Method and apparatus for atrial event detection

Abstract

An intraventricular pacemaker includes: a pulse generator for delivering ventricular pacing pulses; an impedance sensing circuit; and a control circuit in communication with the pulse generator and the impedance sensing circuit. The pacemaker is configured to generate an intraventricular impedance signal, detect an atrial systolic event using the intraventricular impedance signal, set an atrioventricular pacing interval in response to detecting the atrial systolic event, and deliver a ventricular pacing pulse in response to the atrioventricular pacing interval expiring.

Description

Technical Field

[0001] The present disclosure relates to an implantable medical device and method for detecting atrial events using intraventricular impedance signals. Background Art

[0002] An implantable cardiac pacemaker is typically placed in a subcutaneous pocket and is coupled to one or more transvenous medical electrical leads that carry pacing and sensing electrodes positioned in the heart. A subcutaneously implanted cardiac pacemaker may be a single-chamber pacemaker coupled to one transvenous medical lead for positioning electrodes in one heart chamber, the atrium or ventricle, or a dual-chamber pacemaker coupled to two transvenous leads for positioning electrodes in the atrial and ventricular chambers. Multi-chamber pacemakers may also be used, which may be coupled to three leads, for example, three leads for positioning electrodes for pacing and sensing in one atrial chamber and in the left and right ventricles.

[0003] Leadless intracardiac pacemakers are available or have been proposed for implantation within the ventricular chamber of a patient's heart for delivery of ventricular pacing pulses. Such pacemakers can sense the R-wave signal accompanying intrinsic ventricular depolarization and deliver ventricular pacing pulses in the absence of a sensed R-wave. While single-chamber ventricular sensing and pacing by an intracardiac ventricular pacemaker may adequately address a patient's condition, some patients may benefit from atrial and ventricular (dual-chamber) sensing for providing atrial-synchronized ventricular pacing to maintain a more normal heart rhythm. Summary of the invention

[0004] The disclosed technology generally relates to a pacemaker configured to generate an intraventricular impedance signal for sensing an atrial event. In some instances, an atrial event can be sensed directly from the intraventricular impedance signal for use in controlling atrial synchronized ventricular pacing. In other instances, the intraventricular impedance signal can be used to establish atrial event sensing parameters that are used to sense an atrial event from another signal and / or to confirm atrial event sensing from another signal (e.g., from an intraventricular motion signal generated by an accelerometer).

[0005] In one example, the present disclosure provides an intraventricular pacemaker, the intraventricular pacemaker comprising a pulse generator, an impedance sensing circuit, and a control circuit in communication with the impedance sensing circuit and the pulse generator. The pulse generator is configured to generate a ventricular pacing pulse via an electrode connected to the pacemaker and deliver the ventricular pacing pulse to a patient's heart. The impedance sensing circuit is configured to generate an intraventricular impedance signal. The control circuit is configured to use the intraventricular impedance signal to detect an atrial systolic event, set an atrioventricular pacing interval in response to detecting an atrial systolic event, and control the pulse generator to deliver a ventricular pacing pulse when the atrioventricular pacing interval expires.

[0006] In another example, the present disclosure provides a method performed by a ventricular pacemaker in a heart, the method comprising: generating an intraventricular impedance signal by an impedance sensing circuit; using the intraventricular impedance signal by a control circuit of the pacemaker to detect an atrial systolic event; setting an atrioventricular pacing interval by the control circuit in response to detecting the atrial systolic event; and delivering a ventricular pacing pulse when the atrioventricular pacing interval expires.

[0007] In another example, the present disclosure provides a non-transitory computer-readable storage medium comprising a set of instructions that, when executed by a control circuit of a ventricular pacemaker in a heart, cause the pacemaker to generate an intraventricular impedance signal, use the intraventricular impedance signal to detect an atrial systolic event, set an atrioventricular pacing interval in response to detecting the atrial systolic event, and deliver a ventricular pacing pulse at the end of the atrioventricular pacing interval.

[0008] The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the following description. Other features, objects, and advantages of the techniques described in this disclosure will be apparent from the description and drawings, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 is a conceptual diagram illustrating an intracardiac ventricular pacing system that may be used to sense cardiac signals and deliver pacing therapy to a patient's heart.

[0010] Figure 2 yes Figure 1 A conceptual diagram of an intracardiac pacemaker is shown.

[0011] Figure 3 yes Figure 1 A schematic diagram of an exemplary configuration of a pacemaker is shown.

[0012] Figure 4 can be included in Figure 1 Example of a motion sensor signal generated by a motion sensor in a pacemaker.

[0013] Figure 5 Describes the Figure 1 Example motion sensor signals generated by a pacemaker over two different cardiac cycles.

[0014] Figure 6 Describes the Figure 1 The pacemaker generates intraventricular motion signals, intraventricular impedance signals, ventricular electrogram (EGM) signals, and electrocardiogram (ECG) signals.

[0015] Figure 7 Describes the Figure 1 The amplitude waveform and phase angle waveform of the intraventricular impedance signal generated by the pacemaker.

[0016] Figure 8 It can be done by Figure 1 Flowchart of a method of performing ventricular pacing with a pacemaker.

[0017] Fig. 9 According to another example Figure 1 A flow chart of a method performed by a pacemaker for establishing atrial event signal sensing parameters using an impedance signal and for controlling atrial synchronized ventricular pacing.

[0018] Fig.10 According to another example Figure 1 Flow chart of a method performed by a pacemaker for controlling ventricular pacing with atrial synchronization.

[0019] Fig.11 According to another example Figure 1 Flow chart of a method performed by a pacemaker for controlling ventricular pacing. DETAILED DESCRIPTION

[0020] The technology disclosed herein provides a method for sensing atrial events by a ventricular pacemaker, which can be an intracardiac pacemaker fully implantable within a ventricular heart chamber. In general, the present disclosure describes a technology for atrial event sensing using an intraventricular impedance signal by an implantable medical device. As described below, an atrial systolic event (sometimes referred to as an "atrial beat") can be detected based on an impedance signal acquired from an electrode pair implanted in the ventricle of a patient's heart. Atrial events can be detected from within the ventricle for use in controlling the timing of atrial synchronized ventricular pacing pulses. Atrial synchronized ventricular pacing pulses can be delivered by a pacemaker implanted in the ventricle without the need for electrodes for detecting atrial events or another sensor outside the ventricle, such as a sensor in or on the atrium of the patient's heart or elsewhere in the patient's body. In this way, the operation of a pacemaker (e.g., a leadless ventricular pacemaker) can be improved by facilitating reliable, accurate atrial event sensing and thereby achieving atrial synchronized ventricular pacing.

[0021] Achieving reliable atrial event sensing and atrial-synchronized ventricular pacing with an intraventricular pacemaker is a technical challenge because atrial signals, such as electrical P-wave signals, are relatively low amplitude signals compared to ventricular signals, especially when sensed from within the ventricle. The technology disclosed herein addresses this technical challenge by generating an intraventricular impedance signal and using the intraventricular impedance signal in atrial event sensing to facilitate more reliable and accurate atrial event sensing. Achieving atrial-synchronized ventricular pacing with reliable atrial event sensing improves the pacing function of the pacemaker because ventricular pacing that is accurately synchronized with sensed atrial events promotes a more normal heart rhythm compared to pacing the ventricles asynchronously with the atria, such as in patients experiencing atrioventricular (AV) block. Atrial-synchronized ventricular pacing enhances the hemodynamic benefits of ventricular pacing by accurately timing the ventricular pacing pulse (and subsequent ventricular contraction) after the atrial contribution to ventricular filling, compared to asynchronous ventricular pacing or improperly timed ventricular pacing pulses due to unreliable atrial event sensing (e.g., oversensing or undersensing of atrial events).

[0022] Figure 1 is a conceptual diagram illustrating an intracardiac ventricular pacing system 10 that can be used to sense cardiac signals and deliver pacing therapy to a patient's heart 8. The cardiac signals may include electrical signals corresponding to electrical depolarization of the myocardium, intraventricular impedance signals associated with changes in blood volume in the heart during the cardiac cycle, and intraventricular motion signals caused by cardiac motion and flowing blood. The IMD system 10 includes an intracardiac ventricular pacemaker 14 and an external device 20 for sending data to and receiving data from the pacemaker 14.

[0023] The pacemaker 14 may be a transcatheter intracardiac pacemaker adapted to be implanted entirely within a cardiac chamber, such as entirely within the right ventricle (RV) of the heart 8 or entirely within the left ventricle (LV) of the heart 8, for sensing cardiac signals and delivering ventricular pacing pulses. The pacemaker 14 is typically reduced in size compared to a subcutaneously implanted pacemaker and may be typically cylindrical in shape to enable transvenous implantation via a delivery catheter.

[0024] The pacemaker 14 is capable of generating electrical stimulation pulses, such as pacing pulses delivered to the heart 8 via electrodes on the outer housing of the pacemaker. The pacemaker 14 can be a leadless pacemaker configured to sense cardiac electrical signals using shell-based electrodes for generating a ventricular electrogram (EGM) signal. The cardiac electrical signals can be sensed using shell-based electrodes, which are also used to deliver pacing pulses to the right ventricle (RV) at the position shown. The shell-based electrodes can be used to generate an intraventricular impedance signal, which is related to the electrical impedance of the blood volume surrounding the shell-based electrodes when the shell-based electrodes are positioned in the heart chamber. The drive current signal can be injected using the shell-based electrodes, and the resulting voltage signal can be sensed by the shell-based electrodes to generate the intraventricular impedance signal. Alternatively, the drive voltage signal can be applied by the shell-based electrodes, and the resulting current signal can be sensed for generating the intraventricular impedance signal.

[0025] As shown, the pacemaker 14 is positioned in the RV along the endocardial wall, for example, near the RV apex, although other locations are possible. The technology disclosed herein is not limited to Figure 1 The pacemaker locations shown in the example of , and other locations within the heart 8 are possible. For example, an intraventricular pacemaker 14 can be positioned in the LV and configured to detect cardiac signals, including intraventricular impedance signals, and deliver atrial synchronized ventricular pacing to the LV using the techniques disclosed herein. The pacemaker 14 can be positioned in the RV or LV to provide respective right ventricular or left ventricular pacing, and is used to sense cardiac signals within the ventricular chambers in order to control the timing of ventricular pacing pulses.

[0026] The pacemaker 14 is configured to control the delivery of ventricular pacing pulses to the RV in a manner that promotes synchronization between atrial contraction and ventricular contraction, for example, by maintaining an AV interval between an atrial event and a ventricular pacing pulse. In other words, the pacemaker 14 controls pacing pulse delivery to maintain a desired AV interval between atrial contraction corresponding to atrial systole and a ventricular pacing pulse delivered to cause ventricular depolarization and ventricular systole. The AV interval may be a default or programmed value selected by a clinician and is the time interval from detection of an atrial event to delivery of a ventricular pacing pulse.

[0027] According to the techniques described herein, the intraventricular impedance signal is used to detect an atrial systolic event that produces an active ventricular filling phase or an atrial "kick." In some cases, the atrial systolic event can be detected by the pacemaker 14 directly from the intraventricular impedance signal or a derivative signal of the intraventricular impedance signal. In other cases, the intraventricular impedance signal is used to detect an atrial systolic event by confirming an atrial event sensed from a different cardiac signal and / or by using the intraventricular impedance signal to establish a sensing parameter for controlling the sensing of an atrial systolic event from another cardiac signal.

[0028] For example, an atrial systolic event can be sensed from a motion signal generated by a motion sensor (e.g., an accelerometer enclosed by the housing of the pacemaker 14). The acceleration of blood flowing through the tricuspid valve 16 between the right atrium (RA) and the RV into the RV caused by atrial systole can be detected by the pacemaker 14 from a signal generated by the accelerometer included in the pacemaker 14. The motion signal generated by the accelerometer implanted within the ventricular chamber includes motion signals caused by ventricular and atrial events, and may include non-cardiac signals caused by the patient's physical activity and movement. As described in more detail below, the intraventricular impedance signal can be used to confirm atrial systolic events sensed from the motion signal and / or to adjust sensing parameters used to sense atrial systolic events from the motion signal to avoid oversensing other motion signals as atrial systolic events. For example, one challenge in reliably sensing atrial events from a motion signal may occur during physical activity of a patient, which results in the patient's physical activity signal being present in the motion signal, which may interfere with the atrial event signal.

