Heart sound-based conduction system pacing

Abstract

Systems and methods for detecting obstructions in a patient's cardiac conduction system using heart sound information are disclosed. An exemplary medical device system includes a data receiver circuit to receive heart sound information sensed from a patient, and a controller circuit to generate heart sound metrics or characteristics from received heart sound signals. The heart sound metric may include a metric indicative of the presence or absence of split S1 sound. The controller circuit may detect a Beam Branch Block (BBB) based at least in part on the heart sound metric, including to distinguish between a left Beam Branch Block (LBBB) and a right Beam Branch Block (RBBB). The BBB indicator may be provided to the user or a process that may be performed by the medical device system to optimize cardiac pacing and restore cardiac synchronization.

Description

[0001] Related applications

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 443,833, filed February 7, 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present invention relates generally to medical systems and, more particularly, to systems, devices, and methods for detecting blockages in a patient's cardiac conduction system based on heart sounds. Background Art

[0004] The heart is the center of the human circulatory system. It includes an electromechanical system that performs two main pumping functions. The left side of the heart, including the left atrium (LA) and the left ventricle (LV), extracts oxygenated blood from the lungs and pumps it to the organs of the body to provide the organs with metabolic needs for oxygen. The right side of the heart, including the right atrium (RA) and the right ventricle (RV), extracts deoxygenated blood from the organs of the body and pumps it to the lungs, where the blood is oxygenated. These pumping functions are caused by the contraction of the myocardium (myocardium). In a normal heart, the sinoatrial (SA) node, the heart's natural pacemaker, generates an electrical impulse, called an action potential, which propagates to various areas of the heart through a natural electrical conduction pathway called the His-Purkinje system to stimulate the heart's myocardial tissue. For example, the action potential originating from the SA node propagates through the atrioventricular (AV) node, the bundle of His (also known as the bundle of His), the bundle branches, and the Purkinje fibers to reach the ventricular myocardium, resulting in coordinated contraction of the two ventricles.

[0005] The coordinated delay of action potential propagation in the normal cardiac electrical conduction system causes the various parts of the heart to contract synchronously, thereby producing an effective pumping function. Blockage or interruption of the cardiac conduction system and / or deteriorating myocardium may cause asynchronous contraction of the heart, thereby leading to poor hemodynamic performance, including reduced blood supply to the heart and other parts of the body. For example, an abnormal delay in action potential transmission in the His bundle may cause irregular or asynchronous contraction of the ventricles. Blockage or interruption of any part of the bundle branch may cause bundle branch block, such as left bundle branch block (LBBB) or right bundle branch block (RBBB). Although RBBB is more common in the general population, about one-third of heart failure patients suffer from LBBB. LBBB can also be used as an indicator of acute myocardial infarction (MI) that may cause ischemic stroke.

[0006] Artificial cardiac pacing systems have been used to correct cardiac dyssynchrony and improve hemodynamic performance. Artificial cardiac pacing systems can provide electrical stimulation to one or more parts of the heart in order to restore normal cardiac function to a certain extent. For example, right ventricular (RV) pacing via an electrode implanted in the apex of the RV has been used for univentricular and biventricular (BiV) pacing. RV apex pacing directly stimulates the ventricular myocardium in an unnatural manner, involving slow muscle-to-muscle contractions. Typically, ventricular stimulation involves rapid coordinated activation via action potentials that propagate through natural conduction pathways. Studies have shown that in some patients, cardiac dyssynchrony caused by RV apex pacing, in part due to delayed propagation of interventricular impulses to the left ventricle, can lead to adverse ventricular changes, including ventricular enlargement and heart failure with chronic delivery. In addition, these patients may experience permanent changes in myocardial perfusion and structure over time, which may further reduce cardiac output and worsen ventricular function. BiV pacing involves RV pacing via one lead and LV pacing via another lead and has been shown to restore synchronized contraction of the two ventricles. However, the potential adverse effects on ventricular function produced by RV apex pacing may still exist with BiV pacing.It is also known that muscle-to-muscle activation via epicardial LV pacing results in less vigorous contractions.

