Dynamic AV delay optimization

Abstract

A system and method for monitoring and treating a patient with heart failure is discussed. The system may receive atrioventricular (AV) conduction characteristics at different heart rates or different patient conditions. Stimulation parameters, including stimulation timing parameters, may be stored in a memory. The system may include stimulation control circuitry configured to use the patient's AV conduction characteristics to determine a parameter update schedule indicating timings at which stimulation parameters are to be updated, and to dynamically update at least a portion of a stored set of stimulation parameters in the determined parameter update schedule. Stimulation parameters may be selected from the set of stimulation parameters for use during cardiac stimulation for a specified heart rate or heart rate range.

Description

[0001] Related applications

[0002] This application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application Serial No. 62 / 779,786, filed on December 14, 2018, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This document relates generally to medical systems and devices, and more particularly, to systems, devices, and methods for electrical stimulation to treat heart failure. Background Art

[0004] Congestive heart failure (CHF) is a leading cause of death in the United States and worldwide. CHF occurs when the heart cannot adequately pump enough blood to maintain healthy physiology. CHF can be treated with medication or electrical stimulation, such as pacing.

[0005] Implantable medical devices (IMDs) have been used to monitor CHF patients and manage heart failure in a mobile environment. Some IMDs may include sensors to sense physiological signals from the patient and detect heart failure exacerbations, such as heart failure decompensation. Frequent patient monitoring and early detection of heart failure exacerbations may help improve patient prognosis. Identifying patients with elevated risk of future heart failure events may help provide timely treatment and prevent or reduce hospitalization. Identifying and safely managing patients with risk of heart failure exacerbations can avoid unnecessary medical interventions, hospitalizations, and reduce healthcare costs.

[0006] An IMD may include a pulse generator and a circuit that is configured to electrically stimulate the heart or other excitable tissues to help restore or improve cardiac performance, or correct arrhythmias. An example of electrical stimulation therapy is cardiac resynchronization therapy (CRT). CRT, typically delivered as biventricular (BiV) pacing or only synchronous left ventricular (LV) pacing, is applicable to CHF patients with moderate to severe symptoms and ventricular dyssynchrony. CRT keeps the LV and right ventricle (RV) pumping synchronously by sending electrical stimulation to both the LV and RV. Synchronous stimulation can improve cardiac pumping efficiency and increase blood flow in some CHF patients. CRT can reduce hospitalization and morbidity associated with worsening heart failure and improve quality of life. Summary of the Invention

[0007] Among other things, the document discusses a patient management system for monitoring and treating patients with heart failure. The system can receive information about atrioventricular (AV) conduction characteristics of a patient, such as at different heart rates or patient conditions. Stimulation parameters, including stimulation timing parameters, such as atrioventricular delay (AVD) values, can be stored in a memory. The system can include stimulation control circuitry configured to use the received information about AV conduction characteristics to determine a parameter update schedule that indicates timings at which at least a portion of a set of stimulation parameters is to be updated, and to dynamically update at least a portion of the stored set of stimulation parameters at the determined parameter update timings. For a specified heart rate or heart rate range, stimulation parameters, such as AVD values, can be selected from the set of stored stimulation parameters for use during cardiac stimulation.

[0008] Example 1 is a medical device system comprising a stimulation control circuit configured to: determine a parameter update schedule using a patient's atrioventricular conduction characteristics, the parameter update schedule indicating a timing at which stimulation parameters are to be updated; dynamically update at least a portion of a set of stimulation parameters for the patient stored in a memory, including stimulation timing parameters, at the determined parameter update timing; and select stimulation parameters from the set of stimulation parameters for use during cardiac stimulation for a specified heart rate or heart rate range.

[0009] In Example 2, the subject matter of Example 1 may optionally include: a receiving circuit configured to receive atrioventricular conduction information of the patient, and a stimulator circuit configured to deliver cardiac stimulation using the selected stimulation parameters. The stimulation control circuit may be configured to use the received atrioventricular conduction information to determine atrioventricular conduction characteristics of the patient.

[0010] In Example 3, the subject matter of any one or more of Examples 1-2 optionally includes that the stimulation timing parameter may include an atrioventricular delay (AVD) value, and the atrioventricular conduction characteristic includes an intrinsic atrioventricular interval (AVI).

[0011] In Example 4, the subject matter of any one or more of Examples 1-3 may optionally include the stimulation control circuit being configurable to use a variability measure of the atrioventricular conduction characteristic to determine the parameter update timing.

[0012] In Example 5, the subject matter of Example 4 optionally includes parameter update timing, which may include a parameter update frequency. The stimulation control circuitry may be configured to decrease the parameter update frequency corresponding to the heart rate or heart rate range if the measure of variability of the atrioventricular conduction characteristic value is below a variability threshold, and to increase the parameter update frequency if the measure of variability of the atrioventricular conduction characteristic value is above the variability threshold.

[0013] In Example 6, the subject matter of any one or more of Examples 1-5 optionally includes a stimulation control circuit that can be configured to: determine values ​​of an atrioventricular conduction characteristic corresponding to multiple heart rates; and determine parameter update timing using a measure of covariance between the values ​​of the atrioventricular conduction characteristic and the corresponding multiple heart rates.

[0014] In Example 7, the subject matter of Example 6 may optionally include that the covariance metric may include a correlation, and the parameter update timing may include a parameter update frequency. The stimulus control circuit may be configured to decrease the parameter update frequency if the correlation is below a correlation threshold, and to increase the parameter update frequency if the correlation is above the correlation threshold.

[0015] In Example 8, the subject matter of Example 6 optionally includes that the covariance metric can include a rate of change of the atrioventricular conduction characteristic with respect to changes in heart rate. The parameter update timing can include a parameter update frequency. The stimulation control circuit can be configured to decrease the parameter update frequency if the rate of change of the atrioventricular conduction characteristic is below a rate threshold, and increase the parameter update frequency if the rate of change of the atrioventricular conduction characteristic is above the rate threshold.

[0016] In Example 9, the subject matter of any one or more of Examples 1-8 may optionally include the stimulation control circuit being configurable to further use information of one or more of arrhythmias, cardiac conduction abnormalities, or body activity to determine parameter update timing.

[0017] In Example 10, the subject matter of any one or more of Examples 1-9 optionally includes a stimulation control circuit that can be configured to measure atrioventricular conduction characteristics at the determined parameter update timing and use the measured atrioventricular conduction characteristics to dynamically update at least a portion of the stimulation timing parameters.

[0018] In Example 11, the subject matter of Example 10 optionally includes dynamic updating of at least a portion of the stimulation timing parameters, which may include a weighted combination of historical stimulation timing parameter values ​​and measured atrioventricular conduction characteristics, each scaled by a respective weighting factor.

[0019] In Example 12, the subject matter of Example 11 may optionally include the stimulation control circuit being configurable to adjust the one or more weighting factors using information of the patient's physical activity.

[0020] In Example 13, the subject matter of any one or more of Examples 1-12 may optionally include the stimulation control circuit being configurable to store in the memory a set of stimulation timing parameters for each of a plurality of heart rates or heart rate ranges.

[0021] In Example 14, the subject matter of Example 13 may optionally include the stimulation control circuit being configurable to store in a memory a stimulation parameter table including a set of stimulation timing parameters and a corresponding plurality of heart rates or heart rate ranges.

[0022] In Example 15, the subject matter of any one or more of Examples 1-14 optionally includes a stimulation control circuit that is configurable to: generate (1) atrioventricular conduction characteristic values ​​corresponding to multiple heart rates or heart rate ranges and (2) a regression model between the two, and store them in a memory; and use the generated regression model to estimate the value of the atrioventricular conduction characteristic at a specific heart rate; and use the estimated atrioventricular conduction characteristic to dynamically update at least a portion of the stimulation timing parameters.

[0023] Example 16 is a method for controlling cardiac stimulation using an operating system. The method includes the following steps: determining a parameter update timing using atrioventricular conduction characteristics of a patient; dynamically updating at least a portion of a stimulation timing parameter set stored in a memory, including stimulation timing parameters, at the determined parameter update timing; and selecting stimulation parameters from the set of stimulation parameters for use during cardiac stimulation for a specified heart rate or heart rate range.

[0024] In Example 17, the subject matter of Example 16 may optionally include that the stimulation timing parameter may include an atrioventricular delay (AVD) value, and the atrioventricular conduction characteristic includes an intrinsic atrioventricular interval (AVI).

[0025] In Example 18, the subject matter of any one or more of Examples 16-17 may optionally include determining the parameter update timing, which may include using a variability measure of the atrioventricular conduction characteristic.

[0026] In Example 19, the subject matter of any one or more of Examples 16-18 can optionally include determining parameter update timing, which can include using (1) values ​​of the atrioventricular conduction characteristic corresponding to a plurality of heart rates and (2) a measure of covariability between the plurality of heart rates.

[0027] In Example 20, the subject matter of any one or more of Examples 16-19 optionally includes measuring an atrioventricular conduction characteristic at the determined parameter update timing. Dynamically updating at least a portion of the set of stimulation parameters includes using a weighted combination of: (1) historical stimulation timing parameter values ​​and parameters and (2) the atrioventricular conduction characteristic measured at the determined parameter update timing, each scaled by a respective weight factor.

[0028] In Example 21, the subject matter of Example 20 may optionally include using information of the patient's physical activity to adjust one or more weighting factors.

[0029] In Example 22, the subject matter of any one or more of Examples 16-21 optionally includes delivering cardiac stimulation using the selected stimulation parameters.

[0030] Example 23 is a medical device system comprising: a stimulation control circuit configured to deliver a cardiac stimulation signal to a patient based on a set of stimulation parameters; using the patient's atrioventricular conduction characteristics to determine a parameter update schedule indicating the timing at which at least a portion of the stimulation parameters are to be updated; and dynamically updating at least a portion of the set of stimulation parameters based on the determined time.

