Optimizing conduction system pacing atrial ventricular delay

Abstract

A method of operating a cardiac rhythm management (CRM) system includes: measuring a baseline PR interval of cardiac depolarization; measuring one or both of the heart sound and the heart depolarized QRS width; delivering pacing stimulation according to atrial sensing of a ventricular pacing interval (AsVp interval), and measuring one or both of a heart sound and a QRS width of the AsVp interval, where the pacing stimulation is delivered using a conducted system pacing (CSP) vector comprising electrodes positioned in the interventricular septum; delivering a pacing stimulus according to an atrial pacing to ventricular pacing interval (ApVp interval) and measuring one or both of a heart sound and a QRS width of the ApVp interval; and generating a recommended atrial-to-ventricular delay setting for the CSP based on one or both of the measured heart sound and the QRS width.

Description

[0001] Priority requirements

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 466,868, filed May 16, 2023, which is incorporated herein by reference in its entirety. Technical Field

[0003] This document generally relates to cardiac rhythm management systems, and particularly, but not by way of limitation, to methods, systems, and devices for automatically determining the output settings of cardiac rhythm management devices. Background Technology

[0004] The heart is the center of the human circulatory system and comprises an intrinsic electromechanical system that performs two main pumping functions. The left side of the heart, comprising the left atrium (LA) and left ventricle (LV), draws oxygenated blood from the lungs and pumps it to the body's organs to meet their metabolic needs. The right side of the heart, comprising the right atrium (RA) and right ventricle (RV), draws deoxygenated blood from the body's organs and pumps it to the lungs, where it is oxygenated. These pumping functions are caused by the contraction of the heart muscle. In a normal heart, the sinoatrial (SA) node, the heart's natural pacemaker, generates intrinsic electrical impulses that travel through the electrical conduction system to various regions of the heart to stimulate the myocardial tissue. For example, intrinsic electrical impulses originating from the SA node travel through the atrioventricular (AV) node between the RA and RV. From the AV node, the electrical impulses reach the ventricular myocardial tissue using a specialized intrinsic conduction system, resulting in ventricular contraction. This specialized conduction system includes the His bundle, the right and left conduction bundles extending along the ventricular septum between the RV and LV, and Purkinje fibers that contact the myocardial tissue of the ventricle.

[0005] In a normal electrical conduction system, a coordinated delay in the propagation of the intrinsic electrical impulses causes synchronized contractions of different parts of the heart, resulting in effective pumping function. Heart disease can alter the normal intrinsic conduction pathways. Blocked or otherwise abnormal electrical conduction can cause the heart to contract asynchronously, leading to poor hemodynamics, which may reduce the amount of blood supplied to the heart and other parts of the body.

[0006] For example, blockage of electrical impulse conduction in the left bundle branch (LBB) or right bundle branch (RBB) can lead to asynchrony between the ventricles (RV and LV) of the heart. Blockage of the normal conduction pathway can cause the intrinsic electrical impulse to conduct along an alternative pathway, which can cause one ventricle to contract slightly later than the other.

[0007] In electrical cardiac pacing therapy, electrical pacing stimulation is typically delivered to the myocardium to improve the heart's pumping efficiency. Instead of being delivered to the myocardium, pacing energy can be delivered to the conduction pathway of the interventricular septum, but this pacing method may involve unique sensing and stimulation timing due to the different conduction pathways involved. Summary of the Invention

[0008] Device-based stimulation therapy can include techniques for calculating the optimal atrial-ventricular delay (AV delay) when electrodes are present in the conduction pathway of the ventricular septum in a patient or subject. Example 1 includes topics such as methods for operating a cardiac rhythm management (CRM) system, including: measuring the baseline P-wave to intrinsic R-wave interval of cardiac depolarization (baseline PR interval); measuring one or both of the heart sound of the baseline PR interval and the width of the QRS complex of cardiac depolarization (QRS width); delivering a pacing stimulus to the ventricle after a sensed atrial event to set the atrial-sensed ventricular pacing interval (AsVp interval) and measuring one or both of the heart sound of the AsVp interval and the QRS width, wherein the pacing stimulus is delivered using a conduction system pacing (CSP) vector including electrodes positioned in the ventricular septal membrane; delivering the pacing stimulus to the atrium to set the atrial-pacing to ventricular pacing interval (ApVp interval) and measuring one or both of the heart sound of the ApVp interval and the QRS width; and generating a recommended AV delay setting for the CSP based on one or both of the measured heart sound and QRS width.

[0009] In Example 2, the subject of Example 1 may optionally include changing the AsVp interval of multiple cardiac cycles and measuring one or both of the heart sounds and QRS widths of multiple cardiac cycles; changing the ApVp interval of multiple cardiac cycles and measuring one or both of the heart sounds and QRS widths of multiple cardiac cycles; and using one or both of the heart sounds and QRS widths measured for multiple cardiac cycles to generate a recommended AV delay setting.

[0010] In Example 3, the subject of Example 2 may optionally include both measuring heart sounds and QRS width; and multiple AV delay settings are generated, with a recommended AV delay setting presented based on the amplitude of the heart sounds and the narrowness of the QRS width.

[0011] In Example 4, the subject matter of one or any combination of Examples 1 to 3 may optionally include measuring one or both of the left ventricular activation time and the right ventricular activation time for the baseline PR interval, AsVp interval, and ApVp interval; and generating a recommended AV delay based on the measured heart sounds, the measured QRS width, and one or more of the measured left ventricular activation time and the right ventricular activation time.

[0012] In Example 5, the subject matter of Example 4 may optionally include measuring one or both of the following: the ventricular activation time interval between the delivery of pacing stimulation to the ventricle and the peak of a sensed far-field QRS complex, wherein the far-field QRS complex is sensed using a sensing vector of a CAN electrode of a mobile medical device including a CRM system; and the interval between the delivery of pacing stimulation to the ventricle and a sensed electrogram signal, wherein the electrogram signal is sensed using a sensing vector including an electrode for delivering pacing stimulation.

[0013] In Example 6, the subject matter of one or any combination of Examples 1 to 5 may optionally include the impedance of one or more cardiac chambers of a subject measuring the baseline PR interval, AsVp interval, and ApVp interval; and generate a recommended AV delay based on one or more of the measured heart sounds, the measured QRS width, and the measured impedance.