[0029] The atrial P wave, which accompanies atrial depolarization, is a relatively low amplitude signal (e.g., compared to the near-field R wave) in the near-field ventricular cardiac electrical signal received by the pacemaker 14. Therefore, it is difficult to reliably detect the P wave from the cardiac electrical signal acquired by the pacemaker 14 implanted in the ventricular chamber. Atrial-synchronized ventricular pacing or other functions that rely on atrial sensing performed by the pacemaker 14 may be unreliable when based solely on the cardiac electrical signal received by the pacemaker 14. Atrial event sensing from intraventricular motion signals may sometimes be difficult, for example due to increased patient physical activity that contributes to the motion signal. According to the technology disclosed herein, the pacemaker 14 includes an impedance sensing circuit for generating an impedance signal, which is used to detect atrial events and / or confirm an atrial event sensed from another cardiac signal (e.g., a cardiac electrical signal or a motion signal). The ventricular pacing pulses may be synchronized with atrial events detected directly from the impedance signal, which may include determining a derivative of the impedance signal by setting a programmable AV pacing interval that controls the timing of the ventricular pacing pulses relative to the detected atrial systolic event. In other examples, detection of an atrial systolic event for synchronizing the ventricular pacing pulses with atrial systole may include detecting an atrial systolic event from a motion signal or from a cardiac electrical signal by using the impedance signal to confirm detection of an atrial systolic event, which may occur periodically or triggered.

[0030] The pacemaker 14 is capable of bidirectional wireless communication with an external device 20 for programming AV pacing intervals and other pacing control parameters and atrial event sensing parameters for detecting atrial systolic events from a selected signal. Aspects of the external device 20 may generally correspond to the external programming / monitoring unit disclosed in U.S. Pat. No. 5,507,782 (Kieval et al.), which is hereby incorporated by reference in its entirety. The external device 20 is generally referred to as a "programmer" because it is typically used by a physician, technician, nurse, clinician, or other qualified user to program operating parameters in the pacemaker 14. The external device 20 may be located in a clinic, hospital, or other medical facility. The external device 20 may alternatively be embodied as a home monitor or handheld device that may be used in a medical facility, a patient's home, or another location. The operating parameters, including sensing and therapy delivery control parameters, may be programmed into the pacemaker 14 using the external device 20.

[0031] The external device 20 is configured for bidirectional communication with implantable telemetry circuitry included in the pacemaker 14. The external device 20 establishes a wireless communication link 24 with the pacemaker 14. For example, Bluetooth , Wi-Fi, Medical Implant Communications Service (MICS), or other communication bandwidth radio frequency (RF) link to establish the communication link 24. In some instances, the external device 20 may include a programming head that is placed near the pacemaker 14 to establish and maintain the communication link 24, and in other instances, the external device 20 and the pacemaker 14 may be configured to communicate using a distance telemetry algorithm and circuit system that does not require the use of a programming head and does not require user intervention to maintain the communication link. An exemplary RF telemetry communication system that can be implemented in the system 10 is generally disclosed in U.S. Patent No. 5,683,432 (Goedeke et al.), which is hereby incorporated by reference in its entirety. The external device 20 can display data and information related to pacemaker function to the user for checking pacemaker operation and programmed parameters as well as EGM signals, motion sensor signals, impedance signals, or other physiological signals generated and transmitted by the pacemaker 14, or other physiological data determined by and retrieved from the pacemaker 14 during an interrogation session.

[0032] It is contemplated that the external device 20 may be wired or wirelessly connected to a communication network via telemetry circuitry including a transceiver and antenna or via hardwired communication lines for transmitting data to a centralized database or computer to allow remote management of the patient. A remote patient management system including a centralized patient database may be configured to utilize the presently disclosed techniques to enable a clinician to review the EGM, motion sensor signals, impedance signals, and marker channel data, and authorize programming of sensing and therapy control parameters in the pacemaker 14, for example, after viewing a visual representation of the EGM, motion sensor signals, impedance signals, and marker channel data.

[0033] Figure 2 yes Figure 1 Conceptual diagram of an intracardiac pacemaker 14 is shown. The pacemaker 14 includes electrodes 162 and 164 spaced apart along a housing 150 of the pacemaker 14 for sensing cardiac electrical signals and delivering pacing pulses. The housing 150 includes a distal end 102 defining a distal-facing surface of the pacemaker 14, a proximal end 104 defining a proximal-facing surface of the pacemaker 14, and an outer sidewall 105 extending from the distal end 102 to the proximal end 104. The distal end 102 is referred to as "distal" because it is intended to be the leading end when the pacemaker 14 is advanced through a delivery tool (e.g., a catheter) and placed against a target pacing site within the heart. The outer lateral sidewall 105 defines a circumferential or peripheral lateral surface of the pacemaker 14. Electrode 164 is shown as a tip electrode located on the distal end 102 of the pacemaker 14, and electrode 162 is shown as a ring electrode along the middle of the side wall 105, for example adjacent to the proximal end 104 and completely or at least partially surrounding the side wall 105.

[0034] Electrodes 162 and 164 form an anode and cathode pair for bipolar cardiac pacing and cardiac electrical signal sensing. Electrodes 162 and 164 may be, but are not limited to, titanium, platinum, iridium, or alloys thereof, and may include low polarization coatings such as titanium nitride, iridium oxide, ruthenium oxide, platinum black, and the like. Electrode 164 may act as a cathode electrode and be connected to an internal circuit system, such as a pacing pulse generator, cardiac electrical signal sensing circuit system, and impedance sensing circuit enclosed by housing 150, via an electrical feedthrough through housing 150. Electrode 162, defined by a conductive portion of housing 150, serves as a return anode during pacing and sensing. In addition to delivering cardiac pacing pulses and sensing cardiac electrical signals, electrodes 162 and 164 may be used to deliver impedance drive signals and sensed raw impedance signals. Electrodes 162 and 164 may be positioned at other locations along pacemaker 14 other than the locations shown. For example, the electrode 162 can be positioned more proximally or more distally along the housing 150 , and / or the cathode electrode 164 can be a ring electrode at or near the distal end 102 of the pacemaker 14 .

[0035] In other examples, the pacemaker 14 may include two or more ring electrodes and / or a proximal tip electrode at the proximal end 104 for recording an electrode pair for receiving a raw impedance signal generated by an injected impedance drive signal. In some cases, the relative proximity or degree of contact between the electrode 164 and the endocardial surface of the ventricular chamber may vary with cardiac motion, implantation location, and other factors. Changes in the proximity or degree of contact between the tip electrode 164 and the myocardial surface and the resulting relative immersion in the ventricular blood pool during the cardiac cycle may result in changes in the raw signal acquired using the distal tip electrode 164 for generating an intraventricular impedance signal. Thus, in some examples, a second ring electrode, such as the distal ring electrode 168, may be disposed on the lateral sidewall 105 for use with the proximal ring electrode 162 to generate an intraventricular impedance signal. When more than two electrodes are available, the same or different electrode pairs may be used for injecting the drive signal and for receiving the resulting raw impedance signal. The intraventricular impedance signal generated by the pacemaker 14 from raw signals received between the two spaced-apart recording electrodes on the lateral sidewall 105 can be used more reliably to detect atrial events than an intraventricular impedance signal generated from raw signals received using the electrodes 164 on the housing distal end 102 as recording electrodes. The greater reliability of the impedance signal may be associated with more consistent submersion of the two ring electrodes on the peripheral sidewall in the surrounding blood volume compared to the distal tip electrode which may have varying contact with the myocardial tissue during the cardiac cycle.

[0036] Electrode 168 can be coupled to an impedance sensing circuit enclosed by housing 150 via an electrical conductor and can serve as a cathode electrode for injecting a drive current (or voltage) signal and receiving a resulting voltage (or current) signal. Electrode 162 is electrically isolated from electrode 168 and coupled to the impedance sensing circuit via an electrical conductor to serve as a return anode electrode.

[0037] The housing 150 is formed of a biocompatible material, such as stainless steel or a titanium alloy. In some instances, the housing 150 may include an insulating coating. Examples of insulating coatings include polyparaxylene, urethane, PEEK, or polyimide, etc. The entirety of the housing 150 may be insulated, but only the electrodes 162, 164, and 168 are not insulated. The electrodes 162 and 168 may be formed as conductive portions of the housing 150 that define an annular electrode that is electrically isolated from the rest of the housing 150 and from each other. In other instances, instead of providing a local annular electrode such as the anode electrode 162, the entire periphery of the housing 150 may be used as a single electrode electrically isolated from the tip electrode 164.

[0038] Housing 150 includes a control electronics subassembly 152 that houses electronics for sensing cardiac signals, generating pacing pulses, and controlling therapy delivery and other functions of pacemaker 14, as described below in conjunction with Figure 3 The housing 150 further includes a battery subassembly 160 that provides power to the control electronics subassembly 152. The battery subassembly 160 may include features of the batteries disclosed in commonly assigned U.S. Pat. No. 8,433,409 (Johnson et al.) and U.S. Pat. No. 8,541,131 (Lund et al.), both of which are hereby incorporated by reference in their entirety.

[0039] The pacemaker 14 may include a set of fixation tines 166 to secure the pacemaker 14 to patient tissue, for example, by actively engaging the ventricular endocardium and / or interacting with the ventricular trabeculae. The fixation tines 166 are configured to anchor the pacemaker 14 to position the electrode 164 in operable proximity to the target tissue to deliver therapeutic electrical stimulation pulses. Various types of active and / or passive fixation members may be employed to anchor or stabilize the pacemaker 14 in an implanted position. The pacemaker 14 may include a set of fixation tines as disclosed in commonly assigned U.S. Pat. No. 9,775,982 (Grubac et al.), which is hereby incorporated by reference in its entirety.

[0040] The pacemaker 14 may optionally include a delivery tool interface 158. The delivery tool interface 158 may be located at the proximal end 104 of the pacemaker 14 and configured to connect to a delivery device (e.g., a catheter) used to position the pacemaker 14 at an implantation site, such as within a heart chamber, during an implantation procedure.

[0041] Figure 3 yes Figure 1 A schematic diagram of an exemplary configuration of a pacemaker 14 is shown. The pacemaker 14 includes a pulse generator 202, a cardiac electrical signal sensing circuit 204, a control circuit 206, a memory 210, a telemetry circuit 208, a motion sensor 212, a power source 214, and an impedance sensing circuit 216. Figure 3 The various circuits represented may be combined on one or more integrated circuit boards, which may include: a specific integrated circuit (ASIC); an electronic circuit; a processor (shared, dedicated, or grouped) and memory that executes one or more software or firmware programs; a combinational logic circuit; a state machine; or other suitable components that provide the described functionality.

[0042] The pulse generator 202 generates electrical pacing pulses that are delivered to the patient's heart via electrodes coupled to the pacemaker 14 (e.g., the housing-based cathode electrode 164 and the return anode electrode 162). The pulse generator 202 may include a charging circuit 230, a switching circuit 232, and an output circuit 234. The charging circuit 230 may include a holding capacitor that may be charged to a pacing pulse amplitude under the control of a voltage regulator that is a multiple of the battery voltage signal of the power source 214. The pacing pulse amplitude may be set based on a control signal from the control circuit 206. The switching circuit 232 may control when the holding capacitor of the charging circuit 230 is coupled to the output circuit 234 for delivery of a pacing pulse. For example, the switching circuit 232 may include a switch that is activated by a timing signal received from the pacing timing circuit 242 of the control circuit 206 at the end of a pacing interval and remains closed within a programmed pacing pulse width to enable the holding capacitor of the charging circuit 230 to discharge. During the programmed pacing pulse duration, the holding capacitor, which is pre-charged to the pacing pulse voltage amplitude, is discharged between electrodes 162 and 164 through the output capacitor of output circuit 234. Examples of pacing circuit systems generally disclosed in U.S. Pat. No. 5,507,782 (Kieval et al.) and commonly assigned U.S. Pat. No. 8,532,785 (Crutchfield et al.), both of which are incorporated herein by reference in their entireties, may be implemented in pacemaker 14 to charge the pacing capacitor to a predetermined pacing pulse amplitude under the control of control circuit 206 to generate and deliver pacing pulses.

