WO2025199348A1

WO2025199348A1 - Tracking respiration and respirophasic pacing using bioimpedance

Info

Publication number: WO2025199348A1
Application number: PCT/US2025/020740
Authority: WO
Inventors: Subham GHOSH; Eric A. Schilling; Michael D. Eggen
Original assignee: Medtronic Inc
Current assignee: Medtronic Inc
Priority date: 2024-03-21
Filing date: 2025-03-20
Publication date: 2025-09-25
Anticipated expiration: 2026-09-21

Abstract

This disclosure describes techniques for tracking respiration and respirophasic pacing using bioimpedance measurements. In one example, a device includes: therapy delivery circuitry configured to deliver cardiac pacing pulses to a heart of a patient via a plurality of electrodes; sensing circuitry configured to sense a bioimpedance signal of a patient; and processing circuitry configured to: identify a beginning of a current inspiration phase of the patient based on the bioimpedance signal; and control the therapy delivery circuitry to adjust a rate of the cardiac pacing during the current inspiration phase based on the identification of the beginning of the current inspiration phase.

Description

TRACKING RESPIRATION AND RESPIROPHASIC PACING USING

BIOIMPEDANCE

[0001] This application claims the benefit of U.S. Provisional Application Serial No. 63/568,283, filed March 21, 2024, which is entitled “TRACKING RESPIRATION AND RESPIROPHASIC PACING USING BIOIMPEDANCE” and is hereby incorporated by reference in its entirety.

FIELD

[0002] This disclosure generally relates to medical devices and, more particularly, to medical devices that deliver cardiac therapy.

BACKGROUND

[0003] In healthy humans, heart rate naturally increases during inspiration and decreases during expiration. This phenomenon, known as respiratory sinus arrhythmia (RSA), supports ventilation/perfusion matching as blood enters the lungs, i.e., increases pulmonary blood flow when the lungs are inflated.

SUMMARY

[0004] In general, this disclosure describes techniques for delivering cardiac pacing to mimic RSA, e.g., by increasing the cardiac pacing pulse rate during inspiration, and, in some examples, decreasing the pulse rate during expiration.

[0005] Many current pacemakers pace monotonically in view of pulmonary inspiration/expiration, and the monotonic pacing rate increases with increased activity level (e.g., many current pacemakers provide pacing that does not vary within the respiratory cycle). Cardiac pacing to mimic RSA, i.e., respirophasic pacing, can provide therapeutic benefit, e.g., by increasing cardiac output and helping to reverse remodel the heart of heart failure (HF) patients. However, current methods of restoring RSA are based on several averaged prior-detected inspiration and expiration phases based on identified respiration cycles, which may mimic RSA when the patient is breathing at a stable rate, e.g., while the patient is sleeping, but may not accurately mimic RSA when the patient is breathing at a more variable rate, e.g., when the patient is active.

[0006] The techniques of this disclosure may be implemented by a cardiac therapy device, e.g., a pacemaker, that can continuously sense physiological signals, e.g., bioimpedance and/or electrogram (EGM) signals, indicative of inspiration phases and expiration phases and detect inspiration phases and expiration phases independently. In other words, the pacemaker may identify inspiration and expiration phases without first identifying a respiration cycle. In some examples, the pacemaker may control therapy delivery circuitry to adjust cardiac pacing pulses based on the inspiration and/or expiration phases. The pacemaker may in some examples be configured to predict subsequent inspiration and/or expiration phases of the patient based on the detected inspiration and/or expiration and control therapy delivery circuitry to adjust cardiac pacing pulses.

[0007] In some examples, RSA pacing may be unnecessary, ineffective, or counterproductive under certain conditions, e.g., when the patient is already achieving RSA or when the patient’s heart rate exceeds a threshold. The techniques of this disclosure may avoid delivering RSA pacing under such conditions by determining whether one or more criteria for adjusting cardiac pacing to mimic are satisfied based on one or more sensed patient parameters.

[0008] In some examples, the techniques of this disclosure may additionally include further adjusting cardiac pacing based on a patient state, e.g., the pacemaker may increase, or overdrive, cardiac pacing pulses to a lesser extent for patients in one category based on patient state than patients in a different category.

[0009] In some examples, the techniques of this disclosure may include determining one or more stimulation parameters for measuring the bioimpedance signal, such as a stimulation amplitude. In some examples, by determining one or more stimulation parameters may comprise determining whether each of a plurality of stimulation parameters result in a signal associated quality level meeting one or more thresholds.

[0010] In one example, a device includes: therapy delivery circuitry configured to deliver cardiac pacing pulses to a heart of a patient via a plurality of electrodes; sensing circuitry configured to sense a bioimpedance signal of a patient; and processing circuitry configured to: identify a beginning of a current inspiration phase of the patient based on the bioimpedance signal; and control the therapy delivery circuitry to adjust a rate of the cardiac pacing during the current inspiration phase based on the identification of the beginning of the current inspiration phase.

[0011] In another example, a method includes: sensing, by sensing circuitry of a medical device, a bioimpedance signal of a patient; identifying, by processing circuitry of the medical device, a beginning of a current inspiration phase of the patient based on the bioimpedance signal; and controlling, by the processing circuitry, therapy delivery circuitry of the medical device to adjust a rate of cardiac pacing during the current inspiration phase, wherein the therapy delivery circuitry is configured to deliver cardiac pacing pulses to a heart of a patient via a plurality of electrodes based on the identification of the beginning of the current inspiration phase.

[0012] In another example, a device includes: therapy delivery circuitry configured to deliver cardiac pacing pulses to a heart of a patient via a plurality of electrodes; sensing circuitry configured to sense a bioimpedance signal of a patient; and processing circuitry configured to: identify a beginning of a current expiration phase of the patient based on the bioimpedance signal; and control the therapy delivery circuitry to adjust a rate of the cardiac pacing during a respiration cycle associated with the current expiration phase based on the identification of the beginning of the current expiration phase.

[0013] In another example, a method includes: sensing, by sensing circuitry of a medical device, a bioimpedance signal of a patient; identifying, by processing circuitry of the medical device, a beginning of a current expiration phase of the patient based on the bioimpedance signal; and controlling, by the processing circuitry, therapy delivery circuitry of the medical device to adjust a rate of cardiac pacing during a respiration cycle associated with the current expiration phase, wherein the therapy delivery circuitry is configured to deliver cardiac pacing pulses to a heart of a patient via a plurality of electrodes based on the identification of the beginning of the current expiration phase.

[0014] In another example, a non-transitory computer-readable medium storing instructions that when executed by processing circuitry, cause the processing circuitry to: identify a beginning of a current inspiration phase of a patient based on a bioimpedance signal; and control therapy delivery circuitry to adjust a rate of cardiac pacing during the current inspiration phase based on the identification of the beginning of the current inspiration phase.

[0015] In another example, non-transitory computer-readable medium storing instructions that when executed by processing circuitry, cause the processing circuitry to: identify a beginning of a current expiration phase of a patient based on a bioimpedance signal; and control therapy delivery circuitry to adjust a rate of cardiac pacing during a respiration cycle associated with the current expiration phase based on the identification of the beginning of the current expiration phase.

[0016] This summary is intended to provide an overview of the subject matter described in this disclosure. It is not intended to provide an exclusive or exhaustive explanation of the apparatus and methods described in detail within the accompanying drawings and description below. Further details of one or more examples are set forth in the accompanying drawings and the description below.

BRIEF DESCRIPTION OF DRAWINGS

[0017] FIG. l is a conceptual diagram illustrating an example system configured to deliver cardiac pacing to mimic respiratory sinus arrhythmia (RSA), the system including an implantable medical device (IMD) coupled to implantable medical leads, in accordance with one or more techniques of this disclosure.

[0018] FIG. 2 is a conceptual drawing illustrating the example IMD and leads on FIG. 1 in conjunction with a heart, in accordance with one or more techniques of this disclosure.

[0019] FIG. 3 is a functional block diagram illustrating an example configuration of the IMD of FIG. 1, in accordance with one or more techniques of this disclosure.

[0020] FIG. 4 is a flow diagram illustrating an example operation of a device to adjust a rate of cardiac pacing, in accordance with one or more techniques of this disclosure.

[0021] FIG. 5 is a flow diagram illustrating an example operation of a device to determine whether to adjust a rate of cardiac pacing pulses, in accordance with one or more techniques of this disclosure.

[0022] FIG. 6 is a flow diagram illustrating an example operation for determining whether to switch to sensing an EGM signal, in accordance with one or more techniques of this disclosure.

[0023] FIG. 7 is a flow diagram illustrating an example operation for determining whether to adjust a rate of cardiac pacing pulses based on a patient heart rate, in accordance with one or more techniques of this disclosure.

[0024] FIG. 8 is a flow diagram illustrating an example operation for identifying troughs and peaks in a bioimpedance signal, in accordance with one or more techniques of this disclosure.

[0025] FIG. 9 is a graph illustrating an example bioimpedance signal comprising inspiration phase and expiration phase information, which may be identified in accordance with one or more techniques of this disclosure.

[0026] FIG. 10 is a flow diagram illustrating an example operation for selecting one or more stimulation parameters for sensing a bioimpedance signal, in accordance with one or more techniques of this disclosure. 10027] FIG. 11 is a flow diagram illustrating an example operation for adjusting a rate of cardiac pacing pulses based on a patient state, in accordance with one or more techniques of this disclosure.

[0028] FIG. 12 is a flow diagram illustrating an example operation for adjusting cardiac pacing pulses based on predicted inspiration and expiration phases, in accordance with one or more techniques of this disclosure.

[0029] FIG. 13 is a flow diagram illustrating an example operation for dynamically adjusting one or more stimulation parameters for sensing the bioimpedance signal, in accordance with one or more techniques of this disclosure.

[0030] Like reference characters refer to like elements throughout the figures and description.

DETAILED DESCRIPTION

[0031] A variety of types of implantable and external devices are configured to monitor health based on sensed physiological signals. External devices that may be used to non- invasively sense and monitor physiological signals include wearable devices with electrodes configured to contact the skin of the patient, such as patches, watches, rings, necklaces, hearing aids, a wearable cardiac monitor or automated external defibrillator (AED), clothing, car seats, or bed linens. Such external devices may facilitate relatively longer-term monitoring of patient health during normal daily activities.

[0032] Implantable medical devices (IMDs) also sense and monitor physiological signals and detect health events such as episodes of arrhythmia, cardiac arrest, myocardial infarction, stroke, and seizure. Example IMDs include pacemakers and implantable cardioverterdefibrillators, which may be coupled to intravascular or extravascular leads, as well as pacemakers with housings configured for implantation within the heart, which may be leadless, such as the Mi era™ leadless pacing device of Medtronic, Inc. Pacemakers provide cardiac pacing pulses to patients based on monitored physiological signals.

[0033] Many current pacemakers pace monotonically in view of pulmonary inspiration/expiration, and the monotonic pacing rate increases with increased activity (e.g., increases with increased activity level but does not vary within the respiratory cycle). Cardiac pacing to mimic RSA, i.e., respirophasic pacing, can provide therapeutic benefit, e.g., by increasing cardiac output and helping to reverse remodel the heart of heart failure (HF) patients. However, current methods of restoring RSA are based on several averaged prior- detected inspiration and expiration phases based on identified respiration cycles, which may mimic RSA when the patient is breathing at a stable rate, e.g., while the patient is sleeping, but may not accurately mimic RSA when the patient is breathing at a more variable rate, e.g., when the patient is active.

[0034] The techniques of this disclosure may be implemented by a cardiac therapy device, e.g., a pacemaker, that can continuously sense physiological signals, e.g., bioimpedance and/or electrogram (EGM) signals, indicative of inspiration phases and expiration phases and detect inspiration phases and expiration phases independently. In other words, the pacemaker may identify inspiration and expiration phases without first identifying a respiration cycle. In some examples, the pacemaker may control therapy delivery circuitry to adjust cardiac pacing pulses based on the current inspiration and/or expiration phases. By continuously monitoring for inspiration phases and/or expiration phases and adjusting cardiac pacing pulses based on the current inspiration phases and/or expiration phases, the techniques of this disclosure may improve RSA pacing accuracy. As such, patients may receive cardiac pacing that more closely mimics RSA, which may improve patient outcomes.

[0035] RSA pacing may be unnecessary, ineffective, or counterproductive under certain conditions, e.g., when the patient is already achieving RSA or when the patient’s heart rate exceeds a threshold. The techniques of this disclosure may avoid delivering RSA pacing under such conditions by determining whether one or more criteria for adjusting cardiac pacing to mimic are satisfied based on one or more sensed patient parameters. In this manner, the techniques described herein may advantageously improve the operation of a device that delivers cardiac pacing to mimic RSA, e.g., to deliver such pacing when it will likely be effective and avoid delivery of counterproductive therapy, thereby benefitting the patient.

