WO2025188798A1

WO2025188798A1 - Active implantable biatrial pressure sensor

Info

Publication number: WO2025188798A1
Application number: PCT/US2025/018401
Authority: WO
Inventors: Alan Ostroff; Carl Lance Boling; Suresh Gurunathan
Original assignee: Synkopi Inc
Current assignee: Synkopi Inc
Priority date: 2024-03-04
Filing date: 2025-03-04
Publication date: 2025-09-12
Anticipated expiration: 2026-09-04
Also published as: WO2025188798A8

Abstract

The present disclosure is directed to systems and methods for measuring pressure within a patient. In some implementations, an active implantable sensor is provided that is configured to continuously or periodically obtain pressure signal measurements from within a heart of a patient. The pressure sensor can have an operational lifetime up to or exceeding 5-7 years, and can be configured to continuously or periodically transmit recorded information or data or statistics synthesized from the recorded information to an external device, such as a smartphone, tablet, pc, or other electronic device. Methods of use are also provided.

Description

ACTIVE IMPLANTABLE BIATRIAL PRESSURE SENSOR

RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63/560,920, titled “ACTIVE IMPLANTABLE BIATRIAL PRESSURE SENSOR,” and filed on March 4, 2024, which is incorporated herein by reference in its entirety.

INCORPORATION BY REFERENCE

[0002] All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

FIELD

[0003] The present disclosure details novel systems and methods for measuring pressure in a patient with an active implantable sensor. Specifically, this disclosure provides an active implantable sensor for continuously measuring pressure in both the left and right atriums of the heart of the patient over extended operational lifetimes.

BACKGROUND

[0004] Implantable cardiac pressure monitors are used to monitor changes in heart pressure (e.g., pulmonary artery pressure) which can provide early indications of worsening heart failure.

[0005] Previously disclosed implantable pressure monitors, for example CardioMEMs, Endotronix, and Vectorious Medical Technologies, are not active devices; they require a wand or other device to be placed close to an implanted sensor in order to communicate with the passive implant to measure intracardiac pressure. The drawback from using a passive implant is that the sensor can only measure and record information when the wand is in close proximity since there is no internal power source or memory elements in the implant to record activity.

[0006] The CardioMEMs and Endotronix sensor both measure PAP (pulmonary artery pressure). Vectorious Medical measures LAP (left atrial pressure) by fixating their sensor in the atrial septal wall.

SUMMARY OF THE DISCLOSURE [0007] An active implantable biatrial pressure sensor is provided, comprising: a housing adapted to be implanted within a human heart; a cell disposed in the housing; a first pressure sensor disposed in a first end of the housing and configured to measure a first pressure reading outside of the housing; a first deformable lid attached to the housing and being fluidly coupled with the first pressure sensor; a second pressure sensor disposed in a second end of the housing and configured to measure a second pressure reading outside of the housing; a second deformable lid attached to the housing and being fluidly coupled with the second pressure sensor; and electronics disposed in the housing and operatively coupled to the cell and the first and second pressure sensors, the electronics being configured to determine a pressure gradient between the first pressure reading and the second pressure reading, compare the pressure gradient to a predetermined threshold, and output a treatment recommendation.

[0008] In some aspects, the housing comprises first and second separate hermetically sealed cavities for housing the first and second pressure sensors.

[0009] In some aspects, the first and second separate hermetically sealed cavities are oil filled.

[0010] In other aspects, the first and second deformable lids are attached to the first and second separate hermetically sealed cavities.

[0011] In one aspect, the first and second pressure sensors comprises MEMs capacitive sensors.

[0012] In some aspects, the electronics comprise a real time clock, a transceiver, GMR sensor and an accelerometer.

[0013] In other aspects, the electronics comprise an accelerometer.

[0014] In one aspect, the electronics are configured to use measurements from the accelerometer to obtain activity -based pressure measurements.

[0015] In some aspects, the electronics are configured to use measurements from the accelerometer to obtain orientation-based pressure measurements.

[0016] In another aspect, the housing has a volume less than 2 cc.

[0017] In some aspects, the electronics compartment comprises a volume of between 0.25 and 0.75 cc.

[0018] In another aspect, the electronics being configured to synthesize blood pressure statistics from the first and second pressure readings and intermittently transmit the blood pressure statistics to an external device multiple times per day over an operating lifetime of at least 5 years. [0019] An active implantable biatrial pressure sensor is provided, comprising: a housing having a volume less than 2 cc and adapted to be implanted within a human heart; a cell disposed in the housing; a first pressure sensor disposed in a first end of the housing and configured to measure a first pressure reading outside of the housing; a first deformable lid attached to the housing and being fluidly coupled with the first pressure sensor; a second pressure sensor disposed in a second end of the housing and configured to measure a second pressure reading outside of the housing; a second deformable lid attached to the housing and being fluidly coupled with the second pressure sensor; and electronics disposed in the housing and operatively coupled to the cell and the first and second pressure sensors, the electronics being configured to synthesize blood pressure statistics from the first and second pressure readings and intermittently transmit the blood pressure statistics to an external device multiple times per day over an operating lifetime of at least 5 years.

[0020] In some aspects, the housing comprises first and second separate hermetically sealed cavities for housing the first and second pressure sensors.

[0021] In some aspects, the first and second separate hermetically sealed cavities are oil filled.

[0022] In other aspects, the first and second deformable lids are attached to the first and second separate hermetically sealed cavities.

[0023] In one aspect, the first and second pressure sensors comprises MEMs capacitive sensors.

[0024] In some aspects, the electronics comprise a real time clock, a transceiver, GMR sensor and an accelerometer.

[0025] In other aspects, the electronics comprise an accelerometer.

[0026] In one aspect, the electronics are configured to use measurements from the accelerometer to obtain activity -based pressure measurements.

[0027] In some aspects, the electronics are configured to use measurements from the accelerometer to obtain orientation-based pressure measurements.

[0028] In another aspect, the housing has a volume less than 2 cc.

[0029] In some aspects, the electronics compartment comprises a volume of between 0.25 and 0.75 cc.

