WO2025210428A1

WO2025210428A1 - Autonomic nervous stimulation for postural orthostatic tachycardia syndrome

Info

Publication number: WO2025210428A1
Application number: PCT/IB2025/052818
Authority: WO
Inventors: Victoria Ann SCHRIMPF; Alexander R. MATTSON; Lilian Kornet
Original assignee: Medtronic Inc
Current assignee: Medtronic Inc
Priority date: 2024-04-05
Filing date: 2025-03-18
Publication date: 2025-10-09
Anticipated expiration: 2026-10-05

Abstract

A medical device system includes a sensor circuit configured to sense an acceleration signal and a cardiac signal sensing circuit configured to sense at least one cardiac signal. The medical device system includes a control circuit configured to detect a spike from the acceleration signal that meets posture change motion criteria and detect a threshold increase in heart rate from the sensed cardiac signal. The medical device system includes a therapy delivery circuit configured to deliver autonomic nervous stimulation (ANS) for decreasing the heart rate in response to the control circuit detecting the spike and the threshold increase in heart rate.

Description

AUTONOMIC NERVOUS STIMULATION FOR POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63/575,605, filed April 5, 2024, the entire content of which is incorporated herein by reference.

TECHNICAL FIELD

[0002] The disclosure relates generally to a medical device and method for delivering electrical stimulation for altering the parasympathetic tone.

BACKGROUND

[0003] Medical devices may sense electrophysiological signals from the heart, brain, nerve, muscle or other tissue. Such devices may be implantable, wearable or external devices using implantable and/or surface (skin) electrodes for sensing the electrophysiological signals. In some cases, such devices may be configured to deliver a therapy based on the sensed electrophysiological signals. For example, implantable or external cardiac pacemakers, cardioverter defibrillators, cardiac monitors and the like, sense cardiac electrical signals from a patient’s heart. The medical device may sense cardiac electrical signals from the heart and deliver electrical stimulation therapies, such as cardiac pacing pulses and/or cardioversion or defibrillation (CV/DF) shocks, to the heart using electrodes, which may be carried by medical electrical leads extending from the medical device to position electrodes within or near the patient’s heart.

[0004] A cardiac pacemaker or cardioverter defibrillator may deliver therapeutic electrical stimulation to the heart via electrodes carried by one or more medical electrical leads coupled to the medical device. Cardiac signals sensed from the heart may be analyzed for detecting an abnormal rhythm. Upon detection of an abnormal rhythm, such as bradycardia, tachycardia or fibrillation, an appropriate electrical stimulation pulse or pulses may be delivered to restore or maintain a more normal rhythm of the heart. For example, an implantable cardioverter defibrillator (ICD) may deliver bradycardia pacing pulses to the heart of the patient in the absence of sensed intrinsic myocardial depolarization signals, e.g., R-waves, deliver anti-tachycardia pacing pulses in response to detecting tachycardia, or deliver CV/DF shocks to the heart upon detecting tachycardia or fibrillation.

[0005] In patients having intact intrinsic atrioventricular (AV) conduction atrial depolarizations occurring during an atrial tachyarrhythmia can be conducted to the ventricles at a fast and/or irregular rate, which can be symptomatic. Patients, some having an otherwise normal heart rhythm, can experience postural orthostatic tachycardia syndrome (POTS) when atrial tachycardia is triggered in response to a postural change, e.g., when standing up. POTS symptoms can include dizziness, fainting, chest pain, and shortness of breath. POTS can severely disrupt daily living and may or may not improve on its own.

SUMMARY

[0006] In general, the disclosure is directed to a medical device and techniques for controlling and delivering autonomic nervous stimulation (ANS) therapy for preventing or reducing the likelihood of POTS or symptoms associated with POTS. The medical device may be configured to sense cardiac electrical signals, patient posture and patient physical activity. In response to detecting an acceleration signal indicative of patient body motion during a posture change, the medical device may deliver ANS therapy to reduce the likelihood of the patient experiencing POTS or at least alleviating POTS symptoms. In some examples, the medical device may determine that the posture change is accompanied by a patient activity level that is less than a threshold level and that the heart rate increases by at least threshold change and/or to a rate that is greater than a threshold rate.

[0007] In one example, the disclosure provides a medical device system including a sensor circuit configured to sense an acceleration signal, a cardiac signal sensing circuit configured to sense a cardiac signal, and a memory configured to store posture change motion criteria. The medical device system further comprising a control circuit configured to detect a signal spike from the acceleration signal that meets the posture change motion criteria, detect a first heart rate from the cardiac signal sensed by the cardiac signal sensing circuit after the signal spike is detected and detect an increased heart rate based on the first heart rate. The medical device system further comprising a therapy delivery circuit configured to deliver autonomic nervous stimulation (ANS) for decreasing the first heart rate in response to the control circuit detecting the spike and the increased heart rate. [0008] In another example, the disclosure provides a method including sensing an acceleration signal, sensing a cardiac signal, storing posture change motion criteria in a medical device memory and detecting a signal spike from the acceleration signal that meets the posture change motion criteria. The method further including detecting a first heart rate from the cardiac signal sensed after the signal spike is detected, detecting an increased heart rate based on the first heart rate and in response to detecting the spike and the increased heart rate, delivering ANS for decreasing the first heart rate.

[0009] In yet another example, the disclosure provides a non-transitory computer readable medium storing posture change motion criteria and a set of instructions which, when executed by control circuitry of a medical device system, cause the medical device system to sense an acceleration signal, sense a cardiac signal and store in a medical device memory, detect a signal spike from the acceleration signal that meets the posture change motion criteria, detect a first heart rate from the cardiac signal sensed after the signal spike is detect and detect an increased heart rate based on the first heart rate. The instructions further causing the medical device system to, in response to detecting the spike and the increased heart rate, deliver ANS for decreasing the first heart rate.

[0010] 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

[0011] FIG. l is a conceptual diagram of a medical device system configured to sense patient signals and deliver ANS therapy according to some examples.

[0012] FIG. 2 is a conceptual diagram of an IMD for sensing patient signals and delivering ANS according to some examples.

[0013] FIG. 3 is a conceptual diagram illustrating a medical device system that may be configured to sense patient signals and delivery ANS therapy according to yet another example. [0014] FIG. 4 is a conceptual diagram of an IMD configured to sense cardiac signals, sense acceleration signals, and deliver ANS according to some examples.

[0015] FIG. 5 is a flow chart of a method for controlling ANS therapy by a medical device system according to some examples.

[0016] FIG. 6 is a flow chart of a method for controlling ANS therapy by a medical device system according to another example.

[0017] FIG. 7 is a diagram of example accelerometer axis signals that may be sensed by sensor circuit of an IMD configured to deliver ANS therapy.

[0018] FIG. 8 is a diagram of a timeline of ANS therapy trigger conditions and ANS delivery according to some examples.

[0019] FIG. 9 is a diagram of a timeline of ANS trigger conditions and ANS delivery according to another example.

[0020] FIG. 10 is a diagram of different ramp down rates that may be applied to an ANS delivery control parameter for gradually terminating ANS therapy in response to detecting an ANS termination condition.

[0021] FIG. 11 is a timing diagram of ANS pulse trains that may be delivered by an IMD according to some examples.

[0022] FIG. 12 is a flow chart of a method performed by a medical device system for controlling ANS therapy according to another example.

DETAILED DESCRIPTION

[0023] In general, this disclosure describes a medical device and techniques for delivering ANS. ANS delivered by a medical device as disclosed herein is electrical stimulation delivered to an area of the autonomic nervous system to increase parasympathetic tone. Activation of the parasympathetic nervous system, or increased parasympathetic tone, acts to put the body in a resting or relaxation state and is associated with a slow heart rate, slow respiration rate and lower blood pressure. Activation of the sympathetic nervous system, or increased sympathetic tone, acts to put the body in an alert state and is associated with an increased heart rate, increased respiration rate and increased blood pressure. The sympathetic nervous system is triggered by stress and is associated with the “flight or fright” response. By increasing the parasympathetic tone, a fast heart rate during an episode of POTS can be slowed to reduce or prevent symptoms associated with POTS. [0024] ANS for increasing the parasympathetic tone to reduce heart rate can be delivered to the right or left vagus nerve or branches thereof innervating the SA node, atrial myocardium, and/or the AV node. ANS can be delivered at an epicardial site, endocardial site, SA node, AV nodal fat pad, or within the myocardium (e.g., by electrode advanced into the myocardium from an epicardial or endocardial approach), as examples, or any other operative location that results increased parasympathetic tone and decreased heart rate, which can be a decreased atrial rate and/or a decreased ventricular rate.

[0025] FIG. 1 is a conceptual diagram of a medical device system 10 including an implantable medical device (IMD) 14 coupled to transvenous electrical leads 16 and 18. IMD 14 may be configured to deliver electrical stimulation pulses and sense cardiac electrical signals in the right atrium (RA), the right ventricle (RV) and/or the left ventricle (LV). IMD housing 15 encloses internal circuitry corresponding to the various circuits and components described in conjunction with FIG. 4 below, for performing the functionality of IMD 14 as disclosed herein, including delivering ANS.

[0026] IMD housing 15 may form a hermetic seal that protects internal components of IMD 14. Housing 15 may be formed of a conductive material, such as titanium or titanium alloy. Housing 15 may function as an electrode (sometimes referred to as a “can” electrode). Housing 15 may be used as an active can electrode for use in delivering high voltage CV/DF shock pulses to heart 8 for terminating a tachyarrhythmia, e.g., ventricular tachycardia or fibrillation. In other examples, housing 15 may be available for use in delivering unipolar, relatively lower voltage cardiac pacing pulses and/or for sensing cardiac electrical signals in combination with electrodes carried by a lead coupled to IMD 14. In other instances, the housing 15 of IMD 14 may include multiple electrodes on an outer portion of the housing. The outer portion(s) of the housing 15 functioning as an electrode(s) may be coated with a material, such as titanium nitride, e.g., for reducing post-stimulation polarization artifact.

[0027] IMD 14 includes a connector assembly (or “connector block”) 17 that includes insulated electrical feedthroughs crossing housing 15 to provide electrical connections between conductors (not shown in FIG. 1) extending within the leads 16 and 18 to the electronic components enclosed by housing 15. An antenna (not shown in FIG. 1) may be carried in connector assembly 17 for coupling RF signals transmitted to/from an external device 50 to a telemetry circuit enclosed by housing 15. As described below, housing 15 may enclose one or more processing circuits, memories, transceivers, cardiac electrical signal sensing circuitry, therapy delivery circuitry, power sources and other components for sensing cardiac electrical signals, processing and analyzing sensed cardiac electrical signals, and delivering electrical stimulation pulses to the patient’s heart 8 as needed. [0028] In the example shown, connector assembly 17 is configured to receive a proximal lead connector 40 and 42 of each of RA lead 16 and RV lead 18, respectively. Each lead 16 and 18 can be advanced transvenously for positioning electrodes for sensing and stimulation in the atria or ventricles of heart 8. The proximal portion of each lead 16 and 18 may be configured as an industry standard or custom lead connector 40 and 42, respectively. Connector assembly 17 includes connector bores that are appropriately sized for receiving the proximal portion of each lead 16 and 18, e.g., lead connectors 40 and 42. Each connector bore includes electrical contacts that become aligned with and physically mate with a corresponding electrical contact of the respective lead connector 40 or 42 providing physical and electrical connection of leads 16 and 18 with IMD 14.

[0029] RA lead 16 includes an elongated lead body 41, proximal lead connector 40 and distal electrodes 20 and 22 in the example shown. RA lead 16 is equipped with pacing and sensing electrodes 20 and 22, shown as a tip electrode 20 and a ring electrode 22 spaced proximally from tip electrode 20 along RA lead body 41. The electrodes 20 and 22 are each connected to a respective insulated conductor extending within the elongated body 41. Each insulated conductor is coupled at its proximal end to an electrical connector of the proximal lead connector 40, which becomes electrically connected to internal IMD circuitry via respective electrical feedthroughs in IMD connector assembly 17. Tip electrode 20 may be used as a cathode electrode with ring electrode 22 serving as an anode electrode for delivering bipolar electrical stimulation pulses.

[0030] RA lead 16 may be advanced transvenously for positioning its distal end, carrying electrodes 20 and 22, into the RA for delivering ANS, sensing atrial signals and delivering atrial pacing pulses. Tip electrode 20 may be positioned along the inferior portion of the superior vena cava for delivering ANS in the area of the superior right atrial ganglion plexus or the SA node. Tip electrode 20 may be implanted in the area of the cardiac nerve plexus, e.g., along the posterior wall of the RA, adjacent to the coronary sinus ostium 9. In other examples, the distal portion of RA lead 16 carrying tip electrode 20 and ring electrode 22 may be advanced in the right brachiocephalic vein for delivering ANS to the vagal plexus. In some examples, tip electrode 20 may be positioned along an inferior portion of the posterior RA endocardial wall, adjacent the coronary sinus ostium 9, to provide ANS for increasing parasympathetic tone according to the techniques described herein.

[0031] In addition to delivering ANS, tip electrode 20 and ring electrode 22 may be used for delivering bipolar atrial pacing pulses for pacing the RAby capturing the atrial myocardial tissue. Unipolar atrial pacing pulses may be delivered by one of electrodes 20 or 22 and IMD housing 15 in some examples. In other examples, RA lead 16 may include more than two electrodes to provide two or more pairs of electrodes positioned at locations along the RA lead body 43 to facilitate delivering ANS at a desired ANS delivery site, delivering atrial pacing at a desired pacing site which may be the same or different than the ANS delivery site, and for sensing atrial signals.

[0032] RV lead 18 includes an elongated lead body 43 having a proximal connector 42 at its proximal end for coupling lead 18 to IMD connector assembly 17 and electrodes 24, 26, 28 and 30 carried along a distal portion of lead body 43. RV lead 18 may be advanced transvenously through the RA and into the RV to position electrodes 24, 28 and 30 in the RV. RV lead 18 is shown carrying a distal tip electrode 28 and ring electrode 30 spaced proximally from tip electrode 28 for bipolar sensing of cardiac electrical signals in the RV and delivering ventricular pacing pulses. Tip electrode 28 may be used as a cathode electrode for pacing and sensing with ring electrode 30 serving as an anode electrode for delivering bipolar ventricular pacing pulses. In other examples, tip electrode 28 may be paired with IMD housing 15 or one of coil electrodes 24 or 26 for delivering ventricular pacing pulses.

[0033] RV lead tip electrode 28 is shown implanted in the RV apex for delivering ventricular myocardial pacing. It is to be understood, however, that the RV lead electrode locations are illustrative in nature and not intended to be limiting. For example, RV lead tip electrode 28 may be implanted in the interventricular septum to deliver septal pacing, which may include delivering ventricular pacing to an inferior portion of the His bundle, or in the area of the left bundle branch and/or right bundle branch to deliver ventricular pacing pulses via at least a portion of the native conduction system of heart 8.

[0034] RV lead 18 is shown carrying an RV coil electrode 24 spaced proximally from ring electrode 30 and a superior vena cava (SVC) coil electrode 26 spaced proximally from RV coil electrode 24. SVC coil electrode 26 may be carried along the length of RV lead body 43 such that it is positioned at least partially within the RA and/or SVC when the distal end of RV lead 18 is advanced within the RV. Coil electrodes 24 and 26 are elongated electrodes having a relatively high surface area compared to electrodes 20, 22, 28 and 30. Coil electrodes 24 and 26 may have a surface area ranging from 50 to 100 times greater than the surface area of electrodes 20, 22, 28 and 30, for example. For the sake of convenience, electrodes 24 and 26 are referred to herein as “coil electrodes” because they may take the form of a coiled electrode, which may include a single wire or filar or multiple wires or filars (e.g., a braided multi-filar wire, a stranded multi-filar wire, etc.) that winds helically around a longitudinal portion of lead body 43 to provide a relatively high surface area electrode for delivering high voltage CV/DF shocks. Electrodes 24 and 26 may be configured as other types of high surface area electrodes that can be used for delivering CV/DF shocks, which may include ribbon electrodes, plate electrodes, serpentine electrodes, zig-zagging electrodes, segmented electrodes or other types of physical electrode configurations that provide a relatively large surface area and low impedance that do not necessarily include a coiled wire. In other examples, IMD 14 may not be configured to deliver high voltage CV/DF shocks in which case coil electrodes 24 and 26 are optional and may not be included on RV lead 18.

[0035] Each of electrodes 24, 26, 28 and 30 carried by RV lead body 43 are connected to a respective insulated conductor extending within lead body 43 of RV lead 18. Lead body 43 may be a multi-lumen lead body in some examples to accommodate multiple, insulated conductors. The proximal ends of the insulated conductors are coupled to corresponding electrical connectors (not illustrated in FIG. 1) of proximal lead connector 42 for providing electrical connection to IMD 14 via electrical feedthroughs in connector assembly 17.

