120 may be uncoated at evenly spaced portions extending circumferentially around the entrainment region 104 of the flow conditioner 100, thereby forming the opening 108 of the flow conditioner 100. As described above, the uncoated portions of the frame 120 forming the opening 108 may extend at least partially along both the first diverging portion 106a and the second diverging portion 106b. As will be appreciated by those skilled in the art, although Figure 5 Only three openings are shown in FIG. 1 , but the entrainment zone 104 may have fewer or more than three openings, for example, two openings, four openings, five openings, six openings, etc., which are preferably evenly spaced circumferentially around the entrainment zone 104 of the flow conditioner 100 .

[0103] The downstream component 106 may also be coated with a biocompatible material 122 to define a fluid flow path through the downstream component 106 (e.g., the first diverging portion 106a, the second diverging portion 106b, and the third diverging portion 106c) such that the fluid flow from the outlet 103 enters the downstream component 106 along with additional fluid passing through the plurality of openings 108 at the entrainment region 104, decelerates through the diverging portions of the downstream component 106, and exits the outlet 107 back into the body cavity, for example, across an uncovered portion 106d that may remain uncoated (as further described below).

[0104] The biocompatible material 122 can be a fabric and / or polymer such as expanded polytetrafluoroethylene (ePTFE), woven, knitted and / or woven polyester, polyurethane, DACRON (polyethylene terephthalate), silicone, polycarbonate polyurethane, or pericardial tissue from equine, bovine or porcine sources. The biocompatible coating can prevent or block fluid flow when applied to the frame. The order of the coupling and coating processes can be coupling first and then coating or coating first and then coupling. The biocompatible material 122 can be coupled to the frame(s) via suturing, spraying, encapsulation, electrospinning, dip molding and / or different techniques. In some embodiments, the biocompatible material 122 can be expandable, at least along certain portions of the flow regulator 100, thereby adjusting the cross-sectional area of the flow path through the flow regulator 100 in response to a pressure gradient across the flow regulator 100, as further described below.

[0105] Optionally, the flow regulator 100 can be coated with a hydrophilic, hemocompatible coating (active, such as a heparin coating, or passive), or a drug coating. Furthermore, the flow regulator 100 can be selectively coated in different regions. For example, the flow regulator 100 can include a drug coating on the sealing region (the portion of the flow regulator 100 that contacts tissue) to prevent tissue adhesion to the IVC wall, and a heparin coating on the portion of the flow regulator 100 that is in continuous contact with blood, thereby preventing thrombosis.

[0106] In a preferred embodiment, the biocompatible material 122 is fluid-impermeable. However, for some applications, these surfaces need not be impermeable, but may have a permeability low enough to substantially prevent blood from flowing through the longitudinal portion of the body cavity via any flow path other than through the flow channel defined by the inner surface of the flow regulator 100. For some applications, each of these surfaces has a permeability per unit length of less than 0.25 microns (e.g., between 0 and 0.25 microns), where the permeability per unit length is defined based on the following equation, which is based on Darcy's law: k / Δx=Vμ / Δp, where k is the permeability, Δx is the length (in meters), V is the average velocity (in meters per second), μ is the fluid viscosity (measured in Pascal-seconds), and Δp is the pressure difference measured in Pascals).

[0107] like Figure 5 As shown, the frame 120 may define a plurality of cells and may be heat set on a mandrel to form the retracted portion 126, the upstream component 102, the first diverging portion 106a, the second diverging portion 106b, and the third diverging portion 106c, and the portion 106d having the uncovered portion 132. Figure 5 As shown, the retraction portion 126 is illustratively formed from a first plurality of cells of the frame 120 upstream of the upstream component 102, for example, without a joint in the sealing area from the aperture 124 to the upstream component 102, thereby preventing flow interruption. For example, the frame 120 may include straight struts extending from the aperture 124 to the inlet 101 without any joint therebetween. The upstream component 102 is illustratively formed from a second plurality of cells, while the downstream component 106 may be formed from additional cell configurations, such as those described in U.S. Patent No. 11,324,619.

[0108] The retraction portion 126 at the proximal end of the upstream component 102 can be configured to facilitate retraction of the flow regulator 100. The retraction portion 126 may include a contraction section 128 at the upstream end of the flow regulator 100 in the expanded deployed state, where the eyelets 124 converge. The contraction section 128 allows the flow regulator 100 to remain connected to the delivery system. In the expanded deployed state, the cross-sectional area of the retraction portion 126 converges from the inlet 101 to the contraction section 128, where the eyelets 124 of the retraction portion 126 are connected together near the center of the flow path. The retraction portion 126 is preferably uncoated so that the fluid flow flows across the retraction portion 126 and enters the upstream component 102 through the inlet 101. In addition, the uncoated retraction portion 126 can also optionally act as a filter, for example, to prevent thrombi and / or emboli in the blood. As described above, the total length of the downstream component 106 is preferably longer than the total length of the upstream component 102 (excluding the retraction portion 126). Therefore, the length from the inlet 101 to the outlet 103 of the upstream component 102 may be shorter than the length from the inlet 105 to the outlet 107 of the downstream component 106 .

[0109] like Figure 5 As shown, a retrieval device (e.g., a hook 130) can be coupled to the contraction section 128 to pull the retrieval portion 126 toward the delivery sheath, thereby compressing the flow regulator 100 into the delivery sheath for retrieval, as described in further detail below. The hook 130 can be coupled to the contraction section 128 as a separate component that is, for example, molded, glued, compressed, welded, etc. to the frame 120. In this way, a retractor (e.g., a hook or gooseneck snare device) can be coupled to the hook 130 to pull the retrieval portion 126 toward the delivery sheath, thereby compressing the flow regulator 100 into the sheath for retrieval. In addition, the hook 130 can be pulled in a direction away from the entrainment area 104 to partially or completely reduce the diameter of the flow regulator 100 within the body cavity. This reduction will allow any stagnant flow areas created adjacent to the flow regulator 100 to be flushed out. The flow regulator 100 can then be completely removed, repositioned and expanded within the body cavity, or expanded at a previously deployed location within the body cavity. Additionally or alternatively, the flow regulator 100 may include a retrieval portion at the distal end of the downstream component 106 to facilitate retrieval of the flow regulator 100 , such as via the jugular vein.

[0110] Advantageously, after implantation, the flexible region can change diameter in response to changes in vessel diameter, while the more rigid portion of the stent structure remains constant. For example, the maximum outer diameter of the upstream component 102 and the downstream component 106 can change diameter in response to changes in vessel diameter, while the shape of the nozzle outlet of the upstream component 102 and / or the intermediate section of the flow conditioner 100 (e.g., the first diverging portion 106a and the second diverging portion 106b) does not change. In this way, the divergence angles of the first diverging portion 106a and the second diverging portion 106b can remain constant even if the size of the vessel changes. Changes in vessel diameter can be measured using, for example, one or more sensors on the flow conditioner 100 (e.g., at the sealing areas of the upstream component 102 and the downstream component 106); imaging guidance, such as fluoroscopy; ultrasound to assess changes in diameter over time; and / or other external transmitters to measure other derived parameters that can be used to measure changes in diameter over time. Additionally, one or more sensors and / or imaging guidance may be used to measure the diameter of the nozzle and / or the velocity of the fluid through the nozzle over time.