[0031] In Example 24, the subject matter of Example 23 may optionally include a stimulation control circuit that may be configured to dynamically update at least one of a stimulation timing parameter, a number of stimulation electrodes, or a stimulation pattern of the cardiac stimulation signal.

[0032] In Example 25, the subject matter of Example 24 can optionally include a stimulation mode of the cardiac stimulation signal, the stimulation mode can include at least one of a left ventricular-only pacing mode or a biventricular pacing mode.

[0033] In Example 26, the subject matter of any one or more of Examples 23-25 ​​may optionally include stimulation control circuitry that may be configured to select stimulation parameters from a set of stimulation parameters for use with the patient during cardiac stimulation for a specified heart rate or heart rate range.

[0034] The present invention summarizes some teachings of the application and is not intended to be an exclusive or exhaustive treatment of this theme. Further details about this theme can be found in the detailed description and the appended claims. By reading and understanding the following detailed description and viewing the accompanying drawings (each of which should not be considered as having a limiting meaning) forming a part thereof, other aspects of the present invention will be apparent to those skilled in the art. The scope of the present invention is limited by the appended claims and their legal equivalents. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Various embodiments are shown by way of example in the figures of the accompanying drawings. These embodiments are illustrative and are not intended to be exhaustive or exclusive of the present subject matter.

[0036] Figure 1 An example of a patient management system and portions of an environment in which the system may operate is shown.

[0037] Figure 2 An example of a dynamically controlled cardiac stimulation system configured to generate a personalized schedule for updating stimulation parameters and deliver cardiac stimulation to treat HF ​​or other conditions is shown.

[0038] Figure 3is a block diagram illustrating an example of a signature generator circuit configured to generate one or more signatures for use in determining the timing or frequency for updating stimulation parameters.

[0039] Figures 4A-4C is a diagram showing an example of a stimulation parameter table dictated by patient conditions for use in dynamic cardiac pacing.

[0040] Figure 5 is a flow chart illustrating a method for updating stimulation parameters and delivering cardiac stimulation according to the updated stimulation parameters.

[0041] Figure 6 A block diagram of an example machine is shown on which any one or more of the techniques (eg, methodologies) discussed herein may be executed. DETAILED DESCRIPTION

[0042] An ambulatory medical device (AMD) (such as an IMD, subcutaneous medical device, wearable medical device, or other external medical device) can be used to detect worsening heart failure and deliver heart failure (HF) therapy to restore or improve cardiac function. An IMD can be coupled to an implantable lead with electrodes that can be used to sense cardiac activity or deliver HF therapy, such as cardiac stimulation. An AMD can have a programmable treatment function that allows manual or automatic adjustment of electrical stimulation parameters, such as the stimulation chamber or site, stimulation mode, or stimulation timing.

[0043] AMD can be configured to stimulate various cardiac chambers to restore cardiac synchrony and improve hemodynamics. During CRT or BiV pacing, synchronized stimulation can be applied to the LV and RV of the heart. The RV and LV pacing sites can be stimulated simultaneously or sequentially using an RV-LV interventricular pacing delay (VVD). The delivery of LV and RV pacing can be timed relative to a reference point, such as intrinsic atrial depolarization sensed by an atrial electrode (atrial sensing, or AS), or an atrial pacing pulse (AP) that triggers atrial activation. If intrinsic ventricular depolarization is not detected within a period of atrioventricular delay (AVD) following the AS or AP, LV and RV pacing can be delivered at the end of the AVD.

[0044] In addition to BiV pacing, stimulation can also be delivered to only one cardiac chamber, such as the LV. LV-only pacing may improve cardiac synchrony in certain patients, such as those with intact atrioventricular (AV) conduction who require cardiac resynchronization. LV-only pacing may require a simpler implantable procedure, consume less power, and provide increased battery life compared to BiV pacing. As such, it is a clinically effective alternative to more complex BiV treatment regimens. Similar to the timing of BiV pacing, LV pacing can be delivered at the end of a programmed AVD following an AS or AP if no intrinsic LV depolarization is detected within the period of AVD.

[0045] AMD can be configured to stimulate one or more sites of a cardiac chamber simultaneously or sequentially. In conventional single-site pacing (SSP), only one site of a specific cardiac chamber (e.g., LV) is stimulated. Alternatively, multi-site pacing (MSP) can be used as an alternative to SSP. MSP involves electrical stimulation at two or more sites in the intrinsic cardiac chambers during the cardiac cycle. For example, in LV MSP, multiple LV sites may be stimulated simultaneously or separated by one or more intra-LV time offsets (ILVDs). MSP can improve LV function and hemodynamic response in some patients. However, MSP may require more energy than SSP and may also increase the complexity of system design and operation. Not all CHF patients can consistently benefit more from MSP than from SSP.

[0046] Stimulation timing parameters (such as AVD, VVD, or ILVD discussed above) can determine the timing of cardiac stimulation. Because such timing may affect the effectiveness of treatment and the patient's hemodynamic prognosis, the correct selection or programming of stimulation timing parameters may be important in HF management. For example, AVD can be determined using information about the patient's intrinsic AV conduction characteristics, such as the intrinsic AV interval (AVI) between the P wave and the R wave within the cardiac cycle in the electrocardiogram (ECG), or the intrinsic AVI between atrial events (e.g., atrial sensed (AS) or atrial paced (AP) events) and ventricular sensed events (VS) within the cardiac cycle in the subcutaneous electrocardiogram (EGM). In a patient, intrinsic AVI may not remain constant, but rather vary under various physiological or functional conditions. For example, long-term changes in the patient's health status, HF progression (such as remodeling or decompensation), or short-term changes in heart rate, posture, posture changes, physical activity, sleep / wake state, medications, hydration, diet, and other factors may affect AVI. As such, cardiac stimulation using a previously optimized AVD may not provide optimal patient outcomes under different patient conditions.

[0047] The present inventors have recognized several technical challenges in cardiac pacing therapy for treating HF. One challenge relates to personalized and dynamic HF treatment to address inter-patient variability in cardiac pacing therapy effectiveness, as well as intra-patient variability in cardiac pacing effectiveness over time due to at least long-term or short-term changes in patient condition. Timely adjustment of stimulation parameters, such as AVD, can improve overall treatment efficacy. Another challenge involves ensuring adequate ventricular pacing therapy (e.g., CRT), particularly in pacing-dependent patients. For example, during therapy optimization to update stimulation parameters, ventricular pacing therapy may need to be temporarily suspended. Some conventional pacing systems can reconfigure pacing electrodes (e.g., LV pacing electrodes) to sense cardiac electrical activity during therapy optimization. For example, frequent assessment of AV may require reconfiguring pacing electrodes to sensing electrodes to sense ventricular activation as the patient's condition changes. Frequent electrode reconfiguration may increase the complexity of the pacing system, place greater demands on computing resources such as firmware cycles, increase design and operating costs, and reduce battery life. Pausing pacing to reassess AV may adversely affect patient outcomes.

[0048] This document provides technical solutions to the aforementioned challenges in cardiac pacing therapy for HF and, therefore, can improve medical technology for device-based HF management. Among other aspects, this document also provides apparatus and methods for dynamically updating stimulation parameters (including stimulation timing parameters, such as AVD values). The dynamic parameter updates discussed herein can also be applied to other stimulation parameters, such as those used to determine stimulation site or stimulation pattern. Dynamic parameter updates can customize cardiac pacing therapy for individual patients and their physiological or functional conditions. In some examples, stimulation parameter values ​​(e.g., AVD values) corresponding to a variety of patient conditions (e.g., heart rate, atrial paced or atrial sensed events, posture) can be stored in a stimulation parameter table. Adjustments to stimulation parameters dictated by patient conditions can result in personalized pacing therapy to meet the patient's needs. Dynamic adjustments can be specific to heart rate or heart rate range, or on a beat-to-beat basis. In addition to improved treatment outcomes and patient outcomes, the systems and methods discussed herein can also reduce healthcare costs associated with HF management. Furthermore, this document provides for identification of conditions that may affect stimulation timing and treatment effectiveness. This may benefit healthcare providers in tracking patient HF progression and improving patient management.

[0049] This document also discusses a method for determining a parameter update schedule using a patient's AV conduction characteristics (e.g., intrinsic AVI) that indicates the timing at which stimulation parameters are to be updated. At least a portion of the stored set of stimulation parameters can be updated in the determined parameter update schedule. As described above, conventional cardiac pacing therapy may have to be frequently paused during therapy optimization to sense AV conduction characteristics. This not only affects the patient's prognosis, but also increases the complexity and cost of the device. The personalized parameter update timing discussed in this document can be dynamically determined based on the patient's condition (e.g., heart rate, AV conduction characteristics, etc.). This not only allows stimulation parameters and therapy to be customized in a timely manner to the patient's condition, but also reduces overall pacing pause time. Therefore, patient prognosis and device function can be improved.

[0050] In addition to improvements in medical technology for device-based management of heart failure patients across a variety of patient conditions, the systems, devices, and methods discussed herein may also allow for more efficient use of device memory, such as by storing and updating stimulation timing parameters that are more clinically relevant to the patient's long-term and short-term changing conditions. In addition to the therapeutic benefits, the personalized and dynamically adjusted therapies discussed in this document may also conserve device power and extend battery life. Using personalized HF therapies tailored to specific patient conditions, fewer unnecessary interventions or hospitalizations may be scheduled, prescribed, or provided; therefore, overall cost savings may be achieved.

