System and method

Abstract

To provide a system and a method regarding sensing of the amount of body fluid within the inferior vena cava (IVC), which are used to acquire data capable of deriving information on a body fluid state, congestion, and cardiac output.SOLUTION: A system comprises: a sensor configured to acquire a measurement value from a blood vessel; and a processor configured to acquire the degree of cardiac collapse in the blood vessel from the measurement value, acquire the degree of respiratory collapse in the blood vessel from the measurement value, and calculate the ratio between the heartbeat collapse and the respiratory collapse, for representing a body fluid state in the blood vessel.SELECTED DRAWING: Figure 5

Description

Technical Field

[0001] The present disclosure mainly relates to the field of vascular monitoring. In particular, the present disclosure is directed to implants, systems, methods, and software for wireless vascular monitoring. More specifically, the embodiments disclosed herein are capable of obtaining data related to the state of the fluid, congestion, and cardiac output in relation to sensing the amount of fluid in the large veins (inferior vena cava and superior vena cava).

Background Art

[0002] Heart failure, often associated with congestive heart failure, occurs when the myocardium cannot efficiently supply oxygenated blood to the vascular system. Various pathophysiological conditions such as myocardial damage, diabetes, and hypertension gradually disrupt organ function and self-regulatory mechanisms, which may lead to the heart not being properly filled with blood or the blood not being properly discharged into the vascular system. Additionally, heart failure may have unfavorable interactions with a series of complications such as heart valve problems, arrhythmias, liver damage, kidney damage, or renal insufficiency.

[0003] Therefore, conventionally, the development of vascular monitoring devices and technologies, including those aimed at monitoring arterial or venous pressure in blood vessels or the dimensions of the vascular lumen, has been attempted.

[0004] However, many of these existing systems are catheter-based (not wireless), so they can only be used in a clinical setting for a limited period and may carry the risks associated with long-term catheter insertion. In the case of wireless solutions, the complexity of deployment, fixation, and the interrelationships between these elements and detection and communication result in inconsistent outcomes with previously developed devices and technologies.

[0005] Existing wireless systems focus on pressure measurement, and within the IVC, the response to the patient's body fluid state may be blunter than the measurement of the IVC dimensions. However, systems designed to measure blood vessel dimensions also have many drawbacks regarding monitoring in the IVC. Electric impedance-based systems require electrodes specially placed on opposite sides across the blood vessel widthwise. Such devices, like most other blood vessels where monitoring is needed, present special problems when attempting to monitor the IVC dimensions because the IVC does not expand and contract symmetrically. There are still issues not fully addressed regarding the accurate positioning of such position-dependent sensors. Monitoring the IVC presents further challenges arising from the IVC's physiological functions. Since the wall of the IVC is relatively more compliant than other blood vessels, it may be more easily deformed by the forces applied to maintain the implant's position within the blood vessel. Thus, even a device that may function well in other blood vessels may not necessarily enable accurate monitoring in the IVC due to the distortion caused by the forces of the implant acting on the IVC wall.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0007] From the above, especially in the important area of heart failure monitoring, new developments in the field are desired to provide physicians and patients with a reliable and affordable implementation of wireless blood vessel monitoring.

Means for Solving the Problems

[0008] In an embodiment of the present disclosure, a system for determining the body fluid state of a blood vessel is provided, and the system includes a sensor configured to obtain a measurement value from a blood vessel, obtaining the degree of cardiac collapse of the blood vessel from the measurement value, obtaining the degree of respiratory collapse of the blood vessel from the measurement value, a processor configured to calculate a ratio of cardiac collapse to respiratory collapse for indicating the body fluid state of the blood vessel.

[0009] Thereby, an index of the body fluid state can be obtained regardless of inter - individual and intra - individual variations in the quantitative measurement itself. For example, when the sensor obtains a measurement value of a signal type, it is possible to utilize the characteristics of the signal to derive the body fluid state rather than the absolute physical measurement values of the blood vessel such as pressure and volume. As two aspects of the same absolute physical effect, namely, collapse caused by the action of the heart and collapse caused by the action of respiration, are derived from the measurement value in order to calculate the ratio of blood vessel changes corresponding to the activities of the heart and respiration. By doing so, the measurement value is normalized, and the influence of not only the growth effect but also error sources such as inter - individual and intra - individual variations, differences in patient position, or differences in intra - abdominal pressure is eliminated.

[0010] The sensor of the system can be deployed within the blood vessel. This is advantageous in that, when deployed, it can provide simple, accurate, and non - invasive measurements using the sensor as needed. There is no need to repeat invasive measurements on the patient.

[0011] The sensor of the system can be attached to the patient's skin. In this case as well, it is advantageous in that it can provide measurement values using the sensor as needed. Furthermore, applying the sensor to the patient's skin provides an easy and non - invasive method for obtaining patient data.

[0012] The measured value can be a pressure measurement. Measuring the pressure of blood vessels provides an important indicator of the state of body fluids. This pressure measurement can be obtained from something implantable within the blood vessel or externally via an external pressure measuring device.

[0013] The measured value can be in the form of an MRI image. Such an image will provide an important visual indicator of the physical state of the blood vessels and the state of their body fluids. Such an image also provides an important visual clue to potential risks to the patient.

[0014] The measured value can be obtained via ultrasound (external, internal, intravascular, and / or other access for capturing the image region of interest). By using this common tool, it is also possible to obtain raw measurement traces and analyze them to provide information regarding the state of the patient's body fluids.

[0015] The measured value can be a pulse oximetry measurement. This is advantageous in that pulse oximetry provides information regarding the oxygen level in the blood.

[0016] The above measured value can be used to obtain the ratio of cardiac and respiratory collapse such that the calculated ratio provides an indicator of the state of body fluids within the blood vessel.

[0017] The measured value is a temporarily tracked recorded value. Furthermore, the temporarily tracked recorded value is that of a vascular correction value from the blood vessel. This is advantageous in that it provides continuous or progressive measurement and monitoring of the state of body fluids. This is important in that it provides changes in the state of body fluids that are visualized over time. Furthermore, this also gives rise to the possibility of predicting the future state of body fluids. This gives rise to the possibility of assigning preemptive treatment to the patient before the patient's current state deteriorates.