[0036] In some examples, the techniques of this disclosure may additionally include further adjusting cardiac pacing based on a patient state, e.g., the pacemaker may increase, or overdrive, cardiac pacing pulses to a lesser extent for patients in one category based on patient state than patients in a different category.

[0037] In some examples, the techniques of this disclosure may include determining one or more stimulation parameters for measuring the bioimpedance signal, such as a stimulation amplitude. In some examples, by determining one or more stimulation parameters may comprise determining whether each of a plurality of stimulation parameters result in a signal associated quality level meeting one or more thresholds. In some examples, the techniques may additionally comprise selecting stimulation parameters that conserve battery life, which may increase device longevity. As an example, to determine the one or more stimulation parameters, e.g., stimulation amplitude, the techniques of this disclosure may include periodically titrating the stimulation amplitude until one or more features of a bioimpedance signal corresponding to the stimulation amplitude falls within a range defined by an upper and a lower threshold. By titrating the stimulation amplitude until one or more features of the bioimpedance signal corresponding to the stimulation amplitude fall within the range, the techniques of this disclosure may facilitate selecting a stimulation amplitude that conserves battery life while also maintaining a quality level above a quality level threshold.

[0038] In some examples, the techniques of this disclosure may include switching from sensing one physiological signal type to another, e.g., switching from sensing a bioimpedance signal to an EGM signal, responsive to changes in patient activity. In some examples, some physiological signals may be more noise-resistant than others, e.g., particularly during times of relatively high patient activity, but may also require more battery power. By switching between physiological signals in response to changes in patient activity level, the techniques of this disclosure may increase accuracy and battery life, thereby improving RSA pacing, which may improve patient outcomes.

[0039] Additionally, or alternatively, in some examples, the techniques of this disclosure may include predicting, e.g., intermittently predicting and/or predicting for an extended period of time, subsequent inspiration and/or expiration phases of the patient based on the detected inspiration and/or expiration and controlling therapy delivery circuitry to adjust cardiac pacing pulses. By intermittently predicting inspiration and/or expiration phases, e.g., predicting every other or every third inspiration phase and/or expiration phase, and/or predicting inspiration and/or expiration phases for extended periods, e.g., when a baseline patient heart rate is below a certain baseline heart rate threshold, when intrinsic changes in heart rate are less than a heart rate change threshold and/or a level of activity is less than an activity threshold, based on one or more previous phases, the techniques of this disclosure may conserve battery life, which may increase device longevity.

[0040] FIG. 1 is a conceptual diagram illustrating an example system 10 configured to deliver cardiac pacing to mimic respiratory sinus arrhythmia (RSA), i.e., respirophasic pacing, in a patient 14, in accordance with one or more techniques of this disclosure. In the example of FIG. 1, system 10 includes an implantable medical device (IMD) 16, which is coupled to leads 18, 20, and 22, and an external device 24. IMD 16 may be, for example, an implantable pacemaker, cardioverter, and/or defibrillator that provides electrical signals to heart 12 via electrodes coupled to one or more of leads 18, 20, and 22. Patient 14 is ordinarily, but not necessarily, a human patient.

[0041] In the example of FIG. 1, leads 18, 20, 22 extend into the heart 12 of patient 14 to sense electrical activity of heart 12, e.g., one or more bioimpedance signals, one or more cardiac electrogram (EGM) signals, and/or deliver electrical stimulation to heart 12. Leads 18, 20, and 22 may also be used to detect bioimpedance indicative of fluid volume in patient 14 and respiration of patient 14. In addition to bioimpedance, a respiration signature indicative of inspiration and expiration phases may also be present as a component of a cardiac EGM signal.

[0042] In the example shown in FIG. 1, right ventricular (RV) lead 18 extends through one or more veins (not shown), the superior vena cava (not shown), and right atrium 26, and into right ventricle 28. Left ventricular (LV) coronary sinus lead 20 extends through one or more veins, the vena cava, right atrium 26, and into the coronary sinus 30 to a region adjacent to the free wall of left ventricle 32 of heart 12. Right atrial (RA) lead 22 extends through one or more veins and the vena cava, and into the right atrium 26 of heart 12.

[0043] The illustrated number and positions of leads 18, 20, and 22 are examples. In other examples, IMD 16 may be coupled to one, two, or more than three leads that extend to a variety of positions. In some examples, system 10 may additionally or alternatively include one or more leads or lead segments (not shown in FIG. 1) that deploy one or more electrodes within the vena cava, or other veins. Furthermore, in some examples, system 10 may additionally or alternatively include extravascular leads with electrodes implanted outside of heart 12, instead of or in addition to transvenous, intracardiac leads 18, 20 and 22. Such leads may be used for one or more of cardiac sensing, pacing, or cardioversion/defibrillation. Additionally, in some examples, system 10 may include one or more leadless cardiac pacing devices, such as the Micra™ pacemakers commercially available from Medtronic, Inc., instead of or in addition to IMD 16. One or more leadless pacemakers may be configured to deliver cardiac pacing according to an RSA mode in the manner described herein with respect to IMD 16. Furthermore, an external medical device may be configured to deliver cardiac pacing according to an RSA mode in the manner described herein with respect to IMD 16. In some examples, a system may additionally or alternatively include one or more implantable or external monitoring devices that monitor patient parameters but do not provide therapy, such as a Reveal LINQ™ insertable cardiac monitor, commercially available from Medtronic, Inc. [0044] IMD 16 may sense electrical signals attendant to the depolarization and repolarization of heart 12 via electrodes (not shown in FIG. 1) coupled to at least one of the leads 18, 20, 22. In some examples, IMD 16 provides pacing pulses to heart 12 based on the electrical signals sensed within heart 12. The configurations of electrodes used by IMD 16 for sensing and pacing may be unipolar or bipolar. In some examples, IMD 16 may deliver cardiac pacing to provide cardiac resynchronization therapy (CRT). In some examples, IMD 16 may additionally or alternatively be configured to provide conduction system pacing, which may provide a more physiologic activation of heart 12 than conventional pacing. In such examples, leads 18, 20, 22 may be configured/positioned such that their electrode(s) access (are capable of stimulating) the heart’s conduction system, e.g., the His bundle, left bundle branch, or right bundle branch.

[0045] IMD 16 may detect arrhythmia of heart 12, such as tachycardia or fibrillation of the atria 26 and 36 and/or ventricles 28 and 32, and may also provide defibrillation therapy and/or cardioversion therapy via electrodes located on at least one of the leads 18, 20, 22. In some examples, IMD 16 may be programmed to deliver a progression of therapies, e.g., pulses with increasing energy levels, until a fibrillation of heart 12 is stopped. IMD 16 may detect fibrillation employing one or more fibrillation detection techniques known in the art. [0046] IMD 16 may utilize two of any electrodes carried on leads 18, 20, 22 to stimulate and sense bioimpedance signals. In some examples, IMD 16 may also use a housing electrode of IMD 16 (not shown) to stimulate and sense bioimpedance signals and monitor cardiac activity. Although these bioimpedance signals may be used to monitor heart 12 for therapy, in some examples, IMD 16 may also use any two electrodes of leads 18, 20, and 22 or the housing electrode to sense a bioimpedance of patient 14 to monitor the condition of heart 12. For example, IMD 16 may monitor heart rate, heart rate variability, indicators of blood flow, or other indicators of the ability of heart 12 to pump blood or the progression of heart failure (HF) based on the bioimpedance signal or another sensed signal.

[0047] As another example, the tissues within the thoracic cavity of patient 14 increase in fluid content, the impedance between two electrodes may also change. IMD 16 may use this bioimpedance to create a fluid index. As the fluid index increases, more fluid may be more likely to be retained within patient 14 and heart 12 may be stressed to keep up with moving the greater amount of fluid.

[0048] IMD 16 may additionally or alternatively utilize two of any electrodes carried on leads 18, 20, 22 to sense EGM signals. In some examples, IMD 16 may also use a housing electrode of IMD 16 (not shown) to sense EGM signals and monitor cardiac activity. Although these EGM signals may be used to monitor heart 12 for potential arrhythmias and other disorders for therapy, the EGM signals may also be used to monitor the condition of heart 12. For example, IMD 16 may monitor heart rate, heart rate variability, indicators of blood flow, or other indicators of the ability of heart 12 to pump blood or the progression of heart failure (HF) and/or another disease state, e.g., high blood pressure, based on the EGM signal or another sensed signal.

[0049] IMD 16 may communicate with external device 24. In some examples, external device 24 comprises a handheld computing device, computer workstation, or networked computing device. External device 24 may be configured to retrieve data from IMD 16, e.g., for presentation to a clinician or other user, such as sensed parameter data of patient 14 and data regarding the operation of IMD 16. In some examples, external device 24 may provide the retrieved data to a cloud computing system, such as the CareLink™ system available from Medtronic, Inc., which may analyze the data and provide reports of the analysis and/or the data to clinicians or other users. In some examples, a clinician or other user may also interact with external device 24 to program IMD 16, e.g., select values for operational parameters of IMD 16. Although the user is typically a clinician, the user may be patient 14 in some examples.

[0050] In some examples, IMD 16, external device 24, or a cloud computing system may determine HF metrics or other patient state information based on patient parameter data collected by IMD 16. In some examples, IMD 16, external device 24, or a cloud computing system may determine, for example, a HF risk level based on the HF risk metrics. For example, the risk level may be determined based on a predetermined number of metrics exceeding their representative thresholds or a weighted score for each of the patient metrics for exceeding one or more thresholds. Additionally, or alternatively, the risk level may be determined by a Bayesian Belief Network, or other probability technique, using the values or stratified states of each automatically detected patient metric. For example, a Bayesian Belief Network may be applied to the values of the patient metrics to determine the risk level, e.g., the probability, that patient 14 will be admitted to the hospital for HF.

[0051] IMD 16 may determine each of the HF metrics and store them within the IMD for later transmission. For example, the patient metrics may include two or more of a thoracic fluid index, an atrial fibrillation duration, a ventricular contraction rate during atrial fibrillation, a patient activity, a nighttime heart rate, a heart rate variability, a CRT percentage (e.g., the percentage of cardiac cycles for which CRT pacing was provided), or the occurrence of or number of therapeutic electrical shocks. [0052] IMD 16 and external device 24 may communicate via wireless communication using any techniques known in the art. Examples of communication techniques may include, for example, radiofrequency (RF) telemetry or communication according to a Bluetooth® protocol, but other communication techniques such as magnetic coupling are also contemplated.

[0053] IMD 16 is an example of a device configured to deliver cardiac pacing pulses to a heart of a patient via a plurality of electrodes, sense a bioimpedance of the patient, identify an inspiration phase and/or an expiration phase, and adjust cardiac pacing pulses based on the heart rate and inspiration and/or expiration phase during the inspiration and/or expiration phase.

[0054] FIG. 2 is a conceptual drawing illustrating IMD 16 and leads 18, 20, and 22 of system 10 in greater detail, in accordance with one or more techniques of this disclosure. As shown in FIG. 2, IMD 16 is coupled to leads 18, 20, and 22. Leads 18, 20, 22 may be electrically coupled to therapy delivery circuitry and sensing circuitry of IMD 16 via connector block 34. In some examples, proximal ends of leads 18, 20, 22 may include electrical contacts that electrically couple to respective electrical contacts within connector block 34 of IMD 16. In addition, in some examples, leads 18, 20, 22 may be mechanically coupled to connector block 34 with the aid of set screws, connection pins, snap connectors, or another suitable mechanical coupling mechanism.

[0055] Each of the leads 18, 20, 22 includes an elongated insulative lead body, which may carry a number of concentric coiled conductors separated from one another by tubular insulative sheaths. Bipolar electrodes 40 and 42 are located adjacent to a distal end of lead 18 in right ventricle 28. In addition, bipolar electrodes 44 and 46 are located adjacent to a distal end of lead 20 in coronary sinus 30 and bipolar electrodes 48 and 50 are located adjacent to a distal end of lead 22 in right atrium 26. In the illustrated example, there are no electrodes located in left atrium 33. However, other examples may include electrodes in left atrium 33. Furthermore, in examples in which IMD 16 is configured to deliver conduction system pacing, lead 18 may configured/positioned differently than illustrated in FIG. 2 so that electrode 42 may stimulate the conduction system, e.g., His bundle, left bundle branch, or right bundle branch. For example, electrode 42 may be positioned on or in the ventricular septum.

[0056] Electrodes 40, 44, and 48 may take the form of ring electrodes, and electrodes 42, 46 and 50 may take the form of fixed or extendable helix tip electrodes mounted to insulative electrode heads 52, 54 and 56, respectively. In other examples, one or more of electrodes 42, 46 and 50 may take the form of small circular electrodes at the tip of a tined lead or other fixation element. Leads 18, 20, 22 also include elongated electrodes 62, 64, 66, respectively, which may take the form of a coil. Each of the electrodes 40, 42, 44, 46, 48, 50, 62, 64 and 66 may be electrically coupled to a respective one of the coiled conductors within the lead body of its associated lead 18, 20, 22, and thereby coupled to respective ones of the electrical contacts on the proximal end of leads 18, 20 and 22.