[0051] Figure 1 An example of a patient management system 100 and portions of an environment in which the patient management system 100 can operate is shown. The patient management system 100 may include an ambulatory medical device, such as an implantable medical device (IMD) 110 that can be electrically coupled to a heart 105 via one or more leads 108A-108C, and an external system 120 that can communicate with the IMD 110 via a communication link 103. Examples of IMDs 110 may include, but are not limited to, pacemakers, defibrillators, CRT devices, cardiac remodeling control therapy (RCT) devices, neuromodulators, drug delivery devices, biotherapeutic devices, diagnostic devices (such as cardiac monitors or loop recorders), or patient monitors, among others. The IMD 110 may be coupled to, or replaced by, a monitoring medical device, such as a bedside or other external monitor. In addition to or in place of IMD 110, other ambulatory medical devices may be used, which may include subcutaneous medical devices, such as subcutaneous monitors or diagnostic devices, or external monitoring or treatment medical devices, such as automated external defibrillators (AEDs) or Holter monitors; wearable medical devices, such as patch-based devices, smart watches, or smart accessories; or bedside monitors.

[0052] IMD 110 may include a hermetically sealed canister 112 that may house electronic circuitry that may sense physiological signals in heart 105 and may deliver one or more therapeutic electrical pulses to a target area, such as within the heart, such as through one or more leads 108A-108C. Patient management system 100 may include only one lead, such as 108B, or may include two leads, such as 108A-108B.

[0053] Lead 108A may include a proximal end that can be connected to IMD 110 and a distal end that can be placed at a target location, such as the right atrium (RA) 131 of heart 105. Lead 108A may have a first pacing sensing electrode 141 that can be located at or near its distal end, and a second pacing sensing electrode 142 that can be located at or near electrode 141. Electrodes 141 and 142 can be electrically connected to IMD 110, such as via separate conductors in lead 108A, such as to allow sensing of right atrial activity and optional delivery of atrial pacing pulses. Lead 108B may be a defibrillation lead that may include a proximal end that can be connected to IMD 110 and a distal end that can be placed at a target location, such as the right ventricle (RV) 132 of heart 105. Lead 108B can have a first pacing sensing electrode 152 located at the distal end, a second pacing sensing electrode 153 that can be located near electrode 152, a first defibrillation coil electrode 154 that can be located near electrode 153, and a second defibrillation coil electrode 155 that can be located a distance from the distal end (such as for superior vena cava (SVC) placement). Electrodes 152 to 155 can be electrically connected to IMD 110, such as via separate conductors in lead 108B. Electrodes 152 and 153 can allow for sensing of the ventricular EGM and can optionally allow for delivery of one or more ventricular pacing pulses, and electrodes 154 and 155 can allow for delivery of one or more ventricular cardioversion / defibrillation pulses. In an example, lead 108B can include only three electrodes 152, 154, and 155. Electrodes 152 and 154 can be used to sense or deliver one or more ventricular pacing pulses, and electrodes 154 and 155 can be used to deliver one or more ventricular cardioversion or defibrillation pulses. Lead 108C may include a proximal end that may be connected to the IMD 110 and a distal end that may be placed at a target location, such as in the left ventricle (LV) 134 of the heart 105. Lead 108C may be implanted through the coronary sinus 133 and may be placed in a coronary vein above the LV to allow delivery of one or more pacing pulses to the LV. Lead 108C may include an electrode 161 that may be located at the distal end of lead 108C and another electrode 162 that may be located proximal to electrode 161. Electrodes 161 and 162 may be electrically connected to the IMD 110, such as via separate conductors in lead 108C to allow sensing of the LV EGM and optionally allow delivery of one or more resynchronization pacing pulses from the LV. Additional electrodes may be included in or along lead 108C. In an example, as Figure 1 As shown in FIG, the third electrode 163 and the fourth electrode 164 may be included in the lead 108. In some examples ( Figure 1), at least one of leads 108A-108C, or additional leads in addition to leads 108A-108C, may be implanted beneath the skin surface rather than within at least one heart chamber, or at or near heart tissue.

[0054] IMD 110 may include circuitry that can sense physiological signals. Physiological signals may include EGM or signals representing the mechanical function of heart 105. Hermetically sealed canister 112 may serve as electrodes, such as for sensing or pulse delivery. For example, electrodes from one or more of leads 108A-108C may be used with canister housing 112, such as for unipolar sensing of EGM or for delivering one or more pacing pulses. Defibrillation electrodes from lead 108B may be used with canister housing 112, such as for delivering one or more cardioversion / defibrillation pulses. In an example, IMD 110 may sense impedance between electrodes, such as those located on canister housing 112 or one or more of leads 108A-108C. IMD 110 may be configured to inject current between pairs of electrodes, sense the resultant voltage between the same or different pairs of electrodes, and determine impedance using Ohm's law. Impedance can be sensed in a two-pole configuration (where the same pair of electrodes can be used to inject current and sense voltage), a three-pole configuration (where the electrode pair used for current injection and the electrode pair used for voltage sensing can share a common electrode), or a four-pole configuration (where the electrodes used for current injection can be different from the electrodes used for voltage sensing). In an example, the IMD 110 can be configured to inject current between an electrode on the RV lead 108B and the can housing 112 and sense the resultant voltage between the same electrodes or between different electrodes on the RV lead 108B and the can housing 112. Physiological signals can be sensed from one or more physiological sensors that can be integrated within the IMD 110. The IMD 110 can also be configured to sense physiological signals from one or more external physiological sensors or one or more external electrodes that can be coupled to the IMD 110. Examples of physiological signals may include one or more of the following: ECG, intracardiac EGM, heart rate, heart rate variability, intrathoracic impedance, intracardiac impedance, arterial pressure, pulmonary artery pressure, left atrial pressure, RV pressure, LV coronary pressure, coronary blood temperature, blood oxygen saturation, one or more heart sounds, physical activity or exertion level, physiological response to activity, posture, respiration, weight or body temperature, and others.

[0055] In some examples, system 100 may include one or more leadless sensors that are not tethered to IMD 110 via leads 108A-108C. The leadless ambulatory sensors may be configured to sense physiological signals and communicate wirelessly with IMD 110. In some examples, IMD 110 may be a leadless medical device. Figure 1Unlike the tethered device of the IMD 110 shown in , a leadless medical device does not require a lead, wire, or tether extending between the electrode and the device body. The leadless medical device may include an anchoring or fixation mechanism for positioning the device body on a target implant side, such as the endocardial surface of one of the left ventricle, right ventricle, left atrium, or right atrium, or the epicardial surface of a portion of the heart. The leadless medical device can be delivered intravenously and positioned within a blood vessel on the heart, such as a coronary vein, where one or more electrodes on the leadless medical device can directly or indirectly contact the epicardial surface of the heart. An example of such a leadless medical device can include the leadless cardiac pacemaker (LCP) disclosed in commonly assigned U.S. patent application publication US2016 / 0051823 to Maile et al., entitled “LEADLESS CARDIAC PACEMAKER HAVING A SENSOR WITH A LOWER POWER MODE,” the entire contents of which are incorporated herein by reference.

[0056] The arrangement and function of these leads and electrodes are described above by way of example and not by way of limitation. Other arrangements and uses of these leads and electrodes are possible, depending on the needs of the patient and the capabilities of the implantable device.

[0057] The patient management system 100 may include a dynamically controlled stimulation circuit 113. The dynamically controlled stimulation circuit 113 can dynamically determine treatment parameters based on the patient's current physiological or functional condition. Patient conditions (such as patient health status, HF progression, remodeling or decompensation, heart rate, posture, posture transitions, physical activity, sleep / wakefulness, medications, hydration, diet, and other factors) may affect the electrical and mechanical properties of the heart and, thereby, the effectiveness of HF treatment. The dynamically controlled stimulation circuit 113 can use sensor inputs to determine stimulation parameters (e.g., AVD). In an example, the stimulation parameters can be arranged in a table stored in memory along with the corresponding patient physical and physiological conditions. In some examples, the dynamically controlled stimulation circuit 113 can determine a stimulation site (e.g., between LV-only pacing and BiV pacing) or a stimulation mode (e.g., between SSP and MSP) based on the sensor inputs. The dynamically controlled stimulation circuit 113 can use the patient's AV conduction characteristics (e.g., intrinsic AV) to determine a parameter update schedule (e.g., timing at which stimulation parameters are to be updated) and update at least a portion of the stored stimulation parameters at the determined parameter update timings. For a specified heart rate (either intrinsic heart rate or atrial paced heart rate) or heart rate range, the dynamically controlled stimulation circuit 113 can select stimulation parameters (e.g., AVD values) from a set of stimulation parameters and deliver cardiac pacing according to the selected stimulation parameters. Examples of personalized updating of stimulation parameters and dynamically controlled cardiac pacing are described below, such as with reference to Figure 2 .

[0058] The external system 120 can allow the IMD 110 to be programmed and receive information from the IMD 110 via the communication link 103. The external system 120 can include a local external IMD programmer. The external system 120 can include a remote patient management system that can monitor the patient's status or adjust one or more treatments, such as from a remote location. The remote patient management system can evaluate the collected patient data and provide alarm notifications, among other possible functions. In an example, the remote patient management system can include a central server that acts as a central hub for storing and analyzing collected patient data. The server can be configured as a single, multiple, or distributed computing and processing system. The remote patient management system can additionally or alternatively include one or more locally configured clients or remote clients that are securely connected to the server. Examples of clients can include personal desktops, laptops, mobile devices, or other computing devices. System users (such as clinicians or other qualified medical professionals) can use the clients to securely access stored patient data aggregated in the server's database.

[0059] Communication link 103 may include one or more of an inductive telemetry link, a radio frequency telemetry link, or a telecommunication link, such as an internet connection. Communication link 103 may provide for data transmission between IMD 110 and external system 120. The transmitted data may include, for example, real-time physiological data acquired by IMD 110, physiological data acquired by and stored in IMD 110, therapy history data or data indicating the operational status of the IMD, and programming instructions for IMD 110 (to configure IMD 110 to perform one or more actions, including, for example, data acquisition, device self-diagnostic testing, or therapy delivery).