[0018] Furthermore, a method for determining the state of body fluids in blood vessels is provided. The method is Obtaining measurement values from a blood vessel via a sensor, Obtaining the degree of cardiac collapse of the blood vessel from the measurement values, Obtaining the degree of respiratory collapse of the blood vessel from the measurement values, Calculating a ratio of cardiac collapse to respiratory collapse for indicating the state of body fluid in the blood vessel, and comprising.

[0019] This method further comprises adjusting the amount of body fluid in the blood vessel based on an index of the state of body fluid. By such a method, the state of body fluid of a patient can be adjusted based on the provided measurement values. Adjusting the amount of body fluid in the blood vessel may include one or a combination of drug intake, dialysis, ultrafiltration, and a blood pump. Based on the obtained measurement values, it is possible to provide an index regarding the most appropriate treatment schedule for a specific patient.

[0020] Furthermore, a system for determining the state of body fluid in a blood vessel is provided. The system An elastic sensor disposed within the blood vessel and configured to obtain measurement values from the blood vessel, and compressible within a range between a maximum dimension s1 and a minimum dimension s2, Obtaining a measurement value m1 of a change in the dimension of the sensor after being disposed within the blood vessel, where the dimension is between s2 and s1, Obtaining a value r1 of a radial force from the measurement value m1, which is obtained by the sensor attached to the blood vessel after being disposed within the blood vessel, A processor configured to calculate a change rate of the blood vessel dimension r1 after attaching the sensor within the blood vessel with respect to a known blood vessel dimension Ao before attaching the sensor within the blood vessel, as a rate indicating the state of body fluid within the blood vessel, and comprising.

[0021] This is advantageous in that the state of body fluid can be derived based on the force exerted by a spring for compression and extension of the sensor within the blood vessel after deployment within the blood vessel.

[0022] In this system, m1 is the maximum measured value of the dimensions of the sensor after being attached to the blood vessel, m1 is greater than or equal to s2 and less than or equal to s1, the processor obtains a second measured value m2 which is the minimum of the dimensions of the sensor after being placed in the blood vessel, m2 is greater than or equal to s2 and less than or equal to s1, and the value of the radial force r1 obtained by the sensor attached to the blood vessel after being placed in the blood vessel is obtained from m1 and m2.

[0023] By obtaining two measurements (minimum and maximum) of the same absolute physical measurement, the ratio of the change in the blood vessel in response to the applied force can be calculated. As a result, it becomes possible to evaluate the ability of the blood vessel to expand, that is, the ability to accommodate more body fluid. Thereby, the position of the blood vessel on the pressure-volume curve can be confirmed, and thereby it becomes possible to provide an index of the current state of the body fluid of the blood vessel and the patient.

[0024] The processor further provides a MAXCHANGE value by calculating the ratio of the change in m1 to the known maximum blood vessel dimension m native1 and is configured to provide a MINCHANGE value by calculating the ratio of the change in m2 to the known minimum blood vessel dimension m native2

[0025] The state of full body fluid (hypervolemia) is represented by a MAXCHANGE value that is F1 times smaller than the MINCHANGE value, where F1 is approximately 10. This is advantageous in that the display of the state of full body fluid can be confirmed by comparing the obtained values.

[0026] The state of normal body fluid (euvolemia) is represented by a MAXCHANGE value that is F2 times larger or smaller than the MINCHANGE value, where F2 is approximately 2. This is advantageous in that the display of the state of normal body fluid can be confirmed by comparing the obtained values.

[0027] ​Hypovolemia is represented by a MAXCHANGE value that is F3 times greater than the MINCHANGE value, where F3 is between approximately 1.2 and 1.5. This is advantageous in that it allows for confirmation of the display of hypovolemia by comparing the obtained values.

[0028] The processor may further be configured to output a notification of the state of the body fluid in the blood vessel. The indicated state of the body fluid can be calculated by an algorithm incorporating several features from the signal and previously obtained signals. This is advantageous in that it can provide an automatic display of information regarding the state of the body fluid without the need for further analysis or calculation.

[0029] The processor may further be configured to output a notification indicating an action for adjusting the body fluid in the blood vessel. This is advantageous in that it automatically proposes corrective measures when an abnormal state of the body fluid is indicated.

[0030] The action may include a drug treatment schedule or a medical schedule. The obtained measurement values can provide an indicator for the treatment most appropriate for adjusting the body fluid state of a specific patient.

[0031] Furthermore, a method for determining the state of the body fluid in the blood vessel is provided. The method includes obtaining the dimensions of the blood vessel before deploying the sensor into the blood vessel, placing a sensor configured to be compressible within a range between a maximum dimension size s1 and a minimum dimension size s2 and to obtain measurement values from the blood vessel into the blood vessel, obtaining a measurement value m1 of the change in the dimensions of the sensor after being placed in the blood vessel, where the sensor is between s2 and s1, obtaining from m1 the value of the radial force r1 obtained by the sensor in the blood vessel after being placed in the blood vessel, calculating a rate of change of the blood vessel dimensions from r1 after attaching the sensor in the blood vessel with respect to the known blood vessel dimensions before attaching the sensor in the blood vessel as a rate indicating the state of the body fluid in the blood vessel.

[0032] Furthermore, a system for determining congestion within a blood vessel is provided. The system includes a sensor within the blood vessel configured to obtain a first signal indicative of a measured value a1 of a first area of the blood vessel before treatment of a patient and a second signal indicative of a measured value a2 of a second area of the blood vessel after treatment of the patient, and a processor configured to determine congestion within the blood vessel based on the first and second signals.

[0033] This is advantageous in that it enables evaluation of the fluid state without the need for complex invasive procedures, subjects the patient to a controlled treatment to apply a controlled perturbation to the vascular system, and can provide a method of monitoring physiological changes that provide an indicator of the resulting fluid state of the patient.