[0036] The RV lead tip electrode 28 and the RA lead tip electrode 20 can be active fixation electrodes providing fixation of the distal ends of leads 18 and 16, respectively, at an implant site in addition to providing cardiac electrical signal sensing and cardiac pacing functionality. In FIG. 1, RAtip electrode 20 (which can be used in delivering atrial pacing and ANS) and RV tip electrode 28 (for delivering ventricular pacing) are each shown as a helical, screw-in electrode that can be rotatably advanced into cardiac tissue to provide lead fixation. In other examples, tip electrode 20 and/or tip electrode 28 may be configured as fishhook electrodes, hemispherical electrodes, button electrodes or other types of electrodes. When the tip electrode 20 or 28 of the medical lead 16 or 18 does not provide fixation of the distal end of the elongated lead body, the respective RA lead 16 or RV lead 18 may be equipped with other fixation mechanisms, such as tines or hooks, that may engage with cardiac tissue at an implant site for promoting stable fixation of the tip electrodes 20 and 28 at a desired therapy delivery site.

[0037] The proximal ring electrode 22 of RA lead 16 and the proximal ring electrode 30 of RV lead 18 may each be ring electrodes that fully or partially circumscribe the respective lead body 41 or 43. In various examples, the relatively low surface area pace/sense electrodes 20, 22, 28 and 30 may be implemented as ring electrodes, short coil electrodes, button electrodes, hemispherical electrodes, directional electrodes, segmented electrodes, helical electrodes, fishhook electrodes, or other shaped electrode and are not limited to being exclusively ring electrodes and helical screw-in electrodes as shown here.

[0038] RA lead electrodes 20 and 22 and RV lead electrodes 28 and 30 are relatively small surface area electrodes which are available for use in sensing cardiac electrical signals and may be used in for delivering relatively low voltage cardiac pacing pulses, ANS, antitachycardia pacing (ATP) therapy or other therapeutic cardiac pacing pulses. Electrodes 20, 22, 28 and 30 are sometimes referred to as “pace/sense electrodes” because they are generally configured for use in low voltage applications, e.g., used as either a cathode or anode for delivery of pacing pulses and/or sensing of cardiac electrical signals, as opposed to delivering high voltage CV/DF shocks.

[0039] Electrodes 20, 22, 24, 26, 28, and 30 may be formed from titanium, platinum, iridium or alloys thereof, as examples with no limitation intended, and may include a low polarizing coating, such as titanium nitride, iridium oxide, ruthenium oxide, platinum black, among others. Lead bodies 41 and 43 may each be formed from a non-conductive material, including silicone, polyurethane, fluoropolymers, mixtures thereof, and/or other appropriate materials. Each lead body may be shaped to form one or more lumens within which one or more insulated electrical conductors extend between the electrical connectors of the proximal lead connectors 40 and 42 and the respective electrodes carried by the lead body. The lead bodies 41 and 43 may be generally tubular or cylindrical in shape but may have a flattened or ribbon shape in some examples. Lead bodies 41 and 43 may have a pre-formed shape such as a curve or bend, which may be along a distal portion of the lead body, to facilitate guidance and implantation of the lead body distal end at a targeted implant site. In other examples, the lead bodies 41 and 43 may be elongated flexible bodies without any preformed shapes or curves.

[0040] It is to be understood that although IMD 14 is described as a dual chamber device capable of sensing and electrical stimulation therapy delivery in the RA and RV, in other examples, IMD 14 may be a multi-chamber device, e.g., coupled to a third lead that can be advanced in the coronary sinus ostium 9 into a cardiac vein for sensing and pacing the left ventricle (LV). In still other examples, IMD 14 may be coupled only to RA lead 16. Ventricular pacing capabilities, however, may be desired in a medical device system configured to deliver ANS in order to avoid ventricular bradycardia during ANS and/or to provide rate response pacing if patient activity increases during ANS.

[0041] An external device 50 is shown in telemetric communication with IMD 14 by a wireless communication link 51 in FIG. 1. External device 50 may be embodied as a programmer used in a hospital, clinic or physician’s office to retrieve data from IMD 14 and to program operating parameters and algorithms in IMD 14 for controlling IMD functions. External device 50 may alternatively be embodied as a home monitor or handheld device for retrieving data from IMD 14. External device 50 may be used to program cardiac signal sensing parameters, cardiac rhythm detection parameters, therapy delivery control parameters including ANS control parameters and other operating and control parameters used by IMD 14.

[0042] External device 50 may include a processor 52, memory 53, display unit 54, user interface 56 and telemetry unit 58. Processor 52 executes instructions stored in memory 53. Processor 52 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, processor 52 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 processor 52 herein may be embodied as software, firmware, hardware or any combination thereof.

[0043] Memory 53 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. Memory 53 may be configured to store instructions executed by processor 52 for obtaining data received from IMD 14 and for generating a GUI on display unit 54 according to the techniques disclosed herein. Memory 53 may store various operating parameter settings of IMD 14 that may be used in generating various GUI windows, menus, reports, etc. by processor 52.

[0044] Display unit 54 may generate a display of cardiac electrical signals, programmed operating settings of IMD 14 and other device and patient related data received from processor 52 (which may be received from IMD 14 via telemetry unit 58. Display unit 54 may be configured to generate a GUI including various windows, icons, user selectable menus, etc. to facilitate interaction by a user with the external device 50, e.g., for programming ANS control parameters described herein. Display unit 54 may function as an input and/or output device using technologies including liquid crystal displays (LCD), quantum dot display, dot matrix displays, light emitting diode (LED) displays, organic light-emitting diode (OLED) displays, cathode ray tube displays, e-ink, or monochrome, color, or any other type of display capable of generating tactile, audio, and/or visual output. In some examples, display unit 54 is a presence-sensitive display that may serve as a user interface device that operates both as one or more input devices and one or more output devices.

[0045] User interface unit 56 may include a mouse, touch screen, keypad or the like to enable a user to interact with external device 50, e.g., to initiate and terminate an interrogation session for retrieving data from IMD 14, adjust settings of display unit 54, enter programming commands or selections or make other user requests. Telemetry unit 58 includes a transceiver and antenna configured for bidirectional communication with a telemetry circuit included in an IMD 14, e.g., in response to user requests.

[0046] Telemetry unit 58 is configured to operate in conjunction with processor 52 for sending and receiving data relating to IMD functions via a wireless communication link 51 with IMD 14. Communication link 51 may be established using a radio frequency (RF) link such as BLUETOOTH®, Wi-Fi, Medical Implant Communication Service (MICS) or other communication bandwidth. In some examples, external device 50 may include a programming head that is placed proximate IMD 14 to establish and maintain a communication link 51, and in other examples external device 50 and IMD 14 may be configured to communicate using a distance telemetry algorithm and circuitry that does not require the use of a programming head and does not require user intervention to maintain a communication link.

[0047] It is contemplated that external device 50 may be in wired or wireless connection to a communications network via telemetry circuit 58 that includes a transceiver and antenna or via a hardwired communication line for transferring data to a centralized database or computer to allow remote management of the patient. One example of a remote patient management system is the CARELINK® Network (Medtronic, Inc. Minneapolis, MN). Review of operating parameter settings and other data collected from IMD 14 may be performed remotely by a clinician who may authorize programming of operating parameters in IMD 14, e.g., after viewing reports and cardiac electrical signals and other device related data, such as marker channel data, therapy delivery history, IMD generated alerts or the like.

[0048] In some examples, external device 50 may be a handheld device or home monitor that can be used by a patient or caregiver to enter a POTS confirmation signal via user interface 56 when the patient experiences a POTS episode, e.g., during or after experiencing POTS symptoms. The POTS confirmation signal can be transmitted to IMD 14. IMD 14 may respond to the POTS confirmation signal by triggering delivery of ANS therapy in some instances. In some examples, receipt of a POTS confirmation signal from external device 50 may cause IMD 14 to deliver ANS when at least one other ANS trigger condition is met, as further described below.

[0049] Ahistory of POTS episodes and delivered ANS therapies may be logged in memory of IMD 14 and/or memory 53 of external device 50. The history of POTS episodes, which may be confirmed by a user-entered signal, with associated patient activity data, heart rate data, and/or posture change data may enable a clinician to tailor ANS control parameter programming in IMD 14 according to patient need. For example, as further described below, IMD 14 may include an accelerometer for sensing acceleration signals for detection a patient body posture change and for determining activity metrics correlated to the level of patient activity. IMD 14 may detect trigger conditions for initiating ANS therapy from the acceleration signals and from cardiac signals sensed by IMD 14. Various thresholds or other parameters used by IMD 14 for detecting ANS therapy trigger conditions can be programmed into IMD 14 using external device 50 or another device programmer, which can be based on the history of POTS episodes and delivered ANS therapies in some examples. ANS delivery control parameters may be programmed using external device 50 or another programming device and may be adjusted when the patient or other caregiver confirms a POTS episode if ANS is not effective in reducing or preventing the POTS symptoms.

[0050] FIG. 2 is a conceptual diagram of an IMD 114 for sensing cardiac signals and delivering ANS according to some examples. In this example, a leadless IMD 114 is implanted in the RA for providing ANS and ventricular pacing from an atrial location. IMD 114 may be a transcatheter device that can be delivered to the RA via a catheter or other delivery device for being wholly implanted within the RA. In some examples, IMD 114 may be positioned for delivering ventricular pacing pulses via the heart’s native conduction system and/or ventricular myocardium from a right atrial approach. The distal end 102 of IMD 114 may be positioned at the inferior end of the interatrial septum, beneath the AV node and near the tricuspid valve annulus to position tip electrode 128 for advancement into the interatrial septum toward the His bundle of the native His-Purkinje conduction system. Ring electrode 130, spaced proximally from tip electrode 128, may be used as the return electrode with the cathode tip electrode 128 for pacing the right and left ventricles via the His-Purkinje system and/or ventricular myocardium. Tip electrode 128 may be positioned to capture at least a portion of the His bundle and/or ventricular myocardium for delivering ventricular pacing from an atrial implant location of IMD 114. [0051] IMD 114 may be capable of dual chamber sensing and pacing in some examples. For instance, a distal ring electrode 120 may be included on pacemaker housing 115 and can be used in combination with the proximal ring electrode 130 for sensing atrial P- waves and, in some examples, delivering atrial pacing pulses. Distal ring electrode 120 may be referred to as an “atrial electrode” in some examples because it can be used for atrial sensing and pacing when IMD 114 is implanted in the atrium. Distal ring electrode 120, however, may additionally or alternatively be used in delivering ANS in some examples. In other examples, one or more electrodes on or extending from distal end 102 of IMD 114 may be provided for delivering ANS in accordance with the techniques disclosed herein. Examples of various pacing electrode arrangements and medical device configurations for providing ventricular pacing along the native conduction system of the heart, which may be combined with the ANS techniques disclosed herein, are generally disclosed in U.S. Publication No. 2021/0228892 (Kornet, et al., filed January 25, 2021), U.S. Patent No. 11,426,578, (Yang, et al., filed September 13, 2018) and U.S. Patent No. 11,007,369 (Sheldon, et al., filed November 8, 2018), the entire content of all of which incorporated herein by reference.

[0052] In the example of FIG. 2, the cathode tip electrode 128 is shown as a screw-in helical electrode which may provide fixation of IMD 114 at an implant site as well as serving as a pacing and sensing electrode. In other examples, tip electrode 128 may be other types of electrodes that may or may not provide fixation of IMD 114 at the implant site. Other fixation members, such as tines, hooks, barbs or the like may be provided along distal end 102 for providing fixation of IMD 114 at an implant site that enables ANS therapy delivery and ventricular pacing to be delivered. IMD 114 may include one or more ring electrodes (e.g., ring electrodes 120 and 130) circumscribing the housing 115. In other examples, IMD 114 may include other types of electrodes such as hook electrodes, button electrodes, hemispherical electrodes, segmented electrodes or other types of electrodes arranged along housing 115 for providing at least cardiac electrical signal sensing, ventricular pacing, and ANS.

[0053] FIG. 3 is a conceptual diagram illustrating an IMD system 110 that may be used to sense cardiac electrical signals, deliver ANS and deliver ventricular pacing according to another example. IMD system 110 is a multi-device system including IMD 114’ implanted within the RA and an IMD 116 implanted in the RV. IMD 114’ can provide atrial signal sensing, atrial pacing and ANS. IMD 116 can provide ventricular signal sensing and ventricular pacing.

[0054] In some examples, IMD 114’ and IMD 116 are transcatheter leadless pacemakers that can be implanted wholly within a heart chamber. IMDs 114’ and 116 may be reduced in size compared to subcutaneously implanted pacemakers and may be generally cylindrical in shape to enable transvenous implantation via a delivery catheter.

[0055] IMD 114’ may be wholly implanted within the right atrium (RA) and may be implanted along the posterior wall of the RA, adjacent the coronary sinus 9, in operative proximity to the cardiac nerve plexus and AV node for delivering ANS. IMD 114’ may include a distal tip electrode 120’ for delivering atrial pacing pulses, delivering ANS, and for sensing atrial electrical signals. IMD 114’ may include least one proximal electrode 122, which may be a ring electrode circumscribing housing 115, to be used in a sensing and therapy delivery electrode vector in combination with electrode 120’ for delivering atrial pacing pulses, ANS, and for sensing atrial electrical signals. In some examples, IMD 114’ may be implanted at an epicardial location, outside of the heart 8, e.g., with distal tip electrode 120’ implanted in the posterior RA and/or in the atrial septum in an operative location for delivering the ANS therapy, e.g., targeting a vagal branch innervating the SA or AV node.

[0056] IMD 116 may be wholly implanted within the right ventricle (RV) as shown or implanted on a ventricular chamber, e.g., at an epicardial location. Ventricular pacemaker 116 may positioned along the interventricular septum as shown for delivering ventricular pacing pulses to a portion of the native conduction system, e.g., in the area of the right bundle branch, left bundle branch, or an inferior portion of the His Bundle. Other operative locations for IMD 116 are possible, such as near the RV apex.

[0057] IMD 116 may include a distal tip electrode 128 and a proximal ring electrode 130 carried on the housing of IMD 116 for sensing ventricular electrical signals and delivering ventricular pacing pulses. Note that this ventricular pacing and sensing electrode pair 128 and 130 were previously shown in FIG. 2 as being carried by IMD 114 positioned for sensing ventricular electrical signals and delivering ventricular pacing pulses from a RA location via the ventricular sensing and pacing electrodes 128 and 130. The ventricular pacing pulses may be delivered by electrodes 128 and 130 for capturing the ventricular myocardium, a portion of the native conduction system or both.

[0058] As generally described herein, an IMD system 110 may include cardiac electrical signal sensing circuitry. For example, IMD 114’ may include atrial electrical signal sensing circuitry configured to sense atrial P-waves (via electrodes 120’ and 122) attendant to the depolarizations of the atrial myocardium. IMD 116 may include ventricular electrical signal sensing circuitry configured to sense ventricular R-waves (via electrodes 128 and 130) attendant to the depolarizations of the ventricular myocardium.

[0059] The IMD system 110 may further include therapy delivery circuitry configured to deliver ANS and cardiac pacing pulses. For example, IMD 114’ may include therapy delivery circuitry configured to generate and deliver atrial pacing pulses via electrodes 120’ and 122 in the absence of sensed intrinsic atrial P-waves. The therapy delivery circuitry of IMD 114’ may be further configured to generate ANS for suppressing the atrial rate to avoid or alleviate POTS. IMD 116 may include therapy delivery circuitry configured to deliver ventricular pacing pulses in the absence of sensed intrinsic ventricular R-waves.

[0060] IMD 114’ and/or IMD 116 may include one or more fixation members, e.g., fixation tines, a fixation helix, or other fixation members for engaging with cardiac tissue at a respective implant site. In the example shown, IMD 114’ is provided with a distal tip electrode 120’ in the form of a button or hemispherical electrode. IMD 114’ may have fixation member 113 including one or more tines configured to engage with cardiac tissue at the implant site. In the example shown, IMD 116 is provided with a distal tip electrode 128 that is a helical electrode that can provide fixation of IMD 116 at the implant site. It is recognized that IMD 114’ and IMD 116 may be provided with other types of electrodes and/or fixation members than the example shown in FIG. 3, e.g., any of the example electrodes or fixation members listed herein.

[0061] IMDs 114’ and 116 of medical device system 110 may be capable of bidirectional wireless communication with an external device 50 (shown in FIG. 1) for programming sensing and therapy delivery control parameters as generally described above. IMD 114’ and IMD 116 may be configured to communicate with each other via radio frequency communication, tissue conductance communication (TCC) or other communication methods for coordinating dual chamber pacing and sensing in the two device system 110. [0062] FIG. 4 is a conceptual diagram of an IMD configured to sense cardiac electrical signals, sense patient acceleration signals, and deliver ANS according to some examples. FIG. 4 depicts IMD 14 coupled to electrodes 20, 22, 24, 26, 28 and 30 carried by leads 16 and 18 as shown in FIG. 1. However, it is to be understood that the circuitry, components and functionality described in conjunction with FIG. 4 may generally correspond to circuitry, components and functionality of an IMD and electrodes for providing at least cardiac signal sensing, acceleration signal sensing and ANS delivery. For instance, the circuitry, components and functionality described in conjunction with FIG. 4 may correspond to a leadless IMD configured to deliver ANS, e.g., IMD 114 shown in FIG. 2. In still other examples, the circuitry components and functionality described in conjunction with FIG. 4 and other flow charts and diagrams presented herein may be distributed across multiple IMDs in a multi-device system, such as the two device system shown in FIG. 3. For the sake of convenience, FIG. 4 is described with reference to IMD 14 shown in FIG 1. [0063] Electrodes 20, 22, 24, 26, 28, and 30 and/or housing 15 shown in the system 10 of FIG. 1 may be connected to therapy delivery circuit 84 and/or cardiac electrical signal sensing circuit 86 (also referred to herein as “sensing circuit 86”) as shown in FIG. 4, e.g., via switching circuitry included in therapy delivery circuit 84 and sensing circuit 86. The electronic circuitry enclosed within housing 15 (shown conceptually in FIG. 4 as an electrode, sometimes referred to as a “can electrode”) includes software, firmware and hardware that cooperatively monitor cardiac electrical signals, determine when an electrical stimulation therapy is necessary, and deliver therapy as needed according to programmed therapy delivery algorithms and control parameters.

