Dual-electrogram based control for cardiac resynchronization therapy

Abstract

In some examples, controlling delivery of CRT includes controlling an implantable medical device to deliver ventricular pacing according to a sequence of different values of a CRT parameter and acquire first and second electrograms from respective first and second electrode vectors. For each value of the CRT parameter, a value of a comparison metric of a first activation interval between a first fiducial point of a cardiac cycle detected in the first electrogram and an occurrence of a second fiducial point of the cardiac cycle and a second activation interval between the first fiducial point and the occurrence of the second fiducial point detected in the second electrogram can be determined. A target value of the comparison metric can be identified and an updated value of the CRT parameter determined based on the target value. The system can then control the IMD to deliver ventricular pacing at the updated value of the CRT parameter.

Description

TECHNICAL FIELD

[0001] The present disclosure relates generally to medical device systems, and more particularly to medical devices configured for cardiac resynchronization therapy. BACKGROUND

[0002] Some types of implantable medical devices (IMDs), such as cardiac pacemakers or implantable cardioverter-defibrillators, can be used to provide cardiac therapy to a patient via one or more electrodes. The cardiac therapy can be delivered to the heart in the form of pulses or electrical shocks for pacing, cardioversion, or defibrillation, or cardiac resynchronization therapy (CRT). CRT can help to enhance cardiac output by resynchronizing the electrical activity of the heart ventricles of a patient having a condition such as ventricular dyssynchrony. Some IMDs can sense intrinsic depolarizations of the heart and control delivery of CRT to the heart based on the sensed intrinsic depolarizations. SUMMARY

[0003] Generally, the present disclosure relates to techniques for controlling delivery of CRT to a heart of a patient by a medical device, e.g., an IMD. The IMD can be controlled to deliver CRT to the heart at updated (e.g., patient-specific) values of a CRT parameter that can be determined according to the techniques described herein.

[0004] As an example, the techniques can include determining an updated value of a CRT parameter by a medical device system including an IMD based on a target value of at least one comparison metric of a first activation interval and a second activation interval, such as a ratio of the longer of the first activation interval and the second activation interval to the shorter of the first activation interval and the second activation interval and / or a time difference of the first activation interval and the second activation interval. In some examples, the CRT parameter can be an A-V time delay between activation of the right atrium (RA) and electrical stimulation of the ventricles, a V-V time delay between activation of one ventricle and electrical stimulation of the other ventricle, or other CRT parameter. The first activation interval and the second activation interval can be determined from a first cardiac electrogram and a second cardiac electrogram, respectively.

[0005] The target value can correspond to a target physiological response to CRT, such as fusion of ventricular activation during ventricular pacing. The first activation interval and the second activation interval can be intervals between occurrences of a first fiducial point and a second fiducial point of a cardiac cycle. In some examples, an electrical activation time (e.g., an activation time of a ventricle or a time of other local electrical activity of a portion of a heart) can be determined relative to a timing of another fiducial point. One or both of the first fiducial point and the second fiducial point of the cardiac cycle can be indicative of an overall cardiac event, such as a timing of a contraction of a cardiac chamber, a pacing timing of a cardiac chamber, or other such event. For example, one or both of the first fiducial point and the second fiducial point of the cardiac cycle can be an onset of a QRS complex of the cardiac cycle, a peak (e.g., a minimum, a minimum slope, or a maximum slope) of a QRS complex of the cardiac cycle, a zero-crossing, a threshold-crossing, or other aspect of a near-field or far-field EGM associated with the cardiac cycle, an application onset of a pacing electrical stimulus, etc., although any other suitable fiducial point can be used.

[0006] One or both of the first fiducial point and the second fiducial point of the cardiac cycle can be detected in a first electrogram and a second electrogram acquired from respective first and second electrode vectors. The first and second electrode vectors can be formed by a plurality of electrodes of a system including the IMD. In some examples, the first and second electrode vectors can be configured such that the first and second electrograms depict the cardiac cycle from two different angles relative to the heart.

[0007] Such techniques can include determining a target value based on the values of at least one comparison metric of the first activation interval and the second activation interval determined for each value of a sequence of different values of the CRT parameter, the IMD delivering ventricular pacing at the values, and identifying the target value from the values of the at least one comparison metric determined for the values of the sequence. Differences in the at least one comparison metric associated with delivering ventricular pacing at different values of the CRT parameter can correspond to differences in conduction rates of electrical impulses through the heart (e.g., a ventricle) resulting from ventricular pacing at the different values. In some examples in which the comparison metric is at least one of a ratio of the first activation interval and the second activation interval and / or a time difference between the first activation interval and the second activation interval, the target value can be associated with a value of the CRT parameter at which the value of the time difference is at a minimum (or the ratio is closest to 1) or at which the value of the time difference is equal to or less than a threshold (or the value of the ratio is within a threshold distance from the value 1). Such a value of the CRT parameter can result in an increased conduction rate in a patient having a conduction dysfunction. Such techniques can further include determining an updated value of the CRT parameter based on the identified target value of the CRT parameter and controlling the IMD to deliver ventricular pacing at the updated value of the CRT parameter.

[0008] In some examples, the IMD can deliver CRT at the updated values of the CRT parameters until expiration of the time period, until the medical device system determines that a physiological parameter of the patient (e.g., heart rate and / or physical activity level) has changed, or until the medical device system otherwise determines that further adjustment of the values of the one or more CRT parameters can be desirable. Upon expiration of the time period or determination that a physiological parameter of the patient has changed or otherwise adjustment of the values of the CRT parameters is determined, the medical device system can determine new updated values of the CRT parameters and control the IMD to deliver CRT at the new updated values of the CRT parameters.

[0009] In some other example procedures, patient-specific values of CRT parameters (e.g., A-V or V-V delays) can be obtained from visual inspection of cardiac electrograms during ventricular pacing, which can be performed during or shortly after CRT device implantation or at another clinician visit. Thus, determining patient-specific values of CRT parameters based on visual inspection of cardiac electrograms can be limited to a clinical or hospital setting. In such examples, CRT can be delivered according to the same values of the CRT parameters between clinician visits (which can be separated by weeks or months). However, patient-specific preferred values of the CRT parameters can change between clinician visits. In some examples, patient-specific preferred values of the CRT parameters can change as the disease state of the patient progresses (e.g., due to acute heart failure (HF) decompensation events, adverse tissue remodeling occurring in the progression of HF, or otherwise during the course of HF therapy). Additionally or alternatively, patient-specific preferred values of the CRT parameters can change as the patient’s physical activity changes when the conduction properties of the heart change due to activation of the sympathetic and parasympathetic nervous systems. As the preferred patient-specific values of the CRT parameters can change frequently (e.g., one or more times a day), similarly, frequent updating of the values of the parameters by which CRT is delivered can increase ventricular synchrony, which can improve patient outcomes.

[0010] Accordingly, the techniques described herein can provide periodic and / or on-demand adjustment of values of one or more CRT parameters. Such techniques can enable CRT to adapt in real-time to patient conditions, such as wakefulness / sleep, physical activity level, cardiac remodeling due to therapy, disease progression, and / or other conditions. Because determination of updated values of CRT parameters according to the techniques described herein can be performed by a medical device system including an IMD independent of clinician input or other interaction, the techniques described herein are not limited to a clinical or hospital setting. Accordingly, the techniques described herein can enable updated values of CRT parameters to be determined more frequently than techniques for determining updated values of CRT parameters that rely on clinician examination of a patient to whom CRT is delivered between clinician visits (e.g., lasting weeks or months) for the same values of CRT parameters. In this way, updated, patient-specific values of CRT parameters can be determined frequently, such as daily or even semi-continuously, which can provide for improved ventricular synchronization over instances in which patient-specific values of CRT parameters are not determined or are determined less frequently, such as only in a clinical setting.

[0011] In one example, a method for controlling delivery of cardiac resynchronization therapy (CRT) using an implantable medical device configured for implantation in a patient includes, by processing circuitry of a medical device system including the implantable medical device: controlling the implantable medical device to deliver ventricular pacing to a heart of the patient according to a sequence of different values of a CRT parameter; during delivery of ventricular pacing according to the sequence, acquiring a first electrogram from a first vector formed by a plurality of electrodes of the medical device system and a second electrogram from a respective one of a second vector formed by the plurality of electrodes; determining, for each of the different values of the CRT parameter, a first activation interval between a first fiducial point of a cardiac cycle detected in the first electrogram and an occurrence of a second fiducial point of the cardiac cycle and a second activation interval between the first fiducial point of the cardiac cycle detected in the second electrogram and the occurrence of the second fiducial point of the cardiac cycle; determining, for each of the different values of the CRT parameter, a value of a comparison metric of the first activation interval and the second activation interval; identifying a target value of the comparison metric of the first activation interval and the second activation interval; determining an updated value of the CRT parameter according to the identified target value; and controlling the implantable medical device to deliver the ventricular pacing with the updated value of the CRT parameter to provide CRT.

[0012] In another example, a system for controlling delivery of cardiac resynchronization therapy (CRT) to a patient includes a plurality of electrodes, an implantable medical device configured to deliver ventricular pacing to the patient, sensing circuitry configured to sense electrical activity of a heart via the plurality of electrodes, and processing circuitry configured to: control the implantable medical device to deliver ventricular pacing according to a sequence of different values of a CRT parameter, acquire, by the sensing circuitry and during delivery of ventricular pacing according to the sequence, a first electrogram from a respective one of a first vector formed by the plurality of electrodes and a second vector formed by the plurality of electrodes, determine, for each of the different values of the CRT parameter, a first activation interval between a first fiducial point of a cardiac cycle detected in the first electrogram and an occurrence of a second fiducial point of a cardiac cycle and a second activation interval between the first fiducial point of the cardiac cycle detected in the second electrogram and the occurrence of the second fiducial point of the cardiac cycle, determine, for each of the different values of the CRT parameter, a value of a comparison metric of the first activation interval and the second activation interval, determine a target value of at least one of the ratio or the time difference, determine an updated value of the CRT parameter according to the identified target value, and control the implantable medical device to deliver the ventricular pacing with the updated value of the CRT parameter to provide CRT.

[0013] In another example, a system for controlling delivery of cardiac resynchronization therapy (CRT) to a patient includes a plurality of electrodes, an implantable medical device configured to deliver ventricular pacing to the patient, sensing circuitry configured to sense electrical activity of a heart via the plurality of electrodes, and processing circuitry configured to: control the implantable medical device to deliver ventricular pacing according to a sequence of different values of A-V delay, acquire, by the sensing circuitry and during delivery of ventricular pacing according to the sequence, a first electrogram from a respective one of a first vector formed by the plurality of electrodes and a second vector formed by the plurality of electrodes, determine, for each of the different values of A-V delay, a first activation interval between a first fiducial point of a cardiac cycle detected in the first electrogram and an occurrence of a second fiducial point of a cardiac cycle and a second activation interval between the first fiducial point of the cardiac cycle detected in the second electrogram and the occurrence of the second fiducial point of the cardiac cycle, determine, for each of the different values of A-V delay, at least one of a ratio of the first activation interval to the second activation interval or a time difference between the first activation interval and the second activation interval, identify at least one of a minimum value of the time difference or a value of the ratio closest to 1, determine an updated value of A-V delay based on the identified at least one of a minimum value of the time delay or a value of the ratio closest to 1, and control the implantable medical device to deliver the ventricular pacing with the updated value of A-V delay to provide CRT.

[0014] In another example, a non-transitory computer-readable medium storing instructions for causing processing circuitry to perform a method for controlling delivery of cardiac resynchronization therapy (CRT) using a medical device system including the processing circuitry, a plurality of electrodes, an implantable medical device configured for implantation in a patient and including at least one electrode of the plurality of electrodes, and sensing circuitry configured to sense electrical activity through the plurality of electrodes, including: controlling the implantable medical device to deliver ventricular pacing according to a sequence of different values of a CRT parameter; during delivery of ventricular pacing according to the sequence, acquiring a first electrogram from a respective one of a first vector formed by the plurality of electrodes and a second vector formed by the plurality of electrodes; determining, for each of the different values of the CRT parameter, a first activation interval between an occurrence of a first fiducial point of a cardiac cycle determined in the first electrogram and a second fiducial point of a cardiac cycle and a second activation interval between the first fiducial point of the cardiac cycle determined in the second electrogram and the occurrence of the second fiducial point of the cardiac cycle; determining, for each of the different values of the CRT parameter, a value of a comparison metric of the first activation interval and the second activation interval; identifying a target value of the comparison metric of the first activation interval and the second activation interval; determining an updated value of the CRT parameter according to the identified target value; and controlling the implantable medical device to deliver the ventricular pacing with the updated value of the CRT parameter to provide CRT.

[0015] This summary is intended to provide an overview of the subject matter described in this disclosure. It is not intended to provide an exclusive or exhaustive explanation of the apparatus and methods described in detail within the accompanying drawings and description below. The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the description below. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 is a conceptual diagram illustrating an example of a medical device system including an implantable medical device and an external device in conjunction with a heart of a patient;

[0017] Figure 2 is a conceptual diagram illustrating Figure 1 portions of an implantable medical device of Figure 1 a medical device system and electrograms that can be acquired using

[0018] Figure 3A and 3Bis a conceptual diagram illustrating a first activation interval between an occurrence of a first fiducial point of a cardiac cycle depicted in a first electrogram and a second fiducial point of the cardiac cycle, a second activation interval between an occurrence of the first fiducial point of a cardiac cycle depicted in a second electrogram and an occurrence of the second fiducial point of the cardiac cycle, and a time difference between an occurrence of the second fiducial point of the first electrogram and an occurrence of the second fiducial point of the second electrogram;

[0019] Figure 4 is a functional block diagram illustrating an example configuration of an example implantable medical device;

[0020] Figure 5 is a functional block diagram illustrating an example system that includes an external device, such as a server, and an implantable medical device coupled to the external device through a network; Figure 1 one or more computing devices coupled to the implantable medical device and the external device;

[0021] Figure 6 is a flowchart illustrating example techniques for updating a CRT parameter and controlling an implantable medical device to deliver CRT according to the updated CRT parameter; and

[0022] Figure 7 is a flowchart illustrating example techniques for updating an A-V delay and controlling an implantable medical device to deliver CRT according to the updated A-V delay. DETAILED DESCRIPTION

[0023] In general, the present disclosure describes example techniques and systems related to controlling delivery of CRT to a patient by an IMD according to updated values of CRT parameters. Processing circuitry of an IMD or a system that includes the IMD can control the IMD to deliver ventricular pacing to a heart of a patient according to a sequence of different values of a CRT parameter (e.g., an A-V or V-V delay). For example, during delivery of CRT, the processing circuitry can determine that a current time period has elapsed or that an event indicative of a change in a state of the patient has occurred and enter a testing phase to determine an updated value of the CRT parameter.