[0034] The processor may further be configured to determine the fluid state based on a specific signal shape derived from the measured values of the first and second areas. The signal shape may be a square wave shape. This is advantageous in that the signals obtained from the first and second area measurements provide an easily distinguishable shape that serves as an indicator of the fluid state.

[0035] The processor may further be configured to output a notification of the fluid state. This is advantageous in that it enables automatic display of information regarding congestion without the need for further analysis or calculations.

[0036] The processor may further be configured to output a notification indicating an action for reducing congestion. This is advantageous in that it can automatically propose a corrective treatment when congestion is indicated.

[0037] The action may include a change in one or more drug treatment schedules or medical schedules. The obtained measured values can provide an indicator regarding the most appropriate treatment for reducing congestion in a particular patient.

[0038] The medical schedule includes changes to at least a diuretic or vasodilator schedule, a vascular pump, a drug pump, a dialysis or ultrafiltration device, a pacing device, or an extracorporeal membrane oxygenation (ECMO) device.

[0039] Furthermore, a method for determining intravascular congestion is provided. The method acquires a first signal indicating a measured value a1 of a first area before the patient's treatment from a sensor in the blood vessel, performs the patient's treatment, acquires a second signal indicating a measured value a2 of a second area after the patient's treatment from a sensor in the blood vessel, and determines intravascular congestion based on the first and second signals.

[0040] The patient's treatment can be a Valsalva maneuver or a sniff-type treatment. This is advantageous in that the patient does not need to perform complex actions to obtain the necessary measurements. The Valsalva maneuver may involve the use of a device for generating a controlled level of internal pressure on the patient.

[0041] Furthermore, a system for determining cardiac output Oc is provided. The system includes a sensor configured to be deployed within the inferior vena cava (IVC) and to obtain a measured value Area1 of a first area of the IVC at a time point t1 and a measured value Area2 of a second area of the IVC at a time point t2, and a processor configured to determine the cardiac output based on a change in the area of the IVC obtained from the measured values of the first and second areas.

[0042] The system may further be configured to derive the heart rate from an analysis of the change in the area of the IVC.

[0043] This is advantageous in that it can indicate the cardiac output without requiring complex invasive procedures. Since the cardiac output is proportional to the change in the area of the IVC, the processor can be configured to determine the cardiac output.

[0044] The processor can further be configured to output a notification of the cardiac output. This is advantageous in that it can automatically display information regarding the cardiac output without requiring further analysis or calculations.

[0045] The processor can further be configured to output a notification indicating an action for adjusting the cardiac output. This is useful in that it can automatically propose corrective measures when an abnormal output is indicated.

[0046] The action can include a change in one or more drug treatment schedules or medical schedules. The obtained measurement values can provide an indicator regarding the most appropriate treatment for adjusting the cardiac output for a specific patient.

[0047] The medical schedule includes at least changes to a diuretic or vasodilator schedule, a vascular pump, a drug pump, a dialysis or hemofiltration device, a pacing device, or an extracorporeal membrane oxygenation (ECMO) device, etc.

[0048] Furthermore, a method for determining the cardiac output is provided. The method obtains a measurement value Area1 of a first area at a time point t1 from a sensor deployed within the inferior vena cava IVC, obtains a second area Area2 at a time point t2 from a sensor deployed within the IVC, and determines the cardiac output based on the change in the area of the IVC derived from the measurement values of the first and second areas.

[0049] The method further includes deriving a heart rate based on an analysis of the change in the area of the IVC.

Brief Description of the Drawings

[0050]

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Best Mode for Carrying Out the Invention

[0051] <Blood Vessel Area Measurement Method> The applicant of the present application has developed many devices that provide data on the amount of fluid based on direct measurement of physical dimensions of blood vessels such as diameter and area. Examples of these devices are described, for example, in PCT / US2016 / 017902 filed on February 12, 2016 by the present applicant, and WO2018 / 031714 filed on August 10, 2017 by the present applicant, each of which is hereby incorporated by reference in its entirety. Devices of the type described in these previous disclosures facilitate new management and treatment techniques based on normal intermittent (e.g., daily) or substantially continuous (almost real-time) direct feedback regarding the physical dimensions of blood vessels.

[0052] WO2018 / 031714 further describes some advantages of the information that can be derived from performing area type measurements using these devices. As can be seen in Figure 1A (replicated from Figure 1 of WO2018 / 031714), the response of a pressure-based diagnostic tool (B) in the region of normal blood volume (D) is relatively flat, and thus, minimal information is provided regarding exactly where the region corresponding to the patient's body fluid volume is located. Thus, pressure-based diagnostic tools tend to show a measurable response only after the patient's body fluid state enters the reduced circulating blood volume region (O) or the increased circulating blood volume region (R). In contrast, diagnostic approaches based on measurements of diameter or area by respiration and / or the cardiac cycle (A1 and A2) that are directly correlated to rC volume and IVC CI (hereinafter "IVC volume metric") provide relatively consistent and highly sensitive information regarding the patient's body fluid state across the entire state range.

[0053] In WO2018 / 031714, in this example, regarding the inferior vena cava (IVC), since an index of the patient's body fluid volume provides an opportunity for early response as both a sensitive warning of decreased circulating blood volume and an early warning of increased circulating blood volume, vascular area measurement is used. Regarding decreased blood volume, when pressure is used as a monitoring tool, a high pressure threshold may function as a potential sign of congestion, but when the pressure is below the pressure threshold (i.e., along the flat part of curve B), information regarding the body fluid state when the patient approaches decreased circulating blood volume cannot be obtained. Regarding increased circulating blood volume, vascular area measurement may provide a signal earlier than, for example, a pressure-based signal because the measurement of the diameter or area of the IVC changes by a relatively large amount without a significant change in pressure. Therefore, a threshold set for the measured value of the diameter or area of the IVC may indicate an early sign of increased circulating blood volume prior to a pressure-based signal. Figure 1B is a plot of data obtained from experiments on fluid removal and loading in vivo. This shows, as an example of the response of the IVC in experiments on fluid removal and loading in vivo, the right atrial pressure (RAP) as a function of the area of the IVC (upper) and collapse (= Amax - Amin) as a function of the area of the IVC (lower). <Acquisition of measured value of cross-sectional seat of blood vessel>

[0054] A system and sensor for acquiring a measured value of the area of a blood vessel are described in WO2018 / 031714. Figure 2 shows an aspect of such a system 1 for acquiring a measured value from the IVC 2 of a patient 3 using a sensor 4. This system can also be used to acquire measured values from other blood vessel types.

