Vfa cardiac resynchronization therapy using an accelerometer

Abstract

An implantable medical device includes a plurality of electrodes to detect electrical activity, a motion detector to detect mechanical activity, and a controller to determine at least one electromechanical interval based on at least one of the electrical activity and the mechanical activity. The detected activity can be in response to delivery of pacing pulses according to an atrioventricular (AV) pacing interval using a second electrode. The electromechanical interval can be used to adjust the AV pacing interval. The electromechanical interval can be used to determine whether a cardiac therapy is acceptable or whether atrial or ventricular remodeling is successful.

Description

[0001] This technology generally relates to medical devices, and more specifically to medical devices for cardiac resynchronization therapy.

[0002] The cardiac conduction system comprises the sinoatrial (SA) node, atrioventricular (AV) node, the bundle of His, bundle branches, and Purkinje fibers. The heartbeat is initiated in the SA node, which can be described as the heart's natural "pacemaker." Electrical impulses induced by the SA node cause the atrial myocardium to contract. Signals are conducted to the ventricles via the AV node, which inherently delays conduction to allow the atria to stop contracting before the ventricles begin to contract, thereby providing proper AV synchronization. Electrical impulses are conducted from the AV node to the ventricular myocardium via the bundle of His, bundle branches, and Purkinje fibers.

[0003] Patients with conduction system abnormalities, such as poor AV junction conduction or SA junction dysfunction, may receive implantable medical devices (IMDs), such as pacemakers, to restore a more normal heart rhythm and AV synchrony. Some types of IMDs, such as pacemakers, implantable cardioverter-defibrillators (ICDs), or cardiac resynchronization therapy (CRT) devices, deliver therapeutic electrical stimulation to the patient's heart via electrodes positioned in or near the heart on one or more implanted endocardial, epicardial, or coronary leads. Therapeutic electrical stimulation can be delivered to the heart in the form of pulses or shocks for pacing, cardioversion, or defibrillation. In some cases, IMDs can sense the heart's inherent depolarization and control the delivery of therapeutic stimulation to the heart based on this sensing.

[0004] Delivering therapeutic electrical stimulation to the heart can be used to address cardiac symptoms such as ventricular asynchrony that may occur in a patient. Ventricular asynchrony can be described as a lack of synchronicity or difference in the timing of the contractions of different ventricles in the heart. Significant differences in contraction timing can reduce cardiac efficiency. CRT delivered to the heart by an IMD can enhance cardiac output by resynchronizing the electromechanical activity of the heart's ventricles. Because it paces the right atrium, right ventricle, and left ventricle, CRT is sometimes referred to as "triple-chamber pacing."

[0005] In addition to cardiac pacing, cardiac arrhythmias can be treated by delivering electrical shocks from, for example, an ICD (Inductively Coupled Device) for cardioversion or defibrillation. The ICD senses the patient's heart rhythm and classifies it according to an arrhythmia detection protocol to detect tachycardia or fibrillation events. Detected arrhythmias can include ventricular tachycardia (VT), rapid ventricular tachycardia (FVT), ventricular fibrillation (VF), atrial tachycardia (AT), and atrial fibrillation (AT). Antitachycardia pacing (ATP) is a painless therapy that can be used to treat ventricular tachycardia (VT) to essentially terminate many monomorphic rapid rhythms. Although ATP is painless, it may not deliver effective treatment to all types of VT. For example, ATP may be less effective for polymorphic VT with variable morphology. Polymorphic VT and ventricular fibrillation (VF) may be more lethal and may require rapid treatment via electrical shock.

[0006] Dual-chamber medical devices are available, comprising electrodes carried by a transvenous atrial lead that can be placed in the right atrium and electrodes carried by a transvenous ventricular lead that can be placed in the right ventricle via the right atrium. The dual-chamber medical device itself is typically implanted in a subcutaneous pouch, with the transvenous lead tunneled into the pouch. The dual-chamber medical device can sense atrial and ventricular electrical signals and can provide both atrial and ventricular pacing as needed to promote normal heart rhythm and AV synchrony. Some dual-chamber medical devices can treat both atrial and ventricular arrhythmias.

[0007] Proposals have been made to implant intracardiac medical devices, such as leadless pacemakers, entirely within a patient's heart, eliminating the need for transvenous leads. Leadless pacemakers may contain one or more electrodes on their external housing to deliver therapeutic electrical signals and / or sense the heart's inherent depolarization. Intracardiac medical devices can provide cardiac therapeutic functions, such as sensing and pacing, within a single chamber of the patient's heart. Single-chamber intracardiac devices can also treat atrial or ventricular arrhythmias or fibrillation. Some leadless pacemakers are not intracardiac and can be positioned externally, and in some instances, can be anchored to the heart wall via a fixation mechanism.

[0008] In some patients, a single-chamber device can adequately meet their needs. However, a single-chamber device capable only of single-chamber sensing and therapy may not fully address cardiac conduction disorders or abnormalities in all patients, such as those with some form of AV asynchrony or tachycardia. In addition to ICD functionality in some cases, dual-chamber sensing and / or pacing capabilities can be used to restore a more normal heart rhythm. Summary of the Invention

[0009] The technology disclosed herein generally relates to optimizing cardiac resynchronization therapy (CRT) based on the electrical or mechanical activity of a patient's heart, which can be detected using a motion detector such as an accelerometer. Electrical and / or mechanical activity can be used to determine whether an effective cardiac therapy is being delivered or whether it indicates effective remodeling of the patient's heart over time. Various implantable medical devices can provide cardiac therapy using the cardiac conduction system or left ventricular myocardium, for example, via right atrium to left ventricle (e.g., ventricle-atrium or VfA) or via coronary sinus implantation. Non-limiting examples of cardiac therapy include single-chamber or multi-chamber pacing (e.g., dual-chamber or triple-chamber pacing), atrioventricular synchrony pacing, asynchronous pacing, triggered pacing, cardiac resynchronization pacing, or tachycardia-related therapy. Typically, tissue-puncture electrodes can be implanted in the left ventricular myocardium adjacent to the patient's heart or in its basal region, septal region, or baso-septal region.

[0010] In one aspect, this disclosure provides an implantable medical device comprising a plurality of electrodes. The plurality of electrodes includes: a first electrode to be implanted in the atrium of a patient's heart to deliver cardiac therapy or sense electrical activity of the atrium; and a second electrode to be implanted in the septum distal to the first electrode in the patient's heart to deliver cardiac therapy or sense electrical activity of the ventricle. The device further includes: a motion detector for detecting mechanical activity of the patient's heart; a therapy delivery circuit operatively coupled to the plurality of electrodes to deliver cardiac therapy to the patient's heart; and a sensing circuit operatively coupled to the plurality of electrodes to sense electrical activity of the patient's heart and operatively coupled to the motion detector to sense mechanical activity of the patient's heart. The device further includes a controller having a processing circuitry operatively coupled to the therapy delivery circuit and the sensing circuit. The controller is configured to: deliver pacing pulses using the second electrode according to the atrioventricular (AV) pacing interval; determine at least one electromechanical interval based on at least one of electrical activity and mechanical activity in response to the delivery of the pacing pulses; and adjust the AV pacing interval based on the at least one electromechanical interval.

[0011] In another aspect, this disclosure provides an implantable medical device comprising a plurality of electrodes. The plurality of electrodes includes: a first electrode to be implanted in the atrium of a patient's heart to deliver cardiac therapy or sense electrical activity of the atrium; and a second electrode to be implanted in the septum distal to the first electrode in the patient's heart to deliver cardiac therapy to the ventricle or sense electrical activity of the ventricle. The device further includes: a motion detector for detecting mechanical activity of the patient's heart; a therapy delivery circuit operatively coupled to the plurality of electrodes to deliver cardiac therapy to the patient's heart; and a sensing circuit operatively coupled to the plurality of electrodes to sense electrical activity of the patient's heart and operatively coupled to the motion detector to sense mechanical activity of the patient's heart. The device further includes a controller having a processing circuitry operatively coupled to the therapy delivery circuit and the sensing circuit. The controller is configured to: detect electrical activity indicating atrial activation from the first electrode, detect mechanical activity indicating atrial contraction from a motion detector, determine at least one electromechanical interval based on the detected atrial activation and detected atrial contraction, and determine whether repeated measurements of the at least one electromechanical interval indicate atrial remodeling.

[0012] In another aspect, this disclosure provides an implantable medical device comprising a plurality of electrodes. The plurality of electrodes includes: a first electrode to be implanted in the atrium of a patient's heart to deliver cardiac therapy or sense electrical activity of the atrium; and a second electrode to be implanted in the septum distal to the first electrode in the patient's heart to deliver cardiac therapy to the ventricle or sense electrical activity of the ventricle. The device further includes: a motion detector for detecting mechanical activity of the patient's heart; a therapy delivery circuit operatively coupled to the plurality of electrodes to deliver cardiac therapy to the patient's heart; and a sensing circuit operatively coupled to the plurality of electrodes to sense electrical activity of the patient's heart and operatively coupled to the motion detector to sense mechanical activity of the patient's heart. The device further includes a controller having a processing circuitry operatively coupled to the therapy delivery circuit and the sensing circuit. The controller is configured to: detect electrical activity indicating ventricular activation using the second electrode, detect mechanical activity indicating ventricular contraction using the motion detector, determine at least one electromechanical interval based on the detected ventricular activation and detected ventricular contraction, and determine whether repeated measurements of the at least one electromechanical interval indicate atrial remodeling.

[0013] In another aspect, this disclosure provides a method comprising delivering pacing pulses to a patient's heart according to an atrioventricular (AV) pacing interval. The method further comprises, in response to delivering the pacing pulses, determining at least one electromechanical interval based on at least one of detected electrical and mechanical activity. The method further comprises adjusting the AV pacing interval based on the at least one electromechanical interval.

[0014] Details of one or more aspects of this disclosure are set forth in the following drawings and description. Other features, objects, and advantages of the technology described in this disclosure will be apparent from the specification, drawings, and claims. Attached Figure Description

[0015] Figure 1 This is a conceptual diagram of an illustrative cardiac therapy system that includes an intracardiac medical device implanted in the patient's heart and a separate medical device positioned outside the patient's heart.

[0016] Figure 2-4 This is a conceptual diagram of an illustrative cardiac therapy system that includes a medical device comprising leads with electrodes implanted in a patient's heart.

[0017] Figure 5 yes Figure 1 An enlarged conceptual diagram of the anatomy of an intracardiac medical device and a patient's heart.

[0018] Figure 6 This is a conceptual diagram of a patient's heart in a standard 17-segment view of the left ventricle, showing various electrode implantation sites.

[0019] Figure 7 It is used with, for example Figure 1-4 A perspective view of an intracardiac medical device with a distal fixation and electrode assembly for use with the illustrative system and apparatus of 16, the electrode assembly comprising a distal housing-based electrode implemented as a ring electrode.

[0020] Figure 8 It is possible to enclose, for example Figure 1-4 A block diagram of an illustrative circuit system within the housing of a medical device of type 16 to provide the functions and therapies described herein.

[0021] Figure 9 It is used with, for example Figure 1-4 A perspective view of another illustrative intracardiac medical device used in conjunction with the illustrative systems and devices of 16.

[0022] Figure 10 It is used with, for example Figure 1-4A flowchart illustrating a method for detecting atrial activity using an atrial motion detector in conjunction with the illustrative system and apparatus described in section 16.

[0023] Figure 11 It is used with, for example Figure 1-4 A flowchart illustrating a method for detecting heart sounds to represent physiological response information, used in conjunction with the illustrative system and apparatus of 16.

[0024] Figure 12 It is used with, for example Figure 1-4 A flowchart illustrating a method for detecting bioimpedance used to represent physiological response information in conjunction with the illustrative system and apparatus of 16.

[0025] Figure 13 It is used with, for example Figure 1-4 A diagram of an illustrative system comprising an electrode device, a display device, and a computing device, used in conjunction with the illustrative system and apparatus of 16.

[0026] Figure 14-15 It is used with, for example Figure 1-4 A diagram of an illustrative external electrode device for measuring trunk-surface potential, used in conjunction with the illustrative system and apparatus of 16.

[0027] Figure 16 This is a diagram of an illustrative implantable medical device with electrodes and an accelerometer for use with the various systems and methods of this disclosure.

[0028] Figure 17 It is possible to use, for example Figure 16 Plotting of illustrative electrical and mechanical activity signals detected by implantable medical devices.

[0029] Figure 18 It is possible to use, for example Figure 16 A drawing illustrating the results determined by the implantable medical device.

[0030] Figure 19 It shows, for example, Figure 16 A flowchart illustrating a method of cardiac therapy using an electromechanical interval in conjunction with an implantable medical device.

[0031] Figure 20 It shows, for example, Figure 16 A flowchart illustrating a method for detecting remodeling using electromechanical intervals when used with implantable medical devices. Detailed Implementation

[0032] The techniques disclosed herein relate to optimizing cardiac therapies, such as cardiac resynchronization therapy (CRT), based on the electrical or mechanical activity of a patient's heart. Electrical and / or mechanical activity can be used to determine whether an effective cardiac therapy is being delivered or whether the patient's heart is being effectively remodeled over time. These techniques may involve using implantable medical devices to deliver cardiac therapies using the cardiac conduction system or left ventricular myocardium, for example, via right atrium to left ventricle (e.g., ventricle-atrium or VfA) or via coronary sinus implantation. In some embodiments, the various techniques described herein can be applied to His bundle or bundle branch pacing applications. Various non-limiting examples of cardiac therapies include single-chamber or multi-chamber pacing (e.g., dual-chamber or triple-chamber pacing), atrioventricular synchronizing pacing, asynchronous pacing, triggered pacing, cardiac resynchronization pacing, or tachycardia-related therapies. While reference is made herein to implantable medical devices such as pacemakers or ICDs, the methods and procedures can be used with any medical device, system, or method relating to a patient's heart. Various other applications benefiting from this disclosure will become apparent to those skilled in the art.

[0033] It may be beneficial to provide implantable medical devices and techniques that can be used to optimize cardiac therapies based on electrical and / or mechanical activity. Providing implantable medical devices without transvenous leads (e.g., leadless devices) may be beneficial. It may also be beneficial to provide implantable medical devices capable of being used for various cardiac therapies, such as single-chamber or multi-chamber pacing (e.g., dual-chamber or triple-chamber pacing), atrioventricular synchrony pacing, asynchronous pacing, triggered pacing, cardiac resynchronization pacing, or tachycardia-related treatments. Furthermore, it may be beneficial to provide devices for delivering the medical device accurately and precisely to the Koch triangle region or cardiac conduction system of the right atrium to facilitate pacing of the endocardium and / or His bundle conduction system.

[0034] This disclosure provides a technique for implanting a tissue-piercing electrode into the left ventricular myocardium or its basal, septal, or baso-septal region adjacent to a patient's heart. Specifically, the tissue-piercing electrode can be positioned to sense or pace the cardiac conduction system or the left ventricular myocardium and can be implanted, for example, through the right atrium to the left ventricle or through the coronary sinus. The tissue-piercing electrode or another imageable member can be at least partially formed of an imageable material. The technique may include using an imaging device to capture two-dimensional (2D) imaging data and generating three-dimensional (3D) information (e.g., orientation information) based on the 2D imaging data representing the implanted medical device.

[0035] In some embodiments, a tissue-piercing electrode can be implanted from the Koch's triangle region of the right atrium through the right atrial endocardium and central fibrous body into the basal, septal, or baso-septal region of the left ventricular myocardium of a patient's heart. In a leadless implantable medical device, the tissue-piercing electrode can extend leadlessly from a distal region of the device housing, and the right atrial electrode can be leadlessly coupled to the housing (e.g., a portion of the housing or located on the exterior of the housing). A right atrial motion detector can be within the implantable medical device. In a leaded implantable medical device, one or more of the electrodes can be coupled to the housing using implantable leads. When the device is implanted, the electrodes can be used to sense electrical activity in one or more atria and / or ventricles of the patient's heart. The motion detector can be used to sense mechanical activity in one or more atria and / or ventricles of the patient's heart. Specifically, the activity of the right atrium and left ventricle can be monitored, and optionally, the activity of the right ventricle can be monitored. Electrodes can be used to deliver cardiac therapies, such as single-chamber pacing for atrial fibrillation, atrioventricular synchrony pacing for bradycardia, asynchronous pacing, triggered pacing, cardiac resynchronization pacing for ventricular asynchrony, antitachycardia pacing, or electrical shock therapy. Electrical shock therapy can be initiated by an implantable medical device. A standalone medical device (such as an extravascular ICD, which can also be implanted) can communicate operationally with the implantable medical device and can deliver an electrical shock in response to a trigger provided by the device, such as a signaling pulse (e.g., a trigger, signaling, or unique electrical pulse).

[0036] Generally, a variety of techniques available to those skilled in the art to which this disclosure pertains can be used to sense, determine, acquire, or monitor electrical or mechanical activity. As used herein, the term “monitoring” generally refers to sensing, acquiring, or receiving data or information that can be used (e.g., processed or stored).

[0037] This disclosure also provides techniques for delivering and implanting medical devices, for example, within the Koch triangle region in the right atrium. Various devices can be used to identify the general location of the Koch triangle region, which can be described as an implantation site. A flexible lead or another probe can be advanced to the potential implantation site and used to identify the precise location of the implanted medical device (such as an electrode, lead, wire, or intracardiac device). Specifically, the techniques of this disclosure can be used to implant devices to provide synchronized pacing to asynchronous patients and dual-chamber pacing to patients with bradycardia in moderate heart failure.

[0038] Figure 1-4 Examples of various cardiac therapy systems that can be implanted to deliver medical devices to the implantation site are shown. In these views, the left ventricle (LV) is typically located behind the right ventricle (RV).

[0039] Although this disclosure describes leadless and leaded implantable medical devices, reference is first made to a conceptual diagram of a cardiac therapy system 2 shown. Figure 1 The cardiac therapy system includes an intracardiac medical device 10 that can be configured for single-chamber or dual-chamber therapy and implanted in a patient's heart 8. In some embodiments, the device 10 can be configured for single-chamber pacing and can be switched, for example, between single-chamber pacing and multi-chamber pacing (e.g., dual-chamber or triple-chamber pacing). As used herein, "intracardiac" means a device configured to be fully implanted within a patient's heart, for example, to provide cardiac therapy. The device 10 is shown implanted in the right atrium (RA) of a patient's heart 8 in a target implantation region 4. The device 10 may include one or more fixation members 20 that anchor the distal end of the device against the atrial endocardium in the target implantation region 4. The target implantation region 4 may be located between the His bundle 5 (or bundles of His) and the coronary sinus 3 and may be adjacent to the tricuspid valve 6. Device 10 can be described as an atrial-to-ventricular (VfA) device that can simultaneously sense or deliver therapy to one or both ventricles (e.g., the right ventricle, left ventricle, or both ventricles, as appropriate) while typically placed in the right atrium. Specifically, device 10 may include a tissue-piercing electrode that can be implanted from the Koch triangle region of the right atrium through the right atrial endocardium and central fibrous body into the basal region, septal region, or baso-septal region of the left ventricular myocardium of the patient's heart.

