Implantable devices for vena cava occlusion response assessments

Abstract

Systems and methods are described for determining a fluid congestion status of a subject, the method being carried out by at least one processor executing operations comprising: receiving an initial right atrial pressure for the subject; causing, over a time period, a vessel occlusion device to perform an occlusion cycle to change blood flow resistance in a blood vessel of the subject; receiving monitored readings for a right atrial pressure response to the changed blood flow resistance in the blood vessel over the time period; and determining, for the subject and based on the readings representing the right atrial pressure response, a fluid congestion status associated with a heart of the subject.

Description

IMPLANTABLE DEVICES FOR VENA CAVA OCCLUSION RESPONSE ASSESSMENTSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority benefit of U.S. Provisional Patent Application Ser. No. 63 / 673,507, filed July 19, 2024, the contents of which is herein incorporated by reference in its entirety.BACKGROUND

[0002] This disclosure relates generally to the field of medical devices and procedures, and more specifically to the field of blood flow management in blood vessels.

[0003] When a patient is suffering from chronic Congestive Heart Failure (CHF), a clinician can measure right atrial pressure (RAP) values from a pulmonary artery catheterization to evaluate the congestion status of the patient. However, these RAP readings are limited to a hospital or clinic setting and generally provide a snapshot view of hemodynamic status at the time of the measurement. Once a patient exits the hospital or clinic setting, there is no further assessment for RAP until the patient returns to the hospital or clinic to repeat the catheterization. This lack of visibility into understanding levels and excursions of RAP for a patient over time can lead to an incomplete understanding of blood volume status of the patient, which can lead to a suboptimal treatment and hospital reentry.SUMMARY

[0004] Described herein are one or more methods and / or devices to facilitate management and assessment of blood flow through and / or into one or more blood vessels and / or chambers of a heart. There is a need for new and useful systems and methods for monitoring blood flow in the venous system, modulating blood flow in the heart, and providing or withholding fluids based on assessing responses to modulating the blood flow.

[0005] In some aspects, the techniques described herein relate to an implantable device for determining a fluid congestion status of a subject, the implantable device including: a frame including a proximal end opposite a distal end and a longitudinal axis extending therethrough; and a vessel occlusion portion including an inflow end and an outflow end, wherein the inflow end is at least partially installed within the distal end of the frame, and the outflow end is coupled to an end effector configured to modulate blood flow through a blood vessel; and a first sensor positioned at the distal end of the frame and configured to detect afirst pressure in a blood vessel; a second sensor positioned upstream of the first sensor and configured to detect a second pressure in the blood vessel at a location upstream of the first sensor; a processor in communication with the first sensor and the second sensor, wherein the processor is configured to: cause the vessel occlusion portion to actuate to introduce at least a partial occlusion in the blood vessel; monitor, using the first sensor or the second sensor, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period; and determine, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject.

[0006] In some aspects, the techniques described herein relate to a method for determining a fluid congestion status of a subject, the method being carried out by at least one processor executing operations including: receiving an initial right atrial pressure for the subject; causing, over a time period, a vessel occlusion device to perform an occlusion cycle to change blood flow resistance in a blood vessel of the subject; receiving monitored readings for a right atrial pressure response to the changed blood flow resistance in the blood vessel over the time period; and determining, for the subject and based on the readings representing the right atrial pressure response, a fluid congestion status associated with a heart of the subject.

[0007] In some aspects, the techniques described herein relate to an implantable device, including: a flow modulator to modulate blood flow through a blood vessel; at least one sensor for detecting a pressure in the blood vessel; and a processor in communication with the at least one sensor and the flow modulator, wherein the processor is configured to actuate the flow modulator and to monitor the pressure in the blood vessel.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] The foregoing is a summary, and thus, necessarily limited in detail. The above- mentioned aspects, as well as other aspects, features, and advantages of the present technology are described below in connection with various embodiments, with reference made to the accompanying drawings.

[0009] FIG. 1A is a bottom up perspective view of an example flow modulating device for monitoring pressure and modulating blood flow through a blood vessel.

[0010] FIG. IB is a side view of the example flow modulating device of FIG. 1A.

[0011] FIG. 2 is an example system for monitoring right atrial pressure responses during a cycle of blood flow modulation in a blood vessel.

[0012] FIG. 3 is an example system depicting managing time-in-range right atrial pressure for a subject.

[0013] FIG. 4 is an example system depicting maximizing time-in-range right atrial pressure while minimizing a time in which the superior vena cava time exhibits increased pressure.

[0014] FIG. 5 is an example graph depicting an example cycle of blood flow modulation using an implanted flow modulating device.

[0015] FIG. 6 is a block diagram of an example system for modulating blood flow through one or more blood vessels and determining fluid statuses based on the modulating.

[0016] FIG. 7 is a flow diagram depicting an example process for determining a fluid congestion status of a subject.

[0017] FIG. 8 is a flow diagram depicting an example process for determining a fluid volume status of a subject.

[0018] FIG. 9 is a flow diagram depicting an example method of a treatment process for using a right atrial pressure response to adjust an amount of diuretic to introduce to a subject experiencing hypervolemia or hypovolemia.

[0019] FIG. 10 illustrates a schematic representation of portions of a human subject in which the devices described herein may be implanted.

[0020] The illustrated embodiments are merely examples and are not intended to limit the disclosure. The schematics are drawn to illustrate features and concepts and are not necessarily drawn to scale.DETAILED DESCRIPTION

[0021] The foregoing is a summary, and thus, necessarily limited in detail. The above- mentioned aspects, as well as other aspects, features, and advantages of the present technology will now be described in connection with various embodiments. The inclusion of the following embodiments is not intended to limit the disclosure to these embodiments, but rather to enable any person skilled in the art to make and use the contemplated embodiments(s). Other embodiments may be utilized, and modifications may be made without departing from the spirit or scope of the subject matter presented herein. Aspects of the disclosure, as described and illustrated herein, can be arranged, combined, modified, and designed in a variety of different formulations, all of which are explicitly contemplated and form part of this disclosure.

[0022] Conventional fluid management assessment and treatment (e.g., diuresis) for a subject is typically performed by a clinician with a goal to decongest the subject to bring thesubject to a stable euvolemic state appropriate for discharge. When a subject presents with signs of acute decompensated heart failure (ADHF), a clinician may typically perform a visual assessment based on a physical examination of the subject. However, there is a lack of scientific measurement tools to inform the clinician of the blood volume status (e.g., congestion status) of the subject, and physical symptoms between subjects with heart failure can vary. Thus, blood volume status cannot be accurately assessed with visual examination. Without the guidance of measurements, clinicians are prone to (1) inadequate diuresis of the subject, leaving the patient with excess volume even at discharge and therefore at higher risk of heart failure-based readmission, and (2) diuresis that is overly aggressive, leading to intravascular volume depletion and potential worsening of renal function, worsening cardiac function, and / or worsening other end organ function. A similar problem exists in the outpatient / home setting, where a lack of blood volume measurement hampers the ability of the subject to self-manage volume status and avoid decompensation.

[0023] In general, the systems and methods described herein may enable monitoring, assessment, diagnosis, and / or generation of treatment protocols for affecting changes in intravascular (e.g., blood) volume status of a subject (e.g., a living subject). For example, the systems and methods described herein may generate and provide a proxy measurement for volume status of a subject based on one or more right atrial pressure (RAP) responses triggered by introducing vessel pressure elsewhere in the body. In another example, the systems and methods described herein may provide a diagnostic for heart failure by assessing the volume status of a subject. In yet another example, the systems and methods may provide a way to assess changes in volume status of a subject as an indicator for determining treatment steps for hypervolemia, hypovolemia, or other fluid conditions in order to attain (or return the subject to) euvolemia. In a further example, the systems and methods described herein may monitor treatments over time as a way to provide output such as a status, an alert, a treatment change, a treatment recommendation, or other health-based instruction to a subject or clinician. Such an output may be provided in either or both of an in-clinic setting (e.g., inpatient) or an at-home setting (e.g., outpatient). In still further examples, the systems and methods described herein may determine particular thresholds for beginning or ending diuresis treatments and such thresholds may be specific to a particular subject. The systems and methods described herein may further perform other calculations and assessments based on introducing (or increasing) pressure in a vessel (e.g., introducing a partial or full occlusion) and analyzing the response in the subject to the introduced pressure.

[0024] In some examples, the systems and methods described herein may utilize a device implanted either intravascular or extravascular to a vena cava to dynamically occlude (e.g., open, partially open, or close) the vena cava lumen, thereby regulating blood flow and venous return to the right portion of the heart. The device may include at least one pressure sensor, either integrated with a processor (e.g., controller) that transmits commands to the occluding device (“closed-loop” system) or standalone controller having an operator to manually adjust occlusions (“open-loop” system), measuring right atrial pressure (RAP), an appropriate surrogate, or pressure at another location in the body. The systems and methods may include algorithms that utilize venous occlusion, at various rates of opening / closing to perturb hemodynamics in a matter that may indicate a fluid volume status (or congestion status) of a subject to reveal details that can assist a clinician or subject in identifying what treatment actions should be taken to alleviate, treat, or otherwise improve fluid volume status and / or heart failure.

[0025] Measuring the upstream and / or downstream pressures over the course of an occlusion cycle that includes at least an occlusion, a hold time, and a reopening of the occlusion in the vena cava, for example, may introduce certain variables that would inform on the fluid volume status of a subject. For example, if the RAP were to drop during the occlusion or hold time, this may indicate hypervolemia, as the reduction of flow into the RA produces an acute drop in RAP that may be commensurate with hypervolemia. In another example, if the level of RAP drop is quickly undone by reopening the occlusion, this could further indicate that the subject is hypervolemic. For example, a rapid rebound may suggest that the heart is overloaded, whereas a slower rebound may indicate that the heart is more capable of handling additional fluid volume. In yet another example, if the ratio in which RAP drops while the SVC pressure rises, this could inform volume overload. For example, if this ratio exceeds a predefined, nominal ratio, this may indicate that there is significant excess of fluid volume, whereas a ratio at or below the nominal ratio may indicate more available compliance in the venous system and thus euvolemia or hypovolemia. In yet another example, the systems described herein may assess a time to minimum RAP value for a subject to determine how quickly RAP drops to a minimum RAP value. In another example, the systems described herein may assess a time to threshold RAP value for a subject to determine how quickly the RAP drops to a predetermined threshold RAP for the subject. Each of the above examples may be used as measurements alone or in combination to generate a score of severity and / or to generate a probability of hypervolemia for a subject.

[0026] In some examples, the systems and methods described herein may enable monitoring, modulating and / or balancing of blood flow through a blood vessel to reduce pressure in the heart and / or other organs as a result of temporarily decreasing or otherwise modulating blood flow through one or more vessels. The change in blood flow may be performed by the devices described herein to occlude, partially occlude, and / or otherwise manage blood flow to or through a portion of a blood vessel for purposes of assessing fluid changes in the body resulting from modulated blood flow triggered by such occlusions. For example, modulating blood flow in a blood vessel may be performed by the systems and methods described herein for purposes of assessing physical responses to the partial or full occlusion events or cycles. Real time (or near real time) pressure analysis for a subject (e.g., a patient) may be performed in order to generate metrics that provide data indicating a level of congestion or fluid status risks for the subject. The pressure analysis may be performed on data obtained by monitoring pressure in or near to a blood vessel at one or more sites in the body using one or more pressure sensors, for example. The monitoring can be performed to inform the systems (e.g., devices) described herein with instructions for how to perform one or more cycles of occlusion, partial occlusion, and / or otherwise manage or regulate blood flow to or through a portion of a blood vessel(s) and / or to develop treatment protocols for treating particular pressure levels or fluid anomalies such as congestion (e.g., heart congestion).

[0027] The examples presented herein may relate to providing devices, methods, and / or methods of treatment (MOTs) for monitoring, assessing, diagnosing, and / or generating treatment protocols for changes in intravascular (e.g., blood) volume status of a subject (e.g., a living subject). The devices, methods, and / or MOTs may include modulating, regulating and / or otherwise managing blood flow to or through one or more blood vessels. The terminology of restricting blood flow, regulating blood flow, modulating blood flow, managing blood flow, and balancing blood flow causes regulation of blood pressure, modulation of blood pressure, management of blood pressure, and / or balancing of blood pressure. In some examples, the devices described herein may include blood flow management devices for reducing blood flow through a blood vessel, such as the Vena Cava (VC), the Superior Vena Cave (SVC), the Inferior Vena Cava (IVC), or related vessels. Managing blood flow through the VC, SVC, or IVC can be achieved by the devices described herein to provide an advantage of determining how changes in pressure in the VC, SVC, or IVC pertain to a level of volume (e.g., volume status) of a subject. In particular, the devices described herein may generate a pressure gradient by decreasing central venous pressure by restricting, balancing, or otherwise modifying bloodflow through the VC, SVC, and / or IVC, triggering a response in RAP that may correlate to either or both of the rate of occlusion and the volume status of the subject. Managing pressure (e.g., blood flow) through the VC, SVC, or IVC can be achieved by the devices described herein to provide an advantage of improving an assessment of volume status thereby improving which treatment steps are utilized to maintain or achieve euvolemia for the subject.

[0028] In some examples, the devices, methods, and / or MOTs described herein may be utilized to solve a technical problem of determining when to increase, maintain, or decrease fluid therapy such as diuresis therapy. For example, introducing one or more cycles of pressure (triggered by one or more occlusion cycles by the devices described herein) may be performed as a way to assess response in the body of the subject receiving the one or more occlusion cycles. In particular, the devices, methods, and / or MOTs described herein may cause generation of at least one occlusion in a blood vessel, such as a vena cava, and may then monitor and assess a response in RAP over a time period. If the RAP drops in response to the occlusion, the systems may use the amount of decrease in pressure as an indicator of a fluid state (e.g., fluid congestion status, fluid volume status) of the subject. Similarly, if the RAP increases in response to the occlusion, the systems may use the amount of increase in pressure as an indicator of a fluid state of the subject. In addition, if the RAP does not change (or does not change substantially), the systems may use the lack of change as an indicator of a fluid state of the subject. Moreover, the indicated fluid states determined by the systems described herein may be compared to predefined pressure thresholds and used as a basis in which to recommend treatment, perform treatment, or otherwise diagnose and / or treat heart failure, kidney failure, under diuresis states, and / or over diuresis states. The predefined pressure thresholds (or responses to such pressure invocations) may be established for a particular subject such that treatments and recommendations are determined for the specific subject. Such predefined pressure thresholds may be used as a basis to determine whether a subject is exhibiting low vessel pressure (e.g., below the predefined pressure threshold) or high vessel pressure (e.g., above the predefined pressure threshold). The systems and methods described herein provide a technical effect of assessing a subject for hypovolemia, hypervolemia, and / or euvolemia by introducing pressure in a blood vessel within or near to a vena cava and determining a RAP response to the introduced pressure. A further technical effect generated by the systems and methods described herein includes enabling kidneys to improve an efficiency and / or effectiveness when filtering blood based on the outcome of the fluid volume assessments described herein.

[0029] In addition, the devices, methods, and / or MOTs described herein can solve a further technical problem of capturing pressure measurements multiple times a day (e.g., intermittent capture throughout a day, capture on a schedule throughout a day, continuous capture, near continuous capture, etc.) as a way to determine when to begin or end intravenous or oral diuretic administration. Conventional implantable cardiac pressure sensor technologies that capture and transmit intracardiac pressure data are limited to once daily (e.g., static) measurements due to reliance on an external unit to power the sensor with RF energy. These types of conventional snapshot measurement systems lack the temporal resolution to capture the data about how much total time a subject is spending within (or outside of) an optimal pressure range for RAP and / or SVC pressure. The devices, methods, and / or MOTs described herein can use one or more sensor outputs to detect RAP and / or SVC pressures as a way to assess real time congestion risk for subjects with heart failure, for example. The sensor outputs may be captured over time and assessments may be performed in an ambulatory setting or in a clinic or hospital setting, and the assessments can be used as a basis in which to generate recommendations and / or health-based instructions for when to begin or end IV or oral diuretic treatment.

[0030] In some examples, the detected / monitored pressures obtained by the devices described herein may function as a feedback mechanism to maintain a predefined pressure in the venous system. For example, monitoring an upstream SVC pressure may be used as feedback for operating an occlusion device (i.e., occluder) attempting to maintain a particular RAP pressure (or pressure range). Having such a feedback mechanism that collects upstream SVC pressure (detected by a first sensor) in conjunction with RAP (e.g., pressure downstream of the SVC pressure or downstream of the device detected by a second sensor) may allow the device to control occlusion in a manner to optimize the RAP reduction benefit while minimizing the time that the upstream / SVC pressure is in an unsafe range.

[0031] In operation, the devices described herein may be used to invoke pressure in a blood vessel to dynamically monitor responses in the venous system, which can provide an advantage and technical effect of ensuring that pressure is not increased above a safe threshold in the SVC, the cranium, and / or the IVC and ensuring that fluid treatments (e.g., diuresis) are not performed unnecessarily, not performed to over saturate a subject, and / or not prematurely terminated to cause undersaturation of a subject. Such devices can advantageously eliminate excessive hospital readmissions and / or can provide for a long-term blood flow managementtherapy, improving both quality of life and overall survival rates and with a lower cost to a healthcare system.

[0032] The RAP response described herein may be based on output(s) captured by one or more sensors onboard the occlusion devices described herein. The sensors may be battery- powered implantable pressure sensors which can sample pressures frequently, offering continuous or near-continuous measurement of RAP. An onboard processor enables a computation of RAP responses using programmable inputs defining one or more thresholds for which pressure values are considered in range (e.g., healthy pressures) and / or one or more thresholds for which a fluid volume status or fluid congestion status are considered in range (e.g., healthy fluid status), as described elsewhere herein.

[0033] Furthermore, the devices, methods, and / or MOTs described herein can be used to solve a further technical problem of regulating (e.g., modulating) blood flow return, thus further mitigating pressure build-up in the right atrium and SVC. The examples described herein can perform blood flow management actively and / or passively to assist in determining fluid administration recommendations for a subject that is currently undergoing or has previously undergone diuresis treatment. In some examples, such blood flow management may be performed based on monitoring pressures using one or more sensors onboard the occlusion device and algorithms executing on an onboard processor as described in detail elsewhere herein. In some examples, the monitoring may be performed on an external computing device in communication with the occlusion device and / or sensors of the occlusion device.

[0034] In some examples, the devices, methods, and / or MOTs described herein can be used to trigger and perform one or more occlusion cycles to invoke blood flow modulation in a portion of a blood vessel and may then use output from one or more sensors to assess a response of the body to such cycles. In some examples, the response assessed includes RAP changes (or lack thereof). In some examples, the response assessed includes LAP changes (or lack thereof) using one or more sensors for capturing LAP measurements. In some examples, the response assessed includes stress responses. In some examples, the response assessed includes tricuspid regurgitation responses or events. The occlusion cycles may be performed by the devices described herein at a particular rate. Example occlusion cycle times may include introducing an occlusion at an interval of about 0.5 hours to about 3 hours. The occlusion cycle may introduce the occlusion at a predefined rate of occlusion executed for a time frame of about 5 seconds to about 10 minutes.SYSTEMS AND DEVICES

[0035] Disclosed herein are systems and methods for modulating blood flow through a blood vessel and monitoring pressures (and / or responses to modulated blood flow) within the blood vessel. In some examples, the implantable flow modulating devices described herein may be used in diuresis therapy. For example, the devices described herein may relate to diuresis assessment and / or therapy using implantable mechanically, hydraulically, and / or electronically controlled flow restricting devices for the treatment of acute heart failure, assessment of heart failure staging, diagnosis of heart congestion, or other fluid-related events in a subject. Some devices may be non-implantable or partially implantable. In some examples, the devices described herein generally function to occlude or partially occlude a blood vessel, such as the SVC or the IVC and generate outputs indicating pressures, fluid levels, state of disease, recommendations, health-based instructions, or the like. In some examples, the devices described herein have been contemplated for use in a subject having chronic heart failure and / or chronic kidney disease, but may be used in any vessel eligible for flow regulation therethrough.

[0036] FIGS. 1A-1B illustrate views of an example flow modulating device 100 (i.e., flow modulator) for monitoring pressure and modulating blood flow through a blood vessel. The device 100 may be implanted into a blood vessel, such as the SVC, the IVC, or any other blood vessel where modulating blood flow is desired. For example, the device 100 may be implanted in the SVC above a junction between the SVC and the right atrium. The device 100 may modulate a volume of blood flowing from the superior vena cava into a right atrium to decrease right atrial pressure and / or decrease SVC pressure and thus limit intracranial venous pressure. The device 100 may further be operated to modulate blood flow in the blood vessel as a basis in which to monitor or determine a fluid volume status in a subject. Such a status may include any range of values defined for the subject (or a population) to indicate a hypervolemic state, a hypovolemic state, or a euvolemic state.