[0014] In Example 7, the subject matter of one or any combination of Examples 1 to 6 may optionally include measuring the interval between sensed intrinsic atrial depolarization and sensed intrinsic ventricular depolarization (AsVs interval); changing to a pacing atrium to set the interval between pacing atrial depolarization and sensed intrinsic ventricular depolarization (ApVs interval); measuring one or both of the heart sounds and QRS widths of the AsVs interval and ApVs interval; and generating a recommended AV delay setting based on one or both of the measured heart sounds and measured QRS widths of the AsVs interval, ApVs interval, AsVp interval, and ApVp interval.

[0015] In Example 8, the subject matter of one or any combination of Examples 1 to 7 may optionally include measuring one or more heart sounds and measuring the far-field QRS width using the far-field sensing vector of the CAN electrode of a mobile medical device including a CRM system; and generating a recommended AV delay based on the far-field QRS width and the amplitude of one or more heart sounds.

[0016] In Example 9, the subject matter of one or any combination of Examples 1 to 8 may optionally include a recommended range for generating AV delay settings; and the AV delay is changed to an AV delay value within the range based on the subject's heart rate changes.

[0017] Example 10 includes a subject (such as a mobile medical device), or may optionally be combined with one or any combination of Examples 1 to 9 to include a subject comprising: a treatment circuit configured to deliver cardiac pacing stimulation energy when connected to an electrode including at least one CSP electrode positioned in the ventricular septum membrane of a subject; a cardiac signal sensing circuit configured to sense cardiac signals representing cardiac activity when connected to the electrode; a heart sound sensing circuit that generates a heart sound signal; and a control circuit operatively coupled to the treatment circuit, the cardiac signal sensing circuit, and the heart sound circuit. The control circuit is configured to measure the baseline PR interval of the sensed cardiac signal; measure one or both of the heart sound of the baseline PR interval and the QRS width of cardiac depolarization; deliver pacing stimulation to the ventricle using at least one CSP electrode to set the AsVp interval and measure one or both of the heart sound of the AsVp interval and the QRS width; deliver pacing stimulation to an atrial electrode to set the ApVp interval and measure one or both of the heart sound of the ApVp interval and the QRS width; and generate a recommended AV delay setting for the CSP based on one or both of the measured heart sound and the measured QRS width.

[0018] In Example 11, the subject of Example 10 may optionally include control circuitry configured to change the AsVp interval of a plurality of cardiac cycles and measure one or more of the heart sounds and QRS widths of the plurality of cardiac cycles; change the ApVp interval of the plurality of cardiac cycles and measure one or more of the heart sounds and QRS widths of the plurality of cardiac cycles; and use the measured heart sounds and QRS widths of the plurality of cardiac cycles to generate a recommended AV delay setting.

[0019] In Example 12, one or both of the subjects in Examples 10 and 11 may optionally include control circuitry configured to measure one or both of the left ventricular activation time and the right ventricular activation time for the baseline PR interval, AsVp interval, and ApVp interval; and to generate recommended AV delay settings based on the measured heart sounds, the measured QRS width, and one or more of the measured left ventricular activation time and the right ventricular activation time.

[0020] In Example 13, the subject matter of Example 12 may optionally include a housing and a CAN electrode formed using the housing, the CAN electrode formed using the housing, and control circuitry configured to measure one or both of the following: the ventricular activation time interval between the delivery of pacing stimulation to the ventricle and the peak of a sensed far-field QRS complex, wherein the far-field QRS complex is sensed using a sensing vector including the CAN electrode; and the interval between the delivery of pacing stimulation to the ventricle and a sensed electrogram signal, wherein the electrogram signal is sensed using a sensing vector including an electrode for delivering pacing stimulation to the ventricle.

[0021] In Example 14, the subject matter of one or any combination of Examples 10 to 13 may optionally include cardiac impedance sensing circuitry configured to sense an impedance signal representing the electrical impedance of one or more cardiac chambers; and control circuitry configured to measure the impedance of each of the baseline PR interval, AsVp interval, and ApVp interval using the impedance signal; and to generate a recommended AV delay setting based on one or more of the measured heart sounds, the measured QRS width, and the measured impedance.

[0022] In Example 15, the subject matter of one or any combination of Examples 10 to 14 may optionally include control circuitry configured to measure the interval between sensed intrinsic atrial depolarization and sensed intrinsic ventricular depolarization (AsVs interval); deliver pacing stimulation to the atrium and measure the interval between pacing atrial depolarization and sensed intrinsic ventricular depolarization (ApVs interval); measure one or both of the heart sounds and QRS widths of the AsVs interval and ApVs interval; and generate a recommended AV delay setting based on one or both of the measured heart sounds and measured QRS widths of the AsVs interval, ApVs interval, AsVp interval, and ApVp interval.

[0023] In Example 16, the subject matter of one or any combination of Examples 10 to 15 may optionally include communication circuitry coupled to control circuitry and configured to wirelessly transmit information with a separate device; and control circuitry configured to change the AsVp interval of a first plurality of cardiac cycles; change the ApVp interval of a second plurality of cardiac cycles; measure both the heart sound amplitude and QRS width of the first plurality of cardiac cycles and the second plurality of cardiac cycles; generate a plurality of recommended AV delay settings based on the measured heart sound amplitude and QRS width; and transmit the plurality of recommended AV delay settings and the measured heart sound amplitude and QRS width to the separate device.

[0024] In Example 17, the subject matter of one or any combination of Examples 10 to 16 may optionally include a housing, a CAN electrode formed using the housing, and control circuitry configured to measure the amplitude of one or more heart sounds using a heart sound signal; measure the far-field QRS width using a far-field sensing vector including the CAN electrode; and generate a recommended AV delay setting based on the far-field QRS width and the measured amplitude of one or more heart sounds.

[0025] In Example 18, the subject matter of one or any combination of Examples 10 to 17 may optionally include control circuitry configured to generate a recommended range of AV delay settings; and to change the AV delay settings from a first AV delay setting within the recommended range to a second AV delay setting within the recommended range based on changes in heart rate.

[0026] Example 19 includes a subject (such as a programming device for a mobile medical device (AMD)) or may optionally be combined with one or any combination of Examples 1 to 18 to include a subject comprising communication circuitry configured to wirelessly transmit information with the AMD; a user interface; and programming control circuitry operatively coupled to the communication circuitry and the user interface. The programming control circuitry is configured to enable conduction system pacing (CSP) in the AMD, wherein enabling CSP enables the delivery of pacing stimulation to the CSP pacing vector by the AMD; initiate an atrial-to-ventricular delay (AV delay) test for the CSP in the AMD; receive at least one recommended AV delay setting for the CSP from the AMD using the communication circuitry; and present at least one recommended AV delay setting to a user using the user interface.