[0055] Processor 5 can take the form of a laptop or desktop computer. Processor 5 can further be a mobile communication device such as a mobile phone or a tablet. The processor can further be a wearable electronic device or a sensor reader. When the processor is incorporated in a sensor reader, the reader needs to be able to wirelessly transmit and receive the necessary radio frequency pulses, filter and process them as necessary, and control the appropriate software for interpreting the results. The processor is composed of software suitable for interpreting sensor measurements. Further, in some embodiments, sensor 4 and processor 5 are configured to communicate via one or more data links, preferably a remote / wireless data link, with a control and communication module, and one or more remote systems such as a processing system, a user interface / display, a data storage, etc. that communicate with the control and communication module. FIG. 2 shows one aspect of such a system. Such a system may include a control module 6 that communicates with the sensor and, in some embodiments, powers or activates the sensor. The processor may be included within control module 6. Alternatively, processor 5 can be a separate device. Control module 6 can include a controller 7 and a communication module 8. The control module can include a bedside console. A belt reader or antenna 9 can be worn by the patient around the waist for patient comfort and reproducibility of positioning. The antenna is for wirelessly transmitting measurement values from sensor 4 to processor 5. Information can be transferred 11 from communication module 8 to remote system 10 and / or network 12 via Bluetooth®, Wi-Fi, cellular, or a local area network for storage and / or further analysis.

[0056] Sensor 4 can take the form of an implantable device. The insertion of such a device into the circulatory system of a human or animal is well known in the art and will not be described in detail here. To obtain measurements m1 and m2, the sensor is implanted in a blood vessel, with the first sensor at position x1 and the second sensor at position x2. When the sensor is placed at a predetermined position and activated, it can obtain measurements of the modulation region from the blood vessel via inductance and thus frequency modulation. The processor obtains the measurements from the sensor, for example, via a wireless link to the sensor or resonant coupling with the sensor. Once obtained by the processor, the measurements are processed and analyzed as will be described in more detail below to determine the dimensions of the blood vessel.

[0057] The measurement of the diameter or area of the blood vessel by sensor 4 can be performed continuously over one or more respiratory cycles to determine the variation in the dimensions of the blood vessel over said one or more respiratory cycles. Further, these measurement periods can be continuously employed during a preselected period and / or in response to a prompt provided remotely from a signal within the system or from a healthcare provider / patient.

[0058] In one embodiment of the present disclosure, for the first sensor 4, a variable inductance L-C circuit 13 can be used to perform the measurement or monitoring functions described herein, as schematically shown in FIG. 3. Sensor 4 can also include means 14 for firmly fixing the implant within the IVC. Using variable inductor 15 and a known capacitance 16, the L-C circuit 13 generates a resonant frequency that changes as the inductance changes. When the shape and dimensions of the blood vessel change, the configuration of the variable inductor changes, thereby changing the resonant frequency of the circuit.

[0059] Therefore, not only should the sensor be firmly placed at the monitoring position, but at least the variable coil / inductor portion 13 of the implant should be selected and specially configured to have a predetermined compliance (elasticity) such that it can move with the changes while minimizing the distortion of the natural movement of the blood vessel wall and maintaining its position without changing the shape or dimensions of the blood vessel wall. Thus, in some embodiments, the variable inductor is specially configured to change its shape and inductance in proportion to changes in the shape or dimensions of the blood vessel.

[0060] The variable inductor 15 is configured to be energized remotely by an electric field supplied by one or more transmitting coils within the antenna module 9 disposed outside the patient. When energized, the L-C circuit 13 generates a resonant frequency, which is then detected by one or more receiving coils of the antenna module. Since the resonant frequency depends on the inductance of the variable inductor, a change in the shape or dimensions of the inductor caused by a change in the shape or dimensions of the blood vessel wall causes a change in the resonant frequency. Next, the detected resonant frequency is analyzed by the system's processor component to determine the diameter or area of the blood vessel or changes therein. The blood vessel measurements obtained by the sensor are processed and analyzed to determine the dimensions of the blood vessel, as described in more detail below.

[0061] Examples of sensor 4 for use in the systems and methods described herein are shown in FIG. 4 and further described below. The sensor is composed of a frame with eight convex shapes 17. The box in FIG. 5 shows an enlarged detailed cross-section. In this embodiment, sensor 18 includes a plurality of parallel wires 19 formed around frame 20. When using a plurality of wires, a capacitance is generated between the wires 19 of the implant, so the resonant circuit can be created by including discrete capacitors, elements, or by the inherent capacitance of the coil without the need for separate capacitors. Note that in the cross-sectional view of FIG. 5, the individual ends of the very thin wires are too small to be clearly visible. In the drawing, the wires are wound around frame 20 in a way that gives the appearance of a layer. The exact capacitance required for the RC circuit can be achieved by adjusting the capacitance by any one or a combination of the selection of discrete capacitors, the selection of materials, and the configuration of the wires. In certain alternative sensors 18, there may be a relatively small number of wires. For example, there may be about 15 wires and about 20 loops around the sensor. In another alternative implant 18, there may be a relatively large number of wires. For example, there may be about 300 wires forming a single loop around the sensor.