[0111] As an additional or alternative way to increase the rigidity of the middle section of the flow conditioner 100, the struts of the frame 120 at the middle section can be wider and / or thicker than the struts of the frame 120 at the more flexible portions, as described in U.S. Patent No. 11,324,619. Additionally or alternatively, the length of the cells formed by the struts of the frame 120 can be shortened and / or the number of cells of a given length of the frame 120 can be reduced to increase rigidity. According to another aspect of the present invention, cells of different shapes (e.g., diamond or hexagonal) can be used to select the relative flexibility between the various portions of the frame. In addition, cells with a larger total void space area can be stronger than cells with a larger total working area.

[0112] In addition, the downstream end of the uncovered portion 132 of the flow regulator 100 may include one or more anchors 134 to assist in maintaining the downstream component 106 in its collapsed delivery state when exposed from a delivery sheath, as described in U.S. Patent No. 11,324,619. For example, the plurality of anchors 134 may be configured to couple to a delivery device to maintain the downstream component 106 in its collapsed delivery state when exposed from the sheath of the delivery device to a body lumen, thereby facilitating readjustment of the flow regulator 100 within the body lumen. Furthermore, the plurality of anchors 134 may serve as a downstream component retrieval portion in addition to the retrieval portion of the upstream component 102, allowing the flow regulator 100 to be retrieved from the jugular vein.

[0113] According to one aspect of the present invention, the most downstream portion of the downstream component 106 (e.g., portion 132) can form the atraumatic end of the flow regulator 100 to prevent vessel damage and flare out during device folding and to leave the distal end intact. In the expanded deployed state, the atraumatic end of portion 132 bends inwardly away from the inner wall of the body vessel. Thus, even after the downstream component 106 is in its expanded deployed state, the flow regulator 100 can be realigned within the body cavity while reducing the risk of damage to the vessel wall of the body cavity due to the distal end of the flow regulator 100. In this embodiment, the cells of the frame 120 adjacent to the atraumatic end forming portion 132 are preferably uncoated, such as Figure 5 As shown, the fluid flow is caused to exit through the outlet 107 of the downstream component 106 and flow through the uncoated bare metal frame of the atraumatic tip without additional acceleration due to the convergence of the flow paths.

[0114] The flow regulator 10 may further include one or more fixing elements of various types for fixing the flow regulator 100 within the vessel to prevent the flow regulator 100 from migrating within the vessel, as described in International PCT Patent Application Serial No. PCT / IB2022 / 060573 (the entire contents of which are incorporated herein by reference).

[0115] Furthermore, the flow regulators described herein can be used in conjunction with the external pumps and control systems described in WO 2020 / 109979 (the entire contents of which are incorporated herein by reference). For example, the external pump can be an intermittent pneumatic compression (IPC) pump or an enhanced external counterpulsation (EECP) pump (e.g., The device is available from ACI Medical, San Marcos, California. The pump can be programmed to simulate the natural pumping action of the calf and / or foot while walking to mobilize blood in the deep veins of the leg, thereby reducing deep vein thrombosis. In addition, the pump can provide power to the flow regulator. The external pump and control system can be fully mobile and / or battery-operated. For example, the external pump and control system can be worn by the patient, for example, around the patient's leg.

[0116] The flow regulator 100 can be deployed and retracted using a delivery sheath. For example, before being placed in a vessel, the flow regulator 100 can be fully contained in the delivery sheath so that the flow regulator 100 can be delivered to the desired position in the vessel and deployed at the desired position in the vessel. When the distal end of the delivery sheath is positioned at the desired deployment position, the delivery sheath can be retracted (e.g., pulled in the upstream direction) while the flow regulator 100 remains stationary relative to the vessel. When it is desired to remove / retract the flow regulator 100, the flow regulator 100 can be, for example, retracted to its collapsed delivery state by pulling the retraction portion 126 via the hook 130, and the delivery sheath can be advanced (e.g., pushed in the downstream direction on the flow regulator 100) so that the flow regulator 100 is collapsed in the delivery sheath for removal. When the flow regulator 100 is again collapsed in the delivery sheath, the delivery sheath accommodating the flow regulator 100 can be repositioned in the vessel or removed from the vessel.

[0117] Now refer to Figure 6 , provides a graph showing improvement in renal function in response to flow regulator 10 and flow regulator 100. Figure 6 In FIG. 1 , the improvement in renal function caused by the flow regulator 10 is indicated by KF1, while the improvement in renal function caused by the flow regulator 100 is indicated by KF2. Figure 6 As shown, for the flow regulator 10, improvement in renal blood flow (RBF) is limited at very low IVC flow rates, with GFR up to approximately 45 mL / min / 1.73 m 2 With the flow regulator 100, under similar IVC flow conditions, patients can achieve improved RBF and GFR up to approximately 80 mL / min / 1.73 m 2 Thus, use of the flow regulator 100 can increase the patient population to achieve a GFR of at least 80 mL / min / 1.73 m 2 patients included.

[0118] Figure 7 A representative study of survival rates of patient populations with various GFRs is shown. Hillege, Hans L., et al. "Renal function, neurohormonal activation, and survival in patients with chronic heart failure." Circulation 102.2 (2000): 203-210. Figure 7In the present invention, most patients have a GFR above 45 mL / min, for example, 25% of patients have a GFR below 44 mL / min, 25% of patients have a GFR between 44-58 mL / min, 25% of patients have a GFR between 59-76 mL / min, and 25% of patients have a GFR above 76 mL / min. Therefore, the flow regulator described herein can improve RBF to reach a GFR range. By increasing the GFR range, the patient population will be significantly expanded because patients with low GFR face a higher risk of morbidity and mortality, such as lower survival rates.

[0119] Now refer to Figure 8A and Figure 8B , Figure 8A Graph showing improvement in urine output in response to treatment with a flow regulator, such as flow regulator 10 and flow regulator 100. Figure 8A As shown, the flow regulator effectively increased urine output by approximately 690 mL during the 24-hour treatment period. After the flow regulator was removed at the end of the 24-hour treatment period, urine output dropped to approximately the same level as before treatment. Figure 8B Improvements in natriuresis (i.e., sodium excretion through the kidneys) were shown in response to treatment with the flow regulator over a 24-hour treatment period. Figure 8B As shown, during the 24-hour treatment period using the flow regulator, urinary sodium excretion increased by approximately 46 mmol. However, after removing the flow regulator, total sodium excretion decreased to approximately 95 mmol, a decrease of approximately 56 mmol.

[0120] For example, when a flow regulator is implanted for long-term use (e.g., one month, two months, six months, one year, etc.) but only needs to be operable for a predetermined period of time, and wherein the flow regulator remains implanted within a body lumen thereafter, it may be desirable to effectively eliminate the regulation of fluid flow through the body lumen (e.g., the hemodynamic effects of the flow regulator described herein), for example, to avoid having to retract the flow regulator. As used herein, when a flow regulator is in an inoperable state, the hemodynamic effects of the flow regulator are "effectively eliminated" in the sense that the flow regulator no longer regulates flow through the body lumen as intended, although in some cases, a minimal amount of hemodynamic effects (e.g., resistance within the body lumen) may still persist due to the flow regulator remaining implanted within the body lumen in an inoperable state.