[0027] In Example 20, the subject of Example 19 may optionally include programmable control circuitry configured to receive multiple AV delay settings from the CSP using communication circuitry; receive multiple measurements of the heartbeat amplitude and QRS width of the multiple AV delay settings; and present the multiple AV delay settings to the user in an order determined by the measurements of one or both of the heartbeat amplitude and QRS width.

[0028] The present invention is intended to provide an overview of the subject matter of this patent application. It is not intended to provide an exclusive or exhaustive interpretation of this disclosure. Detailed descriptions are included to provide further information regarding this patent application. Other aspects of this disclosure will be apparent to those skilled in the art upon reading and understanding the following detailed descriptions and viewing the drawings that form a part thereof, and none of these should be taken in a limiting sense. Attached Figure Description

[0029] In drawings, they are not necessarily drawn to scale, and similar numbers can describe similar parts in different views. Similar numbers with different letter suffixes can represent different instances of similar parts. Drawings generally illustrate the various embodiments discussed in this document by way of example rather than limitation.

[0030] Figure 1 An example cardiac rhythm management (CRM) system is shown.

[0031] Figure 2 An example of a mobile medical device (AMD) and the environment in which it operates is shown.

[0032] Figure 3 This is a block diagram of AMD's electronic circuitry.

[0033] Figure 4 This is a block diagram of an external device that transmits information to AMD.

[0034] Figure 5This is a flowchart of the method for operating a CRM system. Detailed Implementation

[0035] Mobile medical devices (AMDs) can be used to provide cardiac interval therapy to patients. An AMD may include or be configured to receive physiological information from one or more sensors located inside, on, or near the patient's body. The patient's physiological information may include, among other things, respiratory information (e.g., respiratory rate, respiratory volume (tidal volume), cardiac acceleration information (e.g., cardiac vibration information, pressure waveform information, heart sound information, endocardial acceleration information, acceleration information, activity information, posture information, etc.); impedance information; cardiac electrical information; body activity information (e.g., activity, steps, etc.); posture or position information; pressure information; plethysmography information; chemical information; temperature information; or other physiological information of the patient.

[0036] Conventional right ventricular (RV) pacing therapy delivers pacing pulses to the RV via electrodes, such as to provide relief to subjects with blockage of the normal conduction pathway in the right ventricle. Conduction system pacing (CSP) is direct pacing of the heart's conduction system, resulting in greater physiological activation of the ventricles in lieu of conventional right ventricular pacing. CSP therapy delivers pacing pulses at multiple locations within the conduction system (such as the His bundle and left bundle branch) via electrodes located at these sites, and pacing at these locations can induce various types of capture.

[0037] The availability of multiple pacing electrodes for AMD treatment of heart disease, and the increasing number of programmable features for AMD treatment of heart disease, can create a broad parameter search space for physicians or clinicians. The inventors have recognized, among other things, that systems and methods for device-based data collection and analysis can help reduce the parameter search space.

[0038] Figure 1A portion of an example of a Cardiac Rhythm Management (CRM) system 100 and a portion of an environment in which the CRM system 100 can be used are shown. The CRM system 100 may include an implantable AMD 102, an external system 104, and communication links such as a telemetry link 106. The AMD 102 may include an electronic unit coupled to the heart 110 of a subject 112 via a cardiac lead 108 or an additional lead. Examples of the AMD 102 may include, but are not limited to, multiple pacemakers, pacemaker / defibrillators, cardiac resynchronization devices, cardiac remodeling control devices, and cardiac monitors. In the example, the AMD 102 may be configured to monitor the health of the heart 110 and identify one or more abnormalities associated with the heart 110. The AMD 102 may take necessary actions, such as stimulating one or more portions of the heart 110 via the lead 108, to treat the one or more abnormalities.

[0039] In the example, external system 104 may include external device 107 configured to communicate bidirectionally with AMD 102, such as via telemetry link 106. For example, external device 107 may include a programmer to program AMD 102 to deliver one or more treatments to heart 110. In the example, external device 107 may program AMD 102 to detect the presence of conduction block in the left bundle branch (LBB) of heart 110 and prevent asynchronous contraction of heart 110 by delivering cardiac resynchronization therapy (CRT) to heart 110.

[0040] In the example, external device 107 can be configured to transmit data to AMD 102 via telemetry link 106. Examples of such transmitted data may include programmed instructions for AMD 102 to acquire physiological data, perform at least one self-diagnostic test (such as for device operating status), or deliver at least one treatment or any other data. In the example, AMD 102 can be configured to transmit data to external device 107 via telemetry link 106. The transmitted data may include real-time physiological data acquired by or stored in AMD 102, treatment history data, operating status of AMD 102 (e.g., battery status or lead impedance), and the like. Telemetry link 106 may include an inductive telemetry link or a far-field radio frequency telemetry link.

[0041] In this example, external device 107 may be part of CRM system 100, which may include other devices such as remote system 114 for remotely programming AMD 102. In this example, remote system 114 may be configured to include server 116, which can communicate with external device 107 via telecommunications network 118, such as to access AMD 102 to remotely monitor the health of heart 110 or adjust parameters associated with one or more treatments.

[0042] Figure 2 An AMD 102 is shown, which is implantable and electrically coupled to a heart 110, such as via one or more leads coupled to the AMD 102 (through one or more lead ports in the head 203 of the AMD 102, such as first lead port, second lead port, or third lead port 241, 242, 243)). In the example, the AMD 102 may include an antenna, such as in the head 203, configured to enable communication with one or more electronic circuits (e.g., evaluation circuitry, etc.) in an external system 104 and a hermetically sealed housing (CAN) 201. The AMD 102 illustrates an example mobile medical device (or medical device system) as described herein.

[0043] The AMD 102 may include an implantable cardiac monitor (ICM), pacemaker, defibrillator, cardiac resynchronizer, or other subcutaneous AMD or CRM device configured for implantation in the chest of a subject, having one or more leads to position one or more electrodes or other sensors at various locations in or near the heart 110, such as one or more atria or ventricles. Separate from or in addition to the leads, the AMD 102 may also include one or more electrodes or other sensors (e.g., pressure sensors, accelerometers, gyroscopes, microphones, etc.) powered by a power source within the AMD 102. The leads, one or more electrodes or other sensors of the AMD 102, or combinations thereof, may be configured to detect physiological information from the patient or to provide one or more treatments or stimuli to the patient.