[0064] IMD 14 may include a control circuit 80, memory 82, therapy delivery circuit 84, cardiac electrical signal sensing circuit 86, telemetry circuit 88, and a sensor circuit 92. A power source 98 provides power to the circuitry of IMD 14, including each of the components 80, 82, 84, 86, 88, and 92 as needed. Power source 98 may include one or more energy storage devices, such as one or more rechargeable or non-rechargeable batteries. The connections between power source 98 and each of the other components 80, 82, 84, 86, 88, and 92 are to be understood from the general block diagram of FIG. 4 but are not shown for the sake of clarity. For example, power source 98 may be coupled to one or more charging circuits included in therapy delivery circuit 84 for charging holding capacitors included in therapy delivery circuit 84 and operating output circuitry for discharging the holding capacitor(s) at appropriate times under the control of control circuit 80 for producing electrical pulses according to a therapy protocol. Power source 98 is also coupled to components of cardiac electrical signal sensing circuit 86 (such as sense amplifiers, analog-to-digital converters, switching circuitry, etc.), memory 82, telemetry circuit 88 and sensors 92 as needed.

[0065] The various operating circuits shown in FIG. 4 represent functionality included in IMD 14 and may include any discrete and/or integrated electronic circuit components that implement analog and/or digital circuits capable of producing the functions attributed to the IMD herein. Functionality associated with one or more circuits may be performed by separate hardware, firmware and/or software components, or integrated within common hardware, firmware and/or software components. For example, cardiac electrical signal sensing and analysis may be performed cooperatively by sensing circuit 86 and control circuit 80 and may include operations implemented in a processor or other signal processing circuitry included in control circuit 80 executing instructions stored in memory 82. Therapy delivery may be performed cooperatively by therapy delivery circuit 84 under the control of signals received from control circuit 80 for controlling the timing, pulse amplitude, pulse width, polarity, rate, electrode vector and other therapy delivery parameters used by therapy delivery circuit 84 to generate and deliver electrical stimulation pulses, which may include ANS, cardiac pacing pulses, CV/DF shocks, impedance measurement drive signals or any other electrical pulses delivered via electrodes 20, 22, 24, 26, 28, 30, and/or housing 15 shown in the system of FIG. 1. [0066] The various circuits of IMD 14 may include an application specific integrated circuit (ASIC), an electronic circuit, a processor (shared, dedicated, or group) and memory that execute one or more software or firmware programs, a combinational logic circuit, state machine, hardware subroutine, or other suitable components or combinations of components that provide the described functionality. The particular form of software, hardware and/or firmware employed to implement the functionality disclosed herein will be determined primarily by the particular system architecture employed in the IMD and by the particular sensing, detection and therapy delivery methodologies employed by the IMD. Providing software, hardware, and/or firmware to accomplish the described functionality in the context of any modem medical device system, given the disclosure herein, is within the abilities of one of skill in the art.

[0067] Memory 82 may include any volatile, non-volatile, magnetic, or electrical non- transitory computer readable storage media, such as random access memory (RAM), readonly memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other memory device. Furthermore, memory 82 may include non-transitory computer readable media storing instructions that, when executed by one or more processing circuits, cause control circuit 80 and/or other IMD components to perform various functions attributed to IMD 14 (or IMD 114 or the combination of IMD 114’and IMD 116 in system 110) or those IMD components. The non-transitory computer-readable media storing the instructions may include any of the media listed above.

[0068] Therapy delivery circuit 84 and sensing circuit 86 can be electrically coupled to electrodes 20, 22, 24, 26, 28, 30 and/or housing 15, which may function as a common or ground electrode for sensing electrical signals or delivering therapy or as an active can electrode for delivering CV/DF shock pulses. As such, housing 15 is shown conceptually as an electrode that may be coupled to therapy delivery circuit 84 and/or sensing circuit 86 in FIG. 4. Control circuit 80 communicates, e.g., via a data bus, with therapy delivery circuit 84 and sensing circuit 86 for sensing cardiac electrical signals, detecting cardiac rhythms, and controlling delivery of cardiac electrical stimulation therapies in response to sensed cardiac signals (or the absence thereof).

[0069] Control circuit 80 may include processor 81, timing circuit 83, and therapy control circuit 85. Processor 81 may be configured to process and analyze signals received from sensing circuit 86, which may be in conjunction with time intervals and/or timing related signals received from timing circuit 83, and signals received from physiological sensors 92. Timing circuit 83 may generate clock signals and include various timers and/or counters for use in determining time intervals between sensed cardiac event signals attendant to intrinsic myocardial depolarizations, e.g., sensed intrinsic P-waves and/or R- waves, and/or delivered pacing pulses. Timing circuit 83 may include various timers and/or counters for controlling the timing of delivered ANS, cardiac pacing pulses and CV/DF shocks. Control circuit 80 may further include a therapy control circuit 85 configured to pass signals to and receive signals from therapy delivery circuit 84 for controlling and monitoring electrical stimulation therapies delivered by therapy delivery circuit 84 according to therapy control parameters, such as ANS control parameters described below.

[0070] Sensing circuit 86 may be selectively coupled to electrodes 20, 22, 24, 26, 28, 30 and/or housing 15 in order to monitor electrical activity of the patient’s heart. Sensing circuit 86 may be enabled to receive cardiac electrical signals from at least one sensing electrode vector selected from the available electrodes, e.g., an atrial electrical signal sensed via at least one of RA lead electrodes 20 or 22 and a ventricular electrical signal, which may be sensed via at least one of RV lead electrodes 28 or 30, as examples. Sensing circuit 86 may include switching circuitry for selecting which electrodes are coupled to sensing circuit 86. For example, IMD 14 may include an atrial (A) sensing channel 87 for receiving signals from electrodes carried by RA lead 16 and a ventricular (V) sensing channel 89 for receiving signals from electrodes carried by RV lead 18 (shown in FIG. 1). In some examples, two, three or more cardiac electrical signals from two, three or more different sensing electrode vectors may be received simultaneously by respective sensing channels of sensing circuit 86, e.g., atrial sensing channel 87 and ventricular sensing channel 89. Sensing circuit 86 may monitor cardiac electrical signals for sensing cardiac event signals, e.g., P-waves attendant to intrinsic atrial myocardial depolarizations and R- waves attendant to intrinsic ventricular myocardial depolarizations.

[0071] Each sensing channel 87 and 89 may be configured to amplify, filter and digitize the cardiac electrical signal received from selected electrodes coupled to the respective sensing channel 87 and 89 to improve the signal quality for sensing cardiac event signals, such as P-waves and R-waves. The cardiac event sensing circuitry within sensing circuit 86 may include one or more sense amplifiers, filters, analog-to-digital converters (ADCs), rectifiers, threshold detectors, comparators, timers or other analog and/or digital components. For instance, an amplified, filtered and rectified signal sensed using RA lead electrodes 20 and/or 22 may be passed to a P-wave detector included in atrial sensing circuit 87 for sensing P-waves. The P-wave detector may include a sense amplifier, comparator and/or other electronic circuitry for applying a P-wave sensing threshold to the atrial electrical signal. In response to the atrial electrical signal crossing the P-wave sensing threshold, sensing circuit 86 may pass an Asense signal to control circuit 80 to indicate the timing of the sensed P-wave.

[0072] An amplified, filtered and rectified signal sensed using RV lead electrodes 28 and/or 30 may be passed to an R-wave detector included in ventricular sensing channel 89 for sensing R-waves. The R-wave detector may include a sense amplifier, comparator and/or other electronic circuitry for applying an R-wave sensing threshold to the ventricular electrical signal. In response to the ventricular electrical signal crossing the R- wave sensing threshold, sensing circuit 86 may pass a Vsense signal to control circuit 80 to indicate the timing of the sensed R-wave. The P-wave and R-wave sensing thresholds may each be automatically adjusted by sensing circuit 86 under the control of control circuit 80, based on sensing threshold control parameters, such as various timing intervals and sensing threshold amplitude values that may be determined by control circuit 80, stored in memory 82, and/or controlled by hardware, firmware and/or software of control circuit 80 and/or sensing circuit 86.

[0073] Asense and Vsense signals received from sensing circuit 86 by control circuit 80 can be used by control circuit 80 for determining sensed cardiac event intervals, which can be PP intervals (PPIs) between consecutively received Asense signals from atrial sensing channel 87 (or from a delivered atrial pacing pulse to an Asense signal) and RR intervals (RRIs) extending between consecutively received Vsense signals from ventricular sensing channel 87 (or between two consecutively delivered ventricular pacing pulses or between a delivered ventricular pacing pulse and a Vsense signal). Control circuit 80 may include timing circuit 83 for determining various cardiac sensed event intervals, such as PPIs and/or RRIs, for use in determining heart rate for controlling ANS as further described below in conjunction with accompanying flow charts and diagrams presented herein.

[0074] In some examples, sensing circuit 86 passes a digitized cardiac electrogram (EGM) signal to control circuit 80 for P-wave and/or R-wave morphology analysis for use in detecting cardiac tachyarrhythmias. P-wave and/or R-wave morphology analysis may be performed in combination with cardiac event interval analysis according to an implemented tachyarrhythmia detection algorithm. The ANS techniques disclosed herein may be implemented in conjunction with a variety of cardiac event signal sensing and tachyarrhythmia detection methods and are not limited to any particular method for sensing P-waves and R-waves or for detecting tachyarrhythmias based on an analysis of cardiac event intervals and/or cardiac signal waveform morphology.

[0075] Timing circuit 83 may be configured to control various timers and/or counters used in setting various blanking periods, refractory periods or other time intervals used in sensing atrial and ventricular event signals by sensing circuit 86. The various timers and/or counters may be used in determining time intervals between received Asense and Vsense signals received from sensing circuit 86 and in controlling the timing of ANS, cardiac pacing pulses and other electrical pulses generated by therapy delivery circuit 84. Timing circuit 83 may start one or more timers or counters in response to receiving Asense and Vsense signals from sensing circuit 86 and in response to therapy delivery circuit 84 delivering an atrial pacing pulse or a ventricular pacing pulse for scheduling subsequent pacing pulses and for determining various cardiac event intervals for use in controlling atrial pacing, ventricular pacing, ANS, and/or detecting tachyarrhythmias.

[0076] For example, timing circuit 83 may pass sensed cardiac event intervals determined from received Asense signals and Vsense signals (and delivered ventricular pacing pulses) to processor 81 for use in determining a heart rate. Processor 81 may be configured to count tachyarrhythmia intervals for use in detecting atrial or ventricular tachyarrhythmias. Timing circuit 83 may start pacing escape intervals in response to Asense and Vsense signals received from sensing circuit 86 for controlling the timing of atrial pacing pulses and ventricular pacing pulses according to a pacing mode and pacing rate. As further described below, timing circuit 83 and therapy control circuit 85 may control therapy delivery circuit 84 to deliver ANS pulse trains according to ANS control parameters in response to detecting an increase in heart rate and may terminate ANS delivery in response to a decrease in heart rate.

[0077] Processor 81 may be implemented in control circuit 80 as hardware, software and/or firmware that processes and analyzes signals received from sensing circuit 86 and/or timing circuit 83 and signals from physiological sensors 92 for detecting ANS trigger conditions. In some examples, processor 81 may include comparators and counters for counting PPIs and RRIs determined by timing circuit 83 that are tachyarrhythmia intervals. Processor 81 may compare PPIs and/or RRIs to various heart rate thresholds for use in controlling ANS therapy delivery, for example.

[0078] When IMD 14 is configured to delivery high voltage CV/DF shocks, processor 81 may compare RRIs determined by timing circuit 83 to a ventricular tachycardia detection interval zone and/or a ventricular fibrillation detection interval zone for detecting ventricular tachyarrhythmias. Any of a number of tachyarrhythmia detection methods may be implemented in an IMD performing the ANS methods disclosed herein.

[0079] Control circuit 80 may control therapy delivery circuit 84 to generate an impedance measurement drive signal, which may be a constant current or constant voltage signal, delivered to an electrode pair. A resulting voltage or current signal may be measured between a selected recording pair of electrodes by sensing circuit 86 and passed to control circuit 80 for use in determining an impedance measurement. The impedance measurement may be used by control circuit 80 for monitoring a patient activity metric in some examples. For example, minute ventilation or other respiration metrics may be determined from an impedance signal for determining a patient activity metric. However, some patients experiencing a POTS episode may experience dyspnea or hyperventilation, confounding a determination of an activity metric from an impedance signal measuring changes in thoracic impedance due to respiration. As such, an activity metric determined from an impedance signal may or may not be reliable for use in controlling ANS according to the techniques described below. [0080] Therapy delivery circuit 84 may include at least one charging circuit and one or more charge storage devices such as one or more holding capacitors for generating electrical stimulation pulses for delivery to the patient’s heart via a selected electrode vector. Therapy delivery circuit 84 may include a low voltage therapy delivery circuit for generating relatively low voltage cardiac pacing pulses and ANS pulse trains. Therapy delivery circuit 84 may include a high voltage therapy delivery circuit for generating high voltage CV/DF shock pulses. The low voltage therapy delivery circuit may include a low voltage charging circuit, one or more low voltage holding capacitors and a low voltage output circuit for generating and delivering cardiac pacing pulses and ANS pulse trains, which may have programmable pulse voltage amplitudes up to 12 volts, up to 10 V, up to 8 volts or less or up to 5 volts or less, as examples. Cardiac pacing pulses may be delivered by the low voltage therapy circuit in response to a pacing escape interval or other pacing timing interval expiring, as determined by control circuit 80. Cardiac pacing pulses may be delivered for providing bradycardia pacing, asystole pacing, ATP, postshock pacing, etc.

[0081] The low voltage charging circuit may include a charge pump for charging a low voltage holding capacitor to a pacing voltage amplitude up to a multiple of the battery voltage of power source 98, e.g., up to three or four times the battery voltage. A state machine of control circuit 80 may control charging of a low voltage holding capacitor to a programmed pacing voltage amplitude using a multiple of the battery voltage of power source 98. The low voltage output circuit that may include one or more switching devices and an output or “tip” capacitor through which the low voltage holding capacitor(s) may be discharged for delivering a pacing pulse. A charged low voltage holding capacitor may be discharged via a tip capacitor by switching on an electrode selection switch after charge completion to deliver a pacing pulse to a selected cathode electrode with a return path via a selected anode electrode. The cardiac pacing pulses can be delivered as bipolar pacing pulses via a “tip-to-ring” pacing electrode vector, e.g., in the RV via RV tip electrode 28 to RV ring electrode 30 and/or in the RA via RA tip electrode 20 to RA ring electrode 22, for successfully capturing and pacing the heart.

[0082] The low voltage therapy circuit may generate trains of pulses for delivering ANS for alleviating or preventing POTS. The ANS pulses may each have a pulse amplitude, e.g., up to 10 volts, and pulse width, e.g., up to 200 microseconds, that is less than the myocardial capture threshold of the atria. The pulse amplitude, pulse width, pulse number and frequency of the pulses in an ANS pulse train are controlled by therapy control circuit 85 according to ANS delivery control parameters to suppress the intrinsic atrial rate and/or AV nodal conduction to reduce the likelihood of the patient experience POTS symptoms. Various ANS delivery control parameters that may be used by control circuit 80 in controlling therapy delivery circuit 84 to deliver ANS are described below.

[0083] In some examples, therapy delivery circuit 84 may include a high voltage (HV) therapy circuit, which may include a HV charging circuit, HV holding capacitor(s), and HV output circuit that are operatively controlled by signals from control circuit 80 for charging and subsequently discharging the high voltage capacitor(s) for CV/DF shock delivery when control circuit 80 detects ventricular tachycardia or fibrillation.

[0084] The circuitry included in an IMD system operating according to the techniques disclosed herein includes one or more physiological sensors 92 for sensing various physiological signals, such as an acceleration signal, pressure signal, heart sound signals, temperature signal, or the like. Sensors 92 include an accelerometer 94 for sensing acceleration signals correlated to patient body motion and physical activity. It is noted that POTS can occur without a change in blood pressure or without a decrease in blood pressure. As such the methods disclosed herein may include detecting ANS therapy trigger conditions that do not include sensing blood pressure or correlates thereof for detecting a change in blood pressure.

[0085] Accelerometer circuit 94 may be enclosed by housing 15 of IMD 14. However, it is recognized that when IMD 14 is coupled to one or more medical electrical leads, accelerometer 94 may be carried by the lead, e.g., along a distal portion of the lead, and coupled to circuitry within housing 15 via electrical conductors. Accelerometer may be a one-, two- or three-axis accelerometer in various examples. In FIG. 4, accelerometer 94 is shown as a three dimensional accelerometer having three sensing elements 93a, 93b and 93c, collectively sensing elements 93. The sensing elements 93 may be orthogonal to one another, each aligned with a respective accelerometer axis Al, A2, or A3.