[0037] At a high level, the device 100 may include a self-expanding or balloon expandable frame (e.g., stent) that may be delivered into the blood vessel (e.g., via jugular access, subclavian access, or transfemoral access) using a sheathed catheter (not shown). The frame may include or be coupled to a vessel occlusion portion 150 (e.g., a membrane representing an end effector) that is further coupled to a flexible control wire threaded through a portion of the membrane. The flexible control wire may function as a lasso to be actuated by an actuation device (i.e., actuator) to radially expand and constrict (uniformly or nonuniformly) a perimeter of the end portion of the membrane to function as an adjustable blood flow restrictor.

[0038] FIG. 1A illustrates a bottom up perspective view of an example flow modulating device 100 for monitoring and modulating blood flow through a blood vessel. In this example, the device 100 is shown in an unrestricted blood flow state. The unrestricted blood flow state may represent a state of device 100 in which both an inflow 102 and an outflow 104 are open to receive fluid (e.g., blood, drugs, saline, etc.). The fluid flows through the inflow 102 and through the device 100 to the outflow 104. For example, the device 100 may be in the expanded state when both the inflow 102 and the outflow 104 are open to receive fluid (e.g., blood, drugs, saline, etc.) therethrough when the device 100 is implanted in a blood vessel.

[0039] The device 100 includes a frame 106 that includes a proximal end 108 and a distal end 110, and a longitudinal axis (L) extending therethrough. The proximal end 108 may correspond to the inflow 102 of the device 100. The frame 106 may be a stent, for example constructed of metal wire (e.g., stainless steel, platinum, Nitinol® wire or another shape memory alloy), or other material suitable for implantation in the human body. In some examples, the frame 106 is a bare metal stent, such that the frame 106 may be at least partially incorporated into an inner wall of the blood vessel. In some examples, the frame 106 has a pro- endothelialization coating, such that the expandable frame can be at least partially incorporated into an inner wall of the blood vessel. This incorporation may allow a site of the device 100 to maintain a non-thrombogenic, non-immunogenic environment with respect to the device 100. For example, the coating of the frame 106 may be any pro-endothelial factor including, but not limited to, endothelial growth factor, vascular endothelial growth factor, or any related compound. In some examples, the frame 106 is expandable.

[0040] The device 100 also includes a membrane 112 with an inflow end 114 and an outflow end 116. The inflow end 114 is shown at least partially installed within the distal end 110 of the expandable frame. For example, the membrane 112 is coupled to an inner surface portion of the expandable frame 106, as shown by an overlap 118. The membrane 112 may be installed within (and overlapping) about 25 percent of a length of the frame 106. In some examples, the membrane 112 may be installed within (and overlapping) about 10 percent to substantially covering the entire length of the frame 106. In some examples, the inflow end 114 of the membrane 112 is decoupled from the distal end 110 of the frame 106 and without an overlap. For example, the inflow end 114 may be reversibly coupled to the distal end 110 of the frame 106. The membrane 112 may be formed of a polymer a copolymer, a textile (e.g., woven, knitted, nonwoven, or braided), a tissue (e.g., bovine pericardium, equine pericardium, porcine vena cava, etc.), or a combination thereof.

[0041] In some examples, the membrane 112 is substantially tubular-shaped with a substantially circular cross section about a central axis (C). In some examples, the membrane 112 may be substantially elliptical in shape with a substantially elliptical cross section about the central axis (C). In some examples, the membrane 112 may be substantially flexible such that the shape may take on an irregular perimeter that may form a shape of the blood vessel in which the device 100 is installed, for example, when blood flow is provided from the inflow end 114 through to the outflow end 116.

[0042] In some examples, the membrane 112 is adjustable to any number of positions between expanded and collapsed. The membrane 112 may be adjustable to form a cinched portion at the outflow end 116. The cinching may result in reversibly reducing or closing the circular cross section at the outflow end 116 of the membrane 112. For example, the outflow end 116 may collapse inward toward the central axis (C) associated with the frame 106 and at any interval between fully expanded and fully contracted. The outflow end 116 may also open or expand outward away from the central axis (C) associated with the frame 106. In some examples, the membrane 112 may be expanded or contracted from a particular device state into an expanded position, a partially expanded position, or a collapsed position. For example, when the device 100 is in the expanded position, the device 100 may be caused to be configured into a partially expanded position or a collapsed position by partially or fully collapsing, respectively, the outflow end 116 of the membrane 112 toward the central axis (C). When the device 100 is in the collapsed position, the device 100 may be caused to be configured into a partially expanded position or an expanded position by partially or fully expanding, respectively, the outflow end 116 of the membrane 112 toward the central axis (C).

[0043] The expanded position of the membrane 112 may allow the blood flow through the blood vessel. For example, when the device 100 is implanted in a blood vessel and is configured in the expanded position, the device 100 may allow blood to flow from the inflow end 114 through to the outflow end 116, without substantially hindering the blood flow speed or the blood flow amount.

[0044] The partially expanded position of the membrane 112 may allow partial occlusion of the blood vessel. For example, when the device 100 is implanted in a blood vessel and is configured in the partially expanded position, the device 100 may allow a partial amount of blood to flow from the inflow end 114 through to the outflow end 116 and may hinder a flow of the blood flow by a predefined amount associated with a cross sectional area formed when the outflow end 116 is partially closed (e.g., partially collapsed, partially expanded).

[0045] The collapsed position of the membrane 112 may occlude the blood vessel. In some examples, the occlusion of the blood vessel is a full occlusion. In some examples, the occlusion of the blood vessel is a partial occlusion.

[0046] As shown in FIG. 1A, the outflow end 116 of the membrane 112 is coupled to a plurality of elongate support members 120a, 120b, 120c, 120d, 120e, and 120f. The elongate support members 120a- 120f may be flexible to allow the membrane 112 to bend radially toward the central axis (C) of the frame 106 at the outflow end of the membrane 112 when a connected control wire is actuated.

[0047] In some examples, actuating the membrane 112 is caused by actuation of the control wire coupled to a portion of the membrane 112) or at least one of the elongate support members 120a-120f. For example, actuating the control wire may result in configuring the membrane 112 in an unrestricted blood flow state or a restricted blood flow state. The unrestricted blood flow state may correspond to the membrane 112 radially expanding away from the central axis (C) of the expandable frame 106 to allow blood flow through the blood vessel. The restricted blood flow state may correspond to the membrane 112 radially collapsing toward the central axis (C) of the expandable frame to reduce blood flow through the blood vessel.

[0048] The plurality of support members 120a- 120f may be arranged radially around the membrane 112. For example, the plurality of support members 120a- 120f may be arranged radially around an outer surface or an inner surface of the membrane 112. For example, the plurality of elongate support members 120a-120f may be equidistantly arranged radially around a surface of the membrane 112. In some examples, the plurality of elongate support members 120a- 120f may be arranged non-equidistantly around a surface of the membrane 112. In some examples, the plurality of elongate support members 120a- 120f may be arranged radially around a surface of the membrane 112 such that support members 120a- 120c are arranged around a first semi-circular and surface portion of the membrane 112 while support members 120d-120f are arranged around a second semi-circular portion of the membrane. For example, the support members 120a, 102b, and 120c may be separated by substantially similar distance apart around the first semi-circular and surface portion of the membrane 112 and the support members 120d, 102e, and 120f may be separated by substantially equidistant apart around the second semi-circular and surface portion of the membrane 112. In such an arrangement, the support member 120c may be arranged adjacent to support member 120d, but may be arranged at a closer distance than the distance between support member 120a and 120b or between support member 120b and support member 120c. Similarly, the support member120a may be arranged adjacent to support member 120f, but may be arranged at a closer distance than the distance between support member 120c and 120d or between support member 120e and support member 120c.

[0049] In some examples, the plurality of elongate support members 120a- 120f may extend from the outflow end 116 and toward the inflow end 114 running substantially parallel to the longitudinal axis (L) of the device 100. The support members 120a- 120f may extend a portion of a length ( / ) of the membrane 112. For example, the support members 120a- 120f may extend across about 50 percent to about 90 percent of an outer surface of the membrane 112. In some examples, the support members 120a- 120f may extend a full length ( / ) of the membrane 112. The length of the membrane 112 may be about 5 millimeters to about 5 centimeters. The radius of the membrane 112 may be about 10 millimeters to about 30 millimeters. The thickness of the membrane 112 may be about 0.01 millimeters to about 1 millimeter.

[0050] Although the device 100 includes six support members 120a- 120f, more or fewer support members are possible. For example, the device 100 may have three to five support members; four to six support members; five to seven support members; or five to eight support members.

[0051] As shown in FIG. 1 A, the device 100 further includes an eyelet 126a, an eyelet 126b, an eyelet 126c, an eyelet 126d, an eyelet 126e, and an eyelet 126f. The eyelets 126a- 126f may be coupled to respective support members 120a-120f. For example, the eyelet 126a is coupled to a distal end of the support member 120a; the eyelet 126b is coupled to a distal end of the support member 120b; the eyelet 126c is coupled to a distal end of the support member 120c; the eyelet 126d is coupled to a distal end of the support member 120d; the eyelet 126e is coupled to a distal end of the support member 120e; the eyelet 126f is coupled to a distal end of the support member 120f. Each eyelet 126a-126f may be configured to receive a portion of the control wire 122 threaded therethrough. The eyelets 126a-126f extend beyond the distal end of each respective support member 120a- 120e. Each eyelet 126a- 126f is formed as an aperture having a substantially annular opening. The aperture of each respective eyelet 126a- 126e is arranged to receive the control wire 122 when threaded therethrough such that when the control wire 122 is actuated, the eyelets 126a-126f move radially (e.g., cinching each eyelet together) toward the central axis (C) of the expandable frame 106. For example, actuating the control wire 122 reversibly cinches the membrane 112 toward the central axis (C) by bringing the eyelets 126a-126f together at the outflow end 116 of the membrane 112 to occlude or partially occlude a blood vessel in which the device 100 is implanted.

[0052] Referring again to FIG. 1A, the outflow end 116 of the membrane 112 may correspond to the outflow 104 of device 100. The outflow end 116 of the membrane 112 may be triggered to radially collapse toward the central axis (C) associated with the frame 106 to modulate blood flow in the vessel at the outflow end 116. For example, the outflow end 116 of the membrane 112 may be configured to radially collapse inward at the outflow end 116 by moving the plurality of support members 120a-120f and attached eyelets 126a-126f toward the central axis (C) or radially collapse outward at the outflow end 116 by moving the plurality of support members 120a-120f and attached eyelets 126a-126f away from the central axis (C). The radial collapse or expansion may occur in response to an actuation of a control wire 122. The control wire 122 may be coupled to a portion of the membrane 112 or at least one of the elongate support members 120a- 120f to trigger the expansion or the collapse.

[0053] In some examples, the device 100 may further include a first sensor 140 (e.g., within sensors 606 of FIG. 6) for detecting a pressure (e.g., RAP) in the blood vessel at a first location. The device 100 may also include an optional second sensor 142 (e.g., within sensors 606 of FIG. 6) for detecting a pressure (e.g., SVC pressure) in the blood vessel at a second location upstream from the first location. The output from sensor 140 and / or sensor 142 may be used to sample one or more pressures frequently to provide a continuous or near continuous measurement of RAP pressures / responses, etc. and a feedback mechanism for adjusting the device 100 to occlude more or occlude less based on the sensor output. In general, the sensor 140 and sensor 142 may represent implantable pressure sensors that enable capture and transmission of pressure data for use in dynamically monitoring and dynamically occluding intravascular devices.

[0054] In some examples, the device 100 includes one or more processors (e.g., processor 608) electrically coupled to one or more sensors (e.g., sensor 140, optional sensor 142, sensors 606, etc.), and / or a power source (e.g., power source 614) electrically coupled to an actuator (e.g., actuation device 612) associated with device 100, the processor 608, and / or the sensors described herein. For example, the sensor 140 and / or the optional sensor 142 may sense characteristics of blood flow in the blood vessel (e.g., blood pressure, patterns of blood pressure, subject state, etc.) and may cause the processor to provide signals to the actuator (e.g., actuation device 612) and / or control element 124 and / or control wire 122 (e.g., control devices 610). In operation, the processor 608 can receive a signal from the sensor 606 that is indicative of a pressure (or pressure response) in the blood vessel. The processor 608 can process the signal and generate and provide a control signal (e.g., via control devices 610) to tension thecontrol devices 610, or release tension in the control devices 610 based on the sensed pressure (or pressure response) in the blood vessel. The tensioning and release of tension may be performed based on monitoring performed by the processor while utilizing sensor 140 and / or optional sensor 142.

[0055] In some examples, the sensor 140 and / or optional sensor 142 may be communicatively coupled to device 100. The sensor 140 may include one or more of an image sensor, a strain gauge, a piezoelectric sensor, a fiberoptic sensor, a capacitance sensor, and / or a vacuum pressure sensor. The optional sensor 142 may include one or more of an image sensor, a strain gauge, a piezoelectric sensor, a capacitance sensor, and / or a vacuum pressure sensor. If the device 100 is coupled to a power source (e.g., power source 614), the power source may include an induction coil. The induction coil may be used to operate one or more magnets for controlling and / or operating the device 100.

[0056] In some examples, the device 100 is an implantable device for monitoring blood flow through a blood vessel such as the SVC to determine a fluid congestion status (or fluid volume status associated with the heart) of a subject. For example, the device 100 may be implanted in a subject and may monitor a volume of blood flowing from the SVC into a right atrium and may utilize any number of blood flow occlusion cycles to modulate right atrial pressure, modulate intracranial venous pressure, and / or assess fluid congestion or volume status according to rules and / or parameters programmed into the device 100.

[0057] In some examples, the device 100 is an implantable device for determining a fluid congestion status of a subject. In such examples, the device 100 may include a frame (e.g., frame 106) having a proximal end (e.g., end 108) and a distal end (e.g., end 110) and a longitudinal axis extending therethrough (e.g., L). The device 100 may further include a vessel occlusion portion (e.g., all or a portion of membrane 112). The membrane 112 functioning as a vessel occlusion portion may include an inflow end (e.g., inflow end 114) and an outflow end (e.g., outflow end 116). The inflow end 114 may be at least partially installed within the distal end 110 of the frame 106. The outflow end 116 may be coupled to a vessel occlusion portion 150 (e.g., flap, membrane 112, expandable members, control wire all included in an end effector of device 100) for modulating blood flow through a blood vessel. The device 100 may further include a first sensor (e.g., first sensor 140) positioned at or substantially adjacent to the distal end 110 of the frame. The first sensor 140 may be programmed to detect a first pressure in a blood vessel. The device 100 may also include an optional second sensor (e.g., second sensor 142) positioned upstream of the first sensor 140. The second sensor 142 may beprogrammed to detect a second pressure in the blood vessel at a location upstream of the first sensor. The device 100 may further include one or more processors electrically coupled to the first sensor 140 and the second sensor 142.

[0058] In some examples, the device 100 may include an expandable frame 106 including a proximal end 108, a distal end 110, and a longitudinal axis extending therethrough. The device 100 may also include a membrane 112 (e.g., vessel occlusion portion) with an inflow end 114 and an outflow end 116. The inflow end 114 may be at least partially installed within the distal end 110 of the expandable frame 106. The outflow end 116 may be coupled to a plurality of elongate support members 120a-120f arranged radially around an outer surface of the membrane 112 and extending substantially parallel to the longitudinal axis (L). The device 100 may further include a first sensor 140 positioned at or adjacent to a distal end 110 of the expandable frame. The first sensor 140 may detect a first pressure in a blood vessel and / or response to an increase in pressure. The device 100 may optionally include a second sensor 142 positioned upstream of the first sensor 140 toward a proximal end 108 of the expandable frame 106. The optional second sensor 142 may detect a second pressure (or pressure response) in the blood vessel at a location upstream of the first sensor 140.

[0059] In some examples, the device 100 may include one or more processors (e.g., processor 608, etc.). The processor 608 may be electrically coupled to the first sensor 140 and the optional second sensor 142. The processor 608 may be programmed to carry out instructions for monitoring the first pressure and the second pressure via the sensors 140, 142, for example. The processor may be further programmed to carry out instructions for actuating the membrane 112 to at least partially occlude the blood vessel and further monitor responses in the body.

[0060] In some examples, actuating the membrane to begin an occlusion (or occlusion cycle) reduces blood flow through the blood vessel to reduce the first pressure and reduce the second pressure. For example, the first pressure may represent RAP, and the second pressure may represent SVC pressure upstream of the right atrial pressure. The membrane 112 may radially collapse at the outflow end 116 and toward a central axis (C) of the expandable frame 106 to reduce the RAP. The radial collapse of the membrane 112 may be based on any one or more of predefined occlusion cycles, detected pressure ranges, occlusion rules, and parameter settings, etc.

[0061] In some examples, actuating the membrane increases blood flow through the blood vessel to reduce at least a portion of the second pressure. For example, the membrane 112 may radially expand at least a portion of the membrane 112 away from the central axis (C) of theexpandable frame 106 to alleviate occlusion. In such an example, the device 100 may be triggered to release the occlusion by a particular percentage in response to detecting pressure upstream of the occlusion site. In some examples, the device 100 may be triggered to release the occlusion by a particular percentage in response to reaching the end of a predefined occlusion cycle, as described elsewhere herein. The device 100 may be triggered to release the occlusion by a particular percentage in response to other rules or parameters that may be configured for the device 100 and / or a particular component of device 100.

[0062] In some examples, a range of collapsing or expanding is selected based on one or more of: a predefined occlusion profile, a predefined occlusion schedule (e.g., cycle), a differential between the first pressure (e.g., RAP response detected by sensor 140) and the second pressure (e.g., SVC pressure detected by sensor 142 and upstream from the RAP response), and a detected rate of change in the second pressure. The predefined occlusion profile may include one or more rules and / or parameters as described in FIG. 5. The predefined occlusion schedule may represent an occlusion cycle time and / or per day or per hour based actuation algorithm for the device 100. The detected differential between the first pressure and the second pressure may be used to trigger more or fewer collapsing or expanding events (e.g., occlusion cycles) for the membrane 112. The detected rate of change in the second pressure may be detected by the sensor 142, for example, and used to trigger collapsing or expanding events (e.g., occlusion cycles) for the membrane 112.

[0063] An example rate of change in the first pressure (e.g., RAP) that may cause the occlusion device to begin occluding at a rate of about 5 percent occlusion per minute, or as fast as fully occluded in less than about 5 seconds.

[0064] An example rate of change in the first pressure (e.g., RAP) that may cause the occlusion device to stop occluding may be at a rate of about -5 percent occlusion per minute to about fully open in less than about 5 seconds.

[0065] An example rate of change in the second pressure (e.g., SVC upstream from the detected RAP) that may cause the occlusion device to begin occluding at about a rate of 5 percent occlusion per minute to about fully occluded in less than about 5 seconds; or a rate of about -5 percent occlusion per minute to fully open in less than about 5 seconds.

[0066] An example rate of change in the second pressure (e.g., SVC upstream from the detected RAP) that may cause the occlusion device to stop occluding at a rate of about 5 percent occlusion per minute to fully open in less than about 5 seconds.

[0067] In some examples, the device 100 may be programmed to utilize a set sequence of occlusions and openings such that an ending occlusion may be a set percentage or alternatively, it may be set to an absolute or relative increase of SVCP.

[0068] In some examples, actuating the occlusion device 100 (e.g., actuating the membrane 112 to reduce blood flow through the blood vessel and thus begin occlusion) may be performed in response to monitoring pressure. For example, device 100 may be programmed to monitor pressure in the right atrium using one or more processors, sensors, and / or instructions. In some examples, the membrane 112 may be triggered to radially collapse at the outflow end and toward the central axis (C) of the expandable frame 106 in response to detecting the first pressure is above a predefined pressure threshold. In some examples, the membrane 112 may be triggered to radially expand (at or near at least a portion of the membrane) away from the central axis (C) of the expandable frame 106 in response to determining that the second pressure is increasing at or above a predefined rate. In this way, the device 100 may use the second pressure as a feedback loop to cause actuation of the membrane 112 (e.g., occlusion or release of a prior occlusion) to modulate the first pressure and / or any resulting fluid buildup or lack thereof in other portions of the body.

[0069] In some examples, the monitoring of the first pressure and the monitoring of the second pressure may be performed substantially continuously. In such examples, the monitoring may further include generating an indication to adjust the membrane 112 to a selected one of a plurality of positions between expanded and collapsed in response to detecting, at a second time period, that the first pressure is at or below a predefined pressure threshold. In some examples, the monitoring may include triggering an occlusion cycle when the pressure is at or above a predefined pressure threshold. This threshold may be defined by a clinician and may be specific to each particular subject. In some examples, the predefined pressure threshold may be between about 8 mmHg and about 15 mmHg; about 8 mmHg and about 9 mmHg; about 9 mmHg and about 10 mmHg; about 10 mmHg and about 11 mmHg; about 11 mmHg and about 12 mmHg; about 12 mmHg and about 13 mmHg; about 13 mmHg and about 14 mmHg; or about 14 mmHg and about 15 mmHg.

[0070] In some examples, the plurality of positions between expanded and collapsed may include at least an expanded position configured to allow the blood flow through the blood vessel, a partially expanded position configured to partially occlude the blood vessel, and a collapsed position configured to block the outflow end to occlude the blood vessel.