[0007] Heart sounds are generally associated with the mechanical vibrations of the heart and blood flow through the heart. Heart sounds recur with each cardiac cycle and are separated and categorized based on the activity associated with the vibrations. Historically, heart sounds were assessed by humans, and therefore only the audible portion of the vibrations was used. Devices can now assess the full spectrum of cardiac vibrations, including audible and subaudible components, so the term "sounds" in this article refers to the full spectrum of vibrations. Typically, heart sounds sensed from a subject can include several components within the cardiac cycle, including the first heart sound (S1), the second heart sound (S2), the third heart sound (S3), or the fourth heart sound (S4). S1 is associated with vibrations generated by the heart during the closure of the atrioventricular (mitral and tricuspid) valves, as ventricular pressure exceeds atrial pressure at the beginning of systole. S2 is generated by the closing of the aortic and pulmonary valves and marks the beginning of diastole. S3 is generated by diastolic vibrations in early diastole, corresponding to passive ventricular filling during diastole, when blood rushes into the ventricles. S4 is produced by the end-diastolic oscillation corresponding to active ventricular filling, when the atria contract and push blood into the ventricles. In healthy subjects, S3 is usually weak and S4 is barely audible. However, pathological S3 or S4 may be higher-pitched and louder.

[0008] Heart sounds have been used to assess both systolic and diastolic function. Systole is the contraction or period of contraction of the heart, which causes blood to be forced out of the heart, such as the ventricles, and into the aorta and pulmonary artery. Diastole is the relaxation or period of relaxation of the heart, during which blood flows back into the heart, such as the ventricles. In patients with heart disease, systolic or diastolic function may deteriorate. For example, congestive heart failure (CHF) occurs when the heart cannot supply enough blood to maintain a healthy physiological state. Summary of the Invention

[0009] The hemodynamic response to cardiac pacing may depend on many factors, including pacing site selection and pacing configuration. Many patients receiving cardiac pacing therapy have an intact cardiac conduction system (e.g., His-Purkinje system) in the ventricles and therefore have normal ventricular excitation. Conventional cardiac pacing, such as long-term RV apex pacing (i.e., pacing at the RV apex), may lead to a reduction in cardiac output and efficiency due to uncoordinated contraction sequences. This asynchrony may ultimately lead to adverse long-term effects. Asynchronous contractions of the ventricles occur during conventional RV pacing because the activation sequence may be much slower and slowly propagate from the right ventricle across the ventricular septum to the left ventricle, resulting in ventricular asynchrony. This activation sequence results in uncoordinated contractions, which do not occur during biventricular activation through the heart's natural conduction system.

[0010] Pacing a portion of the natural cardiac conduction system (e.g., the bundle of His, left or right bundle branches, fascicles or Purkinje fibers, and other conductive cardiac tissue) is an alternative to traditional ventricular pacing. Cells of the natural conduction system can propagate activation signals approximately four times faster than working myocardium. Conduction system pacing (CSP), such as His bundle pacing (HBP), septal pacing (such as left bundle branch pacing (LBBP) or right bundle branch pacing (RBBP) at the septal region), or pacing at other sites of the His-Purkinje conduction system, can activate the heart's natural electrical conduction system, restore or improve cardiac synchronization, and reduce or even eliminate the potential long-term adverse hemodynamic effects associated with traditional RV apical pacing.

[0011] However, when unsuccessful, CSP may fail to adequately restore cardiac synchronization. For example, HBP may lose the ability to activate (or capture) the His bundle or adjacent conducting tissue, but only activate the para-His myocardium. Stimulation of the muscles adjacent to the His bundle may result in an asynchronous pattern similar to RV apical pacing. This undesirable outcome is referred to as "para-His capture." Simultaneous capture of the His bundle and para-His muscles (also known as non-selective His capture) may be as clinically effective as capturing only the His bundle (also known as selective His capture) because the resulting ventricular activation and contraction are dominated by the more rapidly conducting Purkinje system. Another adverse consequence of HBP is complete loss of capture (LOC), in which the pacing pulse captures neither the para-His myocardium nor the His bundle.

[0012] The ability of CSP to restore cardiac synchronization may also depend on the pacing site relative to the obstruction site along the His-Purkinje system (such as obstruction of the His bundle or bundle branches). Ventricular dyssynchrony in many CHF patients may be attributed to varying degrees of left bundle branch block (LBBB), which causes LV depolarization to lag behind RV depolarization. In the general population, right bundle branch block (RBBB) is generally more common than LBBB. Only when the pacing pulse is delivered to the distal side of the obstruction site can effective propagation of the action potential through the His-Purkinje system to restore cardiac synchronization be achieved. If the pacing pulse is delivered to the proximal side of the obstruction site, even if the proximal portion of the His bundle is activated, the action potential cannot bypass the obstruction and propagate to the ventricles through the His-Purkinje system. Therefore, cardiac synchronization may not be restored.