[0086] Each sensing element 93 of accelerometer 12 may be defined by a piezoelectric element, micro-electrical mechanical system (MEMS) device or other sensor element capable of producing an electrical signal in response to changes in acceleration imparted on IMD 14 and subsequently the sensor element, e.g., by converting the acceleration to a force or displacement of the accelerometer sensor element that is converted to the electrical acceleration signal by the accelerometer sensor element.

[0087] Each accelerometer sensor element 93a, 93b, and 93c produces an acceleration axis signal, e.g., an Al axis signal, A2 axis signal, or A3 axis signal, respectively, corresponding to the vector component of acceleration imparted on IMD 14 along the respective Al, A2 or A3 axis. Each accelerometer sensor element 93 produces a DC component corresponding to the vector component of gravitational force or other force exerted on the patient along the respective accelerometer axis. Each accelerometer sensor element produces an AC component correlated to the acceleration vector component due to motion of the patient or other acceleration that the patient is subjected to, along the respective axis. Sensor circuit 92 may include an ADC 95 and filter/amplifier 96 for digitizing, amplifying and filtering the accelerometer axis signals that are passed to control circuit 80. Sensor circuit 92 may include a bandpass filter having a bandpass from 1 to 30 Hz, 1 Hz to 20 Hz, or 1 to 10 Hz as examples for generating a body acceleration signal. The bandpass filtered body acceleration signal is correlated to acceleration due to patient body motion, e.g., during body movement such as body posture changes and patient physical activity. Each of the bandpass filtered acceleration axis signals may be received by control circuit 80 for detecting motion of the patient that is indicative of a change from one body posture to another. It is noted that the bandpass filtered signal is analyzed for detecting the motion of the patient associated with movement of the body from one position to another. In contrast, low pass filtered or DC acceleration axis signals representative of the component of gravitational force along each axis may be representative of the patient’s static body posture, e.g., when lying down, sitting standing or other body position. As described below, control circuit 80 may be configured to detect a signal spike in the bandpass filtered acceleration signal that is representative of motion of the patient as the patient changes body position. Processor 81 may be configured to analyze one, two or all three accelerometer axis signals, individually or in a combined signal, for detecting patient body motion associated with a change from one body posture to another body posture.

[0088] The same or a different bandpass filtered patient physical activity signal may be passed from sensor circuit 92 to control circuit 80 for determining an activity metric that is correlated to the level of physical activity of the patient. The bandpass filtered cutoff frequencies for generating a patient physical activity signal may be different than the bandpass filtered cutoff frequencies for generating an acceleration signal used for detecting body posture movement. As further described below, a patient physical activity metric may be determined by control circuit 80 for detecting ANS therapy trigger conditions and/or for controlling termination of ANS delivery.

[0089] Control circuit 80 may determine the patient physical activity metric from the accelerometer signal at a desired frequency for use in determining a sensor-indicated pacing rate (SIR). The activity metric may vary between a minimum resting level and a maximum activity level associated with maximum exertion. In some examples, the activity metric is determined as an activity count. Control circuit 80 may include a counter to track the activity count as the number of times the patient physical activity signal from sensor circuit 92 crosses a threshold during an activity count interval, for example a 0.5, 1, 2 or 3 second interval. The count at the end of each activity count interval is correlated to patient body motion during the activity count interval and is therefore correlated to patient physical activity. The threshold applied to the accelerometer signal, which when crossed by the motion sensor signal causes the activity count to be increased, may be a default or programmable threshold or may be an automatically adjusted threshold.

[0090] In other examples, an activity metric may be obtained from the accelerometer signal by integrating or summing motion signal sample points over an activity count interval, e.g., a 0.5, 1 or 2 second integration interval though longer or shorter intervals of time may be used for determining the activity metric. Example methods for determining a patient physical activity metric are generally disclosed in U.S. Pat. No. Pat. No. 6,449,508 (Sheldon, et al.), incorporated herein by reference in its entirety.

[0091] Control circuit 80 may receive a rectified acceleration signal from sensor circuit 92 and determine the patient physical activity metric from the acceleration signal by summing acceleration signal sample point amplitudes over the activity metric time interval. The activity metric may be converted to a target heart rate to meet the patient’s metabolic demand. The target heart rate may be converted to a sensor indicated rate (SIR) based on an SIR transfer function that includes a lower rate set point and an activities of daily living (ADL) range and a maximum upper rate, for example. The ADL may correspond to nonresting, patient physical activity corresponding to normal daily activities, such as moving about the home, driving a car, light tasks, etc. Exertion above the ADL level may correspond to strenuous exercise and heavy tasks. Resting levels of the activity metric are expected when the patient is sleeping, sitting, or standing but relatively inactive. By determining a patient physical activity metric from the acceleration signal received from sensor circuit 92, control circuit 80 can convert the activity metric to an SIR according to a transfer function stored in memory 82. During a rate response pacing mode, therapy delivery circuit 84 may be controlled by control circuit 80 to deliver atrial or ventricular pacing pulses at a rate response pacing rate determined based on the SIR.

[0092] Other types of sensors may be included in sensor circuit 92, which may produce a signal correlated to patient physical activity or other patient physiological conditions. Such sensors could include a heart sound sensor, oxygen sensor, pressure sensor, gyroscope or the like.

[0093] When IMD 114, 114’ or 116 includes accelerometer 94 and is implanted within or on a heart chamber, control circuit 80 may process and analyze the acceleration signal for sensing ventricular mechanical event signals and/or atrial mechanical event signals. Control circuit 80 may determine ventricular event intervals between consecutively sensed ventricular mechanical event signals for determining a ventricular rate and or determine atrial event intervals between consecutively sensed atrial mechanical event signals for determining an atrial rate. Accordingly, determination of heart rate for controlling ANS therapy by control circuit 80 is not necessarily limited to processing and analysis of cardiac electrical signals. Other physiological sensor signals that include atrial and/or ventricular event signals may be processed and analyzed for detecting atrial and/or ventricular events attendant to atrial depolarization and atrial systole and ventricular depolarization and ventricular systole, respectively, for determining the heart rate and controlling ANS therapy according to the techniques disclosed herein.

[0094] Telemetry circuit 88 includes a transceiver and antenna for communicating with external device 50 (shown in FIG. 1) using RF communication or other communication protocols as described above. Control parameters utilized by control circuit 80 for sensing cardiac event signals, sensing acceleration signals, and controlling therapy delivery including ANS may be programmed into memory 82 via telemetry circuit 88. Under the control of control circuit 80, telemetry circuit 88 may receive downlink telemetry from and send uplink telemetry to external device 50. [0095] FIG. 5 is a flow chart 200 of a method for controlling ANS by an IMD system according to some examples. FIG. 5 and other flow charts presented herein are generally described in conjunction with IMD 14 shown in FIG. 1. However, it is to be understood that the techniques disclosed herein for detecting ANS therapy trigger conditions and delivering ANS may be implemented in a leadless IMD, such as IMD 114 shown in FIG. 2, or in a multi-device system such as the IMD system 110 shown in FIG. 3.

[0096] At block 202, control circuit 80 may monitor accelerometer signals received from sensor circuit 92 for detecting a signal spike indicative of patient body motion during a body posture change. Control circuit 80 may monitor heart rate for tracking a baseline heart rate. When a signal spike is detected, the baseline heart rate may be compared to a post-spike heart rate for use in detecting an increase in heart rate (as described below in conjunction with block 208). The post-spike heart rate increase may be detected for triggering ANS therapy delivery. At block 202, control circuit 80 may monitor the heart rate for detecting atrial and/or ventricular tachyarrhythmias. An acceleration signal spike may be detected at block 204 when the heart rate is a sinus rate, e.g., atrial fibrillation, atrial flutter, ventricular tachycardia or ventricular fibrillation is not being detected by control circuit 80.

[0097] In various examples, at block 202 control circuit 80 may monitor a single accelerometer axis signal, two accelerometer axis signals or all three accelerometer axis signals for detecting an acceleration signal spike. Control circuit 80 may monitor the accelerometer axis signals individually or in any combination, e.g., the weighted or unweighted absolute amplitudes of the Al, A2 and A3 axis signals may be summed or combined in a mathematical combination or used to determine an acceleration vector. Control circuit 80 may compare the accelerometer signal(s) to posture change motion criteria at block 204.

[0098] In order to detect a signal spike that meets posture change motion criteria, control circuit 80 may compare the difference between the i and the i-n sample points of the accelerometer signal(s) to a threshold difference. In some examples, the difference is determined between consecutive sample points (where n=l). In other examples the difference can be determined between sample points that are spaced apart a specified time interval, e.g., n may be 2, 3, 4, 5, 6 or other number of sample points. The difference between sample points of the accelerometer signal(s) may be compared to a threshold difference to detect an acceleration spike that is indicative of a body motion during a posture change, e.g., from sitting to standing, from lying to standing, from lying to sitting, etc. Control circuit 80 may be configured to detect an acceleration signal spike at block 204 by detecting a threshold difference between two sample points of at least one accelerometer axis signal that are within a specified number of sample points (or time interval) from each other. It is noted that the acceleration axis signal may reach a steady state after the spike if the patient is relatively inactive after the body posture change. The post-spike steady state acceleration signal may or may not be different than the pre-spike steady state acceleration signal because, for example, the patient may be in a resting or inactive state in an upright sitting position prior to the signal spike and change to an upright standing position, but still be relatively inactive.

[0099] In one example, an acceleration vector signal at each sample point is acquired by bandpass filtering the output signal of each of the Al, A2 and/or A3 axis sensing elements 93 (see FIG. 4). The magnitude of the acceleration vector signal may be computed as a mathematical combination of the Al, A2 and A3 acceleration signal components of the acceleration vector signal, e.g., as the sum of the accelerometer axis signal magnitudes (absolute amplitudes) or the sum of the squares of the accelerometer axis signal amplitudes. In other examples, the magnitude of the acceleration vector signal may be computed as a Euclidean norm, e.g., the square root of the sum of squares of the three orthogonal Al, A2 and A3 axis signals corresponding to x-, y- and z-components of the acceleration vector, v:

II v||=(x² +y² +z²)^1/2

[0100] During a posture change that could trigger POTS in a given patient, acceleration vector signal is expected to undergo a sudden magnitude change within a short time interval, e.g., within 1 second or less, due to the patient body motion during the posture change. In some examples, a derivative or difference signal (which may be a first order or higher difference signal) may be determined and compared to a threshold for detecting an acceleration signal spike indicative of patient body motion during a posture change. A derivative signal may be determined from a single Al, A2 or A3 axis signal or a combination of axis signals. In some examples, a maximum peak may be compared to a signal spike threshold range. The threshold(s) or threshold range(s) that are applied to one or more acceleration signals or derivatives thereof may depend on the calibration of the accelerometer and ADC range and may be tailored to an individual patient by characterizing the patient’s body motion during a known posture change (e.g., an elderly patient may move more slowly and/or have a different movement profile than a younger patient during a given body posture change, such as standing up from a lying or sitting position).

[0101] The magnitude, slew rate, and/or frequency of the acceleration signal or a derivative thereof may be determined for detecting an acceleration signal spike in the bandpass (or high pass) filtered accelerometer signal that is responsive to changes in acceleration of the patient’s body during movement from one body posture to another. The acceleration signal and/or a derivative of the acceleration signal may be analyzed by control circuit 80 to determine if it meets posture change motion criteria at block 204. In some examples, a slew rate of the acceleration signal may be compared to a slew rate threshold in addition to or alternatively to comparing a change in magnitude of the acceleration vector signal (or one or more axis signals analyzed individually) to a spike detection threshold or threshold range. In some examples, the acceleration signal spike detection may require detecting a first slew rate that is greater than a first threshold followed by a second slew rate that is less than a second threshold. A posture change acceleration signal spike may be associated with a high slew rate in the acceleration signal as the patient moves between one posture and another followed by a relatively stable acceleration signal when the posture change is following by a relatively inactive patient physical activity level. In this way, a relatively high frequency body acceleration signal spike may be detected when the acceleration signal meets posture change motion criteria for triggering ANS therapy.

[0102] In order to capture an acceleration signal spike caused by a body posture change, the three-dimensional (or a two-dimensional or single axis) accelerometer signal may be bandpass filtered to remove DC components and high frequency noise. The accelerometer signal may be filtered by a 1 to 30 Hz bandpass filter or a 1 to 3 Hz bandpass filter, as examples, to obtain an output signal that includes acceleration caused by body motion during posture changes. The filter may be an adjustable filter having cutoff frequencies set tailored to an individual patient to optimize acceleration signal spike detection performance, e.g., to reduce false spike detections or missed true spike detections associated with posture change body motion that can trigger POTS in a given patient. The thresholds applied to the acceleration signal for detecting the acceleration signal spike may be adjustable for tailoring to a given patient, e.g., taking into account POTS episode confirmations that the patient or a caregiver may enter using external device 50 as described in conjunction with FIG. 1. Thresholds may be adjusted when an acceleration signal spike associated with a patient-confirmed POTS episode was not detected, for example. In some examples, a threshold range having a maximum limit may be applied to the acceleration signal to avoid detecting acceleration signal spikes that have a higher magnitude and/or higher slew rate than expected during body motion associated with a posture change. The thresholds or ranges of values applied to the acceleration signal for detecting a signal spike can be stored in memory 82 as posture change motion criteria. [0103] It is noted that the techniques disclosed herein do not necessarily requiring determination of the patient body posture. Some IMDs may be configured to determine patient body posture based on an analysis of a low pass filtered acceleration signal (or averaged or DC acceleration signal) representative of the components of gravitational force along the accelerometer axes. The techniques disclosed herein do not necessarily require determining the patient body posture. Rather, it is the patient body motion associated with a change in body posture from a first body position or posture to a second body position or posture that control circuit 80 is configured to detect by detecting the acceleration signal spike meeting posture change motion criteria. The first body posture and the second body posture may be undetermined or unknown.

[0104] Upon detecting an acceleration signal spike, control circuit 80 may monitor heart rate at block 208 for a specified time period after the acceleration spike to detect a threshold increase in heart rate. In some examples, an increase in heart rate of at least 20 beats per minute (bpm), 25 bpm, 30 bpm, 35 bpm or 40 bpm may be required subsequent to the signal spike detection to trigger ANS therapy. The threshold increase in heart rate may be required to occur within 20 seconds, 30 seconds, 45 seconds, or 60 seconds of the detected signal spike. The threshold increase in heart rate may be based on the heart rate just prior to spike detection or just after spike detection.

[0105] Accordingly, control circuit 80 may receive Asense and/or Vsense signals from sensing circuit 86 and for determining sensed cardiac event intervals, e.g., PPIs or RRIs, that can be compared to corresponding heart rates for detecting the threshold increase in heart rate subsequent to signal spike detection. Control circuit 80 may determine a mean, median, maximum, minimum or other representative sensed cardiac event interval from the sensed cardiac event intervals. For instance, the median sensed cardiac event interval may be determined from the most recent 3, 4, 6, 8, 10, 12, 20 or 30 PPIs or RRIs as examples. A baseline median sensed cardiac event interval may be determined as the most recent median sensed cardiac event interval determined prior to detecting the acceleration signal spike or the earliest median heart rate interval determined after detecting the acceleration signal spike. Control circuit 80 may determine the updated median sensed cardiac event interval at a specified time interval after the acceleration spike detection, e.g., 10, 15, 20, 30, 45 or 60 seconds after the spike detection. In other examples, control circuit 80 may determine the updated median sensed cardiac event interval at multiple time points after the detected signal spike, e.g., every 5 seconds or every 10 seconds up to one to two minutes after the detected signal spike.

[0106] The difference between the heart rate corresponding to the updated sensed cardiac event interval after the detected signal spike and the baseline heart rate corresponding to the baseline sensed cardiac event interval may be compared to the heart rate change threshold at block 208. When the heart rate is not increased by at least the threshold amount, control circuit 80 may return to block 202 and wait for a subsequent spike detection. If a maximum post-spike time interval is not expired, control circuit 80 may continue determining updated sensed cardiac event intervals until a maximum post-spike time interval is expired for detecting the threshold increase in heart rate. The sudden increase in heart rate corresponding to a POTS episode may occur within 2 minutes or less or within one minute or less, for instance. If the threshold change in heart rate is not detected within the maximum post-spike time interval, POTS may not occur such that ANS therapy is not needed. As such, upon detecting the signal spike at block 204, control circuit 80 may start a post-spike timer during which the heart rate is monitored for detecting the threshold increase in heart rate.

[0107] If the threshold increase in heart rate is detected after detecting the acceleration spike, control circuit 80 may control therapy delivery circuit 84 to initiate ANS therapy at block 212. In some examples, in addition to or alternatively to detecting the threshold increase in heart rate, control circuit 80 may determine if the heart rate is greater than a minimum heart rate for triggering ANS therapy. In an illustrative example, control circuit 80 may determine that ANS trigger conditions are met when the heart rate increases by at least 30 bpm within one minute after the detected acceleration signal spike and that the heart rate is at least 90, 100, 110, 120, or 130 bpm as examples.