[0040] Device 10 can be described as a leadless implantable medical device. As used herein, "leadless" means a device without leads extending from the patient's heart 8. In other words, a leadless device may have leads that do not extend from the outside of the patient's heart to the inside of the patient's heart. Some leadless devices can be introduced through a vein, but once implanted, the device has no or may not contain any transvenous leads and can be configured to provide cardiac therapy without the use of any transvenous leads. Further, when the housing of the device is positioned in the atrium, specifically, the leadless VfA device does not use leads to operatively connect to electrodes in the ventricle. Additionally, leadless electrodes can be coupled to the housing of the medical device without the use of leads between the electrodes and the housing.

[0041] Device 10 may include a dart electrode assembly 12 defining or having a straight axis extending from a distal region of device 10. The dart electrode assembly 12 may be placed or at least configured to pass through the atrial myocardium and central fibrous tissue and into the ventricular myocardium 14 or along the interventricular septum, without completely passing through the ventricular endocardial or epicardial surface. The dart electrode assembly 12 may carry or include an electrode at the distal region of the axis, such that the electrode can be positioned within the ventricular myocardium for sensing ventricular signals and delivering ventricular impulses (e.g., depolarizing the left ventricle to induce left ventricular contraction). In some instances, the electrode at the distal region of the axis is a cathode electrode provided for use in a bipolar electrode pair for pacing and sensing. While the illustrated implantation region 4 allows one or more electrodes of the dart electrode assembly 12 to be positioned in the ventricular myocardium, it should be recognized that devices having the aspects disclosed herein can be implanted in other locations where appropriate for multi-chamber pacing (e.g., dual-chamber or triple-chamber pacing), single-chamber pacing with multi-chamber sensing, single-chamber pacing and / or sensing, or other clinical therapies and applications.

[0042] It should be understood that although the device 10 is described herein as comprising a single dart electrode assembly, the device 10 may comprise more than one dart electrode assembly, which is placed or configured to pass through the atrial myocardium and central fibrous body and into the ventricular myocardium 14 or along the interventricular septum, without passing entirely through the ventricular endocardium or epicardial surface. Additionally, each dart electrode assembly may carry or comprise more than one electrode in a distal region of the axis or in other regions along the axis (e.g., a proximal region or a central region).

[0043] The cardiac therapy system 2 may also include a separate medical device 50 (in Figure 1(Illustrated schematically in the diagram), the individual medical device 50 can be positioned outside (e.g., subcutaneously) the patient's heart 8 and can be operatively coupled to the patient's heart 8 to deliver cardiac therapy thereto. In one example, the individual medical device 50 can be an extravascular ICD. In some embodiments, the extravascular ICD can include a defibrillation lead containing or carrying a defibrillation electrode. A therapy carrier can be present between the defibrillation electrode on the defibrillation lead and the housing electrode of the ICD. Further, one or more electrodes of the ICD can also be used to sense electrical signals related to the patient's heart 8. The ICD can be configured to deliver electrical shock therapy comprising one or more defibrillation or cardioversion shocks. For example, if an arrhythmia is sensed, the ICD can send pulses through the lead to shock the heart and restore its normal rhythm. In some instances, the ICD can deliver electrical shock therapy without placing the lead inside the heart or attaching the wire directly to the heart (subcutaneous ICD). Examples of vascular perivascular subcutaneous ICDs that can be used with System 2 described herein can be described in U.S. Patent No. 9,278,229 (Reinke et al.), published March 8, 2016, which is incorporated herein by reference in its entirety.

[0044] In the case of electrical shock therapy (e.g., defibrillation shock delivered by defibrillation electrodes via defibrillation leads), the standalone medical device 50 (e.g., an extravascular ICD) may include control circuitry that uses a therapy delivery circuit to generate a defibrillation shock with any of a variety of waveform characteristics, including leading-edge voltage, slope, delivered energy, pulse phase, etc. The therapy delivery circuitry may, for example, generate monophasic, biphasic, or multiphasic waveforms. Additionally, the therapy delivery circuitry may generate defibrillation waveforms with varying amounts of energy. For example, the therapy delivery circuitry may generate a defibrillation waveform delivering a total of approximately 60-80 joules (J) of energy for subcutaneous defibrillation.

[0045] The individual medical device 50 may further include sensing circuitry. The sensing circuitry may be configured to acquire electrical signals sensed by one or more combinations of electrodes and to process the acquired signals. Components of the sensing circuitry may include analog components, digital components, or combinations thereof. The sensing circuitry may, for example, include one or more sensing amplifiers, filters, rectifiers, threshold detectors, analog-to-digital converters (ADCs), etc. The sensing circuitry may convert the sensed signal into a digital form and provide the digital signal to control circuitry for processing and / or analysis. For example, the sensing circuitry may amplify the signal from the sensing electrodes and may convert the amplified signal into a multi-bit digital signal via an ADC, and then provide the digital signal to control circuitry. In one or more embodiments, the sensing circuitry may also compare the processed signal with a threshold to detect the presence of atrial or ventricular depolarization (e.g., P wave or R wave) and indicate the presence of atrial depolarization (e.g., P wave) or ventricular depolarization (e.g., R wave) to control circuitry.

[0046] Device 10 and standalone medical device 50 can collaborate to deliver cardiac therapy to a patient's heart 8. For example, device 10 and standalone medical device 50 can be used to detect tachycardia, monitor tachycardia, and / or deliver tachycardia-related therapy. For example, device 10 can wirelessly communicate with standalone medical device 50 to trigger electrical shock therapy using standalone medical device 50. As used herein, "wireless" means an operational coupling or connection between device 10 and standalone medical device 50 that does not use a metallic conductor. In one instance, wireless communication can use a unique, signaling, or triggering electrical pulse provided by device 10 that is conducted through the patient's tissue and detectable by standalone medical device 50. In another instance, wireless communication can use a communication interface (e.g., an antenna) of device 10 to provide electromagnetic radiation that propagates through the patient's tissue and can be detected, for example, using a communication interface (e.g., an antenna) of standalone medical device 50.

[0047] refer to Figure 2The cardiac therapy system 402 may include a leaded medical device 408 comprising one or a single implantable lead 410 having a distal region coupled to the lead and implanted within a tissue-puncture electrode assembly 12 in a patient's heart 8. A housing 420 of the leaded medical device 408 may be implanted and positioned externally to the patient's heart 8 and configured to calibrate and / or deliver pacing therapy. The lead 410 may include a right atrial electrode, and the device 408 may function as a dual-channel device (e.g., pacing and / or sensing in both the right atrium and left ventricle). In some embodiments, the lead 410 may not include a right atrial electrode. In other words, the leaded medical device 408 may be a single-channel device that can be used for asynchronous, triggered, or other types of single-channel pacing. The leaded medical device 408, using the lead 410, can puncture the tissue-puncture electrode assembly 12, for example, as per [the relevant information]. Figure 1 The same or similar methods described are implanted to sense activity or deliver pacemakers to the left ventricle (LV).

[0048] refer to Figure 3 The cardiac therapy system 404 may include a leaded medical device 418, which is similar to... Figure 2 The leaded medical device 408, in addition to the device 418 including two implantable leads 410, 412. Specifically, the implantable lead 412 may include an electrode (e.g., a right atrial electrode) coupled to a distal region of the lead 412, and may be implanted in a different location than the lead 410. In some embodiments, the lead 412 is implanted in a different region of the right atrium. In some embodiments, each lead 410, 412 may contribute one channel to the dual-channel device 418. For example, the lead 410 may be a tissue puncture electrode in the tissue puncture electrode assembly 12, for example, as per the description of... Figure 1 When implanted in the same or similar manner as described, it senses activity or delivers pacing to the left ventricle (LV), and lead 412 can sense activity or deliver pacing to the right atrium (RA).

[0049] refer to Figure 4 The cardiac therapy system 406 may include a leaded medical device 428, which is similar to... Figure 3The leaded medical device 418, in addition to device 428 including three implantable leads 410, 412, 414. Specifically, implantable lead 414 may include an electrode (e.g., a right ventricular electrode) coupled to a distal region of lead 414 and may be implanted in a different location than leads 410, 412. As shown, implantable lead 414 extends from the right atrium (RA) to the right ventricle (RV) via tricuspid valve 6. In some embodiments, lead 414 is implanted in a region of the right ventricle. In some embodiments, each lead 410, 412, 414 may contribute a channel to multichannel device 428. For example, lead 410 may puncture electrode assembly 12 in tissue, for example, as per the description of... Figure 1 When implanted in the same or similar manner as described, activity is sensed or paced to the left ventricle (LV), lead 412 can sense activity from pacing to the RA, and lead 414 can sense activity or pace to the RV.

[0050] In some embodiments, the pacing delay (e.g., RV-LV pacing delay, or more generally, VV pacing delay) between the RV electrode on lead 414 for pacing RV and the LV electrode on lead 410 for pacing LV can be calibrated or optimized, for example, using a separate medical device (e.g., an electrode device (e.g., an ECG band)). Various methods can be used to calibrate or optimize the VV delay. In some embodiments, the medical device 428 can be used to test pacing at several different VV delays. For example, RV can be paced approximately 80, 60, 40, and 20 milliseconds (ms) ahead of LV, and LV can be paced approximately 80, 60, 40, and 20 ms ahead of RV, as well as simultaneous RV-LV pacing (e.g., approximately 0 ms VV pacing delay). The medical device 428 can then be configured, for example, to automatically select a VV pacing delay that corresponds to the minimum electrical asynchrony measured using the electrode device when used for pacing. Test pacing at different VV pacing delays can be performed using a specific AV delay (such as the rated AV delay set by the medical device 428) or a predetermined optimal AV delay based on patient characteristics.

[0051] Figure 5 yes Figure 1 An enlarged conceptual diagram of the anatomy of an intracardiac medical device 10 and a patient's heart 8. Specifically, the device 10 is configured to sense electrical activity and / or deliver pacing therapy. The intracardiac device 10 may include a housing 30. The housing 30 may define internal components of the device 10 (such as those used in conjunction with...). Figure 8The generally described sensing circuitry, therapy delivery circuitry, control circuitry, memory, telemetry circuitry, other optional sensors, and power supply reside in a hermetically sealed internal cavity. The housing 30 may be formed of a conductive material comprising titanium or titanium alloys, stainless steel, MP35N (a non-magnetic nickel-cobalt-chromium-molybdenum alloy), platinum alloys, or other biocompatible metals or metal alloys. In other examples, the housing 30 may be formed of a non-conductive material comprising ceramics, glass, sapphire, silicone, polyurethane, epoxy resin, acetyl copolymer plastics, polyetheretherketone (PEEK), liquid crystal polymers, or other biocompatible polymers.

[0052] In at least one embodiment, the housing 30 may be described as extending in a generally cylindrical shape between the distal region 32 and the proximal region 34 to facilitate catheter delivery. In other embodiments, the housing 30 may be prismatic or any other shape to perform the functions and utilities described herein. The housing 30 may include, for example, a delivery tool interface member 26 at the proximal region 34 for engagement with a delivery tool during implantation of the device 10.

[0053] All or a portion of the housing 30 can be used as an electrode during cardiac therapy, such as in sensing and / or pacing. In the illustrated example, the housing-based electrode 24 is shown as a proximal portion of the outer housing 30 (e.g., closer to the proximal region 34 than the distal region 32). When the housing 30 is formed of a conductive material (such as a titanium alloy or other examples listed above), portions of the housing 30 can be electrically insulated by a coating of a non-conductive material (such as parylene, polyurethane, silicone, epoxy, or other biocompatible polymers), thereby exposing one or more discrete regions of the conductive material to define the proximal housing-based electrode 24. When the housing 30 is formed of a non-conductive material such as ceramic, glass, or polymeric materials, a conductive coating or layer such as titanium, platinum, stainless steel, or alloys thereof can be applied to one or more discrete regions of the housing 30 to form the proximal housing-based electrode 24. In other examples, the proximal housing-based electrode 24 can be a component mounted or assembled onto the housing 30, such as a ring electrode. The proximal housing-based electrode 24 can be electrically coupled to the internal circuitry of the device 10, for example, via a conductive housing 30 or, when the housing 30 is a non-conductive material.

[0054] In the example shown, the proximal housing-based electrode 24 is positioned closer to the proximal housing region 34 than the distal housing region 32, and is therefore referred to as the "proximal housing-based electrode" 24. However, in other examples, the housing-based electrode 24 may be positioned at other locations along the housing 30, for example, further away from the location shown.

[0055] At the distal region 32, the device 10 may include a distal fixation and electrode assembly 36, which may include one or more fixation members 20 and one or more dart electrode assemblies 12 of equal or unequal length. In one example, a single dart electrode assembly 12 includes a shaft 40 extending distally away from the distal region 32 of the housing, and one or more electrode elements, such as a tip electrode 42, at or near the free distal region of the shaft 40. The tip electrode 42 may have a conical or hemispherical distal tip with a relatively narrow tip diameter (e.g., less than about 1 mm) for penetration and through tissue layers without the need for sharp or beveled tips or needle-like tips.

[0056] The shaft 40 of the dart electrode assembly 12 can normally be a straight member and can be rigid. In other embodiments, the shaft 40 can be described as relatively rigid, but still possessing limited flexibility in the lateral direction. Further, the shaft 40 can be non-rigid to allow some lateral bending with heart movement. However, in a relaxed state, when not subjected to any external force, the shaft 40 can maintain a straight positioning as shown to space the tip electrode 42 from the distal region 32 of the housing at least by the height 47 of the shaft 40. In other words, the dart electrode assembly 12 can be described as elastic.

[0057] The dart electrode assembly 12 can be configured to pierce one or more tissue layers to position the tip electrode 42 within a desired tissue layer (e.g., ventricular myocardium). Thus, the height 47 or length of the shaft 40 can correspond to the intended pacing site depth, and the shaft 40 can have relatively high compressive strength along its longitudinal axis to resist bending in the lateral or radial directions when pressed against the implantation region 4. If a second dart electrode assembly 12 is used, its length may not be equal to the intended pacing site depth and it can be configured to act as an independent electrode for delivering pacing energy to the tissue. A longitudinal axial force can be applied to the tip electrode 42, for example, by applying a longitudinal thrust to the proximal region 34 of the housing 30, to advance the dart electrode assembly 12 into the tissue within the target implantation region. The shaft 40 can be described as longitudinally non-compressible and / or elastically deformable in the lateral or radial direction when subjected to lateral or radial forces, allowing for temporary bending, for example, with tissue movement, but returning to its normal straight positioning when the lateral force decreases. When shaft 40 is not exposed to any external force or is only exposed to a force along its longitudinal central axis, shaft 40 can maintain a straight linear positioning as shown in the figure.

[0058] The one or more fixation members 20 may be described as one or more “teeth” having a normal bending positioning. The teeth may be held in a distally extending position within the delivery tool. The distal tip of the teeth may penetrate cardiac tissue to a limited depth before elastically bending proximally back to the normal bending positioning (as shown) upon release from the delivery tool. Further, the fixation member 20 may include one or more aspects described, for example, in U.S. Patent No. 9,675,579, issued June 13, 2017 (Grubac et al.) and U.S. Patent No. 9,119,959, issued September 1, 2015 (Rys et al.), each of which is incorporated herein by reference in its entirety.

[0059] In some instances, the distal fixation and electrode assembly 36 includes a distal housing-based electrode 22. When using the device 10 as a pacemaker for multi-chamber pacing (e.g., dual-chamber or triple-chamber pacing) and sensing, the tip electrode 42 can serve as a cathode electrode paired with the proximal housing-based electrode 24, which acts as a return anode electrode. Alternatively, the distal housing-based electrode 22 can serve as a return anode electrode paired with the tip electrode 42 for sensing ventricular signals and delivering ventricular pacing pulses. In other instances, the distal housing-based electrode 22 can be a cathode electrode for sensing atrial signals and delivering pacing pulses to the atrial myocardium in the target implantation region 4. When the distal housing-based electrode 22 acts as an atrial cathode electrode, the proximal housing-based electrode 24 can serve as a return anode paired with the tip electrode 42 for ventricular pacing and sensing, and can also serve as a return anode paired with the distal housing-based electrode 22 for atrial pacing and sensing.

[0060] As illustrated in the diagram, in some pacing applications, the target implantation region 4 is along the atrial endocardium 18, typically below the AV node 15 and His bundle 5. The dart electrode assembly 12 may at least partially define the height 47 or length of the shaft 40 to penetrate the atrial endocardium 18 in the target implantation region 4, through the central fibrous body 16, and into the ventricular myocardium 14 without penetrating the ventricular endocardial surface 17. When the height 47 or length of the dart electrode assembly 12 is fully advanced into the target implantation region 4, the tip electrode 42 may be positioned within the ventricular myocardium 14, and the distal housing-based electrode 22 may be positioned in close contact with or very close to the atrial endocardium 18. In various examples, the dart electrode assembly 12 may have a total combined height 47 or length of the tip electrode 42 and shaft 40 of about 3 mm to about 8 mm. The diameter of the shaft 40 may be less than about 2 mm and may be about 1 mm or less, or even about 0.6 mm or less.

[0061] Device 10 may include an acoustic or motion detector 11 within housing 30. The acoustic or motion detector 11 may be operatively coupled to control circuitry 80. Figure 8 ), sensing circuit 86 ( Figure 8 ) or therapy delivery circuit 84 ( Figure 8 One or more of the following. In some embodiments, the acoustic or motion detector 11 may be with Figure 10-12 Methods 600, 650, or 800 shown can be used together. The acoustic or motion detector 11 can be used to monitor mechanical activity, such as atrial mechanical activity (e.g., atrial contraction) and / or ventricular mechanical activity (e.g., ventricular contraction). In some embodiments, the acoustic or motion detector 11 can be used to detect right atrial mechanical activity. Non-limiting examples of the acoustic or motion detector 11 include an accelerometer or a microphone. In some embodiments, the mechanical activity detected by the acoustic or motion detector 11 can be used to supplement or replace electrical activity detected by one or more electrodes of the device 10. For example, the acoustic or motion detector 11 can be used in addition to or as an alternative to the proximal housing-based electrode 24.

[0062] The acoustic or motion detector 11 can also be used for rate response detection or to provide a rate-responsive IMD. Various techniques related to rate response can be described in U.S. Patent No. 5,154,170, entitled "Optimization for a rate-responsive cardiac pacemaker," issued October 13, 1992 (Bennett et al.), and U.S. Patent No. 5,562,711, entitled "Method and apparatus for rate-responsive cardiac pacing," issued October 8, 1996 (Yerich et al.), each of which is incorporated herein by reference in its entirety.

[0063] In various embodiments, the acoustic or motion detector 11 (or motion sensor) can be used as an HS sensor and can be implemented as a microphone or a 1-axis, 2-axis, or 3-axis accelerometer. In one embodiment, the acoustic sensor is implemented as a piezoelectric crystal mounted within the implantable medical device housing and responsive to mechanical movements associated with heart sounds. The piezoelectric crystal can be a dedicated HS sensor or can be used for multiple functions. In the illustrative embodiment shown, the acoustic sensor is implemented as a piezoelectric crystal, which is also used to generate a patient alarm signal in the form of a perceptible vibration of the IMD housing. Upon detecting an alarm condition, the control circuit 80 can cause the patient warning control circuitry system to generate an alarm signal by activating the piezoelectric crystal.

