ATRIOVENTRICULAR NODAL STIMULATION DEVICE FOR VENTRICULAR RATE CONTROL
[0001] This application claims the benefit of U.S. Provisional Patent Application, Serial No. 63/511,636, filed June 30, 2023, and U.S. Provisional Patent Application, Serial No. 63/625,269, filed January 25, 2024, the entire contents of each are incorporated herein by reference.
TECHNICAL FIELD
[0002] The disclosure relates generally to a medical device and method for delivering atrioventricular nodal stimulation (AVNS) for controlling the ventricular rate.
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 such as atrial flutter or atrial fibrillation, can be conducted at to the ventricles at a fast and/or irregular rate, which can be symptomatic. Some patients experience chronic or persistent atrial fibrillation (AF) that can result a rapid and/or irregular ventricular rate. Patients diagnosed with chronic or persistent AF may undergo AV nodal ablation with implantation of a pacemaker to provide ventricular pacing. The AV nodal ablation can cause permanent AV conduction block to prevent the AF depolarizations from conducting to the ventricles. The pacemaker can provide ventricular pacing to sustain the heartbeat after AV nodal ablation, which causes the patient to become pacemaker dependent.
SUMMARY
[0006] In general, the disclosure is directed to a medical device and techniques for controlling and delivering AVNS therapy. The medical device may be configured to sense cardiac electrical signals and deliver AVNS and cardiac pacing as needed for promoting a regular ventricular rhythm. AVNS therapy is delivered by delivering trains of pulses to lengthen the refractory period of the AV node. AVNS may be delivered when a fast and/or irregular ventricular rate is detected to promote a regular ventricular rate. The AVNS therapy may be delivered in the area of the AV node, along a parasympathetic nerve branch or any operative location that effectively suppresses intrinsic AV conduction by the AVNS pulse trains, e.g., by lengthening the refractory period of the AV node. The AVNS pulse trains can be delivered at a pulse train frequency, amplitude and rate and according to other AVNS control parameters to block conduction of some atrial depolarizations to the ventricles but allow some atrial depolarizations to be conducted to the ventricles to promote a controlled rate of ventricular depolarizations during atrial tachyarrhythmia. When the AVNS over-inhibits or over-suppresses intrinsic AV conduction, the medical device may deliver a ventricular pacing pulse to avoid ventricular asystole. [0007] A medical device system operating according to techniques disclosed herein delivers AVNS, delivers ventricular pacing pulses in the absence of a conducted ventricular depolarization during a ventricular pacing escape interval during the AVNS, and may adjust AVNS control parameters in response to a threshold number of ventricular pacing pulses being delivered during the delivered AVNS therapy. The AVNS control parameters may be adjusted to promote intrinsic AV conduction of atrial depolarizations at a stable rate to thereby inhibit or reduce the likelihood of ventricular pacing during delivery of AVNS therapy. In some examples, the medical device system may monitor for lead issues and adjust or disable AVNS in response to detecting a lead issue.
[0008] In one example, the disclosure provides a medical device system including therapy delivery circuitry configured to deliver an AVNS therapy for suppressing AV node conduction by generating pulse trains according to AVNS control parameters and generate ventricular pacing pulses. The medical device system includes control circuitry configured to determine that a threshold number of ventricular pacing pulses are delivered by the therapy delivery circuitry while the therapy delivery circuitry is delivering the AVNS therapy. The control circuitry may adjust at least one AVNS control parameter in response to determining that the threshold number of ventricular pacing pulses have been delivered. [0009] In another example, the disclosure provides a method including delivering an AVNS therapy for suppressing AV node conduction by generating pulse trains according to AVNS control parameters, delivering ventricular pacing pulses, determining that a threshold number of ventricular pacing pulses are delivered while the AVNS therapy is being delivered and adjusting at least one AVNS control parameter in response to determining that the threshold number of ventricular pacing pulses have been delivered. [0010] In yet another example, the disclosure provides a non-transitory computer readable medium storing a set of instructions that, when executed by control circuitry of a medical device system, cause the medical device system to deliver an AVNS therapy for suppressing AV node conduction by generating pulse trains according to AVNS control parameters, deliver ventricular pacing pulses, determine that a threshold number of ventricular pacing pulses are delivered while the AVNS therapy is being delivered and adjust at least one AVNS control parameter in response to determining that the threshold number of ventricular pacing pulses have been delivered. [0011] 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
[0012] FIG. 1 is a conceptual diagram of a medical device system including an implantable medical device coupled to transvenous electrical leads extending to operative positions relative to a patient’s heart.
[0013] FIG. 2 is a conceptual diagram of a medical device system for sensing cardiac electrical signals and delivering AVNS according to some examples.
[0014] FIG. 3 is a conceptual diagram of a medical device system that may include multiple implantable medical devices for sensing cardiac electrical signals, delivering AVNS and delivering ventricular pacing according to another example.
[0015] FIG. 4 is a conceptual diagram of an implantable medical device (IMD) configured to sense cardiac electrical signals, deliver AVNS and deliver ventricular pacing pulses according to some examples.
[0016] FIG. 5 is a flow chart of a method for controlling AVNS by an IMD system according to some examples.
[0017] FIG. 6 is a diagram of AVNS pulse trains that may be delivered by an IMD according to some examples.
[0018] FIG. 7 is a diagram of AVNS pulse trains that may be delivered by an IMD according to another example.
[0019] FIG. 8 is a diagram of AVNS pulse trains that may be delivered by an IMD according to yet another example.
[0020] FIG. 9 is a flow chart of method for controlling AVNS by an IMD system according to another example.
[0021] FIG. 10 is a flow chart of a method for controlling AVNS by an IMD system according to yet another example.
[0022] FIG. 11 is a flow chart of a method for controlling AVNS by an IMD system according to another example. [0023] FIG. 12 is a diagram of an IMD that may be configured to deliver AVNS therapy according to another example.
[0024] FIG. 13A is a diagram of a cross-sectional view of a distal electrode extension of the IMD shown in FIG. 12 according to some examples.
[0025] FIG. 13B is a diagram of the distal electrode extension of the IMD shown in FIG. 12 according to yet another example.
[0026] FIG. 14 is a diagram of an IMD that may be configured to deliver AVNS therapy according to yet another example.
[0027] FIG. 15 is a flow chart of a method that may be performed by an IMD for selecting an AVNS electrode vector according to some examples.
DETAILED DESCRIPTION
[0028] In general, this disclosure describes a medical device and techniques for delivering AVNS. As used herein, “AVNS” refers to stimulation of the AV node directly or indirectly, e.g., via a branch of the vagal nerve that innervates the AV node. AVNS can also be referred to as AV node vagal stimulation (AVNVS) when the vagal nerve or a branch thereof is stimulated to indirectly stimulate the AV node. AVNS can be delivered at an epicardial site, endocardial site, AV nodal fat pad, cardiac nerve plexus, 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 in suppressed conduction of atrial depolarizations to the ventricles via the AV node. The suppressed AV node conduction due to AVNS may be the result of an increased duration of the refractory period of the AV node following a conducted atrial depolarization. The suppressed conduction can have the effect of altering the rate of intrinsically conducted atrial depolarizations to the ventricles such that the ventricular rate can be decreased and/or regulated to provide ventricular rate stability. A medical device system operating according to the techniques disclosed herein may deliver AVNS and modulate or adjust the AVNS to promote ventricular rate stability.
[0029] The AVNS may be delivered as pulse trains delivered at a rate, frequency and pulse energy that inhibits some atrial depolarizations from being conducted to the ventricles during atrial tachyarrhythmia and allows some atrial depolarizations to be conducted to the ventricles. The AVNS may be delivered according to control parameters that can be adjusted to promote intrinsic AV conduction at a target ventricular rate and reduce the likelihood of a ventricular pacing being delivered while AVNS is being delivered. A ventricular pacing pulse delivered “during AVNS” or “during AVNS therapy” refers to a ventricular pacing pulse delivered during a pulse train or between pulse trains of the AVNS therapy while the AVNS therapy is being delivered. In some examples, the AVNS control parameters may be adjusted in a manner that may reduce the power requirements for generating AVNS pulse trains that result in a stable ventricular rate, e.g., a target ventricular rate and/or stability of ventricular event intervals (e.g., RR intervals), while reducing the likelihood or number of ventricular pacing pulses being delivered during AVNS therapy.
[0030] 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, 18, and 21. 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 AVNS.
[0031] 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.
[0032] 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, 18 and 21 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. [0033] In the example shown, connector assembly 17 is configured to receive a proximal lead connector 40, 42 and 44 of each of RA lead 16, RV lead 18 and LV lead 21, respectively. Each lead 16, 18, and 21 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, 18, and 21 may be configured as an industry standard or custom lead connector 40, 42 and 44, respectively. Connector assembly 17 includes connector bores that are appropriately sized for receiving the proximal portion of each lead 16, 18 and 21, e.g., lead connectors 40, 42 or 44. Each connector bore includes electrical contacts that become aligned with and physically mate with a corresponding electrical contact of the respective lead connector 40, 42 or 44 providing physical and electrical connection of each lead 16, 18 and 21 to IMD 14.
[0034] 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 may be advanced transvenously for positioning its distal end, carrying electrodes 20 and 22, into the RA. 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. Tip electrode 20 may be used as a cathode electrode with ring electrode 22 serving as an anode electrode for bipolar pacing and bipolar sensing in the RA. Furthermore, tip electrode 20 and ring electrode 22 may be used for delivering AVNS in the area of the cardiac nerve plexus, e.g., along the posterior wall of the RA, adjacent to the coronary sinus ostium 9. The electrodes 20 and 22 may be positioned along an inferior portion of the posterior RA endocardial wall, adjacent the coronary sinus ostium 9, to provide high frequency bursts of pulses for inhibiting conduction of the AV node during atrial tachyarrhythmia according to the techniques described herein. Electrodes 20 and 22 may be implanted in operative proximity to cardiac nerves, AV nodal fat pad, or other locations that enable electrical pulse trains to be delivered to effectively suppress conduction of atrial depolarizations through the AV node. When atrial tachyarrhythmia is not being detected atrial pacing pulses may be delivered by electrodes 20 and 22 for pacing the RA by 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.
[0035] 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.
[0036] 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.
[0037] 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.
[0038] 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. However, it is to be understood that 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.
[0039] Coil electrodes 24 and 26 (and in some examples housing 15) are sometimes referred to as “defibrillation electrodes” or “CV/DF electrodes” because they can be utilized, individually or collectively, for delivering high voltage CV/DF shocks. However, in some examples, a coil electrode available for delivering CV/DF shocks may be utilized in a cardiac sensing electrode vector to sense cardiac electrical signals or in a pacing electrode vector for delivering pacing pulses. In this sense, the use of the term “defibrillation electrode” or “CV/DF electrode” herein should not be considered as limiting the coil electrodes 24 and 26 for use in only high voltage CV/DF shock therapy applications. While two coil electrodes 24 and 26 are shown along lead body 43 of RV lead 18, in other examples only one coil electrode, e.g., RV coil electrode 24 (which may be used in combination with housing 15 for delivering high voltage shock pulses), or more than two coil electrodes may be carried by lead body 43. In still other examples, two or more coil electrodes may be carried by two or more different lead bodies extending from IMD 14. In still 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. [0040] 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.
[0041] 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, RA tip electrode 20 (which can be used in delivering atrial pacing and AVNS) 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.
[0042] 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.
[0043] 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, e.g., for delivering AVNS according to techniques disclosed herein, bradycardia pacing, post-shock pacing, anti-tachycardia pacing (ATP) therapy or other therapeutic cardiac pacing pulses. In some cases, RV lead electrodes 28 and 30 may be used to deliver high frequency induction pulses delivered to induce a tachyarrhythmia, e.g., during CV/DF threshold testing. 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. In some instances, electrodes 20, 22, 28 and 30 may provide only pacing functionality, only sensing functionality or both. As disclosed herein, the RA electrodes 20 and 22 are provided for delivering AVNS for AV conduction inhibition, which may be in addition to atrial electrical signal sensing and atrial pacing pulse delivery that may be provided via electrodes 20 and 22. In other examples, atrial lead 16 may carry multiple electrodes such that an electrode pair for delivering AVNS may be different than an electrode pair used for delivering atrial pacing pulses and/or an electrode pair used for sensing atrial electrical signals.
[0044] LV lead 21 includes elongated lead body 45 having a proximal connector 44 and distal electrodes 34 and 36. LV lead 21 may be advanced transvenously into the RA, and further into a cardiac vein 32 via the coronary sinus ostium 9 to position electrodes 34 and 36 along the lateral free wall of the left ventricle. Electrodes 34 and 36 may be used as a bipolar sensing and pacing electrode pair for sensing cardiac electrical signals from the LV and for delivering LV pacing pulses. LV lead 21 may be coupled to IMD 14 for providing ventricular pacing pulses to a left ventricular pacing site. LV lead 21 may be used to deliver ventricular pacing pulses during AVNS when a ventricular pacing interval expires to prevent ventricular asystole when AV node conduction is blocked by the AVNS. When the RV lead 18 is present for providing ventricular pacing, LV lead 21 is optional and may be excluded in some medical device systems that employ the AVNS techniques disclosed herein. In other examples LV lead 21 may be provided and RV lead 18 may be excluded. [0045] RV lead 18 and LV lead 21 are both shown to illustrate different ventricular pacing sites that could be utilized in conjunction with an AVNS therapy. The ventricular pacing site utilized for providing ventricular pacing during AVNS therapy is not limited to a particular pacing site and may be provided in the RV, LV, interventricular septum, along the His-Purkinje conduction system, or any other operative location for pacing and capturing the ventricles to prevent ventricular asystole during AVNS therapy. While LV lead 21 is shown as a bipolar lead having two electrodes 34 and 36 for the sake of convenience, LV lead 21 may be a unipolar lead having one electrode or a multi-polar lead, e.g., having three or four electrodes. In some examples, LV lead 21 is a quadripolar lead having four electrodes, e.g., four ring electrodes or one tip electrode and three ring electrodes, with proximal connector 44 configured as an industry standard IS-4 connector. [0046] Electrodes 20, 22, 24, 26, 28, 30, 34 and 36 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, 43 and 45 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, 42 and 44 and the respective electrodes carried by the lead body. The lead bodies 41, 43, and 45 may be generally tubular or cylindrical in shape but may have a flattened or ribbon shape in some examples. Any of the lead bodies 41, 43 and 45 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, 43 and 45 may be elongated flexible bodies without any preformed shapes or curves.
[0047] In the example shown in FIG. 1, RA lead 16 and RV lead 18 are configured as “true bipolar” leads in that a cardiac electrical signal can be sensed between tip electrode 20 and ring electrode 22 in the RA, and a cardiac electrical signal can be sensed between tip electrode 28 and ring electrode 30 in the RV. In other examples, a lead coupled to IMD 14 may be an “integrated bipolar” lead, referring to a lead that is configured to sense cardiac electrical signals using a tip electrode and a coil electrode, e.g., RV tip electrode 28 and RV coil electrode 24, omitting the need for a ring electrode 30. In an “integrated bipolar” lead, for example, the RV coil electrode 24 may serve the purposes of bipolar sensing of cardiac electrical signals and delivering ventricular pacing pulses when paired with tip electrode 28 and delivering high voltage CV/DF shocks in combination with SVC coil electrode 26 and/or housing 15. [0048] It is to be understood that although IMD 14 is described as a multi-chamber device capable of sensing and pacing in the RA, RV and LV, in other examples, IMD 14 may be a dual chamber device, e.g., coupled to RA lead 16 and RV lead 18. In still other examples, IMD 14 may be a single chamber device, e.g., coupled only to RA lead 16. IMD 14 provided as a single chamber device coupled to RA lead 16 may sense far field R-waves for detecting fast and/or irregular ventricular rates for use in controlling AVNS therapy. While IMD 14 is described above as being capable of delivering both low voltage cardiac pacing and AVNS therapies as well as high voltage CV/DF shocks, an IMD operating according to techniques disclosed herein may be configured to deliver AVNS and dual chamber cardiac pacing (e.g., atrial and ventricular) without high voltage CV/DF shock therapy capabilities.
[0049] 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 AVNS control parameters and other operating and control parameters used by IMD 14.
[0050] 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.
[0051] 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.
[0052] Display unit 54 may generate a display of cardiac electrical signals, lead impedance measurements, 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 AVNS 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.
[0053] 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.
[0054] 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.
[0055] 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.
[0056] External device 50 may be configured to generate a GUI on display unit 54, which may include an alert received from IMD 14. As further described below, IMD 14 may generate an alert indicating that a potential lead dislodgement or other lead related issue has been detected, which may be confirmed by medical imaging or other methods so that corrective action can be taken as needed by a clinician. In some examples, AVNS may be disabled by IMD 14 when AVNS control parameter adjustments do not lead to successful or effective inhibition of rapidly conducted depolarizations and ventricular rate stabilization during atrial tachyarrhythmia. External device 50 may display data relating to an alert that AVNS is disabled. External device 50 may transmit any alerts received from IMD 14 and associated data and information received from IMD 14 to a centralized database or computer or other device in a clinic or hospital to notify a clinician.
[0057] FIG. 2 is a conceptual diagram of an IMD 114 for sensing cardiac electrical signals and delivering AVNS according to some examples. In this example, a leadless IMD 114 is implanted in the RA for providing AVNS 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. [0058] 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 AVNS 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 AVNS 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 AVNS techniques disclosed herein, are generally disclosed in U.S. Publication No. 2021/0228892 (Komet, et al., filed January 25, 2021), U.S. Publication No. 2019/0083779, granted as 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. [0059] 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 AVNS therapy 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. 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 AVNS.