[0071] FIG. IB illustrates a side view of the example flow modulating device of FIG. 1 A. In this example, the device 100 is shown with the membrane 112 in a partially collapsed state. The partially collapsed state may represent a restricted blood flow state in which the membrane 112 radially collapses toward the central axis (C) of the frame 106 to reduce (or stop) blood flow through the blood vessel. Such a state may allow for a partial flow of blood, for example, through a lumen associated with the membrane 112. FIG. 1A, by contrast depicts the device 100 in an unrestricted blood flow state in which the membrane 112 is depicted radially expanded away from the central axis (C) of the expandable frame 106 to allow blood to flow through the blood vessel in which device 100 is implanted.

[0072] Positioning the membrane 112 in the partially collapsed state (e.g., a restricted blood flow state) shown in FIG. IB, the control wire 122 may be actuated by a control element 124 coupled to, or otherwise in communication with, the control wire 122 to cause tensioning of the control wire 122 and closure or partial closure (e.g., cinching) of the membrane 112 at the outflow end 116. For example, the membrane 112 may be adjustable to form a cinched portion at the outflow end 116. For example, the cinching to form a cinched portion may include causing a perimeter of the outflow end 116 to be pleated, folded, or otherwise collapsed toward the central axis (C) by tensioning the control wire 122, which may result in reversibly reducing or closing the cross section at the outflow end 116. Such cinching of the perimeter of the outflow end 116 may be performed by device 100 to fully collapse the outflow end 116 of the membrane 112 resulting in occlusion of the blood vessel associated with the device 100. The cinching of the perimeter of the outflow end 116 may also be performed by device 100 to partially collapse the outflow end 116 of the membrane 112 resulting in a partial occlusion of the blood vessel associated with the device 100.

[0073] The actuating the control wire 122 may result in positioning the membrane 112 and / or device 100 in an unrestricted blood flow state or a restricted blood flow state. The device 100 may include an actuation device (not shown), either active or passive, to actuate the control wire 122. The actuation device may use a power source associated with or coupled to device 100 to induce changes in blood flow states of the membrane 112 and / or other portion of device 100. In some examples, the actuation device may use passively induced movement. For example, passively moving a portion of the device 100 may include manually actuating pull wires (e.g., sutures, actuation wires / cords / elements, etc.) and / or anatomy responses (e.g., changes in vessel inner diameter, intra-vessel pressure, etc.

[0074] In some examples, the actuation device for actuating the control wire 122 of the device 100 may include an actuator coupled to the control wire 122 of the device 100, a first magnet to induce rotation of the actuator, and a control device communicatively coupled to the actuator. In some examples, the first magnet is a permanent magnet, and the second magnet is a permanent magnet. In some examples, the first magnet is a permanent magnet, and the second magnet is an electromagnet. In some examples, the actuation device may be a magnetically driven actuator. In such an example, the control device may include a second magnet for generating a changing magnetic field pole direction to cause rotation of the first magnet and operation of the control wire 122 and device movement to the unrestricted blood flow state or to the restricted blood flow state. For example, the actuation device may cause rotation of the second magnet in a first direction to induce rotation of the first magnet, thereby causing the actuator to tension the control wire 122 to cause the membrane 112 to radially collapse inward and toward the central axis (C) at the outflow end 116. For example, the first direction of rotation of the second magnet may attract the first magnet.

[0075] The actuation device may also cause rotation of the second magnet in a second direction to induce rotation of the first magnet, thereby causing the actuator to release tension in the control wire 122 to cause the membrane 112 to radially open at the outflow end 116. For example, the second direction of rotation of the second magnet may repel the first magnet.

[0076] In some examples, the control device is implanted in the same subject in which the device 100 is implanted. The control device may be implanted adjacent to the device 100 or remote from the device 100. In some examples, the control device is implanted subcutaneously in the subject. In some examples, the control device is disposed external to a body of the subject.

[0077] In operation, the device 100 may receive a signal from an actuator that triggers the control element 124 to cause actuation of the control wire 122 and in turn causes a radial collapse of the membrane 112 at the outflow end 116. Such an actuation of the control wire 122 may cause the control wire 122 to be tensioned and to pull the eyelets radially toward the central axis (C) to collapse or partially collapse the membrane 112. In addition, the outflow end 116 of the membrane 112 may radially expand away from the central axis (C) of the expandable frame 106, in response to an actuation of the control wire 122. The control wire 122 may be actuated by the control element 124 connected to the control wire 122 in a similar fashion as described above to cause the control wire 122 to release the tension and to release the eyelets radially away from the central axis (C) to expand or partially expand the membrane112. The signal received from the actuator may be triggered based on monitoring performed by processors and sensors of device 100.

[0078] While membrane 112, members 120a-120f, and eyelets 126a-126f are described as a cinching occlusion mechanism for the device 100, any occlusion mechanism (e.g., vessel occlusion portion 150) may be employed with the methods described herein. In general, one or more control elements can be coupled to a body of an occlusion device. The control element and / or portion 150 to be moved (or actuated), can include one or more leaflets, flaps, valves, or valve portions (e.g., used to restrict blood flow through a blood vessel).

[0079] In some examples, the plurality of eyelets 126a- 126f (or other cinching elements) may be utilized with the membrane 112 and without the elongate support members 120a-120f. For example, membrane 112 may be closed or opened by respectively cinching or releasing a wire threaded through eyelets 126a-126f. The membrane 112 in this example may be secured or otherwise anchored to a portion of the vessel without the structure provided by elongate support members 120a-120f.

[0080] In some examples, the device 100 may include a power source (e.g., optional power source 614) coupled to the control wire 122 or indirectly coupled to the control wire. The power source may include a battery or a wall outlet that may be electrically connected to the control wire 122 or another portion of device 100. The electrical connection may allow active powering of device 100 operations. In such an example, a processor may be utilized to send and / or receive signals to activate device operations via the actuation device. In some examples, the actuation device may send a first signal to the control wire 122 to activate application of tension to the control wire 122. For example, a processor (e.g., processor(s) 608) may be programmed to trigger tensioning of the control wire 122 in response to detecting a particular condition of the blood vessel or the device 100. The tensioning of the control wire 122 may result in cinching the outflow end 116 of the membrane to place the device in a restrictive blood flow state. Similarly, the actuation device may send a second signal to the control wire to activate releasing of the tension from the control wire 122 in response to detecting another condition of the blood vessel or the device 100. For example, a processor (not shown) may be programmed to trigger a release of tension in the wire 122 in response to detecting a particular condition of the blood vessel or the de vice 100. The release of the tension of the control wire 122 may result in uncinching the outflow end 116 of the membrane to place the device in an unrestrictive blood flow state.

[0081] In some examples, the device 100 may further include an actuation device for actuating the implantable device (e.g., the vessel occlusion portion 150). The actuation device may include an actuator coupled to a control wire of the implantable device. The device 100 may further include a control device communicatively coupled to the actuator to cause the actuation device to actuate the implantable device (e.g., the vessel occlusion portion 150).

[0082] In some examples, when a flow modulating device is in a partially or substantially fully closed, occluded, or restricted state (e.g., one or more membranes 112 are partially or fully expanded at the outflow end 116), blood may pool, exhibit stasis, or create eddies at or proximal to an upstream or inflow end 114 and / or at a downstream or outflow end 116 of the flow modulating device (e.g., flow modulating device 100). This pooling, stopping, or slowing of blood flow may create one or more stasis zones within the IVC, SVC, or peripheral vessel. For example, these stasis zones may be created where the membrane 112 couples to the frame 106; where the membrane 112 and frame 106 together define a pocket, groove, indentation, or concave section; where the membrane 112 contacts a support member 120a- 120f; and the like. To alleviate blood stasis within a potential stasis zone, a flow modulating device may include one or more stasis reduction solutions. For example, a flow modulating device 100 may include the membrane 112 with one or more potential stasis zones (not shown) positioned between a vessel wall and an outside surface of the membrane 112.

[0083] To alleviate blood stasis and / or pooling, stasis reducing (or stasis mitigating) features may be included on membrane 112 to ensure that blood may flow through the one or more of the potential stasis zones (not shown). The devices described herein may include stasis reducing features such as grooves that may function as conduits (e.g., gutters, paths, etc.) to move blood along a surface of the membrane 112 and / or the frame 106. One skilled in the art will appreciate that any number of grooves may be provided on membrane 112 and such grooves may be angled at any angle to promote blood flow from a particular stasis zone (e.g., from the inflow end 114 to the outflow end 116 to reduce blood stasis around the implantable device). One skilled in the art will appreciate that other stasis mitigating features are possible.

[0084] In some examples, the blood stasis (e.g., pooling, stopping, or slowing of blood flow) may be detected by one or more of the sensors described herein. In response to detecting blood stasis, the implanted device 100 may perform one or more agitation cycles to deter the implanted device 100 from remaining stagnant and accumulating thrombus. In some examples, the implanted device 100 may perform one or more agitation cycles to deter the implanted device 100 from adhering to surfaces in which the device 100 encroaches or moves upon duringoperation. The agitation cycle may be performed when the device 100 is in an occluded state, a partially occluded state, and an open state. The agitation cycle may include operation of one or more components of device 100. For example, any two or more of support members 120a- 120f and control wire 122 may be operated (e.g., actuated) to induce an agitation cycle. In some examples, an agitation cycle may include electrical, chemical, or physical stimulation of any portion of the device 100.

[0085] FIG. 2 is an example system 200 for monitoring RAP responses and determining a fluid volume status of a subject 202. The system 200 depicts an example of performing monitoring and analysis in a clinic or hospital setting where a clinician may be prepared to administer diuretics or other heart failure medications to a subject exhibiting fluid-based distress or heart failure, for example. In this example, an occlusion device, such as device 100 may be implanted in a vena cava (e.g., the SVC or an adjacent vessel, the IVC or an adjacent vessel, or the like) of a subject with acute decompensated heart failure. A volume status test may be executed by device 100. The volume status test may include causing the vessel occlusion portion 150 to actuate to introduce at least a partial occlusion in the blood vessel, monitoring, using the first pressure sensor 140 or the second pressure sensor 142, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period, and determining, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject.

[0086] In some examples, the indication is a value determined during a monitoring time period. A patient specific Frank-Starling curve would need to be generated by measuring stroke volume (via standard equipment) and right atrial pressure (via the sensor on occluding device), while a “fluid challenge” (i.e. saline) is administered to get the stroke volume-RAP relationship across a range of volume condition. In one non-limiting example, the device 100 (e.g., operating system 600 of FIG. 6 or another flow modulating device operating system 600) may determine the value by calculating a relative change in right atrial pressure for the subject from a baseline right atrial pressure of the subject and mapping this to a specific degree of volume status and / or cardiac efficiency estimated by the magnitude of leftward shift on the patient’s individualized Frank-Starling curve. Based on the Frank-Starling principle, a greater decrease in right atrial pressure from an elevated baseline right atrial pressure would indicate that the patient was more hypervolemic and the heart was contracting inefficiently. The system 600 may then generate, based on the indication (e.g., value / curve), a treatment recommendation forthe subject to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0087] In one non-limiting example, the system 600 may instead or also determine the value and / or curve by calculating an absolute change in right atrial pressure for the subject and comparing the absolute change in right atrial pressure to a degree of shift along the patient’s individual Frank-Starling curve. The system may then generate, based on the indication, a treatment recommendation for the subject to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0088] The indication representing the fluid volume status may be determined as a basis in which to generate a treatment recommendation to achieve or maintain euvolemia. The indication representing the fluid volume status may include any or all of a message, a value, a graph, a chart, a metric, or a range indicating a classification of the subject during the time period into a hypervolemic state, a hypovolemic state, or a euvolemic state. Other example outputs from system 600 may include trajectories of treatment, trajectories of disease, probabilities of time until a patient reaches the euvolemic state with a recommended or ongoing treatment, etc. In some examples, the metric or the range (and / or other output from system 600) may be used with the indication to generate a treatment recommendation to achieve or maintain euvolemia. For example, the system 600 may generate, based on the indication representing the fluid volume status of a subject, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0089] In some examples, the device 100 may determine a treatment recommendation by comparing the determined indication to one or more of: a hypervolemia threshold range or index, a hypovolemia threshold range or index, or data representing past fluid treatment events, disease information, and / or health information associated with the subject. In some examples, a hypervolemia index may be established. If the hypervolemia index is 125 percent or greater, an aggressive treatment may be recommended (e.g., a maximum diuretic dose, GDMT, etc.) If the index is about 110 percent to about 125 percent, then a treatment that down-titrates the diuretic dose may be recommended to avoid drying out the subject. The aggressiveness of administering diuretics and / or drugs may be adjusted based on such indices.

[0090] In some examples, the threshold ranges or indices may be general baseline values that are population based. In some examples, the threshold ranges may be tailored to the subject having device 100 implanted. In some examples, the treatment recommendation includes one or more instructions to up-titrate intravenous loop diuretic treatment, down-titrate intravenousloop diuretic treatment, or terminate intravenous loop diuretic treatment. In some examples, the treatment recommendation includes one or more instructions to up-titrate oral diuretic treatment, down-titrate oral diuretic treatment, or terminate oral diuretic treatment. These changes may include changes to guideline-directed medical therapy doses based on the knowledge of the responsiveness of pressure on volume changes up or downstream of occlusion.

[0091] In some examples, monitoring of the subject may be performed before, during, and / or after introduction of an occlusion event or cycle. For example, a first pressure may be monitored by sensor 140 and a second pressure may be measured by sensor 142. The first pressure and the second pressure may be provided as output data to one or more other computing devices (e.g., devices 208, 605a, 605b) that are, communicatively coupled to the device 100. Any amount of output data from sensors 140, 142 or device 100, in general, may be provided to such computing devices. In some examples, the output data is used by the one or more computing devices described herein to generate recommendations and health-based instructions. The recommendations and health-based instructions may be triggered for display on such computing devices.

[0092] In a non-limiting example, the system 600 may perform the monitoring of RAP responses over the time period to determine a degree of change in RAP (e.g., decrease, increase, no change) in response to the occlusion generated by device 100. The degree of change may indicate a level of hypervolemia for the subject. For example, if 100 percent volume level represents euvolemia as a reference point, and RAP is detected to decrease 5 mmHg in response to the occlusion, the system 600 may determine that the subject is exhibiting a certain level of hypervolemia based on the magnitude of the % volume level (e.g. for illustrative purposes, values such as 110% could indicate milder hypervolemia, and higher values such as 130% can indicate more severe hypervolemia). A relative percentage decrease from baseline RAP can be used in lieu of an absolute decrease. Based on the percent volume status, the system 600 may calculate a volume status for the subject and generate a recommendation to the clinician.

[0093] Calculating a volume status may include assessing whether a decrease of RAP at the end of an occlusion cycle is greater than or equal to about 2 mmHg and if so, the device 100 and / or system 600 may indicate that the subject is in a state of hypervolemia. A degree in which the pressure is greater than the about 2 mmHg may correlate with the degree of hypervolemia. In some embodiments, a degree of hypervolemia may pertain to a relative percentage change in RAP from a baseline RAP.

[0094] In this example, the recommendation is to up-titrate intravenous loop diuretic by a determined amount. Further, a follow-on volume status occlusion event may be performed for any time between about 1 hour and about 3 hours following the first or prior occlusion event. If the second or follow-on occlusion events shows a new volume status for the subject at 110 percent volume, the system 600 may calculate a diuresis trajectory of about 5 percent volume per hour. The occlusion event cadence can be tuned to occur more frequently (e.g. every 3 hours, every 2 hours, every 1 hour, every half an hour, every 15 minutes, etc.) to provide a higher fidelity of the diuresis trajectory calculation.

[0095] An example diuresis trajectory calculation may include determining a score for hypervolemia of a subject, tracking the subject over time and logging scores in relation to a diuretic dosage. As the diuretics or other drugs are administered, the trajectory of volume may be monitored periodically to inform whether a higher dosage would benefit the subject.

[0096] Based on the calculated diuresis trajectory, the system 600 may adjust the recommendation (e.g., recommended intravenous diuretic dosage to achieve 100 percent volume - i.e., euvolemia). In some examples, the system 600 may detect during monitoring, when the subject is nearing or at about 100 percent fluid volume and may generate a recommendation to down-titrate or terminate intravenous diuretics (and / or transition to oral diuretics). In such examples, the system 600 may suspend further occlusion events and / or cycles until a detected health event or other indication triggers occlusion cycles to begin again. The diuresis trajectory calculation may provide an advantage of minimizing a probability of performing extraneous diuresis ( e.g., drying out) on the subject. The diuresis trajectory calculation and the volume status may be used as a basis in which to determine when the subject exhibits euvolemia. For example, when an occlusion cycle results in substantial lack of RAP response, then the target euvolemia may be determined to be reached. The RAP response may be a change in right atrial pressure or a lack of a change in right atrial pressure. For example, the RAP response may be an increase, a decrease, or a negligible change in right atrial pressure during the time period of a particular monitoring session. As used herein, a negligible change in RAP during a time period refers to a zero percent change up to about 5 percent in RAP over the time period or over an occlusion cycle.

[0097] In another non-limiting example, the system 600 may also be utilized for a subject in an in-home setting. For example, the occlusion device, such as device 100 may be implanted in a vena cava (e.g., the SVC or an adjacent vessel, the IVC or an adjacent vessel, or the like) of a subject with acute decompensated heart failure. The subject may be at home and mayundergo the volume status assessment based on one or more occlusion cycles, as described elsewhere herein. For example, a volume status assessment may be executed by device 100 in an in-home setting. The volume status assessment may include causing the vessel occlusion portion 150 to actuate to introduce at least a partial occlusion in the blood vessel, monitoring, using the first pressure sensor 140 or the second pressure sensor 142, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period, and determining, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject. If the text / measurement, etc. indicates that the RAP drops in response to one or more occlusion cycles, the device 100 may generate an output indicating a trend of hypervolemia. The device 100 may also generate instructions for the subject to up- titrate oral diuretics based on the indicated trend. Further diuretic dosing can be guided by one or more occlusion cycles at some predetermined cadence, until the subject reaches euvolemia, indicated by a lack of RAP response to venous occlusion, for example. The frequency of occlusion events and / or cycles can be increased to capture a higher resolution of changes in RAP and / or subtle decreases in RAP. This higher sensitivity to gradual volume status changes can allow the subject to make real-time dietary adjustments (e.g., minimize fluid intake, sodium intake, etc.) in order to mitigate further volume accumulation. This may provide an advantage of enabling the subject to self-manage diuretic titration (and nutritional choices, in some cases) without clinician intervention.

[0098] Device 100 may include at least one processor (not shown), at least one pressure sensor (e.g., sensor 140) and optionally a second pressure sensor (e.g., sensor 142). In some examples, the device 100 may also include a communication source (e.g., coil, antenna, etc.), a power source (e.g., battery / transmitter / controller circuit 204), and a control wire 206. The system 600 may further include one or more external devices. For example, system 600 may include a first external device (e.g., computing device 208) and optionally a second external device (e.g., a smartphone and / or hub device). The system 600 may be in wireless communication with the external devices and / or other hospital or clinic computing system or servers to share pressure measurements, device configurations, operational parameter changes, user interface content 210, or other data shareable between the devices of system 200 and device 100. The system 200 may include any number of processors amongst the devices of system 200.

[0099] In some examples, the device 100 may capture (e.g., detect, monitor, etc.) changes in RAP over time. For example, a processor onboard device 100 may obtain raw RAP data fromsensors 140, 142 representing data captured from a pressure sensor placed in the right atrium (RA) or in proximity of the RA (e.g., the SVC). In particular, the system 200 may utilize one or more sensors 140, 142 to assess RAP in response to pressure changes (e.g., blood flow resistance changes) caused by device 100 over a time period. Further, the device 100 may monitor the subject 202 during one or more occlusion cycles while sensors 140, 142 detect changes in RAP. The changes in RAP may be used to generate an indicator representing fluid volume status (and / or fluid congestion status) of the subject. For example, the processor of device 100 may generate an indicator (e.g., value, graph, metric, etc.) and / or index indicating fluid congestion levels (e.g., percentages, dryness value, wetness value, etc.) in the subject.

[0100] The indicator and / or index may represent a proportion between volume status and RAP change over a time period. The processor of device 100 may use the indicator and / or index to further calculate treatment recommendations and / or medication dosages based on the change in RAP over the time period. For example, if the system 600 identifies hypervolemia (i.e. 10 percent or more drop in RAP during an occlusion cycle), the system 600 may suggest a combination of increased diuretics, firmer adherence to diet / drinking recommendations, sampling of relevant labs, a clinic visit, and / or a duty cycle of sorts of administering therapeutic intermittent occlusions. In another example, if RAP is determined to be high (e.g., about 12 mmHg), but does not drop more than about 1 mmHg upon administration of an occlusion, then the system 600 may suggest a different combination of diuretics, diet recommendation, fluid intake, etc. The indicator and / or index may represent a proportion between volume status and RAP change over a time period. The processor of device 100 may use the indicator and / or index to further calculate treatment recommendations and / or medication dosages based on the change in RAP over the time period.