[0057] In some examples, as illustrated in FIG. 2, IMD 16 includes one or more housing electrodes, such as housing electrode 58, which may be formed integrally with an outer surface of hermetically-sealed housing 60 of IMD 16, or otherwise coupled to housing 60. In some examples, housing electrode 58 is defined by an uninsulated portion of an outward facing portion of housing 60 of IMD 16. Other division between insulated and uninsulated portions of housing 60 may be employed to define two or more housing electrodes. In some examples, housing electrode 58 comprises substantially all of housing 60. As described in further detail with reference to FIG. 3, housing 60 may enclose therapy delivery circuitry configured to generate therapeutic signals, such as cardiac pacing pulses and defibrillation shocks, as well as sensing circuitry for sensing the rhythm of heart 12 and other patient parameters.

[0058] IMD 16 may sense electrical signals attendant to the depolarization and repolarization of heart 12 via electrodes 40, 42, 44, 46, 48, 50, 62, 64 and 66. The electrical signals are conducted to IMD 16 from the electrodes via the respective leads 18, 20, 22. IMD 16 may sense such electrical signals via any bipolar combination of electrodes 40, 42, 44, 46, 48, 50, 62, 64 and 66. Furthermore, any of the electrodes 40, 42, 44, 46, 48, 50, 62, 64 and 66 may be used for unipolar sensing in combination with housing electrode 58. The combination of electrodes used for sensing may be referred to as a sensing configuration or electrode vector.

[0059] In some examples, IMD 16 delivers pacing pulses via bipolar combinations of electrodes 40, 42, 44, 46, 48 and 50 to produce depolarization of cardiac tissue of heart 12. In some examples, IMD 16 delivers pacing pulses via any of electrodes 40, 42, 44, 46, 48 and 50 in combination with housing electrode 58 in a unipolar configuration. Furthermore, IMD 16 may deliver defibrillation pulses to heart 12 via any combination of elongated electrodes 62, 64, 66, and housing electrode 58. Electrodes 58, 62, 64, 66 may also be used to deliver cardioversion pulses to heart 12. Electrodes 62, 64, 66 may be fabricated from any suitable electrically conductive material, such as, but not limited to, platinum, platinum alloy or other materials known to be usable in implantable defibrillation electrodes. The combination of electrodes used for delivery of therapy or sensing, their associated conductors and connectors, and any tissue or fluid between the electrodes, may define an electrical path.

[0060] In some examples, to stimulate and sense a bioimpedance signal, IMD 16 stimulates via a ring electrode located in RV 28, e.g., electrode 40, and a ring electrode located in LV 32, e.g., electrode 44, and senses the bioimpedance signal via a tip electrode located in RV 28, e.g., electrode 42, and a tip electrode located in LV 32, e.g., electrode 46. IMD 16 may also stimulate via a tip electrode located in RV 28, e.g., electrode 42, and a coil electrode located in RV 28, e.g., electrode 62, and may sense the bioimpedance signal via a ring electrode located in RV 28, e.g., electrode 40, and a coil electrode in RV 28, e.g., electrode 62. IMD 16 may also stimulate via a tip electrode located in right atrium 26, e.g., electrode 50, and a tip electrode in RV 28, e.g., electrode 42, and may sense the bioimpedance signal via a ring electrode located in right atrium 26, e.g., electrode 48, and a ring electrode located in RV 28, e.g., electrode 40. The stimulation and sensing configurations described herein serve merely as examples. Several other stimulation and sensing configurations are also possible.

[0061] In some examples, IMD 16 may additionally or alternatively sense a far-field EGM signal via coil electrode 62 positioned in RV 28 and housing electrode 58. Additionally, or alternatively, IMD 16 may sense the EGM signal via tip electrode 42 and housing electrode 58. Other EGM signal sensing configurations are also possible.

[0062] In addition to sensing bioimpedance to identify inspiration phases and/or expiration phases, any of electrodes 40, 42, 44, 46, 48, 50, 62, 64, 66, and 58 may be used to sense non-cardiac signals. For example, two or more electrodes may be used to measure a bioimpedance, e.g., within the thoracic cavity of patient 14. This bioimpedance may be used to generate a fluid index patient metric that indicates the amount of fluid building up within patient 14. Since a greater amount of fluid may indicate increased pumping loads on heart 12, the fluid index may be used as an indicator of HF risk level. IMD 16 may periodically measure the intrathoracic bioimpedance to identify a trend in the fluid index over days, weeks, months, and even years of patient monitoring.

[0063] In some examples, the two electrodes used to measure the intrathoracic bioimpedance may be located at two different positions within the chest of patient 14. For example, coil electrode 62 and housing electrode 58 may be used as the sensing vector for intrathoracic impedance because electrode 62 is located within RV 28 and housing electrode 58 is located at the IMD 16 implant site generally in the upper chest region. However, other electrodes spanning multiple organs or tissues of patient 14 may also be used, e.g., an additional implanted electrode used only for measuring thoracic bioimpedance.

[0064] FIG. 3 is a functional block diagram illustrating an example configuration of IMD 16, in accordance with one or more techniques of this disclosure. In the illustrated example, IMD 16 includes processing circuitry 80, sensing circuitry 82, one or more sensors 84, therapy delivery circuitry 86, communication circuitry 88, and memory 90. Memory 90 includes computer-readable instructions that, when executed by processing circuitry 80, cause IMD 16 and processing circuitry 80 to perform various functions attributed to IMD 16 and processing circuitry 80 herein. Memory 90 may include any volatile, non-volatile, magnetic, optical, or electrical media, such as a random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other digital or analog media.

[0065] Processing circuitry 80 may include any one or more of a microprocessor, a controller, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or equivalent discrete or analog logic circuitry. In some examples, processing circuitry 80 may include multiple components, such as any combination of one or more microprocessors, one or more controllers, one or more DSPs, one or more ASICs, or one or more FPGAs, as well as other discrete or integrated logic circuitry. The functions attributed to processing circuitry 80 herein may be embodied as software, firmware, hardware or any combination thereof, e.g., may be embodied as software or firmware executed on processing circuitry.

[0066] Processing circuitry 80 controls therapy delivery circuitry 86 to deliver therapy to heart 12 according to a therapy parameters and programs which may be stored in memory 90. An example of therapy parameters stored in memory 90 are RSA pacing parameters 96 for delivery of cardiac pacing. RSA pacing parameters 96 may include timing and duration parameters, such as an amount of time to increase and/or decrease a rate of cardiac pacing pulses to mimic RSA or an extent to which to increase and/or decrease a rate of cardiac pacing pulses to mimic RSA. RSA pacing parameters 96 may additionally include bioimpedance stimulation and sensing configurations and stimulation parameters, such as stimulation amplitudes, and signal quality thresholds. In some examples, processing circuitry 80 may be configured to periodically, e.g., hourly, daily, or weekly, control therapy delivery circuitry 86 to deliver therapy at a plurality of stimulation amplitudes during a searching phase, e.g., a 30 to 60 second searching phase. Based on bioimpedance signals corresponding to the plurality of stimulation amplitudes, processing circuitry 80 selects a stimulation amplitude for use in therapy delivery. In some examples, to select the stimulation amplitude, processing circuitry 80 compares one or more features of the bioimpedance signals to one or more quality thresholds. Processing circuitry 80 may select a lowest stimulation amplitude value associated with the one or more features of the bioimpedance signal that meet the one or more quality thresholds.

[0067] The one or more features and threshold may include one or more of a standard deviation of the intervals between successive troughs threshold, such as 60 milliseconds, a standard deviation of the intervals between successive peaks threshold, such as 60 milliseconds, a coefficient of variation of the amplitudes at each peak in the bioimpedance signal threshold, such as 25, a coefficient of variation of the amplitudes at each trough in the bioimpedance signal threshold, such as 25, and/or a difference between mean peak amplitude and mean trough amplitude threshold, e.g., to measure bioimpedance signal strength. In some examples, the one or more quality and/or periodicity thresholds may additionally or alternatively include one or more of an average dynamic range threshold window, a peak/trough consistency threshold window, or a peak to trough interval consistency threshold window.

[0068] In some examples, to select the stimulation amplitude, processing circuitry 80 may control therapy delivery circuitry 86 to titrate the stimulation amplitude until one or more features of the bioimpedance signal, e.g., an average dynamic range, a peak/trough consistency, and/or a peak to trough interval consistency, fall within one or more corresponding threshold windows. The average dynamic range may comprise an average ratio between largest and smallest measurable signal levels of the bioimpedance signal. In some examples, the average dynamic range may be measured in decibels. Processing circuitry 80 may compare an average dynamic range of a bioimpedance signal associated with a stimulation amplitude to an average dynamic range threshold window. The threshold window may be defined by an upper threshold and a lower threshold. The threshold window may be associated with a range of values at which the average dynamic range meets quality criterion and is also associated with power conservation. If the average dynamic range is within the average dynamic range threshold window, processing circuitry 80 may determine to set the stimulation amplitude. Otherwise, processing circuitry 80 may adjust the stimulation amplitude and repeat the process.

[0069] The peak/trough consistency may comprise a consistency of peak/trough amplitudes. In some examples, processing circuitry 80 may determine the peak/trough consistency by comparing peak/trough amplitudes in the signal over time. More consistent peak/trough amplitudes may be associated with a higher value, and less consistent peak/trough amplitudes may be associated with a lower value. Processing circuitry 80 may compare a peak/trough consistency of a bioimpedance signal associated with a stimulation amplitude to peak/trough consistency threshold window. The threshold window may be defined by an upper threshold and a lower threshold. The threshold window may be associated with a range of values at which the peak/trough consistency meets quality criterion and is also associated with power conservation. If the peak/trough consistency is within the peak/trough consistency threshold window, processing circuitry 80 may determine to set the stimulation amplitude. Otherwise, processing circuitry 80 may adjust the stimulation amplitude and repeat the process.

[0070] The peak to trough interval consistency may comprise a consistency of timing between peaks and troughs, e.g., a timing between consecutive peaks, a timing between consecutive troughs, and/or a timing between a peak and a consecutive trough. In some examples, processing circuitry 80 may determine the peak to trough interval consistency by comparing peak to trough intervals in the signal over time. More consistent peak to trough intervals may be associated with a higher value, and less consistent peak to trough intervals may be associated with a lower value. Processing circuitry 80 may compare a peak to trough interval consistency of a bioimpedance signal associated with a stimulation amplitude to peak to trough interval consistency threshold window. The threshold window may be defined by an upper threshold and a lower threshold. The threshold window may be associated with a range of values at which the peak to trough interval consistency meets quality criterion and is also associated with power conservation. If the peak to trough interval consistency is within the peak to trough interval consistency threshold window, processing circuitry 80 may determine to set the stimulation amplitude. Otherwise, processing circuitry 80 may adjust the stimulation amplitude and repeat the process.

[0071] Therapy delivery circuitry 86 is electrically coupled to electrodes 40, 42, 44, 46, 48, 50, 58, 62, 64, and 66, e.g., via conductors of the respective lead 18, 20, 22, or, in the case of housing electrode 58, via an electrical conductor disposed within housing 60 of IMD 16. In the illustrated example, therapy delivery circuitry 86 is configured to generate and deliver electrical therapy to heart 12. For example, therapy delivery circuitry 86 may deliver defibrillation shocks to heart 12 via at least two electrodes 58, 62, 64, 66. Therapy delivery circuitry 86 may deliver pacing pulses via ring electrodes 40, 44, 48 coupled to leads 18, 20, and 22, respectively, and/or helical electrodes 42, 46, and 50 of leads 18, 20, and 22, respectively. In some examples, therapy delivery circuitry 86 delivers pacing, cardioversion, or defibrillation stimulation in the form of electrical pulses. In other examples, therapy delivery circuitry 86 may deliver one or more of these types of stimulation in the form of other signals, such as sine waves, square waves, or other substantially continuous time signals.

[0072] Therapy delivery circuitry 86 includes circuitry, such as charge pumps, capacitors, current mirrors, or other signal generation circuitry for generating a pulse or other signal. Therapy delivery circuitry 86 may include a switch module, and processing circuitry 80 may use the switch module to select, e.g., via a data/address bus, which of the available electrodes are used to deliver antitachyarrhythmia shocks or pacing pulses. The switch module may include a switch array, switch matrix, multiplexer, or any other type of switching device suitable to selectively couple stimulation energy to selected electrodes.