[0044] AMD 102 may include one or more electronic circuits configured to sense one or more physiological signals, such as electrograms or signals representing the mechanical function of the heart 110. In some examples, CAN 201 may function as electrodes, such as for sensing or pulse delivery. For example, electrodes from one or more of the leads may be used with CAN electrodes, such as for unipolar sensing for electrograms or for delivering one or more pacing pulses. Defibrillation electrodes (e.g., first defibrillation coil electrode 228, second defibrillation coil electrode 229, etc.) may be used with the electrodes of CAN 201 to deliver one or more cardioversion / defibrillation pulses.

[0045] Figure 2 Example lead configurations include first, second, and third leads 220, 225, and 230 placed in the coronary veins 216 (e.g., coronary sinuses) above the right atrium (RA) 206, right ventricle (RV) 207, and left atrium (LA) 208 and left ventricle (LV) 209, respectively. Figure 2 The example also shows a fourth lead 235, which can be positioned in RV 207 near His bundle 211 in the interventricular septum below the sinoatrial (SA) node 210, or in RV 207 near the left bundle branch 213. The fourth lead can be a conduction system pacing lead (CSP lead).

[0046] Each lead can be configured to position one or more electrodes or other sensors at various locations in or near the heart 110 to detect physiological information or provide one or more treatments or stimulations. A first lead 220 positioned in the RA 206 may include a first tip electrode 221 located distal to or near the first lead 220 and a first loop electrode 222 located near the first tip electrode 221. A second lead 225 is positioned in the RV 207 and may include a second tip electrode 226 located distal to or near the second lead 225 and a second loop electrode 227 located near the second tip electrode 226. A third lead 230 positioned in the coronary vein 216 above the LV 209 may include a third tip electrode 231 located distal to or near the third lead 230, a third loop electrode 232 located near the third tip electrode 231, and two additional loop electrodes 233, 234.

[0047] A fourth lead 235 is positioned within RV 207. For simplicity of the figures, lead 235 is shown as optionally positioned near His bundle 211 or optionally near the left bundle branch 213, but the system may include a separate fourth lead near His bundle 211 and a fifth lead near the left bundle branch 213. The fourth lead 235 may include a fourth tip electrode 236 located at or near the distal end of the fourth lead 235 for positioning near the His bundle, and a fourth ring electrode 237 located near the fourth tip electrode 236. The fourth lead 235 may include a fifth tip electrode 238 located at or near the distal end of the lead for positioning near the left bundle branch, and a fifth ring electrode 239 located near the fifth tip electrode 238. The tip and ring electrodes may include pacing / sensing electrodes configured to sense electrical activity or provide pacing stimulation.

[0048] In addition to the tip and loop electrodes, one or more leads may also include one or more defibrillation coil electrodes configured to sense electrical activity or provide cardioversion or defibrillation shock energy. For example, the second lead 225 may include a first defibrillation coil electrode 228 located near the distal end of the second lead 225 in RV 207 and a second defibrillation coil electrode 229 located at a distance from the distal end of the second lead 225, such as for placement in or near the superior vena cava (SVC) 217.

[0049] Different CRM devices may include different numbers of leads and lead placements. For example, some CRM devices are single-lead devices with one lead (e.g., RV lead only, RA lead only, CSP lead only, etc.). Other CRM devices are multi-lead devices with two or more leads (e.g., RA and RV; RA and CSP; RA, RV and CSP; RV and LV; RA, RV and LV, etc.). CRM devices suitable for His bundle pacing or left bundle branch pacing can use lead ports designated for LV or RV leads to deliver stimulation to the His bundle 211 or left bundle branch 213.

[0050] Figure 3 This is a block diagram of a portion of the electronic circuitry of the implantable AMD 102. The AMD 102 can be coupled to multiple implantable electrodes, such as... Figure 2 The electrode arrangement is described in the example. The AMD 102 includes cardiac signal sensing circuitry 304, treatment circuitry 306, heart sound sensor 314, communication circuitry 312, and control circuitry 308. When the pacing electrodes are operatively connected to the system, the treatment circuitry 306 provides electrical pacing stimulation energy to the patient's heart. The pacing electrodes may include... Figure 2 Any pacing electrode, such as electrodes configured to be placed in or near the RA, RV, LV, His bundle or left bundle branch, and CAN electrodes.

[0051] The cardiac signal sensing circuit 304 includes one or more sensing amplifiers to sense one or both of a voltage signal or a current signal at the electrodes. The cardiac signal sensing circuit 304 can be used to sense a patient's cardiac electrical information. Timing measures between different features in the sensed electrical signals (e.g., first cardiac features and second cardiac features, etc.) can be determined, for example, by control circuitry 308. In some examples, the timing measures may include the interval or measure between a first cardiac feature and a second cardiac feature of a patient's first cardiac interval (e.g., the duration of a cardiac cycle or interval, QRS width, etc.), or the interval or measure between the first cardiac features and second cardiac features of corresponding successive first and second cardiac intervals of the patient. In examples, the first and second cardiac features include equivalent detection features in successive first and second cardiac intervals, such as successive R waves (e.g., RR intervals, etc.) or one or more other features of the cardiac electrical signal. Far-field cardiac signals can be sensed using the electrodes of the CAN.

[0052] The heart sound sensor 314 can be used to sense a patient's cardiac acceleration information. Heart sounds are recurring mechanical signals associated with the vibration of the heart or the acceleration from blood flow through the heart or other cardiac motions with each cardiac cycle or interval, and can be separated and classified according to the activities associated with these vibrations, accelerations, motions, pressure waves, or blood flow. Heart sounds include four main characteristics: the first to the fourth heart sounds (S1 to S4, respectively).

[0053] The first heart sound (S1) is a vibration produced by the heart during the closure of the atrioventricular (AV), mitral, and tricuspid valves, and during the opening of the aortic valve at the onset of systole or ventricular contraction. The second heart sound (S2) is a vibration produced by the heart during the closure of the aortic and pulmonary valves at the onset of diastole or ventricular relaxation. The third and fourth heart sounds (S3, S4) are related to the filling pressure of the left ventricle during diastole. A sudden cessation of early diastolic filling can result in the third heart sound (S3). Vibration due to atrial kick can result in the fourth heart sound (S4). Valve closure and changes in blood movement and pressure in the heart can cause acceleration, vibration, or motion of the heart wall, which can be detected using a heart sound sensor 314 (e.g., an accelerometer or microphone), thus providing an output referred to herein as cardiac acceleration information or heart sound information.