[0043] The cardiac electrical signal sensing circuit 204 is configured to sense the cardiac electrical signal via electrodes 162 and 164 and generate an intraventricular EGM signal. The cardiac electrical signal is received by a pre-filter and amplifier circuit 220. The pre-filter and amplifier circuit 220 may include a high-pass filter to remove DC offset, such as a high-pass filter of 2.5 to 5 Hz, or a wideband filter with a passband of 2.5 Hz to 100 Hz to remove DC offset and high-frequency noise. The pre-filter and amplifier circuit 220 may further include an amplifier to amplify the "raw" cardiac electrical signal passed to an analog-to-digital converter (ADC) 226. The digital signal from the ADC 226 may be passed to a rectifier and amplifier circuit 222, which may include a rectifier, a bandpass filter, and an amplifier for passing the filtered and rectified cardiac electrical signal to a cardiac event detector 224.

[0044] The cardiac event detector 224 may include a sense amplifier or other detection circuitry that compares the input rectified cardiac electrical signal to an R-wave detection threshold, which may be an automatically adjusted threshold. When the input signal crosses the R-wave detection threshold, the cardiac event detector 224 generates an R-wave sensed event signal that is transmitted to the control circuit 206. In other examples, the cardiac event detector 224 may receive the digital output of the ADC 226 for detecting the R-wave by a comparator, morphological signal analysis of the digital EGM signal by a processor, or other R-wave detection techniques. The R-wave sensed event signal transmitted from the R-wave detector 224 to the control circuit 206 may be used to schedule or inhibit ventricular pacing pulses, determine ventricular rate intervals, such as the "RR interval" (RRI) between two consecutive received R-wave sensed event signals, and for identifying the timing of ventricular electrical events by the atrial event detector circuit 240 to facilitate detection of atrial systolic events based on signals received from the motion sensor 212 or the impedance sensing circuit 216.

[0045] In some examples, the cardiac event detector 224 can be configured to sense a P wave from the cardiac electrical signal received by the electrodes 162 and 164. The cardiac event detector 224 can compare the input signal to a P wave sensing threshold and generate a P wave sensed event signal that is transmitted to the control circuit 206 in response to the threshold crossing. When the pacemaker 14 is configured to sense R waves and P waves, the sensing circuit 204 can include two different sensing channels, each sensing channel including a filter, an amplifier, an ADC, a rectifier, and a cardiac event detector, which are configured to amplify and filter the cardiac electrical signal received via one or two different sensing electrode pairs (if available) to sense the R wave and the P wave from the cardiac electrical signal, respectively. P wave sensing can be used to verify an atrial event sensed from a motion sensor signal or an impedance signal, and vice versa. In some examples, the control circuit 206 uses the P wave sensed event signal to start an AV interval to control an atrial synchronized ventricular pacing pulse delivered by the pulse generator 202.

[0046] The motion sensor 212 can be a single axis, one-dimensional sensor or a multi-axis sensor, such as a two-dimensional or three-dimensional sensor, where each axis provides a signal that can be analyzed separately or in combination. The motion sensor 212 generates an electrical signal related to the movement or vibration of the sensor 212 (and the pacemaker 14), for example, when subjected to flowing blood, cardiac motion, and patient body motion due to physical activities such as exercise and daily living activities or other motion imparted to the patient such as riding in a vehicle. An example of an accelerometer for use in an implantable medical device is generally disclosed in U.S. Patent No. 5,885,471 (Ruben et al.), which is incorporated herein by reference in its entirety. Implantable medical device arrangements including piezoelectric accelerometers for detecting patient motion are disclosed, for example, in U.S. Patent No. 4,485,813 (Anderson et al.) and U.S. Patent No. 5,052,388 (Sivula et al.), both of which are hereby incorporated herein by reference in their entirety. Examples of three-dimensional accelerometers that may be implemented in the pacemaker 14 and used to detect atrial systolic mechanical events in the technology disclosed herein are generally described in U.S. Pat. No. 5,593,431 (Sheldon) and U.S. Pat. No. 6,044,297 (Sheldon), both of which are incorporated herein by reference in their entirety. Other accelerometer designs may be used to generate electrical signals that are related to the motion imposed on the pacemaker 14 due to ventricular and atrial events and patient physical activity.

[0047] Each axis of a single-dimensional or multi-dimensional accelerometer may be defined by a piezoelectric element, a microelectromechanical system (MEMS) device, or other sensor element capable of generating an electrical signal in response to a change in acceleration applied to the sensor element, for example, by converting the acceleration into a force or displacement that is converted into an electrical signal. In a multi-dimensional accelerometer, the sensor elements may be arranged orthogonally, with each sensor element axis being orthogonal relative to the other sensor element axes. However, an orthogonal arrangement of the elements of a multi-axis accelerometer is not necessarily required.

[0048] The motion sensor 212 may include filters, amplifiers, rectifiers, analog-to-digital converters (ADCs), and / or other components for generating intraventricular motion signals that are communicated to the control circuit 206. For example, each vector signal corresponding to each individual axis of the multi-axis accelerometer may be filtered by a high pass filter (e.g., a 10 Hz high pass filter) and rectified for use by the atrial event detector circuit 240 in sensing atrial systolic events, for example, as described below in conjunction with Figures 4 to 6 If it is desired to detect atrial event signals with lower frequency content, the high pass filter can be lowered (e.g., to 5 Hz). In some examples, high pass filtering is performed without low pass filtering. In other examples, each accelerometer axis signal is filtered by a low pass filter (e.g., a 30 Hz low pass filter) with or without high pass filtering.

[0049] The motion sensor 212 can be used to sense atrial systolic mechanical events to schedule ventricular pacing pulses delivered by the pulse generator 202 during atrial synchronized ventricular pacing. Additionally or alternatively, the motion sensor 212 can provide a motion signal to the control circuit 206 to determine a patient physical activity measure for providing rate-responsive ventricular pacing that supports the patient's metabolic needs. In the examples described herein, the motion sensor 212 is implemented as an accelerometer. However, the motion sensor 212 is not limited to being an accelerometer, and other motion sensors can be used in the pacemaker 14 to generate an intraventricular motion signal for detecting a cardiac motion signal and / or determining a patient physical activity measure. Examples of motion sensors that can be implemented in the motion sensor 212 include piezoelectric sensors and MEMS devices.

[0050] The motion sensor 212 may include separate filtering of the accelerometer signal for delivering the motion signal to the control circuit 206 for use in detecting a patient physical activity level. For example, a 1 Hz high pass filtering of the raw accelerometer signal may produce a patient physical activity signal with a removed DC component, from which a patient physical activity measure may be determined. The control circuit 206 may be configured to determine a sensor indicated ventricular pacing rate (SIR) based on the patient physical activity measure to control the pulse generator 202 to deliver rate-responsive ventricular pacing (asynchronous with atrial systolic events) at the SIR to meet the patient's metabolic needs during periods of increased physical activity.

[0051] Increased patient body activity signals present in the motion signal generated by motion sensor 212 may reduce the reliability of atrial mechanical event sensing based on the motion signal for controlling ventricular pacing for atrial synchronization. As described below, control circuit 206 can control impedance sensing circuit 216 to generate an intraventricular impedance signal for confirming atrial event sensing based on the motion signal during increased patient body activity or increased heart rate. In other examples, impedance sensing circuit 216 can be enabled by control circuit 206 to generate an impedance signal during increased patient body activity or increased heart rate so that atrial systolic events can be sensed directly from the impedance signal (which can include determining a derivative of the impedance signal), rather than detecting atrial systolic events from the motion signal, until atrial event sensing from the intraventricular motion signal is deemed more reliable.

[0052] The impedance sensing circuit 216 includes a drive signal source for injecting an impedance drive signal via electrodes 162 and 164 (or electrode 168 in combination with electrodes 162 and 164). The drive signal source can be a sinusoidal current (or voltage) source, and the resulting impedance signal can be a voltage (or current) signal generated on the recording electrode pair. The resulting signal can be used directly as an impedance signal, or converted to an actual impedance signal using the resulting signal generated on the recording electrode pair and a known drive signal. The drive signal can have a frequency between about 0.1 Hz and about 1 MHz, for example, between 4 Hz and 100 KHz, and is delivered at an amplitude lower than that required to capture the heart to avoid inadvertent pacing or depolarization of the myocardium.

[0053] In one example, the raw impedance signal is received using electrodes 168 and electrodes 162, both of which are positioned along the peripheral sidewall 105 of the pacemaker 14. The impedance sensing circuit 216 further includes one or more filters, amplifiers, and ADCs for generating an intraventricular impedance signal from the resulting raw signal generated on a recording electrode pair selected from electrodes 162, 164, and 168. The intraventricular impedance signal can be a total impedance signal, a real impedance signal, or an imaginary impedance signal. The impedance sensing circuit 216 can include one or more differentiators, such as operational amplifier differentiator circuits, for generating first and / or second order derivatives of the impedance signal.

[0054] The impedance sensing circuit 216 may include a comparator or other threshold detector for comparing the intraventricular impedance signal to a threshold value for detecting or confirming an atrial systolic event. In other examples, the impedance sensing circuit 216 generates a digital impedance signal that may be transmitted to the control circuit 206 for detecting a cardiac event. Figure 6 The flowcharts presented herein describe atrial event detection based on intraventricular impedance signals.

[0055] The control circuit 206 includes an atrial event detector circuit 240, a pacing timing circuit 242, and a processor 244. The atrial event detector circuit 240 is configured to detect an atrial mechanical event based on an intraventricular motion signal received from the motion sensor 212 and / or an intraventricular impedance signal received from the impedance sensing circuit 216. The control circuit 206 can receive an R-wave sensed event signal, a P-wave sensed event signal, and / or a digital cardiac electrical signal from the sensing circuit 204 for detecting and confirming cardiac events and controlling ventricular pacing. For example, the R-wave sensed event signal can be transmitted to the pacing timing circuit 242 for suppressing scheduled ventricular pacing pulses during atrial synchronized ventricular pacing, or for scheduling ventricular pacing pulses when the pacemaker 14 is operating in a non-atrial tracking (asynchronous) ventricular pacing mode. The asynchronous ventricular pacing mode is an operating mode of the pacemaker 14 during which the control circuit 206 controls the pulse generator 202 to deliver ventricular pacing pulses according to a ventricular pacing rate (e.g., a basal or minimum lower pacing rate or a temporary lower rate). The temporary lower rate can be a pacing rate greater than the basal pacing rate and, in some instances, is set according to a measure of patient physical activity determined from a motion signal generated by the motion sensor 212. Examples of asynchronous ventricular pacing modes include VVI(R) and VDI(R) pacing modes. The atrial-synchronized ventricular pacing mode is an operating mode of the pacemaker 14 during which the control circuit 206 senses atrial events, sets an AV pacing interval in response to each sensed atrial event, and delivers a ventricular pacing pulse at the end of the AV pacing interval so that the ventricular pacing pulse is synchronized with the sensed atrial event through the AV pacing interval. The atrial-synchronized ventricular pacing mode is sometimes referred to as the VDI pacing mode.

[0056] The R-wave sensed event signal may be communicated to the atrial event detector circuit 240 for setting an atrial blanking period and / or time window used by the control circuit 206 in sensing an atrial systolic event from the motion sensor signal and / or impedance signal. In some instances, the atrial event detector circuit 240 receives a motion signal from the motion sensor 212 and may initiate an atrial blanking period in response to a ventricular electrical event (e.g., an R-wave sensed event signal from the sensing circuit 204 or a pacing pulse delivered by the pulse generator 202). The blanking period may correspond to a time period following a ventricular electrical event during which a ventricular mechanical event corresponding to ventricular contraction, valve closure, and isovolumetric relaxation is expected to occur. Motion signal peaks occurring during the atrial blanking period are not sensed as atrial events to minimize the possibility of erroneously sensing a ventricular event signal as an atrial systolic event.

[0057] Atrial event detector circuit 240 can set time windows corresponding to the passive ventricular filling phase and the active ventricular filling phase of the cardiac cycle based on the timing of previous ventricular electrical events (R-wave sensed event signals or ventricular pacing pulses). The earliest crossing of the atrial event sensing threshold by the motion sensor signal during these windows can be detected as an atrial systolic event. As described below, two different atrial event sensing threshold amplitude values ​​can be established for application to the motion signal during the passive filling phase window and after the passive filling phase window (during the active filling phase window).