[0062] Frame 20 can be formed from nitinol as either a shaped set wire or a laser cut shape. One advantage of the laser cut shape is that additional anchor features can be cut along the frame shape and folded into the frame for delivery. When using a frame structure as shown in FIG. 5, the frame needs to be discontinuous so as not to complete the electrical loop within the implant. The coil wire can include high-purity, thin, individually insulated wires wound to form a litz wire. The factors that determine the inherent inductance include the number and turns of the wire, and the capacitance, frequency Q, and profile balance. <Deriving the state of body fluids from the ratio of cardiac collapse to respiratory collapse>

[0063] An increase in blood volume can lead to hospitalization or death. The pressure within the blood vessels, and the geometric representation of the size of the blood vessels (i.e., volume, area, diameter) are typically utilized to estimate changes in the state of body fluids. However, such absolute measurements are strongly affected by inaccurate and cumbersome measurement methods that prevent the function of setting unique thresholds for classifying the state of human body fluids. Furthermore, using sensors that touch the inside of the blood vessels in the human body can cause changes in the physiological response of the blood vessels themselves. For example, the interaction between the sensor and the blood vessel can lead to tissue growth on the sensor. Such growth can potentially reduce the ability of a particular sensor for the collapse of a particular blood vessel. Therefore, depending on the degree of interaction between the sensor and the blood vessel, the establishment of the blood vessel dimension threshold is also affected and needs to be appropriately changed.

[0064] System 1 is provided to determine the state of body fluid within blood vessel 2. System 1 includes a sensor 4 configured to obtain measurements from blood vessel 2. A processor 5 is configured to derive a measurement of the collapse of the heartbeat of the blood vessel from the measurements, derive a measurement of the collapse of the respiration of the blood vessel from the measurements, and further calculate a ratio of the collapse of the heartbeat to the collapse of the respiration such that the calculated ratio provides an indicator of the state of body fluid within the blood vessel.

[0065] Therefore, the state of body fluid within the blood vessel can be determined from the ratio of the collapse of the heartbeat and respiration observed from various types of measurements. For example, it can be by means of a temporal trace of a geometric measurement such as pressure, or volume, area, diameter, etc.

[0066] This provides a more simplified measurement technique compared to other techniques used to obtain similar body fluid state information, such as absolute blood volume measurement, external ultrasound, and pulmonary implants with pressure sensors. In such techniques, it is usually necessary to collect a blood sample. Furthermore, the measured values obtained are noisy and may be prone to artifacts due to external factors. Also, such methods are usually "one-shot" and cannot be used for continuous monitoring. These methods only provide a snapshot of the patient's condition at the time of the test.

[0067] Sensors configured to obtain measurements from blood vessels can be placed within the blood vessels. For example, the sensor can be placed within the inferior vena cava (IVC). Once deployed, measurements can be provided as needed by using the sensor. There is no need to repeatedly perform invasive measurements on the patient. The sensor can be of the type shown in FIG. 4 or other types of sensors can also be utilized.

[0068] FIG. 5 shows a plot of the absolute cross-sectional area (mm 2 ) of the sensor over a certain period. The relative changes in area due to both respiratory and cardiac arrest are shown together. The sensor provides raw signal data that can be filtered to separate features related to the patient's cardiac response from features related to the respiratory response. For example, the heart rate response usually appears as a signal indicating 50 - 100 bpm, and the respiratory response usually appears as a signal indicating 2 - 50 bpm. The heart rate in the "dry case" may be difficult to detect due to the influence of noise. By filtering the respiratory signal and subtracting it from the raw signal data, it is possible to leave a signal that provides the cardiac output and noise. Since the noise is Gaussian distributed, further filtering this can provide the cardiac output. As another method, it is possible to determine the respiratory rate by determining the magnitude and phase fluctuations from a sensor signal obtained externally (e.g., a belt-type sensor equipped with an accelerometer). By subtracting this from the raw signal data obtained from the internally placed vascular sensor, a signal of the heart rate can be obtained.

[0069] Figures 6A and 6B show the measured values of the area and pressure of the sensor obtained by loading blood into a healthy sheep weighing 70 kg. The measured values were obtained when the liquid was loaded and the state changed from a dry state (low liquid load), a normal state, to a wet state (high liquid load). These traces show that the ratio of heart rate to respiration is low when dry and high when wet. This can be confirmed with the trace data for both pressure and area.

[0070] Figures 7A and 7B show the changes in IVC area and pressure after deploying a native blood vessel (upper image labeled "native blood vessel") and a device (e.g., the device in Figure 4) into the IVC (lower image labeled "acute after sensor deployment"). Note that cardiac collapse is displayed as a modulation superimposed on the respiratory modulation from a body fluid level of an additional / removed blood volume of -500 ml, in both the native and acute state regions and pressures. Since the higher frequency heart rate pulses are only displayed in waveforms exceeding -500 mls, the accumulation of body fluid is indicated.

[0071] Figure 8 shows additional data obtained using the system described herein from further fluid loading tests in the IVC of a sheep. The magnitude of the heart rate (as a percentage of the magnitude of respiration) is plotted against the sensor area. The data points indicated by the shaded circles show the removal of blood in 250 ml steps. The data points indicated by the unshaded circles show the addition of blood in 250 ml steps. Again, this data shows that the magnitude of the heart rate (as a percentage of the magnitude of respiration) increases with body fluid load and increasing area.

[0072] Figure 9 shows data obtained using the system described herein from a fluid challenge test in the native IVC of a heart failure patient. The graph shows the collapse rate at baseline (left end), after injection of 250 ml of saline (center), and after injection of 500 ml of saline (right end). The cardiorespiratory collapse rate increases with the amount of fluid added. The trace filtered from the raw signal is shown in the lower left figure.

[0073] For the above-described system, in order to obtain measurements from blood vessels, a sensor disposed in a blood vessel, such as the IVC, will be used to explain. Such an arrangement is estimated to achieve a measurement accuracy on the order of 10 times higher than other modalities such as, for example, external ultrasound. The system being described achieves an accuracy in the range of + / - 0.1 mm in the diameter of the blood vessel as compared to external ultrasound. External ultrasound achieves an accuracy in the region of + / - 1 mm in the diameter of the blood vessel. By improving the accuracy in this way, a reliable determination regarding cardiorespiratory collapse becomes possible.

[0074] The measurement can be a pressure measurement. The measurement can be in the form of an MRI image. The measurement can be a pulse oximetry measurement. The measurement can be a time trace recording. Here, the time trace recording relates to the deformation of the blood vessel or the change in the dimension of the blood vessel. Further, the sensor of the system can be applied to the patient's skin, for example, via a patch attached to the skin.