[0030] A method of monitoring a heart of a patient is provided, comprising the steps of positioning an implantable biatrial pressure sensor into the heart such that a first pressure sensor is disposed in a left atrium while a second pressure sensor is disposed in a right atrium; obtaining left atrial pressure readings with the first pressure sensor; obtaining right atrial pressure readings with the second pressure sensor; determining a pressure gradient between the left atrium and the right atrium based on the left and right atrial pressure readings; comparing the pressure gradient to a gradient threshold; and outputting a first treatment recommendation if the pressure gradient is above the gradient threshold.

[0031] In some aspects, the determining and outputting steps are performed by circuitry within the implantable biatrial pressure sensor.

[0032] In one aspect, the method includes transmitting the left and right atrial pressure readings to an external device.

[0033] In some aspects, outputting comprises outputting visual or audio instructions with the external device.

[0034] In another aspect, the method comprises averaging the left and right atrial pressure readings.

[0035] In one aspect, determining the pressure gradient comprises determining the pressure gradient from the averaged left and right atrial pressure readings.

[0036] In another aspect, the method includes outputting a second treatment recommendation if the pressure gradient is below the gradient threshold.

[0037] In some aspects the first treatment recommendation comprises outputting a recommendation to implant an inter-atrial shunt to offload excessive pressure from the left atrium to the right atrium.

[0038] In some aspects, the second treatment recommendation comprises outputting a recommendation to continue guideline-directed medical therapy.

[0039] A method of monitoring a heart of a patient is also provided, comprising the steps of: positioning an implantable biatrial pressure sensor into the heart such that a first pressure sensor is disposed in a left atrium while a second pressure sensor is disposed in a right atrium; obtaining accelerometer readings with an accelerometer disposed within the implantable biatrial pressure sensor; determining that the patient is engaged in a desired activity state based on the accelerometer readings; obtaining left atrial pressure readings with the first pressure sensor; obtaining right atrial pressure readings with the second pressure sensor; storing the left and right atrial pressure readings into memory.

[0040] In one aspect, prior to the obtaining left and right atrial pressure reading steps, determining that left and right atrial pressure readings have not been obtained within a predetermined time period.

[0041] In one aspect, the predetermined time period comprises less than 24 hours, less than 12 hours, less than 6 hours, or less than 1 hour.

[0042] In some aspects, the left and right pressure readings are stored into onboard memory on the implantable biatrial pressure sensor. [0043] In one aspect, the left and right pressure readings are stored into memory on an external device.

[0044] In another aspect, prior to determining that the patient is engaged in the desired activity state, performing a calibration procedure that includes: obtaining accelerometer readings when the patient is engaged in a resting state; obtaining accelerometer readings when the patient is engaged in one or more activity states; and identifying in the implantable biatrial pressure sensor which of the one or more activity states is the desired activity state. [0045] A method of monitoring a heart of a patient is also provided, comprising the steps of: positioning an implantable biatrial pressure sensor into the heart such that a first pressure sensor is disposed in a left atrium while a second pressure sensor is disposed in a right atrium; obtaining accelerometer readings with an accelerometer disposed within the implantable biatrial pressure sensor; determining that the patient is engaged in a desired position or orientation based on the accelerometer readings; obtaining left atrial pressure readings with the first pressure sensor; obtaining right atrial pressure readings with the second pressure sensor; storing the left and right atrial pressure readings into memory.

[0046] In some aspects, the method includes, prior to the obtaining left and right atrial pressure reading steps, determining that left and right atrial pressure readings have not been obtained within a predetermined time period.

[0047] In one aspect, the predetermined time period comprises less than 24 hours, less than 12 hours, less than 6 hours, or less than 1 hour.

[0048] In another aspect, the left and right pressure readings are stored into onboard memory on the implantable biatrial pressure sensor.

[0049] In some aspects, the left and right pressure readings are stored into memory on an external device.

[0050] In another aspect, the desired position or orientation is supine.

[0051] In some aspects, the desired position or orientation is prone.

[0052] In one aspect, prior to determining that the patient is engaged in the desired position or orientation, performing a calibration procedure that includes: obtaining accelerometer readings when the patient is engaged on or more positions or orientations; and identifying in the implantable biatrial pressure sensor which of the one or more positions or orientations is the desired position or orientation.

[0053] A method of monitoring a heart of a patient is provided, comprising the steps of: positioning an implantable biatrial pressure sensor into the heart such that a first pressure sensor is disposed in a left atrium while a second pressure sensor is disposed in a right atrium; determining an increasing pressure cycle of the patient by: obtaining sequential pressure readings with the implantable biatrial pressure sensor and recording a time of each pressure reading; determining when a current pressure reading is less than a prior pressure reading; labeling the current pressure reading as a potential crest and recording the time of the current reading; continuing to obtain pressure readings; identifying an end of the increasing pressure cycle when a difference between the current pressure reading and the potential crest is greater than a hysteresis value and the current pressure reading is less than the potential crest; determining a decreasing pressure cycle of the patient by: obtaining sequential pressure readings with the implantable biatrial pressure sensor and recording a time of each pressure reading; determining when the current pressure reading is greater than the prior pressure reading; labeling the current pressure reading as a potential trough and recording the time of the current reading; continuing to obtain pressure readings; identifying an end of the decreasing pressure cycle when a difference between the current pressure reading and the potential trough is greater than a hysteresis value and the current pressure reading is greater than the potential trough; determining a cardiac interval of the patient from the increasing pressure cycle and the decreasing pressure cycle.

[0054] In some aspects, the method further comprises algorithmically determining a heart rate of the patient based on the cardiac interval.

[0055] In one aspect, algorithmically determining comprises dividing 60,000 by the cardiac interval.

[0056] In another aspect, the method includes repeating algorithmically determining the heart rate of the patient for each of a predetermined number of cardiac cycles

[0057] In some aspects, the method includes computing an average heart rate of the patient over the predetermined number of cardiac cycles; comparing the average heart rate to an atrial fibrillation detection threshold; and outputting a signal indicating that the patient is experiencing atrial fibrillation if the average heart rate exceeds the atrial fibrillation threshold.