[0024] During delivery of ventricular pacing according to the sequence, the processing circuitry can acquire a first cardiac electrogram and a second cardiac electrogram from respective ones of a first vector formed by a plurality of electrodes of the medical device system and a second vector formed by the plurality of electrodes. In some examples, the plurality of electrodes forming the first vector and the second vector can be electrodes that are not used in delivery of CRT by the IMD, but in other examples, one or more electrodes can be commonly used in the first vector or the second vector and in delivery of CRT.

[0025] In some examples, the processing circuitry can obtain the first electrogram from a first electrode vector by subtracting a signal from two component vectors that include at least one common electrode, e.g., by obtaining a signal from a vector that includes at least one electrode on a first lead and obtaining a signal from another vector that includes at least one electrode on a second lead. The processing circuitry can similarly obtain a second electrogram from a second electrode vector by subtracting a signal from a vector that includes the same at least one electrode on the first lead, subtracting a signal from a vector that includes at least one electrode on the second lead (different from the at least one electrode on the second lead used to obtain the first electrogram). In other examples, the processing circuitry can obtain the first electrogram and the second electrogram from other combinations of electrodes on the leads and / or housing electrodes of the medical device system. In any such examples, the signal from the at least one electrode on a lead can be a single signal received from two or more physically distinct electrodes on a lead or from a single electrode on a lead in combination with a housing electrode of the IMD housing or from other indistinguishable electrodes.

[0026] In any such examples, the first electrogram and the second electrogram obtained from the first electrode vector and the second electrode vector can demonstrate cardiac activity from two different angles relative to the heart. For example, the first electrode vector and the second electrode vector can be substantially orthogonal to each other. As discussed further below, the different angles of the cardiac activity demonstrated by the first electrogram and the second electrogram can assist the processing circuitry in determining whether ventricular pacing delivered by the IMD is associated with a target outcome of CRT (e.g., fusion between left ventricular activation and right ventricular activation) according to values of CRT parameters.

[0027] The processing circuitry can then determine, for each of the different values of the CRT parameter, a first activation interval between a first fiducial point of a cardiac cycle detected in the first electrogram and an occurrence of a second fiducial point of the cardiac cycle and a second activation interval between the first fiducial point of the cardiac cycle detected in the second electrogram and the occurrence of the second fiducial point of the cardiac cycle.

[0028] The first fiducial point and the second fiducial point can correspond to features of a cardiac cycle. In some examples, the first fiducial point can correspond to a time at which the IMD delivers a pacing pulse, which can be displayed as a pacing spike in an electrogram. The pacing spike can be a spike in the amplitude of an electrogram corresponding to delivery of a pacing pulse (e.g., a ventricular pacing pulse) to the heart during a cardiac cycle. In examples of ventricular pacing, the processing circuitry can control the IMD to deliver a pacing pulse after atrial activation and before intrinsic ventricular activation. Thus, in such examples, the pacing spike can appear in the first and second electrograms between the P-wave and the QRS complex of a cardiac cycle. Examples in which the pacing spike can be detected can include examples in which one medical device (e.g., a medical device implanted in the patient or external to the patient) is used to sense cardiac electrical signals according to the techniques described herein and another medical device is used to deliver ventricular pacing. In examples in which the pacing spike is detected, the pacing spike can be detected and distinguished from intrinsic cardiac electrical activity based on one or more criteria (e.g., amplitude and / or rate of change), each of which can be expected to be greater than that of an intrinsic cardiac signal.

[0029] Although the techniques herein can include detection of a pacing spike, in some examples, the processing circuitry can determine the timing of a pacing pulse in other ways, for example, based on a time at which the processing circuitry controls the IMD to deliver a pacing pulse, as discussed further below. In some examples, the second fiducial point can correspond to a feature of an electrogram related to depolarization of the heart in response to a pacing pulse, such as one of a start of paced ventricular activation in the electrogram, a maximum of a first derivative of the electrogram (dv / dt), a detected R-wave in the electrogram, or a maximum amplitude of the electrogram.

[0030] In some examples, the processing circuitry can determine the first activation interval and the second activation interval by detecting both the first fiducial point and the second fiducial point of a respective cardiac cycle in the first electrogram and the second electrogram. However, in other examples, the processing circuitry can determine the activation intervals by detecting one of the first fiducial point and the second fiducial point of a cardiac cycle (e.g., the second fiducial point) and determining the time of the other fiducial point (e.g., the first fiducial point) in a different manner. For example, the processing circuitry can determine the time of occurrence of the first fiducial point based on the time at which the IMD delivers a pacing pulse, rather than detecting the first fiducial point in the first electrogram and the second electrogram. In such examples, the time at which the IMD delivers a pacing pulse can be“known” to the timing and / or control aspects of the processing circuitry. Thus, determining the time of occurrence of the first fiducial point of a cardiac cycle does not necessarily depend on signal detection from the electrode vector and analysis of the electrograms, which can simplify and / or enhance the accuracy of determining the first activation interval and the second activation interval by the processing circuitry in some examples.

[0031] For each value of the sequence of different values of the CRT parameter by which the IMD delivers ventricular pacing, the processing circuitry can determine a relationship between the first activation interval and the second activation interval. The relationship between the first activation interval and the second activation interval can be described herein as at least one comparison metric of the first activation interval and the second activation interval. In some examples, the at least one comparison metric can be at least one of a ratio between the first activation interval and the second activation interval (e.g., a ratio of the duration of the longer of the first activation interval and the second activation interval to the duration of the shorter of the first activation interval and the second activation interval), a time difference between the first activation interval and the second activation interval, and / or one or more other suitable metrics. In some examples, the time difference between the first activation interval and the second activation interval can be a time difference between the occurrence of the second fiducial point of a cardiac cycle detected in the first electrogram and the occurrence of the second fiducial point of a cardiac cycle detected in the second electrogram. The processing circuitry can then identify a target value of the at least one comparison metric from the values of the comparison metrics associated with the different values of the CRT parameter.

[0032] The processing circuitry can identify the target value by identifying a minimum value of the time difference (or a ratio value closest to 1) or a value of the time difference that is equal to or less than a threshold value (or a ratio value that is within a threshold distance from the value of 1). That is, the target value of the comparison metric can be associated with a value of the CRT parameter of the sequence that delivers ventricular pacing that results in a maximum or threshold similarity in time between the first activation interval detected in the first electrogram and the second activation interval detected in the second electrogram.

[0033] The similarity in time between the first activation interval and the second activation interval can be associated with a conduction rate of electrical impulses through the heart (e.g., the ventricles). In some examples, patients with conduction dysfunction can experience intraventricular conduction dysfunction, such as left bundle branch block (LBBB) and / or right bundle branch block (RBBB). In LBBB and RBBB, electrical impulses are not conducted in the normal manner along the respective right or left bundle branch. Thus, in patients with bundle branch block, activation of the RV or LV is delayed relative to the other ventricle, resulting in asynchrony between right and left ventricular depolarization. Ventricular asynchrony can be identified by a widened QRS complex (e.g., greater than or equal to about 120 milliseconds) due to the increased time for activation to travel through the ventricular conduction pathway. With respect to some examples described herein, a widened QRS complex or other indication of conduction dysfunction can be more apparent in the second electrogram compared to the first electrogram. For example, the second electrode vector from which the processing circuitry obtains the second electrogram can include electrodes positioned farther from the electrodes through which the IMD delivers ventricular pacing than the electrodes of the first electrode vector.

[0034] In examples in which the patient is experiencing conduction dysfunction, electrical impulses can take longer to reach the electrodes of the second electrode vector compared to examples in which the patient is experiencing a lesser degree of conduction dysfunction or no conduction dysfunction. Thus, in examples in which the patient is experiencing conduction dysfunction, the value of at least one comparison metric, such as the ratio of the longer of the first activation interval and the second activation interval to the shorter of the first activation interval and the second activation interval and / or the time difference between the first activation interval and the second activation interval, can be greater than in examples in which the patient is experiencing a lesser degree of conduction dysfunction or no conduction dysfunction. Ventricular pacing delivered by the IMD can help reduce conduction dysfunction by restoring synchronous depolarization and contraction of one or more chambers of the heart, which can reduce the ratio of the longer of the first activation interval and the second activation interval to the shorter of the first activation interval and the second activation interval and / or the time difference between the first activation interval and the second activation interval. A minimum value of the time difference (or a ratio value closest to 1) or a value of the time difference (or a ratio value within a threshold distance from the value 1) that is equal to or less than a threshold value resulting from ventricular pacing delivered at a value of the CRT parameter relative to other values of the CRT parameter of the sequence can be associated with a target outcome of the ventricular pacing, such as fusion of ventricular activation. Thus, a desired target value can be a minimum value of the time difference (or a ratio value closest to 1) or a value of the time difference (or a ratio value within a threshold distance from the value 1) that is equal to or less than a threshold value.

[0035] In any such examples, the target value of the comparison metric can be associated with a value of the CRT parameter that enhances or optimizes the patient's hemodynamic response relative to one or more other different values of the sequence of CRT parameters. For example, the target value of the comparison metric can be associated with a value of the CRT parameter at which ventricular pacing produces a target outcome, such as fusion between left and right ventricular activation. Accordingly, the processing circuitry can determine an updated value of the CRT parameter based on the identified target value of the comparison metric. After determining the updated value of the CRT parameter, the processing circuitry can control the IMD to deliver ventricular pacing at the updated value of the CRT parameter to provide CRT, such as by controlling the IMD to deliver ventricular pacing at the value of the CRT parameter that produces the target value.

[0036] In some examples, the CRT parameter is an A-V delay, which can be a delay between atrial activation and delivery of a pacing pulse by the IMD to a ventricle (e.g., the left ventricle). In such examples, the processing circuitry can control the IMD to deliver left ventricular pacing according to a sequence of different values of the A-LV delay, control the IMD to deliver the ventricular pacing according to a sequence of different values of the A-V delay, and can control the IMD to deliver the ventricular pacing at the updated value of the CRT parameter by controlling the IMD to deliver LV fusion pacing. For example, the processing circuitry can control the IMD to deliver the ventricular pacing at the updated value of the CRT parameter by controlling the IMD to deliver the ventricular pacing at the value of the CRT parameter that produces the target value. Additionally, although the CRT parameter can be described herein with respect to some example techniques as an A-V delay, such techniques can be adapted to determine values of other CRT parameters, such as V-V delays or others.

[0037] In any such examples, the processing circuitry can control the IMD to deliver CRT at the updated value of the CRT parameter until expiration of a time period, until the medical device system determines that a physiological parameter of the patient (e.g., heart rate and / or physical activity level) has changed, and / or until the processing circuitry otherwise determines that further adjustment of the value of one or more CRT parameters can be desirable, such as upon receiving input from an external device that requires an updated value of the CRT parameter. Accordingly, the techniques described herein can enable frequent or substantially real-time adaptation of CRT to meet the changing needs of an individual patient. In some examples, controlling the IMD to deliver CRT at a patient-specific value of a CRT parameter can increase the hemodynamic benefit of CRT and / or can improve the clinical response of the patient. For example, symptoms experienced by a patient that otherwise does not respond to CRT can be improved by controlling the IMD to deliver CRT at a patient-specific value of a CRT parameter.

[0038] In some examples, the IMD can be an implantable CRT device including processing circuitry. Some example medical device systems including an implantable CRT device (e.g., CRT-D, CRT-P) can include one or more implantable leads configured for implantation within a patient, each of the leads can include one or more electrodes of the plurality of electrodes (from which the first and second electrode vectors can be formed). In some such examples, the implantable CRT device can be coupled to the plurality of electrodes through the one or more implantable leads.

[0039] In some such examples, the implantable CRT device can include a housing. The housing can include one of the plurality of electrodes. The one or more implantable leads can include a first lead configured for implantation within a right ventricle of a heart and a second lead configured for implantation within a left ventricle of a heart. In some examples, the first electrode vector can be between the housing and one of the plurality of electrodes on the first lead, and the second vector can be formed between one of the plurality of electrodes on the first lead and one of the plurality of electrodes on the second lead.

[0040] In some examples, a medical device system including an IMD includes a memory. In some such examples, processing circuitry of the medical device system can be configured to control the IMD to deliver the ventricular pacing to the patient’s heart according to a sequence of different values of a CRT parameter based on determining to update one or more CRT parameters by at least controlling the IMD to deliver the ventricular pacing to the patient’s heart according to the sequence of different values of the CRT parameter. The one or more CRT parameters can include a CRT parameter, and the processing circuitry can be further configured to store the updated CRT parameter as at least one updated value of the one or more CRT parameters in the memory.

[0041] As noted above, although patient-specific values of CRT parameters can be obtained from visual inspection of a cardiac electrogram during ventricular pacing in some other techniques, determining patient-specific values of CRT parameters based on visual inspection of a cardiac electrogram can be limited to a clinical or hospital setting, and thus can be updated only infrequently. Other techniques, such as echocardiography, that can be used to determine patient-specific values of CRT parameters can also be complex, and the measurements derived therefrom can be inaccurate. An additional limitation of echocardiography optimization is that CRT delivered according to patient-specific values of CRT parameters can be more beneficial even under conditions of greater physical activity, but it is performed while the patient is in a fully rested, recumbent position.