[0058] In other examples, the impedance sensing circuit 216 transmits the intraventricular impedance signal to the atrial event detector circuit 240. The atrial event detector circuit 240 can detect the timing of the atrial mechanical contraction period from the impedance signal waveform and generate an atrial event detection signal in response to detecting the mechanical atrial contraction period event. Figure 6 As described, the impedance sensing circuit 240 can generate a first order derivative signal and / or a second order derivative signal of the received impedance signal. The atrial event detector circuit 240 can detect the timing of the mechanical atrial contraction period from the first order or second order derivative signal. Atrial events can be sensed directly from the impedance signal (or its derivative), or the impedance signal (or its derivative) can be used to set a passive ventricular filling phase window and / or an active ventricular filling phase window applied to the motion signal from the motion sensor 212 to sense atrial contraction events from the motion signal.

[0059] In response to detecting an atrial systolic event, the atrial event detector circuit 240 communicates an atrial event detection signal to the processor 244 and / or the pacing timing circuit 242. The processor 244 may include one or more clocks for generating a clock signal that the pacing timing circuit 242 uses to time out an AV pacing interval that begins when the atrial event detection signal is received from the atrial event detector circuit 240. The pacing timing circuit 242 may include one or more pacing escape interval timers or counters for timeout pacing intervals, which may be programmable and stored in the memory 210 and retrieved by the processor 244. Other examples of atrial event sensing for controlling atrial synchronized ventricular pacing by an intracardiac ventricular pacemaker are generally disclosed in U.S. Pat. No. 9,399,140 (Cho et al.) and U.S. Publication No. 2018 / 0161580 (Demmer et al.), both of which are incorporated herein by reference in their entirety.

[0060] The pacing timing circuit 242 (or processor 244) may additionally receive an R-wave sensed event signal from the R-wave detector 224 for controlling the timing of pacing pulses delivered by the pulse generator 202. The pacing timing circuit 242 may include a lower pacing rate interval timer for controlling a lower ventricular pacing rate. For example, if no atrial systolic event is detected before the lower pacing rate interval expires, a ventricular pacing pulse may be delivered by the pulse generator 202 at the expiration of the lower pacing rate interval to prevent ventricular asystole and maintain a minimum ventricular rate. To avoid sudden changes in the ventricular rate, the control circuit 206 may be configured to set the ventricular pacing rate interval to a rate smoothing interval. The rate smoothing interval may be determined based on one or more previous ventricular event intervals. For example, a ventricular pacing pulse delivered without sensing an atrial event may be delivered at an interval set based on a previous ventricular rate interval, such as an average or median Vpace to Vpace interval or an average or median RR interval. For example, the rate smoothing interval may be set to be 100 to 150 ms greater than the actual ventricular rate interval determined from delivered ventricular pacing pulses and / or sensed R-waves.

[0061] The control circuit 206 can control the pulse generator 202 to generate and deliver ventricular pacing pulses according to various pacing modes, and control switching between pacing modes. For example, the control circuit 206 can control the pulse generator 202 to deliver atrial-synchronous ventricular pacing pulses by, for example, sensing atrial systolic events from a motion signal or an impedance signal and setting the AV pacing interval. At other times, the control circuit 206 can control the pulse generator 202 to deliver ventricular pacing pulses in a non-atrial tracking or asynchronous ventricular pacing mode (e.g., a VVI or VDI pacing mode). During periods of increased patient activity, the control circuit 206 can control the pulse generator 202 to deliver ventricular pacing pulses in a rate-responsive, asynchronous ventricular pacing mode (e.g., a VVIR or VDIR pacing mode).

[0062] The control circuit 206 can be configured to determine when to switch between asynchronous, synchronous and rate-responsive pacing modes. For example, the pacing mode switching criteria can be based on the rate of sensed atrial events, a measure of patient physical activity determined from a motion signal, an actual ventricular rate, or other criteria related to the patient's need for pacing and / or the reliability of atrial event sensing for delivering synchronized ventricular pacing. Examples of techniques for controlling pacing mode switching are given in the above-incorporated U.S. Patent No. 9,399,140 (Cho et al.) and U.S. Publication No. 2018 / 0154154 (Sheldon et al.), both of which are incorporated herein by reference in their entirety. Typically, when atrial sensing is considered unreliable or when a higher ventricular pacing rate is required to support the patient's physical activity, the pacing mode can be switched from an atrial synchronized pacing mode. When atrial event sensing is confirmed or when the patient's physical activity is reduced so that ventricular rate support is no longer required, the pacing mode can be switched back from asynchronous pacing to an atrial synchronized pacing mode.

[0063] The control circuit 206 can determine a patient activity measure based on the motion signal received from the motion sensor 212 at a desired frequency (e.g., every second, every 2 seconds, etc.) for determining a sensor indicated pacing rate (SIR). In various examples, the activity measure can be determined as an amplitude threshold crossing count of the motion signal or a sum or integral of the sample point amplitudes of the motion signal. The SIR can vary between a programmed minimum basal rate during rest (activity measure less than or equal to a minimum resting activity threshold level) and a maximum upper pacing rate during maximum exertion (activity measure equal to or greater than a maximum activity threshold level). The SIR can be determined based on a SIR transfer function that defines a relationship between the patient's activity level and a target heart rate, which target heart rate can include different rates of change of the SIR within different ranges of the activity measure. Examples of methods for determining the SIR from an intraventricular motion signal are generally disclosed in U.S. Pat. No. 9,724,518 (Sheldon et al.), which is incorporated herein by reference in its entirety. Any type of patient physical activity sensor that produces a signal related to metabolic demand can be used to control rate-responsive ventricular pacing during an asynchronous pacing mode.

[0064] The processor 244 can retrieve programmable pacing control parameters, such as pacing pulse amplitude and pacing pulse width, from the memory 210, which are passed to the pulse generator 202 to control pacing pulse delivery. In addition to providing control signals to the pacing timing circuit 242 and the pulse generator 202 to control pacing pulse delivery, the processor 244 can also provide sensing control signals to the cardiac electrical signal sensing circuit 204, the impedance sensing circuit 216, the motion sensor 212, and the atrial event detector circuit 240 to sense cardiac events, including sensing atrial events from the motion sensor signal and / or the impedance signal as described below. The control signal can control the sensing threshold amplitude, sensing window, blanking period, refractory period, etc. The memory 210 can include computer readable instructions that, when executed by the processor 244, cause the control circuit 206 to perform various functions attributed to the pacemaker 14 in the present disclosure. The computer readable instructions can be encoded within the memory 210. Memory 210 may include any non-transitory computer-readable storage medium, including any volatile, non-volatile, magnetic, optical, or electrical media, such as random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, or other digital media.

[0065] The power supply 214 is enclosed in Figure 2 The power source 214 may be provided in the battery subassembly 160 shown, and may provide power to each of the other circuits and components of the pacemaker 14 as needed. The power source 214 may include one or more energy storage devices, such as one or more rechargeable or non-rechargeable batteries. For clarity, the connections between the power source 214 and the other pacemaker circuits and components are not shown. Figure 3 However, it should be Figure 3 214 can provide power to the charging circuit 230 for charging the holding capacitor to the pacing voltage amplitude as needed, and provide current to the switch 232 and other circuit systems included in the pulse generator 202 to generate and deliver pacing pulses. The impedance sensing circuit 216 receives power from the power supply 214 for generating a drive signal, and for converting the resulting raw impedance signal into a digital intraventricular impedance waveform and / or a digital derivative signal when impedance signal sensing is enabled. The power supply 214 also provides power to the telemetry circuit 208, the motion sensor 212, the cardiac electrical signal sensing circuit 204, and the memory 210 as needed.

[0066] Telemetry circuit 208 includes transceiver 209 and antenna 211 for transmitting and receiving data, for example, via a radio frequency (RF) communication link. Telemetry circuit 208 is capable of communicating with external device 20 ( Figure 1) bidirectional communication. Motion signals, impedance signals, cardiac electrical signals, and / or data derived therefrom may be transmitted by telemetry circuitry 208 to external device 20. Programmable control parameters and programming commands for performing atrial event detection and ventricular pacing control according to the techniques disclosed herein may be received by telemetry circuitry 208 and stored in memory 210 for access by control circuitry 206.

[0067] The functionality attributed to the pacemaker 14 herein may be embodied as one or more processors, controllers, hardware, firmware, software, or any combination thereof. Depicting different features as specific circuit systems is intended to highlight different functional aspects and does not necessarily imply that such functionality must be implemented by separate hardware, firmware, or software components or any particular circuit architecture. Rather, the functionality associated with one or more circuits described herein may be performed by separate hardware, firmware, or software components, or integrated within general hardware, firmware, or software components. For example, atrial systolic event detection from motion sensor signals and / or impedance signals and ventricular pacing control operations performed by the pacemaker 14 may be implemented in a control circuit 206 that executes instructions stored in a memory 210 and relies on inputs from a sensing circuit 204 and a motion sensor 212.

[0068] As disclosed herein, the operation of the circuitry included in the pacemaker 14 should not be construed as reflecting a specific form of hardware, firmware, and software necessary to practice the described techniques. It is believed that the specific form of the software, hardware, and / or firmware will be determined primarily by the specific system architecture employed in the pacemaker 14, as well as by the specific sensing and therapy delivery circuitry employed in the pacemaker 14. Given the disclosure herein, it is within the ability of those skilled in the art to provide software, hardware, and / or firmware to accomplish the described functions in the context of any modern pacemaker.

[0069] Figure 4is an example of a motion sensor signal 250 that may be generated by the motion sensor 212 during a cardiac cycle. The vertical dashed lines 252 and 262 represent the timing of two consecutive ventricular events (intrinsic ventricular depolarization or ventricular pacing), marking the beginning and end of the ventricular cycle 251, respectively. The motion signals include: A1 event 254, A2 event 256, A3 event 258, and A4 event 260. The A1 event 254 is an acceleration signal that occurs during ventricular contraction and marks the approximate onset of the mechanical contraction period of the ventricles (in this example, when the motion sensor 212 includes an accelerometer). The A1 event is also referred to herein as a "ventricular contraction event." The A2 event 256 is an acceleration signal that may occur during the closure of the aortic and pulmonary valves, and marks the approximate offset or end of the mechanical contraction period of the ventricles. The A2 event can also mark the beginning of ventricular diastole, and is typically an indication of the isovolumetric relaxation phase of the ventricles that occurs with the closure of the aortic and pulmonary valves. A3 events 258 are acceleration signals that occur during passive ventricular filling and mark ventricular mechanical relaxation. A3 events are also referred to herein as "ventricular passive filling events."

[0070] The A4 event 260 is an acceleration signal that occurs during atrial contraction and active ventricular filling, and marks the atrial mechanical contraction period. The A4 event 260 may also be referred to herein as an "atrial contraction event" or simply an "atrial event", and is an atrial contraction event detected by the atrial event detector circuit 240 from the motion sensor signal 250. The A4 event 260 may be sensed during an atrial synchronized ventricular pacing mode, for example, to control the pacing timing circuit 242 to trigger ventricular pacing pulse delivery by starting an AV pacing interval in response to detecting the A4 event 260. In some instances, the control circuit 206 may be configured to detect one or more of the A1, A2, and A3 events from the motion sensor signal 250 for at least some ventricular heart cycles, for positively detecting the A4 event 260 and setting the atrial event detection control parameters. The A1, A2, and / or A3 events may be detected and characterized to avoid false detection of the A4 event and to facilitate reliable A4 event detection to achieve correct timing of the atrial synchronized ventricular pacing pulse.

[0071] Figure 5 Depicted are exemplary motion sensor signals 400 and 410 acquired over two different cardiac cycles. At time 0.0 seconds of both cardiac cycles, a ventricular pacing pulse is delivered. The top sensor signal 400 is received over one cardiac cycle, and the bottom sensor signal 401 is received over a different cardiac cycle. The two signals 400 and 410 are aligned in time at time 0.0 seconds of the ventricular pacing pulse delivery. Although Figure 4The motion signals 400 and 410 and the motion signal 250 are shown as raw accelerometer signals, but it should be recognized that the motion sensor 212 can produce filtered, amplified and rectified signals, which are passed to the control circuit 206 for detecting atrial events by the atrial event detector circuit 240.