[0073] Sensing circuitry 82 monitors signals from at least one of electrodes 40, 42, 44, 46, 48, 50, 58, 62, 64 or 66 in order to monitor bioimpedance signals of the heart and/or electrical activity of heart 12, respiration of patient 14, or other patient parameters, values of which may be stored as patient parameter data 92 in memory 90. Sensing may be done to detect intrinsic cardiac depolarizations, determine heart rates or heart rate variability, or to detect arrhythmias or other electrical signals. Sensing circuitry 82 may include one or more filters, amplifiers, analog-to-digital converters, or other sensing circuitry.

[0074] Sensing circuitry 82 may also include a switch module to select which of the available electrodes are used to sense the heart activity, depending upon which electrode combination, or electrode vector, is used in the current sensing configuration. In some examples, processing circuitry 80 may select the electrodes that function as sense electrodes, i.e., select the sensing configuration, via the switch module within sensing circuitry 82. Sensing circuitry 82 may include one or more detection channels, each of which may be coupled to a selected electrode configuration for detection of cardiac signals via that electrode configuration. Some detection channels may be configured to detect cardiac events, such as P- or R-waves, and provide indications of the occurrences of such events to processing circuitry 80.

[0075] Processing circuitry 80 may be configured to identify inspiration and/or expiration phases of a patient based on the bioimpedance signal, EGM signal, or another physiological signal. To identify inspiration and/or expiration phases, processing circuitry 80 may, for example, detect peaks and troughs in the bioimpedance signature and/or peaks and troughs in a respiration signature of the EGM signal, e.g., identifying maximal or minimal values of the signal, by identifying zero slope points (zero crossings in a derivative or differential of the signal), or using any other peak/trough detection techniques. Processing circuitry 80 may determine an expiration phase as an interval or window from an identified peak to a subsequent trough, and an inspiration phase as an interval or window from an identified trough to a subsequent peak. Processing circuitry 80 may determine respiration effort based on one or more of a peak-to-trough amplitude or a slope of the signal within the inspiration phase. Processing circuitry 80 may determine tidal volume based on an area under the curve during the respiration cycle. In some examples, processing circuitry 80 may determine tidal volume based on a peak-to-trough amplitude, which may vary with tidal volume.

[0076] One or more sensor(s) 84 may include, as examples, one or more accelerometers, microphones, temperature sensors, or optical sensors that are configured to provide signals or data representing one or more patient parameters to processing circuitry 80 via sensing circuitry 82. In some examples, based on a signal from one or more accelerometers, processing circuitry 80 may determine postures and/or activity levels of patient 14. In some examples, processing circuitry 80 may identify inspiration and/or expiration phases using one or more of sensor(s) 84. For example, processing circuitry 80 may identify inspiration and/or expiration using accelerometer signal data. In some examples, processing circuitry 80 may identify inspiration and/or expiration using accelerometer signal data in addition to or instead of bioimpedance and/or EGM signal data. In some examples, local minima and local maxima in the accelerometer signal may be indicative of beginnings of inspiration phases and expiration phases, respectively.

[0077] Processing circuitry 80 may implement programmable counters that control the basic time intervals associated with DDD, VVI, DVI, VDD, AAI, DDI, DDDR, VVIR, DVIR, VDDR, AAIR, DDIR, CRT, and other modes of pacing. Intervals defined by processing circuitry 80 may include atrial and ventricular pacing escape intervals, A-V intervals, V-V intervals, and refractory periods during which sensed P-waves and R-waves are ineffective to restart timing of the intervals. The durations of these intervals may be determined by processing circuitry 80 in response to stored data in memory 90.

[0078] In some examples, processing circuitry 80 may modify escape intervals based on a rate responsive pacing mode. Processing circuitry 80 may determine a sensor indicated pacing rate based on sensed parameters of patient 14, such as one or more of activity level or respiration rate, and thereby modify the escape interval and pacing rate to provide cardiac pacing that supports the activity of patient 14. In some examples, processing circuitry 80 may additionally modify the pacing mode based on a patient disease state or other patient data. In some examples, processing circuitry 80 may control IMD 16 to provide CRT by controlling delivery of pacing pulses to one or both of RV 28 and LV 32 based on atrioventricular timing and interventricular timing specified by one or more A-V intervals and V-V intervals.

[0079] Interval counters implemented by processing circuitry 80 may be reset upon sensing of R-waves and P-waves with detection channels of sensing circuitry 82. In examples in which IMD 16 provides pacing, therapy delivery circuitry 86 may include pacer output circuits that are coupled, e.g., selectively by a switching module, to any combination of electrodes 40, 42, 44, 46, 48, 50, 58, 62, or 66 appropriate for delivery of a bipolar or unipolar pacing pulse to one of the chambers of heart 12. In such examples, processing circuitry 80 may reset the interval counters upon the generation of pacing pulses by therapy delivery circuitry 86, and thereby control the basic timing of cardiac pacing functions, including anti-tachyarrhythmia pacing.

[0080] The value of the count present in the interval counters when reset by sensed R-waves and P-waves may be used by processing circuitry 80 to measure the durations of R-R intervals, P-P intervals, P-R intervals and R-P intervals, which are measurements that may be stored in memory 90. Processing circuitry 80 may use the count in the interval counters to detect a tachyarrhythmia event, such as atrial fibrillation (AF), atrial tachycardia (AT), ventricular fibrillation (VF), or ventricular tachycardia (VT). These intervals may also be used to detect the overall heart rate, ventricular contraction rate, and heart rate variability. A portion of memory 90 may be configured as a plurality of recirculating buffers, capable of holding series of measured intervals, which may be analyzed by processing circuitry 80 in response to the occurrence of a pace or sense interrupt to determine whether the patient’s heart 12 is presently exhibiting atrial or ventricular tachyarrhythmia.

[0081] In some examples, processing circuitry 80 may determine that tachyarrhythmia has occurred by identification of shortened R-R (or P-P) interval lengths. Generally, processing circuitry 80 detects tachycardia when the interval length falls below 220 milliseconds (ms) and fibrillation when the interval length falls below 180 ms. These interval lengths are merely examples, and a user may define the interval lengths as desired, which may then be stored within memory 90. This interval length may need to be detected for a certain number of consecutive cycles, for a certain percentage of cycles within a running window, or a running average for a certain number of cardiac cycles, as examples.

[0082] In the event that processing circuitry 80 detects an atrial or ventricular tachyarrhythmia based on signals from sensing circuitry 82, and an anti-tachyarrhythmia pacing regimen is desired, timing intervals for controlling the generation of anti-tachyarrhythmia pacing therapies by therapy delivery circuitry 86 may be loaded by processing circuitry 80 to control the operation of the escape interval counters therein and to define refractory periods during which detection of R-waves and P-waves is ineffective to restart the escape interval counters for the an anti-tachyarrhythmia pacing. In the event that processing circuitry 80 detects an atrial or ventricular tachyarrhythmia based on signals from sensing circuitry 82, and a cardioversion or defibrillation shock is desired, processing circuitry 80 may control the amplitude, form and timing of the shock delivered by therapy delivery circuitry 86.

[0083] Memory 90 may be configured to store a variety of operational parameters, therapy parameters, sensed and detected data, and any other information related to the therapy and treatment of patient 14. In the example of FIG. 3, memory 90 includes patient parameter data 92, RSA activation criteria 94, and RSA pacing parameters. Patient parameter data 92 may store all of the data generated from the sensing and detecting of patient parameters described herein, such as heart rates, inspiration phases and/or expiration phases, activity, posture, fluid index, an atrial tachycardia or fibrillation burden, a ventricular contraction rate during atrial fibrillation, a nighttime heart rate, a difference between night and day heart rate, a heart rate variability, a cardiac resynchronization therapy percentage, a bradyarrhythmia pacing therapy percentage (in a ventricle and/or atrium), and number or frequency of electrical shock events, blood pressure, right ventricular pressure, pulmonary artery pressure, patient temperature, or biomarkers such as a brain natriuretic peptide (BNP), troponin, or related surrogates. In some examples, processing circuitry 80 may determine HF metrics based on sensed parameter data 92 and determine a HF risk level based on the HF metrics.

[0084] RSA activation criteria 94 includes one or more criteria that processing circuitry 80 may apply to patient parameter data 92 to determine whether to adjust cardiac pacing to mimic RSA. Processing circuitry 80 may adjust pacing to mimic RSA if patient parameter data 92 satisfies RSA activation criteria 94. RSA activation criteria 94 may be fixed, programmable by a user, or variable based on conditions determined by processing circuitry 80. To adjust cardiac pacing to mimic RSA, processing circuitry 80 control therapy delivery circuitry 86 to deliver pacing pulses, according to RSA pacing parameters 96, with increasing rates during an inspiration phase of a respiratory cycle, and, in some examples, decreasing rates during an expiration phase of the cardiac cycle, as described herein. The increasing and decreasing of pacing rates may be sequential, on a beat-to-beat or other basis. [0085] Communication circuitry 88 includes any suitable hardware, firmware, software or any combination thereof for communicating with another device, such as external device 24 (FIG. 1). Under the control of processing circuitry 80, communication circuitry 88 may communicate with external device 24 with the aid of an antenna, which may be internal and/or external.

[0086] FIG. 4 is a flow diagram illustrating an example operation of a device to adjust a rate of cardiac pacing to mimic RSA, in accordance with one or more techniques of this disclosure. Although described in the context of IMD 16, the example operation of FIG. 4 may be additionally or alternatively performed by other devices, as described herein.

[0087] In some examples, processing circuitry 80 of IMD 16 controls therapy delivery circuitry 86 to deliver cardiac pacing according to a base mode, such as a demand mode, rate responsive mode, CRT mode, or conduction system pacing mode. Sensing circuitry 82 and/or sensor(s) 84 sense a physiological signal of patient 14, e.g., a bioimpedance signal, which is indicative of respiration information, i.e., inspiration phase and expiration phase information. Processing circuitry 80 identifies a beginning of an inspiration phase of patient 14 (402). In some examples, to identify the beginning of the inspiration phase inspiration, processing circuitry 80 identifies a trough, or local minimum, in the bioimpedance signal. Based on the identification of the beginning of the inspiration phase of patient 14, processing circuitry 80 controls therapy delivery circuitry 86 to adjust a rate of cardiac pacing pulses during the inspiration phase, e.g., to increase the rate of cardiac pacing pulses relative to a baseline pacing rate or an intrinsic pacing rate (404). Optionally, processing circuitry 80 may identify a beginning of an expiration phase of patient 14 (406). In some examples, to identify the beginning of the expiration phase inspiration, processing circuitry 80 identifies a peak, or local maximum, in the bioimpedance signal. Based on the identification of the beginning of the expiration phase of patient 14, processing circuitry 80 controls therapy delivery circuitry 86 to adjust a rate of cardiac pacing pulses during the expiration phase, e.g., to return pacing to a baseline pacing rate or an intrinsic pacing rate or to otherwise decrease the pacing rate relative to the pacing rate during the inspiration phase (408). In some examples, processing circuitry 80 may control therapy delivery circuitry 86 to adjust a rate of cardiac pacing pulses throughout the duration of a respiration cycle associated with the inspiration phase. Although identifying the beginning of the expiration phase was described as optional in FIG. 4, in other examples, processing circuitry 80 may identify expiration phase, and identifying inspiration phase may be optional. [0088] FIG. 5 is a flow diagram illustrating an example operation of a device to determine whether to adjust a rate of cardiac pacing to mimic RSA, in accordance with one or more techniques of this disclosure. Although described in the context of IMD 16, the example operation of FIG. 5 may be additionally or alternatively performed by other devices, as described herein. In some examples, processing circuitry 80 of IMD 16 controls therapy delivery circuitry 86 to deliver cardiac pacing according to a base mode, such as a demand mode, rate responsive mode, CRT mode, or conduction system pacing mode. Sensing circuitry 82 and/or sensor(s) 84 sense a bioimpedance signal of the patient, which is indicative of respiration information, i.e., inspiration phase and expiration phase information. Processing circuitry 80 identifies a beginning of an inspiration phase of the patient (502). In some examples, identifying the beginning of the prior inspiration phase comprises identifying a trough, or local minimum, in the bioimpedance signal. Processing circuitry 80 additionally identifies a beginning of an expiration phase (504). Processing circuitry 80 continuously determines the heart rate of the patient (506). Based on the heart rate during the inspiration phase and expiration phase, processing circuitry 80 determines whether patient 14 is achieving RSA, e.g., by determining whether the heart rate is increased, e.g., by at least 1 beat per minute, during inspiration phase relative to expiration phase (508). If processing circuitry 80 determines patient 14 is not achieving RSA, (“NO” of 508), processing circuitry 80 controls therapy delivery circuitry 86 to adjust cardiac pacing pulses to mimic RSA, e.g., based on RSA pacing parameters 96 (510). Processing circuitry 80 continues the example operation. If processing circuitry 80 determines patient 14 is achieving RSA (“YES” of 512), the process continues.