[0042] In general, other techniques that can be used to determine patient-specific values of CRT parameters (e.g., A-V or V-V delays) such as different echocardiographic measurements, invasive hemodynamic measurements (dP / dt, stroke work), finger photoplethysmography, or endocardial peak acceleration can waste time and resources, and / or can be subject to large measurement variability. Moreover, most such measurements are typically performed during office visits, and despite some clinical trials of CRT having incorporated some manner of AV delay determination, there is a lack of definitive data supporting its superiority over empirical A-V delays. These and / or other factors have prompted clinicians to leave CRT device settings as default values (i.e., "out-of-the-box" values) rather than determining patient-specific values of CRT parameters for individual patients. Thus, in such other techniques, patient-specific values of one or more CRT parameters can be rarely, if ever, determined.

[0043] The techniques described herein can enable continuous (e.g., periodic or substantially continuous), dynamic determination of patient-specific values of one or more CRT parameters (e.g., A-V delays or V-V delays) based on first and second electrograms acquired from first and second electrode vectors formed by a plurality of electrodes, rather than infrequent determination of patient-specific values of CRT parameters in a clinician's office or hospital. In some examples, the techniques described herein can improve acute hemodynamic benefits of CRT, such as by up to 20-30%, and / or can improve short-term clinical response. In some examples, such improvements in hemodynamic benefits and / or short-term clinical response can improve symptoms of patients that would otherwise not derive significant clinical benefit from CRT.

[0044] In some examples where the CRT parameter is an A-V delay, the value of the A-V delay by which the IMD delivers ventricular pacing can be periodically updated to provide more effective pacing and / or to improve the patient's hemodynamic response to CRT, such as upon expiration of a time period or determination of a change in a physiological parameter of the patient or otherwise determining to adjust the value of the A-V delay. Fusion pacing and biventricular pacing are described in further detail below. While pacing stimuli can be pacing pulses or continuous time signals, for ease of description, pacing stimuli are primarily referred to herein as pacing pulses.

[0045] Fusion-based CRT, also referred to herein as fusion pacing, can be used to restore the depolarization sequence of a patient’s heart in patients with preserved intrinsic atrial-ventricular (AV) conduction that can otherwise be irregular due to ventricular dysfunction. Proper ventricular activation fusion can restore the depolarization sequence of the heart by synchronizing activation of the ventricles, thereby increasing the systolic pressure or maximum rate of pressure increase (LV dP / dtmax) of the paced ventricle. In a fusion pacing configuration, an IMD delivers one or more fusion pacing pulses to one of the ventricles, rather than the other. For example, an IMD can deliver one or more fusion pacing pulses to a post-systolic ventricle (V2) in order to pre-excite V2 and synchronize the depolarization of V2 with the depolarization of an earlier-systolic ventricle (V1). The ventricular activation of V2 can be considered to “fuse” or “merge” with the ventricular activation of V1 due to the intrinsic conduction of the heart. In this way, the intrinsic and pacing-induced excitation wavefronts can fuse together, thereby resynchronizing the depolarization of V2 with the depolarization of V1. In some examples, the ventricular activation of V2 can be considered to “fuse” or “merge” with the ventricular activation of V1 when, for example, the value of LV dP / dt or other measure of contractility is greater than a corresponding threshold or when the far-field QRS width is less than a corresponding threshold.

[0046] The IMD can be configured to deliver fusion pacing pulses to V2 according to a fusion pacing interval. The fusion pacing interval specifies a delay between an atrial pacing or sensing event and the delivery of a fusion pacing pulse to V2 by the IMD. In some examples, the atrial sensing event can be a P-wave of a sensed cardiac electrical signal, and the atrial pacing event can be, for example, the time at which a stimulus is delivered to the atrium.

[0047] In some examples, the right ventricle (RV) can be V1 and the left ventricle (LV) can be V2. In other examples, the LV can be V1 and the RV can be V2. Although the first depolarizing ventricle V1 is described as the RV and the later depolarizing ventricle V2 is described as the LV with respect to some examples described herein, in any such examples, the first depolarizing ventricle V1 can be the LV and the later depolarizing ventricle V2 can be the RV.

[0048] In some fusion pacing techniques, the IMD can deliver a pacing pulse to V2 (V2 P ) at the expiration of a fusion pacing interval. The fusion pacing interval can be determined based on a sensed intrinsic depolarization of V1 (e.g., a sensed ventricular activation (V1 S) ). Ventricular activation can be indicated by, for example, an R-wave of a sensed cardiac electrical signal. Delivering V2 pacing pulses (V2 PAn example of a fusion pacing technique that multiplies the delivery of V1 with the inherent depolarization of V1 is described in the U.S. Patent entitled “Apparatus and Methods of Energy Efficient, Atrial-Based Bi-Ventriculal Fusion-Pacing”, published on February 20, 2007. U.S. Patent No. 7,181,284 to Burnes et al. is incorporated herein by reference.

[0049] In one example disclosed in U.S. Patent No. 7,181,284 to Burnes et al., in atrial pacing or sensing events (A P / S Within a predetermined time period following this, a pacing pulse (V2) is delivered to V2. P ), where the predetermined time period is essentially equal to the atrial pacing or sensing event (A P / S ) and at least one previous cardiac cycle V1 sensing event (V1 S The decreasing duration between these intervals is referred to as the duration of the pre-excitation interval (PEI). Therefore, it can be used to determine the fusion pacing interval (A). P / S –V2 P An example equation:

[0050] Equation (1)A P / S -V2 P =(A P / S -V1 S )–PEI

[0051] The cardiac cycle can include, for example, the time between the start of one heartbeat and the next, as described below. Figure 3A and Figure 3B Further discussion. Atrial pacing or sensing events (A... P / S ) and V1 sensing events (V1 SThe duration between can be, for example, a measure of the intrinsic AV conduction time from the atrium to the first contracting ventricle of the patient's heart. The PEI can indicate the amount of time for a V2 pacing pulse to precede a Vl sensed event in order to achieve fusion of the electromechanical performance of Vl and V2 (e.g., a delay in V2 activation). That is, the PEI can indicate the amount of time needed to pre-activate V2 from delivering a V2 pacing pulse such that the electromechanical performance of Vl and V2 merge into a fusion event. In some examples, the PEI is automatically determined by the medical device delivering the pacing therapy, e.g., based on a determined intrinsic conduction time, while in other examples, the PEI can be pre-determined by a clinician. In some examples, the PEI is a programmed value (e.g., about one millisecond (ms) to about 250 ms or more, such as about 100 ms to about 200 ms, or about 10 ms to about 40 ms) or an adaptive value, such as about 10% of a measured intrinsic A-V2 conduction interval or a measured intrinsic A-A cycle length.

[0052] The magnitude of the PEI can vary based on various factors, such as the heart rate of the patient, the dynamic physiological conduction state of the patient's heart, which can change based on the patient's physiological condition (e.g., ischemic state, myocardial infarction state, etc.) as well as factors related to the therapy system, such as the location of the sensing electrodes of the leads of the therapy system, the location of the pacing electrodes of the therapy system, and internal circuitry processing delays of the medical device.

[0053] In some other example techniques for determining the appropriate A-V delay by which to deliver CRT, such as those in which the A-V interval is measured directly in the absence of pacing, the appropriate A-V delay can have to account for the PEI as shown above. In contrast, to determine the appropriate A-V delay according to the techniques described herein, e.g., using the D-VCG, pacing is performed and the paced A-V delay is varied, e.g., lengthened, in a sequence to detect the onset of the intrinsic non-paced ventricular action. Detecting the onset of the intrinsic non-paced ventricular action in this way is based on an actual measured change in activation, rather than a predicted value. In this way, the techniques described herein can directly measure the timing of fusion, whether or not there is LV delay.

[0054] The techniques described herein can also be used to select an appropriate location for a pacing electrode used to deliver CRT. During example techniques that include controlling the IMD to deliver ventricular pacing to the heart according to a sequence of different values of a CRT parameter and acquiring first and second electrograms from a first electrode vector and a second electrode vector, the IMD can be controlled to deliver ventricular pacing using electrodes different from the electrodes that form the first and second electrode vectors. In some examples in which the IMD includes defibrillation capabilities, one or more of the electrodes that form the first and second electrode vectors can be defibrillation electrodes. In some examples, if a sufficient number of electrodes are available, a clinician can be able to select which electrodes to employ to perform various functions described with respect to example medical device systems (e.g., pacing, acquiring electrograms, and / or defibrillation). For example, during initial implantation of the IMD, the clinician can control the IMD to deliver ventricular pacing while moving one or more pacing electrodes to different locations. Based on the results, the clinician can select a preferred set of locations for the initial implantation of the electrodes.

[0055] In some examples, the combination of electrodes by which the IMD can deliver ventricular pacing and / or sense electrical signals can be selectable after implantation. In such examples, a clinician can select a pacing and / or sensing electrode configuration of the medical device system and input the selected pacing configuration into an external user device, such as a remote computer. In other examples, the IMD can periodically test available pacing and / or sensing electrode configurations. In such examples, the processing circuitry can control the IMD to transmit a recommended pacing and / or sensing electrode configuration to an external user device or automatically select a preferred configuration.

[0056] In some examples, the techniques described herein can enable more accurate data to be collected from a single patient, as it is not necessary in such examples to rely on average data from multiple patients to update values of CRT parameters. In such examples, the techniques described herein can enable values of CRT parameters to adapt substantially continuously to changes in patient physiological function, such as varying physical activity levels, wake / sleep, worsening or improving cardiac function, or other changes in patient physiological function.

[0057] Figure 1 and 2 Components of an example medical device system 2 for controlling an IMD 4 to deliver CRT to a heart 6 (not shown) of a patient in accordance with example techniques described herein are shown.

[0058] Figure 1is a conceptual diagram illustrating an example of a medical device system 2 including an IMD 4 and an external device 8. The medical device system 2 including the IMD 4 and the external device 8 is an example of a medical device system configured to implement the example techniques described herein to control delivery of CRT to a patient’s heart 6. In some examples, the IMD 4 can be an implantable multi-channel cardiac pacemaker, an implantable cardioverter-defibrillator (ICD), an implantable pulse generator (IPG), a leadless (e.g., intracardiac) pacemaker, an extravascular pacemaker, and / or an ICD or other IMD or combination of such IMDs configured to deliver CRT to the heart 6.

[0059] In some examples, the IMD 4 can be configured to sense electrical signals, e.g., cardiac electrograms (EGMs), corresponding to depolarization and repolarization of the heart 6 through electrodes on one or more of the leads 12, 14, and 16 or a housing of the IMD 4. Additionally or alternatively, the IMD 4 can sense electrical signals corresponding to depolarization and repolarization of the heart 6 through extravascular electrodes, e.g., electrodes positioned outside of a patient’s vasculature, such as epicardial electrodes, external surface electrodes, subcutaneous electrodes, etc. In any such examples, the configuration of electrodes used by the IMD 4 for sensing and pacing can be unipolar or bipolar. In some examples, the system 2 can determine a heart rate based on electrical signals sensed through the electrodes, e.g., to detect arrhythmias. The IMD 4 can also deliver therapy to the heart 6 in the form of electrical signals through electrodes positioned on one or more of the leads 12, 14, and 16 or a housing of the IMD 4. In the illustrated example, the IMD 4 is connected to the leads 12, 14, and 16 and can be communicatively coupled to the external device 8.

[0060] The leads 12, 14, and 16 extend into the patient’s heart 6 to sense electrical activity of the heart 6 and to deliver electrical stimulation to the heart 6. In the illustrated example, the leads 12, 14, and 16 are positioned in the right atrium, the right ventricle, and the left ventricle of the heart 6, respectively. In other examples, the leads 12, 14, and 16 can be positioned in other chambers of the heart 6 or outside of the heart 6. Figure 1In the illustrated example, RV lead 12 extends through one or more veins (not shown), the vena cava 20, the RA 22, and into the RV 24 to sense right ventricular cardiac signals and to deliver pacing or shock pulses to the RV 24. Right atrial lead 14 extends through one or more veins and the vena cava 20 and is positioned so that the distal tip of LV lead 16 is located adjacent to the RA 22 and the vena cava 20 to sense right atrial cardiac signals and to deliver pacing or shock pulses to the RA 22. LV lead 16 extends through one or more veins, the vena cava 20, the RA 22, and into the coronary sinus 26 (shown in dashed line) to a region adjacent to a free wall of the LV 28 of the heart 6. In some examples, the electrodes of lead 16 can be used in combination with the electrodes of lead 12 and / or lead 14 to deliver shocks for cardioversion and defibrillation therapy. In other examples, lead 16 can also be equipped with distal tip electrodes and ring electrodes for pacing and sensing functions in the left chambers of the heart 6.

[0061] In the illustrated example, lead 12 includes bipolar electrodes 32 and 34 that can be positioned adjacent to the distal end of lead 12. Lead 14 includes bipolar electrodes 36 and 37 that can be positioned adjacent to the distal end of lead 14. Lead 16 can be a multipolar LV lead and can include electrodes 38 and 40 as well as electrodes 42, 44, 46, and 48. In some examples, electrodes 42, 44, 46, and 48 can be positioned adjacent to the distal end of lead 16, as Figure 1 In the illustrated example, lead 12 includes bipolar electrodes 32 and 34 that can be positioned adjacent to the distal end of lead 12. Lead 14 includes bipolar electrodes 36 and 37 that can be positioned adjacent to the distal end of lead 14. Lead 16 can be a multipolar LV lead and can include electrodes 38 and 40 as well as electrodes 42, 44, 46, and 48. In some examples, electrodes 42, 44, 46, and 48 can be positioned adjacent to the distal end of lead 16, as

[0062] Electrodes 34 and / or 36 can be extendable helical tip electrodes and can be retractably mounted within respective insulating electrode heads. For example, electrode 34 can be retractably mounted within an insulating electrode head 45 positioned on lead 12, and electrode 36 can be retractably mounted within an insulating electrode head (not shown) positioned on lead 14. In some examples, one or both of leads 12 and 14 can also include one or more elongated coil electrodes, such as coil electrode 30 of lead 12 and / or coil electrode 49 of lead 14. In some examples, electrodes 30-49 of leads 12, 14, and 16 can be electrically coupled to respective conductors within the lead bodies of the corresponding ones of leads 12, 14, and 16, and thereby to circuitry within IMD 4.