[0058] A method of monitoring a heart of a patient is provided, comprising the steps of: positioning an implantable biatrial pressure sensor into the heart such that a first pressure sensor is disposed in a left atrium while a second pressure sensor is disposed in a right atrium; obtaining sequential pressure readings with the implantable biatrial pressure sensor; recording a time of each pressure reading; and comparing subsequent pressure readings to identify an increasing pressure cycle duration, a decreasing pressure cycle duration, and a cardiac interval of the patient; algorithmically computing a heart rate of the patient from the cardiac interval; determining an average heart rate over a plurality of cardiac cycles; and providing an output that the patient is experiencing atrial fibrillation if the average heart rate exceeds an atrial fibrillation threshold.

BRIEF DESCRIPTION OF THE DRAWINGS

[0059] The novel features of the invention are set forth with particularity in the claims that follow. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

[0060] FIG. l is a schematic diagram of an active implantable biatrial pressure sensor (AIBPS).

[0061] FIG. 2 is a drawing of an AIBPS.

[0062] FIG. 3 is a drawing of an AIBPS with a fixation mechanism.

[0063] FIG. 4 is a drawing of an AIBPS and delivery system.

[0064] FIG. 5 is a method of providing a treatment recommendation with biatrial pressure measurements.

[0065] FIGS. 6-7 are methods of performing activity -based pressure measurements. [0066] FIGS. 8-9 are methods of performing position-based pressure measurements. [0067] FIGS. 10 is a method of performing time-based pressure measurements.

[0068] FIGS. 11 and 12A-12B show techniques for detecting increasing and decreasing pressure cycles of the heart with an AIBPS.

DETAILED DESCRIPTION

[0069] This disclosure describes an active implantable biatrial pressure sensor (AIBPS) that is configured to be implanted inside the heart and to measure, store, and transmit diagnostic information (e.g., pressure measurement) via wireless communication to a nearby relay. The AIBPS of the present disclosure includes a power source, such as a battery cell, and is designed and configured to perform the pressure sensing and transmission of data over a prescribed implantation lifetime of 5 years or more, without requiring an external device for charging the cell or to activate the device or initiate data collection.

[0070] In a preferred embodiment, the AIBPS is delivered via a catheter to an atrial septal wall inside the heart. The pressure can be cylindrically shaped, leadless, between 0.5 cc and 2 cc in volume, and can be attached to a steerable catheter for delivery inside the heart. The implantable sensor may include two pressure sensors, one that measures pressure in the right atrium and the other that measures pressure in the left atrium. These sensors may be configured to measure pressure throughout the day and wirelessly transmit these data to a nearby relay or external device.

[0071] Typically, the femoral vein is a common entry point for such a device and the pressure sensor can be steered by catheter into the right atrium, right ventricle, pulmonary artery, or delivered transeptally to access the left atrial chamber or left ventricle. Fixation of the pressure sensor is not covered in detail in this disclosure; however screws, barbs, clips, and other fasteners can be incorporated in the pressure sensor to secure the device to the heart wall.

[0072] In a preferred embodiment, a self-powered (e.g., battery powered) AIBPS measures heart pressure and potentially other parameters such as an endocardial electrogram or activity throughout the day and wirelessly transmits this diagnostic data to a nearby relay. The relay could then be configured to send this information to a centrally located data center for further analysis and diffusion. The data center provides a portal for physicians and other care givers. The data center can also send data such as, instructions, messages, thresholds, etc., back to the relay and ultimately to the pressure sensor. The relay may be placed relatively near (within a few meters) the patient and can also incorporate visual and audible outputs such as a display and speaker to alert the patient to one or more actions that should be taken. The relay could also incorporate input devices such as a touch-screen to receive input(s) from the patient, such as allowing the patient to acknowledge instructions or alerts posted to the patient. The relay could conveniently be located anywhere in the home or on person. Multiple relays could also be installed in proximity to the patient.

[0073] In some embodiments, the relay can comprise stand-alone devices such as smartphones, tablets, a pc, or other computing devices that communicate wirelessly with the pressure sensor and connect to the cloud or a remote server.

[0074] It is the objective of this device to make a pressure sensor that requires no patient involvement or clumsy equipment to retrieve diagnostic information from the heart, with the exception of the patient being in proximity to a relay. This disclosure provides a self-powered pressure sensor that records information throughout the day and transmits data wirelessly to a relay regularly.

[0075] It is an objective of this device to be powered by a primary cell so that it can perform the aforementioned functionality with a longevity of 5 years of more. Another embodiment could use a secondary cell or supercapacitor requiring infrequent re-charging. In a preferred embodiment, the pressure sensor would send diagnostic information to the relay at least once per day. [0076] This daily update would include information collected throughout the day, something that passive sensors and others that use a similar principle cannot achieve. [0077] FIG. l is a schematic illustration of an active implantable biatrial pressure sensor 100. The AIBPS 100 which includes electronics such as a cell 101, can further include a microprocessor 102, surrounded by a collection of peripheral devices. All the components illustrated in FIG. 1 can be incorporated into or within a hermetic housing for implantation within a patient’s heart. Included in the block diagram is a right atrial pressure sensor 103 and a left atrial pressure sensor 104. The pressure sensors can be, for example, MEMs capacitive sensors. These pressure sensors are configured to measure dynamic pressure in their respective cavities (e.g., right atrium and left atrium). Accelerometer 105 measures activity and posture, while giant magnetoresistance (GMR) sensor 107 responds to an external magnet. In some examples, the GMR can provide a simple way to aid in testing and configuration of the pressure sensor. For example, the GMR sensor could immediately wakeup the device for communication and instructions from the relay. Real-time clock RTC 106 keeps track of time and wakes-up the microprocessor when tasks are required. When the microprocessor decides to transmit information to a central server, it communicates with the RF transceiver 108 to pass information onto a relay (not shown).