[0101] In some examples, the volume status is determined based on the RAP change and the computing device 208 is notified. The clinician may determine to modify (e.g., up-titrate or down-titrate) diuretic dosage by an amount determined based on the RAP change. The occlusion cycle may be repeated any number of times to continually or intermittently assess the volume status of the subject 202. When the device 100 indicates a change in RAP that is at or above the predefined threshold 214, the device 100 may trigger notifications, recommendations, and / or medication dosage changes. In some examples, the medication may be terminated based on the subject exhibiting a RAP below the predefined threshold 214, as shown by user interface content 210 (e.g., graph), for example.

[0102] In a non-limiting, example operation of device 100, device 100 may trigger an occlusion event or cycle and then may sense RAP using sensors 140, 142. The device 100 may analyze whether the subject 202 is in a volume overload state shown in graph portion 212 by determining how the subject 202 responds to the occlusion cycle. In this example, RAP decreases below a threshold 214 to indicate hypervolemia. The threshold 214 may be a predefined RAP threshold that indicates hypervolemia. The threshold 214 may be a value, a range, or an index defining (e.g., delineating) one or more of a state of hypervolemia for the subject, a state of hypovolemia for the subject, and a state of euvolemia for the subject. A state of hypervolemia for a subject may utilize a range for threshold 214 with a minimum change in RAP of about 2 mmHg to about 10 mmHg. In some embodiments, a percentage change from a baseline RAP may be used for threshold 214. A state of euvolemia for a subject may utilize a range for threshold 214 with a minimum change in RAP of less than about 1 mmHg. A state of hypovolemia for a subject may be determined using an occlusion response, lab data, or other data in combination with a drop in RAP. In some examples, the predefined response threshold 214 may include a lack of response or a negligible change in RAP over a time period. As used herein, a negligible change in RAP over a time period refers to a zero percent change up to about 5 percent in RAP over a time period or over an occlusion cycle.

[0103] In some examples, the predefined response threshold 214 may be based at least in part on medical data associated with the subject including, but not limited to electronic medical records, test results, symptom tracking apps, responses and / or output from prior occlusion cycles, or the like. For example, the system may utilize previously measured RAP values and / or treatments for a subject to determine what limits or thresholds to use when monitoring the same subject at a future date.

[0104] In some examples, the system 200 may obtain and assess pressure change data from device 100, for example, which may be implanted in or around a blood vessel of a subject. The device 100 may include at least one pressure sensor, a processor, and a vessel occlusion portion. The processor may be programmed to carry out operations including causing the vessel occlusion portion to introduce at least a partial occlusion in the blood vessel, monitoring using the at least one pressure sensor, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period, and determining, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject.

[0105] Such a device functioning in system 200 may assess right atrial pressure responses as a basis in which to adjust an amount of diuretic to introduce to a subject experiencinghypervolemia or hypovolemia. For example, the device 100 may be programmed to cause the vessel occlusion portion 150 of device 100 to actuate to introduce at least a partial occlusion in the blood vessel. In this example, the blood vessel may be a vena cava, an inferior vena cava, a superior vena cava, or vessels adjacent to the vena cava, the inferior vena cava, or the superior vena cava. Actuating the vessel occlusion portion 150 may be initially performed by a clinician, but further actuation may be based at least in part on the monitoring performed by device 100. In some examples, occlusion cycles may be performed by portion 150 based on the programming of the device 100. The actuating of vessel occlusion portion 150 (e.g., an end effector of device 100) may include radially collapsing the vessel occlusion portion 150 at the outflow end and toward a central axis (C) of the frame 106 and / or radially expanding at least a portion of the vessel occlusion portion 150 away from the central axis (C) of the frame 106 in response to determining that the right atrial pressure response is increasing or above a predefined pressure range associated with the subject being monitored.

[0106] After actuating the vessel occlusion portion 150 to introduce a pressure, the device 100 may monitor, using the first pressure sensor 140 or the second pressure sensor 142, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period, and determine, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject.

[0107] In some examples, actuating the vessel occlusion portion 150 may be performed based on a determined elapsed time in which the RAP response is within a predefined pressure range (e.g., about 10 mmHg to about 25 mmHg). The elapsed time may be determined based at least in part on pressure detected by the first sensor 140 or pressure detected by the second sensor 142. For example, a processor (e.g., processor 608) of system 600 may utilize sensors 140, 142 to detect when RAP pressure changes and may continuously monitor the changes to generate a graphical representation of the changes. At any point during monitoring, the system 600 may trigger a change to a state of the vessel occlusion portion 150 to alleviate pressure (e.g., an unrestricted blood flow state or partially restricted blood flow state), increase pressure (e.g., a restricted blood flow state), and / or modify an occlusion cycle associated with opening and / or closing of portion 150.

[0108] In some examples, the device 100 may introduce a pressure into the vessel by actuating the vessel occlusion portion 150 while the subject is undergoing diuresis treatment during the time period associated with the monitoring described herein. The device 100 may further detect efficacy of the diuresis treatment by determining a magnitude of the right atrialpressure response during the time period and comparing the determined magnitude to a predefined response threshold (e.g., threshold 214). The comparisons may be performed over the time period associated with the monitoring. The system 600 may use the comparisons to generate an indication to halt the diuresis treatment, for example, in response to determining that the magnitude of the right atrial pressure response is below a predefined response threshold, such as threshold 214, as described elsewhere herein.

[0109] In some examples, the monitoring of the right atrial pressure response further includes communicatively coupling the implantable device 100 to at least one external computing device (e.g., device 208), transmitting, to the at least one external computing device, output data corresponding to the monitored right atrial pressure response (e.g., pressure data, graphical data, measured pressure responses, etc.), and receiving, from the at least one external computing device and based on the transmitted output data, health-based instructions. The health-based instructions may be triggered for display on the at least one external computing device (e.g., device 208).

[0110] In some examples, the health-based instructions may include one or more of: instructions to titrate medication, instructions to visit a clinic, instructions to deliver diuresis therapy, and instructions to perform physical movements. Such instructions may be generated by device 100 over time based at least in part on RAP response to occlusions generated by device 100. In some examples, the health-based instructions may include a treatment recommendation to alter a fluid volume status. For example, the treatment recommendation may include a level of fluid administration to the subject, a level of diuretic administration to the subject, or a particular dietary adjustment for the subject. In some examples, the healthbased instructions may include one or more of: instructions to titrate medication, instructions to visit a clinic, instructions to deliver rescue therapy, instructions to perform physical movements, instructions to modify the diet (e.g., water intake, potassium or salt intake), instruction to collect lab panels or related blood tests for heart failure, or instruction to perform stress reduction activities (e.g., mindful breathing, meditation, etc.).

[0111] Data shared or otherwise obtained from device 100 may be used to calculate values, curves, indices, or other metrics for determining volume and / or congestion status of a subject. In a non-limiting example, the data obtained from device 100 may be wirelessly transmitted to a smartphone or other computing device communicatively coupled to device 100. This data transmission can occur periodically (e.g., intermittently, on a schedule, according to a fixed cadence, etc.) and / or when the implanted sensor 140 (and / or optionally sensor 142) is within apredefined physical range of the smartphone or other computing device. The data may be transferred to or from a cloud platform to a hospital or clinic cloud or other IT infrastructure. Data encryption and decryption steps may occur along the process. The data may be downloaded to a clinician user interface (UI) (e.g., on computing device 208), for remote monitoring purposes. This real time (or near real time) assessment of congestion risk can enable a clinician to take timely medical action including, but not limited to, titrating medications remotely, advising the subject to come into the clinic, delivering rescue therapy (e.g., homebased IV diuresis), etc. With the near continuous temporal resolution of RAP data, the system 600 onboard device 100, for example, may identify excursions, inflection points, or trends that may correspond with positive or negative lifestyle or medication adherence behaviors of the subject. Such insights could be used to make heart failure self-management coaching more effective by tying specific behaviors to specific hemodynamic patterns. In some examples, a clinician may interpret such data and provide insights to provide health-based suggestions and diagnoses. In some examples, the system 600 may determine or obtain such insights from a computing device communicatively coupled to device 100.

[0112] FIG. 3 is an example system 300 for managing right atrial pressure for a subject. In this example, the RAP response can be used as a closed-loop feedback signal to the device 100 implanted in the vena cava (e.g., in the SVC or the 1VC) which can dynamically occlude the vessel. In some examples, the pressure sensor 140 of device 100 may be positioned in the proximity of the RA junction (either SVC or IVC) to capture accurate RAP response measurements. A controller circuit 302 can generate one or more occlusion cycles and perform monitoring of RAP responses over the time of one or more occlusion cycles. In general, labeled datasets of occlusion parameters versus pressure patterns and / or pressure response patterns may be used to assess RAP responses and provide feedback, recommendations, and / or healthbased instructions to a subject or clinician.

[0113] FIG. 4 is an example system 400 for monitoring right atrial pressure and SVC pressure. In this example, device 100 may be implanted in the SVC and be positioned to perform intermittent venous occlusion as a therapy, for example. RAP response measurements can be captured (e.g., detected by sensor 140) in conjunction with SVC pressure measurements (e.g., detected by sensor 142). Other parameters (as described in FIG. 5) may also be tuned to modify operation of the device 100 and system 400.

[0114] In this example, the sensor 140 for detecting RAP / downstream pressure sensor may be positioned in proximity to an SVC-right atrium junction in order to collect an accurate RAPresponse or related measurement. The sensor 142 for detecting the SVC pressure sensor may be positioned upstream of the device 100 (and upstream of sensor 140). In general, the system 400 may function to measure RAP responses and to ensure that the subject maintains safe ranges for pressure while undergoing diaresis treatments and / or assessments. The controller circuit 302 can generate occlusion cycles, perform occlusion ramp up / ramp down speeds, and modify occlusion levels of the occlusion device 100 in order to optimize fluid status assessments for a subject in which device 100 is implanted. The controller circuit 302 may periodically update any or all parameters described herein as the subject adapts to pressure patterns and / or pressure responses from various occlusion permutations. Artificial intelligence and / or machine learning algorithms may be used to enable adaptive learning using labeled datasets of occlusion parameters versus pressure patterns and / or pressure response patterns.

[0115] In some examples, non-physiological measurements may be captured by the sensors. Such measurements may or may not be considered in the RAP assessments described herein. For example, the devices described herein may identify and redact detected non-physiological variations from the RAP data to avoid making occlusion / blood flow changes using the device 100 when particular, unrelated to volume variations are detected (e.g., exercise, atypical physical movements, or the like). When detected, the artifacts generated by the non- physiological variations should be removed from consideration in RAP assessments.

[0116] FIG. 5 is an example graph depicting an example cycle 500 of blood flow modulation and fluid assessment using an implanted or partially implanted flow modulating device. The cycle 500 may be performed using any of the flow restricting devices described herein. As shown, the cycle 500 includes a signal 502 captured by a flow restricting device during operation of the device. The signal 502 is depicted as a percent of occlusion (y-axis) of the device over time (x-axis). A number of parameters (e.g., variables) may be used and / or modified to ensure that a particular occlusion device performs occlusion and de-occlusion of a blood vessel in a programmed or algorithmic fashion. For example, the parameters described below may be used to configure actuation cycles (e.g., occlusion cycles) for the flow modulating devices described herein. In general, any combination of the following parameters may be used to generate an operational actuation / occlusion cycle for the devices described herein.

[0117] The parameters may include a ramp up rate parameter 504 for modulating the flow of blood through the blood vessel. In some examples, the ramp up rate parameter corresponds to an amount of time to reach a selected percentage of occlusion by the device. For example, ifan occlusion cycle is programmed to target an 80 percent occlusion of a blood vessel based on monitoring of the blood vessel performed by an occlusion device, then the ramp up time may be programmed to increase occlusion at a particular rate. The ramp up rate parameter 504 may be programmed to occur in a few seconds or up to a few minutes. In some examples, the ramp up rate parameter 504 may be programmed to occur at a time greater than about three minutes. In some examples, the ramp up rate parameter 504 may be used to program a state transition time for the occlusion device to ensure that the device transitions between occlusion states (or ranges) over a specified and predefined period of time. The ramp up rate parameter 504 may be set and reset according to monitoring performed by one or more sensors of any of the devices described herein. In some examples, the ramp up rate parameter 504 may be preset according to detected pressures, subject-specific anomalies or disease state, and / or clinician instructions.

[0118] The parameters may include a clearance time parameter 506 corresponding to an amount of time for clearing blood volume from one or more portions of the device. For example, the device may be programmed to open to allow clearance of a built up volume of blood and / or to minimize a time that blood is relatively static upstream from the device. In some examples, the clearance time parameter 506 may represent a cycle clearance time that represents a time in which the device is not occluding such that the blood vessel may return to flowing without intervention. Such a break in occlusion may allow for a reduction in pressure upstream of the occlusion site. Reducing upstream pressure may function to reduce cerebral pressure for a period of time (i.e., a clearance time indicated in the clearance time parameter). The clearance time parameter 506 may be set and reset according to monitoring performed by one or more sensors of one of the devices described herein. In some examples, the clearance time parameter 506 may be preset according to detected pressures, subject- specific anomalies or disease state, and / or clinician instructions.

[0119] The parameters may include an active minimum occlusion parameter 508 that represents a period of time when the device is not in an occlusion (e.g., therapy) cycle. In some examples, the active minimum occlusion parameter 508 may be set to conserve or reduce battery usage of the device. In some examples, the active minimum occlusion parameter 508 may be used to arrange a baseline state of occlusion percentage. The baseline occlusion percentage may be programmed for a specific subject based on preliminary testing of the subject, monitoring of the subject, and / or other variable associated with the subject.

[0120] Example baseline occlusion levels may range between about 60 percent to about 95 percent, however, may include ranges between about 60 percent to about 65 percent, about 65percent to about 70 percent, about 70 percent to about 75 percent, about 75 percent to about 80 percent, about 80 percent to about 85 percent, about 85 percent to about 90 percent, about 90 percent to about 95 percent, and / or about 95 percent to about 100 percent. These baseline occlusion levels may be utilized to determine a responsiveness of right atrial pressure during test occlusions as a way to assess pressure responsiveness of the patient. The active minimum occlusion parameter 508 may be set and reset according to monitoring performed by one or more sensors of one of the devices described herein. In some examples, active minimum occlusion parameter 508 may be preset according to detected pressures, subject-specific anomalies or disease state, and / or clinician instructions.

[0121] The parameters may include a peak occlusion parameter 510 corresponding to a maximum occlusion capacity associated with operating the device. The peak occlusion parameter 510 may be set for the device to limit a maximum level of occlusion which may be defined by one or more of: maximum upstream pressure, minimum downstream pressure, and a predetermined maximum percentage of occlusion determined using a cross-sectional area of the vessel or assessing blood flow allowed through the device. This level may be conditional, meaning it could be a maximum for a particular state in which the program is operating in, or it may be an overall maximum level of occlusion enabled for the device. In some examples, the peak occlusion parameter 510 may be an absolute level of occlusion (e.g., about 50 percent, about 90 percent, etc.). The peak occlusion parameter 510 may alternatively be an individualized level based on the subject in which the device is implanted. For example, parameter 510 may be set or reset according to a predefined calibration based on one or more detected pressures for the subject. The peak occlusion parameter 510 may be set and reset according to monitoring performed by one or more sensors of any of the devices described herein. In some examples, peak occlusion parameter 510 may be preset according to detected pressures, safety measures, subject-specific anomalies or disease state, and / or clinician instructions.

[0122] The parameters may include a variable peak cycle occlusion parameter 512 representing a way to vary the peak occlusion parameter 510 for one or more cycles of occlusion, for example. In this way, a different peak occlusion parameter 510 may be set for any number of selected cycles while retaining a setting for the peak occlusion parameter 510 in the remaining cycles. The variable peak cycle occlusion parameter 512 may be set and reset according to monitoring performed by one or more sensors of any of the devices described herein. In some examples, the variable peak cycle occlusion parameter 512 may be presetaccording to detected pressures, subject-specific anomalies or disease state, and / or clinician instructions.

[0123] The parameters may include a cycle time parameter 514 corresponding to an amount of time for completing an occlusion cycle. For example, the cycle time parameter 514 may include a duty cycle (e.g., time interval) for how frequently the device is performing occlusion on the blood vessel. The cycle time parameter 514 may be set and reset according to monitoring performed by one or more sensors of any of the devices described herein. In some examples, the cycle time parameter 514 may be preset according to detected pressures, subject-specific anomalies or disease state, and / or clinician instructions.

[0124] The parameters may include an activation time parameter 516 corresponding to an amount of time in which the device is actively operating (e.g., occluding or holding occlusion). The parameter 516 may refer to a run time representing an elapsed time of occlusion or an intervention period. The activation time parameter 516 may be used to manage an amount of time the device is active for the sake of energy conservation, minimizing an ability of the body of a subject to adapt and compensate for intermittent occlusions performed by the implanted device, and / or minimizing blood stasis around the device or thrombosis events around the device. The activation time parameter 516 may be set and reset according to monitoring performed by one or more sensors of any of the devices described herein. In some examples, the activation time parameter 516 may be preset according to detected pressures, subjectspecific anomalies or disease state, and / or clinician instructions.

[0125] The parameters may further include a ramp down parameter 518 representing a rate at which the device may be opening to begin to release an occlusion process (i.e., stop occluding the blood vessel). In some examples, the ramp down parameter 518 may be a rate that is measured as a decrease in percent occlusion per second. The rate may be characterized as a linear rate of decrease, or alternatively, a rate having a predefined rate profile. In some examples, the ramp down parameter 518 may be a rate of increase in right atrial pressure on a per second basis (e.g., mmHg / sec). In some examples, the ramp down parameter 518 may be a rate of decrease in an upstream pressure (e.g. an SVC pressure in mmHg). In some examples, the ramp down parameter 518 may be defined for different conditions, for example, a predefined rate / profile of ramp up for a decrease in occlusion mid activation (e.g., for a clearance cycle, or a change in conditions during the activation of device occlusion). In some examples, the ramp down parameter 518 may be defined as a final rate of opening (deocclusion) as the device returns to an unrestricted or non-occluded state. The ramp downparameter 518 may be set and reset according to monitoring performed by one or more sensors of one of the devices described herein. In some examples, the ramp down parameter 518 may be preset according to detected pressures, subject- specific anomalies or disease state, and / or clinician instructions.

[0126] The parameters may also include an inactive maximum occlusion parameter 520 representing a length of time in which the device is not in an occlusion (e.g., therapy) cycle. In this example, the blood vessel may be a patent (i.e., open) vessel. The inactive maximum occlusion parameter 520 may be set and reset according to monitoring performed by one or more sensors of one of the devices described herein. In some examples, the inactive maximum occlusion parameter 520 may be preset according to detected pressures, subject-specific anomalies or disease state, and / or clinician instructions.

[0127] The parameters may further include a recovery time parameter 522 corresponding to a minimum time between actuations (i.e., occlusion cycles) performed by the device. For example, the recovery time parameter 522 may represent a time in between adjacent intervention / occlusion cycles such as a refractory period. The refractory period may be set for a time to allow the body to rest between occlusion cycles. For example, the time may range from about 2 minutes to about 30 minutes; about 5 minutes to about 20 minutes; about 30 minutes to about 3 hours; about 1 hour to about 2 hours; or about 3 hours to about 1 day.

[0128] In some examples, the recovery time parameter 522 may be selected to limit the amount of time the device is active for the sake of energy conservation, minimizing an ability of the body of a subject to adapt and compensate for the intermittent occlusions performed by the device, and / or minimizing blood stasis around the device or thrombosis events around the device. In some examples, the device is in an open (e.g., un-occluded or minimally occluded) state during this recovery time period. The recovery time parameter 522 may be set and reset according to monitoring performed by one or more sensors of any of the devices described herein. In some examples, the recovery time parameter 522 may be preset according to detected pressures, subject-specific anomalies or disease state, and / or clinician instructions.

[0129] The parameters may further include an agitation cycle parameter (not shown) corresponding to an amount of time to allow the device to remain stationary before triggering agitation of one or more components of the device. The agitation cycle parameter may be a safety parameter to prevent thrombus and / or reduce blood stasis by ensuring the device is agitated or moved at a predefined interval. In some examples, the device may also operate an agitation cycle according to one or more parameters to keep the implanted device fromremaining static. This agitation cycle may be performed when the device is occluded or open. In some examples, the agitation cycle may be performed passively to ensure a vessel occlusion portion 150 (e.g., an end effector) of the occlusion device is continuously moving.

[0130] The parameters may further include a level of negligible resistance parameter (not shown) corresponding to a level of occlusion determined to have negligible impact on resistance to blood flow through the device. The parameters may further include a hold time parameter (not shown) corresponding to an amount of time the occlusion is held at a particular occlusion level by the device.

[0131] With respect to any of the parameters described in FIG. 5, a range of values may be predefined for one or more parameters. The range may function to allow the devices described herein to operate according to patient-specific data, condition- specific data, or other specified data to customize operation of occlusion or de-occlusion of such devices. In some examples, enable zero or extreme values may be provided to configure any number of parameters as a way to nullify (e.g., effectively ignore) a parameter during operation of the device carrying out the processes described herein.