[0063] In some examples, the leads 12, 14, and 16 include series connectors 50, 52, and 54, respectively. The IMD 4 can further include an IPG 56, which can include a connector block 58 and a hermetically sealed housing 60. The series connectors 50, 52, and 54 can be configured to fit into corresponding bipolar holes of the connector block 58, which can be coupled to electrically insulated conductors within the leads 12, 14, and 16, thereby connecting the electrodes 30-49 to the IPG 56.

[0064] In some examples, one or more outwardly facing portions of the housing 60 can be uninsulated, and thus can enable the housing 60 to function as a housing electrode. In some examples, substantially all of the housing 60 can be uninsulated, such that substantially all of the housing 60 defines a housing electrode. In some other examples, the housing 60 can define one or more additional housing electrodes (not shown) that can be defined by a corresponding division between insulated and uninsulated portions of the housing 60.

[0065] In some examples, the IMD 4 can be configured to bipolarly sense electrical signals corresponding to a cardiac electrogram of the heart 6 by any bipolar combination of the electrodes 30-49. In other examples, the IMD 4 can be configured to bipolarly sense electrical signals corresponding to a cardiac electrogram of the heart 6 by any one of the electrodes 30-49 in combination with the housing electrode 60. In any such examples, the IMD 4 can be configured to deliver CRT to the heart 6 by any combination of the electrodes 30-49.

[0066] In some examples, as part of delivering CRT to heart 6, IMD 4 can be configured to deliver at least one of fusion pacing or biventricular pacing to heart 6. In some examples of fusion pacing, IMD 4 can deliver pacing stimulation (e.g., pacing pulses) to LV 28 of heart 6, where the pacing stimulation is timed such that the evoked depolarization of LV 28 fuses with the intrinsic depolarization of RV 24, resulting in ventricular resynchronization. In this way, in examples where LV 28 is delayed in conduction, the pacing pulses delivered to LV 28 can pre-excite LV 28 and can help fuse the activation of LV 28 with the activation of RV 24 from intrinsic conduction. Fusion of the depolarizations of LV 28 and RV 24 can result in synchronous activation and contraction of LV 28 and RV 24. In examples described herein, a fusion pacing configuration can be referred to as“left-ventricular” pacing. However, it should be understood that in any of the described examples, a fusion pacing configuration can include right-ventricular pacing. In some examples where IMD 4 is in a biventricular pacing configuration, IMD 4 can deliver pacing stimulation (e.g., pacing pulses) to RV 24 and to LV 28 in a manner that synchronizes the activation and contraction of LV 28 and RV 24, for example, based on a selected or determined V-V delay.

[0067] In some examples where a patient has a conduction dysfunction (e.g., a dysfunction in which the natural electrical activation system of heart 6 is disrupted), CRT provided by IMD 4 can be used to maintain cardiac rhythm. The natural electrical activation system of a human heart (e.g., heart 6) involves several sequential conduction pathways that begin at the sinoatrial (SA) node and continue at the atrial level through the Bachmann's bundle and intermodal tracts, followed by the atrioventricular (AV) node, the Common Bundle of His, the left and right bundle branches, and finally distribute to distal myocardial terminals through a network of Purkinje fibers.

[0068] In a normal electrical activation sequence, the cardiac cycle begins with the generation of a depolarization wave at the SA node in the wall of the RA 22. The depolarization wave is transmitted to the left atrial septum (LA; not shown) through the atrial conduction pathways of the Bachmann's bundle and intermodal tracts at the atrial level. The atrium can contract as a result of the electrical activation when the atrial depolarization wave reaches the AV node, interatrial septum, and the most distant walls of the left and right atria. The aggregated right and left atrial depolarization waves can manifest as the P wave of the PQRST complex of the cardiac electrical signal, such as in the first and second electrograms acquired by the processing circuitry of the system 2 (e.g., of the IMD 4) from the corresponding first and second electrode vectors. For example, the processing circuitry can detect a sensed P wave when the amplitude of the atrial depolarization wave passing between a pair of unipolar or bipolar pacing / sensing electrodes positioned on or adjacent to the RA 22 and / or LA exceeds a threshold value. The sensed P wave can also be referred to as an atrial sense event or a RA sense event (RAS). A P wave sensed in the LA can be referred to as an atrial sense event or a LA sense event (LAS).

[0069] During or after the atrial contraction, the AV node distributes a depolarization wave down the bundle of His of the interventricular septum. The depolarization wave can travel to the apical region of the heart 6 and then travel on top through the Purkinje fiber network. The aggregated right and left ventricular depolarization waves and the subsequent T wave that accompanies the repolarization of the depolarized myocardium can manifest as the QRS T portion of the PQRST cardiac cycle complex. The IMD 4 can detect a sensed R wave when the amplitude of the QRS ventricular depolarization wave passing between a pair of bipolar or unipolar pacing / sensing electrodes positioned on or adjacent to the LV 28 or RV 24 exceeds a threshold value. The sensed R wave can also be referred to as a ventricular sense event, a RV sense event (RVS), or a LV sense event (LVS), depending on which ventricle the electrodes of the system 2 are sensing in a particular instance. In some instances, the sensed R wave can be a second fiducial point of the cardiac cycle that the processing circuitry of the system 2 can detect in the first and second cardiac electrograms acquired by the processing circuitry during delivery of ventricular pacing by the IMD 4.

[0070] Some patients, such as patients with congestive heart failure or cardiomyopathy, can have left ventricular dysfunction, in which the normal electrical activation sequence through the heart 6 is impaired within the LV 28. Some patients can experience intra-atrial conduction defects, such as intra-atrial conduction block, in which atrial activation is delayed due to conduction delays between the LV 28 and the RV 24. Some patients with LBBB and / or RBBB can experience intra-ventricular conduction defects, in which the impulse does not conduct in the normal manner along the respective right or left bundle branch. Ventricular dyssynchrony can result from conduction defects along the bundle of His, right or left bundle branch, and / or Purkinje terminals more distally. Typical intra-ventricular peak-to-peak dyssynchrony can be in the range of about 80 milliseconds (ms) to about 200 ms or more. However, in patients experiencing RBBB or LBBB, the QRS complex can exceed the normal range, such as about 120 ms to about 250 ms or more.

[0071] CRT delivered by the IMD 4 can help alleviate heart failure conditions (e.g., LV and / or RV dysfunction) by restoring synchronous depolarization and contraction of one or more chambers of the heart 6. In some examples, as described herein, fusion pacing or other CRT delivered to the heart (e.g., to the heart 6 by the IMD 4) can increase the stroke volume of the heart 6 by improving the synchrony of LV 28 and RV 24 depolarization and contraction. Increasing the stroke volume of the heart 6 can reduce symptoms of cardiac dysfunction experienced by the patient, can improve the patient’s prognosis, or otherwise improve the patient’s clinical outcome. However, the duration of a cardiac cycle of the heart 6 (e.g., the duration of a depolarization-repolarization sequence) can vary with changes in one or more physiological parameters of the patient, such as changes in heart rate. For example, as the patient’s heart rate changes, the timing of pacing pulses delivered by the IMD 4 to the LV 28 during fusion pacing therapy or the timing of pacing pulses delivered by the IMD 4 to the LV 28 and RV 24 during biventricular pacing therapy can need to change to adapt the CRT to the patient’s changing heart rate.

[0072] When processing circuitry determines that a physiological parameter of the patient (e.g., heart rate and / or level of physical activity) has changed, and / or when processing circuitry otherwise determines that further adjustment of the value of one or more CRT parameters can be desirable, the techniques described herein can advantageously adapt CRT to the changing needs of the patient by determining an updated value of a CRT parameter according to which IMD 4 delivers ventricular pacing, as at the expiration of the time period. Thus, despite changes in the patient’s physiological parameters and / or changes in system 2, the techniques described herein can cause IMD 4 to maintain delivery of ventricular pacing pulses at some time that result in fusion of depolarization of LV 28 and RV 24. In some examples in which processing circuitry determines an updated value of a CRT parameter (e.g., an A-V delay for fusion pacing) at a predetermined interval, processing circuitry can determine an updated value of a CRT parameter once per minute, once per hour, semi-continually, or at another predetermined interval. In some examples, processing circuitry can determine an updated value of a CRT parameter based on a detected heart rate change that satisfies a threshold value, which can be indicative of a sleep state or level of physical activity of the patient.

[0073] In any such examples, processing circuitry can determine an updated value of a CRT parameter based on an identified target value of a comparison metric associated with a relationship between: a first activation interval between occurrences of a first fiducial point of a cardiac cycle and a second fiducial point of the cardiac cycle detected in a first electrogram acquired by processing circuitry during delivery of ventricular pacing by IMD 4 according to a sequence and a second activation interval between occurrences of the first fiducial point of the cardiac cycle and the second fiducial point of the cardiac cycle detected in a second electrogram acquired by processing circuitry during delivery of ventricular pacing by IMD 4 according to a sequence of different values of the CRT parameter, as described above. For example, processing circuitry can acquire the first electrogram and the second electrogram from respective ones of a first vector formed by any bipolar combination of electrodes 30-49 and / or housing electrode 60 and a second electrode vector formed by any other bipolar combination of electrodes 30-49 and / or housing electrode 60.

[0074] The processing circuitry can then determine, for each of the different values of the CRT parameter of the sequence, a value of at least one comparison metric of the first activation interval and the second activation interval. In some examples, the at least one comparison metric can be at least one of a ratio between the first activation interval and the second activation interval (e.g., a ratio of a duration of the longer of the first activation interval and the second activation interval to a duration of the shorter of the first activation interval and the second activation interval), a time difference between the first activation interval and the second activation interval, and / or one or more other suitable metrics. The processing circuitry can then control the IMD 4 to deliver ventricular pacing at the updated value of the CRT parameter to provide CRT, as until the processing circuitry determines that it is time to determine another updated value of the CRT parameter.

[0075] Figure 1 The configuration of the medical device system 2 shown is one example configuration and is not intended to be limiting. As discussed below with reference to FIGS. 2A-2B, the configuration of the medical device system 2 can be varied in a number of ways. Figure 4 As discussed in greater detail, the housing 60 can enclose one or more accelerometers, therapy delivery circuitry, which can be configured to generate therapeutic stimulation such as cardiac pacing, cardioversion, and defibrillation pulses, and sensing circuitry configured to sense electrical signals corresponding to a patient's cardiac electrogram signals and / or a patient's activity level or activity. The housing 60 can also enclose one or more of a memory for storing default and / or permitted values of one or more therapy parameters (e.g., CRT parameters), diagnostics, feedback from a patient, and / or a therapy program that can include values of one or more CRT parameters. The housing 60 can also enclose communication circuitry configured for communication between the IMD 4 and the external device 8 and / or other devices, such as external devices located with a clinician or a server. Such components can enable the IMD 4 to perform one or more aspects of the techniques described herein, such as sending data related to a patient's physiological condition and / or one or more recommended values of one or more CRT parameters to the external device 8.

[0076] In some examples, medical device system 2A can include one or more additional sensors, such as one or more accelerometers (not shown) or temperature sensors, for example, for sensing a patient activity level. The one or more accelerometers can include one or more tri-axial accelerometers and can be a component of IMD 4 or a component of another IMD of system 2. Signals generated by such sensors can be indicative of, for example, gross body movement, such as patient posture, exertion, temperature, or activity level. Regardless of the configuration of such sensors, processing circuitry of system 2 can determine a value of one or more physiological parameters of the patient (e.g., patient posture and / or activity level), such as whether the patient’s activity level is low, medium, high, associated with a numerical value, or associated with a particular activity or other value, based on signals obtained from such sensors. In some such examples, processing circuitry can determine an updated value of a CRT parameter based on determining that the value of one or more physiological parameters of the patient has changed relative to a baseline value or other previously determined value.

[0077] Although such processing circuitry can be contained within IMD 4 and / or within another IMD or other device (e.g., external device 8) of system 2, processing circuitry can be described herein as a component of IMD 4 for the sake of clarity. Processing circuitry of IMD 4 can then use the determined patient parameter values related to posture and / or activity level to determine a default value of a therapy parameter, such as a rate at which cardiac pacing is delivered to heart 6. As described further below, IMD 4 can then deliver CRT to heart 6 according to an updated value of a CRT parameter that processing circuitry can determine based on the determined patient parameter values.

[0078] In some examples, IMD 4 can also provide defibrillation therapy and / or cardioversion therapy. For example, IMD 4 can detect an arrhythmia of heart 6, such as fibrillation of the ventricles, and deliver defibrillation therapy to heart 6 in the form of an electric shock. In some examples, IMD 4 can be programmed to deliver a progression of therapy (e.g., pulses with increasing energy levels) until fibrillation of heart 6 ceases. In examples in which IMD 4 provides defibrillation therapy and / or cardioversion therapy, IMD 4 can detect fibrillation by employing one or more suitable fibrillation detection techniques.

[0079] In other examples, instead of or in addition to Figure 1In addition to the electrodes of the illustrated leads 12, 14, and 16, the medical device system 2 can include extravascular electrodes such as subcutaneous electrodes, substernal electrodes, epicardial electrodes, and / or patch electrodes. In some other examples, a medical device configured to deliver cardiac therapy can not necessarily be implanted within a patient. In some such examples, the medical device can deliver defibrillation pulses, pacing pulses, and other therapies to the heart 6 via a percutaneous lead extending through the patient's skin to one or more locations within the heart 6 or outside the heart.