[0054] The AMD102 may optionally include a switching circuit 310 to electrically couple different combinations of electrodes to a treatment circuit 306 and a cardiac signal sensing circuit 304. The switching circuit 310 may configure any combination of electrodes as a pacing vector to deliver cardiac pacing stimulation energy, or configure any combination of electrodes as a sensing vector to sense cardiac signals.

[0055] Control circuitry 308 may include a digital signal processor, an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), a microprocessor, other types of processors, or multiple processors that interpret or execute instructions in software or firmware stored in memory 316 of control circuitry 308. In some examples, control circuitry 308 may include a state machine or sequencer implemented in hardware circuitry. Control circuitry 308 may include any combination of hardware, firmware, or software. Control circuitry 308 includes one or more circuits to perform the functions described herein. Circuitry may include software, hardware, firmware, or any combination thereof. For example, the circuitry may include instructions in software executing on control circuitry 308. Multiple functions may be performed by one or more circuits of control circuitry 308. Control circuitry 308 uses communication circuitry 312 to wirelessly transmit information with individual devices.

[0056] Figure 4 Is with Figure 3 External devices 107 that communicate with the AMD 102 (e.g., Figure 1 This is a block diagram of an example portion of an external device 107 of the neurostimulation system 100. External device 107 may be a programming device for the AMD 102. The programming device includes a storage device 422, programming control circuitry 420, a user interface 424, and communication circuitry 426. Programming control circuitry 420 may be implemented using an application-specific integrated circuit (ASIC) configured to perform one or more specific functions, or one or more general-purpose circuits programmed to perform those functions. General-purpose circuitry may, among other things, include a microprocessor or a portion thereof, a microcontroller or a portion thereof, and programmable logic circuitry or a portion thereof. Storage device 422 may be a memory integrated with programming control circuitry 420, or a separate memory device. Communication circuitry 426 wirelessly transmits information to the AMD 102 using near-field inductive wireless signals or far-field radio frequency (RF) signals. The programming device can be used to program pacing therapy parameters and other information in the AMD 102.

[0057] Figure 5 Is operating a CRM system (such as...) Figure 1The flowchart of method 500 in the example CRM system 100 includes AMD 102 (e.g., Figures 1 to 3 Any AMD in the AMD 102 and an external device 107 (e.g., a programming device) communicating with the AMD 102. The AMD can be configured (e.g., by programming) for conduction system pacing (CSP) and can be operatively coupled to electrodes (e.g., one or more electrodes positioned in the His bundle, left bundle branch, etc.) configured in shape and size for positioning at the location of the ventricular septum membrane in the patient.

[0058] AMD can sense cardiac electrical signals. The sensed cardiac signals can include QRS complexes. A QRS complex is a waveform generated by ventricular depolarization and consists of Q waves, R waves, and S waves. The Q waves, R waves, and S waves follow the P waves associated with atrial depolarization. The interval from the beginning of the Q wave to the end of the S wave is sometimes called the QRS width or QRS duration. The duration of the QRS complex can indicate the effectiveness of cardiac contraction. This can be useful for detecting correct beat-by-beat capture of the heart by a device providing pacing stimulation therapy. Shorter QRS complexes will indicate correct capture, while longer QRS complexes will indicate less effective contraction.

[0059] Method 500 automatically determines the optimal atrial-to-ventricular (AV) delay for configuring the AMD 102 for CSP. The AV delay is the time following a sensed or paced atrial depolarization event (in which the AMD 102 is programmed to deliver pacing stimulation to the ventricle if no intrinsic ventricular depolarization is sensed). If the AV delay is misprogrammed, opportunities to capture the left bundle branch or His bundle may be missed. If intrinsic conduction from the atrium arrives late but before the AV delay times out, the resulting ventricular depolarization may have long QRS complexes or fusion beats, either of which can lead to inefficient cardiac pumping. Appropriate AV delay in CSP results in efficient cardiac pumping.

[0060] However, the conduction pathway delivering pacing stimulation to the ventricular septum membrane complicates determining the AV delay due to the differences in timing involved compared to conventional pacing. For example, there is a delay between pacing the left bundle branch or His bundle and the actual depolarization of the ventricular myocardium. Programming the AV delay can be complicated by the isoelectric interval between the left bundle branch or His bundle and the location where myocardial contraction occurs. For example, the interval from stimulation of the His bundle to depolarization of the ventricular myocardium can be referred to as the His to ventricular (HV) interval. To achieve the same programmed AV delay as conventional RV pacing using electrodes near the RV apex, the AV delay for pacing using electrodes at or near the His bundle will be programmed to be smaller than the HV interval value of the conventional AV delay, so as to pace the His bundle earlier than the pacing RV apex. For pacing the left bundle branch (LBB), the AV delay will be programmed to be smaller than the LBB to ventricular septum value of the conventional AV delay.

[0061] Figure 5 Method 500 optimizes atrial-ventricular timing during pacing stimulation therapy in the presence of CSP electrodes. It can be used in... Figure 3 The AMD 102's control circuitry 308 includes instructions in memory 316, including the illustrated AV delay test 318, to perform optimization. Optimization of atrial-ventricular timing can be achieved through hemodynamic assessment via control circuitry 308.

[0062] At box 505, the baseline P-wave to intrinsic R-wave interval (baseline PR interval) of cardiac depolarization is measured by the AMD's control circuitry. To determine the baseline PR interval, the AMD senses the intrinsic cardiac signal and measures the atrial sense to ventricular sense (AsVs) interval over multiple heartbeats. During measurement, the AMD can be programmed to a DDI mode defined by NASPE / BPEG. The AV delay can be programmed to an extended AV delay value (e.g., 400 ms or 400 milliseconds) to facilitate the measurement of the AsVs interval over intrinsic heartbeats.