[0060] FIG. 3 is a conceptual diagram illustrating an IMD system 110 that may be used to sense cardiac electrical signals, deliver AVNS 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 AVNS. IMD 116 can provide ventricular signal sensing and ventricular pacing.
[0061] 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.
[0062] 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 AVNS. IMD 114’ may include a distal tip electrode 120’ for delivering atrial pacing pulses, delivering AVNS, 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, AVNS pulse trains, 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 AVNS therapy, e.g., targeting a vagal branch innervating the AV node.
[0063] 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., 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. [0064] 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.
[0065] 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.
[0066] The IMD system 110 may further include therapy delivery circuitry configured to deliver AVNS 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 AVNS pulse trains for inhibiting conduction of atrial depolarizations via the AV node during atrial tachyarrhythmia according to the techniques disclosed herein. IMD 116 may include therapy delivery circuitry configured to deliver ventricular pacing pulses in the absence of sensed intrinsic ventricular R-waves.
[0067] 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.
[0068] 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. IMD 116 may transmit a communication signal to IMD 114’ each time an R- wave is sensed by sensing circuitry of IMD 114’ to enable IMD 114’ to determine various cardiac event intervals as further described below. The cardiac event intervals, e.g., RR intervals (RRIs), may be used by IMD 114’ in controlling and adjusting AVNS. In other examples, IMD 114’ may be configured to sense far field R-waves for determining cardiac event intervals, e.g., RRIs, for use in controlling and adjusting AVNS.
[0069] In some examples, IMD 116 may transmit a communication signal to IMD 114’ each time a ventricular pacing pulse is delivered or after a threshold number of pacing pulses are delivered out of a specified number of ventricular electrical events (e.g., sensed intrinsic R-waves and delivered ventricular pacing pulses). In this way, IMD system 110 may be configured to detect when a threshold number of ventricular pacing pulses are delivered during AVNS. IMD 114’ may adjust AVNS control parameters in response to the IMD system 110 detecting the threshold number of delivered ventricular pacing pulses, e.g., as generally described below in conjunction with FIG. 5. Additionally or alternatively, IMD 116 may be configured to determine RRIs between consecutively delivered ventricular pacing pulses and/or sensed intrinsic R-waves and transmit communication signals to IMD 114’ indicating when RRIs do not meet stability criteria. IMD 114’ may adjust AVNS control parameters in response to determining that the RRIs do not meet stability criteria, which may be based at least in part on communication signals received from IMD 116 relating to the timing of delivered ventricular pacing pulses in some examples.
[0070] As used herein, “stability criteria” refers to one or more thresholds, ranges or other values that can be applied to the RRIs as in indication of the consistency or uniformity of the RRIs. An RRI range, difference between the shortest and longest RRIs, standard deviation of the RRIs, sum of differences between consecutive RRIs, average difference between consecutive RRIs, or other metric(s) representative of the spread, dispersion or change between consecutive RRIs in a series of RRIs may be compared to the stability criteria. It is noted that a threshold or other criteria applied to a variability metric for triggering the onset of AVNS therapy delivery as described herein may be different than the stability criteria used for determining when to adjust AVNS control parameters after the AVNS therapy is started. A variability metric that is representative of RRI spread, dispersion or change between consecutive RRIs and is determined for comparison to the variability criteria for triggering the onset of the AVNS therapy may also be determined in the same manner for comparison to the stability criteria for determining when to adjust the AVNS control parameters after the AVNS therapy is started.
[0071] As further described below, an IMD operating according to techniques disclosed herein may detect lead issues that may cause control circuitry of the IMD system to adjust or disable AVNS. In the case of the two device IMD system 110, IMD 116 may detect loss of ventricular capture, an out of range pacing impedance, or other issues that may indicate unreliable ventricular pacing (e.g., dislodgement of electrode 128) and transmit a signal to IMD 114’ to adjust or disable AVNS, e.g., as generally described below in conjunction with FIG. 9. In other examples, dislodgement of an electrode used to deliver AVNS may be detected. AVNS may be disabled to avoid delivering pulse trains to cardiac tissue that could be pro-arrhythmic in some instances.
[0072] FIG. 4 is a conceptual diagram of an IMD configured to sense cardiac electrical signals, deliver AVNS and deliver ventricular pacing pulses according to some examples. FIG. 4 depicts IMD 14 coupled to electrodes 20, 22, 24, 26, 28, 34, and 36, carried by leads 16, 18 and 21 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 adapted to receive a different number of medical electrical leads and associated electrodes for providing at least AVNS stimulation and ventricular pacing to a patient’s heart. Furthermore, the circuitry, components and functionality described in conjunction with FIG. 4 may correspond to a leadless IMD configured to deliver AVNS and ventricular pacing, 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.
[0073] Electrodes 20, 22, 24, 26, 28, 30, 34, 36 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. IMD 14 may include a control circuit 80, memory 82, therapy delivery circuit 84, cardiac electrical signal sensing circuit 86, telemetry circuit 88, an impedance measurement circuit 90 and one or more physiological sensors 95. A power source 98 provides power to the circuitry of IMD 14, including each of the components 80, 82, 84, 86, 88, 90 and 95 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, 90 and 95 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 95 as needed.
[0074] 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 for detecting tachyarrhythmias, such as atrial tachyarrhythmias or ventricular tachycardia (VT) and/or ventricular fibrillation (VF), 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 AVNS, cardiac pacing pulses, tachyarrhythmia induction pulses, CV/DF shocks, impedance measurement drive signals or any other electrical pulses delivered via electrodes 20, 22, 24, 26, 28, 30, 34, 36 and/or housing 15 shown in the system of FIG. 1.
[0075] 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.
[0076] 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.
[0077] Therapy delivery circuit 84, sensing circuit 86 and impedance measurement circuit 90 can be electrically coupled to electrodes 20, 22, 24, 26, 28, 30, 34, 36 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, impedance measurement circuit 90 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).
[0078] Control circuit 80 may include a tachyarrhythmia (“tachy”) detection circuit 92, timing circuit 96, and therapy control circuit 94. Tachyarrhythmia detection circuit 92 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 96. Timing circuit 96 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 96 may include various timers and/or counters for controlling the timing of delivered AVNS, pacing pulses and CV/DF shocks. Control circuit 80 may further include a therapy control circuit 94 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 AVNS control parameters described below.
[0079] Sensing circuit 86 may be selectively coupled to electrodes 20, 22, 24, 26, 28, 30, 34, 36 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 or LV lead electrodes 34 or 36, 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 and/or LV lead 21 (all 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.
[0080] 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. [0081] 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. 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.
[0082] Asense and Vsense signals received from sensing circuit 86 by control circuit 80 can be used by control circuit 80 for determining sensed 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 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). In some examples, PR intervals (PRIs) and/or RP intervals (RPIs) may be determined between consecutively received Asense and Vsense signals and/or consecutively received Vsense and Asense signals, respectively. As further described below, RPIs, for example, may be determined and used to control AVNS delivery to avoid RPIs that are shorter than a threshold interval during AVNS. RRIs may be determined and used to control AVNS delivery to promote a regular ventricular rate at a target rate or within a target rate range, which may be programmable by a user, e.g., using external device 50. RRIs may be determined to control AVNS delivery to promote RRI stability, which may include stability of paced and sensed RRIs. Control circuit 80 may include timing circuit 96 for determining various cardiac sensed event intervals, such as any of the foregoing example intervals, for use in detecting the heart rhythm and controlling therapy delivery.
[0083] 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, e.g., AF or VT/VF. 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 AVNS 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. [0084] Timing circuit 96 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 AVNS, cardiac pacing pulses and other electrical pulses generated by therapy delivery circuit 84. Timing circuit 96 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, AVNS, and/or detecting tachyarrhythmias.
[0085] For example, timing circuit 96 may pass sensed event intervals determined from received Asense signals and Vsense signals (and delivered ventricular pacing pulses) to tachyarrhythmia detection circuit 92 for determining and counting tachyarrhythmia intervals for use in detecting AF and VT/VF. Timing circuit 96 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 96 and therapy control circuit 94 may control therapy delivery circuit 84 to deliver AVNS pulse trains according to AVNS control parameters in response to tachyarrhythmia detection circuit 92 detecting atrial tachyarrhythmia and an unstable ventricular rate. An unstable ventricular rate may refer to a ventricular rate that is faster than a rate threshold and/or includes RRIs that meet RRI variability criteria. The IMD system may trigger the onset of AVNS therapy when an unstable ventricular rate is detected.
[0086] Tachyarrhythmia detection circuit 92 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 96 for detecting atrial and ventricular tachyarrhythmias. In some examples, tachyarrhythmia detection circuit 92 may include comparators and counters for counting PPIs and RRIs determined by timing circuit 96 that are tachyarrhythmia intervals. Tachyarrhythmia detection circuit 92 may compare PPIs to an atrial tachyarrhythmia detection interval to detect and count atrial tachyarrhythmia intervals toward detecting AF, for example. Tachyarrhythmia detection circuit 92 may compare RRIs determined by timing circuit 96 to a VT detection interval zone and/or a VF detection interval zone. RRIs falling into a detection interval zone can be counted by a respective VT interval counter or VF interval counter and in some cases in a combined VT/VF interval counter. When a threshold number of tachyarrhythmia intervals is reached, control circuit 80 may detect an atrial tachyarrhythmia or VT/VF. In some examples, a tachyarrhythmia detection based on the threshold number of tachyarrhythmia intervals being reached may be confirmed or rejected based on morphology analysis of a cardiac electrical signal. Any of a number of tachyarrhythmia detection methods may be implemented in an IMD performing the AVNS methods disclosed herein.
[0087] Impedance measurement circuit 90 is configured to measure the impedance between pairs of electrodes 20, 22, 24, 26, 28, 30, and 34 carried by a lead coupled to IMD 14. A drive signal, which may be a constant current or constant voltage signal, may be delivered to an electrode pair. A resulting voltage or current signal may be measured between a selected recording pair of electrodes and passed from impedance measurement circuit 90 to control circuit 80 for use in determining a lead impedance measurement. The lead impedance measurement may be used by control circuit 80 for detecting lead related issues, such as lead fractures, insulation breach, poor lead connection within connector block 12, lead (or electrode) dislodgement or other functional lead issues. As described below, control circuit 80 may adjust or disable AVNS in response to detecting a lead related issue, e.g., when the ventricular lead impedance, which may be measured between RV tip electrode 28 and ring electrode 30 for example, is outside a threshold impedance range. In other examples, atrial lead impedance may be measured between the RA tip electrode 20 and ring electrode 22 for detecting RA lead dislodgment or other RA lead issues.
[0088] Impedance measurement circuit 90 may include a multiplexer or other switching circuitry for coupling selected electrodes to a drive signal source. Impedance measurement circuit 90 may include a drive circuit for generating an excitation current or voltage signal that can be injected across an excitation pair of electrodes. Impedance measurement circuit 92 may measure the resulting signal between a recording pair of electrodes. In some examples, the excitation pair of electrodes and the recording pair of electrodes may be the same and in other examples two different pairs of electrodes are used for injecting the excitation signal and for recording the resulting voltage and/or current signal. [0089] The excitation current signal or excitation voltage signal may be applied as a subthreshold signal having a pulse amplitude and/or pulse width that is less than the pacing capture threshold of the patient’s heart. In this way, an impedance measurement may be obtained without causing an evoked response (depolarization) of cardiac tissue. The excitation signal may include monophasic or biphasic pulses having a pulse amplitude of less than 0.5 volts or less than 0.25 volts with a pulse width of 10 to 50 microseconds or about 25 to 30 microseconds, as examples. However, other subthreshold signals may be applied as excitation signals. A “subthreshold” signal refers to a signal having a pulse energy below the capture threshold of the heart so that an evoked depolarization of the myocardial tissue does not occur when the excitation signal is injected by impedance measurement circuit 90.
[0090] Impedance measurement circuit 90 may include a sampling circuit for sampling the resulting voltage and/or current signal from a recording pair of electrodes. The sampled signal may be used by processing circuitry of impedance measurement circuit 90 to derive an impedance signal (which may take into account the current or voltage of the delivered excitation signal). Impedance measurement circuit 90 may receive a resulting voltage or current signal from a recording pair of electrodes in response to applying the excitation signal and may use the resulting signal as an impedance measurement signal or convert the resulting signal to an impedance signal by determining the impedance in ohms based on the applied excitation signal and recorded signal. Examples of circuitry and techniques for measuring the electrical impedance of a lead and electrode pair coupled to IMD 14 are generally disclosed in U.S. Patent No. 5,534,018 (Wahlstrand, et al.) and U.S. Patent No. 8,996,111 (Marshall, et al.), both of which are incorporated herein by reference in their entirety.
[0091] The techniques disclosed herein may be implemented in conjunction with a variety of circuits and techniques for performing impedance measurements. In some examples, the impedance measurement circuit 90 may share components with control circuit 80, therapy delivery circuit 84 and/or sensing circuit 86. While impedance measurement circuit 90 is shown conceptually as a separate functional block in the diagram of FIG. 4, impedance measurement circuit 90 is not necessarily a dedicated circuit and may include a combination of components and functionality that is shared between therapy delivery circuit 84 for generating a excitation drive signal, sensing circuit 86 for sensing the resulting signal between a recording pair of electrodes and control circuit 80 for determining the lead impedance measurement based on the drive signal and recorded signal.
[0092] In another example, an excitation pulse may be generated by therapy delivery circuit 84 under the control of processing and control circuitry included in impedance measurement circuit 90 and/or control circuit 80. The excitation pulse may be controlled to have a starting voltage amplitude and processing circuitry of impedance measurement circuit 90 (or control circuit 80) may determine the voltage change on a holding capacitor of therapy delivery circuit 84 at the end of the excitation pulse. The voltage of the holding capacitor may be sampled at the beginning and end of the excitation pulse width. The discharge of the holding capacitor during the excitation pulse, from a starting voltage to an ending voltage, is inversely correlated to the electrode and lead impedance coupled to the therapy delivery circuit 84. The greater the voltage change, the lower the impedance. [0093] 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 AVNS 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 AVNS pulse trains, which may have 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, or in response to detection of a triggering event detected by control circuit 80. Cardiac pacing pulses may be delivered for providing bradycardia pacing, asystole pacing, ATP, post-shock pacing, etc.
[0094] 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.
[0095] The low voltage therapy circuit may generate trains of pulses for delivering AVNS for blocking conduction of atrial depolarizations to the ventricles. The AVNS 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. However, as described below in conjunction with FIGs. 6, 7 and 8, the pulse amplitude, pulse width, and number and frequency of the pulses in a pulse train are controlled to inhibit or suppress AV conduction, e.g., by prolonging the physiological refractory period of the AV node. Various AVNS control parameters that may be used by control circuit 80 in controlling therapy delivery circuit 84 to deliver AVNS are described below. The physiological refractory period of the AV node determines how soon the next atrial depolarization can be conducted to the ventricles via the AV node after a preceding atrial depolarization is conducted to the ventricles via the AV node (and His-Purkinje system). AVNS can prolong the AV node refractory period, e.g., to block at least some rapidly occurring atrial depolarizations during atrial tachyarrhythmia from being conducted to the ventricles at a rapid and/or irregular ventricular rate.
[0096] 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 VT/VF.
[0097] In some examples, the circuitry included in an IMD system operating according to the techniques disclosed herein may include one or more sensors 95 for sensing various physiological signals, such as an acceleration signal, pressure signal, heart sound signals, temperature signal, or the like. Sensors 95 may include an accelerometer, for instance, for sensing acceleration signals correlated to cardiac motion, patient physical activity or other body motion. When IMD 114 or 114’ (shown in FIGs. 2 and 3, respectively) includes an accelerometer in sensors 95, control circuit 80 may process and analyze the acceleration signal received from sensors 95 for sensing ventricular mechanical event signals and/or atrial mechanical event signals. Control circuit 80 may detect atrial fibrillation, for instance, based on a disappearance of atrial systolic event signals present in the acceleration signal. Control circuit 80 may determine that atrial fibrillation is no longer detected based on detection of atrial systolic event signals and corresponding atrial event intervals determined from the acceleration signal. Control circuit 80 may determine ventricular event intervals between consecutively sensed ventricular mechanical event signals for determining a ventricular rate and/or ventricular event interval variability. Accordingly, determination of an atrial rate, atrial tachyarrhythmia detection, ventricular rate and/or ventricular event interval variability (or stability) by control circuit 80 is not necessarily limited to processing and analysis of cardiac electrical signals. During delivery of AVNS, electrical signal noise received by sensing circuit 86 may confound sensing of atrial P-waves and ventricular R-waves in some instances. 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 rhythm and controlling AVNS therapy according to the techniques disclosed herein.
[0098] 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, detecting arrhythmias, and controlling therapy delivery including AVNS 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.