[0064] The control circuitry can be used to control whether the piezoelectric crystal is used in "listening mode" to sense the HS signal via the HS sensing circuitry system, or in "output mode" to generate a patient alarm. During patient alarm generation, the HS sensing circuitry system can be temporarily decoupled from the HS sensor via the control circuitry system.

[0065] Examples of other embodiments of acoustic sensors that may be adapted to be implemented with the technology of this disclosure are generally described in U.S. Patent Nos. 4,546,777 (Groch et al.), 6,869,404 (Schulhauser et al.), 5,554,177 (Kieval et al.), and 7,035,684 (Lee et al.), each of which is incorporated herein by reference in its entirety.

[0066] Various types of acoustic sensors can be used. The acoustic sensor can be any implantable or external sensor that responds to one or more heart sounds generated as described above, thereby producing analog electrical signals that are time- and amplitude-dependent on the heart sounds. The analog signal can then be processed by the HS sensing module (which may include digital conversion) to obtain HS parameters, such as amplitude or relative time intervals, derived by the HS sensing module or control circuitry 80. The acoustic sensor and HS sensing module can be incorporated into an IMD capable of delivering CRT or another cardiac therapy being optimized, or can be implemented in a separate device with wired or wireless communication to the IMD, or in an external programmer or computer used during pacing parameter optimization procedures as described herein.

[0067] Figure 6This is a two-dimensional (2D) ventricular diagram 300 of a patient's heart (e.g., a top-down view), showing the left ventricle 320 and right ventricle 322 in a standard 17-segment view. Figure 300 contains multiple zones 326 corresponding to different regions of the human heart. As shown, zones 326 are numbered from 1 to 17 (e.g., corresponding to the 17 segments of the left ventricle of the human heart). Zones 326 of Figure 300 may include the anterior basal zone 1, the anterior basal septum zone 2, the subbasal septum zone 3, the subbasal zone 4, the subbasal lateral zone 5, the anterior basal lateral zone 6, the anterior mid-septum zone 7, the anterior mid-septum zone 8, the inferior mid-septum zone 9, the inferior mid-septum zone 10, the inferior mid-lateral zone 11, the anterior mid-lateral zone 12, the anterior vertex zone 13, the vertex septum zone 14, the inferior vertex zone 15, the lateral vertex zone 16, and the apex zone 17. The inferior and anterior septal regions of right ventricle 322, as well as the right bundle branch (RBB) and left bundle branch (LBB) are also shown.

[0068] In some embodiments, any of the tissue-piercing electrodes of this disclosure can be implanted into the basal region, septal region, or baso-septal region of the left ventricular myocardium of a patient's heart. Specifically, the tissue-piercing electrode can be implanted through the right atrial endocardium and central fibrous body via the Koch's triangle region of the right atrium.

[0069] Once implanted, the tissue-piercing electrode can be positioned in target implantation areas such as the basal region, septal region, or baso-septal region of the left ventricular myocardium.4 Figure 1-5 Referring to Figure 300, the basal region includes one or more of the following: anterior basal region 1, anterior basal septum region 2, subbasal septum region 3, subbasal region 4, anterior mid-basal region 7, anterior mid-basal septum region 8, infero-mid mid-basal septum region 9, and infero-mid mid-basal region 10. Referring to Figure 300, the septal region includes one or more of the following: anterior basal septum region 2, anterior basal septum region 3, anterior mid-basal septum region 8, infero-mid mid-basal septum region 9, and superior septal region 14.

[0070] In some embodiments, when implanted, the tissue-puncturing electrode may be positioned in the basal septal region of the left ventricular myocardium. The basal septal region may include one or more of the following: anterior basal septal region 2, subbasal septal region 3, anterior mid-septal region 8, and submid-septal region 9.

[0071] In some embodiments, when implanted, the tissue-puncturing electrode can be positioned in the superior / posterior basal septum region of the left ventricular myocardium. The superior / posterior basal septum region of the left ventricular myocardium may include a portion of one or more of the subbasal septum region 3 and the inferior basal septum region 9 (e.g., only the subbasal septum region, only the inferior basal septum region, or both the subbasal septum region and the inferior basal septum region). For example, the superior / posterior basal septum region may include a region 324 generally illustrated as a dashed boundary. As shown, the dashed boundary indicates the approximate location of the superior / posterior basal septum region, and its shape or size may vary slightly depending on the specific application.

[0072] Figure 7 This is a three-dimensional perspective view of the device 10 capable of calibrating and / or delivering pacing therapy. As shown, the distal fixation and electrode assembly 36 includes a distal housing-based electrode 22 implemented as a ring electrode. The distal housing-based electrode 22 can be positioned in close contact with or operatively close to the atrial tissue when the fixation member teeth 20a, 20b, and 20c of the fixation member 20 engage with atrial tissue. The elastically deformable teeth 20a, 20b, and 20c can extend distally during delivery of the device 10 to the implantation site. For example, when the device 10 is ejected from the delivery tool, the teeth 20a, 20b, and 20c can pierce the atrial endocardial surface and bend back to their normal bending position when the teeth are no longer constrained within the delivery tool (as shown). When the teeth 20a, 20b, and 20c bend back to their normal position, the fixation member 20 can pull the distal fixation member and electrode assembly 36 toward the atrial endocardial surface. When the distal fixation member and electrode assembly 36 are pulled toward the atrial endocardium, the tip electrode 42 can be advanced through the atrial myocardium and central fibrous body and into the ventricular myocardium. The distal shell-based electrode 22 can then be positioned on the surface of the atrial endocardium.

[0073] The distal housing-based electrode 22 may comprise a ring formed of a conductive material such as titanium, platinum, iridium, or alloys thereof. The distal housing-based electrode 22 may be a single, continuous ring electrode. In other examples, portions of the ring may be coated with an electrically insulating coating, such as parylene, polyurethane, silicone, epoxy, or another insulating coating, to reduce the conductive surface area of ​​the ring electrode. For example, one or more sectors of the ring may be coated to separate two or more conductive exposed surface areas of the distal housing-based electrode 22. Reducing the conductive surface area of ​​the distal housing-based electrode 22, for example, by covering portions of the conductive ring with an insulating coating, can increase the impedance of the distal housing-based electrode 22 and thereby reduce the current delivered during pacing of pulses capturing myocardium (e.g., atrial myocardial tissue). Lower current consumption can save power to the device 10, such as one or more rechargeable or non-rechargeable batteries.

[0074] As described above, the distal housing-based electrode 22 can be configured as an atrial cathode electrode, which is used in conjunction with the proximal housing-based electrode 24 as a return anode to deliver pacing pulses to atrial tissue at the implantation site. Electrodes 22 and 24 can be used to sense atrial P waves for controlling atrial pacing pulses (delivery in the absence of a sensed P wave) and for controlling atrial-synchronized ventricular pacing pulses delivered using the tip electrode 42 as a cathode and the proximal housing-based electrode 24 as a return anode. In other instances, the distal housing-based electrode 22 can be combined with the cathode tip electrode 42 for ventricular pacing and sensing as a return anode.

[0075] Figure 8 This is a block diagram of a circuit system that can be enclosed in a housing 30 ( Figure 7 The circuitry can be enclosed within a device 10 according to one example to provide the functionality of calibrating pacing therapy and / or delivering pacing therapy, or the circuitry can be enclosed within any other medical device described herein (e.g., Figure 2 Device 408 Figure 3 Device 418 Figure 4 Device 428 or Figure 9 The device 710 is housed within its casing. Individual medical device 50 ( Figure 1-4 The device 10 may contain some or all of the same components that can be configured in a similar manner. The electronic circuitry enclosed within the housing 30 may include software, firmware, and hardware that collaboratively monitor atrioventricular and ventricular electrocardiographic signals, determine when cardiac therapy is needed, and / or deliver electrical pulses to the patient's heart according to programmed treatment modes and pulse control parameters. The electronic circuitry may include control circuitry 80 (e.g., including processing circuitry), memory 82, therapy delivery circuitry 84, sensing circuitry 86, and / or telemetry circuitry 88. In some instances, the device 10 includes one or more sensors 90 (such as patient activity sensors) for generating signals related to the patient's physiological function, state, or condition to determine the need for pacing therapy and / or control of the pacing rate. For example, a sensor 90 may include an inertial measurement unit (e.g., an accelerometer) for measuring motion.

[0076] Power source 98 can provide power as needed to the circuitry of device 10, which includes each of components 80, 82, 84, 86, 88, and 90. Power source 98 may include one or more energy storage devices, such as one or more rechargeable or non-rechargeable batteries. The connections between power source 98 and each of components such as sensors 80, 82, 84, 86, 88, and 90 (not shown) can be understood from the general block diagram shown to those skilled in the art. For example, power source 98 may be coupled to one or more charging circuits included in therapy delivery circuitry 84 to provide power for charging a holding capacitor included in therapy delivery circuitry 84, which is discharged at appropriate times under the control of control circuitry 80 to deliver pacing pulses, for example, according to a dual-chamber pacing mode (such as DDI(R)). Power source 98 may also be coupled to components of sensing circuitry 86 (such as sensing amplifiers, analog-to-digital converters, switching circuitry, etc.), sensor 90, telemetry circuitry 88, and memory 82 to provide power to various circuits.

[0077] The illustrated functional blocks represent functions included in device 10 and may include any discrete and / or integrated electronic circuit components implementing analog and / or digital circuitry capable of producing functions attributable to the medical device 10 herein. Each component may include processing circuitry systems (such as application-specific integrated circuits (ASICs), electronic circuitry, processors (shared, dedicated, or grouped), and memory), combinational logic circuitry, state machines, or other suitable components or combinations thereof providing the described functions, executing one or more software or firmware programs. The specific form of software, hardware, and / or firmware used to implement the functions disclosed herein will be determined primarily by the specific system architecture employed in the medical device and the specific detection and therapy delivery methods used by the medical device.

[0078] Memory 82 may comprise any volatile, non-volatile, magnetic, or electrically non-transitory computer-readable storage medium, such as random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, or any other memory device. Furthermore, memory 82 may comprise a non-transitory computer-readable medium storing instructions that, when executed by one or more processing circuits, cause control circuitry 80 and / or other processing circuitry systems to calibrate pacing therapy and / or perform single-chamber, dual-chamber, or triple-chamber calibrated pacing therapy (e.g., single-chamber or multi-chamber pacing) or other cardiac therapeutic functions attributed to device 10 (e.g., sensing or delivery therapy). The non-transitory computer-readable medium storing instructions may comprise any of the media listed above.

[0079] The control circuit 80 can communicate, for example, via a data bus with the therapy delivery circuit 84 and the sensing circuit 86 to sense cardiac electrical signals and control the delivery of cardiac electrical stimulation therapy in response to sensed cardiac events (e.g., P waves and R waves, or their absence). The tip electrode 42, the distal housing-based electrode 22, and the proximal housing-based electrode 24 can be electrically coupled to the therapy delivery circuit 84 for delivering electrical stimulation pulses to the patient's heart, and electrically coupled to the sensing circuit 86 for sensing cardiac electrical signals.

[0080] Sensing circuit 86 may include an atrial (A) sensing channel 87 and a ventricular (V) sensing channel 89. Distal housing-based electrode 22 and proximal housing-based electrode 24 may be coupled to atrial sensing channel 87 to sense atrial signals, such as P waves associated with atrial myocardial depolarization. In instances including two or more selectable distal housing-based electrodes, sensing circuit 86 may include a switching circuit system for selectively coupling one or more of the available distal housing-based electrodes to a cardiac event detection circuitry system contained in atrial sensing channel 87. The switching circuit system may include a switch array, switch matrix, multiplexer, or any other type of switching device suitable for selectively coupling components of sensing circuit 86 to selected electrodes. Tip electrode 42 and proximal housing-based electrode 24 may be coupled to ventricular sensing channel 89 to sense ventricular signals, such as R waves associated with ventricular myocardial depolarization.

[0081] Each of the atrial sensing channel 87 and the ventricular sensing channel 89 may include a cardiac event detection circuitry for detecting P waves and R waves, respectively, from cardiac electrical signals received by the respective sensing channel. The cardiac event detection circuitry included in each of channels 87 and 89 may be configured to amplify, filter, digitize, and rectify the cardiac electrical signals received from selected electrodes to improve signal quality for detecting cardiac electrical events. The cardiac event detection circuitry within each channel 87 and 89 may include one or more sensing amplifiers, filters, rectifiers, threshold detectors, comparators, analog-to-digital converters (ADCs), timers, or other analog or digital components. The cardiac event sensing thresholds, such as P-wave and R-wave sensing thresholds, may be automatically adjusted by each respective sensing channel 87 and 89 under the control of the control circuitry 80, for example, based on timing intervals and sensing thresholds determined by the control circuitry 80 and stored in memory 82 and / or controlled by the hardware, firmware, and / or software of the control circuitry 80 and / or the sensing circuitry 86.

[0082] When a cardiac electrical event is detected based on a sensing threshold crossing, sensing circuit 86 can generate a sensed event signal that is transmitted to control circuit 80. For example, atrial sensing channel 87 can generate a P-wave sensed event signal in response to a P-wave sensed threshold crossing. Ventricular sensing channel 89 can generate an R-wave sensed event signal in response to an R-wave sensed threshold crossing. Control circuit 80 can use the sensed event signals to set a pacing escape interval timer that controls the basic time interval used to schedule cardiac pacing pulses. Depending on the specific programmed pacing mode, the sensed event signals can trigger or suppress pacing pulses. For example, a P-wave sensed event signal received from atrial sensing channel 87 can cause control circuit 80 to suppress scheduled atrial pacing pulses and schedule ventricular pacing pulses with a programmed atrioventricular (AV) pacing interval. If an R-wave is sensed before the AV pacing interval expires, the ventricular pacing pulse can be suppressed. If the AV pacing interval is cut off before the control circuit 80 receives the R-wave sensing event signal from the ventricular sensing channel 89, the control circuit 80 can use the therapy delivery circuit 84 to deliver a scheduled ventricular pacing pulse synchronized with the sensed P wave.

[0083] In some instances, device 10 can be configured to deliver a variety of pacing therapies, including bradycardia pacing, cardiac resynchronization therapy, post-shock pacing, and / or tachycardia-related therapies (such as ATP). For example, device 10 can be configured to detect non-sinus tachycardia and deliver ATP. Control circuitry 80 can determine cardiac event time intervals, such as the PP interval between consecutive P-wave sensed event signals received from atrial sensing channel 87, the RR interval between consecutive R-wave sensed event signals received from ventricular sensing channel 89, and the PR and / or RP intervals received between P-wave sensed event signals and R-wave sensed event signals. These intervals can be compared to tachycardia detection intervals to detect non-sinus tachycardia. Tachycardia can be detected in a given cardiac chamber based on a threshold number of detected tachycardia detection intervals.

[0084] The therapy delivery circuit 84 may include an atrial pacing circuit 83 and a ventricular pacing circuit 85. Each pacing circuit 83, 85 may include a charging circuit system, one or more charge storage devices (such as one or more low-voltage holding capacitors), an output capacitor, and / or a switching circuit system that controls when the one or more holding capacitors are charged and discharged across the output capacitor to deliver pacing pulses to the pacing electrode vector coupled to the respective pacing circuit 83, 85. The tip electrode 42 and the proximal housing-based electrode 24 may be coupled as a bipolar cathode and anode to the ventricular pacing circuit 85 to deliver ventricular pacing pulses, for example, when the AV or VV pacing interval, set by the control circuit 80 for providing atrial synchronizing ventricular pacing and a basic lower ventricular pacing rate, expires.

[0085] Atrial pacing circuit 83 can be coupled to distal housing-based electrode 22 and proximal housing-based electrode 24 to deliver atrial pacing pulses. Control circuit 80 can set one or more atrial pacing intervals based on a programmed lower pacing rate or a temporarily lower rate set according to a pacing rate indicated by a rate responsive sensor. If the atrial pacing interval is cut off before a P-wave sensed event signal is received from atrial sensing channel 87, the atrial pacing circuit can be controlled to deliver atrial pacing pulses. Control circuit 80 initiates an AV pacing interval in response to the delivered atrial pacing pulses to provide synchronized multi-chamber pacing (e.g., dual-chamber or triple-chamber pacing).

[0086] The therapy delivery circuit 84 can charge the holding capacitors of the atrial or ventricular pacing circuits 83, 85 to a programmed pacing voltage amplitude and discharge the capacitors for a programmed pacing pulse width, based on control signals received from the control circuit 80. For example, the pacing timing circuit included in the control circuit 80 may include a programmable digital counter, set by the microprocessor of the control circuit 80, to control the basic pacing time interval associated with various single-chamber or multi-chamber pacing (e.g., dual-chamber or triple-chamber pacing) modes or anti-tachycardia pacing sequences. The microprocessor of the control circuit 80 can also set the amplitude, pulse width, polarity, or other characteristics of the cardiac pacing pulses based on programmed values ​​stored in memory 82.

[0087] The device 10 may include additional sensors 90 for sensing signals from the patient to determine the need for and / or control of the electrical stimulation therapy delivered by the therapy delivery circuit 84. In some instances, sensors indicating the need for increased cardiac output may include patient activity sensors, such as accelerometers. The increase in the patient's metabolic demand caused by the increased activity indicated by the patient activity sensor can be determined by the control circuit 80 to determine the pacing rate indicated by the sensor.

[0088] Control parameters for sensing cardiac events and controlling the delivery of pacing therapy, utilized by control circuitry 80, can be programmed into memory 82 via telemetry circuitry 88, which can also be described as a communication interface. Telemetry circuitry 88 includes a transceiver and antenna for communicating with external devices such as programmers or home monitors using radio frequency communication or other communication protocols. Control circuitry 80 can use telemetry circuitry 88 to receive downlink telemetry from external devices and transmit uplink telemetry to external devices. In some cases, telemetry circuitry 88 can be used to transmit / receive communication signals to / from another medical device implanted in the patient.

[0089] Figure 9This is a three-dimensional perspective view of another leadless intracardiac medical device 710, according to another example, which can be configured for calibrating and / or delivering pacing therapy for single-chamber or multi-chamber cardiac therapy (e.g., dual-chamber or triple-chamber cardiac therapy). Device 710 may include a housing 730 having an outer wall 735, shown as a cylindrical outer wall, extending from a distal region 732 of the housing to a proximal region 734. Housing 730 may enclose an electronic circuitry system configured to perform single-chamber or multi-chamber cardiac therapy, including atrial and ventricular cardiac electrical signal sensing and pacing of the atrial and ventricular chambers. A delivery tool interface component 726 is shown on the proximal region 734 of the housing.

[0090] The distal fixation and electrode assembly 736 may be coupled to the distal region 732 of the housing. The distal fixation and electrode assembly 736 may include an electrically insulating distal member 772 coupled to the distal region 732 of the housing. A tissue-piercing electrode assembly 712 extends remotely from the distal region 732 of the housing, and a plurality of non-tissue-piercing electrodes 722 may be directly coupled to the insulating distal member 772. The tissue-piercing electrode assembly 712 extends in a longitudinal direction remote from the distal region 732 of the housing and may be coaxial with the longitudinal central axis 731 of the housing 730.