[0132] FIG. 6 is a block diagram of an example system 600 for modulating blood flow through one or more blood vessels and determining fluid statuses based on the modulating. The system 600 may be used with any of the flow restricting devices described herein. As shown, the system 600 includes flow restriction controls 602 and at least one implantable device 604, each of which may be optionally communicatively coupled to a first external computing device 605a and / or a second optional external computing device 605a. The implantable device 604 may correspond to any of the flow restricting devices described herein.

[0133] The flow restriction controls 602 may include one or more sensors 606, one or more processors 608, one or more control devices 610, and one or more actuation devices 612. Optionally, the flow restriction controls may include a power source 614 that may be internal to the controls 602, internal to the implantable device 604, or external to both the flow restriction controls 602 and the implantable device 604. In some examples, the power source may be wired to flow restriction controls 602 or implantable device 604. In some examples, the power source may be remotely accessed (e.g., wirelessly) by flow restriction controls 602 or implantable device 604 via device 605a and / or device 605b.

[0134] The one or more sensors 606 may be optional. In some examples, a single sensor 606 is coupled to implantable device 604. In some examples, a second sensor 606 is also coupled to implantable device 604. In some examples, the sensors 606 representmicroelectromechanical pressure sensors (e.g., MEMS). The one or more sensors 606 may function to sense (e.g., detect) properties of the blood in which the sensor(s) are disposed within. For example, the sensors 606 may detect blood pressure within the blood vessel and / or any other physiological or anatomical parameters or properties of the blood or vessel. The one or more sensors 606 may include one or more of an image sensor, a strain gauge, a piezoelectric sensor, a capacitance sensor, and / or a vacuum pressure sensor. In general, sensor signals from sensors 606 may be transmitted to control devices, device 605a, optional device 605b, and / or elements described herein via a wired or wireless connection. Additionally, and optionally, the sensors 606 may utilize one or more processors 608 to transmit data to remote computing devices. The transmitted data may include sensor measurements, device position data and / or statistics, actuation events, or any other data from the system 600.

[0135] In some examples, the sensors 606 may assess and / or recognize patterns of blood pressures for a patient over time. The patterns may be used as a trigger to perform one or more device occlusions of a blood vessel. In some examples, sensors 606 and processors 603 may perform pattern recognition that may statistically indicate a state of the patient (e.g., different grades of physical activity, illness, volume overload, volume status, arrhythmia, acute kidney injury, etc.) and such data (or patterns of data) may inform the activation of vessel occlusion or de-occlusion.

[0136] The processors 608 may include one or more microprocessors, microcontrollers, or the like, as described elsewhere herein. The control devices 610 may include active or passive controls including, but not limited to wires, sutures, operated switches, motor controllers, and / or antennas. In some examples, the control devices 610 may include external control devices including, but not limited to, remote computers, tablets, smart phones, and / or external control devices for powering and / or controlling the flow restriction controls 602.

[0137] The actuation devices 612 may include mechanically actuating devices, electrically actuated devices, electromechanically actuated devices, or a combination thereof. For example, actuation devices 612 may include any one or more of a wire, a suture, a pull wire, a linear actuator (e.g., a pneumatic linear actuator, an electromechanical linear actuator, or a hydraulic linear actuator), a magnet or coil, etc. The power sources 614 may include, but are not limited to, battery power, wall power, magnets, induction coils, or the like.

[0138] In operation of system 600, the actuation device 612 may be coupled to the control device 610, which may manipulate or move portions of the implantable device 604 based on one or more signals received from one or more sensors 606. In embodiments that utilize aprocessor 608, the processor 608 may be communicatively coupled to the one or more sensors 606, control devices 610, actuation devices 612, power source 614, and / or implantable device 604 to actuate the implantable device 604 into a restricted blood flow state, an unrestricted blood flow state, or any position therebetween.

[0139] In some examples, the processors 603 may utilize a fluid analysis module 615. The fluid analysis module 615 may receive output from one or more sensors 606 and may perform the methods described herein utilizing any or all of device 100 and / or components of system 600.

[0140] Although restricted and unrestricted flow states / configurations or restricted and unrestricted device positions are described herein, it is within the scope of the present disclosure that any number of intermediate positions or states are contemplated and included herein, whether or not expressly indicated.METHODS

[0141] FIG. 7 is a flow diagram depicting an example process 700 for determining a fluid congestion status (e.g., fluid volume status) of a subject. The process 700 may be carried out by one or more processors (e.g., processor 608) onboard implantable device 100 or by an external processor (e.g., computing device 208, 605a, 605b, etc.) in communication with device 100. The process 700 may obtain and utilize data from device 100, for example, which may be implanted in or around a blood vessel of a subject. The device 100 may include at least one pressure sensor (e.g., sensor 140 and / or sensor 142), a processor (e.g., processor 608), and a vessel occlusion portion (e.g., vessel occlusion portion 150). The processor 608 may be programmed to carry out operations including causing the vessel occlusion portion 150 to receiving an initial right atrial pressure for a subject, cause a vessel occlusion device to perform an occlusion cycle to change pressure in a blood vessel of the subject, receive monitored readings for a right atrial pressure response to the changed pressure in the blood vessel, and determine, based on the readings representing the right atrial pressure response, a fluid congestion status associated with a heart of the subject.

[0142] In general, the process 700 may function to monitor and assess pressures and / or fluid volumes associated with cardiac blood flow at a target region in a blood vessel of a heart of a subject. In some examples, the target region includes a portion of a vena cava of the subject, a portion of the superior vena cava of the subject, a portion of an inferior vena cava of the subject, or a portion of an adjacent vessel to the vena cava, the superior vena cava, or the inferior venacava. The process 700 may be used for blood flow regulation in the SVC or the IVC, but can additionally, or alternatively, be used for any suitable applications, clinical or otherwise. In general, process 700 may be used with any of the devices and / or systems described herein.

[0143] At block 702, the process 700 may include receiving an initial right atrial pressure for the subject. For example, an external computing device 605a may receive an output indicating a measured RAP for a subject in which device 100 is implanted. The output of the initial RAP may be received from sensor 140 or onboard processor 608. In some examples, the initial RAP may represent a measurement of the RAP after (or during) performance of an occlusion cycle by device 100. In some examples, the initial RAP may represent a measurement of RAP before a treatment and before performing one or more occlusion cycles.

[0144] At block 704, the process 700 may include causing, over a time period, a vessel occlusion device (e.g., device 100) to perform an occlusion cycle to change pressure in a blood vessel of the subject. For example, the device 100 may be provided instructions (e.g., software instructions for execution by processor 608) to perform one or more occlusion cycles to introduce pressure at a portion of the blood vessel as described elsewhere herein. The time period may refer to an occlusion cycle time, which may be from a few seconds to about greater than 20 minutes. In some examples, the time period may refer to a monitoring window of time. A monitoring window may be about 10 minutes to about 4 hours.

[0145] In some examples, the change in the pressure over the time period may be performed at a predefined rate of occlusion associated with the vessel occlusion device, as described elsewhere herein. The process 700 may determine the fluid congestion status using the rate of occlusion to determine a relationship between the changed pressure and a change in the right atrial pressure response over the time period. For example, the degree in which RAP drops and / or rebounds informs the degree in which the right atrium / heart is volume responsive or volume overloaded. If the immediate rebound is higher after an occlusion cycle, this would indicate volume overload; if the immediate rebound after an occlusion cycle is lower, this would indicate euvolemia, or hypovolemia, in some examples.

[0146] At block 706, the process 700 may include receiving monitored readings for a right atrial pressure response to the changed pressure in the blood vessel over the time period. For example, the device 100 (including sensor 140 and / or sensor 142) may communicate the readings (e.g., RAP responses, measurements, and the like) to processor 608 and processor 608 may provide the monitored readings to an external computing device for further assessment. Alternatively, the device 100 may communicate readings directly to an external computingdevice for further assessment. In some examples, the process 700 may be carried out on processor 608 and thus sensor 140 and / or sensor 142 may send monitored readings of RAP directly to processor 608 for further processing. In some examples, the monitoring may include obtaining or sampling readings of RAP responses (or other physical responses) as detected by one or more sensors 140, 142 during the time period before, during, or after, an occlusion event or cycle.

[0147] At block 708, the process 700 may include determining, for the subject and based on the readings representing the right atrial pressure response, a fluid congestion status associated with a heart of the subject. For example, the processor 608 and / or external computing device 605a may use the RAP readings captured during the time period to determine a fluid congestion status for the subject. Determining the fluid congestion status may include determining, for a plurality of times within the time period, a difference between the initial right atrial pressure and the right atrial pressure response to the changed pressure introduced by the occlusion of device 100. The difference in pressure over time and responsive to introduced occlusion in the vessel can indicate whether or not to treat a subject, change treatment for the subject, or otherwise provide other recommendations to the subject. For example, the process 700 may further include generating a recommendation for continuous infusion of loop diuretics or oral diuretics in response to determining that the difference in pressure is more than about 2 mmHg below the initial right atrial pressure. In some examples, the process 700 may further include generating a recommendation for reduction of one or more occlusion cycles or terminating loop diuretics or oral diuretics in response to determining that the difference in pressure is substantially zero for about 30 seconds to about 10 minutes; about 30 seconds to about 2 minutes; about 2 minutes to about 7 minutes; about 4 minutes to about 6 minutes; about 5 minutes to about 9 minutes; or about 9 minutes to about 10 minutes.

[0148] In some examples, the fluid congestion status includes a threshold range associated with a hypervolemic state, a hypovolemic state, or a euvolemic state, and the process 700 further includes using the threshold range as a basis in which to trigger additional occlusion cycles. For example, based at least in part on the determined difference between the initial right atrial pressure and the right atrial pressure response to the changed pressure, the process 700 may indicate which state the subject is assigned and may also trigger modifications and / or additional or fewer occlusion cycles to be performed to change the state of the subject.

[0149] In some examples, the process 700 is carried out while the subject is undergoing diuresis treatment during the time period. In such an example, the process 700 may furtherinclude detecting efficacy of the diuresis treatment by determining a magnitude of the right atrial pressure response during the time period and generating an indication to halt the diuresis treatment in response to determining that the magnitude of the right atrial pressure response is below a predefined response threshold. In some examples, the predefined response threshold is based at least in part on medical data associated with the subject including, but not limited to, electronic medical records, test results, symptom tracking apps, responses and / or output from prior occlusion cycles, or the like. For example, the process 700 may utilize previously measured RAP values and / or treatments for a subject to determine what limits or thresholds to use when monitoring the same subject at a future date. In some examples, the predefined response threshold includes a lack of response or substantially no pressure change responsive to the occlusion event or cycle.

[0150] Determining the magnitude of RAP may include using (or receiving data from) sensor 140 to measure a pressure level in the vessel over time. The processor 608 or computing device 605a may generate a curve (or table) of magnitudes based on the received data. The processor 608 or computing device 605a, for example, may assess RAP changes over time based on the magnitude curve (or table).

[0151] In some examples, an occlusion cycle is programmed to occlude from about 80 percent to about 100 percent of the blood vessel. The process 700 may further include performing the occlusion event or cycle, and determining, responsive to the occlusion event or cycle, a tricuspid regurgitation grade for the subject.

[0152] In response to determining that the tricuspid regurgitation grade has dropped below a baseline threshold grade for the subject, the processor 608 or computing device 605a may generate a first output indicating that the tricuspid regurgitation in the subject is a result of venous congestion. The baseline threshold may be a range set for the subject. Grades of TR span mild, moderate, severe, massive, to torrential. The baseline may be initially established by assigning the TR grade (from an echocardiogram) to the specific RAP response pattern to occlusion, performed in a hospital setting. The remaining TR grades on the spectrum may then be extrapolated based on that mapping with different RAP response patterns to occlusion. In some examples, the process 700 further includes generating, based on the first output, a diuresis schedule to reduce congestion in the subject.

[0153] In some examples, the process 700 includes generating a second output indicating that the tricuspid regurgitation in the subject is not a result of venous congestion, in response to determining that the tricuspid regurgitation grade has not dropped below the baselinethreshold grade for the subject, for example. The process 700 may further generate a treatment schedule for alleviating or reducing the tricuspid regurgitation. An example treatment schedule may include a diuretic titration escalated in a stepwise manner until TR grade mild or moderate is achieved. In some examples, the process 700 further includes generating, based on the second output, an indication of a stage of the tricuspid regurgitation and generating a treatment schedule according to the indication of the stage of the tricuspid regurgitation.

[0154] In some examples, the process 700 further includes generating a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia in response to determining that a relationship between the rate of occlusion and the right atrial pressure response decreases during performance of an occlusion cycle, as described with respect to FIG. 2. In some examples, the process 700 further includes recommending a modified occlusion cycle or multiple occlusion cycles to treat the determined right atrial pressure response. For example, the monitoring may include determining that the subject would benefit from additional occlusion cycles or altered occlusion cycles and may generate such instructions to the processor(s) and / or recommendations to the subject to perform the cycles.

[0155] The process 700 may further include generating a metric representing an acuity of tricuspid regurgitation in the subject in response to determining that a relationship between the rate of occlusion and a tricuspid regurgitation grade of the subject decreases during performance of the occlusion cycle. The process 700 may then use the metric to generate a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0156] In some examples, the process 700 may include receiving a measurement of left atrial pressure of the subject over the time period from sensors 140, 142, or another sensor and may determine a level of function of a right ventricle of the subject, based on a rate of occlusion in which the occlusion is performed, the right atrial pressure response, and / or the left atrial pressure measurement. The process 700 may then generate an output indicating the level of function of the right ventricle of the subject. The process 700 may further include receiving a measurement of left atrial pressure of the subject over the time period, and determining, based on the rate of occlusion, the right atrial pressure response, and the left atrial pressure measurement, a level of function of a pulmonary vessel of the subject. The process 700 may then include generating an output indicating the level of function of the pulmonary vessel of the subject. For example, the processor 608 and / or computing device 605a may utilize the rate of occlusion, the RAP response, and the left atrial pressure measurement to calculate a level ofpulmonary vessel function and may generate the corresponding output indicating the level for display in a UI on a computing device, such as computing device 605a.

[0157] In some examples, the process 700 may further include determining, based on the rate of occlusion and the right atrial pressure response, a cardiac efficiency of the subject. The process 700 may then generate an output indicating the cardiac efficiency of the subject. The output may be provided for display in a UI on a computing device, such as computing device 605a.

[0158] In some examples, the device 100 may carry out process 700 on processor 608 that is part of device 100. In such an example, the at least one processor 608 may be electrically coupled to at least one pressure sensor 140 and / or 142, the vessel occlusion portion 150 may be implanted in a portion of the blood vessel (e.g., a vena cava, a superior vena cave, an inferior vena cava), and the at least one pressure sensor may include a first pressure sensor 140 positioned at a distal end 110 of the vessel occlusion portion 150 and a second pressure sensor 142 positioned at a location upstream of the first sensor 140. The process may then further include detecting, using the first pressure sensor 140, a first pressure (e.g., RAP) in the blood vessel, detecting, using the second pressure sensor 142, a second pressure (e.g., superior vena cava pressure indicating a level of intracranial venous pressure) in the blood vessel at the location upstream of the first sensor 140, determining a pressure gradient between the first pressure and the second pressure, and generating, based on the pressure gradient, the fluid congestion status.

[0159] FIG. 8 is a flow diagram depicting an example process 800 for determining a fluid volume status of a subject. The process 800 may be carried out by one or more processors (e.g., processor 608) onboard implantable device 100 or by an external processor (e.g., computing device 208, 605a, 605b, etc.) in communication with device 100. The process 800 may obtain and utilize data from device 100, for example, which may be implanted in or around a blood vessel of a subject. In some examples, the device 100 may be implanted extravascular to the blood vessel. In some examples, the device 100 may be implanted intravascularly in the blood vessel. In some examples, the blood vessel is a vena cava.

[0160] At block 802, the process 800 may include providing the device 100 implanted in or around a blood vessel of the subject. The device 100 may include at least one pressure sensor (e.g., sensor 140 and / or sensor 142), a processor (e.g., processor 608), and a vessel occlusion portion (e.g., vessel occlusion portion 150). The processor 608 and / or device 208, 605a, or 605b may be programmed to carry out instructions associated with process 800.

[0161] At block 804, the process 800 may include causing the vessel occlusion portion 150 to introduce at least a partial occlusion in the blood vessel (e.g., a vena cava, a superior vena cava, or an inferior vena cava), as described elsewhere herein.

[0162] At block 806, the process 800 may include monitoring, using the at least one pressure sensor 140, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period, as described elsewhere herein. In general, the monitoring may include obtaining or sampling readings of RAP responses (or other physical responses) as detected by one or more sensors 140, 142 during the time period before, during, or after, an occlusion event or cycle. The monitoring may further include determining whether the subject would benefit from additional occlusion cycles or altered occlusion cycles.

[0163] At block 808, the process 800 may include determining, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject, as described elsewhere herein. In process 800, the right atrial pressure response may be an increase, a decrease, or a negligible change in right atrial pressure during the time period and the indication may be determined as a basis in which to generate a treatment recommendation to achieve or maintain euvolemia. In some examples, the process 800 further includes generating, based on the indication, the treatment recommendation(s) for the subject to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0164] In some examples, the indication may be a value or a curve determined during the time period by calculating a relative change in right atrial pressure for the subject from a baseline right atrial pressure of the subject and comparing the relative change in right atrial pressure to a Frank-Starling curve. The process 800 may use the indication as a basis in which to generate a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia. In some examples, the indication may be a value or a curve determined during the time period by calculating an absolute change in right atrial pressure for the subject and comparing the absolute change in right atrial pressure to a Frank- Starling curve. The process 800 may use the indication as a basis in which to generate a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia. For example, the process 800 may include determining the treatment recommendation by comparing the determined indication to one or more of: a hypervolemia threshold range, a hypovolemia threshold range, or data representing past fluid treatment events or disease information associated with the subject.

[0165] In some examples, the treatment recommendation may include one or more instructions to up-titrate intravenous loop diuretic treatment, down-titrate intravenous loop diuretic treatment, or terminate intravenous loop diuretic treatment. In some examples, the treatment recommendation may include one or more instructions to up-titrate oral diuretic treatment, down-titrate oral diuretic treatment, or terminate oral diuretic treatment.

[0166] In some examples, the process 800 may further include generating, based on the indication, a treatment recommendation to alter the fluid volume status. The treatment recommendation may include fluid administration to the subject, diuretic administration to the subject, or a dietary adjustment for the subject, as described elsewhere herein. In some examples, the process 800 may further include causing provision of the treatment recommendation to the subject, causing (after the time period and after opening e.g., relieving or relaxing vessel occlusion portion 150 and opening of the at least partial occlusion in the blood vessel) introduction of a second at least partial occlusion in the blood vessel. The process 800 may include monitoring, using the at least one pressure sensor 140, an additional right atrial pressure response to the second at least partial occlusion for a second time period, determining, based on the additional right atrial pressure response, a second indication representing an updated fluid volume status associated with the heart of the subject, and determining, based on the second indication, a new treatment recommendation for the subject. The above steps of process 800 may be repeated until the monitoring step indicates that the fluid volume status associated with the heart of the subject maintains a fluid volume status substantially associated with euvolemia. In such an example, the fluid volume status may include a metric or a range for classifying the subject during the time period into a hypervolemic state, a hypovolemic state, or a euvolemic state, as described elsewhere herein. In general, the metric or range may be used with the indication to generate a treatment recommendation to achieve or maintain euvolemia.

[0167] In some examples, the process 800 further includes iteratively causing the vessel occlusion portion 150 to introduce and remove an occlusion in the blood vessel, monitoring, using the at least one pressure sensor 140 and / or processor 608, additional right atrial pressure responses over a second time period responsive to introduction and removal of the occlusion in the blood vessel. The process may further include determining, based on the additional right atrial pressure responses, an updated indication representing the fluid volume status associated with the heart of the subject and generating a cadence for performing the treatment recommendation based on the updated indication. Example time between each iteration mayinclude about 10 minutes to about six hours; about 10 minutes to about one hour; about one hour to about three hours; about three hours to about four hours; about four hours to about five hours; or about five hours to about six hours. For each updated indication generated in an iteration, a fluid volume status may be determined and process 800 may include assessing each fluid volume status as a basis in which to tune the time between each iteration for future monitoring.

[0168] FIG. 9 is a flow diagram depicting an example method of treatment process 900 for using a right atrial pressure response to adjust an amount of diuretic to introduce to a subject experiencing hypervolemia or hypovolemia. In some examples, the diuretic may be automatically delivered, for example via an electrically connected syringe and pump. In some examples, the diuretic may be manually delivered via syringe and / or IV. The process 900 may be carried out by one or more processors (e.g., processor 608) onboard implantable device 100 or by an external processor (e.g., computing device 208, 605a, 605b, etc.) in communication with device 100. The process 900 may obtain and utilize data from device 100, for example, which may be implanted in or around a blood vessel of a subject. The device 100 may include at least one pressure sensor (e.g., sensor 140 and / or sensor 142), a processor (e.g., processor 608), and a vessel occlusion portion (e.g., vessel occlusion portion 150).