[0099] FIG. 5 is a flow chart 200 of a method for controlling AVNS by an IMD system according to some examples. FIG. 5 and other flow charts herein are generally described in conjunction with IMD 14 shown in FIG. 1. However, it is to be understood that the techniques for detecting atrial tachyarrhythmia, detecting an unstable ventricular rate, and controlling AVNS disclosed herein 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. At block 202, control circuit 80 may be operating in an AF monitoring and pacing mode. For the sake of illustration, the methods for controlling AVNS described in conjunction with the various flow charts and diagrams presented herein refer to delivering AVNS after detecting AF. It is to be understood, however, that AVNS may be delivered by IMD 14 in response to detecting atrial tachyarrhythmia that is conducted at a fast and/or irregular rate to the ventricles, which may include any of atrial tachycardia, atrial flutter or atrial fibrillation. As such, while the flow chart 200 of FIG. 4 and other flow charts presented herein refer to AF detection, it is to be understood that control circuit 80 may more generally monitor for and detect any type of atrial tachyarrhythmia at block 204. Control circuit 80 may be configured to detect AF based on Asense signals and/or an atrial EGM signal received from sensing circuit 86. Some AF detection algorithms implemented in IMD 14 may rely on Vsense signals for detecting irregular RRIs as evidence of AF. While monitoring for AF, control circuit 80 may operate according to a programmed pacing mode, which may be a single chamber atrial pacing mode, a single chamber ventricular pacing mode or a dual chamber pacing mode, e.g., a dual chamber AV synchronous pacing mode, which may be programmed in IMD 14 according to patient needs. Atrial pacing pulses and/or ventricular pacing pulses may be scheduled by control circuit 80 and delivered by therapy delivery circuit 84 upon expiration of a pacing interval, e.g., a lower rate interval or an AV pacing interval, for providing pacing rate support to the patient as needed according to the programmed pacing mode.
[0100] If AF is detected at block 204, according to any implemented AF detection algorithm, control circuit 80 may determine RRIs at block 206. Control circuit 80 may determine if unstable ventricular rate criteria are met at block 208 based on the RRIs. In some examples, an unstable ventricular rate may be detected by control circuit 80 when a threshold number of RRIs are less than a short interval threshold. The short interval threshold may be between 300 and 400 ms, for example. When control circuit 80 is configured to detect VT/VF, the short interval threshold may correspond to a VT or VF detection interval. For example, a VT detection interval may be programmed to be between 300 and 350 ms. A VF detection interval may be programmed to be between 250 and 320 ms. RRIs shorter than a VT/VF detection interval or a VT/VF detection interval plus an offset may be counted at block 208 as short RRIs by control circuit 80. When the count of short RRIs reaches a threshold, e.g., 3, 5, 7, 10, 12 or 20 short RRIs as nonlimiting examples, control circuit 80 may determine that unstable ventricular rate criteria are met at block 208. The threshold number of short RRIs may or may not be required to be consecutive RRIs. For example, control circuit 80 may buffer RRIs in memory 82 to enable control circuit 80 to determine when a threshold number X of the most recent Y RRIs is reached. For instance, when 50%, 60%, 70%, 80% or other specified portion of the most recent Y RRIs (where Y can be 5 to 100 in various examples), control circuit 80 may determine that unstable ventricular rate criteria are met at block 208. It is to be understood that the threshold number of short RRIs may be less than a threshold number of VT/VF intervals required to detect VT/VF. Furthermore, while not shown explicitly in FIG. 5, when control circuit 80 is detecting VT/VF, control circuit 80 may withhold starting AVNS in response to an AF detection and may terminate AVNS that is previously started before the onset of a detected VT/VF episode.
[0101] Additionally or alternatively, control circuit 80 may determine that unstable ventricular rate criteria are met at block 208 based on RRI variability criteria. An RRI variability metric is a metric determined from RRIs that is representative of the spread of RRIs, the dispersion of RRIs or the change from one RRI to the next in a series of consecutive RRIs. Control circuit 80 may determine one or more RRI variability metrics at block 208. Control circuit 80 may determine a difference between a longest RRI and shortest RRI out of the most recent Y RRIs, determine a standard deviation of Y RRIs, sum the absolute value of consecutive RRI differences, the RRI range, interquartile range, or determine one or more other RRI variability metrics. Control circuit 80 may compare the RRI variability metric to a respective threshold at block 208 to determine if unstable ventricular rate criteria are met based on RRI variability. When rate based criteria and/or RRI variability criteria are not met by the determined RRIs during a detected AF episode (“no” branch of block 208), control circuit 80 may withhold starting AVNS and return to block 204. If AF is no longer detected (“no” branch of block 204), control circuit 80 may return to block 202. If AF is still being detected (“yes” branch of block 204), control circuit 80 may continue monitoring RRIs for determining if unstable ventricular rate criteria become met at block 208.
[0102] When control circuit 80 determines that the rate and/or variability criteria are met by determined RRIs (which may include RRIs occurring before and/or after the AF detection is made and may include paced and sensed RRIs), control circuit 80 may start delivering AVNS at block 210. Control circuit 80 may withhold AVNS when AF is detected and the ventricular rate is stable, e.g., based on RRIs. In some instances, a detected atrial tachyarrhythmia may not be conducted to the ventricles at a fast or irregular rate such that inhibition of the AV nodal conduction is not necessary. However, when AF is detected and the ventricular rate is determined to be unstable based on short RRIs and/or variable RRIs, therapy delivery circuit 84 may start delivering AVNS to stabilize and/or slow the ventricular rate.
[0103] It is to be understood that, in some examples, processing and analysis of sensed cardiac electrical signals performed by control circuit 80 for detecting AF and for detecting an unstable ventricular rate may be performed in a common algorithm or share common analyses performed for detecting AF and for detecting an unstable ventricular rate (e.g., fast and/or irregular). For example, detecting AF may include an analysis of RRI irregularity. As such, the AF detection and unstable ventricular rate detection may occur concurrently or from overlapping time periods of sensed cardiac electrical signals in some examples instead of in a generally sequential manner as shown in FIG. 5. Example techniques that may be used in detecting AF, which may include detecting unstable or irregular RRIs, are generally described in U.S. Patent No. 7,623,911 (Sarkar, et al., filed on Dec. 29, 2005) and in U.S. Patent No. 10,039,469 (Higgins, et al., filed on Mar. 30, 2016), the entire content of both incorporated herein by reference. Other example techniques for detecting AF are generally disclosed in U.S. Patent No. 9,717,437 (Cao, et al., filed on Oct. 22, 2014) and U.S. Patent No. 9,675,261 (Cao, et al., filed on June 22, 2016), the entire content of both incorporated herein by reference.
[0104] Some patients may be in chronic AF. It is contemplated, therefore, that control circuit 80 may not operate in the AF monitoring mode of block 202 for detecting AF if the patient is known to be in chronic, persistent AF. Control circuit 80 may determine RRIs at block 206 for determining when the ventricular rate is unstable at block 208 for starting AVNS at block 210. In other examples, the patient may have persistent AF that may occasionally or intermittently terminate. In this case, control circuit 80 may be programmed to monitor the sensed cardiac electrical signals for detecting AF at block 204 as described above. Thus, depending on the chronic or persistent nature of AF in a given patient, blocks 202 and 204 may or may not be performed by control circuit 80. Monitoring for AF in a patient known to be persistently in a state of AF may be disabled in IMD 14 to conserve processing power. Instead, monitoring for unstable ventricular rate at block 208 may be performed for controlling when AVNS is started.
[0105] AVNS may be delivered at block 210 according to initial control parameters or most recently used control parameters known to provide effective inhibition of AV conduction for controlling ventricular rate. Examples of AVNS control parameters that may be used by control circuit 80 for controlling therapy delivery circuit 84 in delivering AVNS are described below in conjunction with FIGs. 6-8. When AVNS is started, control circuit 80 may enable a ventricular pacing mode if ventricular pacing is not already enabled. For example, while monitoring for AF, control circuit 80 may be controlling cardiac pacing according to a single chamber atrial pacing mode (e.g., denoted as an AAI or ADI pacing mode), a dual chamber atrial synchronous pacing mode (e.g., a DDD pacing mode), or a single chamber atrial synchronous ventricular pacing mode (e.g., a VDD pacing mode). Control circuit 80 may switch to a single chamber asynchronous ventricular pacing mode (e.g., a VDI pacing mode) or a dual chamber asynchronous pacing mode (e.g., a DDI pacing mode) if the pacing mode at the time that AVNS is started does not include ventricular pacing.
[0106] During AVNS, control circuit 80 may start a ventricular pacing escape interval in response to a Vsense signal received from sensing circuit 86 or a ventricular pacing pulse delivered by therapy delivery circuit 84. The pacing escape interval is set according to a minimum ventricular rate desired during delivery of AVNS. For example, the ventricular pacing escape interval may be set between 1 and 2 seconds to provide a minimum ventricular rate between 60 beats per minute (bpm) and 30 bpm, respectively, during AVNS. If the ventricular pacing interval expires without receiving a Vsense signal from sensing circuit 86, therapy delivery circuit 84 may deliver the scheduled ventricular pacing pulse. If a Vsense signal is received from sensing circuit 86 before the ventricular pacing escape interval expires, control circuit 80 may inhibit the scheduled ventricular pacing pulse by restarting the ventricular pacing escape interval. [0107] At block 212, control circuit 80 may determine if a threshold number of ventricular pacing pulses are delivered during AVNS. The AVNS may be delivered to allow intrinsic AV conduction to occur at time intervals that result in a desired ventricular rate (e.g., target RRI range) without requiring ventricular pacing to maintain the desired ventricular rate. When a threshold number of ventricular pacing pulses are delivered, the AVNS may be over- suppressing AV conduction. The threshold number of ventricular pacing pulses may be 1, 2, 3, 6, 8, 10 or 12 as non-limiting examples. The threshold number of ventricular pacing pulses may or may not be required to be consecutive. When a threshold number of ventricular pacing pulses are delivered by therapy delivery circuit 84 during AVNS, control circuit 80 may adjust the AVNS control parameters at block 214.
[0108] As described below in conjunction with FIG. 6-8, AVNS control parameters may include a start time, end time, pulse train duration, inter-pulse interval, pulse amplitude, pulse width, pulse frequency, number of pulses in a pulse train and a pulse train rate or duty cycle (which may be defined at least in part as a ratio of pulse trains to Vsense signals, e.g., every second Vsense signal or every third Vsense signal, etc.). Adjustments that may be made to the AVNS in response to a threshold number of delivered ventricular pacing pulses are described below in conjunction with FIGs. 6-8 and may include, as examples, a lower pulse amplitude, fewer pulses in the pulse train or lower pulse frequency within the pulse train, shorter pulse train duration, shorter pulse width, longer time interval between pulse trains, or lower duty cycle, etc. In general, the AVNS control parameters are decreased to reduce the suppression of intrinsic AV conduction to allow intrinsic depolarizations to be conducted from the atria to the ventricles at time intervals shorter than the ventricular pacing escape intervals. The AVNS control parameters may be adjusted at block 214 until ventricular pacing pulses are not being delivered, e.g., until a threshold number of Vsense signals are received at a desired rate (e.g., in a target RRI range) and/or RRI stability criteria are met. In some examples, if more than one AVNS electrode vector is available for delivering the AVNS pulse trains, control circuit 80 may adjust the AVNS electrode vector at block 214 in addition to or alternatively to adjusting the pulse train control parameters.
[0109] RRI stability criteria may correspond to RRI variability criteria applied to RRIs for determining when to start AVNS. For example, when RRI variability criteria are not met, RRI stability criteria are met in that the same one or more variability thresholds may be applied to one or more respective variability metrics determined from RRIs. In other examples, however, once AVNS is started due to RRI variability criteria being met, different RRI variability metrics may be determined and/or different thresholds may be applied to the respective RRI variability metrics as RRI stability criteria for determining when stability criteria are met during the AVNS therapy. For instance, the stability criteria applied to RRIs determined during the AVNS therapy may be more stringent (require greater stability) than the variability criteria applied to RRIs determined before AVNS therapy is started for triggering the onset of the AVNS therapy.
[0110] If AF is still being detected (“yes” branch of block 218) after adjusting the AVNS control parameters at block 214, control circuit 80 may return to block 210 to deliver AVNS according to the adjusted control parameters to promote intrinsic AV conduction at the target ventricular rate without requiring ventricular pacing. It is to be understood that at any time during the AVNS, control circuit 80 may determine that AF is no longer being detected (block 218). When AF is no longer being detected, control circuit 80 may terminate the AVNS at block 224 and return to block 202. The current values of AVNS control parameters may be stored in memory 82 for use the next time AVNS is started. As described below, in some examples, therapy delivery circuit 84 may terminate AVNS after an AF timer or an AVNS timer is expired to verify that AF is still being detected, ventricular rate stability criteria are still not being met (e.g., short RRIs and/or RRI variability criteria met), and/or to tune AVNS control parameters for improving ventricular rate stability and/or reducing the energy requirements of the AVNS therapy.
[0111] Referring again to block 212, as long as a threshold number of ventricular pacing pulses is not delivered, control circuit 80 may continue delivering AVNS according to the current control parameters. In addition to monitoring for ventricular pacing during AVNS, control circuit 80 may monitor RRIs to verify that the target ventricular rate and stable RRIs are occurring during the AVNS (block 216). Control circuit 80 may continue determining RRIs after starting the AVNS to verify that the RRIs fall within a target range at block 216. For example, if a stable ventricular rate of about 60 bpm is desired (which may be programmed by a user), control circuit 80 may verify that the RRIs fall within 0.8 to 1.2 seconds or within 0.9 to 1.1 seconds, as examples. It is noted that the ventricular pacing escape intervals may correspond to a rate that is less than the target ventricular rate. For instance, the ventricular pacing escape intervals may be set to 1.2 to 1.5 seconds to provide a minimum ventricular pacing rate between 50 and 40 bpm when the target intrinsically conducted rate is 60 bpm (corresponding to 1.0 second RRIs). In other examples, the ventricular pacing rate may be set equal to an upper limit of the target RRI range. For instance, if a clinician programs a target ventricular rate during AVNS to be 60 beats per minute, the target RRI range may correspond to 55 to 65 beats per minute. The ventricular pacing escape intervals may correspond to a pacing rate of 55 beats per minute. The lower limit of the RRI range applied at block 216 may correspond to a ventricular rate of 65 bpm.
[0112] If the RRIs are within the target range, control circuit 80 may continue delivering AVNS according to the current control parameters by returning to block 210, as long as AF is still being detected (“yes” branch of block 218). Control circuit 80 may determine when a threshold number of RRIs fall outside the target rate range at block 216. For instance, when 3, 5, 8, 10, 12 or other threshold number of RRIs are less than a lower limit of the target RRI range (such that the ventricular rate is faster than the target rate), control circuit 80 may determine if the AVNS output is adjusted to a maximum available combination of AVNS control parameters for suppressing intrinsic AV conduction (block 220). If so, sufficient AV nodal block may not be achievable through AVNS during AF. Control circuit 80 may disable AVNS at block 222. Control circuit 80 may generate an alert to transmit to external device 50 (shown in FIG. 1) by telemetry circuit 88 to alert a clinician that AVNS has been disabled. In other examples, if AVNS is associated with regular RRIs that may be shorter than a target lower RRI limit as determined at block 216, AVNS may continue to at least provide ventricular rate stability even if the ventricular rate is faster than the target rate. Control circuit 80 may return to block 210 and deliver AVNS at the current control parameters.
[0113] If a maximum available combination of AVNS control parameters has not been reached (“no” branch of block 220), control circuit 80 may advance to block 214 to adjust the AVNS control parameters. In this instance, the AVNS control parameters can be adjusted to cause greater suppression of intrinsic AV conduction if the RRIs tend to be shorter than the target RRI range. In some cases, a different AVNS electrode vector may be selected by control circuit 80 at block 214 when the maximum AVNS output is reached for the current AVNS electrode vector that is being used for delivering the pulse trains. For example, the pulse amplitude, pulse width, pulse frequency, pulse train duration (or number of pulses in train), and/or pulse train rate may be increased (up to some maximum output) to increase the suppression of the intrinsic AV conduction. If other AVNS electrode vectors are available, control circuit 80 may adjust the AVNS control parameter at block 214 by selecting a different AVNS electrode vector and determining if a target RRI range is met. It is noted that the upper limit of the RRI target range can correspond to the ventricular pacing escape interval such that when intrinsic AV conduction is oversuppressed, control circuit 80 may detect the threshold number of ventricular pacing pulses as described above and adjust the AVNS control parameters accordingly (to lessen the suppression of AV conduction).
[0114] Control circuit 80 may adjust the AVNS control parameters, e.g., generally increase one or more AVNS control parameters, at block 214 until the RRIs between Vsense signals received from sensing circuit 86 fall within the target RRI range. If AF is still being detected at block 218, therapy delivery circuit 84 may deliver the AVNS according to the adjusted control parameters at block 210. Control circuit 80 may continue monitoring for ventricular pacing pulses and RRIs outside the target RRI range for controlling AVNS during the ongoing AF episode as needed.
[0115] FIG. 6 is a diagram 250 of AVNS pulse trains 252 that may be delivered by an IMD, e.g., IMD 14, 114 or 114’ (shown in FIGs. 1-3), according to some examples. Therapy delivery circuit 84 may start AVNS pulse train 252a in response to control circuit 80 detecting AF and an unstable ventricular rate, e.g., according to the methods described above in conjunction with FIG. 5. An atrial electrical signal 272 that may be sensed by sensing circuit 86 during AF is shown. Sensing circuit 86 may sense atrial fibrillation waves and generate Asense signals 274 that are passed to control circuit 80 in response to P-wave sensing threshold crossings. A ventricular electrical signal 280 that may be sensed by sensing circuit 86 is shown. Sensing circuit 86 may sense R-waves 281, 283 and 285 during delivery of AVNS therapy and generate Vsense signals 282, 284 and 286 that are passed to control circuit 80 in response to R-wave sensing threshold crossings. It is noted that Vsense signals could be received by control circuit 80 during a pulse train (when the pulse train is not effective in blocking AV conduction) or between pulse trains 252 of the AVNS therapy that is being delivered. It is further noted that Vsense signals 282, 284 and 286 may be produced by a sensing circuit of IMD 114 or 114’ in response to sensing far field R-waves. [0116] AVNS pulse trains can be delivered after every nth Vsense signal to suppress conduction of atrial depolarizations to the ventricles at a fast rate, e.g., by extending the AV node refractory period. Each of pulse trains 252 may include multiple pulses having a pulse amplitude 256 and pulse width 254. The pulse energy may be increased by increasing the pulse amplitude 256 and/or pulse width 254. Pulse amplitude 256 may be between 0.25 and 12.0 volts (V), between 1 V and 10 V, or between 4 V and 8 V as nonlimiting examples. The pulse width may be 0.1 to 10 milliseconds (ms) as non-limiting examples. The pulses of each pulse train 252 are shown as monophasic pulses in FIG. 6. In other examples, the pulses in each pulse train 252 may be multi-phasic, e.g., biphasic, triphasic, etc. The pulses of each pulse train 252 are shown as positive polarity pulses in FIG. 6. 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 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.