[0121] Now refer to Figure 9A and Figure 9B, provides an alternative exemplary flow regulator that operates according to the principles of the present disclosure. Flow regulator 200 can be constructed similarly to flow regulator 10 and / or flow regulator 100, except that flow regulator 200 can be transformed between an hourglass configuration for regulating fluid flow therethrough and an expanded cylindrical configuration suitable for long-term implantation when fluid flow regulation is no longer required, as described in further detail below. For example, Figure 9A As shown, the flow conditioner 200 may have an upstream portion 202, a downstream portion 206, and an entrainment region 204 disposed between the upstream portion 202 and the downstream portion 206. Similar to the flow conditioner 10 and the flow conditioner 100, the flow conditioner 200 can be sized and shaped for implantation in a body cavity and can be compressed for delivery (e.g., percutaneous delivery with a delivery sheath) and expanded upon deployment (e.g., self-expanding or balloon-expandable upon release from one end of the delivery sheath). In addition, the upstream portion 202 has an inlet 201 and an outlet 203, and has a cross-sectional flow area that converges in the downstream direction (e.g., from the upstream portion 202 toward the downstream portion 206) along part or all of the length of the upstream portion 202 to form a nozzle. In this way, the upstream portion 202 accelerates the flow of fluid through the upstream portion 202. The downstream portion 206 has an inlet 205 and an outlet 207, and has a cross-sectional flow area that diverges in the downstream direction along part or all of the length of the downstream portion 206 to form a diffuser.

[0122] The entrainment region 204 may include one or more openings 208 designed to entrain fluid into the fluid flow flowing from the upstream portion 202 to the downstream portion 206. Specifically, the fluid flow through the upstream portion 202 to the downstream portion 206 creates a low-pressure region near the entrainment region 204, which entrains fluid into the fluid flow flowing across the entrainment region 204. Fluid entrainment is caused by shear-induced turbulent flux. In accordance with the principles of the present invention, this entrainment is expected to transport blood or other bodily fluids to or from a region to improve organ function (e.g., from the renal vein(s) to the inferior vena cava to promote better kidney(s) function and / or from the hepatic vein(s) to the inferior vena cava to improve liver function, thereby treating disorders and / or diseases such as heart failure).

[0123] like Figure 9AAs shown, the opening 208 can extend longitudinally along at least a portion of the downstream portion 206 (e.g., originating adjacent to the narrowest portion of the downstream portion 206 and extending along at least a portion of the downstream portion 206). For example, the upstream end of the opening 208 can be positioned immediately downstream of the outlet 203 of the upstream portion 202, for example, at the inlet 205 of the downstream portion 206. Alternatively, the upstream end of the opening 208 can be positioned, for example, 0-5 mm downstream of the outlet 203 of the upstream portion 202. The upstream portion 202 can include a distal sealing region that contacts the wall of the body lumen in its expanded, deployed state, and a portion upstream of the sealing region that can conform to the vessel without damaging the vessel to prevent migration of the flow conditioner 200 during, for example, a cough or other event that can cause a dramatic change in vessel diameter. The downstream portion 206 can similarly include a proximal sealing region that contacts the wall of the body lumen in its expanded, deployed state, and a portion downstream of the sealing region.

[0124] The flow regulator 200 can be configured as a graft, stent, stent graft, or the like, and formed from a biocompatible material such as stainless steel or nitinol. For example, the flow regulator 200 can be formed from one or more wire frames and a polymer coating. Unlike the flow regulators 10 and 100, the flow regulator 200 can be configured to move from an hourglass configuration (e.g., Figure 9A ) into a cylindrical configuration (e.g., Figure 9B ), the hourglass configuration provides fluid regulation through the body cavity, and in the cylindrical configuration, the flow regulator 200 expands to fit the inner diameter of the body cavity in which the flow regulator 200 is disposed, thereby not obstructing the flow of fluid through the body cavity in which the flow regulator 200 is disposed. The cylindrical configuration can eliminate entrainment associated with the hourglass configuration. This can be advantageous for flow regulators that are implanted for long-term use (e.g., one month, two months, six months, one year, etc.) that are configured to be operable for a predetermined period of time and thereafter remain implanted in the body cavity, for example, to avoid having to retrieve the flow regulator or in case treatment is no longer required.

[0125] For example, Figure 9A and Figure 9B As shown, the flow conditioner 200 may be formed from a first frame portion 210a forming the upstream portion 202 and a second frame portion 210b forming the downstream portion 206, wherein the second frame portion 210b is not directly coupled to the first frame portion 210a. Figure 9A and Figure 9BAs shown, the frame forming the flow conditioner 200 can include a gap between a first frame portion 210a and a second frame portion 210b. The polymer coating 212 can cover the entire flow conditioner 200 (except at the opening 208) such that the polymer coating 212 extends across the gap between the first frame portion 210a and the second frame portion 210b, thereby forming the flow conditioner 200.

[0126] For example, the first frame portion 210a and the second frame portion 210b can be formed into a cylindrical configuration (e.g., heat set into a cylindrical configuration) and then manipulated into an hourglass configuration, wherein the first frame portion 210a forms a nozzle and the second frame portion 210b forms a diffuser. The polymer coating 212 can then be applied to the first frame portion 210a and the second frame portion 210b in the hourglass configuration so that the flow conditioner 200 is maintained in the hourglass configuration. In some embodiments, the flow conditioner 200 can be maintained in the hourglass configuration via one or more fasteners (e.g., fasteners 216a, 216b, such as wire or filament) that are disposed around (or within or inside) the polymer coating 212 at the stent junction at the inlet 205 of the downstream portion 206 and / or the stent junction at the outlet 203 of the upstream portion 202, such as Figure 9A As shown, when the fasteners 216a, 21b are released / broken, the first frame portion 210a and the second frame portion 210b can return to the heat-set cylindrical configuration, as shown. Figure 9B As shown. Fasteners 216a, 216b can be secured to one or all of the bracket joints in the nozzle portion of the flow regulator 200, such that if the fasteners 216a, 216b are released / broken, for example, due to balloon expansion, the fasteners can remain attached to the first frame portion 210a, thereby preventing the fasteners 216a, 216b from flowing downstream emboli. Alternatively, the flow regulator 200 may not require fasteners for maintaining the flow regulator 200 in the hourglass configuration, such that the polymer coating 212 alone may be sufficient to maintain the flow regulator 200 in the hourglass configuration.

[0127] The polymer coating 212 may also include soft points, e.g., lines of weakness (one or more) 214, to facilitate expansion of the flow regulator 200 into a cylindrical configuration. Because the polymer coating 212 does not have a surface suitable for a cylindrical configuration, the lines of weakness 214 may separate or tear when expanding into the cylindrical configuration. For example, when the fasteners 216a, 216b are released / broken (e.g., via cutting, ablation, degradation, balloon expansion within the lumen of the flow regulator 200), the polymer coating 212 may tear along the lines of weakness (one or more) 214 to allow the flow regulator 200 to transition into the cylindrical configuration. Alternatively, the lines of weakness 214 may be manually separated (e.g., punctured, torn, scored, etc.) prior to removing the fasteners 216a, 216b, such that once the fasteners (one or more) 216a, 216b are released, the flow regulator 200 naturally expands into the cylindrical configuration. The number of lines of weakness 214 can be selected based on the number of cells in the circumferential direction of the first frame portion 210a and the second frame portion 210b and based on the frame design. For example, the polymer coating 212 can include one or more lines of weakness per cell, or alternatively, every other cell in the circumferential direction can include a line of weakness.