[0078] Energy is provided to the pressure sensor by the cell 101, which can include a supply holding capacitor 110 across the cell. Although the preferred embodiment uses a primary cell, secondary cells could also be used. VCC is used to power the system. The external RTC 106 is used to keep the other components in their idle state. When required, the RTC will interrupt the microprocessor 102 to either collect and process pressure sensor data, or activate the transceiver 108 to wirelessly send data to the relay. Not shown is an analog- to-digital-converter (ADC) configured to measure the cell voltage to determine a recommended replacement time. Additionally, the electronics can include memory for pressure measurement data storage.

[0079] The actual implementation may vary due to the level of ASIC integration that might be available. For instance, the RTC function and RF transceiver function may be implemented on a single ASIC to reduce component count.

[0080] Any of the active implantable sensors (AIBPS) disclosed herein can be configured to continuously or periodically measure pressure waveforms within the heart. In some examples, the raw pressure waveforms can be transmitted to an external device (e.g., a relay, or an electronic device such as a smartphone, tablet, PC, or other external component of the pressure measurement system) and/or stored locally on the device. Alternatively, the pressure sensor can be configured to calculate, compile, or synthesize periodic (e.g., hourly or some other user specified time period) measurements of systolic, diastolic and mean pressure, as well as heart rate statistics such as mean heart rate and variability, and transmit those synthesized measurements or statistics to the external device or relay. In some embodiments, the pressure sensor can be configured to store and/or transmit only the last measured pressure, or last calculated statistic.

[0081] The electronics of the pressure sensor can further be configured to extract the patient’s heart rate from the measured pressure waveform. For example, in one embodiment the electronics can include an endocardial electrogram amplifier for direct EGM measurements. In some examples, ECG statistics can be stored periodically such as hourly along with a daily minimum heart rate, max heart rate, and heart rate variability. Any of the extracted or calculated data can be transmitted by the pressure sensor to the external device. [0082] In some examples, the pressure sensor can send a low data, low power “ping” signal to the relay or external device when none of the calculated statistics or data hit a programmable threshold. This can help the pressure sensor to avoid sending data transmissions when there is nothing to report, helping to increase operational life of the pressure sensor.

[0083] The AIBPS can also be configured to receive communications from the external device or relay. In some embodiments, the relay is configured to send an acknowledgement signal to the pressure sensor when a data transmission signal is received by the relay. In one example, the relay or external device can include a received signal strength indicator (RS SI) in the acknowledgement signal so the pressure sensor can modify transmit settings accordingly in real-time to save power during transmissions.

[0084] In some embodiments, the pressure sensor can be automatically configured to measure and store pressure and electrogram snapshots when a patient has an “event” or “alarm condition” as defined within the system. For example, an event or alarm can be defined as a pressure exceeding or falling below a defined threshold, or a heart rate reading that falls above or below a heart rate threshold. In some examples, these “events” can automatically trigger communication of the latest pressure readings and statistics to an external device. In some embodiments, the pressure sensor could detect an alarm or event condition based on pre-set thresholds and rules that interpret the on-board patient statistics that have been collected and send an alert to the relay. The pressure sensor could be configured to continue trying to transmit throughout the day until the alert is acknowledged by the relay. The alarm could be based on analysis of history or could occur immediately following a measurement. [0085] A cross-section of an active implantable biatrial pressure sensor 200 including the configuration of its internal structure is shown in FIG. 2. The AIBPS is shown without a fixation mechanism to hold the device in place, but it should be understood that a fixation mechanism can be included. As described above, the pressure sensor can include a left atrial pressure sensor 203 and a right atrial pressure sensor 204. The left and right atrial pressure sensors can comprise a thin diaphragm 209 bonded to a titanium housing 212 having an electronics compartment 207. The diaphragm can comprise, for example, titanium. The diaphragms of the left and right pressure sensors can be hermetically sealed and filled with silicon oil 214. Within each hermetically sealed compartment is a pressure sensor 216, that is electrically connected to the adjacent electronics compartment 207 using hermetic feedthroughs 211.

[0086] The electronics compartment 207 can contain the electronic components for the system, represented by 218 for example. In some embodiments, the electronics compartment can include an accelerometer configured to detect activity and postural changes and a giant magneto-resistive sensor (GMR) to detect the presence of an external magnet, allowing for control of the implantable device during different use cases. A flexible circuit board may join the various electronic components together with the various connections to the pressure sensors and cell 201. The housing 220 of the electronic compartment 207 may be ceramic or glass to allow for RF propagation to penetrate the housing. The cell 201, may be contained within another titanium section 222. One side of the cell may be positioned against the left atrial pressure sensor compartment. The cell 201, in the preferred embodiment uses a primary cell using either Li/CFx, Li/Mn02 or some combination of these chemistries.

[0087] FIG. 3 is an isometric illustration of an active implantable biatrial pressure sensor 300 depicting an embodiment of the electronics compartment 307 containing a fixation mechanism 324. FIG. 3 shows an atrial pressure sensor 304 and a diaphragm 309 which can be, for example, a left or right atrial pressure sensor. In some embodiments the AIBPS 300 can include both left and right atrial pressure sensors, as described above.

[0088] In the illustrated embodiment, the fixation mechanism 324 is constructed from one or more fixation wings 326/328 between, for example, 8 and 10mm in length. The fixation wing(s) can comprise a super-elastic, material, such as nitinol. As illustrated, the wings are arranged in an opposing radial pattern around, and generally orthogonal to a longitudinal axis of the electronics compartment. In a preferred embodiment, the arrangement is, at minimum but not limited to, two fixation wings, 326/328. The fixation wings can be captured, or mechanically attached to the electronics compartment using a capture tab, 330. The fixation wings can be spaced apart such that they are configured to grasp, compress, or slot into or against the patent foramen ovale of a patient between the two upper chambers of the heart, the left atria and the right atria. When the foramen ovale is positioned between the fixation wings, the left atrial sensor will be disposed in the left atrium while the right atrial sensor is disposed in the right atrium.