[0117] Each pulse within the pulse train is separated from the next pulse by an inter-pulse interval 262. The inter-pulse interval may be 5 to 100 ms as non-limiting examples. The inter-pulse interval 262 may be selected in combination with the pulse width 254 to obtain a desired pulse frequency. The pulse frequency, i.e., the frequency of the pulses within the pulse trains 252, is defined by the inverse of the pulse period defined by the sum of the pulse width 254 and the inter-pulse interval 262. The pulse frequency can be increased by decreasing the pulse width 254 and/or decreasing the inter-pulse interval 262. 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.
[0118] The pulse train duration 258 is defined by the number of pulses in the pulse train and the pulse period (seen more clearly in FIG. 7 below). The pulse train duration may be 100 ms to 1 second long or between 200 and 500 ms long as examples, with no limitation intended. The pulse train duration 258 can be increased by increasing the pulse number and/or decreasing the pulse frequency. Greater suppression of AV conduction (e.g., longer refractory period of the AV node) can generally be achieved by a pulse train having relatively higher pulse energy, higher frequency and/or longer pulse train duration 258. Less suppression of the AV conduction (e.g., shorter AV node refractory period) can be achieved by relatively lower pulse energy, lower pulse frequency, and/or shorter pulse train duration 258.
[0119] In this example, the pulse trains may be delivered during the ventricular refractory period to block conduction of atrial depolarizations to the ventricles during the extended refractory period of the AV node. Each AVNS pulse train 252 may be started upon receiving a Vsense signal or after a start interval 276 following the respective triggering Vsense signal 282, 284 or 286. The rate of the pulse trains 252 can be controlled to control the ventricular rate. Control circuit 80 may control the rate of pulse trains 252 by delivering a pulse train after every nth Vsense signal, e.g., every Vsense signal, every other Vsense signal, every third Vsense signal, every fourth Vsense signal and so on. In the example shown, control circuit 80 delivers an AVNS pulse train on every Vsense signal but may be delivered less often in other examples.
[0120] As shown in FIG. 6, control circuit 80 may deliver a pulse train to block one or more atrial depolarizations (corresponding to Asense signals 274) following the triggering Vsense signal, referring to the nth Vsense signal that is followed by an AVNS pulse train. When an atrial depolarization is conducted to the ventricles to cause a ventricular depolarization as shown by R-waves 281, 283 and 285, sensing circuit 86 may produce respective Vsense signals 282, 284 and 286 that are passed to control circuit 80. Control circuit 80 may trigger an AVNS pulse train 252 in response to receiving each nth Vsense signal according to a specified AVNS duty cycle (e.g., ratio of AVNS pulse trains to Vsense signals). Control circuit 80 uses the Vsense signals for determining RRIs 288 and/or RPIs 290.
[0121] The rate at which intrinsic AV conduction is allowed to occur during AF may be controlled by selecting the ratio of pulse trains 252 to Vsense signals, selecting the pulse train duration 258, pulse amplitude 256, pulse width 254 and pulse train frequency. For example, control circuit 80 may adjust the AVNS pulse train rate by adjusting how often the AVNS pulse train is delivered following a Vsense signal. Control circuit 80 may adjust the AVNS pulse train rate (e.g., the ratio of AVNS pulse trains to Vsense signals) in response to detecting an RRI 288 that is shorter than a lower limit, e.g., as described above in conjunction with FIG. 5. Control circuit 80 may adjust the AVNS pulse train rate in response to detecting variable RRIs. Control circuit 80 may adjust how often the AVNS pulse train is delivered following a Vsense signal in response to a threshold number of ventricular pacing pulses being delivered by therapy delivery circuit 84 during the AVNS therapy.
[0122] In some examples, control circuit 80 may withhold delivering the next AVNS pulse train 252b until a specified number of Vsense signals are received. In some instances, AV conduction may not occur on the first Asense signal after the most recent AVNS pulse train. In order to allow AV conduction to occur, control circuit 80 may wait until a Vsense signal 282, 284 or 286 is received and then deliver an AVNS pulse train after the Vsense signal, e.g., during the ventricular refractory period. Control circuit 80 may control therapy delivery circuit 84 to wait for n Vsense signals until the next pulse train is delivered. In other examples, pulse trains 252 may be delivered having a variable pulse train duration 258 that may extend through a selected number of Asense signals. The pulse train duration 258 may be terminated after the selected number of Asense signals 274 are received to allow conduction of an atrial depolarization to the ventricles. AVNS may be withheld until the next nth Vsense signal is received. Other techniques for controlling AVNS for promoting a regular ventricular rate are described below in conjunction with FIGs. 7 and 8.
[0123] As shown in FIG. 6, when AV conduction is sufficiently suppressed to prevent conduction to the ventricles during pulse trains 252, a rate of conducted depolarizations can be controlled by controlling the rate of pulse trains 252a and 252b (collectively pulse trains 252), e.g., according to a proportion of Vsense signals that trigger an AVNS pulse train. When AV conduction is under-suppressed, however, one or more atrial depolarizations may be conducted to the ventricles during a delivered pulse train. Accordingly, when Vsense signals are received during or early after a delivered pulse train or Vsense signals are received at an RRI that is shorter than an RRI lower limit and/or do not meet RRI stability criteria, one or more AVNS control parameters may be adjusted to increase the likelihood of AV conduction block by a given pulse train 252. The pulse energy (e.g., pulse amplitude 256 and/or pulse width 254) may be increased, the pulse frequency may be increased (e.g., by decreasing the pulse width and/or inter-pulse interval), and/or the pulse train duration 258 may be increased to increase the effectiveness of the pulse train 252 in blocking AV conduction during (or early after) the pulse train. In some examples, the start interval 276 may be too long following a Vsense signal resulting in the atrial depolarization conducting through to the ventricles before AV conduction is blocked by the pulse train 252. As such, in some examples, the start interval 276 may be shortened when Vsense signals are occurring at RRIs that are shorter than a lower limit of the target RRI range and/or are occurring at variable RRIs.
[0124] As further described below, in some examples, control circuit 80 may determine RPIs, e.g., RPI 290, between a Vsense signal 284 and a consecutively following Asense signal 277. Control circuit 80 may compare one or more RPIs to a threshold interval. When the RPI is less than a threshold interval, the AVNS control parameters may be adjusted or AVNS may be withheld. A short RPI (and corresponding long PRI) may lead to elevated left atrial pressure, which could be pro-arrhythmic in some patients.
[0125] FIG. 7 is a diagram 350 of AVNS pulse trains 352a and 352b (collectively 352) that may be delivered by an IMD according to another example. Therapy delivery circuit 84 (shown in FIG. 4) may start AVNS pulse train 352a in response to control circuit 80 detecting AF and an unstable ventricular rate. An atrial electrical signal 372 that may be sensed by sensing circuit 86 during AF is shown. Sensing circuit 86 may sense atrial fibrillation waves and generate Asense signals 374 that are passed to control circuit 80 in response to P-wave sensing threshold crossings. A ventricular electrical signal 380 that may be sensed by sensing circuit 86 is shown. Sensing circuit 86 may sense R-waves 381 and 385 and generate Vsense signals 382 and 386 that are passed to control circuit 80 in response to R-wave sensing threshold crossings.
[0126] As shown in FIG. 7, AVNS can be delivered as pulse trains 352 to suppress conduction of multiple atrial fibrillation waves to the ventricles. It is noted that the pulse trains 352 and other AVNS pulse trains depicted in the accompanying drawings are not necessarily illustrated to scale, for example relative to the atrial electrical signal 372 and ventricular electrical signal 380. For instance, the individual pulses of pulse trains 350 are shown relatively large in FIG. 7 for the sake of clarity, however it is to be understood that it is the AVNS control parameters that control the frequency, amplitude and duration of the AVNS pulse trains as described herein. The individual pulses of pulse trains 352 may have pulse amplitude 356 and pulse width 354, separated by an inter-pulse interval 362, according to any of the example values given above in conjunction with FIG. 6. The frequency of the pulse trains 352a and 352b is defined by the inverse of the pulse period 360. The pulse train duration 358 is defined by the number of pulses in the pulse train and the pulse period 360. As described above, greater suppression of AV conduction may generally be achieved by a pulse train having relatively higher pulse energy (e.g., higher pulse amplitude), higher frequency and/or longer pulse train duration 358. Less suppression of the AV conduction can be achieved by relatively lower pulse energy, lower pulse frequency, and/or shorter pulse train duration 358.
[0127] In the example shown, pulse trains 352 are delivered at a pulse train rate that may be controlled by control circuit 80 by setting a minimum time interval 378 between the starting times of pulse trains 352. Each pulse train 352 may be started at a start interval 376 following the earliest Vsense signal (or in some examples the earliest Asense signal) after the minimum time interval 378 expires. The rate at which intrinsic AV conduction is allowed to occur during AF may be controlled by the minimum rate interval 378 and the pulse train duration 358, along with other pulse train control parameters. After the first pulse train 352a expires, the next AF wave corresponding to Asense signal 375 may conduct to the ventricles resulting in an R-wave 381 and corresponding Vsense signal 382 produced by sensing circuit 86. Control circuit 80 may control therapy delivery circuit 84 to start pulse train 352b in response to the Vsense signal 382 or in response to the earliest Asense signal 377 after the minimum rate interval 378 expires. Pulse train 352b can be started at the expiration of the start interval 376 extending from Asense signal 377. In this case, the start interval 376 extending from Asense signal 377 may be relatively longer than the start interval 276 shown in FIG. 6 so that the next AVNS pulse train 342b begins during the ventricular refractory period following the conducted R-wave 381. In other examples, the next pulse train 352b is triggered by the earliest Vsense signal 382 after the minimum rate interval 378 expires and may be delivered after a start interval from the Vsense signal 384 as described above in conjunction with FIG. 6. One or more atrial fibrillation waves may be blocked from being conducted to the ventricles during each pulse train 352a and 352b. After pulse train 352b expires, a subsequent atrial depolarization may be conducted to the ventricles resulting in the next R-wave 385 and corresponding Vsense signal 386. In some patients, employing a minimum time interval 378 between AVNS pulse trains 352 may promote a more regular rate of pulse trains 352 and conducted ventricular depolarizations. [0128] As shown in FIG. 7, when AV conduction is sufficiently suppressed to prevent conduction to the ventricles during pulse trains 352a and 352b, a rate of conducted depolarizations can be controlled by controlling the rate and duration of the pulse trains 352. When AV conduction is under-suppressed, one or more atrial depolarizations may be conducted to the ventricles during the AVNS pulse train 352a or 352b. Accordingly, when Vsense signals are occurring at RRIs that are shorter than an RRI lower limit and/or do not meet RRI stability criteria, one or more AVNS control parameters may be adjusted to increase the suppression of AV conduction during the pulse trains 352. In some examples, the start interval 376 may be too long following an Asense signal resulting in the atrial depolarization conducting through to the ventricles before AV conduction is blocked by the pulse train 352a or 352b. As such, in some examples, the start interval 376 may be shortened when Vsense signals are occurring at RRIs that are shorter than a lower limit of the target RRI range and/or at variable RRIs.
[0129] When the pulse train duration 358 is increased the rate at which conducted depolarizations can occur can be decreased (e.g., AF waves can be blocked for a relatively longer time duration). The rate of conducted depolarizations may be increased by shortening the pulse train duration 358. The rate of conducted depolarizations may be increased or decreased by decreasing or increasing, respectively, the minimum rate interval 378. Accordingly, when an RRI 388 is shorter than a lower limit, control circuit 80 may adjust the pulse train duration 358, adjust the pulse train rate, e.g., by adjusting the minimum rate interval 378, or adjust both the pulse train duration 358 and pulse train rate in combination to slow the rate of conducted depolarizations. In the examples shown in FIGs. 6-8, Vsense signals are received by control circuit 80 at a rate that is faster than a programmed ventricular pacing rate. As such, ventricular pacing by therapy delivery circuit 84 is inhibited. It is recognized, however, that when the AV node conduction is over- suppressed, a ventricular pacing escape interval may expire before a Vsense signal is received. Therapy delivery circuit 84 may deliver a scheduled ventricular pacing pulse, e.g., by starting a lower rate interval in response to a Vsense signal or delivered ventricular pacing pulse. When a threshold number of ventricular pacing pulses occur, control circuit 80 may adjust the pulse train duration 358 and/or adjust the pulse train rate to promote a faster rate of conducted depolarizations to reduce the occurrence of delivered ventricular pacing pulses, as generally described above in conjunction with FIG. 5. [0130] The minimum rate interval 378 may be started by control circuit 80 at the onset of a pulse train 352a or at the end of the pulse train 352a and may be set to a minimum rate interval accordingly. The difference between the minimum rate interval 378 and the pulse train duration 358 determines the approximate maximum amount of time between one pulse train 352a and the next pulse train 352b, the “inter-train interval,” during which an atrial depolarization may be conducted to the ventricles. This maximum amount of time between pulse trains 352a and 352b is the minimum rate interval 378 minus the pulse train duration 358 plus the time to the next triggering event signal, e.g., Asense 377 (or alternatively a Vsense signal 382), after the minimum rate interval 378 expires. In the example shown, a single Asense 375 occurs after the first pulse train 352a before the minimum rate interval 378 expires and is conducted to the ventricles. However, if the minimum rate interval 378 is longer and/or the pulse train duration is shorter, two or more AF waves may be conducted to the ventricles during the inter-train interval between pulse trains 352a and 352b. As such, the minimum rate interval 378 and the train duration 358 may be adjusted (to thereby adjust the AVNS duty cycle) when one or more short RRIs (e.g., two or more Vsense signals) occur between pulse trains 352 and/or RRI variability is high (stability criteria not met). In some examples, the minimum rate interval 378 and/or pulse train duration 358 may be determined at least in part by control circuit 80 based on the PPIs determined between consecutive Asense signals during AF to increase the likelihood of a single conducted depolarization occurring between AVNS pulse trains. In other examples, two or more conducted depolarizations may be allowed to occur between AVNS pulse trains to promote the target ventricular rate, depending on the atrial rate, intrinsic AV conduction time and other factors.
[0131] In some cases, one or more ventricular pacing pulses may be delivered during an AVNS pulse train 352 (e.g., due to a ventricular pacing interval expiring), which, in combination with an intrinsically conducted ventricular depolarization, may promote a regular ventricular rate (e.g., stable RRIs). As such, in some examples, AVNS control parameters may not necessarily be adjusted in response to a threshold number of ventricular pacing pulses when the combination of ventricular paced and intrinsically conducted ventricular depolarizations result in a stable ventricular rate (e.g., target rate and/or stable RRIs). Example methods for controlling AVNS for promoting stable RRIs that may include paced RRIs are described below in conjunction with FIG. 11. [0132] In some cases, the pulse energy (pulse width and/or amplitude) and/or pulse frequency may be adjusted (e.g., decreased) when a threshold number of ventricular pacing pulses are delivered during AVNS to reduce the suppression of AV conduction. In some cases, the pulse energy and/or pulse frequency may adjusted (e.g., increased) when RRIs are irregular and/or shorter than the lower limit, in addition to or instead of adjusting the pulse train rate and/or pulse train duration. As further described below, in some examples, control circuit 80 may determine the RPIs, e.g., RPI 384, between a Vsense signal and a consecutively following Asense signal 377. Control circuit 80 may compare RPIs to a threshold interval. When the RPI is less than a threshold interval, the AVNS control parameters may be adjusted.
[0133] FIG. 8 is a diagram 450 of AVNS pulse trains 452a, 452b and 452c (collectively 452) that may be delivered by an IMD according to yet another example. The atrial electrical signal 472 sensed by sensing circuit 86 and corresponding Asense signals 474 are shown along with a ventricular electrical signal 480 sensed by sensing circuit 86 and corresponding Vsense signals 482 and 486. In this example, AVNS therapy may be started by starting a pulse train 452a in response to detecting an atrial tachyarrhythmia and unstable ventricular rate (e.g., fast and/or irregular). Pulse train 452a may be started upon expiration of a start interval 476 from an Asense signal 474 or following a triggering Vsense signal as generally described above in conjunction with FIGs. 6 and 7. In other examples, the AVNS pulse train 452 started in response to detecting an unstable ventricular rate may be started independent of the timing of Asense and Vsense signals. During AF or other atrial tachyarrhythmias, AVNS pulse trains may suppress AV nodal conduction without capturing myocardial tissue even when started at a time that is independent of an Asense or Vsense signal.
[0134] In this example, pulse train 452a is terminated after a specified pulse train duration 458. One or more atrial depolarizations may be blocked from conducting to the ventricles during the pulse train 452a. Pulse train duration 452a may be selected by control circuit 80 based on the sensed atrial rate in some examples to allow a desired number of atrial depolarizations to be blocked before one is allowed to conduct to the ventricles.