[0128] Because the length of the flow regulator 200 can change when transitioning from the hourglass configuration to the cylindrical configuration (e.g., due to an increase in diameter along the length of the flow regulator 200), the polymer coating 200 can split circumferentially to separate the first frame portion 210a and the second frame portion 210b, so that the separated components are maintained in place within the body cavity via their respective sealing areas (as described above). In addition, due to the large tearing of the polymer coating 212 when the flow regulator 200 transitions from the hourglass configuration to the cylindrical configuration, the remaining polymer coating on the first frame portion 210a and the second frame portion 210b can not block the flow of fluid from the branch vessel (e.g., the renal vein) into the body cavity (e.g., the IVC). Therefore, when the flow regulator 200 is implanted in the IVC in the cylindrical configuration, most of the renal ostia will be unblocked by the remaining polymer coating on the frame of the flow regulator 200.

[0129] Now refer to Figures 10A to 10C , the first frame portion 210a and / or the second frame portion 210b may further include one or more rings configured to receive and secure one or more fasteners to maintain the flow conditioner 200 in the hourglass configuration. For example, the downstream end of the first frame portion 210a may include a first set of rings 218a, while the upstream end of the second frame portion 210b may include a second set of rings 218b, such as Figure 10A Thus, ring 218a and ring 218b can be configured to receive and secure fastener 216a and fastener 216b, respectively. Figure 10BAs shown, a single fastener 216 can be used to secure the first frame portion 210a to the second frame portion 210b via the ring 218a and the ring 218b so that the gap between the first frame portion 210a and the second frame portion 210b is reduced or eliminated in the hourglass configuration. Thus, when the fastener 216 is released / broken, the flow conditioner 200 can be transformed from the hourglass configuration to the cylindrical configuration, as shown. Figure 10C shown.

[0130] Now refer to Figures 11A to 11C , for a flow regulator formed from a single frame, the hemodynamic effects of the implanted flow regulator can be effectively eliminated. For example, the flow regulator 200 can be formed from a single frame (e.g., frame 210). Figure 11A As shown, the polymer coating 212 may include one or more lines of weakness 214 extending along the length of the upstream region 202 and / or the downstream region 206 of the flow regulator 200, such that the polymer coating 212 can be torn along the lines of weakness 214 upon application of force to create a valve orifice (as described above) while maintaining the hourglass configuration of the flow regulator 200. The lines of weakness 214 may be formed by a plurality of micropores in the polymer coating 212. Additionally or alternatively, as Figure 11B As shown in the figure, the polymer coating 212 may include one or more weakness lines 214 extending within one or more cells of the upstream region 202 and / or downstream region 206 of the flow regulator 200, so that the polymer coating 212 can be torn along the weakness lines 214 within the one or more cells to create a valve orifice, thereby effectively eliminating the hemodynamic effect.

[0131] like Figure 11C As shown, the flow conditioner 200 may include additional openings 208 within the polymer coating 212 along either or both of the upstream portion 202 and the downstream portion 206. For example, these holes / openings may be created via a cutting or puncturing tool, or alternatively, an energy-driven tool (via, for example, heat, RF energy, etc.). The presence of the additional openings may effectively eliminate hemodynamic effects, and therefore, entrapment, within the flow conditioner 200, such that the flow conditioner 200 functions solely as a stent or stent-like device.

[0132] Now refer to 12A to 12C , the flow conditioner 200 may twist between the sealing areas at the upstream and downstream ends of the flow conditioner 200 . Figure 12A The twisted flow conditioner 200 shown may allow the flow conditioner 200 to more easily expand from the hourglass configuration to the cylindrical configuration. Figure 12BAs shown, the line of weakness (one or more) 214 can be formed in the center of the flow conditioner 200 along the twist. For example, the line of weakness (one or more) 214 can be provided in one or more cells extending continuously along the twist between the sealing areas on the polymer coating 212. When transitioning from the hourglass configuration to the cylindrical configuration, the polymer coating 212 can separate along the line of weakness (one or more) 214 to compensate for the increased surface area of the polymer coating 212, such as Figure 12C shown.

[0133] Now refer to 13A to 13F The flow conditioner 200 may further include a hook assembly 220 that is attached to the upstream portion 202 and / or the downstream portion 206 to facilitate placement and / or removal of the flow conditioner 200. Figure 13A and Figure 13D As shown, when the flow conditioner 200 is formed, the radial connector 222 can be extended from the frame 210 so that the distal end of the radial connector 222 is not connected. Figure 13A As shown, the hooked end of the radial connector 222 may not protrude from the sealing area of the flow conditioner 200, or may only minimally protrude from the sealing area of the flow conditioner 200. The radial connector 222 may then be secured to the hook 224 under tension to form the hook assembly 220, as shown. Figure 13B and Figure 13C As shown. Optionally, in some embodiments, the hooked end of the radial connector may at least partially extend in a downstream direction within the flow conditioner 200, such that when coupled to the hook 224, the hook 224 may be positioned downstream of the sealing area at the upstream end of the flow conditioner 200. Similarly, when the radial connector 222 extends from the downstream end of the flow conditioner 200, it may at least partially extend in an upstream direction, such that the hook 224 may be positioned upstream of the sealing area at the downstream end of the flow conditioner 200. The radial stiffness of the sealing area may be significantly greater than the radial stiffness of the radial connector 222. Therefore, when the hook 224 is assembled, the outer diameter of the flow conditioner 200 may not be significantly changed due to the tensile load of the radial connector 222. Thus, the radial connector 222 may act like a spring, such that the hook assembly 220 does not change the structure of the flow conditioner 200, for example, in response to a change in the diameter of the sealing area. In this configuration, any reduction in the diameter of the sealing zone (e.g., due to deployment in an oversized IVC) will not elongate the hook position relative to the sealing zone and the effective length of the hook will remain constant. For example, the sealing zone of the upstream portion 202 with the hook assembly 220 may be increased from an initial diameter D1 ( Figure 13E ) is reduced to the second diameter D1 ( Figure 13F ), causing the radial connector 222 to be compressed in a radially inward direction so that the hook 224 remains within the plane of the sealing area.

[0134] Alternatively, in some embodiments, the radial connector 222 may have a fixed length, such as Figure 14 Thus, additional tension placed on the radial connector 222 having a fixed length can cause the flow conditioner 200 to stretch. This stretch is represented by the following equation:

[0135] To prevent elongation, the radial connector 222 can change length under tension. For example, the radial connector 222 can lengthen under tension and shorten when the tension is released. This is necessary to maintain the position of the flow conditioner 200 within the body cavity so that the sealing area(s) remain in contact with the inner surface of the body cavity.