[0075] A method for determining the state of body fluid in a blood vessel includes obtaining a measurement value from the blood vessel via a sensor, deriving a measurement value of collapse due to heartbeat from the measurement, deriving a measurement value of collapse due to respiration from the measurement value, and calculating a ratio of collapse of heartbeat and respiration for indicating an index of the state of body fluid in the blood vessel.

[0076] Once the state of the patient's body fluid is obtained, the amount of body fluid in the blood vessels can be adjusted based on the display of the state of the body fluid. Therefore, the state of the patient's body fluid can be adjusted based on the measured value of the obtained state of the body fluid. The adjustment can be performed, for example, by recommending a treatment schedule including drug intake, dialysis, ultrafiltration, and blood pumps. The obtained measured value can provide an index regarding the most appropriate treatment schedule for a specific patient. <The state of body fluid derived from the change in radial force>

[0077] This system is for determining the state of body fluid in blood vessels, such as for determining the fluid state in blood vessels like the IVC, and includes an elastic sensor disposed in the blood vessel. The sensor (for example, the sensor in FIG. 4) is configured to acquire a measurement value from the blood vessel. The sensor is compressible between a maximum size s1 (i.e., when the sensor is fully expanded) and a minimum size s2 (i.e., when the sensor is fully folded) (see, for example, FIG. 12). The processor is configured to acquire a measurement value m1 of the change in the sensor size after being disposed in the blood vessel. Note that m1 is a value between s1 and s2. The processor further acquires from m1 the value r1 of the radial force applied to the blood vessel by the sensor after deployment into the blood vessel, and further, from r1 after deploying the sensor into the blood vessel, is configured to calculate the ratio of the change in the blood vessel dimension to the known blood vessel dimension Ao before deploying the sensor. Here, the ratio provides an index of the state of body fluid in the blood vessel.

[0078] A method for determining the fluid state within a blood vessel further includes obtaining the dimensions Ao of the blood vessel before placing a sensor within the blood vessel. The dimensions of the blood vessel can be obtained experimentally (see, for example, the lower part of FIG. 10). The dimensions of the blood vessel can be obtained via ultrasound, X-ray, or MRI imaging. The sensor is placed within the blood vessel and configured to obtain measurements from the blood vessel. The sensor is compressible between a size s1 of the maximum dimension and a size s2 of the minimum dimension. This method provides obtaining a measurement value m1 of the change in the sensor dimension after deployment within the blood vessel, where m1 is a value between s1 and s2, and from m1, obtaining a value of the radial force r1 exerted on the blood vessel by the sensor after placement within the blood vessel, for calculating the ratio of the change in the dimensions of the blood vessel from the dimensions of the blood vessel obtained before placing the sensor within the blood vessel to r1 after placing the sensor within the blood vessel. And this ratio indicates the state of the body fluid within the blood vessel.

[0079] The sensor has known characteristics. Such as tensile characteristics, minimum dimension during compression, maximum dimension during elongation, etc. These can be calculated and calibrated before deployment in the blood vessel. Thus, the sensor exerts a known radial force on the blood vessel wall during deployment due to compression or expansion of the sensor.

[0080] The state of the fluid within the blood vessel is determined based on the ratio of the maximum and minimum measurements of the acute blood vessel to the native blood vessel observed in the time trace of the pressure, or on geometric measurements such as volume, area, diameter, etc., using the known radial force.

[0081] This system determines the reference area of the location of the IVC where the device is implanted using the information on the radial force acquired from the sensor. It is difficult to grasp how much the dimensions of a blood vessel actually change without measuring pressure or geometrically moving the blood vessel throughout its dynamic range. This system utilizes a known calibrated radial force applied to the internal pressure while keeping the blood vessel open. Next, by using the changes in the minimum and maximum blood vessel sizes due to the applied force, it is possible to estimate whether the blood vessel can still expand or contract using an experimentally obtained model of the pressure-volume curve of the blood vessel. In fact, it can be established when the body fluid state of a specific patient is on the CVP-A curve, as in the example of the curve in FIG. 13. Therefore, this can provide an indicator of the body fluid state of a specific patient at the time of sensor implantation and can thus also be used as an input for understanding future changes in sensor output.

[0082] In this system, m1 provides a measurement of the maximum change in sensor dimensions after deployment in the blood vessel. m1 is a value between both including s1 and s2. The processor is further configured to acquire a second measurement m2 of the minimum change in sensor dimensions after placement in the blood vessel, and m2 is a value between both including s1 and s2. The processor calculates the ratio of m1 to the known maximum blood vessel dimension (m native1 ) to provide a MAXCHANGE value and calculates the ratio of m2 to the known minimum blood vessel dimension (m native2 ) to provide a MINCHANGE value.

[0083] Figure 10 shows the measured values for determining the experimental CVP-A / A0 curve of a vein. An example of the curve is shown in the lower right of the figure. Figures 11 and 12 show the calibration procedure for obtaining the corresponding data of the radial force of the expanding sensor and the sensor area. A sensor as shown in Figure 4 is being tested, but other types of sensors can also be used. The sensor is the subject of a series of test forces. In this way, the radial forces exerted by the sensor over the entire range of s1 and s2 of a given sensor, as well as the compression and expansion positions, can be obtained. Figure 13 shows an adjusted model that merges the radial force of the sensor curve with the native vascular curve experimentally obtained for pressure and volume / area. By correlating and using these calibrated numerical values with the measured compression and expansion of the sensor during the patient's inhalation and exhalation, the radial force exerted by the intravascular sensor can be determined. These values can be used to obtain an indicator of the patient's fluid state. Figure 13A shows a schematic diagram of the maximum and minimum sensor sizes s1, s2 in the blood vessel as described above, together with the measurement example m1. In this example, the blood vessel diameter Ao before deployment is expanded to size m1. An increase in the value of m1 corresponds to a decrease in the radial force applied by the sensor.