[0089] In some examples, patient 14 may be fully paced, i.e., IMD 16 may initiate every depolarization. In examples in which patient 14 is fully paced, processing circuitry may increase a rate of, or overdrive, pacing during inspiration phases relative to a baseline heart rate and may decrease the rate of pacing during expiration phases, e.g., decrease the rate of pacing relative to the baseline heart rate or decrease the rate of pacing relative to the pacing rate during inspiration phases. In other examples, patient 14 may not be fully paced, i.e., IMD 16 initiates some depolarizations, e.g., when the heart rate drops below a threshold or when patient 14 experiences a cardiac event, but patient 14’s intrinsic pacing system initiates other depolarizations. In examples in which patient 14 is not fully paced, processing circuitry may increase the rate of pacing during inspiration phases and may allow patient 14’s intrinsic pacing system to drive pacing at a relatively lower baseline heart rate, e.g., an intrinsic baseline heart rate, during expiration phases. [0090] FIG. 6 is a flow diagram illustrating an example operation for determining whether to switch from sensing a bioimpedance signal to sensing an EGM signal to identify respiration information, i.e., inspiration phases and expiration phases, in accordance with one or more techniques of this disclosure. In some examples, bioimpedance signals may be more resistant to noise than other signals that require less battery power, such as EGM signals. In some examples, EGM signals may be particularly susceptible to noise-related sensing issues while the patient is active and may be less susceptible to noise-related sensing issues while the patient is inactive, e.g., sleeping or resting. Processing circuitry 80 determines a patient activity level (602). In some examples, processing circuitry 80 determines a patient activity level based on accelerometer signal data, e.g., an accelerometer of sensor(s) 84, and/or based on patient heart rate. Processing circuitry determines whether the patient activity level meets a threshold activity level (604). If the patient activity level does not meet the threshold (“NO” of 604), the process continues. If the patient activity level does meet the threshold (“YES” of 604), processing circuitry 80 may control sensing circuitry 82 to switch from sensing a bioimpedance signal to sensing an EGM signal to identify respiration information (606). By switching from sensing a bioimpedance signal to an EGM signal during periods of relatively low patient activity, the techniques of this disclosure may advantageously conserve battery power, which may increase a longevity of IMD 16. After switching to sensing an EGM signal, processing circuitry 80 may continuously determine whether to switch back to sensing a bioimpedance signal based on patient activity level and/or based on a signal quality of the EGM signal falling below a quality threshold (608).

[0091] FIG. 7 is a flow diagram illustrating an example operation for determining whether to adjust cardiac pacing to mimic RSA based on patient heart rate information, in accordance with one or more techniques of this disclosure. In some examples, the example operation of FIG. 7 may be part of the determination of whether to adjust cardiac pacing in step 512 of FIG. 5. Processing circuitry 80 determines an average heart rate of the patient (602). In some examples, the average heart rate comprises a running average of the heart rate or a moving average of the heart rate. Processing circuitry 80 compares the average heart rate to a threshold heart rate value (704). In some examples, memory 90 stores the threshold heart rate value in RSA activation criteria 94 and the average heart rate in patient parameter data 92. In some examples, the threshold heart rate value is not patient specific. In other examples, processing circuitry 80 determines a threshold heart rate value based on patient parameter data 92. In some examples, processing circuitry 80 may implement a machine learning model to determine the threshold heart rate value. In other examples, the clinician may determine the threshold heart rate value. In some examples, overdrive RS A pacing may not be desired where pacing burden is already relatively high, and/or the patient is experiencing an elevated heart rate.

[0092] If the average heart rate exceeds the threshold heart rate value (“YES” of 704), processing circuitry 80 determines not to control therapy delivery 86 circuitry to adjust cardiac pacing pulses to mimic RSA (708). If the average heart rate does not exceed the threshold heart rate value (“NO” of 704), processing circuitry 80 controls therapy 86 to adjust cardiac pacing pulses to mimic RSA (706).

[0093] FIG. 8 is a flow diagram illustrating an example operation for identifying troughs and peaks in a bioimpedance signal, in accordance with one or more techniques of this disclosure. Processing circuitry 80 determines one or more bioimpedance signal characteristics, such as a maximum signal amplitude (802). In some examples, processing circuitry 80 stores the one or more bioimpedance signal characteristics in patient parameter data 92. In some examples, processing circuitry 80 determines a baseline signal or other information for use in peak and trough detection based on the one or more signal characteristics. As part of trough detection process 818, processing circuitry 80 determines differences between successive samples of bioimpedance signal data (806). Processing circuitry 80 determines whether the differences between the successive samples are indicative of a trough in the signal, e.g., by determining whether the difference between successive samples changes from a negative value to 0 or a positive value (808). If the differences are not indicative of a trough (“NO” of 808), processing circuitry 80 continues determining differences between successive samples (806). If the differences are indicative of a trough (“YES” of 808), processing circuitry 80 logs a trough (810) and proceeds to determine differences between successive samples (812) as part of peak detection process 820. In some examples, processing circuitry 80 determines the differences are indicative of a peak based on the differences in the successive samples changing from a negative value or 0 to a positive value. Processing circuitry 80 additionally continues to determine differences between successive samples (806) in trough detection process 818. In some examples, before continuing to determine differences between successive samples (806), processing circuitry 80 may skip data for a period of time, e.g., 2 seconds, to, for example, prevent identifying and logging the same trough multiple times. Processing circuitry 80 determines whether the differences between the successive samples are indicative of a peak in the signal (814). If the differences are not indicative of a peak (“NO” of 814), processing circuitry 80 continues determining differences between successive samples (812). If the differences are indicative of a peak (“YES” of 814), processing circuitry 80 logs a peak (816) and continues to determine differences between successive samples (806) in trough detection process 818. In some examples, processing circuitry 80 may apply one or more thresholds during the peak and trough detections processes to prevent false peak and trough detections caused by noise or other sensing issues. For example, processing circuitry 80 may determine whether a sample meets or exceeds a threshold amplitude by comparing the sample amplitude to a threshold amplitude. In some examples, to verify a true peak has occurred, processing circuitry 80 may compare the sample amplitude to the threshold amplitude. In some examples, the threshold amplitude is based on the one or more signal characteristics. For example, the threshold amplitude may be based on a previously identified maximum amplitude of the signal, e.g., the threshold amplitude may be 50% or some other percentage of the maximum amplitude value. [0094] FIG. 9 is a graph illustrating an example bioimpedance signal comprising inspiration phase and expiration phase information, in accordance with one or more techniques of this disclosure. In some examples, to stimulate and sense a bioimpedance signal, IMD 16 stimulates via a ring electrode located in RV 28, e.g., electrode 40, and a ring electrode located in LV 32, e.g., electrode 44, and senses the bioimpedance signal via a tip electrode located in RV 28, e.g., electrode 42, and a tip electrode located in LV 32, e.g., electrode 46. IMD 16 may also stimulate via a tip electrode located in RV 28, e.g., electrode 42, and a coil electrode located in RV 28, e.g., electrode 62, and may sense the bioimpedance signal via a ring electrode located in RV 28, e.g., electrode 40, and a coil electrode in RV 28, e.g., electrode 62. IMD 16 may also stimulate via a tip electrode located in right atrium 26, e.g., electrode 50, and a tip electrode in RV 28, e.g., electrode 42, and may sense the bioimpedance signal via a ring electrode located in right atrium 26, e.g., electrode 48, and a ring electrode located in RV 28, e.g., electrode 40. Other sensing and stimulation electrode configurations are also possible. Trough 904, or local minimum, of bioimpedance signal 900 is indicative of a beginning of an inspiration phase. Peak 902, or local maximum, of bioimpedance signal 900 is indicative of a beginning of an expiration phase. In some examples, processing circuitry 80 is configured to identify inspiration phases and/or expiration phases based on the peaks, such as peak 902, and troughs, such as trough 904. Processing circuitry 80 may identify peaks and troughs using the example operation of FIG. 8.

[0095] FIG. 10 is a flow diagram illustrating an example operation for selecting one or more stimulation parameters for sensing a bioimpedance signal, in accordance with one or more techniques of this disclosure. Processing circuitry 80 may perform the example operation of FIG. 10 periodically and/or in response to a sensed signal, e.g., a sensed change in patient activity level/posture or a change in heart rate or baseline heart rate. In some examples, to stimulate and sense a bioimpedance signal, IMD 16 stimulates via a ring electrode located in RV 28, e.g., electrode 40, and a ring electrode located in LV 32, e.g., electrode 44, and senses the bioimpedance signal via a tip electrode located in RV 28, e.g., electrode 42, and a tip electrode located in LV 32, e.g., electrode 46. IMD 16 may also stimulate via a tip electrode located in RV 28, e.g., electrode 42, and a coil electrode located in RV 28, e.g., electrode 62, and may sense the bioimpedance signal via a ring electrode located in RV 28, e.g., electrode 40, and a coil electrode in RV 28, e.g., electrode 62. IMD 16 may also stimulate via a tip electrode located in right atrium 26, e.g., electrode 50, and a tip electrode in RV 28, e.g., electrode 42, and may sense the bioimpedance signal via a ring electrode located in right atrium 26, e.g., electrode 48, and a ring electrode located in RV 28, e.g., electrode 40. Other sensing and stimulation electrode configurations are also possible. [0096] In some examples, processing circuitry 80 is configured to select one or more stimulation parameters for a predetermined sensing and stimulation configuration. In other examples, processing circuitry 80 may select a sensing and stimulation configuration based on a sensing and stimulation configuration resulting in a bioimpedance signal meeting one or more quality and/or periodicity thresholds. In some examples, processing circuitry 80 may initially select a sensing and stimulation configuration and switch to a different sensing and stimulation configuration responsive to the sensing and stimulation configuration not resulting in a bioimpedance signal meeting one or more quality and/or periodicity thresholds. For one or more of the possible sensing and stimulation electrode configurations, processing circuitry 80 controls one or more electrodes to stimulate at a plurality of stimulation amplitudes (1002). In some examples, the plurality of stimulation amplitudes may be within a stimulation amplitude range, e.g., from 0.5 microamps to 10 microamps. Sensing circuitry 82 may sense each bioimpedance signal of a plurality of bioimpedance signals corresponding to the plurality of stimulation amplitudes. For each of the plurality of stimulation amplitudes, processing circuitry 80 receives the corresponding bioimpedance signal e.g., for a certain number of respiratory cycles, such as 10 cycles, or a certain time period, such as 30 seconds to 60 seconds (1004). For each of the plurality of corresponding bioimpedance signals, processing circuitry 80 compares the bioimpedance signal to one or more quality and/or periodicity thresholds (1006). The one or more quality and/or periodicity thresholds many include one or more of a standard deviation of the intervals between successive troughs threshold, such as 60 milliseconds, a standard deviation of the intervals between successive peaks threshold, such as 60 milliseconds, a coefficient of variation of the amplitudes at each peak in the bioimpedance signal threshold, such as 25, a coefficient of variation of the amplitudes at each trough in the bioimpedance signal threshold, such as 25, and/or a difference between mean peak amplitude and mean trough amplitude threshold, e.g., to measure bioimpedance signal strength. In some examples, the one or more quality and/or periodicity thresholds may additionally or alternatively include one or more of an average dynamic range threshold window, a peak/trough consistency threshold window, or a peak to trough interval consistency threshold window. In some examples, processing circuitry 80 optionally determines a lowest stimulation amplitude with a corresponding bioimpedance signal meeting the one or more quality and/or periodicity thresholds (1008). Processing circuitry 80 selects a stimulation amplitude of the plurality of stimulation amplitudes with a corresponding bioimpedance signal meeting the one or more quality thresholds for stimulation (1010). In examples in which processing circuitry 80 determines the lowest stimulation amplitude with the corresponding bioimpedance signal meeting the one or more quality and/or periodicity thresholds, processing circuitry 80 may select the lowest stimulation amplitude for stimulation at step 1010, e.g., to conserve battery life. In other examples, processing circuitry 80 may select a stimulation amplitude other than the lowest stimulation amplitude with the corresponding bioimpedance signal meeting the quality and/or periodicity thresholds. For example, processing circuitry 80 may determine that a second lowest stimulation amplitude is associated with a bioimpedance signal with higher signal quality and may select the second lowest stimulation amplitude.

[0097] Processing circuitry 80 may, in some examples, implement a cost function to select a stimulation amplitude. The inputs of the cost function may include one or more of, for example, for each stimulation amplitude of the plurality of stimulation amplitudes, the standard deviation of the intervals between successive troughs, the standard deviation of the intervals between successive peaks, the coefficient of variation of the amplitudes at each peak in the bioimpedance signal, the coefficient of variation of the amplitudes at each trough in the bioimpedance signal, and/or the difference between mean peak amplitude and mean trough amplitude.