[0136] Now refer to Figures 15A to 15C , the flow conditioner 200 may further include an anchor 230. Figure 15A As shown, the anchor 230 can be integrally formed and can include a frame portion 232, a strut portion 234, and a loop portion 236. The frame portion 232 can be attached to an end of the frame 210. Figure 15B As shown, when the anchor(s) 230 are attached to the frame 210, the strut portions 234 of each anchor 230 extend toward each other and connect to each other so that all of the anchors 230 form a single, integral structure. The frame portion(s) 232 effectively secures the anchor(s) 230 to the frame 210 without placing the frame 210 under tension. Prior to retraction, the loop portion(s) 236 extend away from the frame 210 toward the retraction end. When tension is applied to the hook assembly 220 to retract the flow conditioner 200 (as described above), the strut portions 234 of each anchor 230 can move toward each other (as described above). Figure 15C ), thereby lowering the loop portion 236 toward the centerline of the retraction sheath and preventing it from interfering with the shaft tip so that the flow regulator 200 can be continuously inserted into the retraction sheath.

[0137] Now refer to Figure 16A and Figure 16B , a delivery sheath 240 can be provided for deploying the flow regulator 200. The flow regulator 200 can be stored within the delivery sheath 240 during delivery. The delivery sheath 240 can be configured to allow the flow regulator 200 to be shortened so that the flow regulator 200 can be partially released from the delivery sheath 240 to a partially expanded state, which can enable a more uniform release without sudden and / or uncontrolled expansion during deployment of the flow regulator 200.

[0138] Now refer to Figure 17A and Figure 17B , the diameter of the nozzle of the flow regulator 200 can be adjusted in vivo. Figure 17AAs shown, the annular balloon 250 can be disposed around the circumference of the nozzle of the flow conditioner 200 (e.g., disposed adjacent the nozzle's outlet) such that expansion of the balloon 250 radially compresses the nozzle's outlet and reduces its inner diameter. Figure 17B As shown, balloon 250 can be fluidly coupled to an access point 254 (e.g., a subcutaneous port) via an inflation line 252 for inflating / deflation of balloon 250. Thus, fluid can be introduced into balloon 250 via access point 254. As will be appreciated by one of ordinary skill in the art, other known techniques for adjusting the size of a shunt can be used to adjust the diameter of the nozzle size in vivo.

[0139] Now refer to 18A to 18C Instead of the annular balloon, the flow regulator 200 may include a band 260 for adjusting the nozzle outlet diameter in vivo. The band 260 may include a motor 262 disposed thereon. The motor 262 may be wrapped around at least a portion of the band 260 so that the motor 262 may be actuated to increase or decrease the diameter of the band 260, thereby expanding or contracting the band 260. Figure 18B As shown, the band 260 may be disposed around the circumference of the flow conditioner 200 adjacent the outlet of the nozzle. The band 260 may be configured to expand or contract based on flow data sensed by one or more sensors upstream and / or downstream of the flow conditioner 200. For example, Figure 18C As shown, the circumference of the belt 260 is selectively adjustable via an external control unit 264 operably coupled to a motor 262 of the belt 260 .

[0140] Now refer to Figure 19A and Figure 19B The frame of the flow conditioner 200 may include connectors 270 disposed at one or more bracket junctions to facilitate expansion of the flow conditioner 200 from the hourglass configuration to the cylindrical configuration (as described above). Figure 19A The connector 270 is shown in a relaxed configuration, while Figure 19B The connector 270 is shown in an expanded configuration. Thus, when the flow regulator 200 transitions from the hourglass configuration to the cylindrical configuration, a section of the strut adjacent to the connector 270 can maintain its overall length. The connector 270 can also minimize tension and / or compression forces on, for example, a blood vessel wall due to contact of the sealing area(s) of the flow regulator 200.

[0141] Although preferred illustrative embodiments of the present invention have been described above, it will be apparent to those skilled in the art that various changes and modifications may be made thereto without departing from the invention. For example, the flow regulator described herein may be installed in the inferior vena cava at a branch that branches to the hepatic vein. Thus, additional blood may be entrained from the hepatic vein into the IVC, thereby improving splanchnic circulation. Acute or chronic implantation of a flow regulator in the IVC adjacent to the hepatic vein may improve liver function and / or may replace or be used in conjunction with a TIPS procedure. Advantageously, the flow regulator improves liver flow to the inferior vena cava, thereby allowing blood to enter the liver for natural filtration (unlike a TIPS procedure in which blood bypasses the liver). Whether used with or in place of a TIPS procedure, the flow regulator is expected to treat conditions such as portal hypertension (often caused by cirrhosis of the liver), which often leads to intestinal bleeding, life-threatening esophageal bleeding (esophageal varices), and an accumulation of fluid within the abdomen (ascites) and / or hepatorenal syndrome.

[0142] Additionally or alternatively, the flow conditioners described herein can be installed in the inferior vena cava to entrain additional blood from both the renal and hepatic veins. For example, the downstream component's outlet port can be downstream of the hepatic vein, while the upstream component's inlet port is upstream of the renal vein. In one study, the average distance from the downstream renal vein to the hepatic vein was 6 cm, while the average distance from the most upstream renal vein to the most downstream renal vein was 2.5 cm, and thus a flow conditioner with a total distance of 8.5 cm between the anchoring areas of the upstream and downstream components 12, 16 can be anchored in the IVC to simultaneously improve both renal and hepatic perfusion.

[0143] In addition, the flow regulator described herein can also be installed in an aneurysm to reduce pressure at the aneurysm site and reduce the risk that the aneurysm will increase in size or rupture, and may even cause the aneurysm to decrease in size. In this case, the flow regulator is expected to provide a beneficial effect even if the aneurysm is not sealed. In addition, if there are one or more side branch lumens at or near the aneurysm site, the device will not only reduce pressure, but will also allow blood to flow to the side branches. In this application, the device of the present invention provides significant benefits compared to previously known circular stent grafts that may adversely block side branches. If there are no side branches, the device is expected to reduce pressure without increasing blood flow. Optionally, a filter can be used with the flow regulator to prevent embolic debris from flowing from the aneurysm to other blood vessels.

[0144] Any of the aforementioned embodiments of the device of the present invention can be used to divert emboli or other debris, thereby eliminating the need for an additional filtering device. One example is using an upstream component or a downstream component to divert emboli or other debris at or near the carotid artery.

[0145] While the preferred illustrative embodiments of the present invention have been described above, it will be apparent to those skilled in the art that various changes and modifications may be made thereto without departing from the present invention. The appended claims are intended to cover all such changes and modifications as fall within the true spirit and scope of the present invention.

Claims

1. A flow regulator device for modifying the flow of a fluid through a body cavity, the body cavity being coupled to a branch lumen, the flow regulator device comprising: an upstream component having an inlet, an outlet, and a cross-sectional flow area converging from the inlet toward the outlet to form a nozzle; a downstream component having an inlet, an outlet, and a cross-sectional flow area that diverges from the inlet toward the outlet to form a diffuser, the downstream component including a first diverging portion and a second diverging portion downstream of the first diverging portion, the average diverging angle of the first diverging portion being greater than the average diverging angle of the second diverging portion; as well as an entrainment region between the inlet of the upstream component and the outlet of the downstream component, the entrainment region comprising one or more openings extending across at least a portion of both the first diverging portion and the second diverging portion of the downstream component; wherein the flow conditioner device is configured to be positioned within the body cavity such that the nozzle accelerates a fluid flow passing through the upstream component toward the downstream component to generate a low pressure region proximate the entrainment region, wherein the low pressure region entrains additional fluid into the fluid flow via the one or more openings as the fluid flow enters the downstream component.