[0072] It is observed that the A1 events 402 and 412 of the respective motion sensor signals 400 and 410, which occur during ventricular contraction, are well aligned in time at time 0.0 seconds after the ventricular pacing pulse. Similarly, the A2 events 404 and 414 and the A3 events 406 and 416 (occurring during passive ventricular filling) are well aligned in time. Since the A1, A2, and A3 events are ventricular events that occur during ventricular contraction, ventricular isovolumetric relaxation, and passive ventricular filling, respectively, these events are expected to occur at relatively consistent intervals after a ventricular electrical event, in this example, a ventricular pacing pulse, and relative to each other. The temporal relationship of the A1, A2, and A3 events may be different after a ventricular pacing pulse than after a sensed intrinsic R-wave; however, during stable pacing or intrinsic ventricular rhythm, the relative timing of the A1, A2, and A3 events to each other and the immediately preceding ventricular electrical event is expected to be consistent.

[0073] The A4 events 408 and 418 of the first motion sensor signal 400 and the second motion sensor signal 410, respectively, are not aligned in time. The A4 event occurs due to atrial contraction, and therefore, the time interval between the immediately preceding ventricular electrical event (a sensed R-wave or a ventricular pacing pulse) and the A4 event following the previous A1 to A3 events may vary between cardiac cycles as the atrial rate changes.

[0074] The consistency of the timing of the A1 to A3 events relative to each other and the immediately preceding ventricular electrical event can be used to determine an atrial blanking period 436 and increase confidence in the reliable detection of A4 events 408 and 418. No atrial systolic events are detected during the atrial blanking period 436, which can, for example, extend from a ventricular electrical event (at time 0.0) to the estimated onset of ventricular diastole. An A3 sensing window 424 can be set with a start time 420 and an end time 422 corresponding to the end of the atrial blanking period 436. As an example, the atrial blanking interval 436 can be 600 ms, and the A3 window 424 can extend 200 ms after the atrial blanking interval 436.

[0075] The A4 events 408 and 418 may be detected based on a multi-level A4 detection threshold 444. As shown by the lower motion sensor signal 410, the A4 event 418 may occur earlier after the A3 window 424 due to a change in atrial rate. In some cases, the A4 event 418 may occur within the A3 window 424 when the atrial rate increases. When this occurs, the A3 event 416 and the A4 event 418 may fuse as passive and active ventricular filling occur together. The fused A3 / A4 event may have a high amplitude, even greater than the amplitude of the A3 event 416 or the A4 event 418 when they occur separately. Thus, in some instances, the A4 detection threshold 444 includes a first higher A4 threshold amplitude 446, which is established to detect an early A4 event that fuses with an A3 event during the A3 window 424. A second, lower A4 threshold amplitude 448 may be established for detecting relatively late A4 events after the end time 422 of the A3 window 424. The A4 window 445 may extend from the end of the A3 window 424 until either an atrial event or a ventricular event is sensed to occur, whichever occurs first. The earliest crossing of the A4 detection threshold 444 by the motion sensor signal after the start time 420 of the A3 window (or after the expiration of the atrial blanking period 436) may be sensed as an atrial systolic event. Various examples of intracardiac pacemakers configured to detect atrial systolic events from motion sensor signals for delivering atrial synchronized ventricular pacing are disclosed in commonly assigned U.S. Publication Nos. 2018 / 0085589 (Splett et al.), 2018 / 0085588 (Sheldon et al.), 2018 / 0117337 (Demmer et al.), 2018 / 0154154 (Sheldon et al.), and 2018 / 0161580 (Demmer et al.), all of which are incorporated herein by reference in their entirety. The techniques disclosed herein for using intraventricular impedance signals in atrial event sensing may be implemented in combination with any of the examples presented in the aforementioned incorporated references.

[0076] Figure 6Depicted are a motion signal 500 that may be generated by the motion sensor 212, an impedance signal 510 that may be generated by the impedance sensing circuit 216, a ventricular electrogram (EGM) signal 540 that may be generated by the cardiac electrical signal sensing circuit 204, and an electrocardiogram (ECG) signal 550. A ventricular pacing pulse marker 542 is shown along the EGM signal 540, followed by an induced R-wave signal 544. A first-order derivative signal 520 and a second-order derivative signal 530 may be generated from the impedance signal 510 by the impedance sensing circuit 216 and communicated to the control circuit 206 for atrial event detection. The relative timing of features of the intraventricular impedance signal 510, shown as the total impedance signal, the motion signal 500, the EGM 540, and the ECG 550, depicts the techniques disclosed herein for detecting atrial systolic events from intraventricular signals using the impedance signal 510. Detecting an atrial systolic event using the impedance signal 510 may include detecting an atrial systolic event directly from the impedance signal 510 (which may include determining a first-order derivative signal 520 and / or a second-order derivative signal 530), confirming an atrial systolic event sensed from the motion signal 500 using the impedance signal 510, and / or establishing A4 event sensing parameters used by the atrial event detector circuit 240 for sensing an atrial systolic event from the motion signal 500.

[0077] A1, A2, A3 and A4 event signals are shown along motion signal 500. Figure 6 The motion signal 500 and other signals depicted in FIG. 5 are shown as non-rectified signals, but it should be appreciated that any of the signals may be rectified and passed to the control circuit 206 for cardiac event detection. The control circuit 206 may initiate an atrial blanking period 436 in response to the ventricular pacing pulse 542 being delivered. No atrial events are sensed during the atrial blanking period 436 to avoid oversensing of ventricular events (e.g., A1 and A2 signals) as atrial events. When an atrial event is sensed from the motion signal 500, the control circuit 206 may set an A3 window 424 having an end time 422. As described above in conjunction with Figure 5 As described, a higher A4 sensing threshold amplitude may be applied during the A3 window 424, and a lower A4 sensing threshold amplitude may be applied after the A3 window end time 422 until an A4 event is sensed (or the next ventricular electrical event occurs).

[0078] In some examples, atrial event detector circuit 240 may receive impedance signal 510, impedance first-order derivative signal 520, and / or second-order derivative signal 530 from impedance sensing circuit 216 for detecting atrial mechanical systolic events. Figure 6As shown, the A4 event of the motion signal 500 accompanying the active ventricular filling phase or "atrial kick" corresponds in time to the minimum peak 524 of the impedance first-order derivative signal 520. Therefore, in one example, the atrial event detector circuit 240 can detect an atrial mechanical systolic event by detecting the minimum negative peak 524 of the first-order derivative signal 520 (or the maximum negative slope of the impedance signal 510). The control circuit 206 can be configured to detect an atrial systolic mechanical event by detecting one or more features of the impedance signal 510, the first-order derivative signal 520, or the second-order derivative signal 530 to trigger a ventricular pacing pulse 542 in an atrial synchronized ventricular pacing mode.

[0079] In some examples, an atrial event sensing window 508 can be established by generating an impedance signal 510 and detecting one or more features of the impedance signal 510 (or its derivative) that are temporally associated with ventricular diastole and atrial systole. In one example, a start time of the atrial event sensing window 508 can be established by generating an impedance signal 510 and detecting a maximum peak 514. The start time can be set at the maximum peak 514 or at an offset earlier or later than the maximum peak 514. As examples, the end time of the window 508 can be based on a fixed time interval, such as identifying a subsequent minimum peak 512, identifying a maximum peak 526 of the first-order derivative signal 520, or identifying a maximum peak 536 of the second-order derivative signal 530.

[0080] The window 508 may be established based on the impedance signal 510 during a setup process in which the impedance signal 510 is generated throughout the cardiac cycle or after the blanking period 436. For example, the start and end times of the window 508 may be determined based on the impedance signal 510 (or its derivative) associated with a ventricular electrical event (e.g., a pacing pulse 542 or an R-wave 544). After the window 508 is established (or updated), an impedance signal for sensing atrial events may be generated on a beat-to-beat basis only during the atrial sensing window 508. In some examples, the start time of the window 508 is determined so that the atrial event detection circuit 240 begins searching for the impedance signal feature at the start time of the window 508, but the end time may be indeterminate. The atrial event detection circuit 240 can search for the inflection point 516 or maximum peak 518 of the impedance signal 510, the maximum peak 522 (corresponding to the positive slope 515 after the inflection point 516), the minimum peak 524 of the first-order derivative signal 520, the minimum peak 538 of the second-order derivative signal 530, or other selected features or combinations of features of the impedance signal 510, the first-order derivative signal 520 and / or the second-order derivative signal 530 during the atrial event sensing window 508 for detecting atrial events.

[0081] It should be appreciated that, depending on the orientation of the recording electrodes used to receive the raw impedance signal and / or the implant orientation of the pacemaker 14, the peaks and valleys of the raw impedance signal may vary with the Figure 6 The intraventricular impedance signal shown is opposite. In some examples, the intraventricular impedance signal generated by the impedance sensing circuit 216 can be a rectified or inverted signal. Atrial events can be sensed from the impedance signal 510 (or its derivative) on a beat-to-beat basis for triggering an atrial-synchronized ventricular pacing pulse delivered at the AV interval set cutoff in response to sensing an atrial event from the impedance signal.

[0082] The triggered ventricular pacing pulse can be scheduled at the AV interval after an identified feature of the impedance signal 510, the first-order derivative signal 520, or the second-order derivative signal 530 that promotes completion of active ventricular filling prior to ventricular contraction induced by the ventricular pacing pulse. For example, when the minimum peak 524 of the first-order derivative signal 520 is detected as an atrial event, the ventricular pacing pulse 542 can be triggered to occur at the end of a relatively short AV pacing interval (e.g., 10 ms). When an earlier feature of the impedance signal 510 or its derivative is identified, such as the inflection point 516 of the impedance signal 510, the maximum peak 522 of the first-order derivative signal 520, or the maximum peak 534 of the second-order derivative signal 530 is detected as an indication of the timing of an atrial systolic event, the AV pacing interval can be set to a longer interval, such as 50 to 200 ms, to provide ventricular pacing with optimized atrial synchronization.

[0083] In other examples, detecting an atrial event using the intraventricular impedance signal includes verifying A4 event sensing from the motion signal 500. Detection of one or more features from the impedance signal 510, the first order derivative signal 520, or the second order derivative signal 530 may be used to verify A4 event sensing from the motion signal 500. A P wave 552 (of the ECG signal 550) accompanying atrial electrical depolarization is observed to correspond in time to a maximum positive peak 522 of the first order derivative signal 520. Detection of the maximum peak 522 after the inflection point 516 or the inflection point 516 (both of which precede the A4 event of the motion signal 500) may be performed by the atrial event detector circuit 240 to confirm a subsequently detected A4 event from the motion signal 500. If an A4 event is not sensed within an expected time interval of an identified feature of the impedance signal 510, the first order derivative signal 520, or the second order derivative signal 530, then the A4 event sensing is not confirmed or may be considered unreliable.

[0084] In some cases, the motion signal 500 can be used by the pacemaker 14 to sense an atrial event during an atrial synchronized ventricular pacing mode. On a periodic basis, or if undersensing or oversensing of an A4 event is suspected, the control circuit 206 can control the impedance sensing circuit 216 to generate an impedance signal 510, a first-order derivative signal 520, and / or a second-order derivative signal 530 for use by the atrial event detector circuit 240 to verify the relative timing of the characteristics of the impedance signal relative to the A4 sensed event. For example, if an A4 event is sensed within a threshold time range of a minimum peak 524 of the first-order derivative signal 520, the control circuit 206 can confirm A4 event sensing. The threshold time range can be a predetermined value, such as within 20 ms before or after the minimum peak 524. In other examples, the threshold time range can be established based on the impedance signal 510 or the second-order derivative signal 530. For example, it may be desirable to sense an A4 event within a time interval extending from a first maximum peak 534 of the second-order derivative signal 530 to a second maximum peak 536.

[0085] If an A4 event is sensed outside of a threshold time range of a characteristic of the impedance signal 510 (which may be determined from the first or second order derivative signal 520 or 530), the event sensed as an A4 event may be a ventricular A3 or A1 event or other non-cardiac motion signal due to patient activity or other motion signal noise. The sensed event is not confirmed as an A4 event. Parameters for controlling A4 event sensing, such as the A3 window 424 and the A4 sensing threshold 444 (in Figure 5 ), may be adjusted by the control circuit 206 and / or other corrective actions may be taken, such as switching to an asynchronous ventricular pacing mode or remaining in an atrially synchronized ventricular pacing mode, but allowing atrial events to be sensed directly from the intraventricular impedance signal until A4 sensing can be confirmed.