[0135] Control circuit 80 waits for a Vsense signal 482 as evidence of a ventricular depolarization (corresponding to R-wave 481) then starts the next pulse train 452b, which may or may not be started during the ventricular physiological refractory period. Pulse train 452b and pulse train 452a may have the same pulse train duration 458. After pulse train 452b, control circuit 80 waits for a Vsense signal 486 (corresponding to R-wave 485) then starts the next pulse train 452c and so on. Pulse trains 452 may each have the same pulse train duration 458 but be separated by different inter-train intervals 460 and 461. The inter-train intervals 460 and 461 may be variable due to the time required for a ventricular depolarization to occur after an ending time of a preceding pulse train (end of pulse duration 458).
[0136] As described above, if one or more RRIs 488 are less than a lower limit threshold or unstable RRIs are detected during the AVNS therapy, the pulse energy, pulse frequency and/or pulse train duration 458 may be adjusted to have the effect of slowing the ventricular rate and/or promoting stable RRIs. If one or more ventricular pacing pulses are delivered during the AVNS therapy, the pulse energy, pulse frequency and/or pulse train duration 458 may be adjusted to have the effect of increasing the intrinsically conducted ventricular rate, unless ventricular pacing pulses in combination with intrinsically conducted ventricular depolarizations are meeting RRI stability criteria, e.g., as described below in conjunction with FIG. 11.
[0137] In still other examples, the AVNS pulse trains may be delivered in a continuous manner that is not interrupted by inter- train intervals. The inter-train interval may be set to zero for example or the duty cycle may be set to 100%. AVNS may be delivered as a continuous pulse train defined by the pulse amplitude, pulse width, inter-pulse interval, pulse period (defined by the pulse width and inter-pulse interval as shown in FIG. 7) and corresponding pulse frequency without defining a pulse train duration and inter-train interval or setting the duty cycle to 100%. The pulse amplitude, pulse width, inter-pulse interval, pulse period and/or pulse frequency of a continuously delivered pulse train may be tuned to suppress AV node conduction while avoiding atrial and ventricular myocardial capture. The continuous AVNS pulse train may or may not achieve total AV block such that in some instances Vsense signals may be received by control circuit 80 during AVNS. Ventricular pacing may be delivered as needed when a ventricular pacing interval expires without a Vsense signal to promote a target ventricular rate and/or RRI stability.
[0138] FIG. 9 is a flow chart 300 of method for controlling AVNS by an IMD system according to another example. Control circuit 80 may monitor for AF at block 302 while providing atrial and/or ventricular pacing as needed according to a programmed pacing mode. If AF is detected at block 304, control circuit 80 may determine RRIs at block 306 for determining if unstable ventricular rate criteria are met at block 308. The operations performed by IMD 14 at blocks 302 through 308 may generally correspond to the methods described above in conjunction with blocks 202 through 208 of FIG. 5.
[0139] In the example of FIG. 9, control circuit 80 may monitor for a lead issue, such as lead (or electrode) dislodgment (block 310). Control circuit 80 may monitor for ventricular lead dislodgement and/or atrial lead dislodgement for example. When AVNS is delivered during AF, over-suppression of AV conduction that leads to complete AV block may result in ventricular asystole. If the ventricular lead (or ventricular pacing electrode) is dislodged, or other lead issues exist such as lead fracture or poor connection to IMD 14, ventricular pacing pulses delivered during AVNS may fail to capture the ventricles to provide minimum ventricular rate support during AVNS -induced AV block. If the lead or electrode used for delivering the AVNS is dislodged, AVNS may be disabled so that high frequency pulse trains are not inadvertently delivered to another part of the heart. As such, before starting AVNS at block 318, in response to detecting an unstable ventricular rate at block 308, control circuit 80 may determine if a lead or electrode issue is detected at block 310. Treatment of patients having persistent atrial tachyarrhythmia using the AVNS techniques disclosed herein has the advantage of reversing the AV block induced by AVNS when ventricular pacing is compromised by a ventricular lead issue or other factors. AV nodal ablation to block AV conduction in patient’s having persistent atrial tachyarrhythmia is not reversible. A ventricular lead dislodgment or other lead issue may result in ventricular asystole in patients that undergo AV nodal ablation in combination with implantation of a ventricular pacemaker.
[0140] Control circuit 80 may be configured to detect lead or electrode dislodgement (and/or other lead or electrode related issues) according to any of a number of techniques. In some examples, lead dislodgement detection may include lead impedance measurements made by impedance measurement circuit 90. It is to be understood that impedance measurements may be performed by a leadless device, such as the IMDs shown in FIGs. 2 and 3, for detecting dislodgment of a housing-based electrode (e.g., any of electrodes 120 or 128. When the lead (or electrode) impedance is less than a threshold, the RV lead tip electrode 28 may be in the ventricular blood pool instead of in ventricular tissue or a lead conductor insulation breach may be present. When the lead impedance is greater than a threshold range, a lead fracture or other lead issue may exist that could impair the function of the IMD system in delivering ventricular pacing pulses that can capture the ventricles. Control circuit 80 may detect lead or electrode dislodgment or another lead/electrode issue when lead impedance is less than a threshold impedance, greater than a threshold impedance, or outside a normal lead impedance range. The normal lead impedance range may be 300 to 700 ohms as an example. The threshold impedance or normal lead impedance range applied to a lead impedance measurement may be based on historical lead impedance measurements made in the patient, e.g., at time of implant, when the ventricular lead (or ventricular pacing electrode) is known to be properly positioned at a ventricular pacing site. Similarly, a threshold impedance or normal impedance measurement range may be applied to an impedance measurement obtained using an AVNS electrode, e.g., RA tip electrode 20 (FIG. 1) or housing based electrode 120 or 120’ (FIGs. 2 and 3, respectively) for detecting a lead/electrode issue associated with the RA lead 16 or dislodgement of IMD 114 or 114’.
[0141] Additionally or alternatively, control circuit 80 may determine a pacing capture threshold during a capture threshold test. Control circuit 80 may verify cardiac capture based on detecting an evoked response signal, e.g., a negative polarity waveform sensed from the pacing tip electrode, following a delivered pacing pulse. If capture is not detected, even when the pacing pulse output is increased (e.g., pacing pulse amplitude and/or pulse width are set to maximum available values), control circuit 80 may detect a lead issue at block 310.
[0142] Additionally or alternatively, control circuit 80 may determine PRIs extending from Asense signals to Vsense signals received from sensing circuit 86. When PRIs are less than a minimum threshold, e.g., less than a minimum expected intrinsic AV conduction time when no AVNS is being delivered, the ventricular lead may have become dislodged and retracted into the RA or the RA lead may have become dislodged and advanced into the RV. In either of these situations, sensing circuit 86 may sense P-waves (and/or R-waves) on both the atrial and ventricular sensing channels substantially simultaneously. Accordingly, very short PRIs may be an indication of lead dislodgment and/or migration.
[0143] Other lead or electrode dislodgment or lead issue detection methods may be used for detecting a condition that may result in loss of capture by ventricular pacing pulses delivered during AVNS. Furthermore lead or electrode dislodgment or other lead issue detection methods may be performed by the IMD 14 (or 114/114’) for detecting a lead or electrode issue that may result in loss of effective stimulation at the AVNS delivery site for suppressing AV conduction. Example methods for detecting lead or electrode issues that may be implemented in conjunction with the techniques disclosed herein are generally disclosed in U.S. Patent No. 8,463,382 (Jorgenson, et al., filed August 26, 2010), U.S. Patent No. 9,572,990 (Gunderson, et al., filed July 11, 2012) and U.S. Patent No. 10,668,277 (Gunderson et al., filed December 8, 2017); the entire content of all of which is incorporated herein by reference.
[0144] When lead dislodgement or another lead or electrode issue is detected that may prevent delivery of ventricular pacing pulses that capture the ventricles or effective delivery of the AVNS for suppressing AV conduction, control circuit 80 may adjust or disable AVNS at block 312. Control circuit 80 may generate an alert signal at block 314 that may be transmitted by telemetry circuit 88 for alerting a clinician to a possible lead issue. In some examples, control circuit 80 may disable AVNS when a lead issue is detected, e.g., based on one or more of a lead impedance measurement, loss of pacing capture, and/or PRIs. When AVNS is disabled, control circuit 80 may generate an alert signal to notify the clinician that AVNS therapy is disabled. The patient may experience symptomatic atrial tachyarrhythmia due to a conducted unstable ventricular rate and require medical intervention.
[0145] In the example shown, AVNS may be adjusted at block 312 instead of being disabled when a ventricular lead issue is detected. In this case, if AF is still being detected at block 316, control circuit 80 may continue delivering AVNS at block 318 according to adjusted control parameters. For example, the AVNS control parameters may be adjusted at block 312 one or more times in an attempt to provide some improvement in ventricular rate stability with relatively low suppression of AV conduction so that the risk of a ventricular pacing escape interval expiring (and a long ventricular pause or asystole) is relatively low. For example, the target RRI range may be increased and/or widened when a ventricular lead or electrode issue is detected to enable conducted ventricular depolarizations to occur at relatively shorter and/or more variable RRIs than when no ventricular lead/electrode issue is detected and ventricular pacing is reliable. Checking for short RRIs may be disabled in some examples when a ventricular lead issue is detected because relatively short RRIs may be acceptable during relatively lower suppression of AV conduction that avoids a need for ventricular pacing. For example, the AVNS pulse train rate may be decreased (e.g., by increasing the number Vsense signals received before triggering an AVNS pulse train, decreasing a minimum rate interval or increasing the number of Asense signals between pulse trains) and/or the pulse train duration may be decreased to promote one or more atrial depolarizations to be conducted to the ventricles between pulse trains. In some examples, the pulse train start interval (e.g., shown as interval 276) may be adjusted (e.g., increased) and/or the pulse energy (e.g., pulse amplitude and/or width) may be decreased and/or the pulse frequency decreased to tune the AVNS to allow depolarizations to be conducted to the ventricles at a rate that is faster than the rate corresponding to the ventricular pacing escape interval.
[0146] When lead dislodgment or another lead/electrode issue is detected, control circuit 80 may set the ventricular pacing pulse output (e.g., pulse amplitude and pulse width) to minimum values (or zero) so that energy is not wasted in delivering ineffective ventricular pacing pulses. However, control circuit 80 may still monitor for and count expired ventricular pacing escape intervals for determining when a threshold number of expired pacing escape intervals is reached, indicating that the intrinsic AV conduction may still be over-suppressed. AVNS control parameters may be adjusted at block 312 to promote conducted depolarizations at a rate that is faster than the ventricular pacing escape interval rate. When an expired ventricular pacing pulse is detected, after one or more attempts at adjusting AVNS control parameters, AVNS may be disabled by control circuit 80.
[0147] Referring again to block 310, when a lead or electrode issue is not detected, control circuit 80 may start AVNS at block 318. AVNS may be delivered according to the most recent control parameter settings. Control circuit 80 may monitor for delivery of a threshold number of ventricular pacing pulses at block 320 to enable adjustments of AVNS control parameters at block 322 as generally described above. While comparing RRIs to stable rate criteria (e.g., a target ventricular rate and RRI stability criteria) is not shown in FIG. 9, it is to be understood that the methods described in conjunction with FIG. 5 for monitoring RRIs and making AVNS control parameter adjustments may be combined with the methods described in conjunction with FIG. 9. AVNS control parameters may be adjusted based on RRIs being less than the lower limit, RRI stability criteria not being met, a threshold number of delivered ventricular pacing pulses, and/or detection of a lead/electrode issue. In some examples, AVNS is disabled in response to lead/electrode issue detection such as lead/electrode dislodgment, insulation breach or lead fracture.
[0148] When AF is no longer being detected by control circuit 80 at block 316, control circuit 80 may terminate AVNS at block 330 and return to block 302. The AVNS control parameters in effect at the time of detecting termination of the AF episode at block 316 may be stored in memory 82 for use in delivering AVNS the next time AF is detected and/or ventricular rate stability criteria are not met. If AVNS was disabled at block 312, control circuit 80 may not re-enable AVNS until IMD 14 (or IMD 114/114’) is reprogrammed to enable AVNS.
[0149] FIG. 10 is a flow chart 400 of a method for controlling AVNS by IMD 14 according to another example. At block 402, therapy delivery circuit 84 starts delivering AVNS. As described above, control circuit 80 may control therapy delivery circuit 84 to start delivering AVNS in response to detecting atrial tachyarrhythmia and an unstable ventricular rate. In other examples, AVNS may be enabled in a patient having chronic atrial tachyarrhythmia when an unstable ventricular rate is detected without requiring atrial tachyarrhythmia detection. At block 404, control circuit 80 may start an AF timer and/or an AVNS timer. When AF is detected control circuit 80 may start an AF timer at block 404 to monitor the time since AF detection. Additionally or alternatively, control circuit 80 may start an AVNS timer to monitor the time since AVNS is started. In some instances, the AVNS timer may be started later than the AF timer. The AF timer may be started upon detecting AF. AVNS may not be started when AF is first detected if the unstable ventricular rate criteria are not yet met (and AVNS not started).
[0150] During AVNS delivery, control circuit 80 may determine RPI intervals at block 406. Each RPI may be determined as the time interval from a Vsense signal received from sensing circuit 86 to the next consecutively received Asense signal received from sensing circuit 86. RPIs may be determined for each Vsense signal received from sensing circuit 86. In other examples, one or more RPIs may be determined less frequently, e.g., after every 5, 10, 15, 20, 30 or other specified number of Vsense signals or after 10 seconds, 30 seconds, 1 minute, 2 minutes, 5 minutes, 10 minutes or other specified time interval. Control circuit 80 may compare the RPIs to an RPI threshold at block 408. The RPI threshold may be 250 to 400 ms and is 300 ms as an example. [0151] When at least one RPI is less than the RPI threshold, control circuit 80 may adjust the AVNS control parameters at block 412. In some examples, control circuit 80 may determine when a threshold number of RPIs are less than the RPI threshold. The threshold number of RPIs may or may not be required to be consecutive. In still other examples, control circuit 80 may determine a mean RPI, median RPI, minimum RPI or other representative value of multiple RPIs and compare the representative value to the RPI threshold at block 408. When the RPI threshold criteria are met at block 408 (“yes” branch), control circuit 80 may adjust at least one AVNS control parameter at block 412. [0152] When the RPI is shorter than the RPI threshold, left atrial pressure could become elevated, which can be pro-arrhythmia in some patients. Accordingly, when a threshold number of short RPIs are detected, control circuit 80 may adjust at least one AVNS control parameter at block 412.
[0153] The AVNS control parameters may be adjusted at block 412 by shortening the pulse train duration (e.g., by reducing the pulse number in each pulse train and/or shortening the pulse period). Additionally or alternatively, control circuit 80 may decrease the pulse amplitude and/or pulse width. Additionally or alternatively, control circuit 80 may decrease the pulse train start interval between a Vsense signal and the start of a pulse train. One or more AVNS control parameters may be adjusted to generally promote ventricular depolarization earlier following an atrial depolarization to increase the RPI following the ventricular depolarization. In various examples, one or more AVNS control parameters may be adjusted up or down in an effort to increase the RPIs. For example, various adjustments to AVNS control parameters may be made at block 412 until the RPIs are no longer less than the threshold applied at block 408. In other examples, in response to the RPI(s) being less than a threshold interval at block 408, control circuit 80 may disable AVNS to avoid elevated left atrial pressure associated with short RPIs.
[0154] In some examples, after adjusting the AVNS control parameter(s) at block 412, control circuit 80 may restart the AVNS timer at block 414. When the AF timer and/or the AVNS timer has/have not expired (“no” branch of block 416), control circuit 80 may return to block 406 and continue delivering AVNS (and monitoring RPIs according to the RPI monitoring protocol).
[0155] As generally described above, during AVNS, control circuit 80 may determine if a threshold number of ventricular pacing pulses are delivered at block 410 due to the ventricular pacing escape interval expiring without a Vsense signal. If a threshold number of ventricular pacing pulses are delivered, control circuit 80 may adjust one or more AVNS control parameter at block 412 to reduce the suppression of intrinsic AV conduction to reduce the likelihood of a ventricular pacing pulse being delivered during AVNS. After adjusting the AVNS, control circuit 80 may restart the AVNS timer at block 414.
[0156] While not explicitly shown in FIG. 10, it is to be understood that control circuit 80 may monitor RRIs during the delivery of AVNS. As described above in conjunction with FIG. 5, if RRIs are shorter than the lower limit and/or more variable than a target RRI range, control circuit 80 may adjust one or more AVNS control parameters at block 412. The AVNS control parameters may be adjusted by control circuit 80 until the RRIs determined from the Vsense signals received from sensing circuit 86 fall into the target RRI range, which may be based on a user programmed target heart rate, and/or meet other RRI stability criteria.
[0157] When the AF timer has expired and/or the AVNS timer has expired, as determined at block 416, control circuit 80 may perform an AVNS control parameter tuning procedure at block 418. In illustrative examples, the AF timer may be set to 10 minutes, 20 minutes, 30 minutes or 60 minutes. Control circuit 80 may be configured to tune the AVNS control parameters after an AF episode has been sustained for a specified time duration. The AVNS timer may be set to 2 minutes, 5 minutes, 10 minutes or other specified time duration, as examples. When the AF timer is expired and the AVNS timer expires without an adjustment to an AVNS control parameter, control circuit 80 may advance to block 418. In some examples, the AVNS timer is set to a shorter time interval than the AF timer. In other examples a single timer can be set to anywhere between 1 minute and 24 hours long for scheduling the AVNS control parameter tuning procedure performed at block 418. In still other examples, the AVNS control parameter tuning procedure may be performed at scheduled time intervals after the AVNS is started, regardless of the time since any AVNS parameter adjustment has been made at block 412 or regardless of the time since AF was detected.