[0169] In some examples, the actuatable device may further include a frame 106 having a proximal end 108 opposite a distal end 110 (see FIGS. 1A, 1BN) and a longitudinal axis (L) extending therethrough. The actuatable device 100 may further include a vessel occlusion portion 150 having an inflow end 114 and an outflow end 116. The inflow end 114 may be at least partially installed within the distal end 110 of the frame 106. The outflow end 116 may be coupled to a plurality of elongate support members 120a-120f arranged radially around an outer surface of the membrane 112 and extending substantially parallel to the longitudinal axis (L). The end effector (e.g., vessel occlusion portion 150) may radially collapse at the outflow end and toward a central axis (C) of the frame, or radially expand away from the central axis (C) of the frame 106, in response to an actuation of a control wire 122 coupled to a portion of the vessel occlusion portion 150.

[0170] At block 902, the process 900 may include introducing an actuatable device 100 in a blood vessel, such as a vena cava, a superior vena cave, or an inferior vena cava. The device 100 may include at least one sensor (e.g., sensor 140, sensor 142, sensors 606, etc.) electrically coupled to the actuatable device 100 where the at least one sensor may detect a pressure in a blood vessel. The device 100 may further include a processing module (e.g., processor 608and / or fluid analysis module 615) electrically coupled to the at least one sensor (e.g., sensor(s) 606) to monitor outputs from the at least one sensor.

[0171] At block 904, the process 900 may include actuating, based on the monitoring of the outputs, the actuatable device 100 to introduce at least a partial occlusion in the blood vessel, as described elsewhere herein.

[0172] At block 906, the process 900 may include monitoring, using the at least one sensor, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period, as described elsewhere herein.

[0173] At block 908, the process 900 may include determining, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject, as described elsewhere herein. For example, determining the fluid volume status may include determining, for a plurality of times within the time period, a difference between an initial right atrial pressure of the subject and the right atrial pressure response to the at least partial occlusion. In some examples, the fluid volume status may include a threshold value associated with a hypervolemic state, a hypovolemic state, or a euvolemic state, as described elsewhere herein. In such examples, the process 900 may further include using the threshold value to trigger additional occlusions (or occlusion cycles) in the blood vessel based at least in part on a determined difference between the initial right atrial pressure and the right atrial pressure response to the at least partial occlusion.

[0174] At block 910, the process 900 may include generating an indication to adjust the amount of diuretic to introduce to the subject in response to determining that a magnitude of the right atrial pressure response is below a predefined response threshold. The predefined response threshold may be based at least in part on medical data associated with the subject and / or the predefined response threshold may include a lack of response.

[0175] In some examples, the process 900 further includes generating a recommendation for administering continuous infusion of loop diuretics or oral diuretics in response to determining that the difference is more than about 2 mmHg below the initial right atrial pressure. In some examples, the process 900 may include generating a recommendation to discontinue loop diuretics or oral diuretics in response to determining that the difference is substantially zero for about 30 seconds to about 10 minutes; about 30 seconds to about 2 minutes; about 2 minutes to about 7 minutes; about 4 minutes to about 6 minutes; about 5 minutes to about 9 minutes; or about 9 minutes to about 10 minutes.

[0176] In some examples, the device utilized in the processes described herein includes a rigid or expandable frame including a proximal end and a distal end and a longitudinal axis extending therethrough and a membrane including an inflow end and an outflow. The outflow end may be coupled to a plurality of elongate support members arranged radially around an outer surface of the membrane and extending substantially parallel to the longitudinal axis. One or more of the elongate support members may radially collapse at the outflow end and toward a central axis of the expandable frame, or radially expand away from the central axis of the expandable frame, in response to an actuation of a control wire coupled to a portion of the membrane / device.

[0177] Further, one or more sensors may be used in conjunction with any of the devices and systems herein to measure one or more physical characteristics of a subject having one of the devices implanted. For example, it may be beneficial to measure whether the subject is standing, sitting, or laying. In addition, the pressure thresholds for activating the device may be influenced by the activity of the subject. For example, it may be beneficial to realize the subject is exercising, as this would elevate pressures and may cause an adjustment in pressure thresholds. Characteristics described above may be measured by a pressure sensor in blood vessels of other portions of the body, a gyroscopic sensor for changes in angular position, an accelerometer for changes in acceleration, a heart rate sensor, a sensor measuring a size of a blood vessel, or any other sensors for measuring physical characteristics. The described characteristics, individually or in combination, may be received by a processor and processed to cause changes in valve / membrane / occlusion device position (using an actuating device) based on the sensed characteristics.EXAMPLE IMPLANTATION OF FLOW MODULATING DEVICES

[0178] FIG. 10 illustrates a schematic representation of portions of a subject 1000. The flow modulating devices described herein of FIGS. 1A-10 (represented in FIG. 10 by device 1002) may be introduced (e.g., implanted) in vasculature of the body. In general, the device 1002 may represent any of the flow modulating devices described herein (e.g., device 100, device 604, system 600, etc.) and may include the same or similar functionality and / or structures. In some examples, the device 1002 may be implanted in or near to a portion of the SVC 1004. In some examples, the device 1002 may be implanted in or near to a portion of the IVC 1006. The subject 1000 is illustrated with a representation of a portion of the vasculature system to generally illustrate the SVC 1004 and the IVC 1006 within the subject 1000. However, it is tobe understood that no dimensions or relative sizes of components may be inferred from the relative sizes and dimensions of elements in the figures.

[0179] The subject 1000 includes a number of vessels and organs that may circulate blood throughout the body. For example, renal veins 1008a and 1008b drain blood from respective right kidney 1010 and left kidney 1012. Renal veins 1008a and 1008b connect to the 1VC 1006. Blood from the aorta 1014 flows to the IVC 1006. Blood travels from the aorta 1014 to the abdominal organs including the stomach (not shown), liver (not shown), spleen (not shown), pancreas (not shown), large intestines (not shown), and small intestine (not shown). Following processing of the blood by the liver, blood collects in the central vein. Blood from these central veins converges in the hepatic veins (not shown) which exit the liver and empty into the IVC 1006 to be distributed to the rest of the body.

[0180] Portions of the above-recited blood circulating vessels and / or organs may be involved in splanchnic venous circulation that includes blood flow originating from the celiac, superior mesenteric, and inferior mesenteric arteries to the abdominal organs. The splanchnic venous circulation may act as a blood reservoir that can support the need for increased stressed blood volume during periods of elevated sympathetic tone, such as during exertion, to support increased cardiac output and vasodilation of peripheral vessels supporting active muscles.

[0181] Heart failure subjects can have multiple comorbidities that cause excessive congestion or accumulation of blood volume in the splanchnic venous circulation and / or resulting increases in intracranial pressure based on the accumulation of blood volume. The excessive congestion or accumulation causes excess load on the heart, over-reactive fight or flight responses, poor oral medication absorption, etc. Example comorbidities can include chronic kidney disease, chronotropic incompetence, inability to increase stroke volume, and / or peripheral microvascular dysfunction. This can lead to venous congestion and / or abrupt rises in central venous pressure, pulmonary artery pressure, and / or pulmonary capillary wedge pressure. To alleviate such pressures, the blood reserves within the blood reservoir described above can be used to support the need for increased stressed blood volume during periods of elevated sympathetic tone. The flow modulating devices described herein may be used to ensure that such blood reserves within the blood reservoir can be utilized. For example, because blood flow from the splanchnic venous circulation is directed through hepatic veins and into the IVC 1006, devices (as described herein) may be placed into the IVC 1006 to limit blood flow to allow the splanchnic venous circulation to expand with increased blood volume. This may also allow the body to accumulate blood volume in the splanchnic venous circulation,which can maximize the downstream drop of pressure relative to upstream increase of pressure. Similarly, devices (as described herein) may be placed into the SVC 1008 to monitor pressures and / or limit blood flow to allow the reservoir to expand with increased blood volume. Furthermore, the flow modulating devices described herein may be placed in either the IVC 1006 and / or SVC 1008 to monitor and / or alleviate pressure in the right side of the atrium of the heart 1016 and / or regulate renal venous pressure and kidney function and / or to diagnose, monitor, or otherwise assess fluid volume status of the body. Another example positioning of a flow modulating device may be in the IVC below the renal veins. This positioning may have a similar effect as the SVC location, as it may allow the flow modulating device to maintain renal venous pressure, which can correlate with sustained renal function and diuresis.

[0182] In some examples, the flow modulating device 1002 (representing the devices described herein) may be used as a method of treatment to treat any combination of heart failure, fluid dysbiosis, chronic kidney disease, chronotropic incompetence, inability to increase stroke volume, and / or peripheral microvascular dysfunction. In addition, the flow modulating device 1002 may be used as a method of treatment to regulate pressure in the right atrium of the heart and / or regulate intracranial venous pressure. Further, the flow modulating device 1002 may be used as a method of treatment to improve function of the kidneys in subjects having reduced kidney function due to pressure in the venous system.

[0183] For example, any of the implantable devices and / or systems described herein may be configured to modulate a volume of blood flowing from a superior vena cava into a right atrium to decrease right atrial pressure and / or to decrease intracranial venous pressure and use such pressure responses to assess and carry out fluid management in a subject in which such a device is implanted.

[0184] Further for example, any of the implantable devices and / or systems described herein may be used to perform a method including restricting blood flow within a blood vessel as a way to increase, maintain, or decrease particular pressure in one or more blood vessels.

[0185] Still further for example, any of the implantable devices and / or systems described herein may be used to perform a method of treatment for a subject having one or both of: congestive heart failure or chronic kidney disease. The method may include restricting blood flow within the blood vessel.

[0186] As used herein, the term “active” with respect to blood flow management may represent operations carried out by the devices described herein using power or controller induced movement. For example, actively moving a portion of the devices described hereinmay include the use of battery power, wall outlet power, magnetic field induction, electromagnetic field induction, magnetic polarization, a piston-based system, a valve based system (e.g., with a manifold), hydraulics, pneumatics, optical actuators, thermal actuators, and / or other actuator using electrical or inductive power.

[0187] In some examples, an active control mechanism may include a microcontroller and / or a power source implanted with or integrated with the flow management device. Alternatively, or additionally, an active control mechanism can include a microcontroller and / or a power source in a remote control device, external to the body, or in an implanted remote device (e.g., subcutaneously, intravascularly, etc.), for example. The remote control device may be in wireless communication with the implanted device or connected to the implanted device through one or more leads.

[0188] In any of the embodiments described herein, an active mechanism may include a pump fluidly connected to a reservoir; a chamber having a first portion and a second portion; a manifold fluidly connected to the pump, the reservoir, and the chamber; and a piston coupled to a control element of a flow modulating device. The manifold may include at least one port that fluidly connects the reservoir to the first portion of the chamber. The piston can move between a restricted blood flow position and an unrestricted blood flow position within the chamber or any position therebetween for intermediate blood flow restriction positions. For example, the piston may move to the restricted blood flow position when a fluid flows from (or is pumped from) the reservoir through the manifold into the first portion of the chamber. The piston can return to the unrestricted blood flow position when the fluid is evacuated from the first portion of the chamber. In some examples, the manifold is fluidly connected to a second portion of the chamber through a second port. In such embodiments, the piston can move to the unrestricted blood flow position when the fluid enters the second port from the reservoir through the manifold, thereby causing the valve of the flow modulating device to move to the unrestricted blood flow state. In some examples, the fluid is evacuated from the second portion of the chamber through the second port when the piston is in the restricted blood flow position. In some implementations, the at least one port further fluidly connects the first portion of the chamber to the pump through the manifold. For example, the at least first port is fluidly connected to the pump through the manifold to evacuate the fluid from the first portion of the chamber thereby moving the piston to the unrestricted blood flow position. In some examples, the piston is a spring -based piston. For example, the spring-based piston canautomatically return to the unrestricted blood flow position when the fluid is evacuated from the first portion of the chamber.

[0189] In any of the embodiments described herein, an active mechanism may include an actuator (e.g., a linear actuator) coupled to a control element of the flow management device. The linear actuator tensions the control element to position the valve of the flow management device in a restricted blood flow state. Alternatively, the linear actuator releases tension in the control element to position a valve, a membrane, or other material in an unrestricted blood flow state. The tensioning and releasing of tension on the control element may be based on a predefined set of parameters or based on a sensed attribute of the blood vessel in which the flow management device is implanted. For example, the sensed attribute may be sensed by a sensor. The sensor may be coupled to the flow management device, a remote control device, or otherwise in wireless or electrical communication with a flow management system. The sensor can be a strain gauge, a piezoelectric sensor, a capacitance sensor, or a vacuum pressure sensor, such that the sensor senses a pressure in the blood vessel.

[0190] In any of the embodiments described herein, the linear actuator is an electromechanical linear actuator having a first magnet that, when caused to rotate by another magnet or actuator, causes a nut to rotate on a lead screw, the nut being coupled to the control element. A second magnet in a control device may cause rotation of the first magnet, for example by changing its magnetic field pole direction. In some examples, a repeater magnet (with or without its own power source) is positioned between the first magnet and the second magnet, for example in cases where the first magnet is beyond a threshold distance from the second magnet.

[0191] In any of the embodiments described herein, the linear actuator is a pneumatic linear actuator having a piston coupled to the control element. Injecting compressed gas moves the piston to tension the control element to move the valve into a restricted blood flow state and venting the compressed gas releases tension in the control element to move the valve to an unrestricted blood flow state.

[0192] In any of the embodiments described herein, the linear actuator is a hydraulic linear actuator having a piston coupled to the control element. Injecting liquid moves the piston to tension the control element to move the valve into a restricted blood flow state and venting the liquid releases tension in the control element to move the valve to an unrestricted blood flow state.

[0193] In any of the embodiments described herein, the linear actuator is a thermal linear actuator having a piston coupled to the control element. For example, decreasing a temperature of a thermal sensitive fluid (e.g., via a heat source, changes in body temperature, etc.) causes the piston to compress the fluid to tension the control element to move the valve into the restricted blood flow state. Alternatively, increasing the temperature of the thermal sensitive fluid causes the piston to decompress the fluid to release tension in the control element to move the valve to the unrestricted blood flow state.

[0194] As used herein, the term “passive” with respect to blood flow management may represent operations carried out by the devices described herein using passively induced movement. For example, passively moving a portion of the devices described herein may include the use of manual pull wires (e.g., sutures, actuation wires / cords, etc.), anatomy responses (e.g., changes in vessel inner diameter, intra-vessel pressure, etc.), blood movement, or the like.

[0195] Any of the implantable or flow modulating devices described herein may be coated with a polymer (e.g., silicones, poly(urethanes), poly(acrylates), or copolymers such as poly(ethylene vinyl acetate), a drug (e.g., heparin, pro-endothelialization drugs, anti- thrombogenic drug, etc.), a textile (e.g., woven, knitted, nonwoven, or braided), tissue (e.g., bovine pericardium, equine pericardium, porcine vena cava, etc.), or a combination thereof. Woven and knitted fabrics may be made from poly(ethylene terephthalate), while the nonwoven fabrics may be made from expanded poly (tetrafluoroethylene). Some textiles may also or alternatively include silk or silk-based materials.

[0196] Further, any of the pull wires, sutures, frames / stents, or actuation wires described herein may include silk, silk-based materials, nylon, synthetic polymer materials (e.g., silicone, polydioxanone, polyglycolic acid, polyglyconate, polylactic acid, etc.), natural materials (e.g., purified catgut, collagen, sheep intestines, cow intestines, etc.), metal (e.g., Nitinol®, palladium, gold and their alloys, etc.), or a combination thereof.

[0197] The flow modulating devices described herein may be part of (or installed within) a stent. The stent may represent a frame or outer frame that provides a support structure for the flow modulating devices when the stent is implanted into a blood vessel. The frame / outer frame may be a self-expanding frame or a balloon-expandable frame. In general, any type of stent may be used with the flow modulating devices. Example stents may include, but are not limited to, bare metal stents, coated stents, drug-eluting stents, biodegradable stents, balloon expandable stents, and self-expandable stents.

[0198] The stents described herein may be configured to house all or a portion of the flow modulating devices described herein. Such stents may include an assembly with strut members interconnected by joints that form a series of linked mechanisms that result in a hollow tubeshaped element. The stents may be positioned and / or repositioned within a blood vessel to introduce or remove flow modulating devices or device members including, but not limited, to valving, control elements, balloons, flexible members, rigid members, adjustment mechanisms, sensors, coils, wires, and / or magnets. One or more of such device members may be actuated to modify stent shape (or device member shape) for purposes of modifying a flow of fluid through the vessel associated with the implanted stent. Moreover, the stents described herein may partially or fully surround a flow modulating device. For example, a stent or stent portion may surround a portion of a flow modulating device to ensure the device remains in a specified position in a blood vessel. In some examples, the stent surrounds the flow modulating device entirely. In some examples, the stent surrounds the flow modulating device and further continues beyond one or both ends of the device.

[0199] The stents described herein may include an outer frame. The outer frame may have a form and structure that varies. For example, the strut members and / or articulated joints may form a mesh-like structure. The strut members may be interconnected in such a way as to form a shaped pattern of cells. For example, any number of strut members may form a ring of the stent such that the strut members are connected by any number of crowns. Any number of rings may form a body of the stent, and the rings may be connected by any number of bridges. Example cell shapes may include, but are not limited to diamond, square, rectangle, triangle, oval, ganglion, or any combination thereof. In some examples, the cells may be evenly shaped and distributed from a first end of the stent to a second end of the stent. In some examples, the cells may include a number of strut members interconnected in such a way that when the stent expands radially, one or more of the cells become longitudinally shorter. Similarly, when the stent constricts radially, one or more of the cells become longitudinally longer.

[0200] Constricting portions of the stents described herein may result in an outer frame woven tighter than other portions of the stent that are not constricted. The constriction may push against one or more portions of the flow modulating devices described herein to narrow a pathway through the frame or outer frame and / or to trigger the flow modulating device to begin or end constriction. Similarly, expanding portions of the stents described herein may result in an outer frame woven looser than other portions of the stent that are not expanded. The expansion may release one or more portions of the flow modulating devices describedherein to widen a pathway through the frame or outer frame and / or to trigger the flow modulating device to begin or end constriction.

[0201] The flow modulating devices described herein may be introduced to a vessel or tissue site using a delivery system. For example, such delivery systems may be used to position catheter tips and / or catheters in various portions of a target vasculature. A delivery system may include a delivery catheter having a pusherwire or the like disposed therein. The pusherwire may be configured to deploy any of the devices described herein, for example by urging the device out of a distal end of the catheter and either actively expanding the device or allowing the device to passively expand once it is no longer constrained by a lumen of the catheter. Any of the devices described herein may be crimped or otherwise compressed such that a cross- sectional area of the device is sized and / or shaped to be delivered through a lumen of a catheter. In some examples, the crimped or compressed device may be transferred to the delivery system using a transfer sheath, or the like. A delivery system can access the vasculature through an access site, such as a radial artery, brachial artery, internal jugular vein, common femoral vein, subclavian veins, or the like.

[0202] For example, for central venous access, a catheter tip and / or catheter may be configured to pass from the femoral vein into the inferior vena cava.

[0203] In some examples, the delivery system may include a trocar or other suitable delivery device used for implanting devices subcutaneously, for example control devices for controlling activation of any of the flow modulating devices described herein. As described elsewhere herein, various control systems may include an implanted remote device that is configured to transmit control signals to a flow modulating device disposed in the vasculature. The control signals may include signals transmitted wirelessly, through a wired connection (e.g., leads), or via magnetic field induction, electromagnetic field induction, or magnetic polarization.

[0204] However, it will be understood that the delivery system can refer or generally apply to positioning of catheter tips and / or catheters from a first body chamber or lumen into a second body chamber or lumen, where the catheter tips and / or catheters may be bent when positioned from the first body chamber or lumen into the second body chamber or lumen. A body chamber or lumen can refer to any one of a number of fluid channels, blood vessels (e.g., superior vena cava, inferior vena cava, renal artery, renal vein, etc.), and / or organ chambers (e.g., heart chambers). Additionally, reference herein to “catheters,” “tubes,” “sheaths,” “steerable sheaths,” and / or “steerable catheters” can refer or apply generally to any type of elongate tubular delivery device including an inner lumen configured to slidably receiveinstrumentation, such as for positioning within an atrium, coronary sinus, superior vena cava, or inferior vena cava, including for example delivery catheters, cannulas, and / or trocars. It will be understood that other types of medical implant devices and / or procedures can be delivered to the coronary sinus, superior vena cava, inferior vena cava, etc. using a delivery system as described herein, including for example ablation procedures, drug delivery, and / or placement of actuator leads.

[0205] Described herein are various example medical implants and / or delivery methods. Some examples described herein may be used in combination and / or may be used independently.

[0206] Provided below is a list of examples, each of which may include aspects of any of the other examples disclosed herein. Furthermore, aspects of any example described above may be implemented in any of the numbered examples provided below.

[0207] Depending on the example, certain acts, events, or functions of any of the processes or algorithms described herein can be performed in a different sequence, may be added, merged, or left out altogether. Thus, in certain examples, not all described acts or events are necessary for the practice of the processes.

[0208] Example 1. A method for determining a fluid congestion status of a subject, the method being carried out by at least one processor executing operations comprising: receiving an initial right atrial pressure for the subject; causing, over a time period, a vessel occlusion device to perform an occlusion cycle to change blood flow resistance in a blood vessel of the subject; receiving monitored readings for a right atrial pressure response to the changed blood flow resistance in the blood vessel over the time period; and determining, for the subject and based on the readings representing the right atrial pressure response, a fluid congestion status associated with a heart of the subject.