[0089] Other fixation embodiments include a larger quantity of wings arranged in various patterns around the circumference of the electronics enclosure, on even spacing or randomly spaced. Other fixation embodiments shapes include large circle patterns, leaf shapes, or other geometry projecting radially from the pressure sensor housing. The fixation may be additionally constructed from other materials, plastics or absorbable materials that provide sufficient retention. Alternate embodiments of the winged fixation mechanism’s shape may include basket or woven shapes, tines, barbs, or other features that project from the circumference and when misshaped, return to the retention position.

[0090] FIG. 4, illustrating an active implantable biatrial pressure sensor 400 installed into a loading tool or delivery catheter 432 with one set of fixation wings, 424 facing distally and tangent to the device body and one set of wings, 426 facing the proximal end of the loading tool. As shown, when the AIBPS is installed or disposed within the catheter, the fixation wings can be compressed to lie or rest against the housing of the pressure sensor, generally along the longitudinal axis of the pressure sensor. When the catheter is in communication with the foramen ovale or an enlarged foramen ovale, the device is deployed from the end of the catheter residing in the right atrium and projects through the enlarged foramen ovale and the most distal wings contained with the catheter, open to a position that is normal to the axis of the device.

[0091] Pressure Gradient Detection between Left Atrium and Right Atrium

[0092] The ability of the active implantable biatrial pressure sensor described herein to measure both left atrial pressure and right atrial pressure allows for differential diagnosis of left and right-sided heart failure. The pressure sensors in the left and right atria can be used to determine an average left atrial pressure (LAP) and right atrial pressure (RAP), which can be used to determine a pressure gradient between the left and right atria. By comparing this pressure gradient against a predetermined threshold, the AIBPS can output a treatment recommendation (e.g., via the relay or external device). This information can assist physicians in reducing vascular resistance by, for example, adjusting diuretics (using left atrial pressure) as well as increasing return blood to the heart by adjusting vasodilators (using right atrial pressure). Monitoring the Pulmonary Artery Pressure (PAP) doesn’t take into account the absolute circulating blood volume. Hence, solely relying on PAP and adjusting diuretics may not help patients who have low blood volume flowing back to the heart (euvolemic or hypovolemic).

[0093] The active implantable biatrial pressure sensor of the present disclosure can also enable determining a pressure gradient between the left and right atria. The ability to quantify the pressure difference between the two atria can be used, for example, to help select patients who may benefit from inter-atrial shunts, to relieve the pressure build up in the left atrium. Use of inter-atrial shunts has been shown to be effective to alleviate left atrial pressure. PAP monitors lack the ability to provide the differential pressure between the two chambers and, hence, the ability to provide a more comprehensive management of heart failure patients.

[0094] A method of sensing pressures in the left and right atria is shown in flowchart 500 of FIG. 5. At step 502, the method can include obtaining a series of pressure measurements in both the left atrium and the right atrium (e.g., with the left and right atrial pressure sensors described above). This can comprise, for example, obtaining nominally 50 samples within each chamber at a rate of 10 samples/sec. At step 504, the method can determine average left and right atrial pressures by calculating the mean of the measurements from step 502, to obtain the average left and right atrial pressure measurements. At step 506, the pressure gradient between left and right atria is then determined by calculating the difference between the average left atrial pressure and right atrial pressure. The pressure gradient is then compared to a predetermined gradient threshold in step 508. At step 510, if the gradient exceeds the threshold, then a determination or recommendation can be made, e.g., by the system, that the patient can benefit from a specific therapy or medical intervention, such as an inter-atrial shunt to offload the excessive pressure from left atrium to the right. If the pressure gradient is equal or less than the threshold, then the AIBPS may determine that a separate or different therapy or medical intervention would benefit the patient (e.g., output a recommendation that the patient should continue the Guideline-Directed Medical Therapy and take the prescribed dosage of heart failure medications). In some examples, the AIBPS may output a first treatment recommendation, e.g., via the relay or external device, if the pressure gradient is above the gradient threshold, and a second treatment recommendation if the pressure gradient is equal to or less than the gradient threshold. The output can take many forms, including audible alerts, visual alerts (e.g., text displayed on an external device), or any other known alert. In some aspects, the determination is performed in the AIBPS, and in other embodiments the determination is performed in the external device.

[0095] Patient Activity -based Pressure Measurement [0096] As discussed above, the AIBPS may include an accelerometer built into device that can be used to detect the patient activity. In some examples, this can automatically trigger measurement of the atrial pressures (left and right) when a particular level of activity is detected. This functionality enables using pressure readings to diagnose various conditions in the heart including potential valve regurgitation on both left (mitral valve) and right side (tricuspid valve) of the heart.

[0097] FIG. 6 is a flowchart 600 showing a method of calibrating an AIBPS to detect activity -based pressures in the left and right atrium of the heart. Prior to programming the AIBPS to trigger a measurement at a desired activity level, it may need to be calibrated to obtain the accelerometer readings specific to a desired patient activity state. For example, the method can begin with the patient in an at rest state. At step 602, the AIBPS can then obtain and store accelerometer calibration readings for the at-rest state. At step 604, the patient can then perform one or more activities at one or more intensity levels, such as walking on a treadmill or performing another activity at a desired intensity level, and the AIBPS can obtain and store accelerometer calibration readings for patient activity state at each of the activity or intensity levels. At step 606, the AIBPS can be programmed to detect when the patient is engaged in a desired activity state. In some examples, the AIBPS can be programmed to detect more than one specific activity state.

[0098] FIG. 7 is a flowchart 700 showing a method of detecting activity-based pressures in the left and right atrium of the heart. The method of FIG. 7 can use, for example, an AIBPS that has been calibrated and programmed according to the method of FIG. 6. In some embodiments, the AIBPS of FIG. 7 can trigger a pressure measurement at a desired patient activity level. At step 702, the AIBPS can monitor or obtain an accelerometer reading periodically (e.g., nominally every 5 minutes or some other pre-programmed interval). If the accelerometer reading matches a desired patient activity level at step 704, and if a pressure reading has not been retrieved within a predetermined time period (e.g., within the last 24 hours, the last 12 hours, the last 6 hours, the last hour, etc.) at step 706, the AIBPS can then at step 708 perform a series of left and right atrial pressure measurements. These measurements can optionally be saved into memory, either onboard the AIBPS or in the external device, optionally including the maximum, minimum and average of each of the measurements.