[0060] Dynamically controlled stimulation circuitry 113 may be implemented at external system 120 (such as using data extracted from IMD 110 or stored in memory within external system 120 ). Portions of dynamically controlled stimulation circuitry 113 may be distributed between IMD 110 and external system 120 .

[0061] Portions of the IMD 110 or external system 120 may be implemented using hardware, software, or any combination of hardware and software. Portions of the IMD 110 or external system 120 may be implemented using dedicated circuitry that may be constructed or configured to perform one or more specific functions, or may be implemented using general-purpose circuitry that may be programmed or otherwise configured to perform one or more specific functions. Such general-purpose circuitry may include a microprocessor or a portion thereof, a microcontroller or a portion thereof, or a programmable logic circuit or a portion thereof. For example, a "comparator" may include, among other things, an electronic circuit comparator that may be constructed to perform the specific function of a comparison between two signals, or may include a comparator that may be implemented as part of a general-purpose circuit that may be driven by code that instructs a portion of the general-purpose circuit to perform a comparison between two signals. Although described with reference to the IMD 110, the patient management system 100 may include a subcutaneous medical device (e.g., a subcutaneous ICD, a subcutaneous diagnostic device), a wearable medical device (e.g., a patch-based sensing device), or other external medical device.

[0062] Figure 2 An example of a dynamically controlled cardiac stimulation system 200 is shown, which can be configured to generate a personalized schedule for updating stimulation parameters. An example of such a personalized schedule is a parameter update timing that can be determined using a patient's AV conduction characteristics or other patient physiological or functional conditions. The system 200 can update stimulation parameters at a time or frequency based on the parameter update timing and select stimulation parameters for use during cardiac stimulation.

[0063] Dynamically controlled cardiac stimulation system 200 can include one or more of sensor circuitry 210, stimulation control circuitry 240, memory circuitry 250, and a user interface 260. In some examples, system 200 can additionally include therapy circuitry 270 configured to deliver or adjust therapy, such as cardiac pacing therapy. At least a portion of cardiac monitoring system 200 can be implemented in an AMD, such as IMD 110, or distributed between an AMD or an external system, such as external system 120.

[0064] The sensor circuit 210 may include a sense amplifier for sensing cardiac signals. Cardiac signals may be sensed from different cardiac chambers, such as one or more of the RA, RV, left atrium (LA), or LV. Cardiac signals may be sensed when the heart is experiencing an intrinsic rhythm, such as sinus rhythm, or when the heart is stimulated according to a stimulation protocol, such as pacing the atria, ventricles, or other locations at a specified frequency or timing. Examples of cardiac signals may include cardiac electrical signals, such as an ECG sensed non-invasively from the body surface, a subcutaneous ECG sensed from electrodes placed subcutaneously, or an intracardiac EGM sensed from electrodes on one or more of the canister housing 112 or leads 108A-108C. By way of example and not limitation, atrial activation (denoted by AS) may be sensed using a sensing vector comprising one of the atrial electrodes 141 or 142, right ventricular activation (RVS) may be sensed using a sensing vector comprising one of the RV electrodes 152-154, and left ventricular activation (LVS) may be sensed using a sensing vector comprising one of the LV electrodes 161-164.

[0065] Additionally or alternatively, the cardiac signal may include a signal indicative of cardiac mechanical activity or the patient's hemodynamic state. In an example, the cardiac signal may include a signal sensed from an accelerometer or microphone configured to sense the patient's heart sounds. In an example, the cardiac signal may include a cardiac or thoracic impedance signal. The cardiac mechanical signal may include a blood pressure sensor signal or any other sensor signal indicative of cardiac mechanical activity or hemodynamic state.

[0066] In some examples, the sensor circuit 210 can sense two or more cardiac signals from different locations of the heart chamber, such as multiple locations at the LV, simultaneously or sequentially. The sensor circuit 210 can sense the LV EGM from two or more LV locations using corresponding sensing vectors. An example of an LV sensing vector may include a bipolar sensing vector, such as between an electrode pair selected from 161-164. Alternatively, the LV sensing vector may be between one of the electrodes 161-164 and another electrode positioned in a different chamber or on a different lead, such as one of 152-155 on the RV lead 108B, or electrode 141 or 142 on the RA lead 108A. Another example of an LV sensing vector may include a unipolar sensing vector that includes the canister housing 112 and one of the electrodes 161-164.

[0067] The sensor circuit 210 can process the sensed cardiac signals, including amplification, digitization, filtering, or other signal conditioning operations. The sensor circuit 210 can include or be coupled to a feature generator 212 that is configured to generate signal features from the processed cardiac signals. Examples of signal features can include temporal or morphological features indicative of intrinsic cardiac activity, such as P waves, Q waves, R waves, QRS complexes, or T waves that can be detected from a surface ECG, subcutaneous ECG, or intracardiac EGM, the timing and intensity of induced cardiac activity, such as induced electrical or mechanical activation in response to cardiac electrical stimulation. Examples of timing measurements can include time delays between cardiac activations sensed at different cardiac chambers (e.g., AVI between the atria and ventricles, or RV-LV intervals), or between different pacing sites (e.g., sensing delays between various LV sites).

[0068] In an example, the feature generator 212 may use the signal received by the sensor circuit 210 to determine the heart rate. In an example, the heart rate is the intrinsic heart rate in the absence of atrial pacing. In another example, the heart rate is detected during atrial pacing. Such atrial paced heart rate is substantially equal to the atrial pacing frequency. The heart rate may be used to schedule parameter updates, such as to determine parameter update timing. In an example, the parameter update timing includes the parameter update frequency. The heart rate may also be used to select stimulation parameters from a set of stimulation parameters stored in the memory 250. In an example, the feature generator 212 may determine intrinsic AV conduction characteristics, such as intrinsic AVI. In an example, the intrinsic AVI is measured when ventricular pacing (e.g., CRT) is temporarily suspended. In an example, the atrial to RV interval (AV R ) and atrial to LV septum (AV L ) to determine the intrinsic AVI. In some examples, the offset between the AVD and the AVI corresponding to the pseudo-fusion beat can be used to estimate the AVI during pacing. The offset can be stored in a memory. Under varying patient conditions, the AVI can be estimated using a combination of the AVD that caused the pseudo-fusion and the stored offset. Examples of AVI estimation based on pseudo-fusion during pacing are disclosed in commonly assigned U.S. Patent Application No. 16 / 007,094 to Ternes et al., entitled “SYSTEMS AND METHODS FOR DYNAMIC CONTROL OF HEART FAILURE THERAPY,” the entire contents of which are incorporated herein by reference.

[0069] In some examples, the sensor circuit 210 may also receive information about the patient's long-term or short-term physiological or functional condition. Changes in the patient's condition over the long term or short term may affect the electrical and mechanical properties of the heart and the patient's hemodynamic response. Therefore, if the treatment is not adjusted promptly and appropriately to the changing patient condition, it may be less effective. Physiological signals such as cardiac, pulmonary, neural, or biochemical signals may be received at the sensor circuit 210. Examples of physiological signals may include an ECG, an intracardiac EGM, a heart rate signal, a heart rate variability signal, a cardiovascular pressure signal, a heart sound signal, a respiratory signal, a thoracic impedance signal, a respiratory sound signal, or a blood chemistry measurement or the expression level of one or more biomarkers. Examples of functional signals may include patient posture, gait, balance, or physical activity signals, among others. The sensor circuit may sense the functional signals using motion sensors such as accelerometers, gyroscopes (which may be one-axis, two-axis, or three-axis gyroscopes), magnetometers (e.g., compasses), inclinometers, goniometers, altimeters, electromagnetic tracking systems (ETS) or global positioning system (GPS) sensors, among others. In another example, the functional signal may include information about a sleep state signal, such as sleep or wakefulness state, frequency or duration of sleep position switching, sleep inclination, or other indicators of sleep quality. In another example, the functional signal may include information about food or beverage intake (e.g., swallowing), coughing, or inhalation detection. In some examples, information about the patient's physiological or functional condition may be stored in a storage device, such as an electronic medical record (EMR) system, and the sensor circuit 210 may be configured to receive the patient's condition from the storage device in response to user input or triggered by a specific event.

[0070] In some examples, the sensor circuit 210 can receive information about the patient's medical history, medication intake, hospitalization, surgery, cardiac remodeling, heart failure exacerbation events (such as heart failure decompensation), or HF comorbidities. In some examples, the sensor circuit 210 can receive device implantation information, such as the location of the implantable lead. For example, the LV lead 108C can be implanted in the free wall, anterior, lateral, or posterior, and other possible LV locations. The LV lead position may affect the treatment effect and can be used to determine the stimulation site, mode, and timing parameters. In some examples, the sensor circuit 210 can additionally include measurements derived from the patient's echocardiogram, such as ejection fraction, cardiac contractility, cardiac timing or aortic velocity, and other hemodynamic parameters or other clinical diagnoses.

[0071] The stimulation control circuit 240 can update one or more stimulation parameters at a specific time or according to a specific update frequency and select stimulation parameters for use during cardiac stimulation. The stimulation parameters can include one or more stimulation timing parameters, such as AVD. The stimulation control circuit 240 can be implemented as part of a microprocessor circuit, which can be a dedicated processor, such as a digital signal processor, an application specific integrated circuit (ASIC), a microprocessor, or other type of processor for processing information including body activity information. Alternatively, the microprocessor circuit can be a general-purpose processor that can receive and implement an instruction set that performs the functions, methods, or techniques described herein.