[0080] In some other examples, the medical device system 2 can include any suitable number of leads coupled to the IPG 56 and extending to any suitable location within or proximate to the heart 6. For example, the medical device system 2 can include a dual-chamber IMD instead of a triple-chamber IMD such as the IMD 4. In one example, the dual-chamber IMD can be electrically connected to a single lead that includes stimulation and sensing electrodes within the LV 28 and sensing and / or stimulation electrodes within the RA 22. In another example of a dual-chamber configuration, the IMD 4 is connected to two leads that extend into respective ones of the RA 22 and the LV 28.

[0081] Instead of or in addition to the IMD 4, the medical device system 2 can include one or more leadless (e.g., intracardiac) pacing devices (LPDs). In such examples, the one or more LPDs can include therapy delivery circuitry and processing circuitry within a housing configured for implantation on or within one of the chambers of the heart 6. In such systems, the one or more pacing devices, which can include one or more LPDs and / or an IMD coupled to one or more leads, can communicate to coordinate sensing and pacing in the various chambers of the heart 6 to provide CRT in accordance with the techniques described herein. The processing circuitry and memory of one or more of the pacing devices and / or another implanted or external medical device can provide functionality for controlling the delivery of CRT described with respect to the processing circuitry of the medical device system 2 and / or the memory of the medical device system 2.

[0082] In some examples, one or more LPDs within or adjacent to the RV 24 and / or the LV 28 can act as a slave device to provide biventricular or fusion CRT. The master device controlling the timing of pacing delivered by the one or more LPDs can be a leadless pacemaker or ICD (e.g., the IMD 4), an extravascular ICD, or an implantable cardiac monitor such as the REVEAL® or LINQ® available from Medtronic plc, of Dublin, Ireland. TM or LINQ TMThe insertable cardiac monitor. The primary device can include or be coupled to electrodes and can be configured to acquire one or more electrograms. The primary device can be configured to determine values for CRT parameters for delivery of ventricular pacing by the one or more LPDs based on electrograms acquired by processing circuitry of medical device system 2 according to techniques described herein.

[0083] External device 8 can be a computing device (e.g., for home, ambulatory, clinic, or hospital settings) to communicate with ICM 10 through wireless telemetry. External device 8 can include or be coupled to a remote patient monitoring system, such as REVEAL® XL available from Medtronic, Inc. of Dublin, Ireland. As an example, external device 8 can be a programmer, an external monitor, or a consumer device (e.g., a smart phone). In some examples, external device 8 can receive data, alerts, patient physiological information, or other information from IMD 4.

[0084] In some examples, external device 8 can be used to program commands or operational parameters into IMD 4 to control its operation (e.g., when configured as a programmer for IMD 4). External device 8 can be used to interrogate IMD 4 to retrieve accumulated data, including device operational data as well as physiological data accumulated in IMD memory. Interrogation can be automatic, such as according to a schedule or in response to a remote or local user command. Programmers, external monitors, and consumer devices are examples of external devices 18 that can be used to interrogate IMD 4. Examples of communication techniques used by IMD 4 and external device 8 include radio frequency (RF) telemetry, which can be an RF link established through Bluetooth, WiFi, or medical implant communication service (MICS). In some examples, external device 8 includes processing circuitry. The processing circuitry of external device 8 can be configured to perform any of the techniques described with respect to processing circuitry of medical device system 2, as further described herein.

[0085] Figure 2 FIG. 1 is a conceptual diagram of portions of IMD 4 coupled to heart 6 and illustrating example vectors for which electrograms can be acquired by processing circuitry of medical device system 2 during example techniques. Figure 1 FIG. 1 is a conceptual diagram of portions of IMD 4 coupled to heart 6 and illustrating example vectors for which electrograms can be acquired by processing circuitry of medical device system 2 during example techniques. Figure 2 FIG. 1 is a conceptual diagram of portions of IMD 4 coupled to heart 6 and illustrating example vectors for which electrograms can be acquired by processing circuitry of medical device system 2 during example techniques. Figure 2 As illustrated, example bipolar electrode vectors 70, 72, 74, and 76 can be formed from two or more electrodes selected from electrodes 30-49 and / or housing electrode 60 of IMD 4. In Figure 2In the example of FIG. 6, electrode vector 70 is formed between electrode 30 on lead 12 and housing electrode 60. Electrode vector 72 is formed between electrode 34 on lead 12 and the combination of electrodes 38 and 40 on lead 16. In electrode vector 72, electrodes 38 and 40 can be used in combination to form a unipolar electrode vector 72. Electrode vector 74 is formed between electrode 32 on lead 12 and electrode 42 on lead 16. Electrode vector 76 is formed between electrode 32 on lead 12 and electrode 48 on lead 16. It should be noted that, Figure 2 Electrode vectors 70-76 illustrated in FIG. 6 are example electrode vectors that can be used in the techniques described herein. In some examples, electrode vectors used in the techniques described herein can include other combinations of electrodes 30-49 and / or housing electrode 60 of IMD 4, such as combinations of electrodes 30-49 and / or housing electrode 60 of IMD 4 that are not used to deliver pacing pulses during the techniques for determining updated values of CRT parameters.

[0086] Additionally or alternatively, an electrode on any one of leads 12, 14, or 16 can be used in combination with one or more of the other electrodes on the same one of leads 12, 14, or 16 to form a unipolar electrode vector in a manner similar to electrodes 38 and 40 of electrode vector 74.

[0087] In some techniques for determining updated values of CRT parameters, processing circuitry can control IMD 4 to deliver ventricular pacing to heart 6 in a sequence of different values of CRT parameters. For example, in other examples, processing circuitry can control IMD 4 to deliver LV fusion pacing, such as by electrodes 44 and 46 on lead 16, but processing circuitry can control IMD 4 to deliver ventricular pacing according to different CRT modes and / or electrode configurations. Processing circuitry can acquire first and second electrograms, which can be unipolar or bipolar, from respective ones of first electrode vectors formed by electrodes 30-49 and / or housing electrode 60 and second electrode vectors formed by electrodes 30-49 and / or housing electrode 60 during delivery of ventricular pacing by IMD 4 according to the sequence. In some examples, the first and second electrode vectors can be Figure 2The two electrode vectors of the electrode vectors 70, 72, 74, and 76 shown in the middle and / or other electrode vectors formed by the electrodes 30-49 and / or the housing electrode 60. For example, the electrode vector 72 can be a first electrode vector and the electrode vector 76 can be a second electrode vector. In some examples, the first electrode vector and the second electrode vector can share an electrode (i.e., include a common electrode), as in the example of the electrode vectors 70 and 72 being the first electrode vector and the second electrode vector or the electrode vectors 74 and 76 being the first electrode vector and the second electrode vector. In other examples, the first electrode vector and the second electrode vector can not share any common electrodes.

[0088] The processing circuitry can obtain the first electrogram by subtracting the signal of the at least one first electrode of the first electrode vector from the signal of the at least one second electrode of the first electrode vector, and can obtain the second electrogram by subtracting the signal of the at least one first electrode of the second electrode vector from the signal of the at least one second electrode of the second electrode vector. For example, in the example technique in which the electrode vector 72 is the first electrode vector and the electrode vector 76 is the second electrode vector, the processing circuitry can obtain the first electrogram by subtracting the signal from the electrode 34 on the lead 12 from the combined signal from the electrodes 38 and 40 on the lead 16. The processing circuitry can obtain the second electrogram by subtracting the signal from the electrode 32 on the lead 12 from the signal from the electrode 48 on the lead 16.

[0089] The processing circuitry can then determine, for each of the different values of the CRT parameter, a first activation interval between the occurrence of the first fiducial point of a cardiac cycle and the second fiducial point of the cardiac cycle detected in the first electrogram and a second activation interval between the occurrence of the first fiducial point of a cardiac cycle and the second fiducial point of the cardiac cycle detected in the second electrogram and at least one comparison metric of the first activation interval and the second activation interval, such as at least one of a ratio between the first activation interval and the second activation interval (e.g., a ratio of a duration of the longer of the first activation interval and the second activation interval to a duration of the shorter of the first activation interval and the second activation interval) and / or a time difference between the first activation interval and the second activation interval. The processing circuitry can then identify a target value of the at least one comparison metric and determine an updated value of the CRT parameter based on the target value.

[0090] In any such examples, the first electrode vector and the second electrode vector can be substantially orthogonal to each other, as are electrode vectors 72 and 76. In some examples, the first electrode vector and the second electrode vector can be considered substantially orthogonal to each other when positioned as close to approximately 90 degrees relative to each other as possible based on the placement of available electrodes. In some examples, the first electrode vector and the second electrode vector can be positioned approximately 90 degrees relative to each other. However, in other examples, as in examples without electrode vectors that are approximately 90 degrees relative to each other, the first electrode vector and the second electrode vector can be considered substantially orthogonal if positioned approximately 45 degrees to approximately 90 degrees relative to each other. In some examples of the technology described herein, the use of orthogonal first and second electrode vectors can facilitate the ability to determine at least one comparison metric of a first activation interval to a second activation interval that the processing circuitry can determine is associated with a value of a CRT parameter. For example, a first electrogram and a second electrogram acquired from respective orthogonal first and second electrode vectors can better demonstrate differences between the first activation interval and the second activation interval because such first and second electrograms can better depict the cardiac cycle from two different angles than a first electrogram and a second electrogram acquired from respective first and second electrode vectors that are more similarly oriented.

[0091] A first electrogram and a second electrogram that depict the cardiac cycle from two different angles, for example, a first electrogram and a second electrogram acquired from orthogonal first and second electrode vectors, can better demonstrate differences in the rate of conduction of electrical impulses through the heart 6 that can result from the delivery of CRT according to different values of a CRT parameter. As described below with respect to Figure 3A and 3BFurther discussed, the difference in the value of the at least one comparison metric of the first activation interval and the second activation interval associated with the delivery of ventricular pacing at different values of the CRT parameter can correspond to a difference in the rate of conduction of electrical impulses through the heart (e.g., the ventricle) resulting from the delivery of ventricular pacing to the heart 6 by the IMD 4 at different values. The target value can be associated with a value of the CRT parameter at which the value of the ratio of the longer of the first activation interval and the second activation interval to the shorter of the first activation interval and the second activation interval is within a threshold distance of the value 1, and / or at which the time difference between the first activation interval and the second activation interval is at a minimum or at or below a threshold, which in instances in which the patient has a conduction dysfunction, can be a value of the CRT parameter that results in an increase (e.g., an increase) in the rate of conduction of electrical impulses through the heart 6. Thus, example techniques in which the first electrode vector and the second electrode vector are orthogonal to one another can provide an indication of the degree of ventricular synchrony that allows the processing circuitry to determine an updated value of the CRT parameter that can be related to an improvement in the conduction dysfunction of the heart 6. Delivery of ventricular pacing by the IMD 4 at a value of the CRT parameter related to an improvement in the conduction dysfunction of the heart 6 can result in an effective CRT outcome (e.g., an improvement in symptoms and / or other markers of effective CRT) for the patient.

[0092] In some instances, the first fiducial point can correspond to a time at which the IMD 4 delivers a pacing pulse to the heart 6. In other instances, the first fiducial point can be a feature of a cardiac cycle that occurs prior to the occurrence of the second fiducial point. The second fiducial point can correspond to a feature of the first electrogram and the second electrogram related to the depolarization of the heart in response to the pacing pulse, such as one of the onset of paced ventricular activation in the first electrogram and the second electrogram (e.g., the onset of activation of the LV 28 in instances in which the IMD 4 delivers LV fusion pacing), the maximum dv / dt, an R-wave detected in the first electrogram and the second electrogram, or the maximum amplitude of the first electrogram and the second electrogram. In some instances in which the second fiducial point is an R-wave, the processing circuitry can detect the occurrence of the second fiducial point in the electrogram by comparing the amplitude of the electrogram to a threshold value and detecting the occurrence of an R-wave when the amplitude of the electrogram satisfies the threshold amplitude. In other such instances, the processing circuitry can detect the occurrence of an R-wave based on the timing of the maximum amplitude of the electrogram or the occurrence of an amplitude associated with the onset of an R-wave.

[0093] In some such instances, the processing circuitry can determine the time of occurrence of the first fiducial point of the cardiac cycle as the time at which therapy delivery circuitry of the IMD 4 delivers a pacing pulse during the cardiac cycle. In other instances, as in instances where the first fiducial point does not correspond to the time at which a pacing pulse is delivered by the IMD 4, the processing circuitry can determine the time of occurrence of the first fiducial point by detecting the first fiducial point in the first and second electrograms (e.g., a feature of the cardiac cycle that occurs before the second fiducial point).

[0094] According to the techniques described herein, the processing circuitry can determine updated values of CRT parameters by determining updated A-V and / or V-V delays based on the target values. In some instances, the processing circuitry can determine both an updated A-V delay (e.g., an A-RV delay and an A-LV delay) or by determining one A-V delay and one V-V delay. Accordingly, the techniques described herein for adjusting A-V and V-V delays should be understood to encompass either approach.

[0095] The techniques described herein can be performed with an IMD 4 operating in a biventricular pacing CRT mode or a fusion pacing CRT mode. For example, during delivery of left ventricular fusion pacing by the IMD 4, the processing circuitry of the medical device system 2 (e.g., processing circuitry of the IMD 4) can determine the RA to RV conduction time, rather than controlling the conduction time through a RA-RV pacing interval, as is the case for biventricular pacing.