[0091] The distal tissue puncture electrode assembly 712 may include an electrically insulating shaft 740 and a tip electrode 742 (e.g., a tissue puncture electrode). In some instances, the tissue puncture electrode assembly 712 is a movable, fixed member comprising a helical shaft 740 and a distal cathode tip electrode 742. The helical shaft 740 may extend from a distal end region 743 to a proximal end region 741, which may be directly coupled to an insulating distal member 772. The helical shaft 740 may be coated with an electrically insulating material, such as parylene or other examples listed herein, to avoid sensing or stimulating cardiac tissue along the shaft length. The tip electrode 742 is located at the distal end region 743 and may serve as a cathode electrode for delivering ventricular pacing pulses and sensing ventricular electrical signals using a proximal housing-based electrode 724 as a return anode when the tip electrode 742 is advanced into ventricular tissue. The proximal housing-based electrode 724 can be an annular electrode of the outer housing 730 and can be defined by the uninsulated portion of the longitudinal sidewall 735. Other portions of the housing 730 that do not function as electrodes can be combined as described above. Figure 7 The described electrical insulating material coating.

[0092] Using two or more tissue-puncture electrodes that penetrate into the LV myocardium (e.g., any type of tissue-puncture electrode) can be used for more localized pacing capture and can reduce ventricular pacing spikes, thereby affecting the capture of atrial tissue. In some embodiments, the multiple tissue-puncture electrodes may comprise two or more dart-shaped electrode assemblies (e.g., Figure 7 Electrode assembly 12), helical electrode (e.g., electrode assembly 712). Non-limiting examples of multiple tissue-piercing electrodes include two dart electrode assemblies, a helical electrode having a dart electrode assembly extending therethrough (e.g., through the center), or a double-wound helix. Multiple tissue-piercing electrodes can also be used for bipolar or multipolar pacing.

[0093] In some embodiments, one or more tissue puncture electrodes (e.g., any type of tissue puncture electrode) penetrating into the LV myocardium can be multipolar tissue puncture electrodes. Multipolar tissue puncture electrodes may include one or more electroactive elements and electrodissociation elements, enabling bipolar or multipolar pacing from one or more tissue puncture electrodes.

[0094] Multiple non-tissue puncture electrodes 722 may be provided along the outer periphery of the insulating distal member 772, located on the outer periphery of the tissue puncture electrode assembly 712. The insulating distal member 772 may define a distally facing surface 738 of the device 710 and a circumferential surface 739 of the device 710 adjacent to the longitudinal sidewall 735 of the housing. The non-tissue puncture electrodes 722 may be formed of a conductive material such as titanium, platinum, iridium, or alloys thereof. In the illustrated embodiment, six non-tissue puncture electrodes 722 are radially spaced at equal distances along the outer periphery of the insulating distal member 772. However, two or more non-tissue puncture electrodes 722 may be provided.

[0095] The non-tissue puncture electrode 722 may be a discrete component, each held within a corresponding recess 774 in the insulating member 772, the size and shape of which are designed to match the non-tissue puncture electrode 722. In other examples, the non-tissue puncture electrode 722 may each be an uninsulated exposed portion of a monolithic member mounted within or on the insulating distal member 772. Intermediate portions of the monolithic member not used as electrodes may be insulated by the insulating distal member 772, or, if exposed to the surrounding environment, may be coated with an electrically insulating coating, such as parylene, polyurethane, silicone, epoxy, or another insulating coating.

[0096] When the tissue-piercing electrode assembly 712 is advanced into the cardiac tissue, at least one non-tissue-piercing electrode 722 may be positioned against, in close contact with, or operatively close to the surface of the cardiac tissue to deliver pulses and / or sense cardiac electrical signals generated by the patient's heart. For example, when the tissue-piercing electrode assembly 712 is advanced into the atrial tissue and passes through the central fibrous body until the distal tip electrode 742 is positioned in direct contact with ventricular tissue (e.g., ventricular myocardium and / or a portion of the ventricular conduction system), the non-tissue-piercing electrode 722 may be positioned to contact the right atrial endocardial tissue for pacing and sensing in the atrium.

[0097] The non-tissue puncture electrode 722 can be coupled to the therapy delivery circuit 84 and sensing circuit 86 enclosed by the housing 730 (see...). Figure 8 The distal non-tissue puncture electrodes 722, in combination with the proximal housing-based electrode 724 serving as the return anode, function as cathode electrodes for delivering atrial pacing pulses and sensing atrial electrical signals (e.g., P waves). A switching circuit system included in the sensing circuit 86 can be activated under the control of the control circuit 80 to couple one or more of the non-tissue puncture electrodes to the atrial sensing channel 87. The distal non-tissue puncture electrodes 722 can be electrically isolated from each other, allowing each individual electrode of the electrodes 722 to be individually selected, either alone or in combination of two or more electrodes of the electrodes 722, to act as an atrial cathode electrode, via a switching circuit system included in the therapy delivery circuit 84. A switching circuit system included in the therapy delivery circuit 84 can be activated under the control of the control circuit 80 to couple one or more of the non-tissue puncture electrodes 722 to the atrial pacing circuit 83. Two or more non-tissue puncture electrodes of the non-tissue puncture electrodes 722 can be selected at once to serve as multi-point atrial cathode electrodes.

[0098] Certain non-tissue puncture electrodes 722 used for atrial pacing and / or atrial sensing can be selected based on atrial capture threshold testing, electrode impedance, P-wave signal intensity in cardiac electrical signals, or other factors. For example, a single non-tissue puncture electrode 722 or any combination of two or more separate said non-tissue puncture electrodes can be selected as the optimal combination of cathode electrodes providing a low pacing capture threshold amplitude and relatively high electrode impedance to achieve reliable atrial pacing using minimal current consumption from power source 98.

[0099] In some cases, when the tissue-piercing electrode assembly 712 anchors the housing 730 at the implantation site, the distally facing surface 738 can uniformly contact the atrial endocardial surface. In this case, all electrodes 722 can be selected together to form an atrial cathode. Alternatively, every other electrode of the electrodes 722 can be selected together to form a multi-center atrial cathode with higher impedance, the atrial cathodes still being uniformly distributed along the distally facing surface 738. Alternatively, a subset of one or more electrodes 722 can be selected along one side of the insulating distal member 772 to provide pacing at a desired site that achieves the lowest pacing capture threshold due to the relative position of the electrodes 722 to the pacing atrial tissue.

[0100] In other cases, depending on the positioning and orientation of the tissue-piercing electrode assembly 712 into the cardiac tissue, the distally facing surface 738 may be oriented at an angle relative to the adjacent endocardial surface. In this case, one or more of the non-tissue-piercing electrodes 722 may be positioned to make closer contact with the adjacent endocardial tissue than other non-tissue-piercing electrodes 722, which may be oriented at an angle away from the endocardial surface. By providing a plurality of non-tissue-piercing electrodes along the periphery of the insulating distal member 772, the angles of the tissue-piercing electrode assembly 712 and the distal housing region 732 relative to the cardiac surface (e.g., the right atrial endocardial surface) need not be substantially parallel. Anatomical and positioning differences may cause the distally facing surface 738 to be angled or tilted relative to the endocardial surface; however, the plurality of non-tissue-piercing electrodes 722 distributed along the periphery of the insulating distal member 772 increases the likelihood of good contact between one or more electrodes 722 and the adjacent cardiac tissue, thereby facilitating acceptable pacing thresholds and reliable cardiac event sensing using at least a subset of the plurality of electrodes 722. It may not be necessary to make circumferential contact or fixation along the entire outer periphery of the insulating distal member 772.

[0101] The non-tissue puncture electrode 722 is shown to each include a first portion 722a extending along a distally facing surface 738 and a second portion 722b extending along a circumferential surface 739. The first portion 722a and the second portion 722b may be continuous exposed surfaces such that the active electrode surface wraps around the outer peripheral edge 776 of the insulating distal member 772, the outer peripheral edge joining the distally facing surface 738 and the circumferential surface 739. The non-tissue puncture electrode 722 may include one or more electrodes 722 along the distally facing surface 738, one or more electrodes along the circumferential surface 739, one or more electrodes each extending along both the distally facing surface 738 and the circumferential surface 739, or any combination thereof. The exposed surface of each non-tissue puncture electrode in the non-tissue puncture electrode 722 may be flush with the corresponding distally facing surface 738 and / or circumferential surface. In other instances, each non-tissue puncture electrode in the non-tissue puncture electrode 722 may have a raised surface protruding from the insulating distal member 772. However, any raised surface of the electrode 722 may define a smooth or rounded non-tissue puncture surface.

[0102] The distal fixation and electrode assembly 736 can seal the distal region of the housing 730 and can provide a base for mounting the electrode 722 thereon. The electrode 722 may be referred to as a housing-based electrode. The electrode 722 may not be carried by a shaft or other extension extending an active electrode portion (such as a distal tip electrode 742 located at the distal tip of a helical shaft 740 extending away from the housing 730) away from the housing 730. Other examples of non-tissue-piercing electrodes coupled to the distally facing surface and / or circumferential surface of an insulating distal member, as presented herein, include distally housing-based annular electrodes 22 (…). Figure 7 ), surrounding assembly 36 ( Figure 7 Circumferentially extending distal shell-based annular electrodes, button electrodes, other shell-based electrodes, and other circumferential annular electrodes. Any non-tissue puncture electrode located on the periphery of the central tissue puncture electrode, directly coupled to the distal insulating member, can be provided as a cathode electrode for delivering pacing pulses to adjacent cardiac tissue, individually, jointly, or in any combination. When annular electrodes, such as distal annular electrode 22, and / or circumferential annular electrodes, portions of the annular electrode may be electrically insulated by a coating to provide a plurality of distributed non-tissue puncture electrodes along the distally facing surface and / or circumferential surface of the insulating distal member.

[0103] Compared to the tissue-piercing electrode provided by the distal fixation and electrode assembly 736, the non-tissue-piercing electrode 722 and other examples listed above are expected to provide more reliable and effective atrial pacing and sensing. The atrial cavity wall is relatively thin compared to the ventricular cavity wall. A tissue-piercing atrial cathode electrode may extend too deeply within the atrial tissue, resulting in unintentional, continuous, or intermittent capture of the ventricular tissue. Because the ventricular signal has a greater signal intensity in the cardiac electrical signals received via the tissue-piercing atrial cathode electrode, which is physically closer to the ventricular tissue, the tissue-piercing atrial cathode electrode can interfere with the sensing of the atrial signal. The tissue-piercing electrode assembly 712 can be securely anchored in the ventricular tissue to stabilize the implantation positioning of the device 710 and provide reasonable assurance that the tip electrode 742 performs sensing and pacing in the ventricular tissue while the non-tissue-piercing electrode 722 reliably performs pacing and sensing in the atrium. When the device 710 is implanted into the target implantation region 4 (e.g., as shown in the image), Figure 1 As shown, when in the ventricular septum, the tip electrode 742 can reach the left ventricular tissue to pace the left ventricle, while the non-tissue-piercing electrode 722 provides pacing and sensing in the right atrium. The length of the tissue-piercing electrode assembly 712 from the distally facing surface 738 can be in the range of about 4 mm to about 8 mm to reach the left ventricular tissue. In some cases, the device 710 can achieve four-chamber pacing by delivering atrial pacing pulses from the atrial pacing circuit 83 via the non-tissue-piercing electrode 722 in the target implantation area 4 to achieve bi-atrial (right and left atrium) capture, and by delivering ventricular pacing pulses from the ventricular pacing circuit 85 via the tip electrode 742 advanced from the target implantation area 4 into the ventricular tissue to achieve bi-ventricular (right and left ventricle) capture.

[0104] Figure 10 It shows, for example, the use of Figure 5 An illustrative method 600 for detecting atrial activity using an acoustic or motion detector 11, the atrial activity being used to represent physiological response information. Specifically, method 600 may include detecting atrial contraction based on analysis of motion signals (e.g., provided by the motion detector 11) that can be performed by an IMD implanted in the patient's heart. In some embodiments, the motion signals may be provided by an IMD implanted within a ventricle (e.g., the right ventricle) of the patient's heart. Method 600 may include initiating an atrial contraction detection delay period 630 upon identifying a ventricular activation event. Method 600 may include initiating an atrial contraction detection window 632 upon the expiration of the atrial contraction delay period. Method 600 may include analyzing the motion signals within the atrial contraction detection window.

[0105] Method 600 may include: filtering the motion signal within an atrial contraction detection window; rectifying the filtered signal; and generating a derivative signal 634 of the filtered and rectified motion signal within the atrial contraction detection window. Method 600 may include determining whether the amplitude of the derivative signal within the atrial contraction detection window exceeds a threshold 636. In response to determining that the amplitude of the derivative signal within the atrial contraction detection window exceeds the threshold (YES in 636), method 600 may proceed to detecting atrial contraction 638. Otherwise (No in 636), method 600 may return to filtering, rectifying, and generating the derivative signal 634. Various techniques for using motion detectors that provide motion signals can be described in U.S. Patent No. 9,399,140 (Cho et al.), entitled “Atrial contraction detection by a ventricular leadless pacing device for atrio-synchronous ventricular pacing,” published on July 26, 2016, which is incorporated herein by reference in its entirety.

[0106] For example, regarding Figure 11 The described method can detect heart sounds (HS) and use them to represent physiological response information. As described herein, the amplitude and / or relative time interval of one or more of the S1 to S4 heart sounds can be used to optimize a patient's hemodynamic response to CRT or other cardiac therapies involving cardiac pacing and / or neurostimulation to achieve hemodynamic benefits. The first heart sound, S1, corresponds to the onset of ventricular systole. Ventricular systole begins when an action potential is conducted through the atrioventricular node (AV node) and rapidly depolarizes the ventricular myocardium. This event is distinguished by the QRS complex on the ECG. As the ventricle systoles, the pressure in the ventricle begins to rise, causing the mitral and tricuspid valves between the ventricle and atrium to close abruptly when the ventricular pressure exceeds the atrial pressure. This valvular closure generates S1. S1 typically has a duration of approximately 150 milliseconds and a frequency of approximately 20 Hz to 250 Hz. The amplitude of S1 can provide a surrogate measure of LV contractility. Therefore, an increase in S1 amplitude can be positively correlated with an improvement in LV contractility. Other measurements, such as the pre-ejection phase measured from QRS to S1, can also be used as substitutes for the myocardial contractility index.

[0107] The separation of mitral and tricuspid valve closure due to ventricular asynchrony can be observed as separate M1 and T1 peaks in the S1 signal. The merging of M1 (mitral closure sound) and T1 (tricuspid closure sound) can be used as an indicator of improved ventricular synchrony.

[0108] Typically, after the QRS complex on an ECG and mitral valve closure, left ventricular pressure (LVP) rises sharply and continues to increase during ventricular systole until the aortic and pulmonary valves open, ejecting blood into the aorta and pulmonary arteries. During ejection, ventricular contractions usually continue to raise blood pressure in the ventricles, as well as in the aorta and pulmonary arteries. As contractions decrease, blood pressure drops until the aortic and pulmonary valves close.

[0109] The second heart sound, S2, is generated by closing the aortic and pulmonary valves near the end of ventricular systole and the beginning of ventricular diastole. Therefore, S2 can be correlated with diastolic pressure in the aorta and pulmonary artery. S2 typically has a duration of approximately 120 milliseconds and a frequency of approximately 25 to 350 Hz. The time interval between S1 and S2, i.e., the S1-S2 interval, can represent the systolic time interval (STI) corresponding to the isovolumetric contraction (pre-ejection) and ejection phases of the cardiac cycle. This S1-S2 interval can provide a surrogate measure of stroke volume. Furthermore, the ratio of the pre-ejection (Q-S1) to the S1-S2 time can be used as an index of myocardial contractility.

[0110] The third heart sound, S3, is associated with early passive diastolic filling of the ventricle, and the fourth heart sound, S4, can be associated with late active ventricular filling due to atrial contraction. Normally, the third sound is difficult to hear with a stethoscope in healthy patients, and the fourth sound is usually not heard. The presence of the third and fourth heart sounds during a stethoscope examination can indicate pathological conditions. The S3 and S4 heart sounds can be used to optimize pacing parameters due to their association with cardiac diastolic function. Typically, these sounds are minimized or absent when optimal pacing parameters are identified. Other aspects of the S1 through S4 heart sounds, as well as their timing, can be used in optimizing cardiac pacing parameters, as is known to those skilled in the art.

[0111] Figure 11 This is a flowchart 800 of a method for optimizing pacing control parameters using heart sounds, according to one embodiment. The method of this disclosure may include one or more blocks shown in flowchart 800. Other examples of using heart sounds to optimize cardiac therapy are generally described in U.S. Patent No. 9,643,0134, entitled “System and method for pacing parameter optimization using heart sounds,” issued May 9, 2017, which is incorporated herein by reference in its entirety.

[0112] The pacing parameter optimization method can be initiated at box 802. The optimization process can be initiated in response to a user command received via an external programmer. At initial IMD implantation, during office follow-up, or during a remote patient monitoring session, the user can initiate the HS-based optimization procedure using an external programmer or a networked computer. Alternatively, the process shown in flowchart 800 can be an automated process that starts periodically or an automated process that starts in response to the sensing of a need for therapy delivery or adjustment based on sensed physiological signals (which may include sensed HS signals).

[0113] At box 804, select the pacing control parameter to optimize. The control parameter can be a timing-related parameter, such as the AV interval or VV interval. The pacing vector is another control parameter that can be selected for optimization at box 804. For example, when using a multipolar lead, such as a coronary sinus lead, multiple bipolar or monopolar pacing vectors can be selected to pac a given cardiac chamber. The pacing site associated with a particular pacing vector can have a significant impact on the hemodynamic benefits of pacing therapy. Thus, the pacing vector is a pacing control parameter that can be optimized using the methods described herein.

[0114] The pacing sequence is initiated at box 806 using the initial parameter settings for the test parameters selected at box 804. In one embodiment, the AV interval is being optimized, and ventricular pacing is delivered with the initial AV interval settings. It should be understood that the initial AV interval setting can be selected at box 806 by first measuring the inherent AV interval of a patient with intact AV conduction (i.e., no AV blockage). The initial AV interval can be the default pacing interval, the last programmed AV interval, or the minimum or maximum AV interval to be tested. Alternatively, if VV interval optimization is selected, the inherent interventricular conduction time can be measured first, and the pacing VV interval can be iteratively adjusted starting with a VV interval that is longer, shorter, or approximately equal to the inherent VV conduction time.

[0115] An iterative process is performed to adjust the selected test parameters to at least two different settings. The parameters can be adjusted to different settings in any desired order (e.g., incremental, decremental, random, etc.). For example, during AV interval adjustment, the initial AV interval can be set to be just longer than or approximately equal to the measured intrinsic AV conduction time, and then said initial AV interval is iteratively reduced to the minimum AV interval test setting. During pacing using each pacing parameter setting, the HS signal is acquired at box 808. At box 812, the iterative process advances to the next test parameter setting until, as determined at box 810, all test parameter settings have been applied and the HS signal has been recorded for each setting.