[0063] AMD is modified to pace the atrium and the atrial pace-to-ventricular sense (ApV) interval is measured over multiple heartbeats. Pacing stimulation is delivered using an atrial pacing vector. The atrial pacing vector includes at least one electrode from an atrial lead and can be a bipolar pacing vector (e.g., Figure 2 (the tip electrode 221 and the ring electrode 222 in the middle) or a unipolar pacing vector (e.g.) Figure 2(The tip electrode 221 and the CAN electrode). AMD can determine the sinus rate from the AsVs interval and set the pacing rate to be faster than the sinus rate (e.g., a pacing rate 10 beats per minute (10 bpm) higher than the sinus rate). The AsVs interval and ApVs interval are used to determine the baseline PR interval, which can be the patient's native PR interval. For example, the intervals can be averaged to determine the baseline PR interval.

[0064] At box 510, AMD performs hemodynamic measurements on the baseline PR interval. For example, AMD measures one or both of heart sound parameters and QRS width as hemodynamic measurements of the baseline PR interval. Figure 3 The parameters are extracted from the heart sound signal sensed by the heart sound sensor 314. The heart sound signal may include one or both of heart sound S1 and heart sound S2, and the heart sound parameters may be, for example, the amplitude of one or both of heart sounds S1 and S2.

[0065] The QRS width can be measured by AMD's control circuitry. This control circuitry may include signal processing circuitry (e.g., a digital signal processor) to measure the QRS width. In some examples, a far-field sensing vector is used to measure the QRS width. This far-field sensing vector may include AMD's CAN electrode and another electrode near the right or left ventricle (e.g., [missing information]). Figure 2 (RV tip electrode 226 to CAN electrode). The heart sound parameters and QRS width of the baseline PR interval can be determined from the heart sound and cardiac signals sensed against the AsVs and ApVs intervals. Baseline measurements can be used to assess a patient's native or intrinsic conduction.

[0066] Other measurements can be used to assess a patient's intrinsic conduction. In some examples, one or both of left ventricular (LV) activation time and right ventricular (RV) activation time can be measured against the baseline PR interval. RV and LV activation times can be determined using the sensed ApVs interval and can be measured as the time interval from the delivery of the pacing stimulus to the peak of the far-field QRS complex. The interval can be measured using the same far-field sensing vector used to measure the QRS width. RV and LV activation times can also be measured as the time interval from the delivery of the pacing stimulus to the peak of the QRS complex on an electrogram sensed using at least one electrode used to deliver the pacing stimulus.

[0067] Another measurement that can be used to assess a patient's intrinsic conduction is intracardiac impedance. Intracardiac impedance is the electrical impedance measured in one or more chambers of a subject's heart. Electrodes placed inside the heart can be used to obtain intracardiac impedance signals, providing a signal of impedance versus time. For example, in Figure 2In this device, a cardiac impedance sensor senses the intracardiac impedance of the right ventricle between an electrode 226 placed at the apex of the right ventricle and a defibrillation electrode 229 placed in or near the SVC. A predetermined excitation current is delivered between the electrodes, and the impedance is determined by the voltage sensed between the electrodes. AMD can assess the patient's condition using one or any combination of heart sound parameters, QRS width, RV activation time, LV activation time, and intracardiac impedance.

[0068] At box 515, AMD enables the delivery of pacing stimulation to the ventricle after a sensed atrial event is detected to set the AsVp interval. Pacing stimulation is delivered using a CSP vector comprising electrodes placed in the patient's ventricular septum membrane. AMD varies the AV delay of the AsVp interval over multiple cardiac cycles. When varying the AV delay, AMD can begin by delivering pacing stimulation with a slightly shorter AV delay than the inherent AV delay measured for the AsVs interval, and gradually decrease the AV delay while measuring heart sound parameters and QRS width. As an example intended to be non-limiting, AMD can repeatedly decrease the AV delay by 10 ms until the AV delay is in the range of 50 ms to 80 ms.

[0069] The AV delay of the AsVp interval is assessed hemodynamically using the same type of measurement performed for the intrinsic assessment of the baseline PR interval (e.g., one or both of heart sound parameters and QRS width). If there is no conduction from the atrium to the ventricle, the control circuitry for AMD can use a predetermined PR interval (e.g., 200 ms) and assess the predetermined PR interval.

[0070] At box 520, AMD enables the delivery of pacing stimulation to both the atria and ventricles to set the atrial-to-ventricular pacing interval (ApVp interval). Atrial pacing stimulation can be delivered using the same atrial pacing vector used for the ApVs interval, and ventricular pacing stimulation can be delivered using the same CSP vector used for the AsVp interval. Atrial and ventricular pacing stimulation are delivered over multiple cardiac cycles. Atrial pacing stimulation can be delivered faster than the intrinsic sinus rate measured for either the AsVs or AsVp interval (e.g., 10 bpm faster). Ventricular pacing stimulation can be delivered using the same AV delay interval as the AsVp interval.

[0071] The AV delay of the AsVp interval is assessed hemodynamically using the same types of measurements performed for the AsVs and AsVp intervals (e.g., one or more of heart sound parameters, QRS width, RV activation time, LV activation time, and the patient's intracardiac impedance). Hemodynamic measurements are recorded for different AV delays across various pacing modes. AMD can store hemodynamic measurements for AsVs, AsVp, and ApVp modes.

[0072] At box 525, a recommended AV delay setting is generated based on the recorded data. The recommended AV delay setting may be an AV delay that results in an increase in the amplitude of the S1 or S2 heart sound, a narrowing of the QRS width, a shortening of the LV or RV activation time, or an improvement in pumping as indicated by intracardiac impedance.

[0073] In some examples, AMD determines recommended AV delay settings. An external device (e.g., an AMD programmer) uploads the recommended AV delay settings and presents them to a user (e.g., a clinician or physician). The user can then select to use the recommended AV delay settings using the external device's user interface. In some examples, AMD uploads stored data to an external device (e.g., using wireless communication circuitry), and the external device determines the recommended AV delay settings and presents them to the user.

[0074] If multiple types of measurements are performed, the types of measurements can be prioritized, and a recommended AV delay setting can be selected based on the priority ranking. For example, heart sound parameters can take precedence over QRS width. If an AV delay value improves both heart sound amplitude and QRS width, and a second AV delay value shows a better improvement in heart sound amplitude but a smaller improvement in QRS width, then the second AV delay value will be selected as the recommended AV delay setting based on the priority ranking given to heart sound improvement. In another example, if there is no difference in improvement for the highest priority measurement (e.g., heart sound amplitude), the next priority measurement (e.g., QRS width) will be used to determine the recommended AV delay setting. If there is again no difference in the next priority measurement, a third priority measurement can be used. The order of priority ranking can be selected by the user.