[0072] The stimulation control circuit 240 may include a circuit group that includes other circuits or sub-circuits, such as one or more of a parameter update scheduler circuit 241, a stimulation timing regulator circuit 242, and a stimulation parameter selector circuit 243. These circuits may perform the functions, methods, or techniques described herein individually or in combination. In an example, the hardware of the circuit group may be immutably designed to perform a specific operation (e.g., hard-wired). In an example, the hardware of the circuit group may include variably connected physical components (e.g., execution units, transistors, simple circuits, etc.) that include a computer-readable medium that is physically modified (e.g., magnetically, electrically, or removably positioned to immutably aggregate particles) to encode instructions for a specific operation. When the physical components are connected, the underlying electrical properties of the hardware components change, for example, from an insulator to a conductor, or vice versa. The instructions enable embedded hardware (e.g., an execution unit or a loading mechanism) to create a member of the circuit group in hardware via the variably connected components to perform a portion of the specific operation when in operation. Thus, when the device is operating, the computer-readable medium is communicatively coupled to the other components of the circuit group members. In an example, any one of the physical components can be used in more than one member of more than one circuit group. For example, in operation, an execution unit can be used in a first circuit of a first circuit group at one point in time and reused by a second circuit in the first circuit group or by a third circuit in the second circuit group at a different time.

[0073] The parameter update scheduler circuit 241 can be configured to determine a personalized parameter update schedule, such as a parameter update timing. The parameter update timing can be generated using patient physiological or functional information, such as heart rate or AV conduction characteristics, such as received by the sensor circuit 210. In some examples, the stimulation timing parameters (e.g., AVD values) can correspond to multiple heart rate ranges. The parameter update scheduler circuit 241 can determine the parameter update timing for multiple heart rates or heart rate ranges separately. The parameter update timing for one heart rate range can be different from the parameter update timing for another heart rate range. For example, for a first heart rate range of 60-70bpm, the AVD can be updated at a first frequency of once every 10 minutes. For a second heart rate range of 80-90bpm, the AVD can be updated at a second frequency of once every 5 minutes. The parameter update timing for multiple heart rate ranges can each be determined using the AV conduction characteristics measured in the corresponding heart rate range. Examples of determining personalized parameter update timing are discussed below, such as reference Figure 3 .

[0074] The stimulation timing regulator circuit 242 can be configured to use patient physiological or functional information, such as measurement results of AV conduction characteristics, to determine or update stimulation timing parameters. The stimulation timing parameters can be determined or updated at a specific time or at a specific periodic update frequency, such as according to the parameter update timing provided by the parameter update scheduler circuit 241. The stimulation timing parameters define the timing for delivering cardiac stimulation pulses. Examples of timing parameters may include AVD, VVD, or ILVD. In an example, the stimulation timing regulator circuit 242 can use the patient's inherent AVI to determine or update the AVD. The AVI can be measured at the determined parameter update timing. In an example, the stimulation timing regulator circuit 242 can set a timer whose duration corresponds to the parameter update timing, such as 10 minutes. The timer can be reset to the duration value immediately after the AVI is evaluated and count down as time passes until the timer duration expires, at which time another AVI measurement can be taken.

[0075] The stimulation timing adjuster circuit 242 may determine or update stimulation timing parameters using a weighted combination of: (1) historical stimulation timing parameter values ​​and (2) determined values ​​of AV conduction characteristics (each scaled by a respective weight factor). In an example, the AVD may be recursively updated using the inherent AVI value as follows:

[0076] AVD(n)=a*AVD(n-1)+b*AVI(n) (1)

[0077] Wherein AVD(n) represents the newly updated AVD value, AVD(n-1) represents the historical AVD value before the update, and AVI(n) represents the current intrinsic AVI value determined at a time or frequency based on the parameter update timing. In an example, the stimulation timing regulator circuit 242 can use information about the patient's physical activity to adjust one or more of the weighting factors "a" or "b". At higher physical activity levels, the intrinsic AVI may change more. The AVD can be adjusted to account for changes indicated by activity in the AVI. In an example, in response to an increased physical activity level, the stimulation timing regulator circuit 242 can reduce the weighting factor "a" to reduce the impact of the historical AVD value, and / or increase the weighting factor "b" to increase the sensitivity of the current AVI.

[0078] In an example, the stimulation timing regulator circuit 242 may be used in the right ventricle (AV R ) and the AVI measured at the left ventricle (AV L ) is used to determine or update the AVD. R Represents the interval between atrial sensed (AS) or atrial paced (AP) activation and sensed RV activation (RVS). L Denotes the interval from AS or AP activation to sensed LV activation (LVS). Commonly assigned U.S. Patent Application No. 16 / 007,094 to Ternes et al., entitled "SYSTEMS AND METHODS FOR DYNAMIC CONTROL OF HEARTFAILURE THERAPY," discusses a method for using AV R and AV L The disclosure of which is incorporated herein by reference in its entirety.

[0079] The memory circuit 250 can be configured to store a set of stimulation parameters, such as an AVD. The stimulation timing parameters can correspond to each of a plurality of heart rates or heart rate ranges. In some examples, the stimulation timing parameters can further correspond to other patient conditions, such as atrial sensed (AS) events or atrial paced (AP) events, different postures, or different times of the day. The memory circuit 250 can be coupled to a stimulation timing adjuster circuit 242, which can update at least a portion of the stored set of stimulation parameters with new values ​​of the stimulation parameters, such as the updated AVD according to equation (1). When the AVD is determined for different heart rates or heart rate ranges, AS or AP events, different postures, or other patient conditions and stored in the memory, the stimulation timing adjuster circuit 242 can update the AVD for the corresponding patient condition accordingly, such as by using the AVI measured during the corresponding patient condition according to the above equation (1). In some examples, the memory circuit 250 can store a stimulation parameter table, which includes stimulation timing parameter values ​​and corresponding multiple heart rates or heart rate ranges, optionally together with information on one or more other patient conditions (e.g., posture), or time of day, as follows Figures 4A-4C As shown in .

[0080] A stimulation parameter selector circuit 243 coupled to the memory circuit 250 can select stimulation parameters from a set of stimulation parameters stored in the memory, including the dynamically updated stimulation timing parameters provided by the stimulation timing adjuster circuit 242, for use during cardiac stimulation. The stimulation parameter selector circuit 243 can search the stored stimulation parameters for a received patient condition (e.g., heart rate, AS or AP events, posture, or time of day) and identify recommended stimulation parameters (e.g., AVD) corresponding to the patient condition.

[0081] The stimulation parameter selector circuit 243 can further be configured to determine a cardiac chamber or one or more cardiac sites on a cardiac chamber for pacing based on the received patient condition. In an example, the stimulation parameter selector circuit 243 can select between LV-only pacing and BiV pacing. BiV pacing refers to stimulating both the LV and RV simultaneously or sequentially with a specified time offset. In some patients, BiV pacing may provide better cardiac synchrony and cardiac contractility than LV-only pacing configured to stimulate only the LV. However, changes in the patient's physiological or functional condition (e.g., an increase in heart rate, or a transition from supine to standing posture) may change the AV condition, ventricular contractility, or other cardiac properties. Switching the pacing chamber and other treatment adjustments may be required to maintain adequate therapeutic effect. The stimulation parameter selector circuit 243 can initiate a stimulation site assessment in response to a change in the patient's condition and determine between LV-only pacing and BiV pacing based on an increase in heart rate and indicators of AV conduction abnormalities (such as a prolonged AVI or increased irregularity in the AVI).

[0082] Additionally or alternatively, the stimulation parameter selector circuit 243 can be configured to determine between single site pacing (SSP) and multiple site pacing (MSP) based on the received patient condition. MSP can be delivered at two or more sites on the interior or epicardial surface of one or more cardiac chambers or any chamber surrounding tissue. During MSP, pulse trains can be delivered simultaneously at two or more cardiac sites, or sequentially with an intraventricular delay less than a sensed or paced time interval value of the cardiac cycle. The stimulation mode selector circuit 243 can initiate stimulation mode evaluation in response to changes in patient condition and determine between SSP pacing and MSP pacing at two or more LV sites using the interventricular interval measured from the RV site to various candidate LV sites (such as those corresponding to LV electrodes 161-164). The interventricular interval represents the degree of asynchrony between the RV and various LV sites. The stimulation parameter selector circuit 243 can scan a plurality of candidate LV electrodes to identify those LV sites whose corresponding interventricular intervals meet a specified condition (such as a threshold indicated by the patient's condition) and select an SSP or MSP based on the candidate electrode identification. Commonly assigned U.S. Patent Application No. 16 / 007,094 to Ternes et al., entitled "SYSTEMS AND METHODS FOR DYNAMIC CONTROL OF HEART FAILURE THERAPY," the disclosure of which is incorporated herein by reference in its entirety, discloses examples of stimulation site selection (e.g., between LV-only pacing and BiV pacing) and stimulation mode selection (e.g., between SSP and MSP) indicated by patient condition.

[0083] The user interface 260 may include an input device that enables a system user to program parameters for electrical stimulation or for sensing cardiac signals. Examples of input devices may include a keyboard, on-screen keyboard, mouse, trackball, touchpad, touch screen, or other pointing or navigation device. The input device may enable a system user to activate automatic programming of HF therapy, such as automatically determining stimulation sites, stimulation patterns, and stimulation timing parameters under specific patient conditions. The input device may also enable a system user to confirm, reject, or otherwise modify an automatically determined therapy program.