[0209] Example 2. The method of example 1, wherein the subject is undergoing diuresis treatment during the time period and the operations further comprise: detecting efficacy of the diuresis treatment by determining a magnitude of the right atrial pressure response during the time period; and generating an indication to halt the diuresis treatment in response to determining that the magnitude of the right atrial pressure response is below a predefined response threshold.

[0210] Example 3. The method of any of one of the preceding examples, but particularly example 2, wherein the predefined response threshold is based at least in part on medical data associated with the subject.

[0211] Example 4. The method of any of one of the preceding examples, but particularly example 2, wherein the predefined response threshold comprises a lack of response.

[0212] Example 5. The method of any of one of the preceding examples, but particularly example 1, wherein determining the fluid congestion status comprises determining, for a plurality of times within the time period, a difference between the initial right atrial pressure and the right atrial pressure response to the changed blood flow resistance.

[0213] Example 6. The method of any of one of the preceding examples, but particularly example 5, wherein the operations further comprise generating a recommendation for continuous infusion of loop diuretics or oral diuretics in response to determining that the difference is more than about 2 mmHg below the initial right atrial pressure.

[0214] Example 7. The method of any of one of the preceding examples, but particularly example 6, wherein the operations further comprise generating a recommendation for reduction of one or more occlusion cycles or discontinuing of loop diuretics or oral diuretics in response to determining that the difference is substantially zero for about 30 seconds to about 10 minutes.

[0215] Example 8. The method of any of one of the preceding examples, but particularly example 5, wherein the fluid congestion status comprises a threshold range associated with a hypervolemic state, a hypovolemic state, or a euvolemic state, and the operations further comprise using the threshold range to trigger additional occlusion cycles based at least in part on the determined difference between the initial right atrial pressure and the right atrial pressure response to the changed blood flow resistance.

[0216] Example 9. The method of any of one of the preceding examples, but particularly example 1, wherein: the occlusion cycle is configured to occlude from about 80 percent to about 100 percent of the blood vessel, and the operations further comprise: determining, responsive to the occlusion cycle, a tricuspid regurgitation grade for the subject, and in response to determining that the tricuspid regurgitation grade has dropped below a baseline threshold grade for the subject, generating a first output indicating that the tricuspid regurgitation in the subject is a result of venous congestion.

[0217] Example 10. The method of any of one of the preceding examples, but particularly example 9, wherein the operations further comprise: in response to determining that the tricuspid regurgitation grade has not dropped below the baseline threshold grade for the subject, generating a second output indicating that the tricuspid regurgitation in the subject is not a result of venous congestion.

[0218] Example 11. The method of any of one of the preceding examples, but particularly example 9, wherein the operations further comprise: generating, based on the first output, a diuresis schedule to reduce congestion in the subject.

[0219] Example 12. The method of any of one of the preceding examples, but particularly example 10, generating, based on the second output, a treatment schedule for alleviating or reducing the tricuspid regurgitation.

[0220] Example 13. The method of any of one of the preceding examples, but particularly example 9, wherein the operations further comprise: generating, based on the first output, a diuresis schedule to reduce congestion in the subject.

[0221] Example 14. The method of any of one of the preceding examples, but particularly example 12, wherein the operations further comprise: generating, based on the second output, an indication of a stage of the tricuspid regurgitation and generating a treatment schedule according to the indication of the stage of the tricuspid regurgitation.

[0222] Example 15. The method of any of one of the preceding examples, but particularly example 1 , wherein: the change in the blood flow resistance over the time period is performed at a predefined rate of occlusion associated with the vessel occlusion device, and determining the fluid congestion status comprises using the rate of occlusion to determine a relationship between the changed blood flow resistance and a change in the right atrial pressure response over the time period.

[0223] Example 16. The method of any of one of the preceding examples, but particularly example 15, wherein the operations further comprise generating a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia in response to determining that a relationship between the rate of occlusion and the right atrial pressure response decreases during performance of an occlusion cycle.

[0224] Example 17. The method of any of one of the preceding examples, but particularly example 16, wherein the operations further comprise recommending a modified occlusion cycle or multiple occlusion cycles to treat the determined right atrial pressure response.

[0225] Example 18. The method of any of one of the preceding examples, but particularly example 15, wherein the operations further comprise generating a metric representing an acuity of tricuspid regurgitation in the subject in response to determining that a relationship between the rate of occlusion and a tricuspid regurgitation grade of the subject decreases during performance of the occlusion cycle; and using the metric to generate a treatmentrecommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0226] Example 19. The method of any of one of the preceding examples, but particularly example 15, wherein the operations further comprise: receiving a measurement of left atrial pressure of the subject over the time period; determining, based on the rate of occlusion, the right atrial pressure response, and the left atrial pressure measurement, a level of function of a right ventricle of the subject; and generating an output indicating the level of function of the right ventricle of the subject.

[0227] Example 20. The method of any of one of the preceding examples, but particularly example 15, wherein the operations further comprise: receiving a measurement of left atrial pressure of the subject over the time period; determining, based on the rate of occlusion, the right atrial pressure response, and the left atrial pressure measurement, a level of function of a pulmonary vessel of the subject; and generating an output indicating the level of function of the pulmonary vessel of the subject.

[0228] Example 21. The method of any of one of the preceding examples, but particularly example 15, wherein the operations further comprise: determining, based on the rate of occlusion and the right atrial pressure response, a cardiac efficiency of the subject; and generating an output indicating the cardiac efficiency of the subject.

[0229] Example 22. The method of any of one of the preceding examples, but particularly example 1, wherein: the at least one processor is electrically coupled to at least one pressure sensor the vessel occlusion device is implanted in a portion of the blood vessel, and the at least one pressure sensor comprises a first pressure sensor positioned at a distal end of the vessel occlusion device and a second pressure sensor positioned at a location upstream of the first sensor, the operations further comprising: detecting, using the first pressure sensor, a first pressure in the blood vessel; detecting, using the second pressure sensor, a second pressure in the blood vessel at the location upstream of the first sensor; determining a pressure gradient between the first pressure and the second pressure; and generating, based on the pressure gradient, the fluid congestion status.

[0230] Example 23. The method of any of one of the preceding examples, but particularly example 22, wherein: the blood vessel is a superior vena cava; the first pressure is right atrial pressure; and the second pressure is superior vena cava pressure indicating a level of intracranial venous pressure.

[0231] Example 24. A method for determining a fluid volume status of a subject, the method comprising: providing a device implanted in or around a blood vessel of the subject, the device comprising at least one pressure sensor, a processor, and a vessel occlusion portion, the processor being configured to carry out operations comprising: causing the vessel occlusion portion to introduce at least a partial occlusion in the blood vessel; monitoring, using the at least one pressure sensor, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period; and determining, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject.

[0232] Example 25. The method of example 24, wherein the operations further comprise generating, based on the indication, a treatment recommendation to alter the fluid volume status, the treatment recommendation comprising fluid administration to the subject, diuretic administration to the subject, or a dietary adjustment for the subject.

[0233] Example 26. The method of any of one of the preceding examples, but particularly example 25, wherein the operations further comprise: causing provision of the treatment recommendation to the subject; causing, after the time period and after opening of the at least partial occlusion in the blood vessel, the vessel occlusion portion to introduce a second at least partial occlusion in the blood vessel; monitoring, using the at least one pressure sensor, an additional right atrial pressure response to the second at least partial occlusion for a second time period; and determining, based on the additional right atrial pressure response, a second indication representing an updated fluid volume status associated with the heart of the subject; determining, based on the second indication, a new treatment recommendation for the subject; and repeating the above steps until the monitoring indicates that the fluid volume status associated with the heart of the subject maintains a fluid volume status substantially associated with euvolemia.

[0234] Example 27. The method as in any of the above examples and in particular example 24, wherein the indication is a value or a curve determined during the time period by calculating a relative change in right atrial pressure for the subject from a baseline right atrial pressure of the subject and comparing the relative change in right atrial pressure to a Frank-Starling curve; and generating, based on the indication, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0235] Example 28. The method as in any of the above examples and in particular example 24, wherein the indication is a value or a curve determined during the time period by calculating an absolute change in right atrial pressure for the subject and comparing the absolute changein right atrial pressure to a Frank-Starling curve; and generating, based on the indication, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0236] Example 29. The method of any of one of the preceding examples, but particularly example 24, wherein: the right atrial pressure response is an increase, a decrease, or a negligible change in right atrial pressure during the time period; and the indication is determined to generate a treatment recommendation to achieve or maintain euvolemia.

[0237] Example 30. The method of any of one of the preceding examples, but particularly example 24, wherein: the fluid volume status comprises a metric or a range for classifying the subject during the time period into a hypervolemic state, a hypovolemic state, or a euvolemic state; and the metric or range is used with the indication to generate a treatment recommendation to achieve or maintain euvolemia.

[0238] Example 31. The method of any of one of the preceding examples, but particularly example 24, wherein the operations further comprise: generating, based on the indication, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0239] Example 32. The method of any of one of the preceding examples, but particularly example 31, wherein determining the treatment recommendation comprises comparing the determined indication to one or more of: a hypervolemia threshold range, a hypovolemia threshold range, or data representing past fluid treatment events or disease information associated with the subject.

[0240] Example 33. The method of any of one of the preceding examples, but particularly example 31, wherein the treatment recommendation comprises an instruction to up-titrate intravenous loop diuretic treatment, down-titrate intravenous loop diuretic treatment, or terminate intravenous loop diuretic treatment.

[0241] Example 34. The method of any of one of the preceding examples, but particularly example 31, wherein the treatment recommendation comprises an instruction to up-titrate oral diuretic treatment, down-titrate oral diuretic treatment, or terminate oral diuretic treatment.

[0242] Example 35. The method of any of one of the preceding examples, but particularly example 31, wherein the operations further comprise: iteratively causing the vessel occlusion portion to introduce and remove an occlusion in the blood vessel; monitoring, using the at least one pressure sensor, additional right atrial pressure responses over a second time period responsive to introduction and removal of the occlusion in the blood vessel; determining, basedon the additional right atrial pressure responses, an updated indication representing the fluid volume status associated with the heart of the subject; and generating a cadence for performing the treatment recommendation based on the updated indication.

[0243] Example 36. The method of any of one of the preceding examples, but particularly example 35, wherein a time between each iteration is about 10 minutes to about one hour.

[0244] Example 37. The method of any of one of the preceding examples, but particularly example 35, wherein a time between each iteration is about five hours to about 6 hours, and each updated indication representing the fluid volume status is assessed as a basis in which to tune the time between each iteration for future monitoring.

[0245] Example 38. The method of any of one of the preceding examples, but particularly example 24, wherein the device is implanted intravascularly in the blood vessel and the blood vessel is a vena cava.

[0246] Example 39. The method of any of one of the preceding examples, but particularly example 24, wherein the device is implanted extravascular to the blood vessel and the blood vessel is a vena cava.

[0247] Example 40. An implantable device for determining a fluid congestion status of a subject, the implantable device comprising: a frame comprising a proximal end opposite a distal end and a longitudinal axis extending therethrough; and a vessel occlusion portion comprising an inflow end and an outflow end, wherein the inflow end is at least partially installed within the distal end of the frame, and the outflow end is coupled to an end effector configured to modulate blood flow through a blood vessel; and a first sensor positioned at the distal end of the frame and configured to detect a first pressure in a blood vessel; a second sensor positioned upstream of the first sensor and configured to detect a second pressure in the blood vessel at a location upstream of the first sensor; a processor electrically coupled to the first sensor and the second sensor, wherein the processor is configured to: cause the vessel occlusion portion to actuate to introduce at least a partial occlusion in the blood vessel; monitor, using the first pressure sensor or the second pressure sensor, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period; and determine, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject.

[0248] Example 41. The implantable device of example 40, wherein the subject is undergoing diuresis treatment during the time period and the processor is further configured to: detect efficacy of the diuresis treatment by determining a magnitude of the right atrialpressure response during the time period; and generate an indication to halt the diuresis treatment in response to determining that the magnitude of the right atrial pressure response is below a predefined response threshold.

[0249] Example 42. The implantable device of any of one of the preceding examples, but particularly example 41 , wherein the predefined response threshold is based at least in part on medical data associated with the subject.

[0250] Example 43. The implantable device of any of one of the preceding examples, but particularly example 41, wherein the predefined response threshold comprises a lack of response.

[0251] Example 44. The implantable device of any of one of the preceding examples, but particularly example 40, wherein actuating the vessel occlusion portion is performed based on a determined elapsed time in which the right atrial pressure response is within a predefined pressure range, the elapsed time being determined based at least in part on pressure detected by the first sensor or pressure detected by the second sensor.

[0252] Example 45. The implantable device of any of one of the preceding examples, but particularly example 40, wherein actuating the vessel occlusion portion is based on the monitoring, the actuating comprising: radially collapsing the vessel occlusion portion at the outflow end and toward a central axis of the frame; and radially expanding at least a portion of the vessel occlusion portion away from the central axis of the frame in response to determining that the right atrial pressure response is increasing or above a predefined pressure range associated with the subject.

[0253] Example 46. The implantable device of any of one of the preceding examples, but particularly example 45, wherein the predefined pressure range comprises about 10 mmHg to about 25 mmHg.

[0254] Example 47. The implantable device of any of one of the preceding examples, but particularly example 40, wherein the monitoring of the right atrial pressure response further comprises: communicatively coupling the implantable device to at least one external computing device; transmitting, to the at least one external computing device, output data corresponding to the monitored right atrial pressure response; and receiving, from the at least one external computing device and based on the transmitted output data, health-based instructions, the health-based instructions being triggered for display on the at least one external computing device.

[0255] Example 48. The implantable device of any of one of the preceding examples, but particularly example 47, wherein the health-based instructions comprise one or more of: instructions to titrate medication, instructions to visit a clinic, instructions to deliver diuresis therapy, and instructions to perform physical movements.

[0256] Example 49. The implantable device of any of one of the preceding examples, but particularly example 47, wherein the health-based instructions comprise a treatment recommendation to alter a fluid volume status, the treatment recommendation comprising fluid administration to the subject, diuretic administration to the subject, or a dietary adjustment for the subject.

[0257] Example 50. The implantable device of any of one of the preceding examples, but particularly example 40, wherein the indication is a value or a curve determined during the time period by calculating a relative change in right atrial pressure for the subject from a baseline right atrial pressure of the subject and comparing the relative change in right atrial pressure to a Frank-Starling curve; and generating, based on the indication, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0258] Example 51. The implantable device of any of one of the preceding examples, but particularly example 40, wherein the indication is a value or a curve determined during the time period by calculating an absolute change in right atrial pressure for the subject and comparing the absolute change in right atrial pressure to a Frank- Starling curve; and generating, based on the indication, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0259] Example 52. The implantable device of any of one of the preceding examples, but particularly example 40, wherein: the right atrial pressure response is an increase, a decrease, or a negligible change in right atrial pressure during the time period; and the indication is determined to generate a treatment recommendation to achieve or maintain euvolemia.

[0260] Example 53. The implantable device of any of one of the preceding examples, but particularly example 40, wherein: the fluid volume status comprises a metric or a range for classifying the subject during the time period into a hypervolemic state, a hypovolemic state, or a euvolemic state; and the metric or the range is used with the indication to generate a treatment recommendation to achieve or maintain euvolemia.

[0261] Example 54. The implantable device of any of one of the preceding examples, but particularly example 40, wherein the processor is further configured to: generate, based on theindication, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0262] Example 55. The implantable device of any of one of the preceding examples, but particularly example 54, wherein determining the treatment recommendation comprises comparing the determined indication to one or more of: a hypervolemia threshold range, a hypovolemia threshold range, or data representing past fluid treatment events or disease information associated with the subject.

[0263] Example 56. The implantable device of any of one of the preceding examples, but particularly example 54, wherein the treatment recommendation comprises an instruction to up-titrate intravenous loop diuretic treatment, down-titrate intravenous loop diuretic treatment, or terminate intravenous loop diuretic treatment.

[0264] Example 57. The implantable device of any of one of the preceding examples, but particularly example 54, wherein the treatment recommendation comprises an instruction to up-titrate oral diuretic treatment, down-titrate oral diuretic treatment, or terminate oral diuretic treatment.

[0265] Example 58. The implantable device of any of one of the preceding examples, but particularly example 40, wherein the blood vessel comprises an inferior vena cava.

[0266] Example 59. The implantable device of any of one of the preceding examples, but particularly example 40, further comprising: a power source coupled to a control wire configured to cause the vessel occlusion device to be configured in an unrestricted blood flow state or a restricted blood flow state; and an actuation device for actuating the implantable device, the actuation device comprising an actuator coupled to the control wire of the implantable device, and a control device communicatively coupled to the actuator to cause the actuation device to actuate the implantable device.

[0267] Example 60. A method of treatment for using a right atrial pressure response to adjust an amount of diuretic to introduce to a subject experiencing hypervolemia or hypovolemia, the method comprising: introducing an actuatable device in a blood vessel, the device comprising: at least one sensor electrically coupled to the actuatable device and configured to detect a pressure in a blood vessel; a processing module electrically coupled to the at least one sensor and configured to monitor outputs from the at least one sensor; actuating, based on the monitoring of the outputs, the actuatable device to introduce at least a partial occlusion in the blood vessel; monitoring, using the at least one sensor, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period; determining, based on the rightatrial pressure response, an indication representing a fluid volume status associated with a heart of the subject; and generating an indication to adjust the amount of diuretic to introduce to the subject in response to determining that a magnitude of the right atrial pressure response is below a predefined response threshold.

[0268] Example 61. The method of treatment of example 60, wherein the predefined response threshold is based at least in part on medical data associated with the subject.

[0269] Example 62. The method of treatment of any of one of the preceding examples, but particularly example 60, wherein the predefined response threshold comprises a lack of response.

[0270] Example 63. The method of treatment of any of one of the preceding examples, but particularly example 60, wherein determining the fluid volume status comprises determining, for a plurality of times within the time period, a difference between an initial right atrial pressure of the subject and the right atrial pressure response to the at least partial occlusion.

[0271] Example 64. The method of treatment of any of one of the preceding examples, but particularly example 63, wherein the method further comprises generating a recommendation for administering a continuous infusion of loop diuretics or oral diuretics in response to determining that the difference is more than about 2 mmHg to about 3 mmHg below the initial right atrial pressure.

[0272] Example 65. The method of treatment of any of one of the preceding examples, but particularly example 63, wherein the method further comprises generating a recommendation to terminate loop diuretics or oral diuretics in response to determining that the difference is substantially zero for about 30 seconds to about 10 minutes.

[0273] Example 66. The method of treatment of any of one of the preceding examples, but particularly example 63, wherein the fluid volume status comprises a threshold range associated with a hypervolemic state, a hypovolemic state, or a euvolemic state, and the method further comprises using the threshold range to trigger additional occlusions in the blood vessel based at least in part on a determined difference between the initial right atrial pressure and the right atrial pressure response to the at least partial occlusion.

[0274] Example 67. The method of treatment of any of one of the preceding examples, but particularly example 60, wherein the device further comprises: a frame comprising a proximal end opposite a distal end and a longitudinal axis extending therethrough; and a vessel occlusion portion comprising an inflow end and an outflow end, wherein the inflow end is at least partially installed within the distal end of the frame, and the outflow end is coupled to an endeffector configured to modulate blood flow through the blood vessel, and wherein the end effector is configured to radially collapse at the outflow end and toward a central axis of the frame, or radially expand away from the central axis of the frame, in response to an actuation of a control wire coupled to a portion of the vessel occlusion portion.

[0275] Example 68. A non-transitory computer-readable medium for determining a fluid volume status of a subject, the computer-readable medium comprising: at least one device implanted in or around a blood vessel of the subject, the device comprising at least one pressure sensor, a processor, and a vessel occlusion portion; at least one processor; and memory storing instructions that, when executed by the at least one processor, cause the at least one processor to perform operations comprising: causing the vessel occlusion portion to introduce at least a partial occlusion in the blood vessel; monitoring, using the at least one pressure sensor, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period; and determining, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject.

[0276] Example 69. The non-transitory computer-readable medium of example 68, wherein the operations further comprise generating, based on the indication, a treatment recommendation to alter the fluid volume status, the treatment recommendation comprising fluid administration to the subject, diuretic administration to the subject, or a dietary adjustment for the subject.

[0277] Example 70. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 69, wherein the operations further comprise: causing provision of the treatment recommendation to the subject; causing, after the time period and after opening of the at least partial occlusion in the blood vessel, the vessel occlusion portion to introduce a second at least partial occlusion in the blood vessel; monitoring, using the at least one pressure sensor, an additional right atrial pressure response to the second at least partial occlusion for a second time period; and determining, based on the additional right atrial pressure response, a second indication representing an updated fluid volume status associated with the heart of the subject; determining, based on the second indication, a new treatment recommendation for the subject; and repeating the above steps until the monitoring indicates that the fluid volume status associated with the heart of the subject maintains a fluid volume status substantially associated with euvolemia.