[0098] FIG. 11 is a flow diagram illustrating an example operation for adjusting a rate of cardiac pacing pulses based on a patient state, in accordance with one or more techniques of this disclosure. In some examples, patient parameter data 92 may include data indicative of a patient state. For example, patient parameter data 92 may include one or more of data sensed by electrodes 40, 42, 62, 44, 46, 64, 48, 50, 66, and/or 58, data sensed by sensor(s) 84, or historical patient data. As examples, patient state can be based on one or more of patient activity level, patient age, or patient disease progression, e.g., HF progression and/or high blood pressure. Based on patient parameter data 92, processing circuitry 80 determines a patient state (1102). Based on the patient state, processing circuitry 80 may adjust the rate of cardiac pacing pulses (1104).

[0099] In examples in which patient state is based on patient activity level, processing circuitry 80 may determine a patient motion level, e.g., via an accelerometer of sensor(s) 84, and/or a patient heart rate, e.g., based on a bioimpedance signal. Based on the patient activity level, processing circuitry 80 may control therapy delivery circuitry 86 to adjust the rate of cardiac pacing pulses. For example, processing circuitry 80 may be configured to adjust cardiac pacing pulses to mimic RSA by overdriving pacing during inspiration phase within a range, e.g., by 5 to 20 beats per minute, relative to a baseline heart rate or a paced expiration phase heart rate. Based on the patient activity level, processing circuitry 80 may determine to adjust cardiac pacing pulses to overdrive pacing at a low end of the range, e.g., 5 beats per minute, or at a high end of the range, e.g., 20 beats per minute.

[0100] In examples in which patient state is based on patient disease progression, processing circuitry 80 may determine disease state progression based on, for example, a HF risk level. Processing circuitry 80 may determine to adjust cardiac pacing pulses to overdrive pacing at the low end of the range, e.g., 5 beats per minute, for patients at a first, e.g., a relatively high, HF risk level and overdrive pacing at the high end of the range, e.g., 20 beats per minute, for patients at a first, e.g., a relatively low, HF risk level different from the first HF risk level.

[0101] In some examples, e.g., if patient 14’ s average heart rate is near an upper tracking rate value, e.g., the threshold in step 604 of FIG. 6, processing circuitry may determine to adjust cardiac pacing to increase a rate of cardiac pacing to a lower extent, e.g., at a low end of the range, such as 5 beats per minute, to, for example, ensure that patient 14’ s average heart rate does not exceed the upper tracking rate value. The threshold in step 604 is provided merely as an example. In other examples, the upper tracking rate value comprises a value other than, e.g., higher or lower than, the value of the threshold in step 604.

[0102] In some examples, a clinician may adjust the range for overdrive pacing, e.g., to tailor pacing to patient specific needs. In other examples, processing circuitry 80 may adjust the range for overdrive pacing, e.g., based on patient parameter data 92. In some examples, processing circuitry 80 may implement a machine learning model to determine a range for overdrive pacing of the patient. [0103] FIG. 12 is a flow diagram illustrating an example operation for adjusting cardiac pacing pulses based on predicted inspiration and expiration phases, in accordance with one or more techniques of this disclosure. The techniques of FIG. 12 may be performed additionally or alternatively to the techniques of FIG. 6. In some examples, the techniques of FIG. 12 can be performed using the bioimpedance signal or using the EGM signal of FIG. 6. In some examples, processing circuitry 80 may determine to predict a subsequent inspiration phase and/or a subsequent expiration phase to control therapy delivery circuitry to adjust cardiac pacing pulses, e.g., to mimic RSA. In some examples, intermittently predicting inspiration and/or expiration phases and/or predicting inspiration and/or expiration phases for an extended period of time, e.g., instead of identifying each inspiration and/or expiration phase, may conserve battery life of IMD 16. In some examples, to determine to predict subsequent inspiration and/or expiration phases, processing circuitry 80 may determine patient 14’s activity level is below a prediction threshold, e.g., the activity level threshold of step 604. For example, patient 14’ s activity level may be below the prediction threshold when patient 14 is resting, e.g., sleeping. Additionally, or alternatively, processing circuitry 80 may determine to predict inspiration and/or expiration when patient 14’s heart rate is below a threshold heart rate, e.g., 75 beats per minute, 70 beats per minute, or 65 beats per minute, and/or when patient 14’s heart rate has not changed by more than a change threshold, e.g., 5 beats per minute. In some examples, processing circuitry 80 may determine to predict inspiration and/or expiration intermittently, e.g., every third inspiration may be predicted. In some examples, processing circuitry 80 predicts inspiration and/or expiration for an extended period of time, e.g., when patient 14 is resting. Processing circuitry 80 predicts a beginning of and/or a duration of a subsequent inspiration phase based on one or more previous inspiration and/or expiration phases (1202). Processing circuitry 80 predicts a beginning of and/or a duration of a subsequent expiration based on one or more previous expiration and/or inspiration phases (1204). Based on the predicted inspiration phase and/or predicted expiration phase, processing circuitry 80 may control the therapy delivery circuitry to adjust cardiac pacing pulses, e.g., to mimic RSA (1206). In some examples, processing circuitry 80 determines patient 14’s activity level has exceeded the prediction threshold and may switch back to sensing all inspiration and/or expiration phases. In some examples, processing circuitry 80 may determine the predictions do not meet an accuracy threshold and may switch back to sensing all inspiration and/or expiration phases, i.e., processing circuitry 80 may stop predicting subsequent inspiration and expiration phases. [0104] FIG. 13 is a flow diagram illustrating an example operation for dynamically adjusting one or more stimulation parameters, e.g., stimulation amplitude, for sensing the bioimpedance signal, in accordance with one or more techniques of this disclosure. Processing circuitry 80 may perform the example operation of FIG. 13 periodically, e.g., hourly, daily, or weekly, and/or in response to a sensed signal, e.g., a sensed change in patient activity level/posture or a change in heart rate or baseline heart rate. In some examples, to stimulate and sense a bioimpedance signal, therapy delivery circuitry 86 of IMD 16 stimulates via a ring electrode located in RV 28, e.g., electrode 40, and/or a ring electrode located in LV 32, e.g., electrode 44, and senses the bioimpedance signal via a tip electrode located in RV 28, e.g., electrode 42, and/or a tip electrode located in LV 32, e.g., electrode 46. IMD 16 may also stimulate via a tip electrode located in RV 28, e.g., electrode 42, and/or a coil electrode located in RV 28, e.g., electrode 62, and may sense the bioimpedance signal via a ring electrode located in RV 28, e.g., electrode 40, and/or a coil electrode in RV 28, e.g., electrode 62. IMD 16 may also stimulate via a tip electrode located in right atrium 26, e.g., electrode 50, and/or a tip electrode in RV 28, e.g., electrode 42, and may sense the bioimpedance signal via a ring electrode located in right atrium 26, e.g., electrode 48, and/or a ring electrode located in RV 28, e.g., electrode 40. Other sensing and stimulation electrode configurations are also possible.

[0105] In some examples, processing circuitry 80 is configured to select one or more stimulation parameters for a predetermined sensing and stimulation configuration. In other examples, processing circuitry 80 may select a sensing and stimulation configuration based on the sensing and stimulation configuration resulting in a bioimpedance signal meeting one or more quality and/or periodicity thresholds. In some examples, processing circuitry 80 may initially select a sensing and stimulation configuration and switch to a different sensing and stimulation configuration responsive to the sensing and stimulation configuration not resulting in a bioimpedance signal meeting one or more quality and/or periodicity thresholds. Processing circuitry 80 measures an impedance signal associated with a stimulation amplitude (1302). In some examples, the stimulation amplitude value is within a stimulation amplitude range, e.g., from 0.5 microamps to 10 microamps. Sensing circuitry 82 senses a bioimpedance signal corresponding to the stimulation amplitude. The duration of the bioimpedance signal may correspond to a certain number of respiratory cycles, such as 10 cycles, or a certain period of time, such as 30 seconds to 60 seconds. Processing circuitry 80 determines one or more features of the bioimpedance signal (1304). In some examples, the one or more features may include one or more of an average dynamic range, a peak/trough consistency, or a peak to trough interval consistency.

[0106] The average dynamic range may comprise an average ratio between largest and smallest measurable signal levels of the bioimpedance signal. In some examples, the average dynamic range may be measured in decibels. A relatively high average dynamic range may be indicative of good signal quality, and a relatively low average dynamic range may be indicative of poor signal quality. The peak/trough consistency may comprise a consistency of peak/trough amplitudes. In some examples, processing circuitry 80 may determine the peak/trough consistency by comparing peak/trough amplitudes in the signal over time. More consistent peak/trough amplitudes may be associated with a higher value and good signal quality, and less consistent peak/trough amplitudes may be associated with a lower value and poor signal quality. The peak to trough interval consistency may comprise a consistency of timing between peaks and troughs, e.g., a timing between consecutive peaks, a timing between consecutive troughs, and/or a timing between a peak and a consecutive trough. In some examples, processing circuitry 80 may determine the peak to trough interval consistency by comparing peak to trough intervals in the signal over time. More consistent peak to trough intervals may be associated with a higher value and good signal quality, and less consistent peak to trough intervals may be associated with a lower value and poor signal quality.

[0107] In some examples, to select the one or more sensing and stimulation parameters, e.g., the stimulation amplitude, processing circuitry 80 may control therapy delivery circuitry 86 to titrate the stimulation amplitude until one or more features of the bioimpedance signal, e.g., an average dynamic range, a peak/trough consistency, and/or a peak to trough interval consistency, fall within one or more corresponding threshold windows. Processing circuitry 80 may compare an average dynamic range of a bioimpedance signal associated with a stimulation amplitude to an average dynamic range threshold window. The threshold window may be defined by an upper threshold and a lower threshold. The threshold window may be associated with a range of values at which the average dynamic range meets quality criterion and is also associated with power conservation.

[0108] Processing circuitry 80 may compare a peak/trough consistency of a bioimpedance signal associated with a stimulation amplitude to peak/trough consistency threshold window. The threshold window may be defined by an upper threshold and a lower threshold. The threshold window may be associated with a range of values at which the peak/trough consistency meets quality criterion and is also associated with power conservation.

[0109] Processing circuitry 80 may compare a peak to trough interval consistency of a bioimpedance signal associated with a stimulation amplitude to peak to trough interval consistency threshold window. The threshold window may be defined by an upper threshold and a lower threshold. The threshold window may be associated with a range of values at which the peak to trough interval consistency meets quality criterion and is also associated with power conservation.

[0110] In examples in which the one or more features include more than one feature, e.g., three features, the techniques of this disclosure may include making an adjustment to the stimulation amplitude in response to all of the features being indicative of the adjustment, e.g., increasing or decreasing. Alternatively, the techniques of this disclosure may include making the adjustment to the stimulation amplitude in response to a majority of the features, e.g., at least two of the three features, being indicative of the adjustment, e.g., increasing or decreasing. In some examples, the techniques may include weighting each of the one or more features. As an example, the dynamic range feature may be assigned a higher weight than the peak/trough consistency feature and the peak to trough interval consistency. Processing circuitry 80 may determine a score based on the weighted features. Based on a comparison of the score to one or more thresholds, e.g., a decrease amplitude threshold and an increase amplitude threshold, processing circuitry 80 may determine whether to increase stimulation amplitude, keep the stimulation amplitude, or decrease the stimulation amplitude.

[OHl] For each of the one or more features, processing circuitry 80 determines whether the feature value of the bioimpedance signal associated with the stimulation amplitude is greater than a corresponding lower threshold of a corresponding threshold window (1306). If the feature value is less than the lower threshold (“NO” of 1306), processing circuitry 80 determines whether the stimulation amplitude value is less than a maximum stimulation amplitude value associated with the range of stimulation amplitude values, e.g., 10 microamps (1308). If the stimulation amplitude is less than the maximum stimulation amplitude value (“YES” of 1308), processing circuitry 80 determines to control therapy delivery circuitry 86 to increase the stimulation amplitude (1310). In examples in which there is more than one feature, processing circuitry 80 may only increase the stimulation amplitude if a threshold number of the features are indicative of an increase in stimulation amplitude or if a weighted score associated with the features meets an increase stimulation threshold. Processing circuitry 80 then controls sensing circuitry 82 to measure a bioimpedance associated with the increased stimulation amplitude (1302). If the stimulation amplitude is not less than the maximum stimulation amplitude value, e.g., if the stimulation amplitude is equal to the maximum stimulation amplitude value (“NO” of 1308), processing circuitry 80 determines to keep the stimulation amplitude value (1312). In examples in which there is more than one feature, processing circuitry 80 may only keep the stimulation amplitude if a threshold number of the features are indicative of keeping the stimulation amplitude or if a weighted score associated with the features falls within a range defined by an increase stimulation window and a decrease stimulation window. In some examples, if the stimulation amplitude is set to the maximum stimulation amplitude value and the feature is greater than the lower threshold value, processing circuitry 80 may switch to sensing a different signal, switch to a different sensing configuration, and/or output an indication to a user.