2. A flow conditioner device according to claim 1, wherein the upstream component and the downstream component are formed by a frame, and wherein the flow conditioner device includes a coating on at least a portion of the upstream component and the downstream component, and the one or more openings are defined by one or more uncoated portions of the frame. The flow conditioner device of claim 2 , wherein the frame defines a plurality of cells.

4. The flow conditioner device of claim 2, wherein at least a portion of a distal portion of the downstream component is uncoated, the distal portion being configured to conform to the body lumen to prevent migration of the flow conditioner device within the body lumen.

5. The flow conditioner device of claim 2 , wherein the coating is configured to tear upon application of a force to the coating to transition the flow conditioner device from an operable state to an inoperable state, wherein the nozzle accelerates the fluid flow passing through the upstream component toward the downstream component to generate the low pressure region near the entrainment region, the low pressure region entraining additional fluid into the fluid flow, and wherein the hemodynamic effect of the flow conditioner device is effectively eliminated in the inoperable state.

6. A flow regulator device according to claim 5, wherein the frame is configured to transition between a contracted hourglass configuration and an expanded cylindrical configuration, wherein the contracted hourglass configuration includes the nozzle and the diffuser in the operable state, and in the expanded cylindrical configuration, the fluid flow is no longer regulated by the flow regulator device in the inoperable state.

7. The flow conditioner device of claim 6, wherein the frame comprises a first frame forming the upstream component and a second frame forming the downstream component, the first frame being coupled to the second frame by the coating.

8. The flow regulator device according to claim 7 further comprises one or more fasteners, wherein the one or more fasteners are configured to maintain the first frame and the second frame in the collapsed hourglass configuration, and the one or more fasteners are configured to break when a force is applied to the one or more fasteners to facilitate the first frame and the second frame to transition from the collapsed hourglass configuration to the expanded cylindrical configuration.

9. A flow regulator device according to claim 8, wherein the coating includes one or more weakness lines, and the one or more weakness lines are configured to promote tearing of the coating when force is applied to the one or more weakness lines, thereby promoting the first frame and the second frame to transform from the contracted hourglass configuration to the expanded cylindrical configuration.

10. The flow regulator device of claim 8, wherein the one or more fasteners include a first fastener configured to couple to a distal end of the first frame, and a second fastener configured to couple to a proximal end of the second frame, thereby maintaining the first frame and the second frame in the collapsed hourglass configuration.

11. The flow conditioner device of claim 8, wherein the distal end of the first frame comprises a first set of rings configured to receive the one or more fasteners therethrough, and wherein the proximal end of the second frame comprises a second set of rings configured to receive the one or more fasteners therethrough.

12. The flow conditioner device of claim 8, wherein the one or more fasteners are configured to break via at least one of cutting, ablation, degradation, or balloon expansion.

13. The flow conditioner device of claim 8, wherein: Upon breaking of the one or more fasteners, the one or more fasteners are configured to remain coupled to the first frame and / or the second frame to prevent the one or more fasteners from embolizing flow downstream of the flow conditioner device.

14. A flow regulator device according to claim 6, wherein the coating includes one or more weakness lines, and the one or more weakness lines are configured to promote tearing of the coating when a force is applied to the one or more weakness lines, thereby promoting the frame to transform from the contracted hourglass configuration to the expanded cylindrical configuration.

15. The flow conditioner device of claim 14, wherein the frame is twisted between sealing areas of the flow conditioner device to form the collapsed hourglass configuration, and wherein the one or more lines of weakness are provided along the twist between the sealing areas.

16. The flow conditioner device of claim 7, wherein the first frame and the second frame are biased toward the expanded cylindrical configuration.

17. A flow regulator device according to claim 5, wherein the coating includes one or more weakness lines, and the one or more weakness lines are configured to promote tearing of the coating when force is applied to the one or more weakness lines, and the one or more weakness lines are arranged on the coating in such a manner that in the inoperable state, the torn coating along the one or more weakness lines forms one or more flaps, and the one or more flaps are configured to effectively eliminate the hemodynamic effect of the flow regulating device.

18. The flow conditioner device of claim 17, wherein the one or more lines of weakness are disposed within one or more cells defined by the frame.

19. The flow conditioner device of claim 17, wherein the one or more lines of weakness extend across one or more cells defined by the frame.

20. The flow conditioner device of claim 5, wherein the coating is configured to tear upon application of a force via at least one of a cutting tool, a piercing tool, or an energy-driven tool.

21. The flow conditioner device of claim 1, wherein the one or more openings comprise a plurality of openings spaced circumferentially around the entrainment zone.

22. The flow conditioner device of claim 1, wherein the downstream component comprises a third diverging portion downstream of the second diverging portion, the third diverging portion having an average diverging angle greater than an average diverging angle of the second diverging portion.

23. The flow regulator device of claim 1, wherein the flow regulator device is configured to transition from a collapsed delivery state to an expanded deployed state within the body lumen.

24. The flow conditioner device of claim 23, wherein in the expanded deployed state, the proximal portion of the upstream component and the distal portion of the downstream component are configured to conform to the body lumen.

25. The flow conditioner device of claim 23, wherein the upstream component and the downstream component are formed from a frame, the flow conditioner device comprising an anchor, the anchor comprising: a frame portion configured to be coupled to the frame; a pair of struts including downstream portions extending from the frame portion and away from each other in an upstream direction, and upstream portions extending from the downstream portions and toward each other in the upstream direction; as well as a collar portion extending axially and radially outwardly from the frame portion in the upstream direction between the pair of struts, the collar portion being configured to engage the body lumen in the expanded, deployed state to secure the flow conditioner device within the body lumen, Wherein, when the flow conditioner device transitions from the expanded deployment state to the collapsed delivery state, the pair of struts are configured to move toward each other to cause the loop portion to contract radially inwardly so that the loop portion does not extend radially beyond the pair of struts.

26. The flow conditioner device of claim 1, further comprising a retraction portion extending from the inlet of the upstream component and converging in an upstream direction toward an upstream end of the flow conditioner device, the retraction portion being configured to facilitate retraction of the flow conditioner device.

27. The flow conditioner device of claim 26, wherein the retraction portion comprises a hook at the upstream end of the flow conditioner device, the hook being configured to be pulled to collapse the upstream component.

28. The flow conditioner device of claim 1, wherein the diffuser decelerates the fluid flow with entrained additional fluid passing through the downstream component.

29. The flow conditioner device of claim 1, wherein the length of the downstream component is greater than the length of the upstream component.

30. The flow conditioner device of claim 1, wherein the average convergence angle of the upstream component is greater than the average divergence angle of the downstream component.