[0096] Figure 3A and 3B is a conceptual diagram illustrating a first activation interval INT1 between the occurrence of the first fiducial point 80 of a cardiac cycle detected in the first electrogram 84 and the second fiducial point 82 of the cardiac cycle, a second activation interval INT2 between the occurrence of the first fiducial point 80 of a cardiac cycle detected in the second electrogram 86 and the second fiducial point 82 of the cardiac cycle, and a time difference D between the occurrence of the second fiducial point of the first electrogram 84 and the occurrence of the second fiducial point of the second electrogram 86. T The cardiac cycle detected in the first electrogram 84 is illustrated as extending between point 88 and point 90 of the first electrogram 84, and the cardiac cycle detected in the second electrogram 86 is illustrated as extending between point 92 and point 94 of the second electrogram 86. Figure 3A Figure 3B The first electrogram 84 of Figure 3A and the second electrogram 86 of Figure 3B ​The illustration of the second electrogram 86 includes, along its X-axis, a time component 96 of the first electrogram 84 and the second electrogram 86 and, along its Y-axis, an amplitude component 98. The processing circuitry (e.g., of the IMD 4) can acquire the first electrogram 84 and the second electrogram 86 from respective first and second electrode vectors formed by the electrodes 30-49 and 60 of the medical device system 2. For example, the processing circuitry can acquire the first electrogram 84 and the second electrogram 86 from respective ones of the electrode vectors 72 and 76. Figure 2 The first electrogram 84 and the second electrogram 86 are acquired from respective ones of the electrode vectors 72 and 76.

[0097] The first electrogram 84 and the second electrogram 86 can be acquired by the processing circuitry during delivery of ventricular pacing by the IMD 4 according to values of the CRT parameters. In examples in which the medical device system 2 includes a single medical device (e.g., the IMD 4) that both senses cardiac electrical signals and delivers ventricular pacing, the first electrogram 84 and the second electrogram 86 can be acquired by the processing circuitry during delivery of ventricular pacing by the IMD 4 according to values of the CRT parameters. Figure 3A and 3B In examples in which the first fiducial point 80 is a paced spike of the amplitude of the electrograms 84, 86, it corresponds to delivery of a pacing pulse by the IMD 4 (e.g., to the LV 28) during a cardiac cycle according to the CRT parameters. In examples in which one medical device (e.g., an implantable cardiac monitor or an external medical device) is used to sense cardiac electrical signals according to the techniques described herein and another medical device (e.g., the IMD 4) is used to deliver ventricular pacing, the first fiducial point 80 can be a paced spike. In such examples, the processing circuitry of the medical device that senses the cardiac electrical signals can detect the paced spike based on one or more criteria (e.g., amplitude and / or rate of change) that can be expected to be greater than those of intrinsic cardiac signals and distinguish it from intrinsic cardiac electrical activity.

[0098] It should be noted that Figure 3A and 3B The illustration of the first fiducial point 80 in Figure 3A and 3B may not necessarily be shown in proportion to a paced spike as can be observed in the electrograms. In other examples, such as examples in which the IMD 4 both senses cardiac electrical signals and delivers ventricular pacing, the processing circuitry can determine the timing of the paced pulse in other ways, such as based on the time at which the processing circuitry controls the IMD 4 to deliver the paced pulse.

[0099] The second fiducial point 82 is the maximum amplitude of the R-wave detected in the electrograms 84, 86, which in this example is also the maximum amplitude of the electrograms 84, 86. INT1 and INT2 represent the time interval between the occurrence of the first fiducial point 80 and the second fiducial point 82 in the first electrogram 84 and the second electrogram 86, respectively. Because the processing circuitry can derive the electrode vector of the first electrogram 84 and the second electrogram 86 from which the electrograms 84, 86 extend in different planes (e.g., orthogonal) relative to the heart 6, the first electrogram 84 and the second electrogram 86 represent the cardiac cycle from different angles relative to the heart 6. The difference in the angle from which the electrograms 84, 86 detect the cardiac cycle is illustrated by the time difference D T between the occurrence of the second fiducial point in the first electrogram 84 and the occurrence of the second fiducial point in the second electrogram 86. In some examples, the time difference D T may be a value that the processing circuitry can determine as a comparison metric of the first activation interval and the second activation interval.

[0100] The magnitude of D T may be associated with a conduction rate of electrical impulses through the heart 6. For example, a larger value of D T may be associated with a lower conduction rate of electrical impulses through the heart 6, and a smaller value of D T may be associated with a higher conduction rate of electrical impulses through the heart 6. Thus, the occurrence of a conduction dysfunction (e.g., a conduction delay) of the heart 6 can be associated with a relatively larger value of D T . In such examples, the delivery of effective CRT to the heart 6 can be reduced by increasing the conduction rate can be associated with a relatively smaller value of D T . In some such examples, the D T associated with the increased conduction rate can be a target value of D T that is equal to or less than a threshold value or other value of D T that is a minimum value relative to other values of D T that result from the delivery of CRT according to other values of the CRT parameter. In some examples, such an increased conduction rate can correspond to a fusion occurring between left ventricular activation and right ventricular activation, which can provide hemodynamic benefits to the patient.

[0101] During the techniques of determining an updated value of the CRT parameter, as Figure 3A and 3BAs illustrated in the example of FIG. 8, processing circuitry can control IMD 4 to deliver ventricular pacing according to a sequence of different values of CRT parameter, and acquire first electrogram 84 and second electrogram 86 during delivery of ventricular pacing by IMD 4. For each of the different values of CRT parameter, processing circuitry can determine INT1 occurring between first fiducial point 80 and second fiducial point 82 in first electrogram 84, and determine INT2 occurring between first fiducial point 80 and second fiducial point 82 in second electrogram 86.

[0102] As described above, in some examples, processing circuitry can determine INT1 and INT2 by detecting both first fiducial point 80 and second fiducial point 82 of the respective electrograms in first electrogram 84 and second electrogram 86. However, in other examples, processing circuitry determines the time of occurrence of first fiducial point 80 based on the time of delivery of a pacing pulse by IMD 4 to heart 6, rather than detecting first fiducial point 80 in first electrogram 84 and second electrogram 86. For example, the time of delivery of a pacing pulse by IMD 4 can be “known” to timing and / or control aspects of processing circuitry. Thus, determining the time of occurrence of first fiducial point 80 does not necessarily depend on signal detection from the electrode vector and analysis of first electrogram 84 and / or second electrogram 86, which can simplify and / or improve the accuracy of determination of INT1 and INT2 by processing circuitry in some examples.

[0103] Processing circuitry can then determine D T for each value of the sequence of different values of delivery of ventricular pacing by IMD 4. T For example, processing circuitry can determine the value of D T by subtracting INT1 from INT2. Processing circuitry can then identify a target value of D T such as by determining a minimum value of D T (e.g., a minimum value of D T in the determined values of D T equal to or less than a threshold value of D T .

[0104] In other examples, in addition to or instead of determining a target value of D T , processing circuitry can determine a target value of D Ttarget value of at least one other comparison metric of the first activation interval and the second activation interval, such as a ratio of the greater of INT1 and INT2 to the lesser of INT1 and INT2 for each value of the CRT parameter of the sequence, and determine a target value of the ratio. The value of the CRT parameter associated with the ratio of INT1 to INT2 can be associated with an increase in the conduction rate of the heart 6 that is closer to 1 : 1 (i.e., a value of 1) than other values of the CRT parameter. Thus, the processing circuitry can identify the target value of the ratio of INT1 to INT2 by determining that the ratio of INT1 to INT2 is closest to a value of 1 or a value that is within a threshold distance from a value of 1 or by determining that the ratio of INT1 to INT2 is a minimum value relative to other values of the ratio of INT1 to INT2 that result from delivery of CRT according to the other values of the CRT parameter. T the ratio of INT1 to INT2 that results from delivery of CRT according to the other values of the CRT parameter.

[0105] In any such examples, the processing circuitry can determine an updated value of the CRT parameter based on the identified target value of D T and / or the identified target value of the ratio of INT1 to INT2. For example, the processing circuitry can determine the updated value of the CRT parameter to be a value of the CRT parameter that results in the target value of D T and / or the target value of the ratio of INT1 to INT2. The processing circuitry can then control the IMD 4 to deliver ventricular pacing at the updated value of the CRT parameter to deliver CRT. For example, in examples where the CRT parameter is the A-LV delay, the processing circuitry can control the IMD 4 to deliver LV fusion pacing at a value of the A-LV delay that results in the target value of D T and / or the target value of the ratio of INT1 to INT2.

[0106] Figure 4 is a functional block diagram illustrating an example configuration of the IMD 4. As Figure 4As shown, IMD 4 includes processing circuitry 102, sensing circuitry 104, therapy delivery circuitry 106, sensors 108, communication circuitry 110, and memory 112. In addition, IMD 4 includes one or more electrodes 116, which can be any one or more of the previously described electrodes of IMD 4, and which one or more electrodes can be disposed on or within a housing of IMD 4 or carried by one or more lead wires 12, 14, and / or 16 connected to IMD 4. In some examples, memory 112 includes computer-readable instructions that, when executed by processing circuitry 102, cause IMD 4 and processing circuitry 102 to perform various functions attributed to IMD 4 and processing circuitry 102 herein. Memory 112 can include any volatile, nonvolatile, magnetic, optical, or electrical media, such as a random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other digital media.

[0107] Processing circuitry 102 can include fixed function circuitry and / or programmable processing circuitry. Processing circuitry 102 can include any one or more of a microprocessor, a controller, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or equivalent discrete or analog logic circuitry. In some examples, processing circuitry 102 can include multiple components, such as any combination of one or more microprocessors, one or more controllers, one or more DSPs, one or more ASICs, or one or more FPGAs, as well as other discrete or integrated logic circuitry. The functions attributed to processing circuitry 102 herein can be embodied as software, firmware, hardware or any combination thereof.

[0108] In some examples, processing circuitry 102 can monitor the passage of time to determine when a period of time has elapsed, such as a period of time during which IMD 4 can deliver cardiac pacing according to initial values for CRT parameters, patient-specific values for CRT parameters previously determined by processing circuitry 102, or values for CRT parameters requested by a user. As Figure 4As shown, memory 112 can include one or more of CRT parameter values 118, metrics 120, and / or diagnostic / feedback data 122. In some examples, CRT parameter values 118 can include updated values of a CRT parameter that processing circuitry 102 can control IMD 4 to deliver ventricular pacing with. CRT parameter values can include a plurality of other different values of a CRT parameter, such as a sequence of different values of a CRT parameter that processing circuitry 102 can control IMD 4 to deliver ventricular pacing with during a technique to determine a patient-specific updated value of the CRT parameter. CRT parameter values can be one or more values of one or more corresponding CRT parameters, such as one or more values of an A-V delay or a V-V delay.

[0109] Metrics 120 can include values associated with a relationship between a first activation interval and a second activation interval corresponding to one or more values of one or more CRT parameters. For example, metrics 120 can include values of a first activation interval and a second activation interval that processing circuitry 102 can determine for different values of one or more CRT parameters, values of a ratio of a first activation interval to a second activation interval associated with different values of one or more CRT parameters, and / or values of a time difference between a first activation interval and a second activation interval associated with different values of one or more CRT parameters (e.g., D T values).

[0110] As described above, in some examples, processing circuitry 102 of IMD 4 can be configured to determine an updated value of a CRT parameter when it is determined that a period of time has passed, a physiological parameter of a patient has changed, and / or otherwise determine that an adjustment of a value of a CRT parameter can be desirable. Processing circuitry 102 can determine an updated value of a CRT parameter according to example techniques described herein and store the updated value in CRT parameter values 118. For example, processing circuitry 102 can control IMD 4 to deliver CRT according to a sequence of different values of a CRT parameter in CRT parameter values 118, acquire a first electrogram and a second electrogram, determine a value of a first activation interval, a second activation interval, and a comparison metric for each of the sequence of CRT parameter values 118, identify a target value of the comparison metric, and determine an updated value of the CRT parameter based on the target value.

[0111] In some examples, processing circuitry 102 can store the determined target values in metrics 120. For example, processing circuitry 102 can store at least one corresponding value of the comparison metric of the first activation interval to the second activation interval determined by processing circuitry 102 in association with one or more of the CRT parameter values 118. In some examples, processing circuitry 102 can also be configured to determine one or more values of one or more corresponding physiological parameters of the patient during delivery of CRT by IMD 4 as a function of the values of the CRT parameter, and store the one or more values of the corresponding physiological parameters in metrics 120 in association with at least the corresponding values of the comparison metric determined by processing circuitry 102 as a function of the values of the CRT parameter during delivery of CRT by IMD 4.

[0112] In some such examples, processing circuitry 102 can determine an updated value of the CRT parameter during delivery of CRT by IMD 4 as a function of the values of the CRT parameter as based on expiration of a time period, one or more of the metrics 120 stored in memory 112 in association with one or more values of one or more corresponding physiological parameters of the patient. For example, if a relatively short time period elapses between one or more previous determinations of updated values of the CRT parameter by processing circuitry 102 and a determination by processing circuitry 102 to again update the values of the CRT parameter, the relationship between one or more values of the physiological parameters of the patient, one or more of the activation interval ratios or time differences 120, and the particular value of the CRT parameter can remain substantially unchanged. In such examples, it can not be necessary to re-determine at least one of the ratio of the first activation interval to the second activation interval and / or the time difference therebetween for the particular value of the CRT parameter for the time. Thus, in some such examples, processing circuitry 102 can select an updated value of the CRT parameter from the CRT parameter values 118 based on one or more determined current values of one or more corresponding physiological parameters of the patient without having to control IMD 4 to deliver CRT according to a sequence of different values of the CRT parameter, which can improve the operational efficiency of medical device system 2. In some such examples, processing circuitry 102 can determine a new relationship between one or more of the values of the one or more physiological parameters of the patient, the activation interval ratios or time differences 120, and the values of the CRT parameter 118, and store such new relationship in memory 112, such as periodically or based on a request received from a remote computer.