[0084] The user interface 260 may include a display for displaying the treatment program, such as automatically determined stimulation sites, stimulation patterns, and stimulation timing parameters. The output unit 230 may include a printing device for producing a hard copy of the information. The information may be presented in a table, chart, trend, graph, or any other type of text, tabular, or graphical presentation format. Additional information for display may include cardiac signals sensed from the sensor circuit 210, signal characteristics or measurements derived from the sensed cardiac signals (e.g., AVI), information received from the sensor circuit 210 regarding the patient's physiological or functional condition, or device status information (such as lead impedance and integrity), battery status (such as remaining battery life), or cardiac stimulation thresholds, or complications associated with stimulation at one or more cardiac sites, and other information.

[0085] The therapy circuit 270 can be configured to generate therapy based on parameter values ​​generated and recommended by the stimulation control circuit 240. The therapy can include electrical stimulation delivered to the pacing site via one or more of the leads 108A-108C and the electrodes attached thereto. The therapy circuit 270 can be configured to deliver LV-only pacing or BiV pacing. Additionally or alternatively, the therapy circuit 270 can be configured to generate an SSP for stimulating one cardiac site, or an MSP for stimulating two or more sites of the heart during the same cardiac cycle. In an example, the MSP can be delivered within the LV. The LV MSP can have a unipolar pacing configuration in which only one electrode (e.g., the cathode) is the LV electrode and the other electrode (e.g., the anode) is the IMD canister housing 112. In another example, a true bipolar configuration can be used in which both the cathode and anode are LV electrodes. In yet another example, an extended bipolar configuration can be used, where one electrode (e.g., cathode) is an LV electrode and the other electrode (e.g., anode) is an RA electrode (such as one of electrodes 141 or 142) or an RV electrode (such as one of electrodes 152-155). In another example, a tripolar configuration can be used, which can include two LV electrodes that serve as cathodes, or two electrodes such as selected from RA and RV electrodes that serve as anodes. In an example, one or more LV electrodes can be distributed among one or more LV leads, catheters, or untethered pacing units.

[0086] In some examples, therapy circuitry 270 can initiate or adjust electrical stimulation or other types of therapy (such as cardioversion therapy, defibrillation therapy, or drug therapy involving the delivery of a drug to a tissue or organ) at non-cardiac tissue (such as neural tissue). In some examples, therapy circuitry 270 can modify an existing therapy, such as adjusting stimulation parameters or drug dosage.

[0087] Figure 3is a block diagram illustrating an example of a feature generator circuit 320 configured to generate one or more features for use by the parameter update scheduler circuit 241 to determine the timing or frequency for updating stimulation parameters. The feature generator circuit 320 may be an embodiment of the feature generator circuit 212 of the system 200. In an example, a variability measure of a patient's AV conduction characteristic, such as AVI variability 321, may be generated using values ​​of the AV conduction characteristic. Examples of variability measures may include range, variance, or standard deviation, among other statistical measures. If the variability measure is below a variability threshold, the parameter update scheduler circuit 241 may reduce the parameter update frequency, and if the variability measure is above the variability threshold, increase the parameter update frequency. In an example, the variability measure of the AV conduction characteristic may be compared to one or more thresholds to categorize the patient into one of multiple levels of variability, such as a high level of variability, a medium level of variability, and a low level of variability. The parameter update scheduler circuit 241 may set the parameter update frequency to coincide with the level of variability, such that, for example, a high level of variability corresponds to a higher parameter update frequency (i.e., more frequent updates). In some examples, the variability metric of the AV conduction characteristic can be recorded over a period of time, such as a specified number of days. The parameter update scheduler circuit 241 can use one or more recorded variability metric values ​​to dynamically update the parameter update frequency.

[0088] As a non-limiting example, the initial parameter update timing can be programmed to update the AVD at a predetermined update frequency, such as every 10 minutes. If the intrinsic AVI is highly variable and exceeds a variability threshold, the parameter update scheduler circuit 241 can increase the AVD update frequency to, for example, every 8 minutes. However, if the variability of the intrinsic AVI measurement is small and below the variability threshold, the AVD update frequency can remain unchanged or be reduced to, for example, every 12 minutes. Increased AVI variability may indicate the occurrence of conduction abnormalities, arrhythmias, or other adverse cardiac conditions. More frequent and timely updates of the AVD can improve cardiac pacing effectiveness and patient hemodynamic outcomes. Conversely, less variable AVI may indicate stable AV conduction and overall stable cardiac conditions. Not updating parameters or updating less frequently does not adversely affect pacing therapy effectiveness and can reduce pacing pause time (e.g., required to reassess AVI and update AVD) and device operating mode switching (e.g., between ventricular pacing and sensing), which can benefit patients, especially those requiring uninterrupted pacing therapy.

[0089] In another example, a covariability metric can be generated between AV conduction characteristics (e.g., intrinsic AVI) and heart rate. AV conduction characteristics can be measured over a range of heart rates. The covariability metric indicates the sensitivity of the AV conduction characteristics to changes in heart rate. With high sensitivity, moderate fluctuations in heart rate can lead to substantial changes in AVI. Therefore, more frequent AVI reassessments and AVD updates can ensure that AVI changes are captured promptly and treatment can be adjusted accordingly to meet the patient's needs.

[0090] An example of a covariance metric is AVI-HR correlation 322, which can be calculated using AVI values ​​and corresponding heart rates. If the correlation is below a correlation threshold, the parameter update scheduler circuit 241 can reduce the parameter update frequency, and if the correlation is above the correlation threshold, increase the parameter update frequency. Another example of a covariance metric can include a rate of change 323 of AVI relative to changes in heart rate. If the relative rate of change of the AV conduction characteristic is below a rate threshold, the parameter update scheduler circuit 241 can reduce the parameter update frequency, and if the relative rate of change of the AV conduction characteristic is above the rate threshold, the parameter update scheduler circuit 241 can increase the parameter update frequency. In an example, the rate of change 323 of AVI can be represented by the slope of a linear regression between the AV conduction characteristic values ​​and the corresponding heart rates. If the slope is below a slope threshold, the parameter update scheduler circuit 241 can reduce the parameter update frequency, and if the slope is above the slope threshold, increase the parameter update frequency.

[0091] The feature generator circuit 320 may additionally or alternatively generate one or more features indicative of changes in cardiac rhythm or cardiac function, including, for example, an arrhythmia indicator 324 or a conduction abnormality indicator 325. An episode of an arrhythmia, or the onset of a conduction abnormality (e.g., rate-dependent bundle branch block), may interfere with the patient's intrinsic AVI. Therefore, the parameter update scheduler circuit 241 may increase the parameter update frequency to ensure that appropriate pacing therapy is delivered to meet the patient's needs. In another example, the feature generator circuit 320 may generate an indicator 326 of physical activity. Increased physical activity may accelerate the heart rate, or trigger rate-dependent conduction abnormalities or certain types of arrhythmias (e.g., sinus tachycardia), thereby introducing changes in the patient's intrinsic AVI. Therefore, more frequent AVD updates may help ensure that appropriate pacing therapy is delivered in a timely manner.

[0092] Figures 4A-4C4 is a graph showing stimulation parameter values ​​indicated by patient conditions that may be stored in a memory for dynamic cardiac pacing. Stimulation parameters may be stored in a table, such as table 410, 420, or 430, which includes recommended stimulation timing values ​​and one or more corresponding patient conditions. Each table entry may include a recommended AVD value for the corresponding patient condition. By way of example and not limitation, Figure 4A A stimulation parameter table 410 is shown, which includes stimulation timing values, such as AVD values, with corresponding heart rate ranges (HR), and atrial activation patterns as atrial sensed (AS) events or atrial paced (AP) events. The AVD of an AS event is referred to as a sensed AVD, and the AVD of an AP event is referred to as a paced AVD. Figure 4B A stimulation parameter table 420 is shown which is a variation of table 410 augmented by patient posture. By way of example, postures included in table 420 include supine, sitting, or standing postures. Figure 4C Stimulation parameter table 430 is shown, which is another variation of table 410, augmented by time of day information (such as daytime or nighttime). Alternatively, the time of day can include multiple time periods during a day within a 24-hour period. In various examples, tables 410, 420, or 430 can be augmented to include other patient conditions, such as activity (walking or running), sleep, diet, hydration, medication intake, heart rate, heart rate variability, arrhythmic events (e.g., atrial fibrillation, ventricular tachycardia, ventricular premature beats, post-arrhythmia). Various combinations or permutations of patient conditions can be implemented in stimulation parameter tables similar to tables 310 or 330 and are within the scope of this document. These patient conditions (alone or in combination) may affect cardiac tissue properties and patient hemodynamics. As a result, a therapy programmed in one setting may not be equally effective in a different setting. Different AVD values ​​can be recommended under different patient conditions to achieve the desired therapeutic effect and patient prognosis.

[0093] In various examples, at least some of the entries of the stimulation parameter table may additionally or alternatively include recommended values ​​for stimulation timing parameters other than AVD. In an example, the table entries may include a recommended RV-LV delay (VVD) under corresponding patient conditions of heart rate, posture, and atrial activation pattern. The VVD represents the offset between LV pacing pulses and RV pacing pulses within a cardiac cycle for BiV pacing or CRT therapy, such as selected by a system user or determined by the stimulation parameter selector circuit 243. In some examples, the VVD may be set to zero so that LV pacing and RV pacing are delivered simultaneously. In another example, at least some of the table entries may include a recommended intra-LV time offset (ILVD). The ILVD represents the offset between LV pacing pulses delivered at different LV sites within the cardiac cycle when the LV MSP is selected by a system user or determined by the stimulation parameter selector circuit 243. The LV MSP may be determined via Figure 1 Two or more of the LV electrodes 161-164 shown in FIG.