[0075] In another example, a table can be presented using the user interface of an external device. This table can list the AV delay settings and their hemodynamic measurements. In some examples, the AV delay settings are sorted by the external device based on hemodynamic performance measured or prioritized.

[0076] In some examples, the recommended AV delay setting is a dynamic AV delay setting that varies with the patient's heart rate. A patient's sinus heart rate may vary at different times of the day, and the AV delay setting can change as a function of the sinus heart rate. In some examples, the recommended AV delay setting is a range of AD delay values, and AMD adjusts the AV delay from a first AV delay value within the recommended range to a second AV delay value within the recommended range based on changes in heart rate.

[0077] AV delay testing and optimization analysis can be performed in a clinical setting (e.g., at implantation or follow-up), and clinicians can set AV delays based on the results of the AV delay test presented to them. AV delay analysis can also be performed outside the clinical setting while the patient is on the move. AV delay analysis can be performed according to a schedule (e.g., a schedule set by the user). In some examples, AMD repeatedly examines hemodynamic measurements (e.g., QRS width) and runs AV delay optimization analysis when hemodynamic measurements are outside a predetermined range.

[0078] In some examples, AMD determines an optimized AV latency setting and resets the AV latency to the new setting when the patient moves. In other examples, when the AV latency optimization analysis produces a recommended latency setting that differs from the device's current AV latency setting or differs by more than a predetermined AV latency difference, AMD generates an alert indicating that the current AV latency setting is suboptimal.

[0079] The systems, methods, and devices described in this paper provide device-based data collection and analysis that help reduce the parameter search space for AMD. The atrial-ventricular timing of electrical pacing therapy is optimized for specific patients with AMD who can receive electrical pacing to their interventricular conduction system.

[0080] Additional Notes

[0081] The above detailed description includes references to the accompanying drawings, which form part of the detailed description. The drawings illustrate, by way of illustration, specific embodiments in which the invention can be practiced. These embodiments are also referred to herein as “examples.” All disclosures, patents, and patent documents mentioned in this document are incorporated herein by reference in their entirety as if individually incorporated by reference. In the event of inconsistencies in usage between this document and those documents so incorporated by reference, the usage in one or more incorporated references shall be considered supplementary to the usage in this document; for irreconcilable inconsistencies, the usage in this document prevails.

[0082] In this document, as is common in patent literature, the terms “a” or “an” are used to include one or more, independent of any other instances or uses of “at least one” or “one or more.” In this document, the term “or” is used to refer to a non-exclusive “or,” such that “A or B” includes “A, but without B,” “B, but without A,” and “A and B,” unless otherwise indicated. In the appended claims, the terms “including” and “in which” are used as concise English equivalents to the respective terms “comprising” and “wherein.” Furthermore, in the following claims, the terms “including” and “comprising” are open-ended, meaning that a system, apparatus, article, or process including elements other than those listed after such terms in the claims is still considered to fall within the scope of the claims. Additionally, in the following claims, the terms “first,” “second,” and “third,” etc., are used merely as labels and are not intended to impose numerical requirements on their objects.

[0083] The method examples described herein may be implemented, at least in part, by a machine or computer. Some examples may include a computer-readable or machine-readable medium encoded with instructions operable to configure an electronic device to perform the methods described in the examples above. Implementations of such methods may include code, such as microcode, assembly language code, or high-level language code or similar code. Such code may include computer-readable instructions for performing various methods. The code may form part of a computer program product. Furthermore, the code may be tangibly stored on one or more volatile or non-volatile computer-readable media during execution or at other times. These computer-readable media may include, but are not limited to, hard disks, removable disks, removable optical discs (e.g., optical discs and digital video discs), magnetic tape cartridges, memory cards or memory sticks, random access memories (RAMs), read-only memories (ROMs), and the like. In some examples, a carrier medium may carry the code implementing the method. The term "carrier medium" may be used to refer to a carrier wave on which the code is transmitted.

[0084] The above description is intended to be illustrative and not restrictive. For example, the above examples (or one or more aspects thereof) may be used in combination with each other. Other embodiments may be used by those skilled in the art upon review of the above description. The abstract is provided to conform to 37 CFR §1.72(b) to allow the reader to quickly determine the nature of the technical disclosure. It is understood that this submission will not be used to interpret or limit the scope or meaning of the claims. Furthermore, in the above detailed description, various features may be grouped together to simplify this disclosure. This should not be construed as meaning that features of the disclosure not claimed are essential to any claim. Rather, inventive subject matter may lie in fewer than all features of a particular disclosed embodiment. Therefore, the following claims are incorporated herein by reference, wherein each claim stands independently as a separate embodiment. The scope of the invention should be determined by reference to the appended claims together with the full scope of the equivalents to which such claims are entitled.

Claims

1. A mobile medical device, the device comprising: The treatment circuit is configured to deliver cardiac pacing stimulation energy when connected to an electrode including at least one conduction system pacing (CSP) electrode positioned in the ventricular septum membrane of the subject. A cardiac signal sensing circuit configured to sense cardiac signals representing cardiac activity when connected to the electrodes; Heart sound sensing circuit that generates heart sound signals; as well as A control circuit operatively coupled to the treatment circuit, the cardiac signal sensing circuit, and the heart sound circuit; wherein the control circuit is configured to: The baseline P-wave to intrinsic R-wave interval (baseline PR interval) of the sensed cardiac signal is measured. Measure one or both of the heart sounds at the baseline PR interval and the width of the QRS complex during cardiac depolarization (QRS width); The at least one CSP electrode is used to deliver pacing stimulation to the ventricle to set the atrial-sensed ventricular pacing event interval (AsVp interval) and to measure one or both of the heart sounds and QRS widths of the AsVp interval. A pacing stimulus is delivered to an atrial electrode to set the atrial-to-ventricular pacing interval (ApVp interval), and one or both of the heart sounds and QRS widths at the ApVp interval are measured; and Based on one or both of the measured heart sounds and the measured QRS width, a recommended atrial-ventricular delay (AV delay) setting is generated for the CSP.

2. The device according to claim 1, wherein, The control circuit is configured as follows: The AsVp interval of multiple cardiac cycles is varied, and one or more of the heart sounds and QRS widths of the multiple cardiac cycles are measured; The ApVp interval was varied across multiple cardiac cycles, and one or more of the heart sounds and QRS widths were measured during the multiple cardiac cycles; and The recommended AV delay settings are generated using the measured heart sounds and QRS widths from the multiple cardiac cycles.