[0013] Correct detection of blockages along the cardiac conduction system, such as detecting and distinguishing LBBB and RBBB, can provide guidance for optimizing cardiac pacing. The pacing site is conventionally determined by analyzing cardiac electrical signals (such as a surface electrocardiogram (ECG)). ECG parameters such as QRS width have been used to quantify the degree of dyssynchrony and to identify the "optimal" or desired pacing site where pacing will result in a shortening of the QRS width. However, complex calculations are generally required to have a robust and accurate QRS width measurement, which can be time consuming. There may be significant differences in the stability of QRS width measurements in some patients after implantation. Additionally, although QRS width or other ECG parameters indicate or are associated with electrical dyssynchrony (or restoration of synchrony), QRS width and ECG parameters may not fully indicate or be associated with mechanical dyssynchrony between the left and right ventricles or parts of the ventricles. The present inventors have recognized the technical challenges in pacing the cardiac conduction system, particularly more effective and efficient techniques for determining a pacing location at or near the cardiac conduction system to reliably capture conductive tissue and restore ventricular synchronization.

[0014] This document describes techniques for detecting blockages in the cardiac conduction system using cardiac sound information, and in particular, techniques for distinguishing between LBBB and RBBB. Information about the detected blockage can be used to optimize cardiac pacing therapy, such as selecting an appropriate CSP pacing site or programming pacing parameters. An exemplary medical device system includes: a data receiver circuit for receiving cardiac sound information sensed from a patient, and a controller circuit for generating a cardiac sound metric or feature based on the received cardiac sound information. The controller circuit can detect bundle branch block (BBB) ​​based at least in part on the cardiac sound metric, including to distinguish between left bundle branch block (LBBB) and right bundle branch block (RBBB). The BBB indicator can be provided to a user (e.g., a clinician) or to a process that can be performed by the medical device system to optimize cardiac pacing to restore cardiac synchronization or improve cardiac performance.

[0015] Example 1 is a medical device system for managing a cardiac condition, comprising: a data receiver circuit configured to receive heart sound information sensed from a patient, the heart sound information including an S1 sound signal; and a controller circuit configured to generate a heart sound metric using the received heart sound information; detect bundle branch block (BBB) ​​based at least in part on the generated heart sound metric, including for distinguishing between left bundle branch block (LBBB) and right bundle branch block (RBBB); and provide information about the detected BBB to a user or a process executable by the medical device system.

[0016] In Example 2, the subject matter of Example 1 optionally includes a heart sound metric indicating the presence or absence of a split S1 sound, wherein, to detect BBB, the controller circuit is configured to: detect LBBB in response to the absence of a split S1 sound or the occurrence of a split S1 sound being below a threshold; and detect RBBB in response to the presence of a split S1 sound or the occurrence of a split S1 being above a threshold.

[0017] In Example 3, the subject matter of Example 2 optionally includes a heart sound metric indicating the presence or absence of a split S1 sound, which may include a signal width of the S1 sound signal, wherein the controller circuit is configured to detect the presence or absence of the split S1 sound based on a comparison of the signal width of the S1 sound signal with a width threshold.

[0018] In Example 4, the subject matter of any one or more of Examples 2-3 optionally includes a heart sound metric indicating the presence or absence of a split S1 sound, which may include a spectral entropy of the S1 sound signal, wherein the controller circuit is configured to detect the presence or absence of the split S1 sound based on a comparison of the spectral entropy of the S1 sound signal with a spectral entropy threshold.

[0019] In Example 5, the subject matter of any one or more of Examples 2-4 optionally includes an electrical stimulator configured to provide cardiac stimulation to a patient, wherein the controller circuit is configured to generate control signals to the electrical stimulator to: deliver cardiac conduction system pacing (CSP) at the His bundle or septal region of the heart via a first one or more electrodes in response to a detected LBBB; and withhold cardiac stimulation or deliver RV pacing at a right ventricle (RV) apex of the heart via a second one or more electrodes in response to a detected RBBB.

[0020] In Example 6, the subject matter of Example 5 optionally includes a lead having a distal portion configured to be inserted into the His bundle or septal region at an adjustable depth to deliver a CSP therein via a first one or more electrodes associated with the lead, wherein, in response to detecting an LBBB, the controller circuit is configured to: receive paced heart sound information in response to the delivery of the CSP; generate a heart sound metric indicating the presence or absence of a split S1 sound using the paced heart sound information; and determine whether to adjust the depth of insertion of the distal portion of the lead into the His bundle or septal region, including not adjusting the insertion depth if the heart sound metric indicates the presence of a split S1 sound, or if the incidence of the split S1 sound exceeds a ratio threshold, and adjusting the insertion depth if the heart sound metric indicates the absence of a split S1 sound, or if the incidence of the split S1 sound is below the ratio threshold.