[0116] Multiple cardiac cycles of HS signals can be acquired, enabling overall averaging or generalization of HS parameter measurements obtained from individual cardiac cycles. It should be understood that amplification, filtering, rectification, noise cancellation techniques, or other signal processing steps can be used to improve the signal-to-noise ratio of the HS signal, and these steps may differ for each heart sound acquired, which may include any or all types of heart sounds.

[0117] At block 814, for each test parameter setting, at least one HS parameter measurement result is determined from the recorded HS signal. For example, an IMD processor included in a programmer, an external processor, or a combination of both can perform the HS signal analysis described herein. In one embodiment, at block 814, S1 and S2 are recorded and HS parameters are measured using the S1 and S2 signals. For example, the amplitude of S1, the V-S2 interval (where the V event can be V pacing or a sensed R wave), and the S1-S2 interval are measured. The presence of S3 and / or S4 can also be noted, or these signals can be measured to determine the relevant parameters. HS signal parameters are determined for at least two different test parameter settings (e.g., at least two different AV intervals, two or more different VV intervals, or two or more different pacing vectors).

[0118] At block 818, the trend of each HS parameter determined at block 810 as a function of the pacing parameter test settings is determined. In one embodiment, the trend of each of the V-S2 interval, S1 amplitude, and S1-S2 interval is determined. Other embodiments may include determining the separation of M1 and T1 sounds during the S1 signal. Based on the trend of one or more HS parameters relative to the changing pacing control parameters, at block 820, the processor may automatically identify the optimal pacing parameter settings. Alternatively or additionally, at block 822, the HS trends are reported and displayed on an external device, such as a programmer, or at a remote networked computer.

[0119] If, when positioning the multipolar electrode along the heart chambers (e.g., along the quadrupole lead of the LV), the pacing parameters being tested are, for example, pacing site or pacing vector, the pacing site or vector can be selected based on maximizing a HS-based surrogate that maximizes ventricular contractility. In one embodiment, the amplitude of S1 is used as a surrogate for ventricular contractility, and the pacing site or vector associated with the maximum S1 is identified at block 820 as the optimal pacing vector setting.

[0120] Determining the trend of each HS parameter at box 818 may include determining whether the V-S2 interval trend exhibits a sudden change in slope, such as from a generally flat trend to a downward trend. The AV interval associated with a sudden change in the VS2 interval trend can be identified as the optimal AV interval setting. The optimal AV interval can be further identified based on other HS trends, such as the maximum S1 amplitude and / or the maximum S1-S2 interval.

[0121] In some embodiments, at block 824, the automatically identified optimal pacing parameter settings can also be automatically programmed in the IMD. In other embodiments, clinicians or users review the reported HS data and the suggested one or more pacing parameter settings and can accept the suggested settings or select another setting based on the HS data.

[0122] The HS sensing module or circuit system can be operatively coupled to the control circuit 80. Figure 8 The system is configured to receive analog signals from an HS sensor used to sense one or more of these heart sounds. For example, the HS sensing module may include one or more "channels" configured to specifically sense a particular heart sound based on its frequency, duration, and timing. For example, an ECG / EGM sensing circuitry may be used by control circuitry 80 to set the HS sensing window used by the HS sensing module for sensing heart sounds. The HS sensing module may include one or more sensing amplifiers, filters, and rectifiers for optimizing the signal-to-noise ratio of the heart sound signal. Individual and unique amplification and filtering characteristics can be provided for sensing each of the S1 to S4 sounds to improve signal quality as needed.

[0123] Bioimpedance or intracardiac impedance can be measured and used to represent physiological response information. For example, any IMD described herein can measure intracardiac impedance signals by injecting current and measuring the voltage between electrodes (e.g., selected electrodes) in an electrode vector configuration. For example, an IMD can measure impedance signals by injecting current (e.g., a non-pacing threshold current) between a first electrode (e.g., the RV electrode) and an electrode located in the RV near the tricuspid valve and measuring the voltage between the first and second electrodes. Another vector that can be used is from the LV electrode to the RV electrode. It will be appreciated that other vector pair configurations can be used for stimulation and measurement. Impedance can be measured between any set of electrodes covering the tissue or chamber of the heart of interest. Thus, an individual can inject current and measure voltage to calculate impedance on the same two electrodes (bipolar configuration), or inject current and measure voltage on two separate pairs of electrodes (e.g., one pair for current injection and one pair for voltage sensing), thus a quadrupole configuration. For a quadrupole electrode configuration, the current injection electrode and the voltage sensing electrode can be aligned (or closely parallel) to each other, and the voltage sensing electrode can be located within the current sensing field. For example, if a current is injected between the SVC coil electrode and the RV tip electrode, voltage sensing can be located between the RV coil electrode and the RV toroidal electrode. In such embodiments, the VfA lead can be used for LV cardiac therapy or sensing. The impedance vector can be configured to cover a specific anatomical region of interest, such as the atrium or ventricle.

[0124] The illustrative methods and / or apparatuses described herein can monitor one or more electrode vector configurations. Further, multiple impedance vectors can be measured simultaneously and / or periodically relative to another vector. In at least one embodiment, the exemplary methods and / or apparatuses can use impedance waveforms to acquire selection data (e.g., finding suitable reference points to allow extraction of measurements from such waveforms, etc.) to optimize the CRT.

[0125] As used herein, the term "impedance signal" is not limited to the original impedance signal. It should be noted that the original impedance signal can be processed, normalized, and / or filtered (e.g., to remove artifacts, noise, static electricity, electromagnetic interference (EMI), and / or foreign signals) to provide an impedance signal. Furthermore, the term "impedance signal" can include its various mathematical derivatives, which include the real and imaginary parts of the impedance signal, the impedance-based conductance signal (i.e., the reciprocal of the impedance), etc. In other words, the term "impedance signal" can be understood as including a conductance signal, i.e., a signal that is the reciprocal of the impedance signal.

[0126] In one or more embodiments of the methods and / or apparatus described herein, various patient physiological parameters (e.g., intracardiac impedance, heart sounds, cardiac cycle intervals such as RR intervals, etc.) can be monitored to acquire selection data for optimizing CRT (e.g., setting AV and / or VV delays, optimizing cardiac contractility by using and / or measuring the first derivative of impedance, selecting pacing sites, selecting pacing vectors, lead placement, or evaluating pacing capture from an electrical and mechanical perspective (e.g., electrical capture may not imply mechanical capture, and heart sounds and impedance can help assess whether electrical stimulation captures the heart by looking at the mechanical information from heart sounds and impedance), selecting an effective electrode vector configuration for pacing, etc.). For example, intracardiac impedance signals between two or more electrodes can be monitored to provide this optimization.

[0127] Figure 12 An example of method 850 for obtaining selection data for one of the device parameter options (e.g., one of the selectable device parameters that can be used to optimize a CRT, such as potential AV delay that may be the optimal parameter) is shown. Other examples of using heart sounds to optimize cardiac therapy are generally described in U.S. Patent No. 9,707,399, entitled “Cardiac resynchronization therapy optimization based on intracardiac impedance and heart sounds,” issued July 18, 2017, which is incorporated herein by reference in its entirety.

[0128] As shown, one of several device options is used to deliver pacing therapy (box 852) (e.g., the multiple device parameter options can be selected, determined, and / or calculated AV delays, such as percentages of inherent AV delay, e.g., 40% inherent AV delay, 50% inherent AV delay, 60% inherent AV delay, 70% inherent AV delay, 80% inherent AV delay, etc.). For the device parameter option used for pacing (box 852), selection data is acquired at each of the multiple electrode vector configurations (e.g., intracardiac impedance is monitored over multiple cardiac cycles, and selection data is extracted using such impedance signals). As indicated in decision box 854, if selection data has not yet been acquired from all desired electrode vector configurations, the loop for acquiring selection data is repeated (e.g., the loops shown in boxes 858, 860, 862, and 864). If selection data has been acquired from all desired electrode vector configurations, another different device parameter option is used to deliver the therapy (box 856), and the process is repeated. Figure 12Method 850 (e.g., for different device parameter options) continues until selection data has been acquired for all different device parameter options (e.g., for each of the different device parameter options and at each of the multiple electrode vector configurations).

[0129] As shown in the repetitive loop of acquiring selection data for each desired electrode vector configuration in the desired electrode vector configurations (e.g., boxes 858, 860, 862, and 864), one of the plurality of electrode vector configurations is selected for acquiring selection data (box 858). For the selected electrode vector configuration, time reference points associated with at least a portion of the systolic portion of at least one cardiac cycle and / or associated with at least a portion of the diastolic portion of at least one cardiac cycle are acquired (box 860) (e.g., using heart sounds, analyzing minimum and maximum values ​​of impedance signals, applying algorithms based on physiological parameters (e.g., RR intervals), etc.). For example, time reference points associated with the systolic and / or diastolic portions of the cardiac cycle may be acquired, time reference points associated with one or more defined segments within the systolic and / or diastolic portions of the cardiac cycle may be acquired, and / or time reference points associated with one or more points and / or portions within or associated with one or more points and / or portions of the systolic and / or diastolic portions of the cardiac cycle may be acquired. Furthermore, for example, time reference points may be acquired that relate only to the systolic or diastolic portion of the cardiac cycle; time reference points may be acquired that relate only to one or more defined segments within the systolic or diastolic portion of the cardiac cycle; and / or time reference points may be acquired that relate to one or more points and / or portions within or related to one or more points and / or portions of the systolic or diastolic portion of the cardiac cycle. In other words, reference points may be acquired that relate to both the systolic and diastolic portions of the cardiac cycle or only to one of such portions of the cardiac cycle. Further, for example, such reference points may represent or indicate measurement windows and / or time periods (e.g., intervals, points, etc.) at or during which intracardiac impedance can be measured for the analysis described herein.

[0130] In approximately the same time frame (e.g., approximately simultaneously with the acquired reference point), an intracardiac impedance signal is acquired at the selected electrode vector configuration (box 862). Using the acquired reference point and the acquired intracardiac impedance signal, measurements from the impedance signal are extracted based on the time reference point (box 864) (e.g., the integral of the impedance signal within a measurement window defined between reference points, the maximum slope of the impedance signal within a measurement window defined between reference points, the time between reference points, the maximum impedance at the reference point, etc.). One or more of these measurements may be comparable to the expected values ​​used for such measurements, thereby allowing determination of whether the measurements indicate that device parameter options may be effective device parameters for optimizing therapy (e.g., a scoring algorithm may be used to determine whether a device parameter option is an optimal parameter based on whether multiple such measurements meet certain criteria or thresholds).

[0131] For at least one cardiac cycle, determine the measurement data for each device parameter in the device parameter options (e.g., such as...). Figure 12 (As described in the document). In one or more embodiments, such measurement data is acquired for multiple cardiac cycles. The cardiac cycle during which the measurement data is acquired can be any suitable cardiac cycle. In one or more embodiments, the selected cardiac cycle during which the measurement data is acquired is based on the respiratory cycle. In at least one embodiment, the measurement data is acquired during a cardiac cycle that occurs at the end of the respiratory cycle (e.g., near the end of exhalation).

[0132] Figure 13 An illustrative system 100 is depicted, comprising an electrode device 110, a display device 130, and a computing device 140. The illustrated electrode device 110 includes a plurality of electrodes incorporated or contained within a band wrapped around the chest or torso of a patient 120. The electrode device 110 is operatively coupled to the computing device 140 (e.g., via a wired or wireless connection) to provide electrical signals from each of the electrodes to the computing device 140 for analysis, evaluation, etc. The illustrative electrode device can be described in U.S. Patent No. 9,320,446, entitled “Bioelectric Sensor Device and Methods,” published April 26, 2016, which is incorporated herein by reference in its entirety. Further reference will be made to… Figure 14-15 The exemplary electrode device 110 will be described in more detail.

[0133] Although not described herein, illustrative system 100 may further include an imaging device. The imaging device can be any type of imaging device configured to noninvasively image or provide an image of at least a portion of a patient. For example, in addition to noninvasive tools such as contrast solutions, the imaging device may provide an image of the patient without using any components or parts that can be positioned within the patient's body. It should be understood that the exemplary systems, methods, and interfaces described herein can be further used to provide noninvasive assistance to a user (e.g., a physician) to calibrate and / or deliver VfA pacing therapy, to locate and place devices to deliver VfA cardiac pacing therapy, and / or to locate or select pacing electrodes or pacing vectors proximal to the patient's heart for atrial-ventricular pacing therapy in conjunction with an assessment of atrial-ventricular pacing therapy.

[0134] For example, illustrative systems, methods, and interfaces can provide image-guided navigation that can be used to navigate leads including leadless devices, electrodes, leadless electrodes, radio electrodes, catheters, etc., within a patient's body, while also providing non-invasive cardiac therapy assessments that include determining whether an atrial-to-ventricular (VfA) pacing setting is optimal, or determining whether one or more selected parameters (e.g., selected location information (e.g., location information for targeting a specific location in the left ventricle)) are optimal) are optimal. Exemplary systems and methods using imaging devices and / or electrode devices can be described in the following: U.S. Patent Publication No. 2014 / 0371832, filed June 12, 2013, entitled "Implantable Electrode Location Selection"; U.S. Patent Publication No. 2014 / 0371833, filed June 12, 2013, entitled "Implantable Electrode Location Selection"; U.S. Patent Publication No. 2014 / 0323892, filed March 27, 2014, entitled "Systems, Methods, and Interfaces for Identifying Effective Electrodes"; and U.S. Patent Publication No. 2014 / 0323892, filed March 27, 2014, entitled "Systems, Methods, and Interfaces for Identifying Optical Electrical Vectors". U.S. Patent Publication No. 2014 / 0323882, entitled “Vectors”, is incorporated herein by reference in its entirety.

[0135] The illustrative imaging device can be configured to capture X-ray images and / or any other alternative imaging modality. For example, the imaging device can be configured to capture images or image data using isocentric fluoroscopy, biplane fluoroscopy, ultrasound, computed tomography (CT), multi-slice computed tomography (MSCT), magnetic resonance imaging (MRI), high-frequency ultrasound (HIFU), optical coherence tomography (OCT), intravascular ultrasound (IVUS), two-dimensional (2D) ultrasound, three-dimensional (3D) ultrasound, four-dimensional (4D) ultrasound, intraoperative CT, intraoperative MRI, etc. Furthermore, it should be understood that the imaging device can be configured to capture multiple consecutive images (e.g., sequentially) to provide video frame data. In other words, multiple images captured by the imaging device over time can provide video frame data or motion picture data. Additionally, images can be acquired and displayed in two, three, or four dimensions. In a more advanced form, four-dimensional surface rendering of the heart or other areas of the body can also be achieved by incorporating cardiac data or other soft tissue data from images or preoperative image data captured via MRI, CT, or echocardiography modalities. Image datasets from mixed modalities, such as positron emission tomography (PET) combined with CT or single-photon emission computed tomography (SPECT) combined with CT, can also provide functional image data superimposed on anatomical data, for example, to navigate therapeutic devices to target locations in adjacent areas of the heart or other areas of interest, such as locations within the left ventricle, the high posterior basement containing the left ventricular cavity, and / or selected locations within the septal region.

[0136] Systems and / or imaging devices that can be used in conjunction with the illustrative systems and methods described herein may be described in the following: U.S. Patent Application Publication No. 2005 / 0008210, Evron et al., January 13, 2005; U.S. Patent Application Publication No. 2006 / 0074285, Zakhah et al., April 6, 2006; U.S. Patent Application Publication No. 2011 / 0112398, Zakhah et al., May 12, 2011; U.S. Patent Application Publication No. 2013 / 0116739, Brada et al., May 9, 2013; and U.S. Patent No. 6, Evron et al., December 27, 2005. U.S. Patent No. 7,286,866 to Okerlund et al., published October 23, 2007; U.S. Patent No. 7,308,297 to Reddy et al., published December 11, 2011; U.S. Patent No. 7,308,299 to Burrell et al., published December 11, 2011; U.S. Patent No. 7,321,677 to Evron et al., published January 22, 2008; U.S. Patent No. 7,346,381 to Okerlund et al., published March 18, 2008; and U.S. Patent No. 7,454,248 to Burrell et al., published November 18, 2008. U.S. Patent No. 7,499,743 to Vass et al., published March 3, 2009; U.S. Patent No. 7,565,190 to Okerlund et al., published July 21, 2009; U.S. Patent No. 7,587,074 to Zakhah et al., published September 8, 2009; U.S. Patent No. 7,599,730 to Hunter et al., published October 6, 2009; U.S. Patent No. 7,613,500 to Vass et al., published November 3, 2009; U.S. Patent No. 7,742,629 to Zakhah et al., published June 22, 2010; and U.S. Patent No. 7,742,629 to Okerlund et al., published June 29, 2010. U.S. Patent No. 7,747,047 to und et al., U.S. Patent No. 7,778,685 to Evron et al., published August 17, 2010, U.S. Patent No. 7,778,686 to Vass et al., published August 17, 2010, U.S. Patent No. 7,813,785 to Okerlund et al., published October 12, 2010, U.S. Patent No. 7,996,063 to Vass et al., published August 9, 2011, U.S. Patent No. 8,060,185 to Hunter et al., published November 15, 2011, and U.S. Patent No. 8,401 to Verard et al., published March 19, 2013.Reference 616, each of which is incorporated herein by reference in its entirety.

[0137] Display device 130 and computing device 140 can be configured to display and analyze data, such as electrical signals (e.g., electrocardiogram data), cardiac information representing one or more of mechanical and electrical cardiac functions (e.g., mechanical cardiac function only, electrical cardiac function only, or both). The cardiac information may include, for example, information on electrical heterogeneity or electrical asynchrony generated using electrical signals gathered, monitored, or collected using electrode device 110, alternative electrical activation information, or data. In at least one embodiment, computing device 140 may be a server, a personal computer, or a tablet computer. Computing device 140 can be configured to receive input from input device 142 and transmit output to display device 130. Furthermore, the computing device 140 may include a data storage device that may allow access to processing programs or routines and / or one or more other types of data, such as a graphical user interface configured to non-invasively assist a user in targeting the placement of a pacing device for calibration and / or delivery of pacing therapy, and / or for evaluating pacing therapy at that location (e.g., the location of an implantable electrode for pacing, the location of pacing therapy delivered by a specific pacing vector, etc.).

[0138] Computing device 140 may be operatively coupled to input device 142 and display device 130 to, for example, transmit data to and from each of input device 142 and display device 130. For example, computing device 140 may be electrically coupled to each of input device 142 and display device 130 using analog electrical connections, digital electrical connections, wireless connections, bus-based connections, network-based connections, Internet-based connections, etc. As further described herein, a user may provide input to input device 142 to manipulate or modify one or more graphic depictions displayed on display device 130, and to view and / or select one or more pieces of information related to cardiac therapy.