[0108] When the ANS trigger conditions expected to be associated with a POTS episode are met, ANS therapy may be delivered by therapy delivery circuit 84 as trains of pulses, e.g., following Asense signals received from sensing circuit 86, or as a continuous, relatively high frequency, train of pulses. Example ANS pulse trains and ANS delivery control parameters used by therapy delivery circuit 84 to deliver the ANS are described below, e.g., in conjunction with FIGs. 8, 10, and 11.

[0109] In some examples, the ANS may be delivered for a specified time interval or number of cardiac cycles and then be terminated. In other examples, as shown in FIG. 5, control circuit 80 may monitor patient physical activity and/or heart rate for detecting an ANS termination condition. For instance, at block 214, control circuit 80 may monitor the accelerometer signal received from sensor circuit 92 for detecting an increase in patient physical activity. Control circuit 80 may determine a patient activity metric from the accelerometer signal. The activity metric may be an activity count as generally described above or an SIR based on the activity count. If the activity metric is greater than a nonresting activity threshold, which may indicate an increase in patient physical activity subsequent to detecting the acceleration signal spike, control circuit 80 may initiate termination of the ANS therapy at block 218. The non-resting activity threshold may be a specified activity level threshold stored in memory 82. The non-resting activity threshold may correspond to physical exertion that is greater than a resting level threshold or an ADL threshold. In some examples, the threshold may be set based on a baseline patient physical activity metric determined by control circuit 80 from the accelerometer signal most recently prior to detecting the acceleration signal spike. In other examples, the baseline patient physical activity metric may be determined by control circuit as the earliest activity metric determined after the signal spike detection. When the activity metric is determined at specified time intervals, e.g., every two seconds, the baseline activity metric may be the activity metric determined closest in time, before or after, the detected acceleration signal spike. In an illustrative example, if the baseline SIR is 60 bpm at the time of (or just prior to or just after) the acceleration signal spike detection and the SIR increases by 10 bpm, 20 bpm, 25 bpm, 30 bpm, 40 bpm or other specified increase from the baseline SIR during ANS delivery, control circuit 80 may detect increased patient physical activity at block 214.

[0110] In response to detecting the increased patient physical activity, control circuit 80 may terminate ANS at block 218, immediately or in a gradual manner, to allow the heart rate to increase physiologically in response to the patient’s increased physical activity. In some examples, as further described below in conjunction with FIGs. 8-10, one or more ANS delivery control parameters may be ramped down until the ANS therapy is fully terminated. The ramp down rate of the control parameter may be relatively faster or slower depending on the level of increased activity metric determined at block 214. As the ANS delivery control parameter is ramped down, therapy delivery circuit 84 may be delivering atrial and/or ventricular pacing pulses according to a rate response pacing rate that is determined by control circuit 80 from the SIR. In other examples, ventricular pacing pulses may be delivered at a rate response rate according to a determined SIR or at the programmed lower pacing rate until the intrinsic heart rate exceeds the pacing rate as ANS is being ramped down. When ANS is completely terminated, the intrinsic heart rhythm may respond physiologically to the increased physical activity such that rate response pacing pulses are inhibited by sensed intrinsic P-waves and/or R-waves. After termination of the ANS therapy, control circuit 80 may return to block 202 to monitor for the next acceleration signal spike.

[oni] When an increased patient physical activity is not detected at block 214, control circuit 80 may determine if a decreased heart rate is detected at block 216. The decrease in heart rate may be a return to the baseline heart rate or to a threshold heart rate that is greater than the baseline heart rate, e.g., the baseline heart rate plus 10 to 20 bpm. The ANS therapy can be expected to increase the parasympathetic tone to cause the heart rate to decrease to a normal resting (or relatively low activity) heart rate. A decreased heart rate may be detected in response to a sensed intrinsic rate that is less than a threshold rate, e.g., less than 70, 80, 90 or 100 bpm. The decreased heart rate may be detected in response to therapy delivery circuit 84 delivering atrial or ventricular pacing at the programmed lower rate interval. A decrease in heart rate may be detected when the atrial or ventricular rate is decreased by at least a threshold change, e.g., at least 10, 15, 20, 25, or 30 bpm less than the heart rate detected as an increased heart rate. When control circuit 80 detects a decreased heart rate at block 216, control circuit 80 may control therapy delivery circuit 84 to terminate the ANS therapy at block 218. The ANS therapy may be terminated abruptly in some examples but may be terminated gradually to avoid sudden changes in autonomic tone and heart rate in other examples.

[0112] For example, ANS therapy may be ramped down by gradually decreasing an ANS therapy delivery control parameter, such as the pulse amplitude, pulse width, and/or the number of pulses per pulse train as examples. When the ANS therapy control parameter has reached a minimum control parameter value, e.g., minimum pulse amplitude, pulse width, or minimum number of pulses per pulse train at block 218, therapy delivery circuit 84 may stop the delivery of ANS. Control circuit 80 may return to block 202 to resume monitoring for another acceleration signal spike. While not shown in FIG. 5, as the ANS therapy is ramped down, control circuit 80 may continue to monitor cardiac event intervals for detecting a rise in heart rate back toward or greater than an increased heart rate threshold. Control circuit 80 may respond by increasing one or more ANS delivery control parameters for a specified time interval and then resume ramping down the ANS therapy again so that a gradual return to a physiologically normal heart rate can occur.

[0113] FIG. 6 is a flow chart 300 of a method for controlling ANS therapy by an IMD according to another example. At block 302, control circuit 80 may monitor patient physical activity, e.g., by determining an activity metric from the accelerometer signal according to any of the examples described above. When the activity metric greater than a low activity threshold control circuit 80 may not detect an acceleration signal spike for triggering ANS therapy. The low activity threshold may correspond to an activity level that is at least higher than a resting level and may correspond to at least ADL or more strenuous activity. Signal spikes present in the acceleration signal may be caused by the patient’s physical activity. Suppression of an increased heart rate by increasing parasympathetic tone may be undesired when the activity metric is greater than the low activity threshold, as determined at block 304.

[0114] In response to the activity metric being greater than the low activity threshold, control circuit 80 may disable acceleration signal spike detection at block 306. In other examples, any signal spikes detected by control circuit 80 may be ignored for the purposes of triggering the ANS therapy. Control circuit 80 may continue monitoring patient physical activity at block 302 but may not detect ANS therapy trigger condition or may not enable ANS delivery when the activity metric is greater than the low activity threshold (block 304).

[0115] When the activity metric is less than the low activity threshold, control circuit 80 may enable acceleration signal spike detection at block 308. In other examples, ANS therapy may be enabled at block 308 for delivery in response to detecting ANS trigger conditions when the activity metric is less than the low activity threshold. In general, the detection of ANS therapy trigger conditions and the initiation of ANS therapy may be disabled when the activity metric is equal to or greater than the low activity threshold and enabled when the activity metric is less than the low activity threshold. The low activity threshold applied to the activity metric at block 304 may be tailored to a given patient based on their activity profile and/or activity levels associated with POTS. When the activity metric meets the low activity threshold, e.g., is equal to or greater than the low activity threshold, ANS may be effectively disabled by disabling or ignoring acceleration signal spike detection or by directly disabling ANS therapy delivery. When the patient activity metric is less than the low activity threshold, ANS therapy is enabled, e.g., by enabling acceleration signal spike detection or responding to acceleration spike detections at block 308.

[0116] At block 310, control circuit 80 monitors the received acceleration signal for detecting an acceleration signal spike according to any of the examples described herein. If a signal spike is not detected, control circuit 80 may return to block 302 and continue to monitor patient physical activity.

[0117] When the activity metric is less than the low activity threshold at block 304 and an acceleration signal spike is detected at block 310, control circuit 80 may monitor the sensed event signals received from sensing circuit 86 as described above for detecting a threshold increase in heart rate subsequent to the signal spike detection. A heart rate increase may be detected at block 312 according to any of the examples described above in conjunction with FIG. 5.

[0118] If an increased heart rate is not detected at block 312, control circuit 80 may return to block 302 to continue monitoring patient physical activity and wait for the next spike detection when the activity metric is less than the low activity threshold. The currently detected signal spike may or may not be caused by a true patient posture change, but in either case ANS therapy may not be delivered if an increased heart rate is not detected. In other examples, the heart rate check at block 312 may be omitted in some examples. When relatively low patient physical activity is detected and an acceleration signal spike is detected, therapy delivery circuit 84 may be configured to initiate ANS therapy in some cases. ANS may be initiated in a patient that experiences POTS frequently in response to posture changes to provide prophylactic treatment without waiting for the anticipated tachycardia heart rate.

[0119] In the example of FIG. 6, before initiating ANS therapy, control circuit 80 may determine if the activity metric has increased at block 314. The acceleration signal spike may have been detected at block 310 when the activity metric was less than the low activity threshold, but the patient may become physically active (e.g., begin walking, jogging, running or engaging in other physical activity) subsequent to a posture change that may have caused the signal spike. The detected signal spike may accompany an onset of physical activity for which an increased heart rate is appropriate. An increase in patient physical activity may be detected at block 314 by comparing the activity metric to the same low activity threshold applied at block 304 or to a different, relatively higher activity threshold associated with an elevated level of physical activity for which sinus tachycardia or at least an increased intrinsic heart rate is expected. The activity count, SIR or other physical activity metric may be compared to an increased activity threshold at block 314. In various examples, the increased activity threshold applied at block 314 may be a specified value stored in memory 82, which may be programmably tailored according to a given patient’s activity profile. In some cases, control circuit 80 may determine the increased activity threshold based on a baseline activity metric determined at or just before or after the signal spike detection. In still other examples, the increased activity threshold may be a specified percentage or difference greater than the low activity threshold.

[0120] In the example of FIG. 6, the trigger conditions for initiating ANS are therefore an initial low physical activity (“yes” branch of block 304) during which an acceleration signal spike is detected (“yes” branch of block 310, optionally followed by a detected increase in heart rate (“yes” branch of block 312) without an accompanying increase in patient physical activity (“no” branch of block 314). When the sequence and combination of conditions for triggering ANS are met, therapy delivery circuit 84 may initiate ANS at block 316. The increased heart rate without the activity metric meeting the increased activity threshold may be detected by control circuit 80 at a specified post-spike time interval. For example, control circuit 80 may wait at least 20 seconds, 30 seconds, 45 seconds or one minute for verifying that the activity metric does not meet the increased activity threshold after the detected signal spike before initiating ANS therapy at block 316.

[0121] After the ANS is started, control circuit 80 may monitor the activity metric at block 318 for detecting an increase in physical activity that may warrant a physiological increase in heart rate as described above in conjunction with FIG. 5. If the activity metric is increased at block 318, control circuit 80 may control therapy delivery circuit 84 at block 320 to perform a scaled ramp down of the ANS therapy according to the physical activity level. An ANS delivery control parameter may be ramped down at a faster rate when the activity metric is relatively high at block 318 and ramped down at a relatively slower rate when the activity metric is relatively lower in some examples.

[0122] In an illustrative example, with no limitation intended, the ANS pulse amplitude may be ramped down to a minimum amplitude within 15 seconds if the activity metric is greater than a high exertion threshold and may be ramped down to the minimum amplitude within 30 seconds if the activity metric is greater than an ADL threshold but less than a high exertion threshold. In another example, the ANS pulse amplitude may be ramped down to the minimum amplitude within 15 seconds if the SIR is greater than 110 bpm and ramped down to the minimum amplitude within 30 seconds if the SIR is greater than 80 bpm. Other time intervals over which the ANS delivery control parameter is ramped down and corresponding threshold activity metric values may be stored in memory 82 and used by control circuit 80 to control therapy delivery circuit 84 to ramp down the ANS in a manner that is scaled according to the activity metric value at block 320. The ANS therapy may be ramped down to complete termination within 5, 10, 15, 20, 30, 45, or 60 seconds as examples with no limitation intended. The ramp down interval may be programmable by a clinician. The ramp down interval may be adjusted by control circuit 80, e.g., to a longer time interval if a short time interval results in a sudden return of a fast heart rate.

[0123] As the ANS is being ramped down by therapy delivery circuit 84, control circuit 80 may return to block 318 to continue monitoring the activity metric. If the activity metric increases higher at block 318 during the scaled ramp down process, control circuit 80 may control therapy delivery circuit 84 to ramp one or more ANS delivery control parameters at a faster ramp down rate. If the activity metric decreases at block 318 while ANS is being ramped down, therapy delivery circuit 84 may continue ramping down the ANS delivery control parameter(s) at the same rate until ANS is completely terminated. In other examples, control circuit 80 may control therapy delivery circuit 84 to decrease the rate of ramping down the ANS delivery control parameter in response to a decrease in the activity metric determined at block 318 after the scaled ramp down of the ANS therapy has started. [0124] Once the ANS delivery control param eter(s) has(have) reached minimum value(s), such that the ANS therapy delivery is effectively terminated, as determined at block 326, control circuit 80 may return to block 302 to resume monitoring for a relatively low level of physical activity during which an acceleration signal spike can be detected for trigging another ANS therapy. If the ANS is not completely terminated at block 326, control circuit 80 may continue to monitor the activity metric at block 318 and heart rate at block 322. [0125] As described above in conjunction with FIG. 5, control circuit 80 may monitor the heart rate during the ANS delivery at block 322, e.g., by monitoring cardiac sensed event intervals determined from Asense and/or Vsense signals received from sensing circuit 86 (and/or cardiac pacing delivered by therapy delivery circuit 84) for detecting a decreased heart rate. It is to be understood from the flow chart of 300 that control circuit 80 may monitor both the activity metric and the heart rate in parallel or in a simultaneous manner and not necessarily in a sequential manner as shown by the order of blocks 318 and 322 in FIG. 6.

[0126] If a decreased heart rate is detected at block 322, control circuit 80 may control therapy delivery circuit 84 to gradually terminate ANS at block 328. One or more ANS delivery control parameters may be ramped down over a specified time interval, e.g., 30 to 60 seconds. As the ANS is being gradually terminated, control circuit 80 may continue to monitor patient physical activity at block 318 and heart rate at block 322 until the ANS is completely terminated as determined at block 326. Complete termination of ANS may be reached when the control parameter(s) being reduced reach zero or a minimum value, for example. If an increase in activity metric is detected at block 318 as the ANS is being gradually terminated, therapy delivery circuit 84 may perform a scaled ramp down at block 320 that may be faster than the gradual termination being performed in response to a lowered heart rate. The faster ramp down in response to increased activity enables the intrinsic heart rate to increase appropriately to support the increased activity. If the heart rate increases during the gradual termination but the activity metric is not increased, therapy delivery circuit 84 may increase the ANS delivery control param eter(s) again by returning to block 316.

[0127] In some examples, as shown in FIG. 6, therapy delivery circuit 84 may terminate ANS at block 328 if a maximum ANS delivery time is reached (as determined by control circuit 80 at block 326) without detecting a decrease in heart rate. In some examples, control circuit 80 may determine if the heart rate has decreased by at least some amount, e.g., by 5 to 10 beats per minute or by at least 10%, 15% or 20% from the increased heart rate detected at block 312. Control circuit 80 may determine if at least some decrease in heart rate occurs to verify that a therapeutic response to the ANS has occurred. If no decrease in heart rate has occurred within a specified number of cardiac cycles (e.g., 10 to 30 beats) or a specified time interval (e.g., 10 to 30 seconds), therapy delivery circuit 84 may begin termination of ANS at block 328. However, control circuit 80 may verify that the heart rate does not reach a tachycardia rate or other high threshold rate as the ANS is being gradually terminated to avoid POTS as the ANS is gradually reduced. The ANS control parameter may be increased again if the heart rate increases. Accordingly, the gradual termination process may include one or more increases in an ANS control parameter followed again by gradually decreasing the ANS control parameter. Once the ANS is completely terminated, control circuit 80 may return to block 302.

[0128] FIG. 7 is a diagram 400 of example accelerometer axis signals 402, 404 and 406 that may be received by control circuit 80. The Al axis signal 402, A2 axis signal 404 and A3 axis signal 406 may be sensed by accelerometer sensor elements 93 that are arranged along orthogonal axes of the accelerometer 94 of IMD 14 (see FIG. 4). In this example, an acceleration signal spike 410 is observed in each of the three axis signals 402, 404 and 406 caused by patient body motion during a body posture change. In the example shown, the patient is moving from a sitting position to a standing position. The average amplitude of each signal 402, 404 and 406 prior to the signal spike 410 may correspond to the component of gravity along the respective axis of the accelerometer. After the signal spike 410, each acceleration signal 402, 404 and 406 may vary as the patient’s body is moving during the posture change time interval 412. Changes in acceleration forces imparted on the accelerometer sensor elements 93 with changing alignment between each sensor element and gravitational force and motion of the patient as the patient’s body moves into the standing position causes variation in each of the three axis signals 402, 404 and 406 during the posture change time interval 412. The signal spike 410 may indicate the onset of the posture change.

[0129] After settling into the new posture, in this case standing, the accelerometer axis signals 402, 404 and 406 may return to the average amplitude observed prior to the signal spike 410. When the patient is sitting upright (pre-spike) and when the patient is standing still (post-spike), the gravitational force acting on each accelerometer axis of the IMD 14 implanted in the chest or torso may be substantially equal. As such, a return to the prespike acceleration signal amplitude may be expected, or at least a return to a relatively steady state amplitude, in each axis signal after the posture change time interval 412, during a post-posture change time interval 414, if the patient is now standing still and relatively inactive. However, it is recognized that a patient may sit back down or change position again, e.g., if a physical activity ensues, after a signal spike is detected. Once the acceleration signal spike is detected, subsequent posture change body motion can be ignored in some examples because the heart rate and patient physical activity are monitored for controlling ANS therapy once the initial signal spike is detected.