[0099] Patient Orientation-based Pressure Measurement

[0100] In some aspects of the disclosure, the accelerometer built into the AIBPS can also be used to detect the patient orientation and trigger the atrial pressures at a desired patient orientation. This allows for using pressure readings with consistent patient orientation (e.g., only supine readings) for drug titration or other medical interventions. [0101] Similar to above with activity -based pressure measurements, prior to programming the AIBPS to trigger a measurement in a desired orientation, it can be calibrated to obtain accelerometer readings specific to a given patient orientation, such as prone or supine. Referring to flowchart 800 of FIG. 8, the patient can orient themselves in one or more unique orientations or positions (e.g., supine, prone, etc.). At step 802, the AIBPS can obtain and store the accelerometer calibration readings for each position or orientation. At step 804, the AIBPS can be programmed to trigger a pressure measurement in a desired patient orientation based on the calibration information from step 802.

[0102] FIG. 9 is a flowchart 900 showing a method of detecting position or orientationbased pressures in the left and right atrium of the heart. The method of FIG. 9 can use, for example, an AIBPS that has been calibrated and programmed according to the method of FIG. 8. In some embodiments, the AIBPS of FIG. 9 can trigger a pressure measurement at a desired patient position or orientation. At step 902, the AIBPS can monitor or obtain an accelerometer reading periodically (e.g., nominally every 5 minutes or some other preprogrammed interval). If the position reading matches a desired position or orientation at step 904, and if a pressure reading has not been retrieved within a predetermined time period (e.g., within the last 24 hours, the last 12 hours, the last 6 hours, the last hour, etc.) at step 906, the AIBPS can then at step 908 perform a series of left and right atrial pressure measurements. These measurements can optionally be saved into memory, either onboard the AIBPS or in the external device, optionally including the maximum, minimum and average of each of the measurements.

[0103] Time-based Pressure Measurement

[0104] In some examples, the AIBPS is programmed to perform pressure measurements based on either certain times of the day or at certain interval, as illustrated with flowchart 1000 of FIG. 10. At step 1002, an internal clock of the AIBPS can be set to expire after an appropriate duration based on the programming and current time of the day. Then, at step 1004, the AIBPS can perform a series of left and right atrial pressure measurements and optionally at step 1006 save the pressure measurements, including the maximum, minimum and average of each of the measurements in memory, either onboard the AIBPS or on an external device.

[0105] Atrial Fibrillation Detection

[0106] The heart rate of a patient can be measured from electrical signals from the heart, namely electro-cardio grams. However, according to one aspect of the disclosure, a patient’s heart rate can also be measured from atrial pressure signals. Referring to FIG. 11, an atrial pressure plot is shown, that can include atrial pressure signals measured by an AIBPS of the present disclosure. The AIBPS can be configured to detect peak pressures during the cardiac cycle and measure the time 1101 between successive peak pressures. Much like the electrical activity of the heart, the pressure waveform has small deviations 1102 that can be rejected (hysteresis) by the AIBPS as noise.

[0107] Referring now to FIGS. 12A-12B, a method and flowchart 1200 for detecting atrial fibrillation with an AIBPS is provided. First step is to determine the cardiac interval. To detect the successive crests and troughs in the pressure waveform measured by the AIBPS, the algorithm will initialize the very first sample as zero and record the time at step 1202. This is to assume the algorithm starts with an increasing pressure waveform.

[0108] Increasing pressure sequence (FIG. 12A):

[0109] At step 1204, at the start of a pressure increasing sequence, the AIBPS can obtain a new pressure sample. The pressure sample can be obtained from, for example, the left atrium, the right atrium, or optionally both the left atrium and right atrium. The system can compare these new pressure samples with the initial pressure sample from step 1202. At step 1206, if the new sample is less than the previous sample, the system can record the previous sample as ‘potential crest’ and record the time. If not, the AIBPS can continue obtaining a new pressure samples and comparing subsequent samples. Once a ‘potential crest’ is detected, the AIBPS can continue to monitor new samples as they decrease or increase. If, at step 1208, the signal had reached a point where the difference between the latest sample and the ‘potential crest’ is greater than the ‘hysteresis’ value, the system can check if the latest sample is less than the potential crest. If so, start method the decrease pressure sequence. Else resume the pressure increase sequence.

[0110] Decreasing pressure sequence (FIG. 12B):

[OHl] At step 1212, the AIBPS can obtain a new pressure sample. The pressure sample can be obtained from, for example, the left atrium, the right atrium, or optionally both the left atrium and right atrium. At step 1214, the system can compare new pressure samples with the pressure samples from step 1212, and if the new sample is greater than the previous sample, the system can record the previous sample as ‘potential trough’ and record the time. Else resume obtaining a new pressure sample at step 1212. Once a ‘potential trough’ is detected, the AIBPS can continue to monitor new samples as they decrease or increase. [0112] If, at step 1216 the signal had reached a point where the difference between the latest sample and the ‘potential trough’ is greater than the ‘hysteresis’ value, the system can check if the latest sample is greater than the potential trough. If so, at step 1218, the system can calculate the time difference between latest sample and that when the increase sequence started and save it as the latest cardiac interval duration, and again start the increase pressure sequence (back to FIG. 12A). Else the system can resume the pressure decrease sequence. In some embodiments, the very first cardiac interval can be ignored since it is typically a partial interval.

[0113] The cardiac interval duration is the sum of the increasing sequence and the decreasing sequence. Since the AIBPS knows when the increasing pressure sequence started (from the time stamped and recorded pressure readings) and knows when the decreasing sequence ends (when the difference between the latest sample and the trough is greater than a hysteresis value), the duration of the cardiac interval can be calculated. So, it could be either the sum of increasing sequence followed by the next decreasing sequence or vice versa. In other embodiments, the cardiac interval could be measured either between two successive crests or two successive troughs.