[0112] If the feature value is greater than the lower threshold (“YES” of 1306), processing circuitry 80 determines whether the feature value is greater than a corresponding upper threshold of the corresponding threshold window (1314). If the feature value is less than the upper threshold (“NO” of 1314), processing circuitry 80 determines to keep the stimulation amplitude value (1312). In such examples, the feature value is within the threshold window. In examples in which there is more than one feature, processing circuitry 80 may only keep the stimulation amplitude if a threshold number of the features are indicative of keeping the stimulation amplitude or if a weighted score associated with the features falls within a range defined by an increase stimulation window and a decrease stimulation window.

[0113] If the feature value is greater than the upper threshold (“YES” of 1314), processing circuitry 80 determines whether the stimulation amplitude is greater than a minimum stimulation amplitude value associated with the range of stimulation amplitude values, e.g., 0.5 microamps (1316). If the stimulation amplitude is not greater than the minimum stimulation amplitude value, e.g., if the stimulation amplitude is equal to the minimum stimulation amplitude value (“NO” of 1316), processing circuitry 80 determines to keep the stimulation value (1312). In examples in which there is more than one feature, processing circuitry 80 may only keep the stimulation amplitude if a threshold number of the features are indicative of keeping the stimulation amplitude or if a weighted score associated with the features falls within a range defined by an increase stimulation window and a decrease stimulation window.

[0114] If the stimulation amplitude is greater than the minimum stimulation amplitude value (“YES” of 1316), processing circuitry 80 determines to control therapy delivery circuitry 86 to decrease the stimulation amplitude (1318). In examples in which there is more than one feature, processing circuitry 80 may only decrease the stimulation amplitude if a threshold number of the features are indicative of a decrease in stimulation amplitude or if a weighted score associated with the features meets a decrease stimulation threshold. Processing circuitry 80 then controls sensing circuitry 82 to measure a bioimpedance associated with the decreased stimulation amplitude (1302).

[0115] In some examples, processing circuitry 80 may apply a hysteresis to prevent frequent transitions associated with changes to stimulation amplitude from disrupting signal processing. In some examples, processing circuitry 80 may store a diagnostic value indicative of which stimulation amplitudes have been used and/or how often each stimulation amplitude has been used in memory 90. Based on the diagnostic value, processing circuitry 80 may estimate battery longevity. For example, if IMD 16 uses relatively high stimulation amplitude values, the battery longevity may be shorter than if IMD 16 uses relatively low stimulation amplitude values. In some examples, the diagnostic value may be pooled with diagnostic values for other patients. In some examples, the diagnostic values may be used for research. As an example, the diagnostic values may be used to determine initial stimulation values and/or default stimulation values based on patient type, e.g., patient disease state, patient comorbid conditions, patient age, patient sex, and/or patient ethnicity for use in future algorithms. For example, processing circuitry 80 may transmit the diagnostic value to external device 24 and/or a computing system (not depicted) to determine or adjust initial and/or default stimulation values for similar patients.

[0116] Although the example operation of FIG. 13 was described primarily with respect to adjusting stimulation amplitude, the techniques of this disclosure are not so limited. For example, processing circuitry 80 may implement the example operation of FIG. 13 to set a measurement frequency, e.g., between 16 Hertz and 32 Hertz or any other sensing and stimulation parameters.

[0117] Example 1. A device comprising: therapy delivery circuitry configured to deliver cardiac pacing pulses to a heart of a patient via a plurality of electrodes; sensing circuitry configured to sense a bioimpedance signal of a patient; and processing circuitry configured to: identify a beginning of a current inspiration phase of the patient based on the bioimpedance signal; and control the therapy delivery circuitry to adjust a rate of the cardiac pacing during the current inspiration phase based on the identification of the beginning of the current inspiration phase. [0118] Example 2. The device of example 1, wherein the processing circuitry is further configured to: identify, following the current inspiration phase, a beginning of a current expiration phase of the patient based on the bioimpedance signal; and based on the identification of the beginning of the current expiration phase, control the therapy delivery circuitry to either: decrease a rate of the cardiac pacing during the current expiration phase relative to a rate associated with the current inspiration phase; or stop providing cardiac pacing at the rate associated with current inspiration phase during the current expiration phase.

[0119] Example 3. The device of any one or more of examples 1-2, wherein the processing circuitry is further configured to: determine a patient activity level; and responsive to the patient activity level being below a threshold activity level, control sensing circuitry to switch to sensing an electrogram (EGM) signal of the patient to identify the beginning of the current inspiration phase.

[0100] Example 4. The device of any one or more of examples 1-3, wherein adjusting the rate of the cardiac pacing comprises causing the delivery of the cardiac pacing pulses to more closely mimic respiratory sinus arrhythmia (RSA).

[0101] Example 5. The device of any one or more of examples 2-4, wherein the processing circuitry is further configured to: determine a patient heart rate; determine the patient is not achieving RSA based on the patient heart rate and one or more of a prior inspiration phase or a prior expiration phase; and control the therapy delivery circuitry to adjust the rate of the cardiac pacing during one or more of the current inspiration phase or the current expiration phase based on the determination that the patient is not achieving RSA. [0102] Example 6. The device of any one or more of examples 1-5, wherein the processing circuitry is further configured to: during an initialization phase, receive the sensed bioimpedance signal; and determine at least one signal characteristic based on the sensed bioimpedance signal.

[0103] Example 7. The device of any one or more of examples 1-6, wherein the processing circuitry is further configured to: compare an average heart rate to a threshold; and control the therapy delivery circuitry to adjust the cardiac pacing pulses to mimic RSA responsive to the average heart rate falling below the threshold.

[0104] Example 8. The device of any one or more of examples 1-7, wherein the processing circuitry is configured to select one or more stimulation parameters for sensing the bioimpedance signal. [0105] Example 9. The device of example 8, wherein selecting one or more stimulation parameters comprises selecting a stimulation amplitude, and wherein to select the stimulation amplitude, the processing circuitry is configured to: control one or more of the plurality of electrodes to stimulate at a plurality of stimulation amplitudes; for each of the plurality of stimulation amplitudes, determine whether a corresponding bioimpedance signal meets one or more quality thresholds; and select the stimulation amplitude of the plurality of stimulation amplitudes responsive to the corresponding bioimpedance signal meeting the one or more quality thresholds.

[0106] Example 10. The device of example 9, wherein the processing circuitry is further configured to: determine a lowest stimulation amplitude with the corresponding bioimpedance signal meeting the one or more quality thresholds; and select the lowest stimulation amplitude with the corresponding bioimpedance signal meeting the one or more quality thresholds.

[0107] Example 11. The device of any of examples 1-10, wherein the processing circuitry is further configured to: determine a patient state; and control the therapy delivery circuitry to adjust the rate of the cardiac pacing pulses based on the patient state.

[0108] Example 12. The device of example 11, wherein the patient state comprises one or more of: a patient disease state; or a patient activity level.

[0109] Example 13. The device of any one or more of examples 2-12, wherein the processing circuitry is further configured to: predict a subsequent inspiration phase based on a prior inspiration phase; predict a subsequent expiration phase based on a prior expiration phase; and control the therapy delivery circuitry to deliver the cardiac pacing pulses to mimic respiratory sinus arrhythmia (RSA) during the subsequent inspiration phase and the subsequent expiration phase based on the prior inspiration phase and the prior expiration phase.

[0110] Example 14. The device of any one or more of examples 1-13, wherein the device comprises a pacemaker.

[0111] Example 15. A method comprising: sensing, by sensing circuitry of a medical device, a bioimpedance signal of a patient; identifying, by processing circuitry of the medical device, a beginning of a current inspiration phase of the patient based on the bioimpedance signal; and controlling, by the processing circuitry, therapy delivery circuitry of the medical device to adjust a rate of cardiac pacing during the current inspiration phase, wherein the therapy delivery circuitry is configured to deliver cardiac pacing pulses to a heart of a patient via a plurality of electrodes based on the identification of the beginning of the current inspiration phase.

[0112] Example 16. The method of example 15, further comprising: identifying, following the current inspiration phase, by the processing circuitry, a beginning of a current expiration phase of the patient based on the bioimpedance signal; and based on the identification of the beginning of the current expiration phase, controlling, by the processing circuitry, the therapy delivery circuitry to either: decrease a rate of the cardiac pacing during the current expiration phase relative to a rate associated with the current inspiration phase during the current expiration phase; or stop providing cardiac pacing at the rate associated with the current inspiration phase during the current expiration phase.

[0113] Example 17. The method of any one or more of examples 15-16, further comprising: determining, by the processing circuitry, a patient activity level; and controlling, by the processing circuitry, sensing circuitry to switch to sensing an electrogram (EGM) signal of the patient to identify the beginning of the current inspiration phase responsive to the patient activity level being below a threshold activity level.

[0114] Example 18. The method of any one or more of examples 15-17, wherein adjusting the rate of the cardiac pacing comprises causing the delivery of the cardiac pacing pulses to more closely mimic respiratory sinus arrhythmia (RSA).

[0115] Example 19. The method of any one or more of examples 16-18, further comprising: determining, by the processing circuitry a patient heart rate; determining, by the processing circuitry, the patient is not achieving RSA based on the patient heart rate and one or more of a prior inspiration phase or a prior expiration phase; and controlling, by the processing circuitry, the therapy delivery circuitry to adjust the rate of the cardiac pacing during one or more of the current inspiration phase or the current expiration phase based on the determination that the patient is not achieving RSA.

[0116] Example 20. The method of any one or more of examples 15-19, further comprising: during an initialization phase, sensing, by the sensing circuitry, the bioimpedance signal; and determining, by the processing circuitry, at least one signal characteristic based on the sensed bioimpedance signal.

[0117] Example 21. The method of any one or more of examples 15-20, further comprising: comparing, by the processing circuitry, an average heart rate to a threshold; and controlling, by the processing circuitry, the therapy delivery circuitry to adjust the cardiac pacing pulses to mimic RSA responsive to the average heart rate falling below the threshold. [0118] Example 22. The method of any one or more of examples 15-21, further comprising: selecting, by the processing circuitry, one or more stimulation parameters for sensing the bioimpedance signal.

[0119] Example 23. The method of example 22, wherein selecting one or more stimulation parameters comprises selecting a stimulation amplitude, wherein selecting the stimulation amplitude comprises: controlling, by the processing circuitry, one or more of the plurality of electrodes to stimulate at a plurality of stimulation amplitudes; for each of the plurality of stimulation amplitudes, determining, by the processing circuitry, whether a corresponding bioimpedance signal meets one or more quality thresholds; and selecting, by the processing circuitry, the stimulation amplitude of the plurality of stimulation amplitudes responsive to the corresponding bioimpedance signal meeting the one or more quality thresholds.

[0120] Example 24. The method of example 23, further comprising: determining, by the processing circuitry, a lowest stimulation amplitude with the corresponding bioimpedance signal meeting the one or more quality thresholds; and selecting, by the processing circuitry, the lowest stimulation amplitude with the corresponding bioimpedance signal meeting the one or more quality thresholds.

[0121] Example 25. The method of any of examples 15-24, further comprising: determining, by the processing circuitry, a patient state; and controlling, by the processing circuitry, the therapy delivery circuitry to adjust the rate of the cardiac pacing pulses based on the patient state.

[0122] Example 26. The method of example 25, wherein the patient state comprises one or more of: a patient disease state; or a patient activity level.

[0123] Example 27. The method of any one or more of examples 16-26, further comprising: predicting, by the processing circuitry, a subsequent inspiration phase based on a prior inspiration phase; predicting, by the processing circuitry, a subsequent expiration phase based on a prior expiration phase; and controlling, by the processing circuitry, the therapy delivery circuitry to deliver the cardiac pacing pulses to mimic respiratory sinus arrhythmia (RSA) during the subsequent inspiration phase and the subsequent expiration phase based on the prior inspiration phase and the prior expiration phase.

[0124] Example 28. The method of any one or more of examples 15-27, wherein the medical device comprises a pacemaker.

[0125] Example 29. A device comprising: therapy delivery circuitry configured to deliver cardiac pacing pulses to a heart of a patient via a plurality of electrodes; sensing circuitry configured to sense a bioimpedance signal of a patient; and processing circuitry configured to: identify a beginning of a current expiration phase of the patient based on the bioimpedance signal; and control the therapy delivery circuitry to adjust a rate of the cardiac pacing during a respiration cycle associated with the current expiration phase based on the identification of the beginning of the current expiration phase.

[0126] Example 30. The device of example 29, wherein the processing circuitry is further configured to: identify a beginning of a current inspiration phase of the patient based on the bioimpedance signal; and control the therapy delivery circuitry to increase the rate of the cardiac pacing during the current inspiration phase relative to a rate associated with the current expiration phase based on the identification of the beginning of the current inspiration phase.