[0021] In Example 7, the subject matter of Example 6 optionally includes a controller circuit that can be configured to generate a control signal to a user interface to display a heart sound metric indicating the presence or absence of a split S1 sound in real time when the distal portion of the lead is positioned at different insertion depths so that the CSP is being delivered.

[0022] In Example 8, the subject matter of any one or more of Examples 5-7 optionally includes a controller circuit that can be configured to, in response to detecting an LBBB: generate a control signal to an electrical stimulator to deliver cardiac resynchronization pacing (CRT) pacing to the left ventricle and the right ventricle of the heart according to CRT pacing parameters; receive paced heart sound information in response to the delivery of CRT; generate a heart sound metric indicating the presence or absence of a split S1 sound using the paced heart sound information; and determine whether to adjust the CRT pacing parameters, including: not adjusting the CRT pacing parameters if the heart sound metric indicates that a split S1 sound is present, or if the incidence of the split S1 sound exceeds a ratio threshold; and adjusting the CRT pacing parameters if the heart sound metric indicates that a split S1 sound is not present, or if the incidence of the split S1 sound is below a ratio threshold.

[0023] In Example 9, the subject matter of Example 8 can optionally include, wherein adjusting CRT pacing parameters comprises adjusting pacing dose parameters or pacing timing parameters, or switching from single-site ventricular pacing to multi-site ventricular pacing.

[0024] In Example 10, the subject matter of any one or more of Examples 8-9 optionally includes a controller circuit that can be configured to generate a control signal to a user interface to display a heart sound metric indicating the presence or absence of a split S1 sound in real time while CRT is being delivered according to different values ​​of CRT pacing parameters.

[0025] In Example 11, the subject matter of any one or more of Examples 1-10 optionally includes a data receiver circuit that may be configured to receive respiratory information sensed from a patient, the respiratory information including an inspiratory phase and an expiratory phase in a respiratory cycle, wherein the controller circuit is configured to generate a heart sound metric using a portion of the received heart sound information corresponding to the inspiratory phase of the respiratory cycle, and to detect the BBB based on the heart sound metric during the inspiratory phase.

[0026] In Example 12, the subject matter of any one or more of Examples 1-11 may optionally include the heart sound metric comprising an intensity of an S1 sound signal, wherein the controller circuit is configured to detect the BBB further based on the S1 sound intensity.

[0027] In Example 13, the subject matter of any one or more of Examples 1 to 12 optionally includes a data receiver circuit that can be configured to receive cardiac electrical activity information sensed from the patient, wherein the controller circuit is configured to use the received heart sound information and the cardiac electrical activity information to generate a heart sound metric including a pre-ejection period measurement value, and further detect the BBB based on the pre-ejection period measurement value.

[0028] In Example 14, the subject matter of any one or more of Examples 1 to 13 may optionally include a risk assessment circuit configured to generate a risk of cardiac or pulmonary disease in the patient based at least on the detected information of the BBB.

[0029] In Example 15, the subject matter of any one or more of Examples 1 to 14 may optionally include a user interface configured to generate an alert of a detected BBB.

[0030] Example 16 is a method for managing a cardiac condition using a medical device system, the method comprising: receiving heart sound information sensed from a patient, the heart sound information including an S1 sound signal; generating a heart sound metric using the received heart sound information; detecting bundle branch block (BBB) ​​based at least in part on the generated heart sound metric, including for distinguishing between left bundle branch block (LBBB) and right bundle branch block (RBBB); and providing information about the detected BBB to a user or process.

[0031] In Example 17, the subject matter of Example 16 optionally includes a heart sound metric that can indicate the presence or absence of a split S1 sound, wherein detecting BBB includes detecting LBBB in response to the absence of a split S1 sound or the incidence of a split S1 sound being below a threshold, and detecting RBBB in response to the presence of a split S1 sound or the incidence of a split S1 being above a threshold.

[0032] In Example 18, the subject matter of Example 17 optionally includes a heart sound metric indicating the presence or absence of a split S1 sound, which may include a signal width of the S1 sound signal, the method including detecting the presence or absence of the split S1 sound based on a comparison of the signal width of the S1 sound signal with a width threshold.