[0130] Control circuit 80 may detect the acceleration signal spike 410 by detecting a slew rate of an axis signal 402, 404 or 406 that is greater than a threshold slew rate. As described above, control circuit 80 may detect the acceleration signal spike 410 by comparing sample point amplitudes that are a specified sample time apart. For example, when the difference between the ith sample point and i-n sample point is greater than a threshold difference, an acceleration signal spike 410 may be detected. In some examples, control circuit 80 may analyze a single axis signal 402, 404 or 406 for detecting signal spike 410. In the example shown, the A2 axis signal 404 and the A3 axis signal 406 present larger signal spikes than the Al axis signal 402. A given one of the Al, A2 or A3 axis signals may present a larger signal spike for posture changes to upright positions that may be associated with POTS. The axis signal 402, 404 or 406 having the largest signal spike marking body motion during a posture change can depend on the orientation of the IMD 14 relative to the patient’s body. Th

[0131] In some examples, the axis signal used by control circuit 80 for detecting the signal spike may be programmable. Control circuit 80 may transmit the axis signals via telemetry circuit 88 when the patient is instructed to change body position, e.g., stand up from sitting, after IMD implantation or during a follow up visit. A clinician may observe the axis signals for selecting a programmed axis signal 402, 404 or 406 to be used by control circuit 80 for detecting signal spikes.

[0132] In some examples the axis signal used by control circuit 80 for detecting a signal spike may be selected by control circuit 80 based on an analysis of the axis signals 402, 404 or 406 by control circuit 80. For example, control circuit 80 may detect a signal spike based on one or all three individual axis signals and may determine which of the three axis signals 402, 404 or 406 has the highest absolute peak amplitude and/or highest slew rate. The axis signal determined to have highest peak amplitude and/or highest slew rate when a signal spike 410 is detected based on all three axis signals may be selected as the axis signal used for signal spike detection for triggering ANS delivery. By selecting one axis signal for signal spike detection, IMD power source 98 may be conserved because only one sensor element 93a, 93b or 93c need powered on for monitoring for the signal spike 410.

[0133] In other examples, control circuit 80 may use a combination of all three axis signals 402, 404 and 406. Control circuit 80 may sum the magnitudes (absolute amplitudes) of each axis signal 402, 404 and 406 at each sample time point (e.g., sampled at 128 Hz, 256 Hz or other sampling rate) to obtain a combined acceleration signal that is analyzed for detecting the signal spike 410, e.g., based on a threshold change in magnitude being met within a specified number of sample points, comparing a derivative of the acceleration signal to a threshold, and/or a threshold slew rate being met.

[0134] In some examples, as described in conjunction with FIG. 6, control circuit 80 may require that the activity metric be less than a low activity threshold prior to the signal spike 410 being detected in order to trigger ANS therapy. Additionally or alternatively, control circuit 80 may require that the activity metric be less than the low activity metric or not increased after the posture change time interval 412 in order to trigger ANS therapy. For example, control circuit 80 may determine if an activity metric determined after the signal spike 410 is less than an increased activity threshold as described above in conjunction with FIG. 6 (block 314). When the activity metric is greater than the increased activity threshold, ANS delivery may not be triggered because an increase in sinus heart rate is expected. [0135] In some examples, control circuit 80 may determine the average acceleration signal amplitude during the post-posture change time interval 414 for comparison to the baseline (pre-spike) average signal amplitude. If the average signal amplitude has not returned to a threshold range of the baseline average signal amplitude during a post-posture change time interval 414, control circuit 80 may not trigger ANS therapy. In other examples, the frequency content of the acceleration signal may be analyzed post-spike to verify that a steady state is reached indicating that the patient is relatively inactive after the signal spike is detected. The acceleration signal amplitudes during the posture change time interval 412 corresponding to body motion during the posture change may not be analyzed by control circuit 80 for determining if ANS is triggered or not in some examples.

[0136] FIG. 8 is a diagram 450 of a timeline of ANS therapy trigger conditions and ANS delivery according to some examples. An acceleration (ACC) signal 451, activity (ACT) metrics 462, heart rate (HR) 472 and ANS pulse train 480 are shown. The acceleration signal 451 may be a single axis signal or represent a combination of the axis signals, e.g., the summed magnitudes of the time-aligned axis signal sample points.

[0137] Control circuit 80 may determine activity metrics 462 from the acceleration signal received from accelerometer 212 according to any of the examples described above. The activity metrics 462 may represent activity counts in some examples. In other examples, the activity metrics 462 may represent an SIR determined from the activity counts, which can be used by control circuit 80 for determining a rate response pacing rate (if rate response pacing is enabled). The activity counts (and corresponding SIRs) may be determined every 0.5 seconds, 1 second, 2 seconds or other desired activity monitoring time interval.

[0138] HR 472 may be determined as the heart rate corresponding to a running mean, median or other representative sensed cardiac event interval or may be determined as the heart rate corresponding to each individual sensed cardiac event interval (e.g., each PPI or RRI) that is determined as Asense or Vsense signals are received from sensing circuit 86. [0139] An acceleration signal spike 452 is detected by control circuit 80. Control circuit 80 may detect the signal spike 452 when the most recent activity metric 462 is less than a low activity threshold 464, indicating that the patient is at rest or relatively inactive when the posture change that causes signal spike 452 takes place. As described in conjunction with FIG. 6, when the activity metric 462 is less than the low activity threshold 464, acceleration signal spike detection may be enabled so that signal spike 452 can be detected by control circuit 80 for triggering ANS therapy.

[0140] Control circuit 80 may start a post-spike time interval 454 during which HR 472 is monitored for detecting an increase that is an indication of the onset of POTS. The HR may be compared to a HR change threshold 474 by control circuit 80. The HR change threshold 474 may represent a threshold increase 477 from the baseline HR 476. Control circuit 80 may determine the baseline HR 476 at the time of the most recent activity metric 462 prior to detecting the signal spike 452 or at the time of the signal spike detection 452. The HR change threshold 474 can be determined by control circuit 80 by adding the threshold increase 477 (which may be stored in memory 82) to the baseline HR 476. In some examples, the threshold increase 477 is 30 bpm, with no limitation intended.

[0141] Additionally or alternatively, control circuit 80 may detect an increased HR when the HR 472 meets a high rate threshold 475, which may be in addition to meeting the HR change threshold 474. The high rate threshold 475 may be 90 to 140 bpm and may be programmed according to a given patient’s heart rate profile. The high rate threshold 475 may be higher or lower than the HR change threshold 474 at different times depending on the baseline HR 476 at the time of signal spike detection. In some examples, control circuit 80 may detect an increased HR for triggering ANS delivery when the baseline HR increases by at least 30 bpm (or other threshold change) within the post-spike time interval 454 and reaches at least the high rate threshold 475.

[0142] In the example shown, the HR 472 increases from the baseline HR 476 by at least the threshold change 477, crossing the heart rate threshold 474, within the post-spike time interval 454. The HR 472 also meets the high rate threshold 475 within the post-spike time interval 454. Control circuit 80 determines that ANS trigger conditions are met and controls therapy delivery circuit 84 to initiate the ANS pulse train 480.

[0143] In this example, the ANS pulse train 480 is a continuous pulse train delivered according to ANS delivery control parameters. For example, the ANS pulse train 480 may be delivered independent of the timing of Asense or Vsense signals. In some examples, The ANS pulse train 480 may be started upon receiving an Asense signal and be delivered continuously until a termination condition is detected.

[0144] The pulses of the ANS pulse train 480 have a starting pulse amplitude 482, a pulse with 484, and a pulse period 486 that defines the frequency of the pulse train 480, in accordance with the ANS delivery control parameters stored in memory 82. It is to be understood that the illustrated pulse train 480 is scaled to illustrate features of the individual pulses in the pulse train for the sake of clarity. As such, pulse train 480 may not be illustrated to scale in time relative to the HR changes, activity metrics 462, acceleration signal 451, and post-spike time interval 454.

[0145] In this example, the activity metrics 462 remain below the low activity threshold 464 after the ANS pulse train 480 is initiated. When no increase in activity metrics 462 occur during the ANS pulse train 480, the ANS pulse train 480 is not adjusted based on activity metrics 462. In the example shown, control circuit 80 detects a decrease in HR 472 during the ANS pulse train 480. In some examples, if the HR 472 falls to or below a normal HR threshold 478, therapy delivery circuit 84 may begin terminating the ANS by gradually ramping down one or more ANS delivery control parameters. For the sake of illustration, the pulse amplitude 482 is gradually decreased according to a ramp down rate 490 in response to the HR 472 falling below the normal HR threshold 478 during ANS therapy delivery. When the pulse amplitude reaches a minimum amplitude, which may be zero or greater than zero, the ANS may be completely terminated. In other examples, the pulse width 484 may be decreased, instead of or in addition to decreasing the pulse amplitude (with or without a concomitant increase in the inter-pulse interval to either maintain or increase the pulse train frequency, respectively).

[0146] The HR 472 may fall below the normal HR threshold 478 but remain higher than the baseline HR 476 in some instances because the HR may normally be higher if the patient is standing, for example, compared to the sitting HR. As such the normal HR threshold 478 may be greater than the baseline HR but may be less than the HR change threshold 474 that represents the threshold increase 477 in HR above the baseline HR 476. For example, the normal HR threshold 478 may be 5, 10, 15 or 20 bpm greater than the baseline HR 472. In other examples, the normal HR threshold 478 may be a specified rate, e.g., 70 to 100 bpm, below which the patient is expected not to experience POTS symptoms.

[0147] FIG. 9 is a diagram 500 of a timeline of ANS trigger conditions and ANS delivery according to another example. An acceleration (ACC) signal 502, activity (ACT) metrics 512, HR 522 and ANS pulse train 580 are shown. Control circuit 80 may detect the acceleration signal spike 502 and start a post-spike time interval 504 for monitoring HR and activity metrics for determining whether to trigger therapy delivery circuit 84 to start delivering of ANS. Control circuit 80 may determine that the most recent activity metric 512a prior to the detected signal spike 502 is less than a low activity threshold 514 in order to enable signal spike detection and/or start the post-spike time interval 504 for detecting additional ANS triggering conditions in response to a signal spike detection. If the activity metric 512a was greater than the low activity threshold 514, control circuit 80 may ignore or not enable detection of the signal spike 502 or withhold starting the post-spike time interval 504 for monitoring for HR related and activity metric related ANS trigger conditions.

[0148] The HR 522 reaches the HR change threshold 524, representing at least a threshold increase 527 from the baseline HR 526, within the post-spike time interval 504. In this example, a high rate threshold is not applied to HR 522 as described above in conjunction with FIG. 8. It is to be understood, however, that in addition to applying the HR change threshold 524, a high rate threshold may be applied to HR 522 for determining if a HR related trigger condition for initiating ANS is met.

[0149] In the example of FIG. 9, control circuit 80 may compare the next activity metric 512b determined after signal spike detection 502 to the low activity threshold 514 or to a second slightly higher threshold 516 corresponding to a standing activity level to verify that the detected HR increase has occurred following the acceleration signal spike 502 but without an accompanying increase in physical activity. The first activity threshold 514 may be referred to as a “spike detection enabling threshold” and the second activity threshold 516 may be referred to as an “ANS trigger condition threshold.” The second activity threshold 516 may be greater than the first activity threshold 514. In other examples, the first activity threshold 514 and the second activity threshold 516 are equal. [0150] In response to the pre-spike activity metric 512a being less than the low activity threshold 514, the detected signal spike 502, the detected increased HR after the detected signal spike 502, and the post-spike activity metric 512b being less than the second activity threshold 516, therapy delivery circuit 84 initiates the ANS pulse train 580. Control circuit 80 determines that the ANS trigger conditions are met when the signal spike is detected and followed by the HR and the activity metrics meeting ANS trigger conditions. [0151] In this example, the ANS pulse train 580 is a continuous pulse train delivered according to ANS delivery control parameters. As described below, in other examples ANS may be delivered as discontinuous pulse trains, e.g., with each pulse train being started in response to an Asense (or Vsense signal) or a delivered pacing pulse and delivered during the atrial refractory period and/or AV nodal refractory period. In this example, the ANS pulse train 580 has a starting pulse amplitude 582 and a pulse width 584 and a pulse train frequency defined by the pulse period. The pulse width 584 of individual pulses of ANS pulse train 580 are scaled for the sake of clarity and not necessarily scaled in time relative to the other signals and events shown in FIG. 9. The frequency of pulse train 580 may be 20 to 100 Hz, 30 to 80 Hz or 40 to 60 Hz in various examples.

[0152] In this example, the HR 522 begins to decrease during the ANS pulse train 580 but does not fall to the normal HR threshold 528 before an activity metric 512c is determined to meet an increased activity threshold 518. An increased physical activity onset 506 can be observed in the acceleration signal 502 after the posture change associated with signal spike 502. For instance, the patient may begin walkingjogging, running or engaging in other increased physical activity after sitting up or standing up. As described in conjunction with FIG. 6, if control circuit 80 detects an increase in patient physical activity (e.g., an activity count that is greater than at least an ADL threshold or a higher physical exertion threshold) after ANS is started, control circuit 80 may control therapy delivery circuit 84 to begin terminating the ANS pulse train 580.

[0153] As shown in FIG. 9, when the activity metric 512c meets the increased activity threshold 518, therapy delivery circuit 84 begins ramping down an ANS delivery control parameter, in this case pulse amplitude, according to a ramp down rate 590. The ramp down rate 590 may be the same as the ramp down rate 490 shown in FIG. 8 applied in response to detecting a decrease in HR to the normal HR threshold 478. In other examples, when the HR needs to increase to support the increased physical activity, the ramp down rate 590 applied in response to an increased activity metric during ANS may be a faster ramp down rate than the ramp down rate 490 applied in response to detecting a decreased HR.

[0154] The HR 522 is allowed to increase as the ANS pulse train 580 is ramped down and may reach a sinus rate 532 that is appropriate for the increased activity metrics 512c/512d. In some cases, the increased HR following the increased activity metric 512c may be caused by rate responsive pacing being delivered by therapy delivery circuit 84 rather than an intrinsic heart rate. If only HR is monitored after initiating ANS therapy for determining when to terminate the ANS therapy, the ANS therapy may continue during the increased activity, when sympathetic tone should increase with decreased parasympathetic tone. As such, when rate response pacing is enabled and being delivered by therapy delivery circuit 84, control circuit 80 may initiate termination of ANS based on the increased activity metric. By terminating the ANS pulse train 580, the intrinsic heart rate may increase to the exercising heart rate 532 needed to support the activity level of the patient, precluding the need for rate response pacing.

[0155] As long as the activity metrics 512, e.g., activity metrics 512c and 512d, remain above the low activity threshold 514, control circuit 80 may disable acceleration signal spike detection or ignore any subsequently detected signal spikes. In this way, ANS therapy is not triggered again due to signal spikes in the acceleration signal 501 until the activity metrics 512 fall below the low activity threshold 514.

[0156] FIG. 10 is a diagram 600 of different ramp down rates that may be applied to an ANS delivery control parameter for gradually terminating ANS therapy in response to detecting a decreased HR or an increased activity metric during ANS delivery. The value of an ANS delivery control parameter may be at its maximum (MAX) or starting value at the time that an increased activity metric or decreased HR is detected after starting ANS delivery. The maximum value here does not necessarily mean the maximum available setting for the ANS delivery control parameter. Rather, the maximum value here refers to the highest value of the ANS delivery control parameter that is applied during the ANS therapy, e.g., the highest pulse amplitude, longest pulse width, or highest pulse number per pulse train, as examples, delivered according to the programmed ANS delivery control parameter values.

[0157] At time point 602, control circuit 80 may detect a HR decrease (e.g., less than a normal HR threshold) or an activity metric increase (e.g., greater than an increased activity threshold) that warrants termination of the ANS therapy according to any of the examples described above. The ANS delivery control parameter value (plotted on the y-axis) may be adjusted from the current value, e.g., the maximum value 604, down to the minimum value 614. The minimum value may be zero for a given ANS delivery control parameter but may be a non-zero value in some examples. The minimum value may be a value below which the ANS pulse train is not expected to have a therapeutic effect of increasing parasympathetic tone.

[0158] The ramp down rate at which the ANS delivery control parameter is decreased may be scaled according to the patient’s activity level at time 602. If a most recent activity metric indicates a resting level of activity at time 602, therapy delivery circuit 84 may ramp down the ANS delivery control parameter at the slowest ramp down rate 620. The ANS pulse train(s) may be delivered according to the ramped down control parameter value until the minimum value 614 is reached, at which point the ANS therapy is fully terminated (until the next time the ANS triggering conditions are met).

[0159] If the most recently determined activity metric is greater than an ADL threshold at time point 602, therapy delivery circuit 84 may ramp down the ANS delivery control parameter according to the second, faster ramp down rate 622. In this way, the intrinsic heart rate may be allowed to increase appropriately in response to the higher, non-resting activity level.