[0139] Although the input device 142 depicted is a keyboard, it should be understood that the input device 142 may include any device capable of providing input to the computing device 140 for performing the functions, methods, and / or logic described herein. For example, the input device 142 may include a mouse, a trackball, a touchscreen (e.g., a capacitive touchscreen, a resistive touchscreen, a multi-touch touchscreen, etc.), etc. Similarly, the display device 130 may include any device capable of displaying information to a user, such as a graphical user interface 132 containing cardiac information, text commands, graphical depictions of electrical activation information, graphical depictions of the anatomy of the human heart, images or graphical depictions of a patient's heart, graphical depictions of a leadless pacemaker for calibrating and / or delivering pacing therapy, graphical depictions of a leadless pacemaker positioned or placed to provide VfA pacing therapy, graphical depictions of the location of one or more electrodes, graphical depictions of the human torso, images or graphical depictions of a patient's torso, graphical depictions or actual images of implanted electrodes and / or leads, etc. Furthermore, the display device 130 may include a liquid crystal display, an organic light-emitting diode screen, a touchscreen, a cathode ray tube display, etc.

[0140] The processing programs or routines stored and / or executed by the computing device 140 may include programs or routines for computational mathematics, matrix mathematics, deviation determination (e.g., standard deviation, variance, range, quartile range, mean absolute difference, mean absolute deviation, etc.), filtering algorithms, maximum value determination, minimum value determination, threshold determination, moving window algorithms, decomposition algorithms, compression algorithms (e.g., data compression algorithms), calibration algorithms, image construction algorithms, signal processing algorithms (e.g., various filtering algorithms, Fourier transform, fast Fourier transform, etc.), normalization algorithms, comparison algorithms, vector mathematics, or any other processing required to implement one or more of the illustrative methods and / or processes described herein. The data stored and / or used by the computing device 140 may include, for example, electrical signal / waveform data from the electrode device 110, deviation signals, windowed deviation signals, locations or portions of various signals, electrical activation times from the electrode device 110, graphics (e.g., graphic elements, icons, buttons, windows, dialog boxes, drop-down menus, graphics areas, graphics regions, 3D graphics, etc.), graphical user interfaces, results of one or more processing procedures or routines adopted according to this disclosure (e.g., electrical signals, cardiac information, etc.), or any other data necessary for performing one or more processes or methods described herein.

[0141] In one or more embodiments, the illustrative systems, methods, and interfaces may be implemented using one or more computer programs that execute on a programmable computer, such as a computer including, for example, processing power, data storage devices (e.g., volatile or non-volatile memory and / or storage elements), input devices, and output devices. The program code and / or logic described herein may be applied to input data to perform the functions described herein and generate desired output information. The output information may be applied as input to one or more other means and / or methods as described herein or to be applied in a known manner.

[0142] The one or more programs described herein for implementing the systems, methods, and / or interfaces can be provided using any programmable language (e.g., high-level programs and / or object-oriented programming languages ​​suitable for communicating with computer systems). Any such program can be stored, for example, on any suitable means, such as a storage medium readable by a general-purpose or special-purpose program running on a computer system (e.g., containing a processing device) for configuring and operating the computer system. In other words, at least in one embodiment, exemplary systems, methods, and / or interfaces can be implemented using a computer-readable storage medium configured with computer programs, wherein such a storage medium causes a computer to operate in a specific and predefined manner to perform the functions described herein. Further, in at least one embodiment, exemplary systems, methods, and / or interfaces can be described as being implemented by logic (e.g., object code) encoded in one or more non-transitory media, the logic containing code for execution and, when executed by a processor, operable to perform operations such as the methods, processes, and / or functions described herein.

[0143] The computing device 140 can be, for example, any fixed or mobile computer system (e.g., controller, microcontroller, personal computer, microcomputer, tablet computer, etc.) and can generally be described as containing a system of processing circuitry. The exact configuration of the computing device 140 is not limiting, and substantially any device capable of providing suitable computing and control capabilities (e.g., graphics processing, etc.) can be used. As described herein, a digital file can be any medium (e.g., volatile or non-volatile memory, CD-ROM, punched card, magnetically recordable media such as disks or magnetic tapes, etc.) containing digital bits (e.g., encoded in binary or ternary) that can be read and / or written by the computing device 140 described herein. Furthermore, as described herein, a user-readable format file can be any representation of data (e.g., ASCII text, binary numbers, hexadecimal numbers, decimal numbers, graphics, etc.) that can be presented on any medium (e.g., paper, display, etc.) that can be read and / or understood by a user.

[0144] In view of the foregoing, it will be apparent that the functions described in one or more embodiments of this disclosure may be implemented in any manner known to those skilled in the art. Thus, the computer language, computer system, or any other software / hardware intended for implementing the processes described herein should not limit the scope of the systems, processes, or programs described herein (e.g., the functions provided by such systems, processes, or programs).

[0145] The patient's cardiac electrical activation time can be used to assess the patient's cardiac symptoms and / or to calibrate, deliver, or evaluate atrium-to-ventricle (VfA) cardiac therapies to be delivered or being delivered to the patient. This can be achieved using methods such as... Figure 13-15 The illustrated electrode device 110 is used to monitor or determine alternative electrical activation information or data in one or more regions of a patient's heart. The exemplary electrode device 110 can be configured to measure the body surface potential of the patient 120, and more specifically, to measure the trunk surface potential of the patient 120.

[0146] like Figure 14 As shown, the illustrative electrode device 110 may include a group or array of electrodes 112, a strip 113, and an interface / amplifier circuitry system 116. In at least one embodiment, a portion of the electrode set may be used, wherein the portion corresponds to a specific location on the patient's heart. Electrodes 112 may be attached to or coupled to strip 113, and strip 113 may be configured to wrap around the torso of patient 120 such that electrodes 112 surround the patient's heart. As further shown, electrodes 112 may be positioned around patient 120, including posterior, lateral, posterolateral, anterolateral, and anterior locations of patient 120's torso.

[0147] Furthermore, electrode 112 can be electrically connected to interface / amplifier circuitry 116 via wired connection 118. Interface / amplifier circuitry 116 can be configured to amplify the signal from electrode 112 and provide the signal to computing device 140. Other exemplary systems can use wireless connections (e.g., as data channels) to transmit signals sensed by electrode 112 to interface / amplifier circuitry 116, and further to computing device 140. For example, interface / amplifier circuitry 116 can be electrically coupled to each of computing device 140 and display device 130 using, for example, analog electrical connections, digital electrical connections, wireless connections, bus-based connections, network-based connections, Internet-based connections, etc.

[0148] Despite Figure 14In one example, electrode device 110 includes strips 113, but in other examples, any of a variety of mechanisms, such as tape or adhesive, can be used to assist in the spacing and placement of electrodes 112. In some examples, strips 113 may comprise elastic bands, tape strips, or cloth. In other examples, electrodes 112 may be placed individually on the torso of patient 120. Further, in other examples, electrodes 112 (e.g., arranged in an array) may be patches, vests, and / or other means of securing electrodes 112 to or within the torso of patient 120.

[0149] Electrodes 112 can be configured to surround the heart of patient 120 and record or monitor electrical signals associated with cardiac depolarization and repolarization after a signal has propagated through the torso of patient 120. Each electrode in the electrodes 112 can be used in a monopolar configuration to sense torso surface potentials reflecting cardiac signals. Interface / amplifier circuitry 116 can also be coupled to return electrodes or unrelated electrodes (not shown) that can be used in combination with each electrode 112 for monopolar sensing. In some instances, there may be about 12 to about 50 electrodes 112 spatially distributed around the patient's torso. Other configurations may have more or fewer electrodes 112.

[0150] The computing device 140 can record and analyze electrical activity (e.g., trunk surface potential signals) sensed by the electrodes 112 and amplified / modulated by the interface / amplifier circuitry 116. The computing device 140 can be configured to analyze signals from the electrodes 112 to provide anterior and posterior electrode signals as described further herein and to replace cardiac electrical activation time, such as representing the actual or local electrical activation time of one or more regions of the patient's heart. The computing device 140 can also be configured to analyze signals from the electrodes 112 to provide anterior septal electrode signals as described further herein for calibrating, delivering, and / or evaluating VfA pacing therapy and to replace cardiac electrical activation time, such as representing the actual or local electrical activation time of one or more anterior septal regions of the patient's heart. Furthermore, the electrical signal measured at a location on the left anterior surface of the patient's torso can represent or substitute for the electrical signal of the left anterior left ventricular region of the patient's heart; the electrical signal measured at a location on the left lateral surface of the patient's torso can represent or substitute for the electrical signal of the left lateral left ventricular region of the patient's heart; the electrical signal measured at a location on the left posterior surface of the patient's torso can represent or substitute for the electrical signal of the posterior left ventricular region of the patient's heart; and the electrical signal measured at a location on the posterior surface of the patient's torso can represent or substitute for the electrical signal of the left posterior ventricular region of the patient's heart. In one or more embodiments, the measurement of activation time can be performed by measuring the time interval between an episode of cardiac depolarization (e.g., an episode of a QRS complex) and an appropriate reference point (e.g., peak, minimum, minimum slope, maximum slope, zero crossover, threshold crossover, etc.).

[0151] Additionally, computing device 140 may be configured to provide a graphical user interface depicting the alternative electrical activation time obtained using electrode device 110. Exemplary systems, methods, and / or interfaces may be used non-invasively to assess a patient's cardiac condition and / or calibrate, deliver, or evaluate VfA pacing therapy to be delivered or being delivered to the patient using electrical information collected by electrode device 110.

[0152] Figure 15 Another illustrative electrode device 110 is shown, comprising a plurality of electrodes 112 configured to surround the heart of a patient 120 and to record or monitor electrical signals associated with cardiac depolarization and repolarization after the signals have propagated through the torso of the patient 120. The electrode device 110 may include a vest 114 to which the plurality of electrodes 112 may be attached or coupled. In at least one embodiment, the plurality of electrodes 112 or an array of the electrodes may be used to collect electrical information, such as alternative electrical activation time.

[0153] and Figure 14 The electrode device 110 is similar. Figure 13 The electrode device 110 may include an interface / amplifier circuitry 116 electrically coupled to each of the electrodes 112 via a wired connection 118 and configured to transmit signals from the electrodes 112 to the computing device 140. As shown, the electrodes 112 may be distributed over the torso of the patient 120, including, for example, the anterior, lateral, posterior, anterior, and posterior surfaces of the torso of the patient 120.

[0154] Vest 114 may be formed of fabric, with electrodes 112 attached to the fabric. Vest 114 may be configured to maintain the positioning and spacing of electrodes 112 on the torso of patient 120. Further, vest 114 may be marked to aid in determining the position of electrodes 112 on the torso surface of patient 120. In one or more embodiments, vest 114 may include about 17 or more anterior electrodes that can be positioned near the patient's anterior torso, and about 39 or more posterior electrodes that can be positioned near the patient's anterior torso. In some instances, about 25 to about 256 electrodes 112 may be distributed around the torso of patient 120, but other configurations may have more or fewer electrodes 112.

[0155] As described herein, electrode device 110 can be configured to measure electrical information (e.g., electrical signals) representing different regions of a patient's heart. For example, the activation time of different regions of the patient's heart can be estimated from surface electrocardiogram (ECG) activation times measured using surface electrodes proximate to surface regions corresponding to different regions of the patient's heart. In at least one instance, the activation time of the anterior septum region of the patient's heart can be estimated using surface ECG activation times measured using surface electrodes proximate to surface regions corresponding to surface regions of the anterior septum region of the patient's heart. That is, a portion, rather than the entire set, of electrodes 112 can be used to generate activation times corresponding to specific locations of the patient's heart corresponding to portions of the electrode set.

[0156] The illustrative systems, methods, and interfaces can be used to provide noninvasive assistance to a user when assessing a patient's cardiac health or condition and / or evaluating cardiac therapies such as atrioventricular (VfA) pacing therapy using electrode device 110 (e.g., currently the cardiac therapy is being delivered to the patient during or after implantation). Furthermore, the exemplary systems, methods, and interfaces can be used to assist a user in configuring or calibrating cardiac therapies (e.g., VfA pacing therapy) to be delivered to or being delivered to a patient.

[0157] VfA pacing can be described as providing synchronized, homogeneous activation of the heart's ventricles. As an example, patients with atrial-ventricular (AV) block or prolonged AV timing that may lead to heart failure and otherwise have intact (e.g., normal) QRS can benefit from VfA pacing therapy. Additionally, as an example, VfA pacing can provide beneficial activation in heart failure patients with inherent ventricular conduction disorders. Furthermore, proper placement of the VfA pacing device can provide optimal ventricular activation in such patients. Further, in left ventricular (LV) resynchronization in heart failure patients with left bundle branch block (LBBB), VfA pacing has been found to facilitate easier access to the left ventricular endocardium, or endocardial blood pools, without exposing the leadless device. Simultaneously, in the aforementioned examples, this can help engage portions of the conduction system to potentially correct LBBB and effectively resynchronize the patient.

[0158] Multiple external electrodes can be used (e.g.) Figure 13-15Electrode 112) is used to monitor electrical activity. Electrical activity can be monitored via multiple electrodes during or without VfA pacing therapy. The monitored electrical activity can be used to evaluate VfA pacing therapy on a patient. Electrical activity monitored using the described ECG band can be used to evaluate at least one pacing setting for VfA pacing therapy on the heart. As an example, the pacing setting can be any parameter or combination of parameters, including but not limited to electrode positioning, pacing polarity, pacing output, pacing pulse width, timing of VfA pacing relative to the atrium (A), pacing rate, etc. Further, as an example, the location of the leadless device or pacing lead can include a location in the left ventricle that enters or is closely adjacent to the high posterior basal and / or septal (HPBS) region of the left ventricular cavity through the right atrium. Furthermore, pacing in or close to the HPBS region can be selective (e.g., involving stimulation of a specific region of the HPBS only) or non-selective (e.g., combined pacing at locations in the HPBS and other atrial and / or ventricular septal regions).

[0159] Furthermore, the monitored electrical activity can be used to construct a surface isochron of ventricular activation during or without VfA pacing therapy. The monitored electrical activity and / or ventricular activation map can be used to generate electrical heterogeneity information (EHI). EHI can include measures that determine electrical heterogeneity. Measures of electrical heterogeneity can include a measure of the standard deviation of activation time (SDAT) of electrodes on the left side of the patient's trunk and / or a measure of the mean left ventricular activation time (LVAT) of electrodes on the left side of the patient's trunk. The LVAT can be determined from electrodes on both the anterior and posterior surfaces closer to the left ventricle. Measures of electrical heterogeneity information can also include a measure of the mean right ventricular activation time (RVAT) of electrodes on the right side of the patient's trunk. The RVAT can be determined from electrodes on both the anterior and posterior surfaces closer to the right ventricle. Measures of electrical heterogeneity may include a measure of the mean total activation time (mTAT) obtained from multiple electrode signals from both sides of the patient's trunk, or they may include a range or deviation of activation times on multiple electrodes located on the right or left side of the patient's trunk, or other measures combining the right and left sides of the patient's trunk (e.g., standard deviation, quartile deviation, the difference between the most recent and the earliest activation times). Measures of electrical heterogeneity information may include a measure of the anterior septal activation time (ASAT) of electrodes on the trunk located close to the anterior septum of the heart.

[0160] Electrical heterogeneity information (EHI) can be generated during VfA pacing therapy delivery in one or more VfA pacing settings. EHI can be generated using measures of electrical heterogeneity. As examples, measures of electrical heterogeneity may include one or more of SDAT, LVAT, RVAT, mTAT, and ASAT. In at least one embodiment, only ASAT can be determined and further used, and / or the weight of ASAT may be greater than other values.

[0161] One or more pacing settings associated with VfA pacing therapy can be evaluated. A pacing setting may include multiple pacing parameters. These multiple pacing parameters may be optimal if the patient's cardiac symptoms improve, if VfA pacing therapy effectively captures the desired portion of the left ventricle (e.g., the high posterior basal region and / or septal region), and / or if a measure of electrical heterogeneity improves by a certain threshold compared to the baseline rhythm or therapy. In at least one embodiment, determining whether a pacing setting is optimal may be based on at least one measure of electrical heterogeneity generated by electrical activity during VfA pacing (and also in some embodiments, during natural conduction or in the absence of VfA pacing). The at least one measure may include one or more of SDAT, LVAT, RVAT, mTAT, and ASAT.

[0162] Furthermore, the plurality of pacing parameters may be optimal if the measure of electrical heterogeneity is greater than or less than a specific threshold, and / or if the location of the pacing therapy used to stimulate the left ventricle evokes a specific stimulation pattern in the cardiac muscle fibers. Additionally, the plurality of pacing parameters may be optimal if the measure of electrical heterogeneity indicates correction of left bundle branch block (LBBB), and / or if the measure of electrical heterogeneity indicates full engagement of the Purkinje system, etc. As an example, the measure of electrical heterogeneity of ASAT less than or equal to a threshold (e.g., a threshold of 30 ms) and LVAT less than or equal to a threshold (e.g., a threshold of 30 ms) can indicate correction of LBBB, and therefore, the pacing setting is optimal. As an example, the measure of electrical heterogeneity of RVAT less than or equal to a threshold (e.g., a threshold of 30 ms), ASAT less than or equal to a threshold (e.g., a threshold of 30 ms), and LVAT less than or equal to a threshold (e.g., a threshold of 30 ms) can indicate full engagement of the Purkinje system, and therefore, the pacing setting can be optimal.

[0163] The pacing setting can be determined optimally in response to VfA pacing therapy using acceptable, beneficial pacing settings that indicate full engagement of the patient's natural cardiac conduction system, correction of ventricular conduction obstructions (e.g., left bundle branch block), etc. The pacing setting may include one or more of the following: pacing electrode positioning (including one or more of depth, angle, number of turns of a screw-based fixation mechanism, etc.), voltage, pulse width, intensity, pacing polarity, pacing vector, pacing waveform, pacing timing delivered relative to an intrinsic or pacing atrial event or relative to an intrinsic His bundle potential, and / or pacing location, etc. The pacing vector may include any two or more pacing electrodes, such as a tip electrode for delivering VfA pacing therapy to a canister electrode, a tip electrode for delivery to a ring electrode, etc. The pacing location may refer to the position of any of the one or more pacing electrodes located using a leaded, leadless device, and / or any device or apparatus configured to deliver VfA.

[0164] The pacing settings for VfA pacing therapy can be adjusted. In at least one embodiment, the pacing settings can be adjusted in response to a non-optimal pacing setting. In at least one embodiment, however, the pacing settings can be adjusted in response to a pacing setting within the optimal range in order to determine whether the pacing settings are within the optimal range for VfA pacing therapy to be more beneficial, useful, or practical. The pacing settings can be adjusted to find the optimal amount of electrical heterogeneity.

[0165] In one or more embodiments, the optimal pacing setting can be determined based on a specific metric of the electrical heterogeneity of the ECG band. In at least one instance, the pacing setting can be adjusted at intervals related to changes in the metric of electrical heterogeneity until the metric of electrical heterogeneity equals or approaches a specific metric value. For example, adjustments to the pacing setting may bring the metric of electrical heterogeneity closer to a specific threshold metric of electrical heterogeneity, and the rate of adjustment of the pacing setting may be slowed as the metric approaches the specific threshold. In other words, the pacing setting can be adjusted more quickly when the metric of electrical heterogeneity is far from the specific threshold metric; and the pacing setting can be adjusted more slowly as the metric of electrical heterogeneity approaches the specific threshold metric until the metric of electrical heterogeneity is at the specific threshold metric.