[0086] In other examples, the intraventricular impedance signal 510 is used in detecting atrial systolic events by identifying one or more features of the impedance signal 510 (or its derivative) during the process of establishing the A4 sensing control parameters. For example, the end time 422 of the A3 window 424 can be set based on a feature of the impedance signal 510, such as the maximum peak 514 of the impedance signal 510 or the time of the earliest minimum peak 532 of the second-order derivative signal 530 that occurs after the atrial blanking period 436. During the initial setup process or when A4 sensing is not confirmed, the control circuit 206 can update the A3 window end time 422 based on the features identified from the impedance signal 510. In other examples, during the initial setup process or when atrial event sensing based on the motion signal is not confirmed, the A4 sensing threshold amplitude 446 ( Figure 5 ) and the second lower sensing threshold amplitude 448 after the A3 window 424 ( Figure 5 ) may be updated or adjusted until A4 event sensing is confirmed based on the relative timing of the associated features of the impedance signal 510. Adjustment of the A4 sensing threshold amplitude may restore A4 event sensing within a threshold time interval or range of the identified features of the impedance signal 510, thereby confirming A4 event sensing.

[0087] Figure 7 Depicted is an amplitude waveform 560 and a phase waveform 590 of an intraventricular impedance signal that may be generated by the impedance sensing circuit 216. Also shown are corresponding ventricular electrogram signals 570 and ECG signals 580 to indicate the relative timing of an R wave 572 that may be sensed by the cardiac electrical signal sensing circuit 204 and a P wave 582 that may be observed on the ECG signal 580. As may be seen in FIG. Figure 7 582, the features of the impedance phase waveform 590 correspond in time to similar features of the impedance magnitude waveform 560. For example, both the inflection point 562 of the magnitude waveform and the inflection point 592 of the phase waveform occur just before the P-wave 582. The P-wave 582 is immediately followed by the local maximum peak 564 of the magnitude waveform 560 and the local maximum peak 594 of the phase angle waveform 590.

[0088] Thus, the characteristics of the phase waveform 590 of the complex impedance signal generated by the sinusoidal drive signal can be used as the characteristics of the amplitude waveform 560 in atrial event sensing and / or in combination with the above Figure 6 As an alternative or in any combination with the total impedance signal characteristics described herein. As an example, the inflection point 592, the local maximum peak 594, the peak negative slope 596, or the minimum 598 of the complex impedance phase waveform, or any combination thereof, can be detected by the control circuit 206 for atrial event sensing according to any of the methods disclosed herein. In this way, the "intraventricular impedance signal" generated by the impedance sensing circuit 216 and used for atrial systolic event sensing can be the amplitude and / or phase of the total impedance signal.

[0089] Figure 8 6 is a flow chart of one method of ventricular pacing that may be performed by the pacemaker 14. At block 602, the control circuit 206 is programmed to operate in an atrial synchronized ventricular pacing mode. The control circuit 206 enables the impedance sensing circuit 216 to generate an impedance signal that is communicated to the atrial event detector circuit 240 for sensing an atrial event. At block 604, the impedance signal 510, the first derivative signal 520, or the second derivative signal 530 (all in FIG. 1 ) is detected by detecting one or more features of a corresponding signal corresponding in time to an A4 event of the motion signal 500, using the impedance signal 510, the first derivative signal 520, or the second derivative signal 530 (all in FIG. 1 ). Figure 6In one example, the control circuit 206 detects a reduced impedance signal indicative of ventricular filling. In response to detecting the reduced impedance signal, for example, following the maximum peak 514 ( Figure 6 ), the control circuit 206 searches for a rising or maximum positive peak of the first or second order derivative signal 520 or 530 or a minimum peak 524 or 538 of the first or second order derivative signal 520 or 530, respectively. The maximum or minimum peak of the first or second order derivative signal can be detected as an atrial systolic event, which corresponds in time to the motion signal and the A4 event signal of the atrial mechanical contraction.

[0090] In some examples, at block 604, sensing an atrial event may include sensing an atrial event within an atrial event sensing window (eg, Figure 6 By enabling impedance sensing circuit 216 to generate an impedance drive signal during atrial event sensing window 508, power required to generate an intraventricular impedance signal may be conserved compared to generating an impedance signal throughout the cardiac cycle. Atrial event detector circuit 240 may search for impedance signal 510, first order derivative signal 520, or second order derivative signal 530 ( Figure 6 ) for sensing an atrial event from an impedance signal generated by the impedance sensing circuit 216 during the atrial event sensing window 508.

[0091] At box 606, the pacing timing circuit 242 begins an AV pacing interval in response to the atrial event detector circuit 240 detecting an atrial systolic event from the impedance signal. The AV interval can be set to an appropriate interval that facilitates synchronization of ventricular pacing pulse delivery with the sensed atrial event so that the onset of ventricular contraction is synchronized with the end of the A4 or atrial beat event without interfering with ventricular filling. As an example, the AV pacing interval can be set to 10 ms to 200 ms, depending on the timing of the A4 event relative to the detected impedance signal characteristics of the motion signal. At the end of the AV interval, at box 608, the pulse generator 202 is configured to deliver a ventricular pacing pulse. Although at Figure 8 6. It is not explicitly shown in the diagram, but it is understood that if an intrinsic R-wave is sensed by the cardiac electrical signal sensing circuit 204 during the AV interval, the scheduled ventricular pacing pulse may be retained. During the atrial synchronized ventricular pacing mode, the ventricular pacing pulse is triggered by a sensed atrial event and suppressed by a sensed R-wave. At block 604, the control circuit 206 begins an atrial blanking period in response to the sensed R-wave or delivered ventricular pacing pulse, and waits for the next sensed atrial event.

[0092] Fig. 9700 is a flow chart of a method performed by a pacemaker 14 for establishing an A4 sensing parameter using an impedance signal and for controlling atrial synchronized ventricular pacing according to another example. At box 702, the control circuit 206 enables the impedance sensing circuit 216 to generate an impedance signal. The impedance sensing circuit 216 can be powered by the power supply 214 to generate a drive signal and generate a resulting impedance signal at a time interval controlled by the control circuit 206. For example, the control circuit 206 can control the impedance sensing circuit 216 to generate an impedance signal for one or more continuous or non-continuous ventricular cycles or for one or more continuous or non-continuous predetermined time intervals. For example, the control circuit 206 can enable the impedance sensing circuit 216 to generate an impedance signal for multiple ventricular cycles based on the timing of the R wave sensed event signal received from the cardiac electrical signal sensing circuit 204 or based on the timing of the delivered ventricular pacing pulse.

[0093] During R-wave sensing by sensing circuit 204, when AV conduction is intact, a process for establishing A4 sensing parameters (e.g., as represented by blocks 702 to 708) may be performed. The process may be performed when the heart rate is below a threshold rate and, in some instances, when the heart rate is stable. At other times, when the patient is experiencing AV block and ventricular pacing is required, the process for establishing A4 sensing parameters may be performed. As described above in conjunction with Figure 8 As described above, control circuit 206 may control pulse generator 202 to deliver atrial synchronized ventricular pacing based on sensing atrial mechanical contraction period from the impedance signal.

[0094] The impedance signal generated at block 702 may be a voltage or current signal generated at a pair of recording electrodes selected from electrodes 162, 164, and 168, which is filtered, amplified, and in some instances rectified. The impedance signal generated at block 702 may include determining a derivative of the impedance signal, such as Figure 6 The first and / or second derivative signals are shown.

[0095] At block 704, the control circuit 206 receives the impedance signal generated at block 702, and the processor 244 included in the control circuit 206 may detect one or more atrial systolic timing features from the impedance signal or a derivative thereof. Figure 6, the maximum peak 518 of the impedance signal 510, the maximum peak 522 of the first derivative signal 520, the minimum peak 538 of the second derivative signal 530, or other features of the impedance signal may be detected after a ventricular electrical event or after the maximum peak impedance 514 (corresponding to the end of ventricular systole) as an indication of the approximate onset of atrial systole. If AV conduction is intact, the control circuit 206 may detect atrial systole timing features from the impedance signal after each R-wave sensed event signal during one or more ventricular cycles.

[0096] If the patient is experiencing AV block, the control circuit 206 can control the pulse generator 202 to deliver a ventricular pacing pulse after detecting an atrial systolic event characteristic of the impedance signal or its derivative. In one example, when the A4 sensing parameter is established, a ventricular pacing pulse can be triggered by detecting a minimum peak 512 of the impedance signal 510 (corresponding to the end of ventricular diastole and maximum filling of the ventricle). After delivering each ventricular pacing pulse, the control circuit 206 can search for a maximum peak 514 of the impedance signal 510, a minimum peak 532 of the second-order derivative signal 530, or another characteristic associated with the end of ventricular systole and the onset of atrial systole. An atrial blanking period can be applied after the ventricular pacing pulse so that the impedance signal characteristic can be searched after the ventricular systole.

[0097] At block 706, the control circuit 206 may optionally confirm the sensing of an A4 event from the motion signal during an expected time window relative to one or more impedance signal features determined at block 704. For example, the control circuit 206 may detect the minimum peak 524 of the first-order derivative signal 520. The control circuit 206 may confirm that an A4 event is sensed from the motion signal 500 within an expected time interval of the minimum peak 524 of the first-order derivative signal 520. At block 706, one or more A4 sensing parameters may be set based on a time interval determined from a ventricular electrical event (R-wave sensed event signal or ventricular pacing pulse) to a feature of the impedance signal. The time interval may be an average or median time interval determined over a plurality of ventricular cycles.

[0098] For illustration, the time interval from the ventricular pacing pulse triggered in response to the minimum impedance 512 to the subsequent maximum peak impedance 514 can be determined for each of three to twelve ventricular cycles (or other predetermined number of ventricular cycles). A median time interval representing the time from the beginning of ventricular systole to the end of ventricular systole can be determined. At box 708, the median time interval can be used to establish the A3 window end time 422. The median time interval can be used directly as the A3 window end time 422, or the median plus or minus an offset interval can be set as the A3 window end time. The above combined Figure 6Other exemplary characteristics of the impedance signal that can be used to establish the A3 window are described.

[0099] In an example including confirming an A4 signal relative to one or more features identified from the impedance signal (block 706), a peak amplitude of the confirmed A4 signal may be determined and used to establish an A4 sensing threshold amplitude at block 708. In this manner, the impedance signal generated by the impedance sensing circuit 216 is used by the control circuit 206 to establish atrial event sensing parameters for sensing atrial systolic events based on the motion signal generated by the motion sensor 212. Figure 6 Other examples of using impedance signals to establish A4 event signal sensing parameters are described.

[0100] At block 710, the control circuit 206 uses the motion signal for sensing atrial events (e.g., using A4 event sensing in VDD pacing mode) to enable atrial-synchronized ventricular pacing (if not already enabled). In some cases, the control circuit 206 may already be operating in an atrial-synchronized ventricular pacing mode, but uses the impedance signal to detect atrial mechanical systolic events, e.g., as combined with Figure 8 This may occur if the patient experiences AV block during the process used to establish the A4 sensing parameters.

[0101] If the A4 sensing parameter is established during ventricular sensing, then when AV conduction is intact, the control circuit 206 may operate in an asynchronous ventricular pacing mode (e.g., VVI(R) or VDI(R) mode) in which the basal ventricular pacing rate is set to a relatively low rate (e.g., 40 to 50 pulses per minute or less) to allow AV conduction to occur but avoid ventricular asystole. At block 710, the control circuit 206 may switch from the asynchronous ventricular pacing mode to an atrial synchronized pacing mode in response to detecting AV block. In one example, AV block may be detected based on a predetermined number of ventricular pacing pulses delivered at the basal pacing rate.

[0102] At box 712, control circuit 206 senses an A4 signal from the motion signal received from motion sensor 212 using the A4 sensing parameters established at box 708. In one example, at least an A3 window end time established based on the impedance signal is used during A4 sensing based on the motion signal. An A4 sensing threshold that may include a first higher amplitude during the A3 window and a second lower amplitude after the A3 window end time is applied to the motion signal. The earliest crossing of the A4 sensing threshold by the motion signal is detected as an A4 event. In response to detecting an A4 event at box 712, an AV pacing interval is started at box 714. At the end of the AV interval, at box 716, pulse generator 202 delivers a ventricular pacing pulse.