[0084] For example, referring to Figure 14, the change in area due to the deployment of the sensor occurring at 174 mm 2 is shown to be similar to the change occurring at 128 mm 2 The inhalation value corresponds to the MINCHANGE value, and the exhalation value corresponds to the MAXCHANGE value. This indicates that the inhalation region was in the flat part of the CVP-A curve. This further suggests that the exhalation region was in the flat part of the CVP-A curve. This indicates a "near-normal" fluid state.

[0085] Referring to Figure 15, the change in area due to the deployment of the sensor occurring at 271 mm 2 is 338 mm 2It has been shown to be twice the change that occurred. This indicates that the inhalation region was at the end of the flat part of the CVP-A curve. This further suggests that the exhalation region was at the beginning of the steep part of the CVP-A curve. This indicates a "normal to moderately full" body fluid state.

[0086] Referring to Figure 16, 429 mm 2 The change in area due to the deployment of the sensor that occurred at is 360 mm 2 It has been shown to be one-tenth compared to the change that occurred at. This indicates that the inhalation region was at the end of the flat part of the CVP-A curve. This further suggests that the exhalation region was at the steep gradient of the flat part of the CVP-A curve. This indicates a "full" body fluid state.

[0087] Therefore, these figures make it possible to show guidelines for evaluating the position on the P-V curve by evaluating the change in area of the vessel with the sensor deployed from the native vessel. This is summarized in Table 1 below.

Table 1

[0088] A large change can be considered as an area change at a level exceeding 20%, and a small change can be considered as an area change at a level less than 10%.

[0089] Therefore, in the state of full body fluid, it is shown that the MAXCHANGE value is F1 times smaller than the MINCHANGE value. Here, F1 is about 10. In the state of normal to moderately full body fluid, it is shown that the MAXCHANGE value is F2 times smaller than the MINCHANGE value. Here, F2 is about 2. In the state of normal body fluid, it is shown that the MAXCHANGE value is F3 times smaller than the MINCHANGE value. Here, F3 is about 1.2 - 1.5. <Method for Detecting Congestion>

[0090] There are several existing techniques for detecting congestion in patients. For example, monitoring blood pressure and heart rate, jugular vein compression, points of maximum impulse measurement, detection of the third and fourth heart sounds, lung examination, liver size examination, hepatojugular reflux, lower limb edema, etc. All of these techniques have the drawback that they must be performed by skilled technicians in a clinic.

[0091] Blood pressure measurement during the Valsalva maneuver was described in 1976 by Wilkinson et al. in relation to cardiac congestion assessment. However, this method requires obtaining invasive pressure measurements and is not suitable for home use.

[0092] A system including an intravascular sensor is provided for determining intravascular congestion. The sensor is configured to obtain a first area measurement value a1 of the blood vessel before treatment of the patient and a second area measurement value a2 of the blood vessel after treatment of the patient.

[0093] The processor is configured to determine intravascular congestion in the blood vessel based on the measurement values of the first and second areas. The sensor may be a sensor as shown in FIG. 4, but other types of sensors can also be used. The sensor can be placed in the patient's IVC.

[0094] The processor is configured to provide a signal output based on the area measurement values taken before and after treatment of the patient. The processor is further configured to determine the state of the fluid in the blood vessel based on the identified signal shape obtained from the measurement values of the first and second areas. When the patient's treatment is the Valsalva method, the shape of the identified signal is a square wave shape. In fact, the system is for evaluating the response of the IVC to the treatment. When a square wave pattern of the IVC dimension is observed in the signal, this indicates that the patient is in a state of fluid overload in the same way as described above using blood pressure as the input signal (see FIG. 17).

[0095] The processor is further configured to provide a notification of congestion detected within a blood vessel. This notification can be in a computer-readable format. Alternatively, the notification can be sent to a remote monitoring server or to a wireless mobile device. The processor is further configured to provide a notification indicating an action to reduce congestion of the blood vessel.

[0096] For example, the action can include a change in drug therapy, or a treatment schedule. The treatment schedule can include at least a diuretic or vasodilation schedule, a change in a medical device such as a blood vessel pump, a drug pump, a dialysis or hemofiltration device, a pacing device, or an extracorporeal membrane oxygenation (ECMO) device.

[0097] Thus, when the sensor is embedded in the manner described above, routine measurement of congestion at home by the patient becomes feasible. This enables early detection and a treatment schedule tailored specifically to the patient's needs.

[0098] A method for determining blood congestion is as follows. Before the patient's treatment, a measurement value of a first area a1 is obtained from a sensor within the blood vessel. As the patient's treatment, for example, the Valsalva maneuver or the like is performed. After the patient's treatment, a measurement value of a second area a2 is obtained from the sensor within the blood vessel. Based on the measurement values of the first and second areas, blood congestion within the blood vessel is obtained.

[0099] The first and second measurements provide a signal output. Detection of a square wave pattern from the signal output indicates that the patient is in a state of fluid overload. <Evaluation of cardiac output by monitoring changes in IVC area>

[0100] Changes in cardiac output are an important indicator for patients with heart failure. Since cardiac output can be remotely monitored, optimal care for patients with heart failure becomes possible, and physicians can improve the quality of life and average life expectancy of such patients.

[0101] Cardiac output is usually determined by performing angiography. However, this requires a hospital visit and is invasive.

[0102] A system for determining cardiac output Oc includes a sensor disposed in the inferior vena cava (IVC) and a sensor configured to obtain a measurement Area1 of a first area of the IVC at time t1. The sensor is further configured to obtain a measurement Area2 of a second area of the IVC at time t2. A processor is configured to determine cardiac output based on the change in the area of the IVC obtained from the measurements of the first and second areas.

[0103] Since cardiac output Oc is proportional to the change in the area of the IVC, the processor is configured to determine cardiac output from the obtained area measurements.

[0104] The processor is further configured to provide a notification of the cardiac output. Thereby, information regarding cardiac output is automatically displayed without the need for further analysis or calculation.

[0105] This notification can be in a computer-readable format. Alternatively, it is also possible to send the notification to a remote monitoring server or to a wireless mobile device. The processor is further configured to provide a notification indicating an action for adjusting the cardiac output within the blood vessel.