[0094] In various examples, the stimulation parameter tables can be expanded to include information in addition to stimulation timing parameters. In an example, at least some of the entries of tables 410-430 can additionally or alternatively include information about the stimulation site, such as an indication of LV pacing only or BiV pacing, or information about the stimulation mode, such as an indication of SSP or MSP. Thus, the expanded tables provide comprehensive treatment recommendations regarding stimulation site, mode, and timing values ​​under various patient conditions. In an example, the entries of the expanded tables can be constructed as a class structure in the memory circuit 250 that contains values ​​for one or more of the stimulation site, mode, and timing parameters. For example, one table entry can include (AVD, LV pacing only) and another table entry can include (AVD, BiV pacing, VVD, MSP, ILVD). In an example, one element in a table entry (e.g., AVD value, BiV pacing, or MSP) can apply to multiple table entries that share a common condition. For example, if BiV pacing is recommended for a condition defined by a sitting posture, AS, and a HR greater than 100 bpm, then BiV pacing may be recommended for all conditions, regardless of the heart rate range or atrial activation pattern (AS or AP), as long as the "sitting" posture is included. In another example, if MSP is recommended for a condition defined by a standing posture, AS, and a HR within 70-80 bpm, then MSP may be recommended for all conditions, regardless of the heart rate range or atrial activation pattern, as long as the "standing" posture is included.

[0095] In some examples, multiple stimulation timing parameter value tables can be constructed and stored in the memory circuit 250, such as an AVD table that only includes AVD values ​​for various patient conditions, a VVD table that only includes VVD values ​​for various patient conditions, or an ILVD table that only includes ILVD values ​​for various patient conditions. The table can include different patient physiological or functional conditions. In an example, the stimulation parameter selector circuit 243 can refer to the VVD table to determine the optimal VVD value for a particular patient condition when BIV pacing is selected. In another example, the stimulation parameter selector circuit 243 can refer to the ILVD table to determine the optimal ILVD value for a particular patient condition when MSP mode is selected. In another example, the stimulation parameter selector circuit 243 can refer to the AVD table to determine the optimal AVD for a particular patient condition, regardless of the pacing site or pacing mode.

[0096] Figure 5 1 is a flow chart illustrating a method 500 for updating stimulation parameters and delivering cardiac stimulation according to the updated stimulation parameters. Stimulation parameters, such as stimulation timing parameters, can be updated at a personalized parameter update timing. The personalized parameter update timing can tailor stimulation parameters to patient needs and can reduce overall pacing pause time due to stimulation parameter updates. The method 500 can be implemented in and performed by an implanted device, such as an IMD 110 or a dynamically controlled cardiac stimulation system 200.

[0097] Method 500 begins at 510, where a patient's atrioventricular (AV) conduction characteristics may be assessed using cardiac signals, such as received by sensor circuit 210. Examples of cardiac signals may include electrocardiographic signals, such as sensed from electrodes on one or more leads 108A-C or can housing 112, such as a surface ECG, subcutaneous ECG, or intracardiac EGM. The cardiac signals may additionally or alternatively include signals indicative of cardiac mechanical activity or the patient's hemodynamic state. Examples of AV conduction characteristics may include the intrinsic atrioventricular interval (AVI) between atrial activation (e.g., an atrial sensed (AS) event or an atrial paced (AP) event) and a ventricular sensed event. The intrinsic AVI may be measured when ventricular pacing is temporarily ceased. In some examples, the AVI measured at the RV (atrial to RV interval, AVI) may be used. R ) and AVI measured at the LV (atrial to RV interval, AVI R ) to determine the intrinsic AVI. In some examples, instead of pausing ventricular pacing to directly measure the AVI, the AVI can be estimated during pacing, such as through a test procedure, using the offset between the AVD and the AVI corresponding to the pseudo fusion beat. The offset can be stored for future use.

[0098] At 520, a personalized parameter update schedule, such as parameter update timing, may be determined using the measured or otherwise estimated AV conduction characteristic (e.g., AVI) from step 510. In an example, the parameter update timing includes a parameter update frequency. In an example, the parameter update timing may be determined or updated using a variability measure of the values ​​of the AV conduction characteristic. If the variability measure is below a variability threshold, the parameter update frequency may be decreased, and if the variability measure is above a variability threshold, the parameter update frequency may be increased. In an example, the variability measure of the AV conduction characteristic may be compared to one or more thresholds to classify a patient into one of a plurality of levels of variation, such as a high level of variation, a medium level of variation, and a low level of variation. The parameter update frequency may be set to coincide with the level of variation, such that, for example, a high level of variation corresponds to a higher parameter update frequency (i.e., more frequent updates). In another example, the parameter update timing may be determined or updated using a covariance measure between: (1) the values ​​of the AV conduction characteristic corresponding to a plurality of heart rates and (2) a plurality of heart rates. The heart rate may be an intrinsic heart rate in the absence of atrial pacing. Alternatively, the heart rate can be acquired during atrial pacing, which is substantially equivalent to the atrial pacing rate. The covariability metric represents the sensitivity of the AV conduction characteristic (e.g., intrinsic AVI) to changes in heart rate. The covariability can include a correlation between the AVI value and the corresponding heart rate. If the correlation is below a correlation threshold, the parameter update frequency can be reduced, and if the correlation is above the correlation threshold, the parameter update frequency can be increased. Alternatively, the covariance metric can be represented by the rate of change of AVI relative to changes in heart rate. If the relative rate of change of the AV conduction characteristic is below a rate threshold, the parameter update frequency can be reduced, and if the relative rate of change of the AV conduction characteristic is above the rate threshold, the parameter update frequency can be increased. In some examples, information about changes in heart rhythm or cardiac function, such as indications of arrhythmias or cardiac conduction abnormalities, can be used to determine or update the parameter update timing. Information about physical activity can additionally or alternatively be used to determine or adjust the parameter update timing. For example, increased physical activity may accelerate the heart rate or trigger a rate-dependent conduction abnormality, thereby introducing changes in the patient's intrinsic AVI. Therefore, the parameter update frequency may be increased such that more frequent AVD updates may help ensure timely delivery of appropriate pacing therapy.

[0099] In some examples, multiple parameter update timings may be determined for multiple heart rates or heart rate ranges, respectively. The parameter update timing for one heart rate or heart rate range may be different from the parameter update timing for another heart rate range. For example, for a heart rate range of 60-70 bpm, a stimulation parameter (e.g., AVD) may be updated at a first frequency of once every 10 minutes; however, for a heart rate range of 80-90 bpm, AVD may be updated at a second frequency of once every 5 minutes. The parameter update timings corresponding to various heart rate ranges may each be determined using signal characteristics (e.g., heart rate, AV conduction characteristics (such as AVI)) at the corresponding heart rate range.

[0100] At 530, at least a portion of the set of stimulation parameters stored in the memory may be updated at a specific time or a specific periodic update frequency, such as the parameter update timing determined at step 520. The stimulation timing parameters may be updated using patient physiological or functional information, such as measurements of AV conduction characteristics. The stimulation timing parameters define the timing of delivering cardiac stimulation and may be important for ensuring therapeutic efficacy and patient hemodynamic response. The timing parameters may include AVD, VVD, or ILVD. In an example, the AVD may be updated using the patient's intrinsic AVI measured at a time and frequency according to the parameter update timing determined at 520. In an example, the AVD may be recursively updated using a weighted combination of: (1) historical stimulation timing parameter values ​​and (2) determined values ​​of the AV conduction characteristics, such as according to equation (1) above. In another example, the AVD may be updated using a weighted combination of historical stimulation timing parameter values ​​and (2) determined values ​​of the AV conduction characteristics, such as according to equation (1) above. R ) and the AVI measured at the left ventricle (AV L ) to update the AVD based on the combination of AVIs measured at )

[0101] A dynamically updated portion of a set of stimulation parameters can be stored in memory. The stimulation timing parameters can correspond to each of a plurality of heart rates or heart rate ranges. In some examples, the stimulation timing parameters can further correspond to other patient conditions, such as atrial sensed (AS) events or atrial paced (AP) events, different postures, or different times of day. In some examples, a stimulation parameter table can be created and stored in memory. The table can include stimulation timing parameter values ​​and corresponding plurality of heart rates or heart rate ranges, optionally with one or more other patient conditions (e.g., posture), or time of day information, such as Figures 4A-4C As shown in .

[0102] At 540, stimulation parameters can be selected from a set of stimulation parameters stored in memory, including dynamically updated stimulation timing parameters, for use during cardiac stimulation. For a received patient condition (e.g., heart rate, AS or AP events, posture, or time of day sensed from the patient), recommended stimulation parameters corresponding to the patient condition (e.g., AVD) can be identified. Cardiac stimulation (e.g., CRT) can be delivered using the selected stimulation parameters. In various examples, the cardiac chamber (e.g., LV pacing only, or BiV pacing of both left and right ventricles), or the pacing mode for pacing the cardiac chamber (e.g., single site pacing (SSP) of the left ventricle, or multi-site pacing (MSP)) can be determined based on the patient condition, as described above with reference to Figure 2 discussed.

[0103] Figure 6 A block diagram of an example machine 600 is shown on which any one or more of the techniques (eg, methods) discussed herein may be performed. Portions of this description may apply to the computing framework of various portions of an LCP device, an IMD, or an external programmer.

[0104] In alternative embodiments, the machine 600 can operate as a standalone device or can be connected (e.g., networked) to other machines. In a networked deployment, the machine 600 can operate in the capacity of a server machine, a client machine, or both in a server-client network environment. In an example, the machine 600 can act as a peer machine in a peer-to-peer (P2P) (or other distributed) network environment. The machine 600 can be a personal computer (PC), a tablet PC, a set-top box (STB), a personal digital assistant (PDA), a mobile phone, a network appliance, a network router, a switch or a bridge, or any machine capable of executing instructions (sequentially or otherwise) specifying the actions to be taken by the machine. Furthermore, although only a single machine is shown, the term "machine" should also be construed to include any collection of machines that individually or collectively execute one (or more) sets of instructions to implement any one or more of the methods discussed herein, such as cloud computing, software as a service (SaaS), or other computer cluster configurations.