[0103] The process of flowchart 700 may be repeated to periodically update the A4 sensing parameters. In some instances, if A4 is suspected of being under-sensed or over-sensed, the process may be repeated. Fig. 9 In other examples, each time the control circuit 206 switches to an atrial synchronized ventricular pacing mode (e.g., in response to a user-programmed command or detection of AV block or other switching condition), the A4 sensing parameter may be reestablished. Fig. 9 process to establish or update A4 sensing parameters.

[0104] In some examples, the control circuit 206 can verify the proper timing of A4 sensing and / or ventricular pacing pulses during the atrial synchronized ventricular pacing mode. The verification can be performed beat by beat by beat by enabling the impedance sensing circuit 216 to generate an impedance signal during at least a selected time window during the cardiac cycle, for verifying the A4 event sensed from the motion signal and / or verifying the proper timing of the ventricular pacing pulse relative to the minimum impedance corresponding to the maximum ventricular filling based on the characteristics of the impedance signal. In order to save the power supply 214, the verification of A4 sensing and / or ventricular pacing pulse timing can be performed periodically or triggered in response to a condition that can indicate a change in the reliability of A4 sensing. For example, the control circuit 206 can set a timer when enabling atrial synchronized ventricular pacing based on A4 event sensing at box 710. The control circuit 206 can determine at box 718 that it is time to verify A4 event sensing and / or proper ventricular pacing timing in response to the expiration of the timer. The verification can be performed once a minute, once an hour, once a day, or at other selected frequencies.

[0105] In other instances, conditions that may indicate a change in A4 signal timing, A4 signal amplitude, the presence or timing of other signals present in a motion signal such as a patient's physical activity signal, or other conditions that warrant A4 sensing verification may trigger verification. For example, the control circuit 206 may be configured to detect a change in heart rate (e.g., based on an A4 to A4 interval or a Vpace to Vpace interval), a change in an A3 to A4 interval, or a change in patient physical activity at block 718 to trigger verification at block 720. If a triggering event has not occurred or a predetermined verification time interval has expired, the control circuit 206 returns to block 712 to continue sensing A4 events and controlling atrial synchronized ventricular pacing.

[0106] When the control circuit 206 determines that it is time to verify A4 event sensing and / or ventricular pacing timing (block 718), the control circuit 206 enables the impedance sensing circuit 216 at block 720 to generate an impedance signal, which may be continuous or only during a predetermined time window corresponding to ventricular diastole and atrial systole. Based on the relative timing of the A4 event sensed from the characteristics of the impedance signal, any of the above methods may be used to verify A4 event sensing. In other examples, verification of appropriate ventricular pacing pulse timing may be based on determining that the ventricular pacing pulse occurs within a threshold time of the minimum impedance 512, the corresponding positive peak 526 of the first-order derivative signal 520, or the maximum peak 536 of the second-order derivative signal 530.

[0107] In some instances, the ventricular pacing pulse may be delayed, for example, by temporarily extending the AV interval over one or more cardiac cycles to verify that the ventricular pacing pulse scheduled to occur at the programmed AV interval after the A4 sensed event will occur at or near the minimum peak 524 of the first order derivative signal. If the scheduled ventricular pacing pulse delivery time is found to be earlier or later in the impedance signal 510 based on the A4 sensed event time and the programmed AV interval at block 720, and / or if the A4 event is found to be sensed outside of a threshold range of a reference feature of the impedance signal 510 or its derivative, then proper A4 and / or ventricular pacing timing is not verified at block 720. The control circuit 206 may return to block 702 for reestablishing the A4 sensing parameters. In this manner, the impedance signal may be used intermittently during atrial synchronized ventricular pacing, utilizing A4 sensing based on the motion signal to verify A4 sensing and proper timing of ventricular pacing pulse delivery that does not compromise ventricular filling.

[0108] Fig.10 800 is a flow chart of a method for controlling atrial-synchronized ventricular pacing performed by a pacemaker 14 according to another example. At block 802, the pacemaker 14 operates in an atrial-synchronized ventricular pacing mode. As indicated at block 804, the pacing mode includes sensing A4 events from a motion signal and delivering a ventricular pacing pulse at an AV pacing interval after each sensed A4 event.

[0109] At box 806, the control circuit 206 determines that the pacing mode switching criteria are met. The pacing mode switching criteria can be met by one or more monitored parameters indicating reduced reliability of A4 event sensing, which can include oversensing of A4 events and / or undersensing of A4 events. Examples of techniques for controlling pacing mode switching are given in U.S. Patent No. 9,399,140 (Cho et al.) and U.S. Publication No. 2018 / 0154154 (Sheldon et al.), incorporated above, both of which are incorporated herein by reference in their entirety. As an example, the control circuit 206 can determine that the pacing mode switching criteria are met in response to a sensed atrial rate exceeding a threshold, an actual ventricular rate exceeding a threshold, a threshold number of cardiac cycles without A4 sensed events, a patient activity measure exceeding a threshold, or any combination thereof.

[0110] In other examples, in response to failure to use the above combination Figure 6 Any of the described techniques validates A4 event sensing based on the motion signal based on the impedance signal, and the mode switching criteria are met at box 806. During the atrial synchronized ventricular pacing mode, the control circuit 206 can periodically enable the impedance sensing circuit 216 to generate an impedance signal for validating A4 event sensing based on the timing of the sensed A4 event relative to the characteristic corresponding to the atrial systole determined from the impedance signal. If an A4 event is not sensed from the motion signal within a threshold interval from the characteristic of the impedance signal, then A4 event sensing is not confirmed at box 806 and the mode switching criteria can be met. If A4 event sensing is confirmed, the control circuit 206 continues to sense A4 events and deliver synchronized ventricular pacing pulses (box 804).

[0111] When the pacing mode switching criteria are met, the control circuit 206 switches to the asynchronous ventricular pacing mode at block 808. During the asynchronous ventricular pacing mode, the control circuit 206 controls the pulse generator 202 to deliver ventricular pacing pulses according to a programmed lower ventricular pacing rate or according to a patient activity-based pacing rate, for example, in a rate-responsive pacing mode during which a target heart rate is determined according to a measure of patient activity determined from a motion signal.

[0112] During the asynchronous ventricular pacing mode, A4 event sensing and impedance signal generation may be enabled continuously or intermittently for determining whether A4 sensing is confirmed based on the impedance signal characteristics. For example, at box 810, the control circuit 206 may enable the impedance sensing circuit 216 to generate an impedance signal and compare the relative timing of the sensed A4 event to one or more characteristics of the impedance signal or its derivative. If A4 sensing is confirmed based on the expected timing of the sensed A4 event relative to the impedance signal characteristics, the control circuit 206 may switch back to atrial synchronized ventricular pacing at box 802, wherein the ventricular pacing pulse is synchronized with the sensed A4 event.

[0113] In the illustrated example, the control circuit 206 may not switch back immediately after confirming A4 sensing, but may wait until other pacing mode switching criteria are met at box 812. For example, switching back to the atrial synchronized ventricular pacing mode may require, in addition to confirming A4 sensing, patient physical activity and / or actual ventricular rate being less than a corresponding threshold. In other examples, when A4 sensing is confirmed at box 810 based on analysis of the impedance signal and the sensed A4 event timing, the control circuit 206 may be configured to immediately switch back to the atrial synchronized ventricular pacing mode without waiting for other pacing mode switching criteria to be met. As long as A4 sensing is deemed reliable, ventricular pacing pulses may be synchronized with the sensed A4 event.

[0114] In other examples, the control circuit 206 may initiate the process of confirming A4 sensing at block 810 in response to determining that other mode switching criteria satisfied at block 806 are no longer satisfied during the asynchronous ventricular pacing mode. For example, if an increased heart rate or increased patient physical activity causes the control circuit 206 to switch to asynchronous ventricular pacing, the control circuit 206 may wait for the conditions to reverse, such as a decrease in heart rate and / or a decrease in patient physical activity to below a corresponding threshold rate or level, before checking at block 810 whether to confirm A4 sensing.

[0115] The process of confirming A4 sensing during asynchronous ventricular pacing may require extending the ventricular pacing interval or reserving a ventricular pacing pulse to reduce the possibility that the asynchronous ventricular contraction interferes with the detection of atrial systolic events. When A4 event sensing is confirmed based on the analysis of the impedance signal, the control circuit 206 switches back to the atrial synchronized ventricular pacing mode using A4 event sensing at box 802.

[0116] Fig.11850 is a flow chart of a method for controlling ventricular pacing performed by the pacemaker 14 according to another example. The control circuit 206 operates in an atrial synchronized ventricular pacing mode at box 852 by sensing an A4 event from the motion signal and controlling the pulse generator 202 to deliver a ventricular pacing pulse synchronized with the sensed A4 event as indicated at box 854. In the absence of a sensed A4 event, the ventricular pacing pulse may be delivered at a programmed basal or lower rate VV pacing interval. In some examples, when a rate smoothing interval expires without sensing an A4 event, a ventricular pacing pulse is delivered at a rate smoothing interval. The rate smoothing interval may be determined by the control circuit 206 based on an actual ventricular rate, such as a median RR interval determined from a predetermined number of previous RR intervals (which may include paced and intrinsic ventricular beats).

[0117] At block 856, the control circuit 206 may determine that A4 event sensing is unreliable or may become unreliable. Unreliable A4 event sensing is determined when an A4 event is undersensed (sensed intermittently or not sensed at all) or oversensed (other cardiac or non-cardiac motion signals are erroneously sensed as A4 event signals) for one or more cardiac cycles. Although a single undersensed or oversensed A4 event may not reach a threshold for unreliability, A4 undersensing or oversensing for multiple cardiac cycles may result in unacceptable variations or irregularities in the ventricular rate.

[0118] At box 856, one or more conditions can be monitored to detect or predict unreliable A4 sensing. When a threshold number of ventricular pacing pulses are delivered at a ventricular pacing interval (e.g., a rate smoothing interval) without sensing an A4 event, the control circuit 206 can detect A4 undersensing. The ventricular pacing pulses delivered without an A4 sensed event can be continuous or non-continuous pacing pulses. For example, at box 856, three consecutive ventricular pacing pulses delivered without sensing an A4 event can be detected as unreliable A4 sensing because undersensing may be suspected.

[0119] When the ventricular rate increases above a threshold rate, A4 oversensing may be suspected. Thus, in other examples, unreliable A4 sensing may be suspected or predicted if the patient's physical activity measure exceeds a predetermined threshold, or when the A3 to A4 time interval decreases (indicating an increased atrial rate) or an A4 event is sensed during the A3 window. Various criteria for detecting or predicting an increased likelihood of A4 undersensing or oversensing may be defined for determining unreliable A4 sensing at block 856.

[0120] If it is determined at block 856 that A4 sensing is unreliable, the control circuit 206 enables atrial event sensing from the impedance signal at block 858. The control circuit 206 enables the impedance sensing circuit 216 to generate the impedance signal. The atrial event detector circuit 240 detects the timing of an atrial event based on the impedance signal or its derivative, for example, based on the above combined Figure 6 Any of the examples described. Control circuit 206 continues to operate in the atrial-synchronized ventricular pacing mode by detecting an atrial systolic event from the impedance signal and setting the AV pacing interval in response to detecting the atrial systolic event. The AV pacing interval may be different from the AV pacing interval used during A4 sensing for atrial-synchronized ventricular pacing.

[0121] While continuing atrial-synchronized ventricular pacing based on atrial event sensing from the impedance signal, the control circuit 206 can confirm A4 event sensing based on one or more detected features of the impedance signal (or its derivative) and the relative timing of the sensed A4 event. If A4 event sensing is not confirmed, for example, based on the sensed A4 event being greater than a threshold time interval from the impedance signal feature, atrial-synchronized ventricular pacing with atrial event sensing from the impedance signal can continue until A4 sensing is confirmed. Once confirmed, the control circuit 206 can return to box 854 to disable the impedance sensing circuit 216 to save power and switch back to A4 sensing based on the motion signal for triggering ventricular pacing pulses. In this way, when it is determined that A4 sensing based on the motion signal is unreliable, by switching to the impedance signal for atrial event sensing, the pacemaker 14 can remain in an atrial-synchronized ventricular pacing mode even during periods when A4 sensing may be unreliable.

[0122] Embodiment 1: In one example, a method performed by a ventricular pacemaker in the heart includes: generating an intraventricular impedance signal by an impedance sensing circuit; detecting an atrial systolic event by a control circuit of the pacemaker using the intraventricular impedance signal; setting an atrioventricular pacing interval by the control circuit in response to detecting the atrial systolic event; and delivering a ventricular pacing pulse by a pulse generator of the pacemaker when the atrioventricular pacing interval expires.