[0114] With the cardiac interval now known, the AIBPS can then determine the heart rate from the cardiac interval as follows:

[0115] Heart rate (bpm) = 60,000/(cardiac interval measured in milliseconds)

[0116] The AIBPS can determine if the patient is experiencing atrial fibrillation by continually monitoring and determining the cardiac interval with the algorithm described above and averaging the heart rates of the last several cardiac cycles (e.g., nominally 5, but any number of cycles can be used). The average heart rate can then be compared to a preprogrammed Atrial Fibrillation Detection Threshold which may, for example, be customized to a particular patient based on age, gender, or other physiological factors. If the average heart rate exceeds the Atrial Fibrillation Detection Threshold, the AIBPS can provide an output or alert indicating that atrial fibrillation has been detected. In some examples, the timestamp of atrial fibrillation detection is saved in memory along with the average heart rate.

[0117] As for additional details pertinent to the present invention, materials and manufacturing techniques may be employed as within the level of those with skill in the relevant art. The same may hold true with respect to method-based aspects of the invention in terms of additional acts commonly or logically employed. Also, it is contemplated that any optional feature of the inventive variations described may be set forth and claimed independently, or in combination with any one or more of the features described herein. Likewise, reference to a singular item, includes the possibility that there are plural of the same items present. More specifically, as used herein and in the appended claims, the singular forms “a,” “and,” “said,” and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The breadth of the present invention is not to be limited by the subject specification, but rather only by the plain meaning of the claim terms employed.

Claims

CLAIMS What is claimed is:

1. An active implantable biatrial pressure sensor, comprising: a housing adapted to be implanted within a human heart; a cell disposed in the housing; a first pressure sensor disposed in a first end of the housing and configured to measure a first pressure reading outside of the housing; a first deformable lid attached to the housing and being fluidly coupled with the first pressure sensor; a second pressure sensor disposed in a second end of the housing and configured to measure a second pressure reading outside of the housing; a second deformable lid attached to the housing and being fluidly coupled with the second pressure sensor; and electronics disposed in the housing and operatively coupled to the cell and the first and second pressure sensors, the electronics being configured to determine a pressure gradient between the first pressure reading and the second pressure reading, compare the pressure gradient to a predetermined threshold, and output a treatment recommendation.

2. The sensor of claim 1, wherein the housing comprises first and second separate hermetically sealed cavities for housing the first and second pressure sensors.

3. The sensor of claim 2, wherein the first and second separate hermetically sealed cavities are oil filled.

4. The sensor of claim 2, wherein the first and second deformable lids are attached to the first and second separate hermetically sealed cavities.

5. The sensor of claim 1, wherein the first and second pressure sensors comprises MEMs capacitive sensors.

6. The sensor of claim 1, wherein the electronics comprise a real time clock, a transceiver, GMR sensor and an accelerometer.

7. The sensor of claim 1, wherein the electronics comprise an accelerometer.

8. The sensor of claim 7, wherein electronics are configured to use measurements from the accelerometer to obtain activity -based pressure measurements.

9. The sensor of claim 7, wherein electronics are configured to use measurements from the accelerometer to obtain orientation-based pressure measurements.

10. The sensor of claim 1, wherein the housing has a volume less than 2 cc.

11 The sensor of claim 1, wherein the electronics compartment comprises a volume of between 0.25 and 0.75 cc.

12. The sensor of claim 1, wherein the electronics being configured to synthesize blood pressure statistics from the first and second pressure readings and intermittently transmit the blood pressure statistics to an external device multiple times per day over an operating lifetime of at least 5 years.

13. An active implantable biatrial pressure sensor, comprising: a housing having a volume less than 2 cc and adapted to be implanted within a human heart; a cell disposed in the housing; a first pressure sensor disposed in a first end of the housing and configured to measure a first pressure reading outside of the housing; a first deformable lid attached to the housing and being fluidly coupled with the first pressure sensor; a second pressure sensor disposed in a second end of the housing and configured to measure a second pressure reading outside of the housing; a second deformable lid attached to the housing and being fluidly coupled with the second pressure sensor; and electronics disposed in the housing and operatively coupled to the cell and the first and second pressure sensors, the electronics being configured to synthesize blood pressure statistics from the first and second pressure readings and intermittently transmit the blood pressure statistics to an external device multiple times per day over an operating lifetime of at least 5 years.

14. The sensor of claim 13, wherein the housing comprises first and second separate hermetically sealed cavities for housing the first and second pressure sensors.

15. The sensor of claim 14, wherein the first and second separate hermetically sealed cavities are oil filled.

16. The sensor of claim 14, wherein the first and second deformable lids are attached to the first and second separate hermetically sealed cavities.

17. The sensor of claim 1, wherein the first and second pressure sensors comprises MEMs capacitive sensors.

18. The sensor of claim 13, wherein the electronics comprise a real time clock, a transceiver, GMR sensor and an accelerometer.

19. The sensor of claim 13, wherein the electronics comprise an accelerometer.

20. The sensor of claim 19, wherein electronics are configured to use measurements from the accelerometer to obtain activity -based pressure measurements.

21. The sensor of claim 19, wherein electronics are configured to use measurements from the accelerometer to obtain orientation-based pressure measurements.

22. The sensor of claim 13, wherein the electronics compartment comprises a volume of between 0.25 and 0.75 cc.

23. A method of monitoring a heart of a patient, comprising the steps of: positioning an implantable biatrial pressure sensor into the heart such that a first pressure sensor is disposed in a left atrium while a second pressure sensor is disposed in a right atrium; obtaining left atrial pressure readings with the first pressure sensor; obtaining right atrial pressure readings with the second pressure sensor; determining a pressure gradient between the left atrium and the right atrium based on the left and right atrial pressure readings; comparing the pressure gradient to a gradient threshold; and outputting a first treatment recommendation if the pressure gradient is above the gradient threshold.

24. The method of claim 23, further comprising transmitting the left and right atrial pressure readings to an external device.

25. The method of claim 24, wherein outputting comprises outputting visual or audio instructions with the external device.