[0106] For example, actions can include a drug treatment schedule, a medical schedule. The treatment schedule can include a dialysis schedule, Treatment Y, Treatment Z. Thus, when the sensor is embedded in the manner described above, daily measurement of cardiac output at home by the patient becomes feasible. This enables early detection and a special treatment schedule tailored to the patient's needs.

[0107] Furthermore, a method for determining cardiac output is provided. The method comprises obtaining a measurement value Area1 of a first area from a sensor disposed in the inferior vena cava (IVC) at time t1, obtaining a measurement value Area2 of a second area from the sensor disposed in the IVC at time t2, and determining the cardiac output based on the change in the area of the IVC obtained from the measurement values of the first and second areas.

[0108] Therefore, the change in the monitored area of the IVC can be an indicator of the patient's cardiac output Co. The sensor can be disposed on the patient as described above to obtain a measurement value of the area of the IVC. <Derivation of cardiac output Oc from measurement of the area of the IVC>

[0109] The change in the area of the IVC can be used to derive an indicator of cardiac output.

[0110] The change in cardiac output Co is related to the change in venous return. Venous return can be determined from the combination of IVC flow and SVC flow. Here, SVC is the superior vena cava. Factor IVC flow milking is derived from the sum of the changes in the volume of the IVC with respect to time. This is based on the premise that the change in the volume of the IVC is dominated by the change in the area of the IVC. Furthermore, it is assumed that the change in pressure in the respiratory cycle dominates the pressure drive of the change in volume related to the IVC flow milking Since the IVC

[0111] IVC flow milking is directly correlated with cardiac output, the change in the area of the IVC can be an indicator of cardiac output Oc. <Venous Resistance>

[0112] Furthermore, venous resistance can be measured. First, venous return is defined as follows. (Equation 1) TIFF2025087794000003.tif50166Here, MCFP = mean circulatory filling pressure RAP = right atrial pressure That is. As a result, it becomes as follows. (Equation 2) TIFF2025087794000004.tif41166

[0113] The change in venous flow is assumed to be governed by venous milking, which is a factor in flow. It is assumed that the pressure change in the respiratory cycle dominates the driving of the pressure of volumemilking. Venresistance is assumed not to change over the respiratory cycle.

[0114] Regarding the respiratory cycle, volumemilking correlates with the volume of the IVC.

[0115] At the minimum IVC pressure during respiration, the flow of volumemilking = 0. And at the maximum IVC pressure, the flow of volumemilking is maximum.

[0116] Venous resistance (VenResistance) can be defined as follows. (Equation 3) TIFF2025087794000005.tif41166Here, ΔPmilking can be derived from the change in the pressure of the IVC determined from the change in the area of the IVC.

[0117] In addition, when the RAP increases or the MCFP decreases, the venous blood flow changes. The MCFP is the case when the venous flow is zero. When the milking flow rate is close to zero at a low pressure, the associated minimum pressure is related to the MCFP.

[0118] As used herein, the terms "comprising" and "having" are used to specify the presence of the recited features, integers, steps or components, but do not preclude the presence or addition of one or more other features, integers, steps, components, or groups thereof.

[0119] Specific features of the present disclosure that are described in the context of separate embodiments for clarity may also preferably be provided in combination in a single embodiment. Conversely, the various features of the present disclosure that are described in the context of a single embodiment for brevity may also be provided separately or in any suitable sub-combination.

Claims

1. A system for determining congestion in a blood vessel, comprising: a sensor in the blood vessel configured to obtain a first signal indicative of a first area measurement a1 of the blood vessel before treatment of the patient, and a second signal indicative of a second area measurement a2 of the blood vessel after treatment of the patient; and a processor configured to acquire the first signal and the second signal, and determine congestion in the blood vessel based on a difference between the first signal indicative of the first area measurement a1 obtained before treatment of a patient and the second signal indicative of the second area measurement a2 obtained after treatment of a patient.

2. The system of claim 1 , wherein the processor further outputs a notification indicating an action to reduce congestion in the blood vessel.

3. The system of claim 2 , wherein the action comprises a drug treatment schedule.

4. The system of claim 2 , wherein the action includes a medical schedule.

5. 5. The system of claim 4, wherein the medical schedule includes at least a diuretic or vasodilator schedule or changes to a vascular pump, a drug pump, a dialysis or autofiltration device, a pacing device or an extracorporeal membrane oxygenation (ECMO) device.

6. 1. A system for determining cardiac output, comprising: a sensor deployed within the inferior vena cava (IVC) and configured to obtain a first area measurement (Area1) of the IVC at a time t1 and a second area measurement (Area2) of the IVC at a time t2; and a processor configured to determine the cardiac output based on a change in area of ​​the IVC derived from a measurement of a first area of ​​the IVC, Area1, obtained at a time t1, and a measurement of a second area of ​​the IVC, Area2, obtained at a time t2.

7. The system of claim 6 , wherein the processor is further configured to determine heart rate from analysis of changes in area of ​​the IVC.

8. The system of claim 6 or 7, wherein the processor is further configured to output a notification of cardiac output.

9. The system of claim 8 , wherein the processor is further configured to output a notification indicating an action to adjust cardiac output.

10. The system of claim 9 , wherein the action includes a schedule of a medication.

11. The system of claim 9 , wherein the action includes a medical schedule.

12. 12. The system of claim 11, wherein the medical schedule includes at least a diuretic or vasodilator schedule or changes to a vascular pump, a drug pump, a dialysis or autofiltration device, a pacing device or an extracorporeal membrane oxygenation (ECMO) device.

13. 1. A method for determining cardiac output, comprising: obtaining a first area measurement m1 from a sensor deployed within the inferior vena cava IVC; acquiring a second area m2 from a sensor deployed within the IVC; determining the cardiac output based on a change in the area of ​​the IVC derived from a measurement m1 of a first area of ​​the IVC obtained at a time t1 and a measurement m2 of a second area of ​​the IVC obtained at a time t2.

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