[0113] In some examples, processing circuitry 102 can send data to a remote computer, such as data related to changes in patient physiological parameters and / or one or more updated values of one or more corresponding CRT parameters 118 determined by processing circuitry 102 according to the techniques described herein. For example, processing circuitry 102 can send data related to one or more aspects of patient cardiac function determined by processing circuitry 102 at different levels of patient physical activity, which can help a clinician determine whether changes in patient disease state have occurred and / or whether CRT delivered by IMD 4 is still an appropriate therapy for the patient.

[0114] Sensing circuitry 104 and therapy delivery circuitry 106 can be selectively coupled to electrodes 116, for example, through switching circuitry (not shown) controlled as by processing circuitry 102. The switching circuitry can include one or more transistors or other circuitry for selectively coupling electrodes 116 to IMD 4. Sensing circuitry 104 can monitor signals from electrodes 116 in order to monitor electrical activity of the heart (e.g., to detect depolarizations for heart rate determination and / or to generate electrograms for determining CRT parameter updated values). Sensing circuitry 104 can also monitor signals from one or more other sensors 108, for example, to determine a patient’s activity level or activity. In some examples, sensors 108 can be one or more accelerometers (e.g., one or more three-axis accelerometers), one or more temperature sensors, or one or more other sensors configured to sense a patient’s physical parameter. Signals generated by such sensors can be indicative of a patient’s physical parameter, such as overall body motion, posture, exertion, temperature, activity level, or other physical parameter. Sensing circuitry 104 can monitor signals from electrodes 116 and sensors 108. In some examples, sensing circuitry 104 can include one or more filters and amplifiers for filtering and amplifying signals received from one or more of electrodes 116 and / or one or more of sensors 108. Sensing circuitry 104 can also include rectification circuitry, sample-and-hold circuitry, one or more comparators, and / or analog-to-digital conversion circuitry. The functions provided by this circuitry can be applied to signals in the analog or digital domain.

[0115] Based on the signal or indication or value determined from the signal received from sensing circuitry 104, processing circuitry 102 can determine a current value of one or more physiological parameters of the patient. For example, processing circuitry can determine one or more of a heart rate, an awake / sleep state, or an activity level of the patient as responsive to determining that a period of time has elapsed. In some examples, processing circuitry 102 can determine an activity level or activity of the patient based on a signal received from sensing circuitry 104 that can be indicative of one or more physiological parameters, such as a signal received from one or more accelerometers that is indicative of movement. In some examples, processing circuitry 102 can additionally determine an activity level or activity of the patient based on a transthoracic impedance signal received from sensing circuitry 104 that can be indicative of respiration (e.g., indicative of a magnitude or depth and / or rate of respiration of the patient).

[0116] In some examples, processing circuitry 102 can determine whether to determine an updated value of a CRT parameter based on the current value of one or more physiological parameters of the patient. For example, processing circuitry 102 can compare the current value of a physiological parameter of the patient to a previously determined value or baseline value of the physiological parameter. If a difference between the current value of the physiological parameter and the previously determined value or baseline value of the physiological parameter satisfies a threshold difference, processing circuitry 102 can determine an updated value of a CRT parameter according to the techniques described herein and control IMD 4 to deliver CRT to heart 6 at the updated value of the CRT parameter. In this way, processing circuitry enables medical device system 2 to adapt one or more values of a CRT parameter at which IMD 4 delivers CRT to changes in a physiological parameter of the patient.

[0117] Therapy delivery circuitry 106 can include circuitry for generating signals (such as one or more capacitors, charge pumps, and / or current sources) and circuitry for selectively coupling the signals with electrodes 116 (e.g., transistors or other switching circuitry). In some examples, therapy delivery circuitry 106 can include a timer for determining that a period of time corresponding to an A-V or V-V delay at which IMD 4 delivers CRT has elapsed since delivery of a preceding beat-by-beat pulse or intrinsic depolarization. Upon determining that this period of time has elapsed, processing circuitry 102 can control therapy delivery circuitry 106 to deliver a pacing pulse at a value of a CRT parameter. For example, processing circuitry 102 can generate a trigger signal that triggers output of a pacing pulse by therapy delivery circuitry 106.

[0118] Communication circuitry 110 can include any suitable hardware, firmware, software, or any combination thereof for communicating with another device, such as external device 8, or another IMD or sensor. For example, communication circuitry 110 can include voltage regulators, current generators, oscillators or circuitry for generating signals, resistors, capacitors, inductors, and other filtering circuitry for processing received signals, and circuitry for modulating and / or demodulating signals according to a communication protocol. Communication circuitry 110 can also include transistors or other switching circuitry for selectively coupling transmitted signals to or receiving signals from antennas (not shown) or electrodes 116 of IMD 4. Under the control of processing circuitry 102, communication circuitry 110 can receive downlink telemetry from and send uplink telemetry to external device 8 or another device. In some examples, communication circuitry 110 can communicate with external device 8. In addition, communication circuitry 110 can communicate with networked computing devices through an external device, e.g., external device 8, and a computer network, such as the Medtronic CareLink® Network by Medtronic, Inc., of Dublin, Ireland, as further described below with respect to networking. Figure 5

[0119] An external device 8 can be used by a patient, clinician, or another user, or by using another local or networked computing device configured to communicate with processing circuitry 102 through communication circuitry 110, to retrieve data from IMD 4. In some examples, a clinician can also program parameters of IMD 4 using external device 8 or another local or networked computing device. Diagnostics / feedback 122 of memory 112 can store data related to patient physiological parameters and / or efficacy of CRT delivered by IMD 4. For example, diagnostics / feedback 122 can store efficacy determinations associated with delivery of CRT by IMD 4 at one or more values of one or more corresponding CRT parameters.

[0120] ​In some such examples, diagnostics / feedback 122 can store efficacy determinations based on indications of efficacy of CRT entered by the patient into external device 8 and received by IMD 4. Diagnostics / feedback 122 can also store efficacy determinations made by processing circuitry 102 based on data related to symptoms or undesired effects experienced by the patient before, during, and / or after IMD 4 delivers CRT. In some examples, diagnostics / feedback 122 can store system diagnostics related to the functioning of IMD 4 or other components of the medical device system that includes IMD 4. In any such examples, communication circuitry can transmit data related to patient physiological parameters and / or efficacy of CRT to a remote computer, such as a remote computer located with a clinician.

[0121] Although the above describes processing circuitry 102 of IMD 4 as being configured to control IMD 4 to deliver ventricular pacing according to a sequence of different values of a CRT parameter, acquire first and second electrograms from respective first and second electrode vectors formed by a plurality of electrodes of medical device system 2, determine updated values of the CRT parameter, control IMD 4 to deliver ventricular pacing at the updated values of the CRT parameter, and perform other steps of the techniques described herein, any of the steps described herein as being performed by processing circuitry 102 of IMD 4 can be performed by processing circuitry of one or more other devices. For example, processing circuitry of external device 8, a remote computer, or any other suitable implantable or external device or server can be configured to perform one or more of the steps of the techniques described herein, such as by communication circuitry 110 of IMD 4.

[0122] Figure 5 is a functional block diagram illustrating an example system including access point 140, network 142, an external computing device such as server 144 which can include memory 146 and / or processing circuitry 148, and one or more other computing devices 150A-150N which can be coupled with IMD 4 and external device 8 through network 142. In this example, IMD 4 can communicate with external device 8 through a first wireless connection using communication circuitry 110, and with access point 140 through a second wireless connection. In this example, external device 8 can communicate with server 144 through a third wireless connection, and server 144 can communicate with computing devices 150A-150N through network 142. Figure 5 In the example of FIG. 1, access point 140, external device 8, server 144, and computing devices 150A-150N are interconnected and can communicate with each other through network 142.

[0123] The access point 140 can include a device that connects to the network 142 through any of a variety of connections, such as a telephone dial-up, digital subscriber line (DSL), or cable modem, or other suitable connections. In other instances, the access point 140 can be coupled with the network 142 through different forms of connections, including wired or wireless connections. In some instances, the access point 140 can be a user device, such as a tablet or smartphone, that can be co-located with the patient. As discussed above, the IMD 4 can be configured to transmit data, such as current values and heart failure status, to the external device 8. Additionally, the access point 140 can interrogate the IMD 4, such as periodically or in response to a command from the patient, clinician, or network 142, in order to retrieve data related to one or more of patient symptoms, undesirable effects, efficacy indications, CRT parameter values 118, metrics 120, diagnostics / feedback 122, or other information stored in the memory 112 of the IMD 4. The access point 140 can then communicate the retrieved data to the server 144 through the network 142.

[0124] In some cases, the memory 146 of the server 144 can be configured to provide a secure storage site for data collected from the IMD 4 and / or external device 8. In some cases, the server 144 can assemble the data in a web page or other document for viewing by a trained professional, such as a clinician, through a computing device 150A-150N. The general network technology and functionality can be implemented with commonly available network technology and functionality, such as the Medtronic CareLink® Network Figure 5 One or more aspects of the illustrated system, the general network technology and functionality can include or be similar to the Medtronic CareLink® Network Hub provided by Medtronic, Inc. of Dublin, Ireland. In some instances, such network technology and functionality can enhance the security of communications transmitted between components of the Figure 5 In some instances, such network technology and functionality can enhance the security of communications transmitted between components of the

[0125] ​In some examples, one or more of the computing devices 150A-150N (e.g., device 150A) can be a remote computer, such as a smartphone, tablet, or other smart device positioned with a clinician, through which the clinician can program, receive alerts from, and / or interrogate IMD 4. For example, the clinician can access data related to patient physiological parameters, updated values of CRT parameters, efficacy of delivered CRT, or other data through device 150A, such as when the patient is between office visits with the clinician, such as to check one or more aspects of CRT delivered by IMD 4, as desired. In some examples, the clinician can enter medical instructions for the patient into an application in device 150A based on data retrieved by device 150A from IMD 4 or based on other patient data known to the clinician, such as instructions for the patient to schedule a visit to the clinician or for the patient to seek other medical care. Device 150A can then send instructions for medical intervention to external device 8, which can help improve clinical outcomes for the patient, such as by helping enable the patient to seek timely medical intervention.

[0126] Figure 6 is a flowchart illustrating example techniques for updating CRT parameters and controlling IMD 4 to deliver CRT to heart 6 in accordance with the updated CRT parameters. The CRT parameters can be, for example, A-V delays or V-V delays. According to Figure 6 In examples, IMD 4 can deliver CRT (e.g., ventricular pacing) to heart 6 in accordance with current values of CRT parameters (160). In some examples, one or more current values of the CRT parameters can be initial values through which IMD 4 can deliver CRT to heart 6 as part of a startup phase after IMD 4 is implanted in the patient, such as until a user prompts IMD 4 to begin automatically updating values of the CRT parameters or until an initial post-implantation time period has elapsed. In other examples, the one or more current values of the one or more CRT parameters can be one or more values determined by processing circuitry 102 during a previous iteration of the techniques of Figure 6 Although one or more steps of the example techniques illustrated in the flowcharts of Figure 6 and 7 may be described as being performed by processing circuitry 102 of IMD 4, it should be noted that such steps can alternatively be performed by other processing circuitry, such as processing circuitry of external device 8.

[0127] During delivery of CRT to heart 6 by IMD 4 according to the current values of the CRT parameters, processing circuitry 102 can determine whether to update the CRT parameters (162). In some examples, processing circuitry 102 can determine whether to update the CRT parameters by determining whether a time period has elapsed. In some examples, the time period can be on the order of minutes, hours, or days. In other examples, the time period can be shorter, such as several times per minute or approximately once per cardiac cycle, in order to update the CRT parameters on a near-continuous or pseudo-continuous basis. In other examples, processing circuitry 102 can determine whether to update the CRT parameters by determining whether a change in a physiological parameter of the patient (e.g., heart rate and / or physical activity level) has occurred or by determining whether an update to the CRT parameters can otherwise be desired. In any such examples, if processing circuitry 102 determines that the time period has not elapsed, that a change in the physiological parameter of the patient has not occurred, and / or that an update to the CRT parameters is otherwise not desired (‘No’ at 162), processing circuitry 102 can continue to control IMD 4 to deliver CRT to heart 6 at the current values of the one or more CRT parameters (160).

[0128] If processing circuitry 102 determines that the time period has elapsed, that a change in the physiological parameter of the patient has occurred, and / or that an update to the CRT parameters is otherwise desired (‘Yes’ at 162), processing circuitry 102 can then control IMD 4 to deliver CRT to heart 6 according to a sequence of different values of the CRT parameters (164). For example, processing circuitry 102 can control IMD 4 to deliver CRT according to a sequence of different values of A-V delay. During delivery of CRT to heart 6 by IMD according to the sequence of different values of the CRT parameters, processing circuitry 102 can acquire a first electrogram (e.g., ‘EGM1’) and a second electrogram (e.g., ‘EGM2’) from respective ones of a first vector formed by a plurality of electrodes of medical system 2 and a second vector formed by the plurality of electrodes of medical system 2. For example, processing circuitry 102 can acquire the first electrogram and the second electrogram from respective ones of the first electrode vector and the second electrode vector (e.g., the first electrode vector and the second electrode vector of electrode vectors 70, 72, 74, and 76 shown in FIG. 7A), and the first electrogram and the second electrogram (e.g., electrograms 80 and 82 shown in FIG. 7B). Figure 2 Figure 3A 3B

[0129] ​​​Next, processing circuitry 102 can identify a target value for at least one comparison metric of the first activation interval and the second activation interval (166). In some instances, the processing circuitry can determine, for each of the different values of the CRT parameter of the sequence, a first activation interval between a first fiducial point of a cardiac cycle detected in the first electrogram and an occurrence of a second fiducial point of a cardiac cycle and a second activation interval between the first fiducial point of the cardiac cycle detected in the second electrogram and the occurrence of the second fiducial point of the cardiac cycle.