[0158] The procedure for tuning the AVNS control parameters performed at block 418 may be performed to conserve the power source 98 of IMD 14. In a patient experiencing chronic and persistent AF, AVNS may be delivered for relatively long periods of time if not all the time. As such, the AVNS control parameters may be adjusted to allow AVNS pulse trains to be generated that require a minimized or relatively low current drain from IMD power source 98 while maintaining a target rate and/or RRI stability of conducted ventricular depolarizations.
[0159] At block 418, control circuit 80 may adjust at least one AVNS control parameter from the current setting or value to a test setting or value that requires less energy for generating the AVNS pulse trains. For example, the pulse amplitude, pulse width, pulse frequency, pulse train duration and/or pulse train rate or duty cycle may be decreased at block 418. Control circuit 80 may monitor the ventricular rate response to the test AVNS control parameter setting(s). If RRIs are shorter than a lower limit of a target RRI range and/or more variable than the target RRI range or other RRI stability criteria are not met and/or RPIs are shorter than the threshold RPI, control circuit 80 may restore the most recent setting(s) of the respective AVNS control parameter(s). Control circuit 80 may restart the AVNS timer at block 404 and continue delivering AVNS according to the most recent, unadjusted control parameter settings.
[0160] If the RRIs remain within the target RRI range and/or RRI stability criteria are met and RPIs are greater than the threshold RPI during AVNS using the test control parameter setting(s), control circuit 80 may decrease one or more AVNS control parameters to a next, lower test setting. Control circuit 80 may continue the AVNS control parameter tuning procedure, e.g., in an iterative manner, in which at least one AVNS control parameter is decreased (e.g., pulse amplitude, pulse width, pulse number, pulse frequency, pulse train duration and/or pulse train rate or duty cycle as examples). Analysis of RRIs may be performed during AVNS according to multiple test control parameters or multiple combinations of test control parameters until RRIs are shorter than or fall outside the target RRI range, RRI stability criteria are not met and/or the RPIs are shorter than the RPI threshold. Control circuit 80 may adjust the test AVNS control parameter setting(s) back to the most recent (e.g., lowest) setting(s) at which RRIs meet the target RRI range and/or RRI stability criteria and/or RPIs meet the RPI threshold. Control circuit 80 may establish adjusted AVNS control parameter settings as the lowest settings (e.g., lowest pulse output, pulse frequency, pulse train duration and/or pulse train rate) at which the target RRI range and RRI stability criteria (and threshold RPI) are met. Control circuit 80 may advance to block 404 and restart the AVNS timer. Therapy delivery circuit 84 may continue delivering AVNS pulse trains according to the tuned AVNS control parameter settings. [0161] FIG. 11 is a flow chart 500 of a method for controlling AVNS by an IMD system according to another example. AVNS is started at block 502, e.g., in response to detecting an atrial tachyarrhythmia and/or detecting an unstable ventricular rate (e.g., short RRIs and/or RRI variability criteria met). An AF and/or AVNS timer may be started at block 504 as generally described above in conjunction with FIG. 10. At block 506, control circuit 80 may determine RRIs for monitoring the ventricular rate and/or RRI stability during the delivery of the AVNS therapy. The RRIs may include paced and/or sensed RRIs. The RRIs may be determined based on Vsense signals received by control circuit 80 from sensing circuit 86. As described above, an IMD 114 implanted in the RA (see FIG. 2) may sense far field R-waves for determining RRIs. An IMD 114’ implanted in the RA in an IMD system 110 including IMD 116 implanted in the RV (see FIG. 3) may receive communication signals indicating the timing of any delivered ventricular pacing pulses for determining RRIs.
[0162] Control circuit 80 may determine, at block 508, if the RRIs meet a target ventricular rate and RRI stability criteria. A target rate may be defined as a ventricular rate between 55 and 65 bpm, 60 and 75 bpm, 50 and 60 beats per minute, or other target rate range. The RRI stability criteria may be defined by an RRI range associated with the target rate range. In other examples, the RRI stability criteria may be defined by a maximum standard deviation of RRIs. In still other examples, the RRI stability criteria may be defined as a maximum difference between the maximum and minimum RRIs determined out of the most recent Y RRIs, e.g., 8 to 30 RRIs. Any one or more of numerous RRI variability metrics, e.g., any of the example RRI variability metrics listed herein, may be determined for comparison to RRI stability criteria for determining when the ventricular rate is being maintained at a regular rate during the AVNS therapy.
[0163] If the rate or stability criteria are not met at block 508, control circuit 80 may advance to block 514 to adjust the AVNS control parameters until at least the RRI stability criteria are met. In some patients, stable RRIs may be a greater priority than a target ventricular rate. When the target rate and/or RRI stability criteria are met at block 508, control circuit 80 may continue delivering AVNS therapy according to the current control parameters and monitor the percentage of RRIs that are paced ventricular cycles at block 510. Ventricular pacing pulses can be delivered during the AVNS therapy due to oversuppression of the AV node conduction. The threshold percentage of paced ventricular cycles may be 10%, 20%, 30%, 40% or other specified percentage of all ventricular cycles. The percentage of paced ventricular cycles may be determined out of the most recent 10, 20, 30 or other specified number of ventricular cycles.
[0164] If the threshold percentage of paced ventricular cycles is met (“yes” branch of block 510), control circuit 80 may advance to block 514 to adjust the AVNS control parameters to decrease suppression of AV node conduction, e.g., to promote more frequent intrinsically conducted ventricular depolarizations. A high percentage of ventricular cycles being paced ventricular cycles may indicate over- suppression of the AV node conduction, which can be an inefficient use of the IMD power source. Therapy delivery circuit 84 may be delivering the AVNS pulse trains with a higher energy demand than needed to regulate the intrinsically conducted ventricular rate. The high percentage of paced ventricular cycles further increases the current drain from the IMD power source when conduction through the AV node is over-suppressed. After adjusting the AVNS control parameters at block 514, the AVNS timer may be restarted at block 516, and the process may return to block 506 to continue delivering AVNS therapy (according to the adjusted control parameters) and monitoring RRIs.
[0165] If the paced ventricular cycles do not meet the threshold percentage of ventricular cycles (“no” branch of block 510), control circuit 80 may determine if the number of paced ventricular cycles meets a second lower threshold percentage of ventricular cycles. For example, the first threshold percentage applied at block 510 may be 20%, 30%, 40% or 50%. The second lower threshold percentage of ventricular cycles applied at block 511 may be 10%, 15%, or 20%, as examples, but can generally be less than the first threshold percentage. The first and second threshold percentages applied by control circuit 80 at blocks 510 and 511 may be user programmable values.
[0166] If the percentage of paced ventricular cycles is less than the first threshold applied at block 510 but greater than (or equal to) the second threshold applied at block 511, it may be desirable to reduce the energy required to deliver AVNS to provide less inhibition of AV node conduction and reduced percentage of ventricular paced cycles. However, control circuit 80 may determine if RRI stability criteria are met at block 512 if more than the second percentage of ventricular cycles are paced ventricular cycles. If RRI stability criteria are met at block 511, and less than the first threshold percentage of ventricular cycles are paced, the number of paced ventricular cycles may be an acceptable trade-off for meeting RRI stability criteria. As such, if RRI stability criteria are met at block 512, control circuit 80 may advance to block 518 to check if a timer has expired. If not, AVNS therapy and RRI monitoring continues by returning to block 506.
[0167] If greater than the second percentage of ventricular cycles are paced ventricular cycles at block 511 (“yes” branch) and RRI stability criteria are not met, however, control circuit 80 may advance from block 512 to block 514 to adjust the AVNS control parameters. A percentage of paced ventricular cycles that falls between the first percentage threshold applied at block 510 and the second percentage threshold applied at block 512 may be acceptable when RRI stability criteria are met. However, if more than the second percentage of ventricular cycles are paced and RRI stability criteria are not met (“no” branch of block 512), control circuit 80 may adjust the AVNS control parameters to improve RRI stability and/or reduce the percentage of paced ventricular cycles. After adjusting the AVNS at block 514, control circuit 80 may restart the AVNS timer at block 516 and return to block 506 (as long as the AF and/or AVNS timers are not expired at block 518) to continue delivering AVNS therapy and monitoring RRIs.
[0168] When the percentage of paced ventricular cycles is less than the second threshold percentage (“no” branch of block 511), control circuit 80 may advance to block 518. If the AF and/or AVNS timers have expired (“yes” branch of block 518, control circuit 80 may advance to block 520 to tune the AVNS control parameters. As described above in conjunction with FIG. 10, when the AVNS has been delivered for a threshold time interval without being adjusted, therapy delivery circuit 84 may be able to deliver the AVNS using adjusted control parameters that require less energy, e.g., by reducing the pulse amplitude, pulse frequency, pulse train duration and/or pulse train rate or duty cycle, while still achieving a target ventricular rate and/or RRI stability. As such, control circuit 80 may tune the AVNS control parameters to reduce the energy requirements of the AVNS pulse trains but still meet at least RRI stability criteria and/or a target ventricular rate, without exceeding the first threshold percentage of paced ventricular cycles. In the process of tuning AVNS parameters, it is to be understood that control circuit 80 may verify that the criteria for delivering AVNS are still being met, e.g., AF still being detected and/or ventricular rate stability criteria not met. AVNS may be paused or terminated when an AF and/or AVNS timer has expired to verify that criteria for restarting or continuing AVNS are still met. If AF is no longer being detected or ventricular rate stability criteria are met, control circuit 80 may terminate AVNS therapy until the next time AF is detected and/or ventricular rate stability criteria are not met. If AF is still being detected and/or ventricular rate stability criteria are not met (e.g., short RRIs and/or variable RRIs), control circuit 80 may control therapy delivery circuit 84 to restart/continue the AVNS therapy, which may be restarted and continued at the same or adjusted AVNS control parameters based on the tuning procedure performed block 520.
[0169] In some examples, multiple AVNS electrode vectors may be available for delivering the AVNS therapy. The AVNS control parameters that may be adjusted at block 514 and/or at block 520 may include the AVNS electrode vector. As described below in conjunction with FIGs. 12 — 14, multiple electrodes may be available for selection by control circuit 80 in different AVNS electrode vectors. Control circuit 80 may select a different AVNS electrode vector at block 514 in response to a target ventricular rate not being met, RRI stability criteria not being met and/or in response to a threshold number of ventricular pacing pulses being delivered during the AVNS therapy.
[0170] Additionally or alternatively, control circuit 80 may select a different AVNS electrode vector at block 520 during testing of different AVNS pulse train control parameters. In some instances, a desired ventricular rate and/or RRI stability may be achieved by delivering a lower AVNS pulse energy, lower pulse train frequency, and/or lower duty cycle using one AVNS electrode vector compared to a different AVNS electrode vector. For instance, if the ventricular rate and RRI stability criteria are not met when control circuit 80 decreases a given AVNS pulse train control parameter (e.g., decreased pulse energy, pulse frequency, pulse train duration or pulse train duty cycle), control circuit 80 may change the AVNS electrode vector to test one or more different AVNS electrode vectors using the decreased pulse train control parameter(s). If the ventricular rate and/or RRI stability criteria are met using a different AVNS electrode vector and the decreased pulse train control parameter(s), control circuit 80 may select the new AVNS electrode vector for use in delivering the AVNS therapy by therapy delivery circuit 84. In this way, by changing the AVNS electrode vector at block 520 during the process of testing different AVNS pulse train parameters, control circuit 80 may be able to reduce the energy demand of the AVNS therapy by selection of a different AVNS electrode vector.
[0171] While not shown explicitly in FIGs. 10 and 11, it is to be understood that when control circuit 80 determines that AF is no longer detected, AVNS may be terminated. Furthermore, as described above in conjunction with FIG. 9, control circuit 80 may disable or adjust AVNS in response to detecting a lead or electrode issue. It is to be understood that the techniques described herein, for example in conjunction with the flow charts of FIGs. 5, 9, 10 and 11 and the diagrams of FIGs. 6-8 may be combined in any combination other than the particular examples provided herein. In various examples, some actions or events described herein for controlling AVNS may be added, omitted or performed in a different order than the particular combinations and orders of actions and events depicted by the flow charts presented herein.
[0172] FIG. 12 is a diagram 600 of an IMD 614 that may be configured to deliver AVNS therapy according to another example. IMD 614 includes a housing 615, which may be generally cylindrical in some examples, having a longitudinal sidewall 617 extending between a proximal end face 604 and a distal end face 602. IMD housing 615 encloses sensing circuitry, therapy delivery circuitry and control circuitry, e.g., as described above in conjunction with FIG. 4, for controlling atrial pacing and sensing, AVNS therapy, and ventricular pacing and sensing according to the techniques disclosed herein. IMD 614 may include a delivery tool interface 612 for connecting to a delivery tool to facilitate advancement to an implant site and deployment of IMD 614 at the implant site. IMD 614 may include a fixation member, e.g., one or more fixation tines 613 configured to anchor IMD 614 at the implant site. In this example, IMD 614 may include a distal electrode extension 610 carrying one or more electrodes. IMD 614 may include one or more electrodes 632 positioned on the distal end face 602 (as shown) and/or adjacent to the distal end face 602. IMD 614 may include at least one proximal ring electrode 630 circumscribing longitudinal sidewall 617 of IMD housing 615.
[0173] The distal electrode extension 610 may extend from the distal end face 602 and carry one or more electrodes, e.g., a distal tip electrode 628 and a ring electrode 620. The distal tip electrode 628 may be advanced to a position in the interventricular septum from a right atrial approach, as generally described above in conjunction with FIG. 2, for delivering ventricular pacing, e.g., in the area of the His bundle for capturing at least a portion of the His-Purkinje conduction system and/or myocardial tissue. The ring electrode 620 may be electrically isolated from tip electrode 628. Each of tip electrode 628 and ring electrode 620 of distal electrode extension 610 may be coupled to respective electrical conductors for electrical connection to IMD circuitry enclosed by housing 615. Tip electrode 628 may be a tissue piercing electrode to facilitate advancement into the interventricular septum or cardiac tissue at another implant site.
[0174] Distal electrode extension 610 is shown as a straight or generally linear member extending from distal end face 602. In other examples, however, distal electrode extension 610 may be helical, hook shaped, C-shaped or have another curving or non-linear shape. While two electrodes, tip electrode 628 and ring electrode 620, are shown on distal electrode extension 610, it is contemplated that distal electrode extension 610 may have a single electrode (e.g., at or near the distal tip of extension 610) or more than two electrodes spaced apart along the distal electrode extension 610. In other examples, distal electrode extension 610 may be a unitary or segmented electrode.
[0175] Non-electrode portions of distal electrode extension 610 (e.g., extending between tip electrode 628 and ring electrode 620) may formed of a non-electrical conductive material or have an insulating coating, e.g., parylene, silicone, urethane, or other biocompatible insulating coating. The ring electrode 620 may circumscribe shaft 628 and serve as an anode electrode paired with tip electrode 628 serving as a cathode for delivering ventricular pacing pulses and sensing ventricular signals. In other examples, the ring electrode 620 may be a cathode electrode and tip electrode 628 may be an anode electrode for delivering ventricular pacing pulses. In still other examples, tip electrode 628 and/or ring electrode 620 may be a cathode electrode paired with proximal housing based ring electrode 630 serving as the return anode for delivering ventricular pacing pulses, which may be delivered via the His-Purkinje conduction system. Ring electrode 620 may serve as an atrial pacing and sensing electrode in some examples, e.g., paired with proximal ring electrode 630.
[0176] In the example shown, IMD 615 may include multiple electrodes 632a, 632b, and 632c, collectively “electrodes 632,” which may be carried on the distal end face 602 of housing 615 and employed for delivering AVNS therapy and for sensing atrial signals and delivering atrial pacing. AVNS may be delivered by any combination of distal end face electrodes 632, ring electrode 620 of distal electrode extension 610 and/or proximal ring electrode 630 in various examples. While three electrodes 632a-632c are shown in FIG.
12, one or more electrodes may be provided on and/or adjacent to the distal end face 602 of IMD 614 for providing multiple, selectable AVNS electrode vectors.
[0177] Electrodes 632 may be electrically isolated from one another such that an AVNS electrode vector may be selected as electrode 632a and 632b, electrode 632b and electrode 632c or electrode 632a and electrode 632c. In some examples, one or more of the distal end face electrodes 632 may function as a cathode electrode paired with another one or more of distal end face electrodes 632 serving as an anode electrode. For example, electrodes 632a and 632b may together function as an AVNS cathode and electrode 632c may function as the AVNS anode. In other examples, one or more of distal end face electrodes 632 may function as a segmented cathode electrode paired with ring electrode 620 as the anode electrode or vice versa. In still other examples, one or more of the distal end face electrodes 632 may function as a cathode electrode paired with proximal ring electrode 630 as the anode electrode. Any one, two or all three of electrodes 632 may be selected as a cathode electrode paired with proximal ring electrode 630 for delivering atrial pacing pulses (when AVNS is not being delivered) and for sensing an atrial EGM signal. In some examples, a cathode and anode pair may be selected from electrodes 632 to function as a bipolar atrial sensing and/or atrial pacing electrode pair.