[0105] As described herein, examples may include or be operated by logic or multiple components or mechanisms. A circuit group is a collection of circuits implemented in a tangible entity including hardware (e.g., simple circuits, gates, logic, etc.). The membership of a circuit group can be flexible over time and with underlying hardware variability. A circuit group includes members that can, individually or in combination, perform a specified operation when in operation. In an example, the hardware of a circuit group can be invariably designed to perform a specific operation (e.g., hardwired). In an example, the hardware of a circuit group can include variably connected physical components (e.g., execution units, transistors, simple circuits, etc.) that include a computer-readable medium that is physically modified (e.g., magnetically, electrically, or removably positioned to invariably aggregate particles) to encode instructions for a specific operation. When the physical components are connected, the underlying electrical properties of the hardware components change, for example, from an insulator to a conductor, or vice versa. The instructions enable embedded hardware (e.g., an execution unit or loading mechanism) to create members of the circuit group in hardware via the variably connected components to perform portions of a specific operation when in operation. Thus, when the device is in operation, the computer-readable medium is communicatively coupled to the other components of the circuit group members. In an example, any one of the physical components can be used in more than one member of more than one circuit group. For example, in operation, an execution unit can be used in a first circuit of a first circuit group at one point in time and reused by a second circuit in the first circuit group, or reused by a third circuit in a second circuit group at a different time.

[0106] Machine (e.g., computer system) 600 may include a hardware processor 602 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), a hardware processor core, or any combination thereof), main memory 604, and static memory 606, some or all of which may communicate with each other via an interconnection link (e.g., a bus) 608. Machine 600 may also include a display unit 610 (e.g., a raster display, a vector display, a holographic display, etc.), an alphanumeric input device 612 (e.g., a keyboard), and a user interface (UI) navigation device 614 (e.g., a mouse). In an example, display unit 610, input device 612, and UI navigation device 614 may be a touch screen display. Machine 600 may additionally include a storage device (e.g., a drive unit) 616; a signal generating device 618 (e.g., a speaker); a network interface device 620; and one or more sensors 621, such as a global positioning system (GPS) sensor, a compass, an accelerometer, or other sensors. The machine 600 may include an output controller 628, such as a serial (e.g., universal serial bus (USB)), parallel, or other wired or wireless (e.g., infrared (IR), near field communication (NFC), etc.) connection to communicate with or control one or more peripheral devices (e.g., a printer, a card reader, etc.).

[0107] The storage device 616 may include a machine-readable medium 622 having stored thereon one or more data structure sets or instruction sets 624 (e.g., software) embodying or used by any one or more of the techniques or functionality described herein. The instructions 624 may also reside, completely or at least partially, within the main memory 604, within the static memory 606, or within the hardware processor 602 during execution thereof by the machine 600. In an example, one or any combination of the hardware processor 602, the main memory 604, the static memory 606, or the storage device 616 may constitute a machine-readable medium.

[0108] Although the machine-readable medium 622 is illustrated as a single medium, the term “machine-readable medium” may include a single medium or multiple media (eg, a centralized or distributed database, and / or associated caches and servers) configured to store one or more instructions 624 .

[0109] The term "machine-readable medium" may include any medium that can store, encode, or carry instructions for execution by the machine 600 and that causes the machine 600 to perform any one or more of the techniques of the present disclosure, or that can store, encode, or carry data structures used by or associated with such instructions. Non-limiting examples of machine-readable media may include solid-state memory and optical and magnetic media. In an example, a bulk machine-readable medium includes a machine-readable medium having a plurality of particles having a constant (e.g., stationary) mass. Thus, a bulk machine-readable medium is a non-transitory propagating signal. Specific examples of bulk machine-readable media may include: non-volatile memory, such as semiconductor memory devices (e.g., electrically programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM)) and flash memory devices; magnetic disks, such as internal hard disks and removable disks; magneto-optical disks; and CD-ROM and DVD-ROM disks.

[0110] Instructions 624 may also be sent or received over a communication network 626 using a transmission medium via a network interface device 620 using any of a variety of transmission protocols (e.g., Frame Relay, Internet Protocol (IP), Transmission Control Protocol (TCP), User Datagram Protocol (UDP), Hypertext Transfer Protocol (HTTP), etc.). Example communication networks may include a local area network (LAN), a wide area network (WAN), a packet data network (e.g., the Internet), a mobile telephone network (e.g., a cellular network), a plain old telephone (POTS) network, and a wireless data network (e.g., a wireless network known as a Wi-Fi network). The Institute of Electrical and Electronics Engineers (IEEE) 802.11 series of standards, known as .16 family of standards), IEEE 802.15.4 family of standards, peer-to-peer (P2P) networks, etc. In an example, the network interface device 620 may include one or more physical jacks (e.g., Ethernet, coaxial, or telephone jacks) or one or more antennas to connect to the communication network 626. In an example, the network interface device 620 may include multiple antennas to enable wireless communication using at least one of single-input multiple-output (SIMO), multiple-input multiple-output (MIMO), or multiple-input single-output (MISO) technology. The term "transmission medium" shall be deemed to include any intangible medium capable of storing, encoding, or carrying instructions for execution by the machine 600, and includes digital or analog communication signals or other intangible media to facilitate communication of such software.

[0111] Various embodiments are shown in the above figures. One or more features from one or more of these embodiments can be combined to form other embodiments.

[0112] The method examples described herein may be at least partially machine or computer implemented. Some examples may include a computer-readable medium or machine-readable medium encoded with instructions that are operable to configure an electronic device or system to perform the methods described in the above examples. Implementations of such methods may include code, such as microcode, assembly language code, or high-level language code. Such code may include computer-readable instructions for performing various methods. The code may form part of a computer program product. In addition, the code may be tangibly stored on one or more volatile or non-volatile computer-readable media during execution or at other times.

[0113] The foregoing detailed description is intended to be illustrative rather than limiting.The scope of the disclosure should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

1. A medical device system comprising: Stimulation control circuitry configured to deliver a cardiac stimulation signal to a patient according to a set of stimulation parameters: determining a parameter update schedule using the patient's atrioventricular conduction characteristics that indicates timings at which at least a portion of the set of stimulation parameters is to be updated; and dynamically updating at least a portion of the stimulation parameter set according to the determined timing, In which, in order to determine the parameter update schedule, the stimulation control circuit is configured to: if the variability measure of the atrioventricular conduction characteristic is lower than the variability threshold, reduce the parameter update frequency corresponding to the heart rate or heart rate range, and if the variability measure of the atrioventricular conduction characteristic is higher than the variability threshold, increase the parameter update frequency.

2. The system according to claim 1, wherein: The stimulation control circuit is configured to dynamically update at least one of a stimulation timing parameter, a number of stimulation electrodes, or a stimulation pattern of the cardiac stimulation signal.

3. The system according to claim 2, wherein: The stimulation mode of the cardiac stimulation signal includes at least one of a left ventricle-only pacing mode or a biventricular pacing mode.

4. The system according to claim 1, wherein: The stimulation control circuit is configured to select stimulation parameters from the set of stimulation parameters for use with the patient during cardiac stimulation for a specified heart rate or heart rate range.

5. The system according to any one of claims 2 to 4, comprising: a receiver circuit configured to receive atrioventricular conduction information from the patient; as well as a stimulator circuit configured to deliver cardiac stimulation using selected stimulation parameters, Wherein, the stimulation control circuit is configured to use the received atrioventricular conduction information to determine the atrioventricular conduction characteristics of the patient.

6. The system according to any one of claims 2 to 4, wherein: The stimulation timing parameters include an atrioventricular delay (AVD) value, and the atrioventricular conduction characteristics include an intrinsic atrioventricular interval (AVI).

7. The system according to any one of claims 2 to 4, wherein: The stimulation control circuit is configured to: determining values ​​of atrioventricular conduction characteristics corresponding to a plurality of heart rates; and A parameter update schedule is determined using a measure of covariance between the determined values ​​of the atrioventricular conduction characteristic and the corresponding plurality of heart rates.

8. The system according to claim 7, wherein: The covariance measure is correlation, the parameter update schedule includes a parameter update frequency, and wherein the stimulation control circuit is configured to reduce the parameter update frequency if the correlation is below a correlation threshold and to increase the parameter update frequency if the correlation is above the correlation threshold.

9. The system according to claim 7, wherein: The covariability measure is a rate of change of the atrioventricular conduction characteristic relative to changes in heart rate, the parameter update schedule includes a parameter update frequency, and wherein the stimulation control circuit is configured to reduce the parameter update frequency if the rate of change of the atrioventricular conduction characteristic is below a rate threshold, and to increase the parameter update frequency if the rate of change of the atrioventricular conduction characteristic is above the rate threshold.

10. The system according to any one of claims 2 to 4, wherein: The stimulation control circuit is further configured to determine the parameter update schedule using information from one or more of the following: Arrhythmias; cardiac conduction abnormalities; or Physical activity.

11. The system according to any one of claims 2 to 4, wherein: The stimulation control circuit is configured to: measuring the atrioventricular conduction characteristic at the determined parameter update schedule; and At least a portion of the stimulation timing parameters are dynamically updated using the measured atrioventricular conduction characteristics.

12. The system according to claim 11, wherein The dynamic updating of at least a portion of the stimulation timing parameters includes a weighted combination of historical stimulation timing parameter values, each scaled by a respective weighting factor, and the measured atrioventricular conduction characteristic.

13. The system according to any one of claims 1 to 4, wherein: The stimulation control circuit is configured to store in memory a set of stimulation timing parameters for each of a plurality of heart rates or heart rate ranges.

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