[0160] If the most recently determined activity metric is greater than an exertion threshold level, indicating relatively high physical exertion at time point 602 that is greater than ADL, therapy delivery circuit 84 may ramp down the ANS delivery control parameter according to the third, fastest ramp down rate 624. In this way, the intrinsic heart rate may be allowed to increase according to a normal physiological response to the higher, nonresting activity level. It is recognized that in some cases ANS therapy may be terminated as therapy delivery circuit 84 is delivering atrial or ventricular pacing at a rate response rate as described above in conjunction with FIG. 9.

[0161] While three different ramp down rates 620, 622 and 624 are shown in FIG. 10, it is contemplated that one, two or more than three ramp down rates may be defined for corresponding activity metric levels and/or HR for controlling how quickly or slowly the ANS therapy is terminated after detecting a decreased HR and/or an increased activity level.

[0162] FIG. 11 is a timing diagram 700 of ANS pulse trains 720 that may be delivered by therapy delivery circuit 84 according to some examples. An atrial EGM signal 702 and a ventricular EGM signal 710 may be sensed by sensing circuit 86. Sensing circuit 86 may sense atrial P-waves 704 and pass Asense signals 706 to control circuit 80, e.g., in response to P-wave sensing threshold crossings. Sensing circuit 86 may sense R-waves 712 and pass Vsense signals 716 to control circuit 80, e.g., in response to R-wave sensing threshold crossings.

[0163] In response to ANS therapy trigger conditions being met, according to any of the examples described above, therapy delivery circuit 84 may start delivering ANS pulse trains 720. In some examples, each of the ANS pulse trains 720 is started in response to a received Asense signal 706. In this way, each of the ANS pulse trains 720 may be delivered, at least in part, during the atrial refractory period following an atrial depolarization.

[0164] The ANS pulse trains 720 are delivered according to ANS delivery control parameters that avoid capturing the myocardium. The ANS pulse trains 720 are delivered according to ANS delivery control parameters to increase the parasympathetic tone and promote a decrease in the intrinsic atrial rate. The ANS delivery control parameters can include the starting pulse amplitude 722 and starting pulse width 724. The pulse energy may be increased or decreased by increasing or decreasing the programmed starting pulse amplitude 722 and/or pulse width 724 as needed to promote a therapeutic effect of decreasing the atrial rate when an increased HR is detected after a detected signal spike. [0165] The starting pulse amplitude 722 may be between 0.25 and 12.0 volts (V), between 1 V and 10 V, or between 4 V and 8 V as non-limiting examples. The pulse width 724 may be 0.1 to 10 milliseconds (ms) or about 0.2 to 1 ms as non-limiting examples. The individual pulses of each of the ANS pulse trains 720 are shown as monophasic pulses in FIG. 11. In other examples, the pulses in each pulse train 720 may be multi-phasic, e.g., biphasic, triphasic, etc. The pulses of each pulse train 720 are shown as positive polarity pulses in FIG. 11. In other examples, the pulses may be negative polarity pulses or a combination of positive and negative polarity pulses, e.g., alternating positive and negative pulses or n positive pulses followed by n negative pulses, etc. In still other examples, therapy delivery circuit 84 may control the polarity of the ANS pulse trains 252 to alternate, e.g., one pulse train may be all negative polarity pulses and the next pulse train may be all positive polarity pulses.

[0166] Each pulse within the pulse train is separated from the next pulse by an inter-pulse interval 726. The inter-pulse interval 726 may be 5 to 100 ms as non-limiting examples. The inter-pulse interval 726 may be selected in combination with the pulse width 724 to obtain a desired pulse frequency. The pulse frequency, i.e., the frequency of the pulses within each one of the ANS pulse trains 720, is defined by the inverse of the pulse period defined by the sum of the pulse width 724 and the inter-pulse interval 726. The pulse frequency can be increased by decreasing the pulse width 724 and/or decreasing the interpulse interval 726. The pulse frequency may be 20 to 100 Hz, 30 to 80 Hz or 40 to 60 Hz in various examples. For instance, to achieve a pulse frequency of approximately 40 to 60 Hz when the pulse width is about 0.2 ms in duration, the inter-pulse interval may be between approximately 16 and 25 ms.

[0167] The pulse train duration 728 is defined by the number of pulses in the pulse train and the pulse period. The pulse train duration 728 may be 100 ms to 1 second long or between 200 and 500 ms long as examples, with no limitation intended. The pulse trains may be, with no limitation, 1 to 20 pulses long or 3 to 6 pulses long with a frequency of 10 to 20 Hz as examples. The pulse train duration 728 can be increased by increasing the pulse number and/or decreasing the pulse frequency. A relatively greater increase in parasympathetic tone for achieving the therapeutic benefit of reduced atrial rate and alleviation of symptoms associated with POTS may be achieved by ANS pulse trains 720 having relatively higher pulse energy, higher frequency and/or longer pulse train duration 728. A relative lower increase in parasympathetic tone may be achieved by relatively lower pulse energy, lower pulse frequency, and/or shorter pulse train duration 728. As such, the ANS delivery control parameters may be tuned to achieve a desired parasympathetic response as evidenced by a decreasing HR. The HR decrease may occur more rapidly or less rapidly depending on the strength (e.g., pulse energy and pulse frequency) and duration 728 of the ANS pulse trains.

[0168] As described above, control circuit 80 may detect an ANS termination condition. The ANS termination condition may be an increased activity metric during ANS delivery, a decreased HR during ANS delivery or a maximum ANS delivery time out, as examples. Therapy delivery circuit 84 may begin a ramp down process to gradually terminate the ANS therapy in response to the AND termination condition.

[0169] In the example shown, control circuit 80 may detect a decrease in HR in response to the PPI 732 (between consecutive Asense signals 706) meeting a normal HR threshold interval. In other examples, control circuit 80 may detect a decrease in HR in response to the PPI 732 being longer than the preceding PPI 730. While a single longer PPI 732 is shown in FIG. 11 for the sake of illustration, it is to be understood from the examples given above that control circuit 80 may detect a decreased HR based on an analysis of multiple sensed cardiac event intervals.

[0170] In response to detecting the decreased HR, therapy delivery circuit 84 may deliver the next ANS pulse train 740 at a lower pulse energy. The pulse energy may be ramped down by decreasing the pulse amplitude and/or the pulse width on successive ANS pulse trains. In this example, the pulse amplitude 736 is reduced from the starting pulse amplitude 722, with the pulse width, pulse frequency and the pulse train duration remaining the same. In other examples, one or more of the pulse amplitude, pulse width, pulse frequency and/or pulse train duration may be progressively decreased over one or more ANS pulse trains to ending or minimum values at which point ANS therapy is fully terminated. It is to be understood that the pulse frequency may not be reduced or is reduced to a minimum frequency, e.g., not less than 20 Hz, to avoid capturing myocardial tissue.

[0171] In this example, the ANS pulse trains 720 are delivered during the atrial refractory period and may or may not extend later than the atrial refractory period after each Asense signal 706. In some examples, the pulse train duration 720 may extend into at least a portion of the ventricular refractory period. In other examples, the ANS pulse trains are terminated prior to the Vsense signals to avoid any excessive prolongation of AV nodal conduction. In still other examples, the ANS pulse trains may be triggered on each Vsense signal 716 instead of by each of the Asense signals 706 as shown. The pulse train duration may defined to be as long as or shorter than the atrial refractory period or as long as or shorter than the ventricular refractory period when the Asense signals 706 or the Vsense signals 716, respectively, are used by control circuit 80 as the trigger for starting the ANS pulse trains. For instance, the Asense signals 706 may be used to trigger each ANS pulse train unless atrial fibrillation is detected or the atrial rate is faster than a threshold fast atrial rate. In this case, the Vsense signals 716 may be used by control circuit 80 to trigger the ANS pulse trains. In still other examples, ANS pulse trains may be triggered by both Asense signals and Vsense signals and delivered during both of the respective atrial refractory periods and ventricular refractory periods. It is contemplated that when the IMD is configured to detect ventricular tachyarrhythmias, ANS may be withheld or terminated if ventricular tachycardia or ventricular fibrillation is being detected. [0172] FIG. 12 is a flow chart 800 of a method performed by a medical device system for controlling ANS therapy according to another example. At block 802, control circuit 80 receives sensed cardiac event signals from sensing circuit 86 and acceleration signals from sensor circuit 92 for detecting when ANS therapy trigger conditions are met according to any of the examples described above. At block 804, control circuit 80 may determine that ANS therapy trigger conditions are met when at least an acceleration signal spike is detected. As described above, the ANS therapy trigger conditions may be determined to be met when the acceleration signal spike is detected and an increased HR is detected within a post-spike time interval without an increase in an activity metric.

[0173] As long as ANS trigger conditions remain unmet, ANS therapy is not delivered. In some examples, the medical device system may receive a POTS confirmation signal entered by the patient or another caregiver via an external device, as described in conjunction with FIG. 1. In some examples, the patient may be able to trigger ANS therapy by overriding the ANS trigger condition requirements using external device 50. In other examples, when IMD 14 receives a POTS confirmation signal from external device 50, control circuit 80 may determine if secondary ANS trigger conditions are met at block 808.

[0174] In some examples, if a POTS confirmation signal is received and at least one other ANS therapy trigger conditions is met, control circuit 80 may determine that secondary ANS trigger conditions are met at block 808. For instance, if an acceleration signal spike has been detected and a POTS confirmation signal is received, control circuit 80 may trigger delivery of ANS therapy by therapy delivery circuit 84 at block 814, even if other ANS trigger conditions relating to HR and activity are not met. In other examples, if a POTS confirmation signal is received and a threshold increase is HR has been detected, control circuit 80 may trigger the delivery of ANS therapy at block 814. In yet another example, if the POTS confirmation signal is received at block 806 and a signal spike has been detected but ignored because the pre-spike activity metric is greater than the low activity threshold, control circuit 80 may trigger ANS therapy delivery at block 814. If secondary ANS trigger conditions are unmet at block 808, control circuit 80 may advance to block 810.

[0175] In response to receiving the POTS confirmation signal at block 806 by the external device, acceleration signal data and/or HR data corresponding to the confirmed POTS episode may be logged in the medical device system memory at block 810. In some examples, external device 50 may transmit an interrogation signal to IMD 14 to request a transmission of data from IMD 14. In other examples, the external device 50 may transmit the POTS confirmation signal to IMD 14 at block 806 so that IMD 14 can log acceleration signal and/or HR data in memory 82 as an untreated POTS episode at block 810.

[0176] Control circuit 80 may buffer a most recent segment of the acceleration signal used for signal spike detection in memory 82 so that when the POTS confirmation signal is received, a segment of the acceleration signal is available for analysis. In some cases a signal spike may have been detected but other ANS trigger conditions unmet. In other examples, no signal spike may have been detected precluding the ANS trigger conditions from being met. If the signal spike was not detected, control circuit 80 may adjust one or more thresholds or ranges stored in memory 82 as the posture change motion criteria used for detecting an acceleration signal spike. For example, a slew rate threshold or a magnitude change threshold applied to the acceleration signal may be lowered so that a signal spike present in the buffered acceleration signal segment would now be detected. [0177] In addition to or alternatively to buffering the acceleration signal segment, control circuit 80 may buffer HR data and/or activity metrics in memory 82 that can be logged in response to receiving the POTS confirmation signal. When a signal spike is detected but HR related and/or activity related ANS therapy trigger conditions are unmet, but a POTS confirmation signal is received, control circuit 80 may analyze the HR data and/or activity metrics to adjust one or more thresholds or other criteria applied by control circuit 80 for detecting the ANS therapy trigger conditions.

[0178] In some instances, the patient activity level may be higher than the low activity threshold at the time of an undetected or ignored signal spike when a POTS confirmation signal is received. In this case, the low activity threshold (e.g., see low activity threshold 464 in FIG. 8) may be increased by control circuit 80 so that signal spike detection can be enabled at relatively higher patient activity levels.

[0179] In other examples, the HR related trigger conditions may be adjusted. For instance, the increased HR threshold 474 may be decreased (e.g., by decreasing the threshold increase 476 from a baseline HR as shown in FIG. 8) based on the HR change determined from the logged data associated with the untreated POTS episode. Additionally or alternatively, the high rate threshold 475 (shown in FIG. 8) may be decreased or the requirement may be removed from the ANS therapy trigger conditions in some examples. In general, if the logged data associated with one or more confirmed but untreated POTS episodes indicates that POTS is occurring when a smaller increase in HR and/or at lower HRs than the HR related trigger condition requires, the HR related trigger condition can be adjusted by control circuit 80.

[0180] In still other examples, activity related trigger conditions may be adjusted at block 812 based on logged activity metrics associated with confirmed POTS episodes. As described above, the pre-spike low activity threshold may be increased. Additionally or alternatively, a post-spike ANS trigger condition threshold, e.g., the second activity threshold 516 shown in FIG. 9, may be increased to enable ANS therapy trigger conditions to be met if the patient activity metrics associated with the confirmed POTS episode(s) is higher than the current post-spike ANS trigger condition threshold, preventing ANS therapy from being delivered.

[0181] In some examples, multiple POTS confirmation signals may be received so that any adjustments to the ANS trigger condition detection control parameters performed at block 812 may be based on data logged for multiple POTS episodes. Furthermore, while the adjustment to the ANS trigger condition detection parameters at block 812 is shown to occur in the flow chart 800 after ANS trigger conditions are not met, it is contemplated that the ANS trigger condition data may be logged when ANS therapy is triggered and/or when POTS confirmation signals are received. In this way, control circuit 80 may determine when activity metrics, HRs, and/or signal spike features are just meeting ANS trigger conditions such that in some instances the ANS trigger conditions are not met and in other instances ANS trigger conditions are met. Control circuit 80 may identify one or more ANS trigger condition detection control parameter that, if adjusted, can increase the likelihood of triggering ANS therapy for POTS episodes that have been confirmed by a user entered signal but were not treated by ANS therapy.

[0182] Furthermore it is contemplated that the data logged at block 810, with or without episode data logged in memory 82 when ANS therapy trigger conditions are met, may be presented to a clinician or other user by external device 50. In some examples, the clinician may review confirmed POTS episode data to manually adjust ANS therapy trigger condition detection control parameters programmed into IMD 14 to increase the likelihood of ANS therapy being delivered when the patient is likely to experience POTS. [0183] Further disclosed herein is the subject matter of the following examples: [0184] Example 1. A medical device system comprising a sensor circuit configured to sense an acceleration signal, a cardiac signal sensing circuit configured to sense a cardiac signal, and a memory configured to store posture change motion criteria. The medical device system further comprising a control circuit configured to detect a signal spike from the acceleration signal that meets the posture change motion criteria, detect a first heart rate from the cardiac signal sensed by the cardiac signal sensing circuit after the signal spike is detected and detect an increased heart rate based on the first heart rate. The medical device system further comprising a therapy delivery circuit configured to deliver autonomic nervous stimulation (ANS) for decreasing the first heart rate in response to the control circuit detecting the spike and the increased heart rate.

[0185] Example 2. The medical device system of example 1 wherein the control circuit is further configured to determine a pre-spike patient physical activity metric from the acceleration signal sensed by the sensor circuit before the detected posture signal spike and determine that the pre-spike patient physical activity metric is less than a low activity threshold. The therapy delivery circuit is further configured to deliver the ANS for decreasing the first heart rate in response to the control circuit detecting the signal spike, detecting the increased heart rate and determining that the pre-spike patient activity level is less than the activity threshold.

[0186] Example 3. The medical device system of any one of examples 1 — 2 wherein the sensor circuit is further configured to sense a patient activity signal. The control circuit is further configured to determine a post-spike patient physical activity metric from the patient activity signal sensed by the sensor circuit after detecting the signal spike and determine that the post-spike patient physical activity metric is less than an increased activity threshold. The therapy delivery circuit is further configured to deliver the ANS for decreasing the first heart rate in response to the control circuit determining that the postspike patient physical activity metric is less than the increased activity threshold after the signal spike is detected and detecting the increased heart rate.

[0187] Example 4. The medical device system of any one of examples 1 — 3 wherein the control circuit is further configured to determine a baseline heart rate from the cardiac signal sensed by the cardiac signal sensing circuit and determine a heart rate change as a difference between the baseline heart rate and the first heart rate. The control circuit may detect the increased heart rate by determining that the heart range change meets a threshold increase and determining that the first heart rate is greater than a high rate threshold.

[0188] Example 5. The medical device system of any one of examples 1 — 4 wherein the cardiac signal sensing circuit is configured to sense the cardiac signal by sensing an atrial signal. The control circuit is further configured to detect the increased heart rate by determining a baseline atrial rate from atrial signal sensed within a first time interval of the detected signal spike, determining the first heart rate from the atrial signal, determining an atrial rate difference between the baseline atrial rate and the first heart rate and detecting the increased heart rate by at least determining that the atrial rate difference is greater than a threshold increase.

[0189] Example 6. The medical device system of any one of examples 1 — 5 wherein the sensor circuit is further configured to sense a patient activity signal. The control circuit is further configured to determine a patient physical activity metric from the patient activity signal sensed by the sensor circuit after the therapy delivery circuit starts delivering the ANS and detect increased patient physical activity based on the patient physical activity metric determined after the therapy delivery circuit starts delivering the ANS. The therapy delivery circuit is further configured to terminate the ANS in response to the control circuit detecting the increased patient physical activity.