[0178] In the example of FIG. 12, distal end face electrodes 632 are shown as button electrodes spaced apart along the distal end face 602 of IMD housing 615. In other examples, the distal end face electrodes 632 may be ribbon, coil, hemispherical, a segmented ring electrode or other types of electrodes. As described below in conjunction with FIG. 15, control circuitry of IMD 614 may perform an electrode selection algorithm for selecting an AVNS electrode vector that may include one or more of electrodes 632 for delivering the AVNS therapy.
[0179] FIG. 13A is a diagram 650 of a cross-sectional view of the distal electrode extension 610 of IMD 614 shown in FIG. 12 according to another example. In FIG. 12, ring electrode 620 carried by distal electrode extension 610 is shown as a continuous ring electrode circumscribing the elongated body of distal electrode extension 610. In other examples, ring electrode 620 may be a segmented electrode as shown in FIGs. 13A and 13B. In FIG. 13 A, electrodes 620a, 620b, 620c and 620d may be spaced apart circumferentially around the distal electrode extension 610. Each of electrodes 620a, 620b, 620c and 620d may be electrically isolated from each other to function as individual electrodes that may be selected alone one at a time or in any combination to function as a cathode, an anode, or a cathode and anode pair. The electrodes 620a, 620b, 620c and 620d may be spaced apart from each other circumferentially along the outer circumferential surface of distal electrode extension 610 and/or longitudinally along the outer circumferential surface of distal electrode extension 610. While four circumferentially spaced electrodes 620a-620d are shown in FIG. 13 A, it is contemplated that two, three or more than four electrodes may be spaced apart circumferentially on distal electrode extension 610. The circumferentially spaced electrodes may be aligned longitudinally or spaced apart longitudinally or any combination thereof.
[0180] FIG. 13B is a diagram 652 of distal electrode extension 610 of IMD 614 of FIG. 12 according to yet another example. In FIG. 13B, multiple ring electrodes 620f, 620g, and 620h may be spaced apart from each other longitudinally along the elongated body of distal electrode extension 610. Each of the ring electrodes 620f, 620g, and 620h may wholly circumscribe the outer surface of distal electrode extension 610. In other examples, one or more of electrodes 620f, 620g, and 620h may partially circumscribe the outer surface of distal electrode extension 610, e.g., as an arc or C-shaped electrode extending around a portion of the outer circumference of distal electrode extension 610. Each of electrodes 620f, 620g, and 620h may be electrically isolated from each other to function as individual electrodes that may be selected alone one at a time or in any combination to function as a cathode, an anode or an anode and cathode pair. While three ring electrodes 620f, 620g, and 620h are shown in FIG. 13B, it is to be understood that one, two or more than three electrodes may be spaced apart along the distal electrode extension 610 in various examples.
[0181] In diagram 652, a single ring electrode 632 may be carried on (or adjacent to) the distal end face 602 for use in combination with any of electrodes 620f, 620g, and 620h for delivering AVNS (or electrodes 620a-d shown in FIG. 13A). Alternatively, as described above in conjunction with FIG. 12, multiple electrodes, e.g., 632a-632c, may be carried on the distal end face 602 of IMD 614. The one or more distal end face electrodes 632 may be selected in any combination with ring electrodes 620f, 620g, and 620h as shown in FIG. 13B or circumferentially spaced electrodes 620a-620d as shown in FIG. 13A for selecting an AVNS electrode vector. [0182] FIG. 14 is a diagram 670 of an IMD 614’ that may be configured to deliver AVNS therapy according to another example. IMD 614’ includes a distal helical electrode 678 extending from the distal end face 602 of housing 615. Instead of the distal electrode extension 610 and set of fixation tines 613, as shown in FIG. 12, IMD 614’ configured to deliver AVNS and ventricular pacing may include the distal helical electrode 678 for providing ventricular pacing and sensing, e.g., from a right atrial approach as described above (e.g., in conjunction with FIG. 2), and for serving as a fixation member for anchoring IMD 614’ at the implant site, in operative proximity to a vagal branch innervating the AV node or other AVNS position, e.g., at an epicardial site, endocardial site, AV nodal fat pad, cardiac nerve plexus, or within the myocardium.
[0183] As described above, IMD housing 615 may be generally cylindrical having a longitudinal sidewall 617 extending between a proximal end face 604 and a distal end face 602. IMD housing 615 encloses sensing circuitry, therapy delivery circuitry and control circuitry, e.g., as described above in conjunction with FIG. 4, for controlling atrial pacing and sensing, AVNS therapy, and ventricular pacing and sensing according to the techniques disclosed herein. IMD 614’ may include a delivery tool interface 612 for connecting to a delivery tool to facilitate advancement to an implant site and deployment of IMD 614’ at the implant site.
[0184] The distal helical electrode 678 may be formed of an electrically conductive material, e.g., titanium, platinum, iridium or alloys thereof, as examples. The one or more proximal turns 682 of distal helical electrode 678 may be coated with an electrically insulative coating, such as parylene, silicone, polyurethane, fluoropolymer, mixtures thereof, and/or other appropriate materials. The distal tip 680 may remain uninsulated to provide a distal active electrode portion for sensing ventricular signals and delivering ventricular pacing. The distal tip 680 that is uninsulated may include a low polarizing coating, such as titanium nitride, iridium oxide, ruthenium oxide, platinum black, among others. IMD 614’ may include at least one proximal ring electrode 630 circumscribing longitudinal sidewall 617 of IMD housing 615. Ventricular pacing and ventricular sensing may be performed using the active electrode distal tip 680 of helical electrode 678 paired with proximal ring electrode 630. In other examples, a proximal turn of distal helical electrode 678 may be uninsulated and electrically isolated from distal tip 680 for providing another electrode, which may be selectable in any ventricular pacing and sensing, atrial pacing and sensing, or AVNS electrode vector.
[0185] IMD 614’ may include one or more electrodes 632 positioned on the distal end face 602 as described above in conjunction with FIG. 12 for providing atrial pacing and sensing and for delivering AVNS. Electrodes 632 may include one or more button, ring, segmented ring, hemispherical, hook, short coil or other types of electrodes on and/or adjacent to the distal end face 602 for providing multiple, selectable AVNS electrode vectors. As described above, an AVNS electrode vector may be selected as any pair of electrodes 632a, 632b, and 632c, for example. Any one, two or all three of electrodes 632 may be selected as an atrial pacing cathode paired with proximal ring electrode 630 for delivering atrial pacing pulses when an AVNS pulse train is not being delivered. Atrial sensing may be performed using one or more of electrodes 632 in an atrial sensing vector, which may include proximal ring electrode 630.
[0186] While multiple AVNS electrode vectors are described in conjunction with FIGs. 12-14 that can be selectable by control circuitry of a leadless IMD, it is to be understood that multiple circumferentially spaced and/or longitudinally spaced electrodes may be carried by a lead that is implantable in the RA, e.g., lead 16 of FIG. 1. For example, instead of being carried by a distal end face of IMD 614 and/or along a distal electrode extension 610, multiple selectable electrodes for delivering AVNS may be carried by lead 16. For instance, the multiple ring electrodes 620f, 620g and 620h shown in FIG. 13B could be spaced longitudinally near the distal end of lead body 41 of lead 16. The multiple electrodes 620a-620d (of FIG. 13b) may be spaced circumferentially around the lead body 41 of lead 16 shown in FIG. 1. In some examples, the distal tip electrode 20 of lead 16 may be a segmented electrode or carry multiple, electrically isolated electrodes that are spaced apart circumferentially and/or longitudinally to provide multiple, selectable AVNS electrode vectors.
[0187] FIG. 15 is a flow chart 700 of a method that may be performed by an IMD for selecting an AVNS electrode vector according to some examples. The process of flow chart 700 may be performed for identifying an AVNS electrode vector that results in the greatest prolongation of the AV node refractory period or at least results in an increase in AV conduction time compared to the intrinsic AV conduction time. The process of FIG.
15 is described with reference to IMD 614 of FIG. 12 or IMD 614’ of FIG. 14 for the sake of illustration. It is to be understood, however, that the process of flow chart 700 could be performed by control circuitry of IMD 14 when a lead, e.g., lead 16, coupled to IMD 14 for delivering AVNS is carrying multiple electrodes selectable in two or more AVNS electrode vectors.
[0188] IMD 614/614’ having multiple available AVNS electrode vectors may include sensing circuitry for sensing cardiac electrical and/or mechanical signals, therapy delivery circuitry for delivering AVNS and cardiac pacing pulses, and control circuitry for controlling the sensing and therapy delivery functions as generally described above in conjunction with FIG. 4. With reference to FIG. 4 and continued reference to FIG. 15, at block 702, control circuit 80 may select a test AVNS electrode vector. The process of flow chart 700 may be initiated by control circuit 80 at the time of implant of IMD 614/614’. The process of flow chart 700 may be repeated at regular time intervals, e.g., hourly, daily, weekly, etc. or at one or more scheduled times of day when a tachyarrhythmia is not being detected. The process of flow chart 700 may be initiated by control circuit 80 when AVNS therapy has been terminated after performing multiple AVNS control parameter adjustments and/or reaching a maximum number of adjustments or maximum AVNS control parameter limit using a current AVNS electrode vector. By selecting a different electrode vector for delivering AVNS therapy, ventricular rate and/or RRI stability may be regulated using AVNS control parameters that require less energy from power source 98 and/or result in improved RRI stability for example. As such, if the ventricular rate and/or RRI variability metric do not meet stability criteria during AVNS therapy one or more times, after AF is no longer being detected, control circuit 80 may perform the process of flow chart 700 for identifying an AVNS electrode vector that may result in the greatest prolongation of the AV node refractory period or at least some prolongation of the AV node refractory period with minimized or relatively lower energy AVNS pulse train control parameters.
[0189] At block 702, control circuit 80 may select a first test AVNS electrode vector which may be any combination of the available electrodes, e.g., any of the example AVNS electrode vectors described above in conjunction with FIGs. 12-14. At block 704, control circuit 80 may control therapy delivery circuit 84 to deliver one or more AVNS pulse trains. The AVNS pulse trains may be delivered according to a set of default control parameters or according to the most recent AVNS control parameters used during AVNS therapy delivery for controlling the AVNS pulse trains. For example, a default or most recent pulse amplitude, pulse width, pulse train frequency, pulse train duration, and pulse train start time relative to an Asense or Vsense event and/or AVNS duty cycle may be used for delivering at least one AVNS pulse train at block 704 via the test AVNS electrode vector.
[0190] At block 706, control circuit 80 may determine one or more PRIs as a measure of AV conduction time. Control circuit 80 may determine the AV conduction time from a delivered atrial pacing pulse or Asense signal to a subsequent Vsense signal received during and/or after the AVNS pulse train. After starting at least one AVNS pulse train using the test AVNS electrode vector, the time from the next received Vsense signal to the most recent preceding Asense signal (or Apace) may be determined as the PRI. Control circuit 80 may determine the PRI for one or more cardiac cycles during AVNS delivered using the test AVNS electrode vector and a first set of pulse train control parameters. AVNS pulse trains may be delivered by therapy delivery circuit 84 for a specified time interval (or specified number of AVNS pulse trains) during which PRIs may be determined for assessing the effectiveness of the test AVNS electrode vector in suppressing AV node conduction. The PRI is correlated to the time delay between an atrial event signal (sensed or paced) and a conducted ventricular event signal due to the AV node refractory period and is expected to increase with greater AV node conduction suppression by the AVNS.
[0191] It is recognized that other measurements may be determined by control circuit 80 at block 706 that are correlated to the PRI and the AV node refractory period. For example, EGM signal analysis may be performed to determine a PQ interval between a fiducial point of a sensed P-wave (or time of a delivered atrial pacing pulse) and the Q wave of the QRS complex. In some examples, the PRI may be measured as the time interval between an atrial electrical event (P-wave or atrial pacing pulse) and a subsequent ventricular mechanical event signal or between an atrial mechanical event signal corresponding to atrial systole and a ventricular mechanical event signal corresponding to ventricular systole. A mechanical event signal may be an acceleration signal, a pressure signal, an impedance signal, a heart sound signal, etc., which may be sensed by sensors 95 shown in FIG. 4. As such, while a PRI measurement is referred to here as a measure of AV node conduction time, it is to be understood that the measurement performed by control circuit 80 at block 706 may be determined as a time interval between an atrial event signal (paced or sensed as an electrical or mechanical signal) and a ventricular event signal (mechanical or electrical signal), that is correlated to the AV node conduction time and changes with changes in the AV node refractory period due to AVNS.
[0192] In some examples, control circuit 80 may determine the PRI for one or more cardiac cycles during AVNS delivered using the test AVNS electrode vector and two or more sets of pulse train control parameters. For example, control circuit 80 may control therapy delivery circuit 84 to deliver AVNS pulse trains via the test AVNS electrode vector and using two or more pulse amplitudes and/or pulse train frequencies. At block 706, control circuit 80 may determine and store measured PRIs in memory 82 labeled according to the test AVNS electrode vector and AVNS pulse train control parameters used.
[0193] At block 708, control circuit 80 may determine if additional test AVNS electrode vectors are available. If so, control circuit 80 may return to block 702 to select the next test AVNS electrode vector. The process of blocks 704, 706 and 708 may be repeated until all desired test AVNS electrode vectors have been used. It is contemplated that instead of returning to block 702, control circuit 80 may return to block 701 after completing PRI measurements for a given test AVNS electrode vector to redetermine the intrinsic PRI. In some examples, control circuit 80 may wait a specified time interval between measuring PRIs for two different test AVNS electrode vectors (and/or two different sets of AVNS pulse train control parameters) to allow any prolonged effect of the AVNS to disappear. Furthermore, in some examples, control circuit 80 may wait a specified time interval or number of AVNS pulse trains delivered by a test AVNS electrode vector prior to determining the PRIs at block 706 to allow time for the AVNS to take effect on the AV node conduction time.
[0194] When a maximum number of AVNS electrode vectors have been tested or all available test AVNS electrode vectors have been tested (“no” branch of block 708), control circuit 80 may advance to block 710. At block 710, control circuit 80 may identify a maximum PRI of the determined PRIs. In other examples, control circuit 80 may identify a PRI that represents a greatest increase from an intrinsic PRI. In still other examples, control circuit 80 may identify a PRI that is at least a threshold percentage or time interval greater than an intrinsic PRI (e.g., as measured at block 701). [0195] At block 712, control circuit 80 may select an AVNS electrode vector from among the tested AVNS electrode vectors as the AVNS therapy delivery electrode vector. The AVNS therapy delivery electrode vector may be selected as the test AVNS electrode vector that resulted in the maximum PRI in some examples. In other examples, control circuit 80 may select the AVNS therapy delivery electrode vector as a test AVNS electrode vector that is associated with a PRI that is least a threshold greater than the intrinsic PRI. In some examples, control circuit 80 may select the AVNS therapy delivery electrode vector as the test AVNS electrode vector that resulted in at least a threshold increase in AV conduction time (e.g., PRI) using the AVNS pulse train parameters having the lowest energy cost. The next time AVNS therapy is started in response to detecting AF and/or an unstable ventricular rate, therapy delivery circuit 84 may deliver the AVNS pulse trains using the selected AVNS therapy delivery electrode vector.
[0196] In any of the examples described above in conjunction with the flow charts of FIGs. 5 and 9-11, when control circuit 80 adjusts the AVNS control parameters, control circuit 80 may, in some instances, select a different AVNS therapy delivery electrode vector based on the PRI data stored in memory 82. For example, if a threshold number of ventricular pacing pulses, unstable ventricular rate (e.g., fast and/or irregular RRIs), and/or short RPIs are detected, control circuit 80 may adjust the AVNS control parameters, e.g., at block 214 of FIG. 5, block 322 of FIG. 9, block 412 of FIG. 10, or block 514 of FIG. 11. At any time that AVNS control parameters are being adjusted, control circuit 80 may select a different AVNS therapy delivery electrode vector as one of the AVNS control parameter being adjusted. Two or more test AVNS electrode vectors may be identified during the process of flow chart 700 as being acceptable or optimal AVNS electrode vectors based on the longest PRIs measured at block 706 and/or greatest increase relative to the intrinsic PRI. The acceptable or optimal AVNS electrode vectors may be identified and stored in memory 82. Subsequently, when AVNS therapy is being delivered according to any of the flow charts of FIGs. 5 and 9-11, control circuit 80 may change the AVNS electrode vector being used to deliver the AVNS pulse trains if an AVNS adjustment is needed to improve the ventricular rate regulation with minimized ventricular pacing requirements.
[0197] Further disclosed herein is the subject matter of the following examples: [0198] Example 1. A medical device system comprising therapy delivery circuitry configured to deliver an AVNS therapy for suppressing atrioventricular node conduction by generating pulse trains according to AVNS control parameters and generate ventricular pacing pulses. The medical device system may further include control circuitry configured to determine that a first threshold number of ventricular pacing pulses are delivered by the therapy delivery circuitry while the therapy delivery circuitry is delivering the AVNS therapy and adjust at least one AVNS control parameter in response to determining that the first threshold number of ventricular pacing pulses have been delivered.
[0199] Example 2. The medical device system of example 1 further comprising sensing circuitry configured to sense ventricular event signals. The control circuitry may be further configured to determine ventricular event intervals from the sensed ventricular event signals and the ventricular pacing pulses delivered by the therapy delivery circuitry during the AVNS therapy and determine that the ventricular event intervals do not meet ventricular interval stability criteria. The control circuitry may be further configured to determine that a second threshold number of ventricular pacing pulses are delivered by the therapy delivery circuitry while the therapy delivery circuitry is delivering the AVNS therapy, the second threshold number less than the first threshold number. The control circuitry may adjust at least one AVNS control parameter in response to determining that the second threshold number of ventricular pacing pulses have been delivered and the ventricular interval stability criteria are not met.