[0166] Various techniques for monitoring electrical activity from patient tissues using an electrode device with multiple external electrodes, which can be used with the apparatus, systems and methods described herein, are disclosed in U.S. Patent Application Serial No. 15 / 934,517 entitled “Evaluation of Ventricle from Atrium Pacing Therapy”, filed March 23, 2018, which is incorporated herein by reference in its entirety.

[0167] Various embodiments of the implantable medical device can be used to optimize CRT using electrical and / or mechanical activity. Alternatively, or in addition to using heart sounds, for example, a motion detector can provide one or more signals indicative of mechanical activity within a patient's heart, which can be used in conjunction with electrical activity detected using one or more electrodes of the implantable medical device. Detected electrical and / or mechanical activity can also be used to assess markers of cardiac remodeling, such as left atrial and left ventricular remodeling that may occur over a long period.

[0168] Figure 16 An implantable medical device, particularly an LPD 500, is schematically illustrated attached from the right atrium (RA) 510 to the atrioventricular (AV) septum 512 or AV septum. Although an LPD is shown, in other embodiments, the implantable medical device may include leads. The LPD 500 may include any one or more of the other components included in the medical devices described in this disclosure. In the illustrated embodiment, the LPD 500 includes at least an activity sensor or motion detector 502, such as an accelerometer, which may be coupled to the sensing circuitry of the LPD. In some cases, the motion detector 502 may be similar to motion detector 11 ( Figure 5 The LPD 500 also includes: at least one atrial electrode 504, which can be implanted in the atrium of a patient's heart to deliver cardiac therapy or sense electrical activity of the atrium; and at least one ventricular electrode 506, which can be implanted in the septum, for example, on the ventricular side of the septum, to deliver cardiac therapy to the ventricle or sense electrical activity of the ventricle.

[0169] In one or more embodiments, the housing of the LPD 500 extends from the proximal region 501 to the distal region 503. The atrial electrode 504 may be coupled to the housing without leads. The ventricular electrode 506 may also be coupled to the distal region 503 of the housing without leads, and in particular, may extend without leads from the distal region. Typically, the ventricular electrode 506 is located distal to the atrial electrode 504. Each of the motion detector 502, the therapy delivery circuitry, the sensing circuitry, and the controller with a processor may be enclosed or contained within the housing of the LPD 500.

[0170] In some embodiments, the atrial electrode 504 may be an RA electrode positioned on the surface of the AV septum 512 within the RA 510, and the ventricular electrode 506 may be a tissue-piercing electrode positioned within the AV septum 512. As shown, the atrial electrode 504 is implanted in the RA 510 in contact with the AV septum 512, and the ventricular electrode 506 is implanted on the left ventricular side of the AV septum 512. In one or more embodiments, the ventricular electrode 506 is implanted from the Koch triangle region of the RA of the patient's heart into the basal region, septal region, or baso-septal region of the LV myocardium of the patient's heart to deliver cardiac therapy to the left ventricle (LV) and sense the electrical activity of the left ventricle.

[0171] The LPD 500 may include one or more motion detectors 502 configured to detect mechanical motion or activity of a patient's heart. Other leads, structures, or the LPD may be located in or not located in other chambers of the heart (e.g., the left atrium or right ventricle for cardiac therapy). When the LPD 500 includes two or more electrodes carried on an outer housing of the LPD 500, additional leads for the structures may not be necessary.

[0172] Motion detector 502 may include one or more accelerometers or other such devices capable of detecting motion and / or positioning of LPD 500. For example, motion detector 502 may include a 3-axis accelerometer configured to detect acceleration in any direction in space. Specifically, the 3-axis accelerometer may be used to detect LPD 500 motion that can indicate cardiac events. For example, LPD 500 may move with the walls of the heart (such as septum 512 in the AV), and detected changes in acceleration may indicate contraction or other mechanical activity within the heart. The acceleration detected by motion detector 502 may be used by the processor of LPD 500 to identify potential noise in the signal detected by sensing circuitry.

[0173] It is possible to distinguish various contractions of a patient's heart from data from a motion detector. Figure 17 The following is an example from an LPD (such as the LPD 500). Figure 16A plot 520 of signal readings from one or more electrodes and motion detectors of the RA. Specifically, plot 520 shows EGM signal 522 and motion signal 524 over a time period. Motion signal 524 shows characteristics from an accelerometer in, for example, an LPD 500 implanted in the RA. Characteristics of mechanical activity can indicate the onset of atrial systolic event 528, LV systolic event 530 (or opening of mitral valve closure), and the onset of diastolic event 532 (or closure of aortic valve). EGM signal 522 and motion signal 524 also show association with atrial activation 526 and ventricular activation 534, either of which can be intrinsic or pacing events. For example, pacing atrial activation can be detected in response to the delivery of a pacing pulse from a therapy delivery circuit.

[0174] The use of motion detectors and electrodes allows the electrical activity of a patient's heart to serve as an electrical reference for the mechanical activity of the heart. Specifically, atrial activation can serve as a reference for atrial contraction. Electrical and mechanical activity can be used not only as markers of conventional AV pacing but also as markers of electromechanical timing intervals.

[0175] Various electromechanical intervals can be identified and assessed to indicate a range of cardiac conditions in a patient. As used herein, the term electromechanical interval describes the interval between electrical and mechanical events, between two electrical events, or between two mechanical events. Specifically, an electromechanical interval represents the interval between different events during a single heartbeat.

[0176] One example of the electromechanical interval 536 is based on atrial activation 526 and atrial contraction event 528. The atrial activation-to-contraction interval 536 can be used to determine the AV pacing interval, which can also be described as an AV pacing delay. Specifically, the AV pacing interval can be set to be only greater than the value of the atrial activation-to-contraction interval 538. Alternatively or additionally, the AV pacing interval can be set to be no greater than a certain percentage (e.g., 80%) of the interval between atrial activation 526 and intrinsic ventricular activation.

[0177] The AV pacing interval can be used to pace the ventricles (such as the left ventricle) after the detection of inherent activation of the atria (such as the renal artery). One or more pacing pulses can be delivered to the ventricle using a ventricular electrode 506 implanted in the septum 512 of the AV. The AV pacing interval can be determined during or after implantation of the LPD, and it can be used by the LPD after implantation when the patient moves around.

[0178] In some embodiments, the AV pacing interval can be determined based on monitored electrical activity from an electrode device having multiple external electrodes. For example, an ECG device can be used to optimize one or more pacing parameters based on SDAT or LVAT. Such parameters may include, but are not limited to, the AV pacing interval, pacing vector, and pacing output. A specific AV pacing interval determined based on the monitored electrical activity can be described as an optimized AV pacing interval.

[0179] Another example of the electromechanical interval 538 is based on the onset of ventricular activation 534 and LV systolic event 530 (such as mitral valve closure). The ventricular activation-systolic interval 538 can be used to determine whether the AV pacing interval is acceptable for cardiac therapy.

[0180] For example, the intrinsic ventricular activation to the systolic interval can be compared to the pacing ventricular activation to the systolic interval. Comparison of intrinsic and pacing measurements of this interval from different heartbeats can be used to determine whether the AV pacing interval is acceptable for cardiac therapy.

[0181] In another example, an optimized AV pacing interval, such as the ventricular activation-to-systolic interval 538 measured when the patient is in the clinic post-implantation, can be compared with the ventricular activation-to-systolic interval 538 measured over a period after the initial measurement (e.g., while the patient is walking). To assess long-term changes in the patient's heart, the time period can be on the order of weeks or months. Comparison of earlier and later pacing measurements of this interval at different time points can be used to determine whether the AV pacing interval is acceptable for the cardiac therapy. The optimal AV pacing interval for a patient's heart can change over time, for example, due to remodeling.

[0182] In some embodiments, the threshold electromechanical interval can be determined, for example, based on the inherent measurement interval or an earlier measurement interval, and the pacing measurement interval or a later measurement interval can be compared with the corresponding threshold to determine whether the AV pacing interval is acceptable for cardiac therapy.

[0183] In one or more embodiments, a pacing ventricular activation to systolic interval 538 that is longer than a predetermined percentage of intrinsic ventricular activation to systolic interval 538 may be considered unacceptable. For example, the threshold or predetermined percentage may be equal to about 90%, about 85%, or even about 80% of intrinsic ventricular activation to systolic interval 538.

[0184] Another example of the electromechanical interval 540 is based on the onset of the LV systolic event 530 and the onset of the diastolic event 532. The ventricular systolic-diastolic interval 540 can be used to determine whether the AV pacing interval is acceptable for cardiac therapy. The ventricular systolic-diastolic interval 540 can be assessed in the same or similar manner as assessing the ventricular activation-systolic interval 538. Specifically, the intrinsic LV systolic-diastolic interval can be compared with the pacing LV systolic-diastolic interval, or an earlier LV systolic-diastolic interval can be compared with a later LV systolic-diastolic interval. In either case, the comparison can be used to determine whether the AV pacing interval is acceptable for cardiac therapy, for example, using a threshold based on the intrinsic interval or the earlier interval.

[0185] In one or more embodiments, a pacing ventricular systolic-diastolic interval 540 may be considered unacceptable if it is shorter than a predetermined percentage of the intrinsic ventricular systolic-diastolic interval 540. For example, the threshold or predetermined percentage may be equal to about 110%, about 115%, or even about 120%, about 130%, about 140%, or even about 150% of the intrinsic ventricular systolic-diastolic interval 540.

[0186] The AV pacing interval may be adjusted in response to one or more measured electromechanical intervals being unacceptable. Typically, the AV pacing interval may be shortened in response to at least one electromechanical interval being deemed unacceptable for cardiac therapy.

[0187] Heart sound measurements can be used to confirm, reference, or calibrate mechanical activity events detectable in motion signal 524, which can be viewed on a phonocardiogram. The term heart sound refers to a characteristic of a heart sound signal, such as S1, S2, S3, or S4 heart sounds. For any given cardiac cycle or heartbeat, multiple heart sounds may exist, such as each of S1, S2, S3, and S4 heart sounds. Heart sounds can be detected or measured using any suitable technique known to those skilled in the art who benefit from this disclosure. For example, a heart sound sensor may be included in a medical device system, such as in LPD 500, and may be formed of a piezoelectric material, which may be a piezoelectric ceramic, a thin film, or a polymer, or may include a miniature microphone. Piezoelectric materials may be described as passive sensors, and microphones may be described as active sensors that may require power to detect sound.

[0188] Typically, heart sounds are associated with the mechanical vibrations of a patient's heart and the flow of blood through the heart valves, and therefore can be highly correlated with pressure gradients and blood pressure on the heart valves. Heart sounds may be caused not only by vibrations and pressure within the heart, but also by the entire cardiovascular system, such as blood, the heart, and aorta. Heart sounds can repeat with each cardiac cycle and can be differentiated and classified based on the activity associated with the vibrations.

[0189] The first heart sound is called "S1" and can be considered as the vibrational sound produced by the heart during the closure of the atrioventricular (AV) valves (i.e., the mitral and tricuspid valves). The S1 sound can sometimes be broken down into an M1 component (from mitral valve closure) and a T1 component (from tricuspid valve closure). The second heart sound is called "S2" and is caused by the closure of the semilunar valves (i.e., the pulmonary and aortic valves). The S2 heart sound can be considered a marker of the onset of diastole. The S2 sound can also be broken down into components. The P2 component comes from pulmonary valve closure, and the A2 component comes from aortic valve closure. The third and fourth heart sounds are called "S3" and "S4," respectively, and can be conceptualized as relating to ventricular filling during diastole. S3 is due to rapid ventricular filling and may occur when a large amount of blood flows from the atria into the ventricles before the ventricular walls relax. S4 is caused by atrial contraction leading to a rapid influx of blood from the atria into the ventricles.

[0190] Typically, the S4 heart sound can be used to confirm or reference atrial systolic event 528. The S1 heart sound, or more specifically the M1 component of the S1 heart sound, can be used to confirm or reference the onset of LV systolic event 530. The S2 heart sound, or more specifically the A2 component of the S2 heart sound, can be used to confirm or reference the onset of diastolic event 532.

[0191] Repeated measurements over different time intervals can be used to indicate whether a patient's heart is undergoing effective remodeling due to cardiac therapy. Figure 18 As can be seen in the plot 550, which shows two example results of cardiac therapy (such as CRT) against time range (T), the example interval (t) can be any electromechanical interval suitable for indicating remodeling, such as the ventricular activation to systolic interval 538 or the ventricular systolic to diastolic interval 540.

[0192] Trends in interval data can indicate whether remodeling is effective. For example, a specific electromechanical interval, as represented by the first dataset 552, showing a decrease in intervals over a long period, can indicate effective atrial or ventricular remodeling. A specific electromechanical interval, as represented by the second dataset 554, showing an increase in intervals over the same time period, can indicate ineffective atrial or ventricular remodeling, which can also be described as atrial or ventricular diastole.

[0193] Trends in interval data can be based on measurements taken over time. In some embodiments, individual measurements can be repeated, for example, on a periodic basis. Non-limiting examples of periodically repeated measurements include hourly, daily, weekly, or monthly measurements. These individual measurements can be used to plot trends over time periods, which can be one or more days, several weeks, or several months. In one instance, a time period can be approximately six months.

[0194] Measurement results can also be aggregated in any suitable way to provide a practical view of trends. Measurement results over shorter time periods can be aggregated. Typically, the time period used to aggregate a single measurement result is shorter than the time period used to assess the trend. The time period used to aggregate a single measurement result can be limited to an interval longer than one heartbeat.

[0195] Multiple aggregated measurements can be used to plot trends over time. Non-limiting examples of techniques for aggregating measurements include using sums, products, averages, weighted averages, medians, variances, or other aggregation functions over a time period. Any suitable time period can be used to aggregate individual measurements, such as one minute or several minutes, hours, days, weeks, or months. In one instance, the time period used to aggregate the individual measurements could be one week, while the time period used to assess the trend could be three months.

[0196] A confirmed failure of atrial or ventricular remodeling can indicate a high risk of heart failure or atrial fibrillation in a patient. This can prompt a visit to the clinic. At the clinic, the clinician can be informed, and the patient can be titrated to obtain better medication, or other interventions can be used to improve heart failure management.

[0197] Figure 19 An example of a method 560 for cardiac therapy using an electromechanical interval is shown. Method 560 may include delivering a pacing pulse in process 562. The pacing pulse may be delivered according to an AV pacing interval. The method may include determining at least one electromechanical interval in process 564. The electromechanical interval may be based on at least one of electrical and mechanical activity. Method 560 may include adjusting the AV pacing interval in process 566. The AV pacing interval may be adjusted based on the electromechanical interval.

[0198] In some embodiments, adjusting the AV pacing interval in process 566 may further include determining whether the at least one electromechanical interval is acceptable for cardiac therapy and adjusting the AV pacing interval in response to the at least one electromechanical interval being unacceptable for cardiac therapy.

[0199] Method 560 can be repeated any appropriate number of times to update the AV pacing interval, for example, to ensure that pacing based on the AV pacing interval is effective over a long period of time. For example, the AV pacing interval can be updated continuously or once per heartbeat, per minute, per hour, per day, or per week.

[0200] Figure 20 An example of a method 570 for detecting cardiac chamber remodeling using an electromechanical interval is shown. Method 570 may include detecting electrical activity indicating activation in process 572. In some embodiments, atrial electrodes may be used to detect atrial activation or ventricular electrodes may be used to detect ventricular activation to detect electrical activity.

[0201] Method 570 may include detecting mechanical activity indicative of contraction in process 574. In some embodiments, a motion detector may be used to detect the mechanical activity. The mechanical activity may indicate atrial contraction or ventricular contraction. In one or more embodiments, activation and contraction of the same cardiac chamber may be detected. For example, atrial activation and atrial contraction may be detected. In another instance, ventricular activation and ventricular contraction may be detected.

[0202] Method 570 may include determining an electromechanical interval in process 576. In some embodiments, the electromechanical interval may be determined as the time interval between an electrical activity event and a mechanical activity event. For example, at least one electromechanical interval may be determined based on atrial activation and atrial contraction. In another instance, at least one electromechanical interval may be determined based on ventricular activation and ventricular contraction.

[0203] Method 570 may also include determining in process 578 whether repeated measurements of at least one electromechanical interval indicate remodeling. Intervals of the same type may be repeatedly measured over time. In one instance, repeated measurements of atrial activation to systolic interval may indicate atrial remodeling. In another instance, repeated measurements of ventricular activation to systolic interval may indicate ventricular remodeling.

[0204] Determining whether the interval indicates remodeling in process 578 may include determining whether the remodeling is effective. In one instance, in response to a decrease in the atrial activation-to-systole interval over time, chamber remodeling may be effective. In another instance, in response to a decrease in the ventricular activation-to-systole interval over time, chamber remodeling may be effective.

[0205] Illustrative Examples

[0206] Although this disclosure is not so limiting, an understanding of various aspects of this disclosure will be gained through the discussion of the illustrative embodiments provided below. Various modifications to the examples and illustrative embodiments, as well as other embodiments of this disclosure, will become apparent herein.

[0207] In illustrative embodiment A1, an implantable medical device includes a plurality of electrodes. The plurality of electrodes includes: a first electrode to be implanted in the atrium of a patient's heart to deliver cardiac therapy or sense electrical activity of the atrium; and a second electrode to be implanted in the septum distal to the first electrode in the patient's heart to deliver cardiac therapy to the ventricle or sense electrical activity of the ventricle. The device further includes: a motion detector for detecting mechanical activity of the patient's heart; a therapy delivery circuit operatively coupled to the plurality of electrodes to deliver cardiac therapy to the patient's heart; and a sensing circuit operatively coupled to the plurality of electrodes to sense electrical activity of the patient's heart and operatively coupled to the motion detector to sense mechanical activity of the patient's heart. The device further includes a controller having a processing circuitry operatively coupled to the therapy delivery circuit and the sensing circuit. The controller is configured to: deliver pacing pulses using the second electrode according to the atrioventricular (AV) pacing interval; determine at least one electromechanical interval based on at least one of electrical activity and mechanical activity in response to the delivery of the pacing pulses; and adjust the AV pacing interval based on the at least one electromechanical interval.

[0208] In illustrative embodiment A2, an apparatus includes the means according to any one of embodiments A, wherein, in order to adjust the AV pacing interval, the controller is further configured to: determine whether the at least one electromechanical interval is acceptable for cardiac therapy; and adjust the AV pacing interval in response to the at least one electromechanical interval being unacceptable for cardiac therapy.

[0209] In illustrative embodiment A3, an apparatus includes the apparatus according to any one of embodiments A, wherein the controller is further configured to: determine an atrial activation-to-contraction interval based on electrical activity indicating atrial activation using the first electrode and mechanical activity indicating atrial contraction using the motion detector; and determine the AV pacing interval based on the determined atrial activation-to-contraction interval.