[0190] Example 7. The medical device system of any one of examples 1 — 6 wherein the control circuit is further configured to determine a second heart rate from the cardiac signal sensed by the cardiac signal sensing circuit after the therapy delivery circuit starts delivering the ANS and determine that the second heart rate is less than the first heart rate. The therapy delivery circuit is further configured to terminate the ANS in response to the control circuit determining that the second heart rate is less than the first heart rate.

[0191] Example 8. The medical device system of any one of examples 1 — 7 wherein the therapy delivery circuit is further configured to deliver the ANS according to a therapy delivery control parameter and terminate the ANS by ramping down the therapy delivery control parameter.

[0192] Example 9. The medical device system of any one of examples 1 — 8 wherein the sensor circuit is further configured to sense a patient activity signal. The control circuit is further configured to detect an increased patient physical activity from the patient activity signal sensed by the sensor circuit after the therapy delivery circuit starts delivering the ANS and determine a ramp down rate based on the detected increased patient physical activity. The therapy delivery circuit is further configured to deliver the ANS according to a therapy delivery control parameter and terminate the ANS by ramping down the therapy delivery control parameter according to the ramp down rate determined by the control circuit.

[0193] Example 10. The medical device system of any one of examples 1 — 9 wherein the control circuit is further configured to receive a patient confirmation signal confirming an episode of postural orthostatic tachycardia syndrome and buffer, in the memory, data determined from the acceleration signal and the cardiac signal in response to receiving the patient confirmation signal.

[0194] Example 11. The medical device system of example 10 wherein the control circuit is further configured to adjust an ANS trigger condition detection control parameter in response to receiving the patient confirmation signal and detect an ANS trigger condition in response to at least one of the acceleration signal or the cardiac signal meeting the adjusted ANS trigger condition detection control parameter. The therapy delivery circuit is further configured to deliver the ANS in response to the control circuit detecting the ANS trigger condition.

[0195] Example 12. The medical device system of example 11 wherein the control circuit is further configured to adjust the ANS trigger condition detection control parameter by adjusting at least one of a pre-spike low activity threshold; a signal spike detection threshold; a post-spike activity threshold; an increased heart rate threshold; or a high heart rate threshold.

[0196] Example 13. The medical device system of any one of examples 10 — 12 further comprising an external device having a display unit and a user interface for receiving the patient confirmation signal. The medical device system comprising an implantable medical device comprising the sensor circuit, the cardiac signal sensing circuit, the memory, the control circuit and the therapy delivery circuit. The implantable medical device further comprising a telemetry circuit for transmitting the buffered data. The external device being configured to display the buffered data by the display unit.

[0197] Example 14. The medical device system of any one of examples 1 — 13 wherein the control circuit is further configured to determine a second heart rate from the cardiac signal sensed by the cardiac signal sensing circuit after the therapy delivery circuit starts delivering the ANS, determine that the second heart rate is not decreased compared to the first heart rate and adjust an ANS delivery control parameter in response to determining that the second heart rate is not decreased compared to the first heart rate. The therapy delivery circuit is further configured to deliver the ANS according to the adjusted ANS delivery control parameter.

[0198] Example 15. The medical device system further comprising an electrode coupled to the therapy delivery circuit for delivering the ANS to a therapy delivery site for increasing parasympathetic tone.

[0199] Example 16. The medical device system of any one of examples 1 — 15 wherein the therapy delivery circuit is further configured to deliver the ANS by delivering a continuous pulse train.

[0200] Example 17. The medical device system of any one of examples 1 — 16 wherein the cardiac signal sensing circuit is further configured to sense cardiac event signals from the cardiac signal by sensing at least one of atrial P-waves or ventricular R-waves from the cardiac signal. The therapy delivery circuit is further configured to deliver the ANS by delivering a plurality of discontinuous pulse trains, wherein each pulse train is triggered in response to one of an atrial P-wave sensed by the cardiac signal sensing circuit or a ventricular R-wave sensed by the sensing circuit.

[0201] Example 18. A method comprising sensing an acceleration signal, sensing a cardiac signal, storing posture change motion criteria in a medical device memory and detecting a signal spike from the acceleration signal that meets the posture change motion criteria. The method further including detecting a first heart rate from the cardiac signal sensed after the signal spike is detected, detecting an increased heart rate based on the first heart rate and in response to detecting the spike and the increased heart rate, delivering autonomic nervous stimulation (ANS) for decreasing the first heart rate.

[0202] Example 19. The method of example 18 further comprising determining a prespike patient physical activity metric from the acceleration signal sensed before the detected posture signal spike, determining that the pre-spike patient physical activity metric is less than a low activity threshold. In response to detecting the signal spike, detecting the increased heart rate and determining that the pre-spike patient activity level is less than the activity threshold, delivering the ANS for decreasing the first heart rate. [0203] Example 20. The method of any one of examples 18 — 19 further comprising sensing a patient activity signal, determining a post-spike patient physical activity metric from the patient activity signal sensed after detecting the signal spike and determining that the post-spike patient physical activity metric is less than an increased activity threshold. In response to determining that the post-spike patient physical activity metric is less than the increased activity threshold after the signal spike is detected and detecting the increased heart rate, delivering the ANS for decreasing the first heart rate.

[0204] Example 21. The method of any one of examples 19 — 20 further comprising determining a baseline heart rate from the cardiac signal, determining a heart rate change as a difference between the baseline heart rate and the first heart rate and detecting the increased heart rate by determining that the heart range change meets a threshold increase and determining that the first heart rate is greater than a high rate threshold.

[0205] Example 22. The method of any one of examples 18 — 21 further comprising sensing the cardiac signal by sensing an atrial signal and detecting the increased heart rate by determining a baseline atrial rate from atrial signal sensed within a first time interval of the detected signal spike, determining the first heart rate from the atrial signal, determining an atrial rate difference between the baseline atrial rate and the first heart rate and detecting the increased heart rate by at least determining that the atrial rate difference is greater than a threshold increase.

[0206] Example 23. The method of any one of examples 18 — 22 further comprising sensing a patient activity signal, determining a patient physical activity metric from the patient activity signal sensed after the ANS is started and detecting an increased patient physical activity based on the patient physical activity metric determined after the ANS delivery is started. The method further including terminating the ANS in response to detecting the increased patient physical activity.

[0207] Example 24. The method of any one of examples 18 — 23 further comprising detecting, from the cardiac signal sensed after the ANS delivery is started, a second heart rate that is less than the first heart rate and terminating the ANS in response to detecting the second heart rate less than the first heart rate.

[0208] Example 25. The method of any one of examples 18 — 24 further comprising delivering the ANS according to a therapy delivery control parameter and terminating the ANS by ramping down the therapy delivery control parameter. [0209] Example 26. The method of any one of examples 18 — 25 further comprising sensing a patient activity signal, detecting an increased patient physical activity from the patient activity signal sensed after the ANS delivery is started and determining a ramp down rate based on the detected increased patient physical activity. The method further including delivering the ANS according to a therapy delivery control parameter and terminating the ANS by ramping down the therapy delivery control parameter according to the determined ramp down rate.

[0210] Example 27. The method of any one of examples 18 — 26 further comprising receiving a patient confirmation signal confirming an episode of postural orthostatic tachycardia syndrome and buffering data determined from the acceleration signal and the cardiac signal in response to receiving the patient confirmation signal.

[0211] Example 28. The method of example 27 further comprising, in response to receiving the patient confirmation signal, adjusting an ANS trigger condition detection control parameter. The method further including detecting an ANS trigger condition in response to at least one of the acceleration signal or the cardiac signal meeting the adjusted ANS trigger condition detection control parameter and delivering the ANS in response to detecting the ANS trigger condition.

[0212] Example 29. The method of example 28 wherein adjusting the ANS trigger condition detection control parameter comprises adjusting at least one of: a pre-spike low activity threshold; a signal spike detection threshold; a post-spike activity threshold; an increased heart rate threshold; or a high heart rate threshold.

[0213] Example 30. The method of any one of examples 27 — 29 further comprising receiving the patient confirmation signal via an external device having a display unit and a user interface, transmitting the buffered data from an implantable medical device to the external device and displaying the buffered data by the display unit.

[0214] Example 31. The method of any one of examples 18 — 30 further comprising determining a second heart rate from the cardiac signal sensed after the ANS delivery starts, determining that the second heart rate is not decreased compared to the first heart rate, adjusting an ANS delivery control parameter in response to determining that the second heart rate is not decreased from the first heart rate and delivering the ANS according to the adjusted ANS delivery control parameter. [0215] Example 32. The method further comprising delivering the ANS to a therapy delivery site for increasing parasympathetic tone.

[0216] Example 33. The method of any one of examples 18 — 32 further comprising delivering the ANS by delivering a continuous pulse train.

[0217] Example 34. The method of any one of examples 18 — 32 further comprising sensing cardiac event signals from the cardiac signal by sensing at least one of atrial P- waves or ventricular R- waves from the cardiac signal and delivering the ANS by delivering a plurality of discontinuous pulse trains, wherein each pulse train is triggered in response to one of an atrial P-wave sensed from the cardiac signal or a ventricular R-wave sensed from the cardiac signal.

[0218] Example 35. A non-transitory computer readable medium storing posture change motion criteria and a set of instructions which, when executed by control circuitry of a medical device system, cause the medical device system to sense an acceleration signal, sense a cardiac signal and store in a medical device memory, detect a signal spike from the acceleration signal that meets the posture change motion criteria, detect a first heart rate from the cardiac signal sensed after the signal spike is detect and detect an increased heart rate based on the first heart rate. The instructions further causing the medical device system to, in response to detecting the spike and the increased heart rate, deliver autonomic nervous stimulation (ANS) for decreasing the first heart rate.

[0219] It should be understood that, depending on the example, certain acts or events of any of the methods described herein can be performed in a different sequence, may be added, merged, or left out altogether (e.g., not all described acts or events are necessary for the practice of the method). Moreover, in certain examples, acts or events may be performed concurrently, e.g., through multi -threaded processing, interrupt processing, or multiple processors, rather than sequentially. In addition, while certain aspects of this disclosure are described as being performed by a single circuit or unit for purposes of clarity, it should be understood that the techniques of this disclosure may be performed by a combination of units or circuits associated with, for example, a medical device.

[0220] In one or more examples, the functions described may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be stored as one or more instructions or code on a computer-readable medium and executed by a hardware-based processing unit. Computer-readable media may include computer-readable storage media, which corresponds to a tangible medium such as data storage media (e.g., RAM, ROM, EEPROM, flash memory, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer).

[0221] Instructions may be executed by one or more processors, such as one or more digital signal processors (DSPs), general purpose microprocessors, application specific integrated circuits (ASICs), field programmable logic arrays (FPLAs), or other equivalent integrated or discrete logic circuitry. Accordingly, the term “processor,” as used herein may refer to any of the foregoing structure or any other structure suitable for implementation of the techniques described herein. Also, the techniques could be fully implemented in one or more circuits or logic elements.

[0222] Thus, a medical device has been presented in the foregoing description with reference to specific examples. It is to be understood that various aspects disclosed herein may be combined in different combinations than the specific combinations presented in the accompanying drawings. It is appreciated that various modifications to the referenced examples may be made without departing from the scope of the disclosure and the following claims.

Claims

WHAT IS CLAIMED IS:

1. A medical device system comprising: a sensor circuit configured to sense an acceleration signal; a cardiac signal sensing circuit configured to sense a cardiac signal; a memory configured to store posture change motion criteria; a control circuit configured to: detect a signal spike from the acceleration signal that meets the posture change motion criteria; detect a first heart rate from the cardiac signal sensed by the cardiac signal sensing circuit after the signal spike is detected; and detect an increased heart rate based on the first heart rate; and a therapy delivery circuit configured to deliver autonomic nervous stimulation (ANS) for decreasing the first heart rate in response to the control circuit detecting the spike and the increased heart rate.

2. The medical device system of claim 1 wherein: the control circuit is further configured to: determine a pre-spike patient physical activity metric from the acceleration signal sensed by the sensor circuit before the detected posture signal spike; and determine that the pre-spike patient physical activity metric is less than a low activity threshold; and the therapy delivery circuit is further configured to deliver the ANS for decreasing the first heart rate in response to the control circuit detecting the signal spike, detecting the increased heart rate and determining that the pre-spike patient activity level is less than the activity threshold.

3. The medical device system of any one of claims 1 — 2 wherein: the sensor circuit is further configured to sense a patient activity signal; the control circuit is further configured to: determine a post-spike patient physical activity metric from the patient activity signal sensed by the sensor circuit after detecting the signal spike; and determine that the post-spike patient physical activity metric is less than an increased activity threshold; and the therapy delivery circuit is further configured to deliver the ANS for decreasing the first heart rate in response to the control circuit determining that the post-spike patient physical activity metric is less than the increased activity threshold after the signal spike is detected and detecting the increased heart rate.

4. The medical device system of any one of claims 1 — 3 wherein the control circuit is further configured to: determine a baseline heart rate from the cardiac signal sensed by the cardiac signal sensing circuit; determine a heart rate change as a difference between the baseline heart rate and the first heart rate; and detect the increased heart rate by: determining that the heart rate change meets a threshold increase; and determining that the first heart rate is greater than a high rate threshold.

5. The medical device system of any one of claims 1 — 4 wherein: the sensor circuit is further configured to sense a patient activity signal; the control circuit is further configured to: determine a patient physical activity metric from the patient activity signal sensed by the sensor circuit after the therapy delivery circuit starts delivering the ANS; and detect increased patient physical activity based on the patient physical activity metric determined after the therapy delivery circuit starts delivering the ANS; and the therapy delivery circuit is further configured to terminate the ANS in response to the control circuit detecting the increased patient physical activity.

6. The medical device system of any one of claims 1 — 5 wherein: the control circuit is further configured to: detect a second heart rate from the cardiac signal sensed by the cardiac signal sensing circuit after the therapy delivery circuit starts delivering the ANS; and determine that the second heart rate is less than the first heart rate; and the therapy delivery circuit is further configured to terminate the ANS in response to the control circuit determining that the second heart rate is less than the first heart rate.

7. The medical device system of any one of claims 1 — 6 wherein the therapy delivery circuit is further configured to: deliver the ANS according to a therapy delivery control parameter; and terminate the ANS by ramping down the therapy delivery control parameter.

8. The medical device system of any one of claims 1 — 7 wherein: the sensor circuit is further configured to sense a patient activity signal; the control circuit is further configured to: detect an increased patient physical activity from the patient activity signal sensed by the sensor circuit after the therapy delivery circuit starts delivering the ANS; and determine a ramp down rate based on the detected increased patient physical activity; and the therapy delivery circuit is further configured to: deliver the ANS according to a therapy delivery control parameter; and terminate the ANS by ramping down the therapy delivery control parameter according to the ramp down rate determined by the control circuit.

9. The medical device system of any one of claims 1 — 8 wherein the control circuit is further configured to: receive a patient confirmation signal confirming an episode of postural orthostatic tachycardia syndrome; and buffer, in the memory, data determined from the acceleration signal and the cardiac signal in response to receiving the patient confirmation signal.

10. The medical device system of any one of claims 1 — 9 wherein: the control circuit is further configured to: determine a second heart rate from the cardiac signal sensed by the cardiac signal sensing circuit after the therapy delivery circuit starts delivering the ANS; determine that the second heart rate is not decreased compared to the first heart rate; and adjust an ANS delivery control parameter in response to determining that the second heart rate is not decreased compared to the first heart rate; and the therapy delivery circuit is further configured to deliver the ANS according to the adjusted ANS delivery control parameter.

11. The medical device system of any one of claims 1 — 10 further comprising an electrode coupled to the therapy delivery circuit for delivering the ANS to a therapy delivery site for increasing parasympathetic tone.

12. The medical device system of any one of claims 1 — 11 wherein the therapy delivery circuit is further configured to deliver the ANS by delivering a continuous pulse train.

13. The medical device system of any one of claims 1 — 12 wherein: the cardiac signal sensing circuit is further configured to sense cardiac event signals from the cardiac signal by sensing at least one of atrial P-waves or ventricular R- waves from the cardiac signal; and the therapy delivery circuit is further configured to deliver the ANS by delivering a plurality of discontinuous pulse trains, wherein each pulse train is triggered in response to one of an atrial P-wave sensed by the cardiac signal sensing circuit or a ventricular R- wave sensed by the sensing circuit.

14. A method comprising: sensing an acceleration signal; sensing a cardiac signal; storing posture change motion criteria in a medical device memory; detecting a signal spike from the acceleration signal that meets the posture change motion criteria; detecting a first heart rate from the cardiac signal sensed after the signal spike is detected; detecting an increased heart rate based on the first heart rate; and in response to detecting the spike and the increased heart rate, delivering autonomic nervous stimulation (ANS) for decreasing the first heart rate.

15. The method of claim 14 further comprising: determining a pre-spike patient physical activity metric from the acceleration signal sensed before the detected posture signal spike; determining that the pre-spike patient physical activity metric is less than a low activity threshold; and in response to detecting the signal spike, detecting the increased heart rate and determining that the pre-spike patient activity level is less than the activity threshold, delivering the ANS for decreasing the first heart rate.