[0123] Embodiment 2: The method according to embodiment 1, wherein detecting an atrial contraction event using an intraventricular impedance signal comprises: determining a derivative signal of the impedance signal; and detecting a feature of the derivative signal corresponding to a mechanical contraction period of the atrial contraction.

[0124] Embodiment 3: The method according to embodiment 1 further comprises generating a motion signal by a motion sensor of a pacemaker, wherein the motion signal comprises an atrial systolic event signal; wherein detecting an atrial systolic event using an intraventricular impedance signal comprises: detecting at least one feature of the intraventricular impedance signal; setting a time window based on the feature of the intraventricular impedance signal; and detecting an atrial systolic event signal from the motion signal during the time window.

[0125] Embodiment 4: The method according to embodiment 1 further comprises: a motion signal is generated by a motion sensor of a pacemaker, the motion signal comprises an atrial systolic event signal; wherein detecting an atrial systolic event using an intraventricular impedance signal comprises: detecting at least one feature of the intraventricular impedance signal; setting an end time of a passive ventricular filling window based on the feature of the intraventricular impedance signal; setting an atrial event sensing threshold, the atrial event sensing threshold comprising a first threshold amplitude before the end time of the passive ventricular filling window and a second threshold amplitude less than the first threshold amplitude after the passive ventricular filling window; and detecting the atrial systolic event from the motion signal in response to the motion signal crossing the atrial event sensing threshold at the earliest.

[0126] Embodiment 5: The method according to embodiment 1 further comprises: a motion signal is generated by a motion sensor of a pacemaker, the motion signal comprising an atrial systolic event signal; wherein detecting an atrial systolic event using an intraventricular impedance signal comprises: sensing the atrial systolic event signal from the motion signal; detecting at least one feature of the intraventricular impedance signal corresponding to atrial systole; and confirming the atrial systolic event signal sensed from the motion signal in response to the features of the atrial systolic event signal and the intraventricular impedance signal being within a threshold time interval of each other.

[0127] Embodiment 6: A method according to embodiment 5, wherein detecting at least one feature of the intraventricular impedance signal comprises detecting at least one of the following: an inflection point of the intraventricular impedance signal; a maximum peak value of the intraventricular impedance signal; a minimum peak value of the intraventricular impedance signal; a maximum peak value of the first-order derivative signal of the intraventricular impedance signal; a minimum peak value of the first-order derivative signal of the intraventricular impedance signal; a maximum peak value of the second-order derivative signal of the intraventricular impedance signal; and a minimum peak value of the second-order derivative signal of the intraventricular impedance signal.

[0128] Example 7: The method according to Example 5 further includes: determining that no atrial systolic event signal is sensed from the motion signal within the threshold time interval based on at least one characteristic of the intraventricular impedance signal; and in response to determining that the atrial systolic event signal is not sensed, switching to an asynchronous ventricular pacing mode for controlling the pulse generator to deliver ventricular pacing pulses according to the ventricular pacing rate.

[0129] Example 8: The method according to Example 5 further includes: switching from an atrial-synchronous ventricular pacing mode to an asynchronous ventricular pacing mode; confirming the sensing of an atrial systolic event signal during the asynchronous ventricular pacing mode; and switching back to the atrial-synchronous ventricular pacing mode in response to confirming the sensing of the atrial systolic event signal.

[0130] Example 9: The method according to Example 1 further includes: generating a motion signal by a motion sensor of the pacemaker, the motion signal including an atrial systolic event signal; operating in an atrial-synchronous ventricular pacing mode includes: sensing an atrial systolic event signal from the motion signal; and controlling a pulse generator to deliver an atrial-synchronous ventricular pacing pulse at an atrioventricular pacing interval from the sensed atrial systolic event signal; determining by a control circuit that sensing an atrial systolic event signal from the motion signal is unreliable; in response to determining that sensing an atrial systolic event signal from the motion signal is unreliable, enabling an impedance sensing circuit to generate an intraventricular impedance signal; and switching from sensing an atrial systolic event signal from the motion signal to detecting an atrial systolic event from an impedance signal for controlling the pulse generator to deliver an atrial-synchronous ventricular pacing pulse.

[0131] Embodiment 10: The method of Embodiment 9, wherein determining that sensing of an atrial systolic event signal from the motion signal is unreliable comprises at least one of detecting increased patient body activity determined from the motion signal or detecting an increased heart rate.

[0132] Example 11: The method according to Example 1 further includes: receiving a raw impedance signal from a recording electrode pair, wherein the recording electrode pair includes two electrodes on a lateral side wall of a pacemaker housing, wherein the pacemaker housing surrounds a pulse generator, an impedance sensing circuit, and a control circuit, and includes a proximal end, a distal end, and a lateral side wall extending from the proximal end to the distal end; and generating an intraventricular impedance signal from the raw impedance signal.

[0133] Embodiment 12: A non-transitory computer-readable storage medium comprises a set of instructions which, when executed by a control circuit of a ventricular pacemaker in the heart, cause the pacemaker to perform the following operations: generate an intraventricular impedance signal; use the intraventricular impedance signal to detect an atrial systolic event; set an atrioventricular pacing interval in response to detecting the atrial systolic event; and deliver a ventricular pacing pulse at the end of the atrioventricular pacing interval.

[0134] It should be understood that, depending on the example, certain actions or events in any of the methods described herein may be performed in a different order, may be added, merged, or excluded entirely (e.g., not all described actions or events are necessary for the practice of the method). In addition, in some instances, actions or events may be performed simultaneously, rather than sequentially, such as by multithreading, interrupt processing, or multiple processors. In addition, for purposes of clarity, although certain aspects of the present disclosure are described as being performed by a single circuit or unit, it should be understood that the techniques of the present disclosure may be performed by a combination of units or circuits associated with, for example, a medical device.

[0135] In one or more instances, the functions described may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be stored in the form of one or more instructions or codes on a computer-readable medium and may be performed by a hardware-based processing unit. A computer-readable medium may include a computer-readable storage medium, which corresponds to a tangible medium, such as a data storage medium (e.g., RAM, ROM, EEPROM, flash memory, or any other medium that can be used to store the desired program code in the form of instructions or data structures and can be accessed by a computer).

[0136] 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 (FPGAs), or other equivalent integrated or discrete logic circuit systems. Thus, the term "processor" as used herein may refer to any of the foregoing structures or any other structure suitable for implementing the techniques described herein. Furthermore, the techniques may be fully implemented in one or more circuits or logic elements.

[0137] Thus, in the foregoing description, medical devices have been presented with reference to specific examples. It should be understood that the various aspects disclosed herein may be combined in different combinations other than the specific combinations presented in the drawings. It should be understood that various modifications may be made to the referenced examples without departing from the scope of the present disclosure and the following claims.

Claims

1. A cardiac ventricular pacemaker, comprising: an impedance sensing circuit configured to generate an intraventricular impedance signal; a motion sensor configured to generate a motion signal; a control circuit in communication with the impedance sensing circuit and the motion sensor, the control circuit being configured to: Detecting an atrial systolic event using at least one feature of the intraventricular impedance signal by: sensing an event signal from the motion signal; detecting at least one characteristic of the intraventricular impedance signal; determining that the features of the event signal and the intraventricular impedance signal sensed from the motion signal are within a threshold time interval of each other; detecting the atrial systolic event in response to the features of the event signal and the intraventricular impedance signal sensed from the motion signal being within a threshold time interval of each other; as well as setting an atrioventricular pacing interval in response to detecting the atrial systolic event; as well as A pulse generator is in communication with the control circuit and is configured to deliver a ventricular pacing pulse when the atrioventricular pacing interval expires.

2. The pacemaker of claim 1 , wherein the control circuit is configured to detect the atrial systolic event using the intraventricular impedance signal by: determining a derivative signal of the impedance signal; and Features of the derivative signal corresponding to a period of mechanical contraction of the atria are detected.

3. The pacemaker according to claim 1 or 2, wherein the control circuit is configured to detect the atrial systolic event using the intraventricular impedance signal by: setting a time window based on the at least one characteristic of the intraventricular impedance signal; and It is determined that the event signal sensed from the motion signal is sensed during the time window.

4. The pacemaker according to any one of claims 1 to 3, The control circuit is configured as follows: setting an end time of a passive ventricular filling window based on the at least one characteristic of the intraventricular impedance signal; setting an atrial event sensing threshold, the atrial event sensing threshold comprising a first threshold amplitude before the end time of the passive ventricular filling window and a second threshold amplitude less than the first threshold amplitude after the passive ventricular filling window; as well as detecting the atrial systolic event from the motion signal during at least one subsequent ventricular cycle in response to the motion signal crossing the atrial event sensing threshold at the earliest; as well as setting the atrioventricular pacing interval in response to detecting the atrial systolic event from the motion signal; and The pulse generator is configured to deliver a ventricular pacing pulse upon expiration of the atrioventricular pacing interval.

5. The pacemaker of claim 1 , wherein the control circuit is configured to detect the at least one characteristic of the intraventricular impedance signal by detecting at least one of: an inflection point of the intraventricular impedance signal; The maximum peak value of the intraventricular impedance signal; The minimum peak value of the intraventricular impedance signal; the maximum peak value of the first-order derivative signal of the intraventricular impedance signal; a minimum peak value of the first-order derivative signal of the intraventricular impedance signal; The maximum peak value of the second-order derivative signal of the intraventricular impedance signal; and The minimum peak value of the second-order derivative signal of the intraventricular impedance signal.

6. The pacemaker of claim 1 , wherein the control circuit is configured to: determining that the event signal is not sensed from the motion signal during at least one subsequent ventricular cycle; and In response to determining that the event signal is not sensed during at least one subsequent ventricular cycle, switching to an asynchronous ventricular pacing mode for controlling the pulse generator to deliver ventricular pacing pulses according to a ventricular pacing rate; and The pulse generator is configured to deliver ventricular pacing pulses at a ventricular pacing rate in response to the control circuit switching to the asynchronous ventricular pacing mode.

7. The pacemaker according to claim 1, wherein the control circuit is further configured to switch from an atrial synchronous ventricular pacing mode to an asynchronous ventricular pacing mode; the pulse generator being configured to deliver ventricular pacing pulses according to a ventricular pacing rate in response to the control circuit switching to the asynchronous ventricular pacing mode; The control circuit is further configured to: confirming detection of the atrial systolic event using the intraventricular impedance signal during the asynchronous ventricular pacing mode; and Responsive to confirming detection of the atrial systolic event, switching back to the atrial synchronized ventricular pacing mode.

8. The pacemaker according to any one of claims 1 to 7, wherein the control circuit is further configured to: In response to detecting the atrial systolic event, operating in an atrial synchronized ventricular pacing mode, comprising: sensing an event signal from the motion signal; and controlling the pulse generator to deliver atrial-synchronized ventricular pacing pulses at atrioventricular pacing intervals from the sensed event signal; determining that sensing an event signal from the motion signal is unreliable; responsive to determining that sensing of the phase event signal from the motion signal is unreliable during the atrial synchronized ventricular pacing mode, enabling the impedance sensing circuit to generate the intraventricular impedance signal; as well as Switching from sensing the event signal from the motion signal to detecting the atrial systolic event from the impedance signal for controlling the pulse generator to deliver the atrial-synchronized ventricular pacing pulse during the atrial-synchronized ventricular pacing mode.

9. The pacemaker of claim 8, wherein the control circuit is configured to determine that sensing the event signal from the motion signal is unreliable by: determining at least one of increased patient physical activity or increased heart rate; and Responsive to detecting at least one of the increased patient physical activity or the increased heart rate, it is determined that sensing the event signal from the motion signal is unreliable.

10. The pacemaker according to any one of claims 1 to 9, further comprising: a pacemaker housing enclosing the pulse generator, the impedance sensing circuit, and the control circuit, the pacemaker housing comprising a proximal end, a distal end, and lateral sidewalls extending from the proximal end to the distal end; and two electrodes on the lateral sidewall, the two electrodes defining an impedance recording electrode pair, the impedance recording electrode pair coupled to the impedance sensing circuit for receiving a raw impedance signal, The impedance sensing circuit is configured to generate the intraventricular impedance signal from the raw impedance signal.

Images