[0033] In Example 19, the subject matter of any one or more of Examples 17-18 optionally includes a heart sound metric indicating the presence or absence of a split S1 sound, which may include a spectral entropy of the S1 sound signal, the method including detecting the presence or absence of the split S1 sound based on a comparison of the spectral entropy of the S1 sound signal with a spectral entropy threshold.

[0034] In Example 20, the subject matter of any one or more of Examples 17-19 optionally includes: in response to a detected LBBB, delivering cardiac conduction system pacing (CSP) at the His bundle or septal region of the heart via a first one or more electrodes; and in response to a detected RBBB, withholding cardiac stimulation or delivering RV pacing at a right ventricle (RV) apex of the heart via a second one or more electrodes.

[0035] In Example 21, the subject matter of Example 20 optionally includes, in response to detecting LBBB: receiving paced heart sound information in response to delivering a CSP at the His bundle or septal region of the heart; using the paced heart sound information to generate a heart sound metric indicating the presence or absence of a split S1 sound; and determining whether to adjust the depth of insertion of a distal portion of the lead into the His bundle or septal region to deliver the CSP therein via a first one or more electrodes associated with the lead, including: if the heart sound metric indicates the presence of a split S1 sound, or if the incidence of the split S1 sound exceeds a ratio threshold, not adjusting the insertion depth; and if the heart sound metric indicates the absence of a split S1 sound, or if the incidence of the split S1 sound is below the ratio threshold, adjusting the insertion depth.

[0036] In Example 22, the subject matter of any one or more of Examples 20-21 optionally includes, in response to detecting LBBB: delivering cardiac resynchronization pacing (CRT) to the left ventricle and the right ventricle of the heart according to CRT pacing parameters; receiving paced heart sound information in response to the delivery of CRT; generating a heart sound metric indicating the presence or absence of a split S1 sound using the paced heart sound information; and determining whether to adjust the CRT pacing parameters, including: not adjusting the CRT pacing parameter value if the heart sound metric indicates that a split S1 sound is present, or if the incidence of the split S1 sound exceeds a ratio threshold, and adjusting the CRT pacing parameter if the heart sound metric indicates that a split S1 sound is not present, or if the incidence of the split S1 sound is below a ratio threshold.

[0037] In Example 23, the subject matter of any one or more of Examples 16-22 optionally includes receiving respiratory information sensed from a patient, the respiratory information including an inhalation phase and an expiratory phase in a respiratory cycle, wherein detecting the BBB is based at least in part on a heart sound metric generated using a portion of the received heart sound information corresponding to the inhalation phase of the respiratory cycle.

[0038] The systems, devices, and methods discussed in this document improve upon device-based monitoring and management techniques for cardiac conditions, such as BBB, with little additional cost or system complexity. Heart sound-based techniques for detecting blockages or interruptions in the cardiac conduction system, particularly techniques for distinguishing between LBBB and RBBB, can help determine appropriate pacing sites and electrode configurations for cardiac pacing (e.g., CSP) to restore cardiac synchrony or improve cardiac performance in patients with heart failure. CSP can activate the His-Purkinje system, thereby maintaining ventricular synchrony and improving cardiac performance without causing structural and functional damage to the heart. Compared to traditional ECG-based pacing optimization techniques, the heart sound-based pacing optimization described in this document utilizes existing sensors (e.g., accelerometers) that can measure heart sounds. Heart sound metrics can be derived from heart sound signals using less complex techniques that require less computational time. Heart sound-based optimization of pacing sites and pacing parameters can increase the chances of capturing the cardiac conduction system, thereby improving the overall success rate of CSP treatment, promoting synchronization via the patient's natural His-Purkinje system, and resulting in favorable cardiac performance and hemodynamic outcomes. By more effective and efficient pacing site optimization as described in this document, ineffective pacing (i.e., loss of capture) can be reduced, battery power of the cardiac pacing system or device can be conserved, and extended device life can be achieved without compromising effective CSP therapy. Thus, the subject matter discussed in this document improves the functionality of a cardiac pacing system or device.

[0039] In addition to optimizing cardiac pacing such as CSP, the heart sound-based BBB detection and the distinction between LBBB and RBBB described in this document according to various embodiments can also be used for detection, risk stratification, and treatment titration of other cardiac or pulmonary conditions. For example, RBBB can be caused by pulmonary hypertension, which is a risk factor for coronary artery disease such as acute myocardial infarction (MI). Heart sound-based RBBB detection as described herein can be used to predict the risk of pulmonary hypertension and thus help prevent pulmonary hypertension. Heart sound-based LBBB detection as described herein can be used to predict the risk of acute MI and ischemic stroke and thus help prevent acute MI and ischemic stroke.