[0210] In illustrative embodiment A4, an apparatus includes the apparatus according to embodiment A3, wherein the detected atrial activation is intrinsic atrial activation detected using the first electrode.

[0211] In illustrative embodiment A5, an apparatus includes the means according to embodiment A3 or A4, wherein the detected mechanical activity indicating atrial contraction corresponds to heart sound S4.

[0212] In illustrative embodiment A6, an apparatus includes the device according to any one of embodiments A, the apparatus further having a housing including a distal region. A first electrode is coupled to the housing without leads, and a second electrode extends without leads from the distal region of the housing. The motion detector, the therapy delivery circuit, the sensing circuit, and the controller are all enclosed within the housing.

[0213] In illustrative embodiment A7, an apparatus includes the means according to any one of embodiments A, wherein the first electrode is a right atrial electrode and the second electrode is a tissue puncture electrode.

[0214] In illustrative embodiment A8, an apparatus includes the means according to any one of embodiments A, wherein the first electrode is implantable in the right atrium (RA) of the patient's heart to deliver cardiac therapy to the RA of the patient's heart or to sense the electrical activity of the RA, and the second electrode is implantable from the Koch triangle region of the RA of the patient's heart to deliver cardiac therapy to the left ventricle (LV) or to sense the electrical activity of the LV in the basal region, septal region, or baso-septal region of the left ventricular myocardium of the patient's heart.

[0215] In illustrative embodiment A9, an apparatus includes the means according to any one of embodiments A, wherein the at least one electromechanical interval includes an interval from electrical activity indicating ventricular pacing to mechanical activity indicating mitral valve closure.

[0216] In illustrative embodiment A10, an apparatus includes the apparatus according to embodiment A9, wherein the interval from ventricular pacing to mitral valve closure is unacceptable in response to being longer than a predetermined percentage of the interval from intrinsic ventricular activation to mitral valve closure.

[0217] In illustrative embodiment A11, an apparatus includes the means according to embodiment A9 or A10, wherein the mechanical activity indicating mitral valve closure corresponds to heart sound S1.

[0218] In illustrative embodiment A12, an apparatus includes the means according to any one of embodiments A, wherein the at least one electromechanical interval includes an interval responsive to ventricular pacing from a mechanical activity instructing mitral valve closure to a mechanical activity instructing aortic valve closure.

[0219] In illustrative embodiment A13, an apparatus includes the apparatus according to embodiment A12, wherein, in response to a predetermined percentage shorter than the interval from intrinsic mitral valve closure to intrinsic aortic valve closure, the interval of ventricular pacing from mitral valve closure to aortic valve closure is unacceptable.

[0220] In illustrative embodiment A14, an apparatus includes the means according to embodiment A12 or A13, wherein the mechanical activity indicating aortic valve closure corresponds to heart sound S2.

[0221] In illustrative embodiment A15, an apparatus includes the means according to any one of embodiments A, wherein the AV pacing interval is shortened in response to the at least one electromechanical interval being unacceptable for cardiac therapy.

[0222] In illustrative embodiment A16, an apparatus includes the means according to any one of embodiments A, wherein determining whether the at least one electromechanical interval is acceptable for cardiac therapy includes comparing the at least one electromechanical interval with a corresponding threshold electromechanical interval, wherein the corresponding threshold electromechanical interval is determined using a specific AV pacing interval. The specific AV pacing interval is determined based on electrical activity monitored from an electrode device comprising a plurality of external electrodes.

[0223] In illustrative embodiment B1, an implantable medical device includes a plurality of electrodes. The plurality of electrodes includes: a first electrode to be implanted in the atrium of a patient's heart to deliver cardiac therapy or sense electrical activity of the atrium; and a second electrode to be implanted in the septum distal to the first electrode in the patient's heart to deliver cardiac therapy to the ventricle or sense electrical activity of the ventricle. The device further includes: a motion detector for detecting mechanical activity of the patient's heart; a therapy delivery circuit operatively coupled to the plurality of electrodes to deliver cardiac therapy to the patient's heart; and a sensing circuit operatively coupled to the plurality of electrodes to sense electrical activity of the patient's heart and operatively coupled to the motion detector to sense mechanical activity of the patient's heart. The device further includes a controller having a processing circuitry operatively coupled to the therapy delivery circuit and the sensing circuit. The controller is configured to: detect electrical activity indicating atrial activation from the first electrode, detect mechanical activity indicating atrial contraction from a motion detector, determine at least one electromechanical interval based on the detected atrial activation and detected atrial contraction, and determine whether repeated measurements of the at least one electromechanical interval indicate atrial remodeling.

[0224] In illustrative embodiment B2, an apparatus includes the means according to any one of embodiments B, wherein the controller is further configured to determine whether repeated measurements of the at least one electromechanical interval indicate effective atrial remodeling based on the time-decreasing atrial activation-to-systole interval.

[0225] In illustrative embodiment C1, an implantable medical device includes a plurality of electrodes. The plurality of electrodes includes: a first electrode to be implanted in the atrium of a patient's heart to deliver cardiac therapy or sense electrical activity of the atrium; and a second electrode to be implanted in the septum distal to the first electrode in the patient's heart to deliver cardiac therapy to the ventricle or sense electrical activity of the ventricle. The device further includes: a motion detector for detecting mechanical activity of the patient's heart; a therapy delivery circuit operatively coupled to the plurality of electrodes to deliver cardiac therapy to the patient's heart; and a sensing circuit operatively coupled to the plurality of electrodes to sense electrical activity of the patient's heart and operatively coupled to the motion detector to sense mechanical activity of the patient's heart. The device further includes a controller having a processing circuitry operatively coupled to the therapy delivery circuit and the sensing circuit. The controller is configured to: detect electrical activity indicating ventricular activation using the second electrode, detect mechanical activity indicating ventricular contraction using the motion detector, determine at least one electromechanical interval based on the detected ventricular activation and detected ventricular contraction, and determine whether repeated measurements of the at least one electromechanical interval indicate atrial remodeling.

[0226] In illustrative embodiment C2, an apparatus includes the means according to any one of embodiments C, wherein the controller is further configured to determine whether repeated measurements of the at least one electromechanical interval indicate effective ventricular remodeling based on the time-decreasing ventricular activation to systolic interval.

[0227] In illustrative embodiment C3, an apparatus includes the means according to any one of embodiments C, wherein the at least one electromechanical interval includes an interval from electrical activity indicating ventricular pacing to mechanical activity indicating mitral valve closure.

[0228] In illustrative embodiment C4, an apparatus includes the apparatus according to embodiment C3, wherein the mechanical activity indicating mitral valve closure corresponds to heart sound S1.

[0229] In illustrative embodiment C5, an apparatus includes the means according to any one of embodiments C, wherein the at least one electromechanical interval includes an interval responsive to ventricular pacing from a mechanical activity instructing mitral valve closure to a mechanical activity instructing aortic valve closure.

[0230] In illustrative embodiment C6, an apparatus includes the apparatus according to embodiment C5, wherein the mechanical activity indicating aortic valve closure corresponds to heart sound S2.

[0231] In illustrative embodiment D1, a method includes delivering a pacing pulse to a patient's heart according to an atrioventricular (AV) pacing interval. The method further includes determining at least one electromechanical interval based on at least one of detected electrical and mechanical activities in response to the delivery of the pacing pulse. The method further includes adjusting the AV pacing interval based on the at least one electromechanical interval.

[0232] In illustrative embodiment D2, a method includes the method according to any one of embodiments D, wherein adjusting the AV pacing interval includes determining whether the at least one electromechanical interval is acceptable for cardiac therapy; and adjusting the AV pacing interval in response to the at least one electromechanical interval being unacceptable for cardiac therapy.

[0233] In illustrative embodiment D3, a method includes the method according to any one of embodiments D, wherein the method further includes determining whether repeated measurements of the at least one electromechanical interval indicate effective atrial remodeling.

[0234] In illustrative embodiment D4, a method includes the method according to any one of embodiments D, wherein the method further includes determining whether repeated measurements of the at least one electromechanical interval indicate effective ventricular remodeling.

[0235] Therefore, various embodiments of VFA cardiac resynchronization therapy using an accelerometer are disclosed. Although reference has been made to the set of drawings that form part of this disclosure, it will be understood, at least by one of ordinary skill in the art, that various adaptations and modifications of the embodiments described herein are within or do not depart from the scope of this disclosure. For example, various aspects of the embodiments described herein can be combined with each other in multiple ways. Therefore, it should be understood that the claimed invention may be practiced in ways other than those expressly described herein within the scope of the appended claims.

[0236] It should be understood that the various aspects disclosed herein can be combined in different combinations than those specifically presented in the specification and drawings. It should also be understood that, depending on the instance, certain actions or events of any of the processes or methods described herein may be performed in different sequences, added, combined, or omitted entirely (e.g., all described actions or events may not be necessary for performing these techniques). Furthermore, for clarity, although some aspects of this disclosure are described as being performed by a single module or unit, it should be understood that the techniques of this disclosure can be performed by a combination of units or modules associated with, for example, a medical device.

[0237] In one or more instances, the described techniques can be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, functionality can be stored on a computer-readable medium in the form of one or more instructions or code and can be executed by a hardware-based processing unit. The computer-readable medium can include non-transitory computer-readable media, which corresponds to tangible media such as data storage media (e.g., RAM, ROM, EEPROM, flash memory, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer).

[0238] Instructions can be executed by one or more processors, such as one or more digital signal processors (DSPs), general-purpose microprocessors, application-specific integrated circuits (ASICs), field-programmable arrays (FPGAs), or other equivalent integrated or discrete logic circuit systems. Therefore, the term "processor" as used herein can refer to any of the foregoing structures or any other physical structure suitable for implementing the described techniques. Furthermore, the techniques can be fully implemented in one or more circuit or logic elements.

[0239] All references and publications cited herein are expressly incorporated in full unless in any way directly contradicts this disclosure.

[0240] Unless otherwise specified, all scientific and technical terms used herein have the meaning generally understood in the art. The definitions provided herein are intended to aid in understanding certain terms that are frequently used herein and are not intended to limit the scope of this disclosure.

[0241] Unless otherwise specified, all figures representing the size, quantity, and physical properties of features used in the specification and claims are to be understood to be modified by the terms “precise” or “about”. Therefore, unless indicated otherwise, the numerical parameters set forth in the foregoing specification and appended claims are approximations that may vary depending on the desired properties sought by those skilled in the art using the teachings disclosed herein, or, for example, within typical experimental error ranges.

[0242] The numerical ranges listed by endpoints include all numbers included within the range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5) as well as any range within the range. In this document, the terms "up to" or "not greater than" a numerical value (e.g., up to 50) include the numerical value (e.g., 50), and the term "not less than" a numerical value (e.g., not less than 5) includes the numerical value (e.g., 5).

[0243] Terms related to orientation, such as “proximal” or “far”, are used to describe the relative positioning of components and do not imply a limitation on the orientation of the contemplated embodiments.

[0244] The terms “coupled” or “connected” refer to components being directly connected to each other (in direct contact) or indirectly connected (having one or more components between two components and connecting them). Both terms can be modified by “operatively” and “operably”, which are used interchangeably to describe a connection or linkage configured to allow components to interact to perform at least some functions.

[0245] As used herein, unless otherwise expressly indicated by the contents of this disclosure, the term “configured as” may be used interchangeably with the terms “suitable” or “structured as”.

[0246] Unless the context clearly indicates otherwise, the singular forms “a / an” and “the” cover embodiments with plural indicators.

[0247] Unless otherwise expressly stated in the content, the term "or" is usually used in its implied meaning, such as "and / or".

[0248] The term “and / or” means one or all of the listed elements or a combination of at least two of the listed elements.

[0249] The phrases “at least one,” “including at least one,” and “one or more” that follow a list refer to any item in the list as well as any combination of two or more items in the list.

[0250] As used in this article, terms such as “have,” “having,” “include,” “including,” “comprise,” and “comprising” are used in their open-ended sense and generally mean “including but not limited to.” It should be understood that phrases such as “basically composed of” or “composed of” are included within the term “including.”

[0251] The references to "one embodiment," "an embodiment," "certain embodiments," or "some embodiments," etc., mean that a particular feature, configuration, composition, or characteristic described in connection with the embodiment is included in at least one embodiment of this disclosure. Therefore, the appearance of such phrases throughout the text does not necessarily refer to the same embodiment of this disclosure. Furthermore, in one or more embodiments, particular features, configurations, compositions, or characteristics may be combined in any suitable manner.

Claims

1. An implantable medical device comprising: Multiple electrodes, the multiple electrodes comprising: A first electrode, to be implanted in the atrium of a patient's heart to deliver cardiac therapy or sense the electrical activity of the atrium; and The second electrode is to be implanted in the septal wall of the patient's heart distal to the first electrode and to deliver cardiac therapy to the ventricles of the patient's heart or sense the electrical activity of the ventricles; A motion detector, used to detect the mechanical activity of the patient's heart; A therapy delivery circuit, operatively coupled to the plurality of electrodes to deliver cardiac therapy to the patient's heart; A sensing circuit operatively coupled to the plurality of electrodes to sense the electrical activity of the patient's heart, and operatively coupled to the motion detector to sense the mechanical activity of the patient's heart; and A controller, comprising a processing circuitry system operatively coupled to the therapy delivery circuitry and the sensing circuitry, the controller being configured to: The second electrode is used to deliver pacing pulses according to the atrioventricular (AV) pacing interval; In response to the delivery of the pacing pulse, at least one electromechanical interval is determined based on at least one of electrical and mechanical activities, wherein the at least one electromechanical interval includes an interval from electrical activity indicating ventricular pacing to mechanical activity indicating mitral valve closure; and The AV pacing interval is adjusted based on the at least one electromechanical interval.

2. The apparatus of claim 1, wherein, for adjusting the AV pacing interval, the controller is further configured to: Determine whether the at least one electromechanical interval is acceptable for cardiac therapy; and The AV pacing interval is adjusted in response to the fact that the at least one electromechanical interval is unacceptable for cardiac therapy.

3. The apparatus of claim 1, wherein the controller is further configured to: The interval between atrial activation and contraction is determined based on the electrical activity indicating atrial activation using the first electrode and the mechanical activity indicating atrial contraction using the motion detector; and The AV pacing interval is determined based on the established atrial activation-to-contraction interval.

4. The apparatus of claim 3, wherein the detected atrial activation is intrinsic atrial activation detected using the first electrode.

5. The apparatus of claim 3, wherein the detected mechanical activity indicating atrial contraction corresponds to heart sound S4.

6. The device according to any one of claims 1-5, further comprising a housing including a distal region, wherein the first electrode is leadlessly coupled to the housing, and the second electrode extends leadlessly from the distal region of the housing, wherein the motion detector, the therapy delivery circuit, the sensing circuit, and the controller are all enclosed within the housing.

7. The device according to any one of claims 1-5, wherein the first electrode is a right atrial electrode and the second electrode is a tissue puncture electrode.

8. The device according to any one of claims 1-5, wherein the first electrode is implantable in the right atrium (RA) of the patient's heart to deliver cardiac therapy to the RA of the patient's heart or to sense electrical activity of the RA, and the second electrode is implantable from the Koch triangle region of the RA of the patient's heart to deliver cardiac therapy to the left ventricle (LV) or to sense electrical activity of the LV in the basal region, septal region, or baso-septal region of the left ventricular myocardium of the patient's heart.

9. The device of claim 1, wherein the interval from ventricular pacing to mitral valve closure is unacceptable if it is longer than a predetermined percentage of the interval from intrinsic ventricular activation to mitral valve closure.

10. The apparatus of claim 1, wherein the mechanical activity indicating mitral valve closure corresponds to heart sound S1.

11. The device of claim 1, wherein the AV pacing interval is shortened in response to the at least one electromechanical interval being unacceptable for cardiac therapy.

12. The apparatus of any one of claims 1-5, wherein determining whether the at least one electromechanical interval is acceptable for cardiac therapy comprises comparing the at least one electromechanical interval with a corresponding threshold electromechanical interval, wherein the corresponding threshold electromechanical interval is determined using a specific AV pacing interval, wherein the specific AV pacing interval is determined based on electrical activity monitored from an electrode device comprising a plurality of external electrodes.

13. An implantable medical device comprising: Multiple electrodes, the multiple electrodes comprising: A first electrode, to be implanted in the atrium of a patient's heart to deliver cardiac therapy or sense the electrical activity of the atrium; and The second electrode is to be implanted in the septal wall of the patient's heart distal to the first electrode and to deliver cardiac therapy to the ventricles of the patient's heart or sense the electrical activity of the ventricles; A motion detector, used to detect the mechanical activity of the patient's heart; A therapy delivery circuit, operatively coupled to the plurality of electrodes to deliver cardiac therapy to the patient's heart; A sensing circuit operatively coupled to the plurality of electrodes to sense the electrical activity of the patient's heart, and operatively coupled to the motion detector to sense the mechanical activity of the patient's heart; and A controller, comprising a processing circuitry system operatively coupled to the therapy delivery circuitry and the sensing circuitry, the controller being configured to: The second electrode is used to deliver pacing pulses according to the atrioventricular (AV) pacing interval; In response to the delivery of the pacing pulse, at least one electromechanical interval is determined based on at least one of electrical and mechanical activities, wherein the at least one electromechanical interval includes an interval between two mechanical activity events; and The AV pacing interval is adjusted based on the at least one electromechanical interval.

14. The device of claim 13, wherein the at least one electromechanical interval comprises an interval responsive to ventricular pacing from a mechanical activity indicative of mitral valve closure to a mechanical activity indicative of aortic valve closure, and If the interval between ventricular pacing and aortic valve closure is shorter than a predetermined percentage of the interval between mitral valve closure and aortic valve closure, then the interval is unacceptable.

15. The device of claim 14, wherein the mechanical activity indicating aortic valve closure corresponds to heart sound S2.

16. An implantable medical device comprising: Multiple electrodes, the multiple electrodes comprising: A first electrode, to be implanted in the atrium of a patient's heart to deliver cardiac therapy or sense the electrical activity of the atrium; and The second electrode is to be implanted in the septal wall of the patient's heart distal to the first electrode and to deliver cardiac therapy to the ventricles of the patient's heart or sense the electrical activity of the ventricles; A motion detector, used to detect the mechanical activity of the patient's heart; A therapy delivery circuit, operatively coupled to the plurality of electrodes to deliver cardiac therapy to the patient's heart; A sensing circuit operatively coupled to the plurality of electrodes to sense the electrical activity of the patient's heart, and operatively coupled to the motion detector to sense the mechanical activity of the patient's heart; and A controller, comprising a processing circuitry system operatively coupled to the therapy delivery circuitry and the sensing circuitry, the controller being configured to: The second electrode is used to deliver pacing pulses according to the atrioventricular (AV) pacing interval; In response to the delivery of the pacing pulse, at least one electromechanical interval is determined based on at least one of electrical and mechanical activity; and The AV pacing interval is adjusted based on the at least one electromechanical interval. The AV pacing interval is shortened in response to the at least one electromechanical interval being unacceptable for cardiac therapy.

Images