31. The flow conditioner device of claim 1, wherein the one or more openings extend into a narrowest portion of the flow conditioner device.

32. The flow conditioner device of claim 1, further comprising an adjustment device disposed around a circumference of the upstream component adjacent the outlet of the upstream component, the adjustment device configured to be actuated to adjust an inner diameter of the outlet in vivo.

33. The flow conditioner device of claim 32, wherein the adjustment device comprises: an annular balloon disposed around the circumference of the upstream component adjacent the outlet of the upstream component; as well as An access port is fluidly coupled to the annular balloon via an inflation line, the access port being configured to receive and discharge fluid to inflate and deflate the annular balloon to adjust the inner diameter of the outlet port in vivo.

34. The flow conditioner device of claim 32, wherein the adjustment device comprises: a band disposed about the circumference of the upstream component adjacent the outlet of the upstream component; a motor operably coupled to the belt; as well as An external control unit is operably coupled to the motor, the external control unit being configured to actuate the motor to adjust the diameter of the band, thereby adjusting the inner diameter of the outlet in vivo.

35. A method for modifying fluid flow through a body lumen coupled to a branch lumen, the method comprising: providing a flow conditioner device configured to be positioned within the body lumen such that an upstream component of the flow conditioner device is positioned in a first portion of the body lumen upstream of the branch lumen, a downstream component of the flow conditioner device is positioned in a second portion of the body lumen downstream of the branch lumen, and an entrainment region of the flow conditioner device is positioned adjacent the branch lumen, the upstream component having an inlet, an outlet, and a cross-sectional flow area converging from the inlet toward the outlet, the downstream component having an inlet, an outlet, and a cross-sectional flow area diverging from the inlet toward the outlet, and the entrainment region includes one or more openings extending across at least a portion of both a first diverging portion of the downstream component and a second diverging portion of the downstream component, an average divergence angle of the first diverging portion being greater than an average divergence angle of the second diverging portion; receiving a fluid flow through the inlet of the upstream component; as well as The fluid flow passing through the upstream component toward the downstream component is accelerated to generate a low pressure region adjacent the entrainment region and to entrain additional fluid from the branch cavity into the fluid flow as the fluid flow enters the downstream diffuser.

36. The method of claim 35, wherein the upstream component is configured to be positioned in the inferior vena cava upstream of a branch that branches to the renal vein, and the downstream component is configured to be positioned in the inferior vena cava downstream of the branch that branches to the renal vein, such that the entrainment zone is near the branch that branches to the renal vein, thereby drawing blood from the renal vein and improving renal function.

37. The method of claim 36, wherein blood is withdrawn from the renal vein to improve renal function further reducing excess fluid to treat heart failure.

38. A method according to claim 35, wherein the flow regulator device is configured to be delivered to the body cavity in a collapsed delivery state and to transition from the collapsed delivery state to an expanded deployment state within the body cavity so that the proximal portion of the upstream component is adapted to the first portion of the body cavity and the distal portion of the downstream component is adapted to the second portion of the body cavity.

39. A method according to claim 38, wherein the flow regulator device further includes a retraction portion, which extends from the inlet of the upstream component in an upstream direction toward the upstream end of the flow regulator device, and the method further includes pulling the retraction portion to cause the flow regulator device to transition toward the collapsed delivery state.

40. The method of claim 35, wherein the upstream component and the downstream component are formed by a frame, and wherein the flow conditioner device comprises a coating on at least a portion of the upstream component and the downstream component, the one or more openings being defined by one or more uncoated portions of the frame.

41. A flow conditioner device for modifying the flow of a fluid through a body lumen, the body lumen being coupled to a branch lumen, the flow conditioner device comprising: an upstream component having an inlet, an outlet, and a cross-sectional flow area converging from the inlet toward the outlet to form a nozzle; a downstream component having an inlet, an outlet, and a cross-sectional flow area diverging from the inlet toward the outlet to form a diffuser, the upstream component and the downstream component being formed by a frame; a coating disposed on at least a portion of the upstream component and the downstream component; as well as an entrainment zone between the inlet of the upstream component and the outlet of the downstream component, the entrainment zone comprising one or more openings defined by one or more uncoated portions of the frame, wherein the coating is configured to tear upon application of a force to the coating to transition the flow conditioner device from an operable state to an inoperable state, wherein in the operable state, the nozzle accelerates a fluid flow passing through the upstream component toward the downstream component to generate a low pressure region proximate the entrainment region, wherein when the fluid flow enters the downstream component, the low pressure region entrains additional fluid into the fluid flow via the one or more openings, and wherein in the inoperable state, the hemodynamic effect of the flow conditioner device is effectively eliminated.

42. A flow regulator device according to claim 41, wherein the frame is configured to transition between a contracted hourglass configuration and an expanded cylindrical configuration, wherein the contracted hourglass configuration includes the nozzle and the diffuser in the operable state, and in the expanded cylindrical configuration, the fluid flow is no longer regulated by the flow regulator device in the inoperable state.

43. The flow conditioner device of claim 42, wherein the frame comprises a first frame forming the upstream component and a second frame forming the downstream component, the first frame being coupled to the second frame by the coating.

44. The flow regulator device according to claim 43 further comprises one or more fasteners, wherein the one or more fasteners are configured to maintain the first frame and the second frame in the collapsed hourglass configuration, and the one or more fasteners are configured to break when a force is applied to the one or more fasteners to facilitate the first frame and the second frame to transition from the collapsed hourglass configuration to the expanded cylindrical configuration.

45. A flow regulator device according to claim 44, wherein the coating includes one or more weakness lines, and the one or more weakness lines are configured to promote tearing of the coating when force is applied to the one or more weakness lines, thereby promoting the first frame and the second frame to transform from the contracted hourglass configuration to the expanded cylindrical configuration.

46. A flow regulator device according to claim 44, wherein the one or more fasteners include a first fastener configured to be connected to the distal end of the first frame, and a second fastener configured to be connected to the proximal end of the second frame, thereby maintaining the first frame and the second frame in the collapsed hourglass configuration.

47. A flow regulator device according to claim 44, wherein the distal end of the first frame includes a first set of rings, the first set of rings being configured to receive the one or more fasteners therethrough, and wherein the proximal end of the second frame includes a second set of rings, the second set of rings being configured to receive the one or more fasteners therethrough.

48. The flow conditioner device of claim 44, wherein the one or more fasteners are configured to break via at least one of cutting, ablation, degradation, or balloon expansion.

49. The flow conditioner device of claim 44, wherein Upon breaking of the one or more fasteners, the one or more fasteners are configured to remain coupled to the first frame and / or the second frame to prevent the one or more fasteners from embolizing flow downstream of the flow conditioner device.

50. A flow regulator device according to claim 42, wherein the coating includes one or more weakness lines, and the one or more weakness lines are configured to promote tearing of the coating when a force is applied to the one or more weakness lines, thereby promoting the frame to transform from the contracted hourglass configuration to the expanded cylindrical configuration.

51. The flow conditioner device of claim 50, wherein the frame is twisted between sealing areas of the flow conditioner device to form the collapsed hourglass configuration, and wherein the one or more lines of weakness are provided along the twist between the sealing areas.