[0130] As discussed above, the occurrence of the first fiducial point can occur as a pacing spike in the first electrogram and the second electrogram. In some other instances, the processing circuitry can determine the timing of a pacing pulse, e.g., based on a time at which the processing circuitry controls the IMD to deliver the pacing pulse. In some instances, the second fiducial point can correspond to a feature of the first electrogram and the second electrogram related to a depolarization of the heart in response to a pacing pulse delivered by the IMD 4, such as a start of a paced ventricular activation, a maximum dv / dt, an R-wave detected in the first electrogram and the second electrogram, or a maximum amplitude of the first electrogram and the second electrogram. In some instances in which the comparison metric is at least one of a ratio of the first activation interval to the second activation interval and a time difference between the first activation interval and the second activation interval, the target value for the comparison metric can be a minimum value of the time difference (or a ratio value closest to 1) or a value of the time difference that is equal to or less than a threshold value (or a value of the ratio that is within a threshold distance from the value of 1).

[0131] In any such instances, the target value can correspond to a desired outcome of the CRT delivered by the IMD 4, such as fusion occurring between left ventricular activation and right ventricular activation. Thus, the processing circuitry 102 can then determine an updated value for the CRT parameter based on the value of the CRT parameter associated with the identified target value for the comparison metric (170). The processing circuitry 102 can then control the IMD 4 to deliver the CRT to the heart 6 with the updated value of the CRT parameter to provide CRT to the patient (172). Upon delivery of the CRT to the heart 6 by the IMD 4 with the updated value of the CRT parameter, the updated value of the CRT parameter can be considered a new current value of the CRT parameter (160). The techniques of FIG. 1 can then be repeated, where the processing circuitry 102 controls the IMD 4 to deliver the CRT to the heart 6 according to the new current value of the CRT parameter until the processing circuitry 102 again determines to update the CRT parameter. Figure 6

[0132] Figure 7 ​is a flowchart illustrating example techniques for updating an A-LV delay and controlling an implantable medical device to deliver CRT to a heart 6 in accordance with the updated A-LV delay. According to Figure 7 In some examples, the processing circuitry 102 can adjust the pacing A-LV delay relative to an initial A-LV delay at which the IMD 4 can be programmed to deliver ventricular pacing. In other examples, the processing circuitry 102 can adjust the pacing A-LV delay relative to an updated A-LV delay determined by the processing circuitry 102 during a previous iteration of the techniques of Figure 7 In some examples, the processing circuitry 102 can adjust the pacing A-LV delay relative to an initial A-LV delay at which the IMD 4 can be programmed to deliver ventricular pacing. In other examples, the processing circuitry 102 can adjust the pacing A-LV delay relative to an updated A-LV delay determined by the processing circuitry 102 during a previous iteration of the techniques of

[0133] During delivery of CRT to the heart 6 by the IMD in accordance with the adjusted pacing A-LV delay, the processing circuitry 102 can acquire a first electrogram (e.g., “EGM1”) and a second electrogram (e.g., “EGM2”) from respective ones of a first vector formed by a plurality of electrodes of the medical system 2 and a second vector formed by the plurality of electrodes of the medical system 2 (182). For example, the processing circuitry 102 can acquire the first electrogram and the second electrogram from respective ones of the first and second electrode vectors (e.g., the first and second electrode vectors of the electrode vectors 70, 72, 74, and 76 illustrated in Figure 2 the first and second electrode vectors of the electrode vectors 70, 72, 74, and 76 illustrated in Figure 3A and 3B the first and second electrode vectors of the electrode vectors 70, 72, 74, and 76 illustrated in

[0134] Next, processing circuitry 102 can determine a first activation interval between a first fiducial point of a cardiac cycle detected in the first electrogram and an occurrence of a second fiducial point of the cardiac cycle and a second activation interval between the first fiducial point of the cardiac cycle detected in the second electrogram and the occurrence of the second fiducial point of the cardiac cycle (184). In some examples, the first fiducial point can correspond to a time at which IMD 4 delivers a pacing pulse during a cardiac cycle. In some examples, the second fiducial point can correspond to a feature of the first and second electrograms related to depolarization of the heart in response to the pacing pulse, such as one of a start of paced ventricular activation in EGM 1 and EGM 2, one of a start of paced ventricular activation in EGM 1 and EGM 2, a maximum dv / dt, an R-wave detected in EGM 1 and EGM 2, or a maximum amplitude of EGM 1 and EGM 2. In some examples in which the comparison metric is at least one of a ratio of the first activation interval to the second activation interval and / or a time difference between the first activation interval and the second activation interval, the target value of the comparison metric can be a minimum value of the time difference (or a ratio value closest to 1) or a value of the time difference equal to or less than a threshold value (or a ratio value within a threshold distance from the value of 1).

[0135] Next, processing circuitry 102 can determine a value of at least one comparison metric of the first activation interval to the second activation interval (186) and determine whether the value of the at least one comparison metric is a target value of the at least one comparison metric (188). In any such examples, the target value can correspond to a desired outcome of CRT delivery to heart 6 by IMD 4, such as fusion occurring between left ventricular activation and right ventricular activation.

[0136] If processing circuitry 102 determines that the value of the at least one comparison metric is not the target value (NO at 188), processing circuitry 102 can adjust the pacing A-LV delay and control IMD 4 to deliver CRT to heart 6 according to the new adjusted pacing A-LV delay (180). If processing circuitry 102 determines that the value of the at least one comparison metric is the target value (YES at 188), processing circuitry 102 can then determine an updated A-LV delay for controlling IMD 4 to deliver CRT to heart 6 (190). For example, the updated A-LV delay can be the adjusted pacing A-LV delay at (180) at which IMD 4 is to deliver CRT to heart 6.

[0137] The processing circuitry 102 can then control the IMD 4 to deliver CRT to the heart 6 with the updated A-LV delay to provide CRT (192). The processing circuitry 102 can control the IMD 4 to deliver CRT to the heart 6 with the updated A-LV delay to provide CRT until a determined period of time has passed, a physiological parameter of the patient has changed, and / or it is otherwise determined that it is desirable to again update the A-LV delay. The techniques of Figure 7 may then be repeated, where the processing circuitry 102 again adjusts the A-LV delay and controls the IMD 4 to deliver CRT to the heart 6 according to the newly adjusted paced A-LV delay (180).

[0138] In this way, Figure 6 example techniques of Figure 7 example techniques of Figure 6 may improve acute hemodynamic benefits of CRT and / or can improve short-term clinical response. In some examples, such improvements in hemodynamic benefits and / or short-term clinical response can improve symptoms experienced by the patient, such as examples where the patient would not otherwise have obtained significant clinical benefit from CRT.

[0139] Various aspects of these techniques can be implemented within one or more processors, including one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components, embodied in programmers, such as physician or patient programmers, electrical stimulators, or other devices. The term “processor” or “processing circuitry” can generally refer to any of the foregoing circuitry, alone or in combination, or any other equivalent circuitry.

[0140] In one or more examples, the functions described in this disclosure can be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions can be stored as one or more instructions or code on a computer-readable medium and executed by a hardware-based processing unit. Computer-readable media can include computer-readable storage media forming a tangible, non-transitory medium. Instructions can be executed by one or more processors, such as one or more DSPs, ASICs, FPGAs, general purpose microprocessors, or other equivalent integrated or discrete logic circuitry. Accordingly, the terms "processor" or "processing circuitry," as used herein can refer to one or more of any of the foregoing structures or any other structure suitable for implementation of the techniques described herein.

[0141] Additionally, in some aspects, the functions described herein can be implemented in software and / or hardware. The terms "module" or "programming module" as used herein refer to any type of software, firmware, or combination thereof, and / or any type of hardware, whether integrated or discrete. The different aspects described herein can be implemented alone or in any combination with one another. It should also be noted that many of the methods described herein can include more steps than those expressly described above. Additionally, those steps can be performed in any order, unless otherwise expressly stated in the steps or steps are expressly stated to be conditional on other steps being performed first.

[0142] Additionally, the functions and techniques described in this disclosure can be provided by a medical device system that includes multiple IMDs. In some such examples, an IMD that can be controlled by processing circuitry to deliver ventricular pacing can not include a sensing electrode by which electrograms are acquired. For example, some such medical device systems can include a leaded IMD that includes one or more intravascular leads, or an extravascular ICD can include electrodes that form first and second electrode vectors in combination with an LPD that is configured to be placed on or within the left ventricle and deliver ventricular pacing thereto.

[0143] In some such examples, processing circuitry of the medical device system (e.g., of a leaded IMD or extravascular IMD) can control the LPD to deliver ventricular pacing at a series of A-LV delays. The leaded IMD or extravascular IMD can detect the pacing pulses delivered by the LPD and resulting ventricular activation in the electrodes acquired by the processing circuitry from the first and second electrode vectors. The processing circuitry can then determine updated values of CRT parameters according to the techniques described herein and control the LPD to deliver LV pacing at the updated values of the CRT parameters to provide CRT.

[0144] Various aspects of the disclosure have been described. These and other aspects are within the scope of the following claims.

Claims

1. A system for controlling delivery of cardiac resynchronization therapy, CRT, to a patient, the system comprising: a plurality of electrodes; an implantable medical device configured to deliver ventricular pacing to the patient; sensing circuitry configured to sense electrical activity of a heart through the plurality of electrodes; and processing circuitry configured to: control the implantable medical device to deliver ventricular pacing according to a sequence of different values of a CRT parameter; acquire, by the sensing circuitry and during delivery of ventricular pacing according to the sequence, a first electrogram from a respective one of a first vector formed by the plurality of electrodes and a second vector formed by the plurality of electrodes; determine, for each of the different values of the CRT parameter, a first activation interval between a first fiducial point of a cardiac cycle detected in the first electrogram and an occurrence of a second fiducial point of the cardiac cycle and a second activation interval between the first fiducial point of the cardiac cycle detected in the second electrogram and the occurrence of the second fiducial point of the cardiac cycle; determine, for each of the different values of the CRT parameter, a value of a comparison metric of the first activation interval and the second activation interval, wherein the comparison metric comprises at least one of a ratio of the first activation interval and the second activation interval and a time difference between the first activation interval and the second activation interval; determine an updated value of the CRT parameter using the comparison metric; and control the implantable medical device to deliver the ventricular pacing at the updated value of the CRT parameter.

2. The system of claim 1, wherein the processing circuitry is configured to determine the updated value of the CRT parameter based on a comparison of the comparison metric to a defined target value.

3. The system of claim 2, wherein processing circuitry is configured to determine which of the different values of the CRT parameter is closest to the target value and select the value of the CRT parameter that is closest to the target value as the updated value of the CRT parameter.

4. The system of claim 2, wherein the target value corresponds to fusion occurring between left ventricular activation and right ventricular activation.

5. The system of claim 3, wherein the time difference is a time difference between the occurrence of the second fiducial point of the cardiac cycle detected in the first electrogram and an occurrence of the second fiducial point of the cardiac cycle detected in the second electrogram, and wherein the processing circuitry is further configured to identify the target value of the comparison metric by identifying a minimum value of the time difference.

6. The system of claim 3, wherein the target value comprises one of a minimum value of the time difference or a value of the ratio that is closest to a value of 1.

7. The system of claim 3, wherein the target value comprises one of a value of at least one of the ratio or the time difference that is equal to or less than a threshold value or a value of the ratio that is within a threshold distance from a value of 1.

8. The system of claim 1, wherein the CRT parameter is an A-V delay.

9. The system of claim 1, wherein the CRT parameter is a V-V delay.

10. The system of claim 1, wherein the CRT parameter comprises an A-V delay, wherein the processing circuitry is configured to control the implantable medical device to deliver the ventricular pacing according to a sequence of different values of the A-V delay by at least controlling the implantable medical device to deliver left ventricular pacing according to a sequence of different values of an A-LV delay, and wherein controlling the implantable medical device to deliver the ventricular pacing at the updated value of the CRT parameter comprises controlling the implantable medical device to deliver LV fusion pacing.

11. The system of claim 2, wherein the processing circuitry is configured to control the implantable medical device to deliver the ventricular pacing at the updated value of the CRT parameter by at least controlling the implantable medical device to deliver the ventricular pacing at the value of the CRT parameter that produces the target value.

12. The system of claim 1, wherein the first fiducial point corresponds to a time at which the implantable medical device delivers a ventricular pacing pulse within the cardiac cycle.

13. The system of claim 1, wherein the second fiducial point corresponds to one of a start of paced ventricular activation, a maximum dv / dt, a detected R-wave, or a maximum amplitude of the first and second electrograms.

14. The system of claim 1, wherein the first and second vectors are orthogonal to each other.

15. The system of claim 1, wherein the first and second vectors each include a common electrode of the plurality of electrodes.

16. The system of claim 1, wherein the implantable medical device comprises an implantable CRT device that includes the processing circuitry, the system further comprising one or more implantable leads configured for implantation within the patient, wherein the implantable CRT device is coupled to the plurality of electrodes through the one or more implantable leads, each of the one or more implantable leads including one or more electrodes of the plurality of electrodes.

17. The system of claim 16, wherein the implantable CRT device comprises a housing that includes an electrode of the plurality of electrodes, and more than one implantable lead comprises a first lead configured for implantation within a right ventricle of a heart and a second lead configured for implantation within a left ventricle of a heart, wherein the first vector is between the housing and at least one of the plurality of electrodes on the first lead, and wherein the second vector is between at least one of the plurality of electrodes on the first lead and at least one of the plurality of electrodes on the second lead.

18. The system of claim 1, wherein the system further comprises a memory, and the processing circuitry is configured to control the implantable medical device to deliver the ventricular pacing to the patient’s heart according to the sequence of different values of the CRT parameters based on determining to update one or more CRT parameters, including the CRT parameters, by at least controlling the implantable medical device to deliver the ventricular pacing to the patient’s heart according to the sequence of different values of the CRT parameters, and wherein the processing circuitry is further configured to store the updated CRT parameters in the memory as at least one updated value of the one or more CRT parameters.

Images