[0200] Example 3. The medical device system of any one of examples 1 or 2 further comprising sensing circuitry configured to sense cardiac event signals attendant to intrinsic depolarizations. The control circuitry may be further configured to detect an atrial tachyarrhythmia based on at least the sensed cardiac event signals and determine that the sensed cardiac event signals meet unstable ventricular rate criteria. The control circuitry may control the therapy delivery circuitry to start delivering the AVNS therapy in response to detecting the atrial tachyarrhythmia and the sensed cardiac event signals meeting unstable ventricular rate criteria.
[0201] Example 4. The medical device system of example 3 wherein the control circuitry is further configured to determine ventricular sensed event intervals from the sensed cardiac event signals, compare the ventricular sensed event intervals to a short interval threshold, determine that a threshold number of the ventricular sensed event intervals are less than the short interval threshold, and determine that the sensed cardiac event signals meet unstable ventricular rate criteria based on at least the threshold number of the ventricular sensed event intervals being less than the short interval threshold.
[0202] Example 5. The medical device of any one of examples 3 - 4 wherein the control circuitry may be further configured to determine ventricular sensed event intervals from the sensed cardiac event signals, determine a variability metric from the ventricular sensed event intervals, determine that the variability metric meets a variability threshold and determine that the sensed cardiac event signals meet unstable ventricular rate criteria based on at least the variability metric meeting the variability threshold.
[0203] Example 6. The medical device system of any of one of examples 1 - 5 further comprising sensing circuitry configured to sense cardiac event signals by sensing ventricular event signals. The control circuitry may be further configured to determine that a threshold time interval of delivering the AVNS therapy by the therapy delivery circuitry without adjustment of an AVNS control parameter has expired. The control circuitry may adjust at least one AVNS control parameter from a first value to a second value associated with reduced suppression of atrioventricular conduction in response to the threshold time interval expiring. The control circuitry may control the therapy delivery circuitry to deliver the AVNS therapy according to the second value of the at least one AVNS control parameter and determine sensed ventricular event intervals from the sensed ventricular event signals sensed by the sensing circuitry during the AVNS therapy delivered according to the second value. The control circuitry may determine if stability criteria are met based on the sensed ventricular event intervals. The control circuitry may restore the at least one AVNS control parameter to the first value in response to the stability criteria not being met and control the therapy delivery circuitry to continue delivering the AVNS therapy according to the second value in response to the stability criteria being met.
[0204] Example 7. The medical device system of any one of examples 1 - 6 further comprising sensing circuitry configured to sense cardiac event signals attendant to intrinsic depolarizations by sensing atrial event signals and ventricular event signals. The control circuitry may be further configured to determine at least one RP interval from a sensed ventricular event signal to a sensed atrial event signal and determine that the RP interval is less than a threshold interval. The control circuitry may, in response to the at least one RP interval being less than the threshold interval, disable or adjust the AVNS therapy.
[0205] Example 8. The medical device system of any one of examples 1 - 7 wherein the control circuitry is further configured to detect a lead or electrode issue and adjust or disable delivery of the AVNS therapy by the therapy delivery circuitry in response to detecting the lead or electrode issue.
[0206] Example 9. The medical device system of any one of examples 1 - 8 further comprising an impedance measurement circuit configured to perform an impedance measurement. The control circuitry may be further configured to determine that the impedance measurement is outside a threshold range and disable or adjust delivery of the AVNS therapy when the impedance measurement is outside the threshold range.
[0207] Example 10. The medical device system of any one of examples 1 - 9 further comprising sensing circuitry configured to sense atrial event signals attendant to atrial depolarizations and sense ventricular event signals attendant to ventricular depolarizations. The control circuitry may be further configured to determine at least one PR interval extending from an atrial event signal to a ventricular event signal sensed by the sensing circuitry, determine that the PR interval is less than a threshold and disable or adjust delivery of the AVNS when the PR interval is less than the threshold interval.
[0208] Example 11. The medical device system of any one of examples 7 - 10 wherein the control circuitry may be further configured to generate an alert in response to disabling or adjusting delivery of the AVNS therapy. The medical device may further include a telemetry circuit configured to transmit the alert.
[0209] Example 12. The medical device system of any one of examples 1 - 11 wherein the control circuitry is further configured to adjust the at least one AVNS control parameter by adjusting at least one of: a pulse amplitude, a pulse width, adjusting a pulse frequency, a pulse train duration, a pulse train rate, an inter-train interval, a duty cycle or an AVNS electrode vector.
[0210] Example 13. The medical device system of any one of examples 1 - 12 further comprising sensing circuitry configured to sense cardiac event signals attendant to intrinsic cardiac depolarizations by sensing atrial event signals and ventricular event signals. The therapy delivery circuitry may be further configured to deliver the AVNS therapy by generating a pulse train according to the AVNS control parameters on every nth ventricular event signal sensed by the sensing circuitry.
[0211] Example 14. The medical device system of any one of examples 1 - 13 further comprising sensing circuitry configured to sense cardiac event signals attendant to intrinsic cardiac depolarizations by sensing atrial event signals and ventricular event signals. The therapy delivery circuitry may be further configured to deliver the AVNS therapy by starting a pulse train of the AVNS therapy in response to a sensed cardiac event signal and terminating the pulse train of the AVNS therapy after n atrial event signals are sensed by the sensing circuitry.
[0212] Example 15. The medical device system of any one of examples 1 - 14 further comprising sensing circuitry configured to sense cardiac event signals attendant to intrinsic cardiac depolarizations by sensing ventricular event signals. The therapy delivery circuitry may be further configured to deliver the AVNS therapy by delivering a first pulse train having a pulse train duration, waiting for the sensing circuitry to sense a ventricular event signal after the pulse train duration of the first pulse train and delivering a second pulse train after the ventricular event signal is sensed by the sensing circuitry, the second pulse train having the pulse train duration.
[0213] Example 16. The medical device system of any one of examples 1 - 15 further comprising sensing circuitry configured to sense cardiac event signals attendant to intrinsic cardiac depolarizations. The therapy delivery circuitry is further configured to deliver the AVNS therapy by delivering a first pulse train, waiting for a minimum rate interval to expire after the first pulse train, waiting for a cardiac event signal to be sensed by the sensing circuitry after the minimum rate interval expires and delivering a second pulse train in response to the cardiac event signal sensed by the sensing circuitry after the minimum rate interval expires.
[0214] Example 17. The medical device system of any one of examples 1-16 further comprising a first implantable medical device including a first therapy delivery circuit of the therapy delivery circuitry and a first communication circuit. The first therapy delivery circuit being configured to deliver the AVNS therapy. The medical device system further including a second implantable medical device including a second therapy delivery circuit of the therapy delivery circuitry and a second communication circuit. The second therapy delivery circuit being configured to generate the ventricular pacing pulses and the second communication circuit being configured to transmit a communication signal to the first communication circuit in response to at least one ventricular pacing pulse being delivered by the second therapy delivery circuit. The control circuitry may be further configured to determine that the threshold number of ventricular pacing pulses are delivered based on the transmitted communication signal.
[0215] Example 18. The medical device system of any one of examples 1 - 17 further including sensing circuitry configured to sense ventricular event signals. The control circuitry is further configured to determine ventricular event intervals from ventricular event signals sensed by the sensing circuitry and adjust one or more of the AVNS control parameters until the determined ventricular event intervals meet at least one of a target rate or stability criteria.
[0216] Example 19. The medical device system of any one of examples 1 - 18 wherein the therapy delivery circuitry is configured to deliver the AVNS therapy via an electrode implanted in operative proximity to the AV node.
[0217] Example 20. The medical device system of any one of examples 1 — 19 further including a plurality of electrodes and sensing circuitry configured to sense atrial event signals and ventricular event signals. The control circuitry being further configured to, for each of a plurality of test AVNS electrode vectors selected from the plurality of electrodes: control the therapy delivery circuitry to deliver at least one AVNS pulse train via each of a plurality of test AVNS electrode vectors and determine an AV conduction time from an atrial event signal to a ventricular event signal sensed by the sensing circuitry after the at least one AVNS pulse train is started. The control circuitry may select an AVNS therapy delivery electrode vector based on the determined AV conduction time. The therapy delivery circuitry may be further configured to deliver the AVNS therapy via the selected AVNS therapy delivery electrode vector.
[0218] Example 21. The medical device system of any one of examples 1 — 20 further including a housing enclosing the therapy delivery circuitry and the control circuitry, the housing having a distal end face, and a plurality of electrodes based on the distal end face. The therapy delivery circuitry can be configured to deliver the AVNS therapy via an AVNS electrode vector comprising at least one of the plurality of electrodes based on the distal end face. [0219] Example 22. The medical device system of example 21 further comprising a distal electrode extension extending from the distal end face carrying at least one of the plurality of electrodes based on the distal end face.
[0220] Example 23. The medical device system of any one of examples 1 — 22 wherein the therapy delivery circuitry is further configured to terminate the AVNS therapy. The control circuitry is further configured to determine that ventricular interval stability criteria are not met after the AVNS therapy is terminated, and the therapy delivery circuitry is further configured to restart the AVNS therapy in response to the ventricular interval stability criteria not being met.
[0221] Example 24. A method including delivering an AVNS therapy for suppressing atrioventricular node conduction by generating pulse trains according to AVNS control parameters, delivering ventricular pacing pulses, determining that a first threshold number of ventricular pacing pulses are delivered while the AVNS therapy is being delivered and adjusting at least one AVNS control parameter in response to determining that the first threshold number of ventricular pacing pulses have been delivered.
[0222] Example 25. The method of example 24 further including sensing ventricular event signals, determining ventricular event intervals from the sensed ventricular event signals and the ventricular pacing pulses delivered during the AVNS therapy and determining that the ventricular event intervals do not meet ventricular interval stability criteria. The method may further include determining that a second threshold number of ventricular pacing pulses are delivered while the AVNS therapy is being delivered, the second threshold number being less than the first threshold number. The method may further include adjusting at least one AVNS control parameter in response to determining that the second threshold number of ventricular pacing pulses have been delivered and the ventricular interval stability criteria are not met.
[0223] Example 26. The method of any one of examples 24 or 25 further including sensing cardiac event signals attendant to intrinsic depolarizations and detecting an atrial tachyarrhythmia based on at least the sensed cardiac event signals. The method may further include determining that the sensed cardiac event signals meet unstable ventricular rate criteria and starting delivery of the AVNS therapy in response to detecting the atrial tachyarrhythmia and the sensed cardiac event signals meeting unstable ventricular rate criteria. [0224] Example 27. The method of example 26 further including determining ventricular sensed event intervals from the sensed cardiac event signals, comparing the ventricular sensed event intervals to a short interval threshold, determining that a threshold number of the ventricular sensed event intervals are less than the short interval threshold and determining that the sensed cardiac event signals meet unstable ventricular rate criteria based on at least the threshold number of the ventricular sensed event intervals being less than the short interval threshold.
[0225] Example 28. The method of any one of examples 24 - 27 further comprising determining ventricular sensed event intervals from the sensed cardiac event signals, determining a variability metric from the ventricular sensed event intervals, determining that the variability metric meets a variability threshold, and determining that the sensed cardiac event signals meet unstable ventricular rate criteria based on at least the variability metric meeting the variability threshold.
[0226] Example 29. The method of any of one of examples 24 - 28 further comprising sensing cardiac event signals by sensing ventricular event signals. The method may further include determining that a threshold time interval of delivering the AVNS therapy without adjustment of an AVNS control parameter has expired. In response to the threshold time interval expiring, the method may include adjusting at least one AVNS control parameter from a first value to a second value associated with reduced suppression of atrioventricular conduction and delivering the AVNS therapy according to the second value of the at least one AVNS control parameter. The method may include determining sensed ventricular event intervals from the ventricular event signals sensed during the AVNS therapy delivered according to the second value and determining if stability criteria are met based on the determined sensed ventricular event intervals. The method may include restoring the at least one AVNS control parameter to the first value in response to the stability criteria not being met or continue delivering the AVNS therapy according to the second value in response to the stability criteria being met.
[0227] Example 30. The method of any one of examples 24 - 29 further including sensing cardiac event signals attendant to intrinsic depolarizations by sensing atrial event signals and ventricular event signals, determining at least one RP interval from a sensed ventricular event signal to a sensed atrial event signal, and determining that the RP interval is less than a threshold interval. In response to the at least one RP interval being less than the threshold interval, the method may include disabling or adjusting the AVNS therapy. [0228] Example 31. The method of any one of examples 24 - 30 further including detecting a lead or electrode issue and adjusting or disabling delivery of the AVNS therapy in response to detecting the lead or electrode issue.
[0229] Example 32. The method of any one of examples 24 - 31 further including performing an impedance measurement, determining that the impedance measurement is outside a threshold range and disabling or adjusting delivery of the AVNS therapy when the impedance measurement is outside the threshold range.
[0230] Example 33. The method of any one of examples 24 - 32 further including sensing atrial event signals attendant to atrial depolarizations, sensing ventricular event signals attendant to ventricular depolarizations, determining at least one PR interval extending from an atrial event signal to a ventricular event signal and determining that the PR interval is less than a threshold. The method may further include disabling or adjusting delivery of the AVNS when the PR interval is less than the threshold interval.
[0231] Example 34. The method of any one of examples 30 - 33 further including generating an alert in response to disabling or adjusting delivery of the AVNS therapy and transmitting the alert.
[0232] Example 35. The method of any one of examples 24 - 34 wherein adjusting the at least one AVNS control parameter includes adjusting at least one of: a pulse amplitude, a pulse width, a pulse frequency, a pulse train duration, a pulse train rate, an inter-train interval, a duty cycle or an AVNS electrode vector.
[0233] Example 36. The method of any one of examples 24 - 35 further including sensing cardiac event signals attendant to intrinsic cardiac depolarizations by sensing atrial event signals and ventricular event signals and delivering the AVNS therapy by generating a pulse train according to the AVNS control parameters on every nth ventricular event signal sensed by the sensing circuitry.
[0234] Example 37. The method of any one of examples 24 - 36 further including sensing cardiac event signals attendant to intrinsic cardiac depolarizations by sensing atrial event signals and ventricular event signals and delivering the AVNS therapy by starting a pulse train of the AVNS therapy in response to a sensed cardiac event signal. The method may further include terminating the pulse train of the AVNS therapy after n atrial event signals are sensed by the sensing circuitry.
[0235] Example 38. The method of any one of examples 24 - 37 further including sensing cardiac event signals attendant to intrinsic cardiac depolarizations by sensing ventricular event signals. The method may include delivering the AVNS therapy by delivering a first pulse train having a pulse train duration, waiting for the sensing circuitry to sense a ventricular event signal after the pulse train duration of the first pulse train and delivering a second pulse train after the ventricular event signal is sensed, the second pulse train having the pulse train duration.
[0236] Example 39. The method of any one of examples 24 - 38 further comprising sensing cardiac event signals attendant to intrinsic cardiac and delivering the AVNS therapy by delivering a first pulse train, waiting for a minimum rate interval to expire after the first pulse train, waiting for a cardiac event signal to be sensed after the minimum rate interval expires and delivering a second pulse train in response to the cardiac event signal sensed after the minimum rate interval expires.
[0237] Example 40. The method of any one of examples 24 - 39 further including delivering the AVNS therapy by a first therapy delivery circuit of a first implantable medical device and delivering the ventricular pacing pulses by a second therapy delivery circuit of a second implantable medical device. The method may further include, in response to at least one ventricular pacing pulse being delivered by the second therapy delivery circuit, transmitting a communication signal from a second communication circuit of the second implantable medical device to a first communication circuit of the first implantable medical device. The method may further include determining that the threshold number of ventricular pacing pulses are delivered based on the transmitted communication signal.
[0238] Example 41. The method of any one of examples 24 - 40 further including sensing ventricular event signals, determining ventricular event intervals from the sensed ventricular event signals and adjusting one or more of the AVNS control parameters until the determined ventricular event intervals meet at least one of a target rate or stability criteria. [0239] Example 42. The method of any one of examples 24 - 41 further including delivering the AVNS therapy via an electrode implanted in operative proximity to the AV node.
[0240] Example 43. The method of any one of examples 24 — 42 further including sensing atrial event signals and sensing ventricular event signals. The method may further include, for each of a plurality of test AVNS electrode vectors, delivering at least one AVNS pulse train and determining an AV conduction time interval from an atrial event signal to a ventricular event signal sensed after the at least one AVNS pulse train is started. The method may include selecting an AVNS therapy delivery electrode vector based on the determined atrioventricular conduction time intervals and delivering the AVNS therapy via the selected AVNS therapy delivery electrode vector.
[0241] Example 44. The method of any one of examples 24 — 43 further comprising terminating the AVNS therapy, determining that ventricular interval stability criteria are not met after the AVNS therapy is terminated, and restarting the AVNS therapy in response to the ventricular interval stability criteria not being met.
[0242] Example 45. A non-transitory computer readable medium storing a set of instructions which, when executed by control circuitry of a medical device system, cause the medical device system to deliver an AVNS therapy for suppressing atrioventricular node conduction by generating pulse trains according to AVNS control parameters. The instructions may further cause the medical device system to deliver ventricular pacing pulses, determine that a threshold number of ventricular pacing pulses are delivered while the AVNS therapy is being delivered, and adjust at least one AVNS control parameter in response to determining that the threshold number of ventricular pacing pulses have been delivered.
[0243] 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.
[0244] 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).
[0245] 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.
[0246] 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.