26. The method of claim 23, further comprising averaging the left and right atrial pressure readings.

27. The method of claim 26, wherein determining the pressure gradient comprises determining the pressure gradient from the averaged left and right atrial pressure readings.

28. The method of claim 23, further comprising outputting a second treatment recommendation if the pressure gradient is below the gradient threshold.

29. The method of claim 23, wherein the first treatment recommendation comprises outputting a recommendation to implant an inter-atrial shunt to offload excessive pressure from the left atrium to the right atrium.

30. The method of claim 28, wherein the second treatment recommendation comprises outputting a recommendation to continue guideline-directed medical therapy.

31. A method of monitoring a heart of a patient, comprising the steps of positioning an implantable biatrial pressure sensor into the heart such that a first pressure sensor is disposed in a left atrium while a second pressure sensor is disposed in a right atrium; obtaining accelerometer readings with an accelerometer disposed within the implantable biatrial pressure sensor; determining that the patient is engaged in a desired activity state based on the accelerometer readings; obtaining left atrial pressure readings with the first pressure sensor; obtaining right atrial pressure readings with the second pressure sensor; storing the left and right atrial pressure readings into memory.

32. The method of claim 31, further comprising, prior to the obtaining left and right atrial pressure reading steps, determining that left and right atrial pressure readings have not been obtained within a predetermined time period.

33. The method of claim 32, wherein the predetermined time period comprises less than 24 hours, less than 12 hours, less than 6 hours, or less than 1 hour.

34. The method of claim 31, wherein the left and right pressure readings are stored into onboard memory on the implantable biatrial pressure sensor.

35. The method of claim 31, wherein the left and right pressure readings are stored into memory on an external device.

36. The method of claim 31, prior to determining that the patient is engaged in the desired activity state, performing a calibration procedure that includes: obtaining accelerometer readings when the patient is engaged in a resting state; obtaining accelerometer readings when the patient is engaged in one or more activity states; and identifying in the implantable biatrial pressure sensor which of the one or more activity states is the desired activity state.

37. A method of monitoring a heart of a patient, comprising the steps of: positioning an implantable biatrial pressure sensor into the heart such that a first pressure sensor is disposed in a left atrium while a second pressure sensor is disposed in a right atrium; obtaining accelerometer readings with an accelerometer disposed within the implantable biatrial pressure sensor; determining that the patient is engaged in a desired position or orientation based on the accelerometer readings; obtaining left atrial pressure readings with the first pressure sensor; obtaining right atrial pressure readings with the second pressure sensor; storing the left and right atrial pressure readings into memory.

38. The method of claim 37, further comprising, prior to the obtaining left and right atrial pressure reading steps, determining that left and right atrial pressure readings have not been obtained within a predetermined time period.

39. The method of claim 38, wherein the predetermined time period comprises less than 24 hours, less than 12 hours, less than 6 hours, or less than 1 hour.

40. The method of claim 37, wherein the left and right pressure readings are stored into onboard memory on the implantable biatrial pressure sensor.

41. The method of claim 31, wherein the left and right pressure readings are stored into memory on an external device.

42. The method of claim 31, wherein the desired position or orientation is supine.

43. The method of claim 31, wherein the desired position or orientation is prone.

44. The method of claim 31, prior to determining that the patient is engaged in the desired position or orientation, performing a calibration procedure that includes: obtaining accelerometer readings when the patient is engaged on or more positions or orientations; and identifying in the implantable biatrial pressure sensor which of the one or more positions or orientations is the desired position or orientation.

45. A method of monitoring a heart of a patient, comprising the steps of: positioning an implantable biatrial pressure sensor into the heart such that a first pressure sensor is disposed in a left atrium while a second pressure sensor is disposed in a right atrium; determining an increasing pressure cycle of the patient by: obtaining sequential pressure readings with the implantable biatrial pressure sensor and recording a time of each pressure reading; determining when a current pressure reading is less than a prior pressure reading; labeling the current pressure reading as a potential crest and recording the time of the current reading; continuing to obtain pressure readings; identifying an end of the increasing pressure cycle when a difference between the current pressure reading and the potential crest is greater than a hysteresis value and the current pressure reading is less than the potential crest; determining a decreasing pressure cycle of the patient by: obtaining sequential pressure readings with the implantable biatrial pressure sensor and recording a time of each pressure reading; determining when the current pressure reading is greater than the prior pressure reading; labeling the current pressure reading as a potential trough and recording the time of the current reading; continuing to obtain pressure readings; identifying an end of the decreasing pressure cycle when a difference between the current pressure reading and the potential trough is greater than a hysteresis value and the current pressure reading is greater than the potential trough; determining a cardiac interval of the patient from the increasing pressure cycle and the decreasing pressure cycle.

46. The method of claim 45, further comprising algorithmically determining a heart rate of the patient based on the cardiac interval.

47. The method of claim 46, wherein algorithmically determining comprises dividing 60,000 by the cardiac interval.

48. The method of claim 46, further comprising repeating algorithmically determining the heart rate of the patient for each of a predetermined number of cardiac cycles.

49. The method of claim 48, further comprising: computing an average heart rate of the patient over the predetermined number of cardiac cycles; comparing the average heart rate to an atrial fibrillation detection threshold; and outputting a signal indicating that the patient is experiencing atrial fibrillation if the average heart rate exceeds the atrial fibrillation threshold.

50. A method of monitoring a heart of a patient, comprising the steps of: positioning an implantable biatrial pressure sensor into the heart such that a first pressure sensor is disposed in a left atrium while a second pressure sensor is disposed in a right atrium; obtaining sequential pressure readings with the implantable biatrial pressure sensor; recording a time of each pressure reading; and comparing subsequent pressure readings to identify an increasing pressure cycle duration, a decreasing pressure cycle duration, and a cardiac interval of the patient; algorithmically computing a heart rate of the patient from the cardiac interval; determining an average heart rate over a plurality of cardiac cycles; and providing an output that the patient is experiencing atrial fibrillation if the average heart rate exceeds an atrial fibrillation threshold.