52. The flow conditioner device of claim 42, wherein the first frame and the second frame are biased toward the expanded cylindrical configuration.

53. A flow regulator device according to claim 42, wherein the frame defines a plurality of cells, and wherein the frame includes one or more connectors at one or more joints between adjacent cells of the plurality of cells, the one or more connectors being configured to facilitate the transition of the frame from the contracted hourglass configuration to the expanded cylindrical configuration, such that when the frame transitions from the contracted hourglass configuration to the expanded cylindrical configuration, a section of the frame adjacent to the one or more connectors maintains its total length.

54. A flow regulator device according to claim 41, wherein the coating includes one or more weakness lines, and the one or more weakness lines are configured to promote tearing of the coating when force is applied to the one or more weakness lines, and the one or more weakness lines are arranged on the coating in such a manner: in the inoperable state, the torn coating along the one or more weakness lines forms one or more flaps, and the one or more flaps are configured to effectively eliminate the hemodynamic effect of the flow regulating device.

55. The flow conditioner device of claim 54, wherein the one or more lines of weakness are disposed within one or more cells defined by the frame.

56. The flow conditioner device of claim 54, wherein the one or more lines of weakness extend across one or more cells defined by the frame.

57. The flow conditioner device of claim 41, wherein the coating is configured to tear upon application of a force via at least one of a cutting tool, a piercing tool, or an energy-driven tool.

58. The flow regulator device of claim 41, wherein the flow regulator device is configured to transition from a collapsed delivery state to an expanded deployed state within the body lumen.

59. The flow conditioner device of claim 58, further comprising an anchor, the anchor comprising: a frame portion configured to be coupled to the frame; a pair of struts including downstream portions extending from the frame portion and away from each other in an upstream direction, and upstream portions extending from the downstream portions and toward each other in the upstream direction; as well as a collar portion extending axially and radially outwardly from the frame portion in the upstream direction between the pair of struts, the collar portion being configured to engage the body lumen in the expanded, deployed state to secure the flow conditioner device within the body lumen, Wherein, when the flow conditioner device transitions from the expanded deployment state to the collapsed delivery state, the pair of struts are configured to move toward each other to cause the loop portion to contract radially inwardly so that the loop portion does not extend radially beyond the pair of struts.

60. The flow conditioner device of claim 41 , further comprising: a retrieval portion extending from the inlet of the upstream component; as well as A hook is coupled to the retrieval portion, the hook being configured to be pulled to crimp the upstream component, thereby facilitating retrieval of the flow conditioner device.

61. The flow conditioner device of claim 41, further comprising an adjustment device disposed around a circumference of the upstream component adjacent the outlet of the upstream component, the adjustment device configured to be actuated to adjust an inner diameter of the outlet in vivo.

62. The flow conditioner device of claim 61 , wherein the adjustment device comprises: an annular balloon disposed around the circumference of the upstream component adjacent the outlet of the upstream component; as well as An access port is fluidly coupled to the annular balloon via an inflation line, the access port being configured to receive and discharge fluid to inflate and deflate the annular balloon to adjust the inner diameter of the outlet port in vivo.

63. The flow conditioner device of claim 61 , wherein the adjustment device comprises: a band disposed about the circumference of the upstream component adjacent the outlet of the upstream component; a motor operably coupled to the belt; as well as An external control unit is operably coupled to the motor, the external control unit being configured to actuate the motor to adjust the diameter of the band, thereby adjusting the inner diameter of the outlet in vivo.

64. The flow conditioner device of claim 41 , wherein the downstream component comprises a first diverging portion and a second diverging portion downstream of the first diverging portion, the first diverging portion having an average diverging angle greater than the second diverging angle, and wherein the one or more openings extend across at least a portion of both the first diverging portion and the second diverging portion of the downstream component.

65. A method for modifying fluid flow through a body lumen coupled to a branch lumen, the method comprising: providing a flow conditioner device configured to be positioned within the body lumen such that an upstream component of the flow conditioner device having an inlet, an outlet, and a cross-sectional flow area converging from the inlet toward the outlet is positioned in a first portion of the body lumen upstream of the branch lumen, a downstream component of the flow conditioner device having an inlet, an outlet, and a cross-sectional flow area diverging from the inlet toward the outlet is positioned in a second portion of the body lumen downstream of the branch lumen, and an entrainment region of the flow conditioner device including one or more openings is positioned adjacent the branch lumen, the upstream component and the downstream component being formed by a frame, and at least a portion of the upstream component and the downstream component including a coating such that the one or more openings are defined by one or more uncoated portions of the frame; receiving a fluid flow through the inlet of the upstream component; as well as When the flow conditioner device is in an operable state, it accelerates the fluid flow passing through the upstream component toward the downstream component to generate a low pressure region near the entrainment region and to entrain additional fluid from the branch chamber into the fluid flow as the fluid flow enters the downstream diffuser. wherein the coating is configured to tear upon application of a force to the coating to transition the flow regulator device from the operable state to an inoperable state, wherein the hemodynamic effect of the flow regulator device is effectively eliminated.

66. The method of claim 65, further comprising applying a force to the coating to tear the coating and transition the flow conditioner device from the operable state to the inoperable state.

67. The method of claim 66, wherein the frame comprises a collapsed hourglass configuration including the nozzle and the diffuser in the operable state; and an expanded cylindrical configuration in the inoperable state.

68. A method according to claim 67, wherein applying force to the coating to tear the coating and cause the flow regulator device to transition from the operable state to the inoperable state includes applying force to one or more fasteners maintaining the frame in the collapsed hourglass configuration to break the one or more fasteners.

69. The method of claim 68, wherein applying a force to the one or more fasteners to cause the one or more fasteners to break comprises applying a force via at least one of cutting, ablation, degradation, or balloon expansion.

70. A method according to claim 67, wherein the frame is twisted between the sealing areas of the flow regulator device to form the collapsed hourglass configuration, and wherein applying a force to the coating to tear the coating and causing the flow regulator device to transition from the operable state to the inoperable state includes applying a force to the coating to tear the coating along one or more lines of weakness, wherein the one or more lines of weakness are arranged along the twisted portion between the sealing areas.

71. A method according to claim 66, wherein applying force to the coating to tear the coating and causing the flow regulator device to transition from the operable state to the inoperable state includes applying force to the coating to tear the coating along one or more lines of weakness provided on the coating to form one or more valves configured to effectively eliminate the hemodynamic effect of the flow regulator device.

72. The method of claim 66, wherein applying a force to the coating to tear the coating comprises applying a force via at least one of a cutting tool, a piercing tool, or an energy-driven tool.

73. The method of claim 65, further comprising adjusting an inner diameter of the outlet of the upstream component in vivo.

74. A method according to claim 73, wherein adjusting the inner diameter of the outlet of the upstream component in vivo includes inflating or deflating the annular balloon via an inlet port fluidically connected to the annular balloon through an inflation line, and the annular balloon is arranged around the circumference of the upstream component adjacent to the outlet of the upstream component.

75. The method of claim 73, wherein in vivo adjusting the inner diameter of the outlet of the upstream component comprises actuating a motor operably coupled to a band disposed about the circumference of the upstream component adjacent the outlet of the upstream component to adjust the diameter of the band.

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