[0278] Example 71. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 68, wherein the indication is a value or a curvedetermined during the time period by calculating a relative change in right atrial pressure for the subject from a baseline right atrial pressure of the subject and comparing the relative change in right atrial pressure to a Frank-Starling curve; and generating, based on the indication, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0279] Example 72. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 68, wherein the indication is a value or a curve determined during the time period by calculating an absolute change in right atrial pressure for the subject and comparing the absolute change in right atrial pressure to a Frank-Starling curve; and generating, based on the indication, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0280] Example 73. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 68, wherein: the right atrial pressure response is an increase, a decrease, or a negligible change in right atrial pressure during the time period; and the indication is determined to generate a treatment recommendation to achieve or maintain euvolemia.

[0281] Example 74. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 68, wherein: the fluid volume status comprises a metric or a range for classifying the subject during the time period into a hypervolemic state, a hypovolemic state, or a euvolemic state; and the metric or range is used with the indication to generate a treatment recommendation to achieve or maintain euvolemia.

[0282] Example 75. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 68, wherein the operations further comprise: generating, based on the indication, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0283] Example 76. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 75, wherein determining the treatment recommendation comprises comparing the determined indication to one or more of: a hypervolemia threshold range, a hypovolemia threshold range, or data representing past fluid treatment events or disease information associated with the subject.

[0284] Example 77. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 75, wherein the treatment recommendationcomprises an instruction to up-titrate intravenous loop diuretic treatment, down-titrate intravenous loop diuretic treatment, or terminate intravenous loop diuretic treatment.

[0285] Example 78. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 75, wherein the treatment recommendation comprises an instruction to up-titrate oral diuretic treatment, down-titrate oral diuretic treatment, or terminate oral diuretic treatment.

[0286] Example 79. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 75, wherein the operations further comprise: iteratively causing the vessel occlusion portion to introduce and remove an occlusion in the blood vessel; monitoring, using the at least one pressure sensor, additional right atrial pressure responses over a second time period responsive to introduction and removal of the occlusion in the blood vessel; determining, based on the additional right atrial pressure responses, an updated indication representing the fluid volume status associated with the heart of the subject; and generating a cadence for performing the treatment recommendation based on the updated indication.

[0287] Example 80. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 79, wherein a time between each iteration is about 10 minutes to about one hour.

[0288] Example 81. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 79, wherein a time between each iteration is about 5 hours to about 6 hours, and each updated indication representing the fluid volume status is assessed as a basis in which to tune the time between each iteration for future monitoring.

[0289] Example 82. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 68, wherein the device is implanted intravascularly in the blood vessel and the blood vessel is a vena cava.

[0290] Example 83. The non-transitory computer-readable medium of any of one of the preceding examples, but particularly example 68, wherein the device is implanted extravascular to the blood vessel and the blood vessel is a vena cava.

[0291] Example 84. An implantable device for determining a fluid congestion status of a subject, the implantable device comprising: a frame comprising a proximal end opposite a distal end and a longitudinal axis extending therethrough; and a vessel occlusion portion comprising an inflow end and an outflow end, wherein the inflow end is at least partially installed within the distal end of the frame, and the outflow end is coupled to an end effectorconfigured to modulate blood flow through a blood vessel; and a first sensor positioned at the distal end of the frame and configured to detect a first pressure in a blood vessel; a second sensor positioned upstream of the first sensor and configured to detect a second pressure in the blood vessel at a location upstream of the first sensor; a processor in communication with the first sensor and the second sensor, wherein the processor is configured to: cause the vessel occlusion portion to actuate to introduce at least a partial occlusion in the blood vessel; monitor, using the first sensor or the second sensor, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period; and determine, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject.

[0292] Example 85. The implantable device of example 84, wherein the subject is undergoing diuresis treatment during the time period and the processor is further configured to: detect efficacy of the diuresis treatment by determining a magnitude of the right atrial pressure response during the time period; and generate an indication to halt the diuresis treatment in response to determining that the magnitude of the right atrial pressure response is below a predefined response threshold.

[0293] Example 86. The implantable device of any of one of the preceding examples, but particularly example 85, wherein the predefined response threshold comprises a lack of response.

[0294] Example 87. The implantable device of any of one of the preceding examples, but particularly example 84, wherein actuating the vessel occlusion portion is performed based on a determined elapsed time in which the right atrial pressure response is within a predefined pressure range, the elapsed time being determined based at least in part on pressure detected by the first sensor or pressure detected by the second sensor.

[0295] Example 88. The implantable device of any of one of the preceding examples, but particularly example 84, wherein actuating the vessel occlusion portion is based on the monitoring, the actuating comprising: radially collapsing the vessel occlusion portion at the outflow end and toward a central axis of the frame; and radially expanding at least a portion of the vessel occlusion portion away from the central axis of the frame in response to determining that the right atrial pressure response is increasing or above a predefined pressure range associated with the subject.

[0296] Example 89. The implantable device of any of one of the preceding examples, but particularly example 84, wherein the monitoring of the right atrial pressure response further comprises: communicatively coupling the implantable device to at least one externalcomputing device; transmitting, to the at least one external computing device, output data corresponding to the monitored right atrial pressure response; and receiving, from the at least one external computing device and based on the transmitted output data, health-based instructions, the health-based instructions being triggered for display on the at least one external computing device.

[0297] Example 90. The implantable device of any of one of the preceding examples, but particularly example 84, wherein the indication is a value or a curve determined during the time period by calculating a relative change or absolute change in right atrial pressure for the subject from a baseline right atrial pressure of the subject and comparing the relative change or the absolute change in right atrial pressure to a Frank-Starling curve; and generating, based on the indication, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

[0298] Example 91. The implantable device of any of one of the preceding examples, but particularly example 84, wherein: the right atrial pressure response is an increase, a decrease, or a negligible change in right atrial pressure during the time period; and the indication is determined to generate a treatment recommendation to achieve or maintain euvolemia.

[0299] Example 92. The implantable device of any of one of the preceding examples, but particularly example 84, wherein: the fluid volume status comprises a metric or a range for classifying the subject during the time period into a hypervolemic state, a hypovolemic state, or a euvolemic state; and the metric or the range is used with the indication to generate a treatment recommendation to achieve or maintain euvolemia.

[0300] Example 93. The implantable device of any of one of the preceding examples, but particularly example 84, wherein the blood vessel comprises an inferior vena cava or a superior vena cava.

[0301] Example 94. The implantable device of any of one of the preceding examples, but particularly example 84, further comprising: a power source coupled to a control wire configured to cause the vessel occlusion portion of the implantable device to be configured in an unrestricted blood flow state or a restricted blood flow state; and an actuation device for actuating the implantable device, the actuation device comprising an actuator coupled to the control wire of the implantable device, and a control device communicatively coupled to the actuator to cause the actuation device to actuate the implantable device.

[0302] Example 95. An implantable device, the implantable device comprising: a flow modulator to modulate blood flow through a blood vessel; at least one sensor for detecting apressure in the blood vessel; and a processor in communication with the at least one sensor and the flow modulator, wherein the processor is configured to actuate the flow modulator and to monitor the pressure in the blood vessel.

[0303] Example 96. The implantable device of example 95, wherein the flow modulator comprises an occlusion device.

[0304] Example 97. The implantable device of any of one of the preceding examples, but particularly example 95, wherein the processor actuates the occlusion device to introduce at least a partial occlusion in the blood vessel.

[0305] Example 98. The implantable device of any of one of the preceding examples, but particularly example 97, wherein the pressure in the blood vessel includes a right atrial pressure response.

[0306] Example 99. The implantable device of any of one of the preceding examples, but particularly example 98, wherein the right atrial pressure response to the modulated blood provides an indication representing a fluid volume status, the fluid volume status includes a threshold value that triggers additional occlusions in the blood vessel based on a difference between an initial reading of the right atrial pressure response and the right atrial pressure response to the at least partial occlusion.

[0307] Example 100. The implantable device of any of one of the preceding examples, but particularly example 98, wherein the subject is undergoing diuresis treatment during a time period of the modulation of the blood flow and the processor is further configured to: detect efficacy of the diuresis treatment by determining a magnitude of the right atrial pressure response during the time period; and generate an indication to halt the diuresis treatment in response to determining that the magnitude of the right atrial pressure response is below a predefined response threshold.

[0308] Example 101. The implantable device of any of one of the preceding examples, but particularly example 100, wherein the predefined response threshold comprises a lack of response.

[0309] Example 102. The implantable device of any of one of the preceding examples, but particularly example 95, wherein the at least one sensor comprises a first pressure sensor and a second pressure sensor, the first pressure sensor is positioned at a distal end of the flow modulator and the second sensor is positioned at a location upstream of the first sensor, the processor monitoring the first sensor and the second sensor to determine a pressure gradient to provide an indication of a fluid congestion status.

[0310] Example 103. The implantable device of any of one of the preceding examples, but particularly example 102, wherein actuating the vessel occlusion portion is performed based on a determined elapsed time in which the pressure is within a predefined pressure range, the elapsed time being determined based at least in part on pressure detected by the first sensor or pressure detected by the second sensor.

[0311] Example 104. The implantable device of any of one of the preceding examples, but particularly example 95, wherein the processor provides a fluid congestion status comprising a relationship between a rate of occlusion and a change in the right atrial pressure response over a time period, wherein the change in the pressure is due to the modulated blood flow in the blood vessel during the occlusion cycle performed by the flow modulator performed at the rate of occlusion.

[0312] The spatially relative terms “outer,” “inner,” “upper,” “lower,” “below,” “above,” “vertical,” “horizontal,” and similar terms, may be used herein for ease of description to describe the relations between one element or component and another element or component as illustrated in the drawings. It should be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation, in addition to the orientation depicted in the drawings. For example, in the case where a device shown in the drawing is turned over, the device positioned “below” or “beneath” another device may be placed “above” another device. Accordingly, the illustrative term “below” may include both the lower and upper positions. The device may also be oriented in the other direction, and thus the spatially relative terms may be interpreted differently depending on the orientations.

[0313] The systems and methods of the embodiments and variations described herein can be embodied and / or implemented at least in part as a machine configured to receive a non- transitory computer-readable medium storing computer-readable instructions. The instructions may be executed by computer-executable components integrated or in communication with the system and one or more portions of the processor on or in communication with the control device and / or computing device. The computer-readable medium can be stored on any suitable computer-readable media such as RAMs, ROMs, flash memory, EEPROMs, optical devices (e.g., CD or DVD), hard drives, floppy drives, or any suitable device. The computer-executable component is preferably a general or application-specific processor, but any suitable dedicated hardware or hardware / firmware combination can alternatively or additionally execute the instructions.

[0314] As used in the description and claims, the singular form “a”, “an” and “the” include both singular and plural references unless the context clearly dictates otherwise. For example, the term “projection” may include, and is contemplated to include, a plurality of projections. At times, the claims and disclosure may include terms such as “a plurality,” “one or more,” or “at least one;” however, the absence of such terms is not intended to mean, and should not be interpreted to mean, that a plurality is not conceived.

[0315] The term “about” or “approximately,” when used before a numerical designation or range (e.g., to define a length or pressure), indicates approximations which may vary by ( + ) or ( - ) 5 percent, 1 percent or 0.1 percent. All numerical ranges provided herein are inclusive of the stated start and end numbers. The term “substantially” indicates mostly (i.e., greater than 50 percent) or essentially all of a device, substance, or composition.

[0316] As used herein, the term “comprising” or “comprises” is intended to mean that the devices, systems, and methods include the recited elements, and may additionally include any other elements. “Consisting essentially of’ shall mean that the devices, systems, and methods include the recited elements and exclude other elements of essential significance to the combination for the stated purpose. Thus, a system or method consisting essentially of the elements as defined herein would not exclude other materials, features, or steps that do not materially affect the basic and novel characteristic(s) of the claimed disclosure. “Consisting of” shall mean that the devices, systems, and methods include the recited elements and exclude anything more than a trivial or inconsequential element or step. Embodiments defined by each of these transitional terms are within the scope of this disclosure.

[0317] The examples and illustrations included herein show, by way of illustration and not of limitation, specific embodiments in which the subject matter may be practiced. Other embodiments may be utilized and derived therefrom, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein individually or collectively by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any single invention or inventive concept, if more than one is in fact disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments,and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description.

Claims

WHAT IS CLAIMED IS:

1. An implantable device for determining a fluid congestion status of a subject, the implantable device comprising: a frame comprising a proximal end opposite a distal end and a longitudinal axis extending therethrough; and a vessel occlusion portion comprising an inflow end and an outflow end, wherein the inflow end is at least partially installed within the distal end of the frame, and the outflow end is coupled to an end effector configured to modulate blood flow through a blood vessel; and a first sensor positioned at the distal end of the frame and configured to detect a first pressure in a blood vessel; a second sensor positioned upstream of the first sensor and configured to detect a second pressure in the blood vessel at a location upstream of the first sensor; a processor in communication with the first sensor and the second sensor, wherein the processor is configured to: cause the vessel occlusion portion to actuate to introduce at least a partial occlusion in the blood vessel; monitor, using the first sensor or the second sensor, a right atrial pressure response to the at least partial occlusion in the blood vessel for a time period; and determine, based on the right atrial pressure response, an indication representing a fluid volume status associated with a heart of the subject.

2. The implantable device of claim 1, wherein the subject is undergoing diuresis treatment during the time period and the processor is further configured to: detect efficacy of the diuresis treatment by determining a magnitude of the right atrial pressure response during the time period; and generate an indication to halt the diuresis treatment in response to determining that the magnitude of the right atrial pressure response is below a predefined response threshold.

3. The implantable device of claim 2, wherein the predefined response threshold comprises a lack of response.

4. The implantable device of claim 1, wherein actuating the vessel occlusion portion is performed based on a determined elapsed time in which the right atrial pressure response is within a predefined pressure range, the elapsed time being determined based at least in part on pressure detected by the first sensor or pressure detected by the second sensor.

5. The implantable device of claim 1, wherein actuating the vessel occlusion portion is based on the monitoring, the actuating comprising: radially collapsing the vessel occlusion portion at the outflow end and toward a central axis of the frame; and radially expanding at least a portion of the vessel occlusion portion away from the central axis of the frame in response to determining that the right atrial pressure response is increasing or above a predefined pressure range associated with the subject.

6. The implantable device of claim 1, wherein the monitoring of the right atrial pressure response further comprises: communicatively coupling the implantable device to at least one external computing device; transmitting, to the at least one external computing device, output data corresponding to the monitored right atrial pressure response; and receiving, from the at least one external computing device and based on the transmitted output data, health-based instructions, the health-based instructions being triggered for display on the at least one external computing device.

7. The implantable device of claim 1, wherein the indication is a value or a curve determined during the time period by calculating a relative change or absolute change in right atrial pressure for the subject from a baseline right atrial pressure of the subject and comparing the relative change or the absolute change in right atrial pressure to a Frank- Starling curve; and generating, based on the indication, a treatment recommendation to achieve or maintain a fluid volume status substantially associated with euvolemia.

8. The implantable device of claim 1, wherein: the right atrial pressure response is an increase, a decrease, or a negligible change in right atrial pressure during the time period; and the indication is determined to generate a treatment recommendation to achieve or maintain euvolemia.

9. The implantable device of claim 1, wherein: the fluid volume status comprises a metric or a range for classifying the subject during the time period into a hypervolemic state, a hypovolemic state, or a euvolemic state; andthe metric or the range is used with the indication to generate a treatment recommendation to achieve or maintain euvolemia.

10. The implantable device of claim 1, wherein the blood vessel comprises an inferior vena cava or a superior vena cava.

11. The implantable device of claim 1, further comprising: a power source coupled to a control wire configured to cause the vessel occlusion portion of the implantable device to be configured in an unrestricted blood flow state or a restricted blood flow state; and an actuation device for actuating the implantable device, the actuation device comprising an actuator coupled to the control wire of the implantable device, and a control device communicatively coupled to the actuator to cause the actuation device to actuate the implantable device.

12. A method for determining a fluid congestion status of a subject, the method being carried out by at least one processor executing operations comprising: receiving an initial right atrial pressure for the subject; causing, over a time period, a vessel occlusion device to perform an occlusion cycle to change blood flow resistance in a blood vessel of the subject; receiving monitored readings for a right atrial pressure response to the changed blood flow resistance in the blood vessel over the time period; and determining, for the subject and based on the readings representing the right atrial pressure response, a fluid congestion status associated with a heart of the subject.

13. The method of claim 02, wherein the subject is undergoing diuresis treatment during the time period and the operations further comprise: detecting efficacy of the diuresis treatment by determining a magnitude of the right atrial pressure response during the time period; and generating an indication to halt the diuresis treatment in response to determining that the magnitude of the right atrial pressure response is below a predefined response threshold.

14. The method of claim 13, wherein the predefined response threshold comprises a lack of response.

15. The method of claim 02, wherein determining the fluid congestion status comprises determining, for a plurality of times within the time period, a difference between the initial right atrial pressure and the right atrial pressure response to the changed blood flow resistance, wherein operations further comprise using a threshold range of the fluidcongestion status to trigger additional occlusion cycles or altered occlusion cycles based at least in part on the determined difference between the initial right atrial pressure and the right atrial pressure response to the changed blood flow resistance.

16. The method of claim 15, wherein the operations further comprise generating a recommendation for continuous infusion of loop diuretics or oral diuretics in response to determining that the difference is more than about 2 mmHg below the initial right atrial pressure.

17. The method of claim 02, wherein: the occlusion cycle is configured to occlude from about 80 percent to about 100 percent of the blood vessel, and the operations further comprise: determining, responsive to the occlusion cycle, a tricuspid regurgitation grade for the subject, and in response to determining that the tricuspid regurgitation grade has dropped below a baseline threshold grade for the subject, generating a first output indicating that a tricuspid regurgitation in the subject is a result of venous congestion.

18. The method of claim 17, wherein the operations further comprise: in response to determining that the tricuspid regurgitation grade has not dropped below the baseline threshold grade for the subject, generating a second output indicating that the tricuspid regurgitation in the subject is not a result of venous congestion.

19. The method of claim 02, wherein: the change in the blood flow resistance over the time period is performed at a predefined rate of occlusion associated with the vessel occlusion device, and determining the fluid congestion status comprises using the rate of occlusion to determine a relationship between the changed blood flow resistance and a change in the right atrial pressure response over the time period.

20. The method of claim 02, wherein: the at least one processor is electrically coupled to at least one pressure sensor the vessel occlusion device is implanted in a portion of the blood vessel, and the at least one pressure sensor comprises a first pressure sensor positioned at a distal end of the vessel occlusion device and a second pressure sensor positioned at a location upstream of the first pressure sensor, the operations further comprising: detecting, using the first pressure sensor, a first pressure in the blood vessel; detecting, using the second pressure sensor, a second pressure in the blood vessel atthe location upstream of the first pressure sensor; determining a pressure gradient between the first pressure and the second pressure; and generating, based on the pressure gradient, the fluid congestion status.

21. An implantable device, comprising: a flow modulator to modulate blood flow through a blood vessel; at least one sensor for detecting a pressure in the blood vessel; and a processor in communication with the al least one sensor and the flow modulator, wherein the processor is configured to actuate the flow modulator and to monitor the pressure in the blood vessel.

22. The implantable device of claim 21, wherein the flow modulator comprises an occlusion device.

23. The implantable device of claim 22, wherein the processor actuates the occlusion device to introduce at least a partial occlusion in the blood vessel.

24. The implantable device of claim 23, wherein the pressure in the blood vessel includes a right atrial pressure response.

25. The implantable device of claim 24, wherein the right atrial pressure response to the modulated blood provides an indication representing a fluid volume status, the fluid volume status includes a threshold value that triggers additional occlusions in the blood vessel based on a difference between an initial reading of the right atrial pressure response and the right atrial pressure response to the at least partial occlusion.

26. The implantable device of claim 24, wherein the subject is undergoing diuresis treatment during a time period of the modulation of the blood flow and the processor is further configured to: detect efficacy of the diuresis treatment by determining a magnitude of the right atrial pressure response during the time period; and generate an indication to halt the diuresis treatment in response to determining that the magnitude of the right atrial pressure response is below a predefined response threshold.

27. The implantable device of claim 26, wherein the predefined response threshold comprises a lack of response.

28. The implantable device of claim 21, wherein the at least one sensor comprises a first pressure sensor and a second pressure sensor, the first pressure sensor is positioned at a distal end of the flow modulator and the second sensor is positioned at a location upstream of thefirst sensor, the processor monitoring the first sensor and the second sensor to determine a pressure gradient to provide an indication of a fluid congestion status.

29. The implantable device of claim 28, wherein actuating the vessel occlusion portion is performed based on a determined elapsed time in which the pressure is within a predefined pressure range, the elapsed time being determined based at least in part on pressure detected by the first sensor or pressure detected by the second sensor.

30. The implantable device of claim 24, wherein the processor provides a fluid congestion status comprising a relationship between a rate of occlusion and a change in the right atrial pressure response over a time period, wherein the change in the pressure is due to the modulated blood flow in the blood vessel during the occlusion cycle performed by the flow modulator performed at the rate of occlusion.

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