3. The device according to claim 2, wherein, The control circuit is configured as follows: For the baseline PR interval, the AsVp interval, and the ApVp interval, measure one or both of the left ventricular activation time and the right ventricular activation time; and The recommended AV delay settings are generated based on one or more of the measured heart sounds, the measured QRS width, and the measured left ventricular activation time and right ventricular activation time.

4. The device according to claim 3, comprising: Housing and CAN electrode formed using said housing; and The control circuit is configured to measure the left ventricular activation time and the right ventricular activation time by measuring one or both of the following: The ventricular activation time interval between the delivery of the pacing stimulus to the ventricle and the peak of the sensed far-field QRS complex, wherein the far-field QRS complex is sensed using a sensing vector including the CAN electrode; and The interval between delivering the pacing stimulus to the ventricle and the sensed electrogram signal, wherein the electrogram signal is sensed using a sensing vector comprising electrodes for delivering the pacing stimulus to the ventricle.

5. The device according to any one of claims 1 to 4, comprising: A cardiac impedance sensing circuit, configured to sense an impedance signal representing the electrical impedance of one or more cardiac chambers; The control circuit is configured as follows: The impedance of each of the baseline PR interval, the AsVp interval, and the ApVp interval is measured using the impedance signal; and The recommended AV delay settings are generated based on one or more of the measured heart sounds, measured QRS width, and measured impedance.

6. The device according to any one of claims 1 to 5, wherein, The control circuit is configured as follows: The interval between sensed intrinsic atrial depolarization and sensed intrinsic ventricular depolarization (AsVs interval) is measured. The pacing stimulus is delivered to the atrium, and the interval between the pacing atrial depolarization and the sensed intrinsic ventricular depolarization (ApVs interval) is measured. Measure one or both of the heart sounds and QRS widths of the AsVs interval and the ApVs interval; and The recommended AV delay setting is generated based on one or both of the measured heart sounds and the measured QRS width of the AsVs interval, ApVs interval, AsVp interval, and ApVp interval.

7. The device according to any one of claims 1 to 6, comprising: A communication circuit, coupled to the control circuit, is configured to wirelessly transmit information with individual devices; and The control circuit is configured as follows: Change the AsVp interval of the first multiple cardiac cycles; Change the ApVp interval of the second or more cardiac cycles; Measure both the heart sound amplitude and QRS width in the first plurality of cardiac cycles and the second plurality of cardiac cycles; Multiple recommended AV delay settings are generated based on the measured heart sound amplitude and QRS width; and The recommended AV delay settings, along with the measured heart rate amplitude and QRS width, are transmitted to the individual devices.

8. The device according to any one of claims 1 to 7, comprising: Housing and CAN electrode formed using said housing; and The control circuit is configured as follows: The amplitude of one or more heart sounds is measured using the heart sound signal; The far-field QRS width is measured using a far-field sensing vector including the CAN electrode; and The recommended AV delay setting is generated based on the far-field QRS width and the measured amplitude of the one or more heart sounds.

9. The device according to any one of claims 1 to 8, wherein, The control circuit is configured as follows: Generate a recommended range for AV delay settings; and Based on changes in heart rate, the AV delay setting is changed from the first AV delay setting within the recommended range to the second AV delay setting within the recommended range.

10. A method of operating a cardiac rhythm management (CRM) system, the method comprising: The baseline P-wave to intrinsic R-wave interval (baseline PR interval) of cardiac depolarization in the subjects was measured. Measure one or both of the heart sounds at the baseline PR interval and the width of the QRS complex during cardiac depolarization (QRS width); After a sensed atrial event, a pacing stimulus is delivered to the ventricle to set an atrial-sensed ventricular pacing interval (AsVp interval) and to measure one or both of the heart sounds and QRS widths of the AsVp interval, wherein the pacing stimulus is delivered using a conduction system pacing (CSP) vector comprising electrodes positioned in the ventricular septal membrane. The pacing stimulus is delivered to the atrium to set the atrial-to-ventricular pacing interval (ApVp interval), and one or both of the heart sounds and QRS widths of the ApVp interval are measured; and Based on one or both of the measured heart sounds and the QRS width, a recommended atrial-ventricular delay (AV delay) setting is generated for the CSP.

11. The method of claim 10, comprising: The AsVp interval of multiple cardiac cycles is varied, and one or both of the heart sounds and QRS width of the multiple cardiac cycles are measured. The ApVp interval was varied across multiple cardiac cycles, and one or both of the heart sounds and QRS widths were measured during said multiple cardiac cycles; and The process of generating the recommended AV delay settings includes using one or both of the heart sounds and QRS widths measured for the plurality of cardiac cycles.

12. The method according to claim 11, in, Measuring one or both of the heart sounds and the QRS width includes measuring both the heart sounds and the QRS width; and The process of generating the recommended AV delay settings includes generating multiple AV delay settings and presenting the recommended AV delay settings based on the amplitude of the heart sounds and the narrowness of the QRS width.

13. The method according to any one of claims 10 to 12, comprising: For the baseline PR interval, the AsVp interval, and the ApVp interval, measure one or both of the left ventricular activation time and the right ventricular activation time; and The process of generating the recommended AV delay settings includes generating the recommended AV delay based on one or more of the measured heart sounds, the measured QRS width, and the measured left ventricular activation time and right ventricular activation time.

14. The method according to claim 13, wherein, Measuring one or both of the left ventricular activation time interval and the right ventricular time interval includes measuring one or both of the following: The ventricular activation time interval between the delivery of the pacing stimulus to the ventricle and the peak of the sensed far-field QRS complex, wherein the far-field QRS complex is sensed using a sensing vector of a CAN electrode of a mobile medical device including the CRM system; and The interval between delivering the pacing stimulus to the ventricle and the sensed electrogram signal, wherein the electrogram signal is sensed using a sensing vector comprising electrodes for delivering the pacing stimulus.

15. The method according to any one of claims 10 to 14, comprising: The electrical impedance of one or more cardiac chambers of a subject is measured for the baseline PR interval, the AsVp interval, and the ApVp interval; and The recommended AV delay setting is generated based on one or more of the measured heart sounds, measured QRS width, and measured impedance.

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