[0127] Example 31. The device of any one or more of examples 29-30, wherein the processing circuitry is further configured to: determine a patient activity level; and control sensing circuitry to switch to sensing an electrogram (EGM) signal of the patient to identify the beginning of the current expiration phase responsive to the patient activity level being below a threshold activity level.

[0128] Example 32. The device of any one or more of examples 29-31, wherein adjusting the rate of the cardiac pacing comprises causing the delivery of the cardiac pacing pulses to more closely mimic respiratory sinus arrhythmia (RSA).

[0129] Example 33. The device of any one or more of examples 30-32, wherein the processing circuitry is further configured to: determine a patient heart rate; determine the patient is not achieving RSA based on the patient heart rate and one or more of a prior inspiration phase or a prior expiration phase; and control the therapy delivery circuitry to adjust the rate of the cardiac pacing during one or more of the current inspiration phase or the current expiration phase based on the determination that the patient is not achieving RSA.

[0130] Example 34. The device of any one or more of examples 29-33, wherein the processing circuitry is configured to: during an initialization phase, receive the sensed bioimpedance signal; and determine at least one signal characteristic based on the sensed bioimpedance signal.

[0131] Example 35. The device of any one or more of examples 29-34, wherein the processing circuitry is further configured to: compare an average heart rate to a threshold; and control the therapy delivery circuitry to adjust the cardiac pacing pulses to mimic RSA responsive to the average heart rate falling below the threshold. [0132] Example 36. The device of any one or more of examples 29-35, wherein the processing circuitry is configured to select one or more stimulation parameters for sensing the bioimpedance signal.

[0133] Example 37. The device of example 36, wherein to selecting one or more stimulation parameters comprises selecting a stimulation amplitude, and wherein to select the stimulation amplitude, the processing circuitry is configured to: control one or more of the plurality of electrodes to stimulate at a plurality of stimulation amplitudes; for each of the plurality of stimulation amplitudes, determine whether a corresponding bioimpedance signal meets one or more quality thresholds; and select the stimulation amplitude of the plurality of stimulation amplitudes responsive to the corresponding bioimpedance signal meeting the one or more quality thresholds.

[0134] Example 38. The device of example 37, wherein the processing circuitry is further configured to: determine a lowest stimulation amplitude with the corresponding bioimpedance signal meeting the one or more quality thresholds; and select the lowest stimulation amplitude with the corresponding bioimpedance signal meeting the one or more quality thresholds.

[0135] Example 39. The device of any of examples 29-38, wherein the processing circuitry is further configured to: determine a patient state; and based on the patient state, control the therapy delivery circuitry to adjust the rate of the cardiac pacing pulses.

[0136] Example 40. The device of example 39, wherein the patient state comprises one or more of: a patient disease state; or a patient activity level.

[0137] Example 41. The device of any one or more of examples 30-40, wherein the processing circuitry is further configured to: predict a subsequent inspiration phase based on a prior inspiration phase; predict a subsequent expiration phase based on a prior expiration phase; and control the therapy delivery circuitry to deliver the cardiac pacing pulses to mimic respiratory sinus arrhythmia (RSA) during the subsequent inspiration phase and the subsequent expiration phase based on the prior inspiration phase and the prior expiration phase.

[0138] Example 42. The device of any one or more of examples 29-41, wherein the device comprises a pacemaker.

[0139] Example 43. A method comprising: sensing, by sensing circuitry of a medical device, a bioimpedance signal of a patient; identifying, by processing circuitry of the medical device, a beginning of a current expiration phase of the patient based on the bioimpedance signal; and controlling, by the processing circuitry, therapy delivery circuitry of the medical device to adjust a rate of cardiac pacing during a respiration cycle associated with the current expiration phase, wherein the therapy delivery circuitry is configured to deliver cardiac pacing pulses to a heart of a patient via a plurality of electrodes based on the identification of the beginning of the current expiration phase.

[0140] Example 44. The method of example 43, further comprising: identifying, by the processing circuitry, a beginning of a current inspiration phase of the patient based on the bioimpedance signal; and controlling, by the processing circuitry, the therapy delivery circuitry to increase the rate of the cardiac pacing relative to a rate associated with expiration phase during the current inspiration phase based on the identification of the beginning of the current inspiration phase.

[0141] Example 45. The method of any one or more of examples 43-44, further comprising: determining, by the processing circuitry, a patient activity level; and controlling, by the processing circuitry, sensing circuitry to switch to sensing an electrogram (EGM) signal of the patient to identify the beginning of the current expiration phase responsive to the patient activity level being below a threshold activity level.

[0142] Example 46. The method of any one or more of examples 43-45, wherein adjusting the rate of the cardiac pacing comprises causing the delivery of the cardiac pacing pulses to more closely mimic respiratory sinus arrhythmia (RSA).

[0143] Example 47. The method of any one or more of examples 44-46, further comprising: determining, by the processing circuitry a patient heart rate; determining, by the processing circuitry, the patient is not achieving RSA based on the patient heart rate and one or more of a prior inspiration phase or a prior expiration phase; and controlling, by the processing circuitry, the therapy delivery circuitry to adjust the rate of the cardiac pacing during one or more of the current inspiration phase or the current expiration phase based on the determination that the patient is not achieving RSA.

[0144] Example 48. The method of any one or more of examples 43-47, further comprising: during an initialization phase, sensing, by the sensing circuitry, the bioimpedance signal; and determining, by the processing circuitry, at least one signal characteristic based on the sensed bioimpedance signal.

[0145] Example 49. The method of any one or more of examples 43-48, further comprising: comparing, by the processing circuitry, an average heart rate to a threshold; and controlling, by the processing circuitry, the therapy delivery circuitry to adjust the cardiac pacing pulses to mimic RSA responsive to the average heart rate falling below the threshold. [0146] Example 50. The method of any one or more of examples 43-49, further comprising: selecting, by the processing circuitry, one or more stimulation parameters for sensing the bioimpedance signal.

[0147] Example 51. The method of example 50, wherein selecting one or more stimulation parameters comprises selecting a stimulation amplitude, wherein selecting the stimulation amplitude comprises: controlling, by the processing circuitry, one or more of the plurality of electrodes to stimulate at a plurality of stimulation amplitudes; for each of the plurality of stimulation amplitudes, determining, by the processing circuitry, whether a corresponding bioimpedance signal meets one or more quality thresholds; and selecting, by the processing circuitry, a corresponding stimulation amplitude of the plurality of stimulation amplitudes responsive to the corresponding bioimpedance signal meeting the one or more quality thresholds.

[0148] Example 52. The method of example 51, further comprising: determining, by the processing circuitry, a lowest stimulation amplitude with the corresponding bioimpedance signal meeting the one or more quality thresholds; and selecting, by the processing circuitry, the lowest stimulation amplitude with the corresponding bioimpedance signal meeting the one or more quality thresholds.

[0149] Example 53. The method of any of examples 43-52, further comprising: determining, by the processing circuitry, a patient state; and controlling, by the processing circuitry, the therapy delivery circuitry to adjust the rate of the cardiac pacing pulses based on the patient state.

[0150] Example 54. The method of example 53, wherein the patient state comprises one or more of: a patient disease state; or a patient activity level.

[0151] Example 55. The method of any one or more of examples 44-54, further comprising: predicting, by the processing circuitry, a subsequent inspiration phase based on a prior inspiration phase; predicting, by the processing circuitry, a subsequent expiration phase based on a prior expiration phase; and controlling, by the processing circuitry, the therapy delivery circuitry to deliver the cardiac pacing pulses to mimic respiratory sinus arrhythmia (RSA) during the subsequent inspiration phase and the subsequent expiration phase based on the prior inspiration phase and the prior expiration phase.

[0152] Example 56. The method of any one or more of examples 43-55, wherein the medical device comprises a pacemaker.

[0153] Example 57. A non-transitory computer-readable medium storing instructions that when executed by processing circuitry, cause the processing circuitry to: identify a beginning of a current inspiration phase of a patient based on a bioimpedance signal; and control therapy delivery circuitry to adjust a rate of cardiac pacing during the current inspiration phase based on the identification of the beginning of the current inspiration phase.

[0154] Example 58. A non-transitory computer-readable medium storing instructions that when executed by processing circuitry, cause the processing circuitry to: identify a beginning of a current expiration phase of a patient based on a bioimpedance signal; and control therapy delivery circuitry to adjust a rate of cardiac pacing during a respiration cycle associated with the current expiration phase based on the identification of the beginning of the current expiration phase.

[0155] Various examples have been described. These and other examples are within the scope of the following claims.

Claims

WHAT IS CLAIMED IS:

1. A device comprising: therapy delivery circuitry configured to deliver cardiac pacing pulses to a heart of a patient via a plurality of electrodes; sensing circuitry configured to sense a bioimpedance signal of a patient; and processing circuitry configured to: identify a beginning of a current inspiration phase of the patient based on the bioimpedance signal; and control the therapy delivery circuitry to adjust a rate of the cardiac pacing pulses during the current inspiration phase based on the identification of the beginning of the current inspiration phase.

2. The device of claim 1, wherein the processing circuitry is further configured to: identify, following the current inspiration phase, a beginning of a current expiration phase of the patient based on the bioimpedance signal; and based on the identification of the beginning of the current expiration phase, control the therapy delivery circuitry to either: decrease the rate of the cardiac pacing pulses during the current expiration phase relative to a rate associated with the current inspiration phase; or stop providing the cardiac pacing pulses at the rate associated with the current inspiration phase during the current expiration phase.

3. The device of any one or more of claims 1-2, wherein the processing circuitry is further configured to: determine a patient activity level; and responsive to the patient activity level being below a threshold activity level, control sensing circuitry to switch to sensing an electrogram (EGM) signal of the patient to identify the beginning of the current inspiration phase.

4. The device of any one or more of claims 1-3, wherein adjusting the rate of the cardiac pacing pulses comprises causing the delivery of the cardiac pacing pulses to more closely mimic respiratory sinus arrhythmia (RSA).

5. The device of any one or more of claims 2-4, wherein the processing circuitry is further configured to: determine a patient heart rate; determine the patient is not achieving RSA based on the patient heart rate and one or more of a prior inspiration phase or a prior expiration phase; and control the therapy delivery circuitry to adjust the rate of the cardiac pacing pulses during one or more of the current inspiration phase or the current expiration phase based on the determination that the patient is not achieving RSA.

6. The device of any one or more of claims 1-5, wherein the processing circuitry is further configured to: during an initialization phase, receive the sensed bioimpedance signal; and determine at least one signal characteristic based on the sensed bioimpedance signal.

7. The device of any one or more of claims 1-6, wherein the processing circuitry is further configured to: compare an average heart rate to a threshold; and control the therapy delivery circuitry to adjust the cardiac pacing pulses to mimic RSA responsive to the average heart rate falling below the threshold.

8. The device of any one or more of claims 1-7, wherein the processing circuitry is configured to select one or more stimulation parameters for sensing the bioimpedance signal.

9. The device of claim 8, wherein selecting one or more stimulation parameters comprises selecting a stimulation amplitude, and wherein to select the stimulation amplitude, the processing circuitry is configured to: control one or more of the plurality of electrodes to stimulate at a plurality of stimulation amplitudes; for each of the plurality of stimulation amplitudes, determine whether a corresponding bioimpedance signal meets one or more quality thresholds; and select the stimulation amplitude of the plurality of stimulation amplitudes responsive to the corresponding bioimpedance signal meeting the one or more quality thresholds.

10. The device of claim 9, wherein the processing circuitry is further configured to: determine a lowest stimulation amplitude with the corresponding bioimpedance signal meeting the one or more quality thresholds; and select the lowest stimulation amplitude with the corresponding bioimpedance signal meeting the one or more quality thresholds.

11. The device of any of claims 1-10, wherein the processing circuitry is further configured to: determine a patient state; and control the therapy delivery circuitry to adjust the rate of the cardiac pacing pulses based on the patient state.

12. The device of claim 11, wherein the patient state comprises one or more of: a patient disease state; or a patient activity level.

13. The device of any one or more of claims 2-12, wherein the processing circuitry is further configured to: predict a subsequent inspiration phase based on a prior inspiration phase; predict a subsequent expiration phase based on a prior expiration phase; and control the therapy delivery circuitry to deliver the cardiac pacing pulses to mimic respiratory sinus arrhythmia (RSA) during the subsequent inspiration phase and the subsequent expiration phase based on the prior inspiration phase and the prior expiration phase.

14. The device of any one or more of claims 1-13, wherein the device comprises a pacemaker.

15. A non-transitory computer-readable medium storing instructions that when executed by processing circuitry, cause the processing circuitry to: identify a beginning of a current inspiration phase of a patient based on a bioimpedance signal; and control therapy delivery circuitry to adjust a rate of cardiac pacing pulses during the current inspiration phase based on the identification of the beginning of the current inspiration phase.