[0040] While His bundle pacing or bundle branch pacing (e.g., LBB pacing or RBB pacing) is specifically discussed in various examples of this document, this is meant to be illustrative only and not limiting. It is within the contemplation of the inventors and within the scope of this document that the systems, devices, and methods described in accordance with various embodiments herein can be similarly applied to controllably stimulate other locations at or near the cardiac conduction system, including, for example, the His bundle, bundles, Purkinje fibers, and other conducting tissues of the cardiac conduction system, and to determine optimal or desired pacing locations and optimal or desired pacing parameters.

[0041] This summary provides some teachings of the present application and is not intended to be an exclusive or exhaustive treatment of the subject matter. Further details about the subject matter can be found in the detailed description and the appended claims. Other aspects of the present disclosure will be apparent to those skilled in the art upon reading and understanding the following detailed description and upon examining the accompanying drawings, each of which should not be construed as limiting. The scope of the present disclosure is defined by the appended claims and their legal equivalents. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Various embodiments are shown by way of example in the figures of the accompanying drawings. Such embodiments are exemplary and are not intended to be exhaustive or exclusive embodiments of the subject matter.

[0043] Figure 1 An example of a patient management system and a portion of an environment in which the system may operate are generally shown.

[0044] Figure 2 An example of a cardiac management system and a portion of an environment in which the system may operate are generally shown.

[0045] Figure 3 An example of a heart sound-based cardiac monitor and pacing system is generally shown.

[0046] Figures 4A-4CConceptual illustration of the different patterns of split S1 sounds in a normal heart (with an intact cardiac conduction system), RBBB, and LBBB.

[0047] Figures 5A-5B Examples of changes in S1 morphology and S1 intensity before and after myocardial infarction associated with LBBB in patients are shown.

[0048] Figure 6 Example methods for detecting and managing blockages in a patient's cardiac conduction system, such as the BBB, are generally described.

[0049] Figures 7A-7C An example method for optimizing cardiac pacing therapy to restore cardiac synchronization using heart sound-based BBB detection is generally presented.

[0050] Figure 8 A block diagram generally illustrates an example machine upon which any one or more of the techniques (eg, methodologies) discussed herein may be performed. DETAILED DESCRIPTION

[0051] Disclosed herein are systems, devices, and methods for detecting a blockage in a patient's cardiac conduction system using heart sound information sensed from the patient. An exemplary medical device system includes: a data receiver circuit for receiving heart sound information sensed from the patient, and a controller circuit for generating a heart sound metric or feature based on the received heart sound signal. The controller circuit can detect bundle branch block (BBB) ​​based at least in part on the heart sound metric, including for distinguishing between left bundle branch block (LBBB) and right bundle branch block (RBBB). The BBB indicator can be provided to a user (e.g., a clinician) or a process that can be performed by the medical device system to optimize cardiac pacing to restore cardiac synchronization or improve cardiac performance.

[0052] Figure 1 An example patient management system 100 and a portion of an environment in which the patient management system 100 can operate are generally shown. The patient management system 100 can perform a range of activities, including remote patient monitoring and diagnosis of disease conditions. These activities can be performed near the patient 101, such as at the patient's home or office, through a centralized server, such as at a hospital, clinic, or doctor's office, or through a remote workstation, such as a secure wireless mobile computing device.

[0053] The patient management system 100 may include one or more ambulatory medical devices, an external system 105, and a communication link 111 that provides communication between the one or more ambulatory medical devices and the external system 105. The one or more ambulatory medical devices may include an implantable medical device (IMD) 102, a wearable medical device (WMD) 103, or one or more other implantable, leadless, subcutaneous, external, wearable, or ambulatory medical devices configured to monitor, sense, or detect information from the patient 101, determine physiological information about the patient 101, or provide one or more therapies to treat various conditions of the patient 101, such as one or more cardiac or non-cardiac conditions (e.g., dehydration, sleep-disordered breathing, etc.).

[0054] In an example, IMD 102 may include one or more conventional cardiac rhythm management devices implanted in the chest of a patient, with IMD 102 having a lead system including one or more transvenous, subcutaneous, or non-invasive leads or catheters to position one or more electrodes or other sensors (e.g., heart sound sensors) in, on, or around the heart or at one or more other locations on the chest, abdomen, or neck of patient 101. In another example, IMD 102 may include a monitor implanted, for example, subcutaneously in the chest of patient 101, with IMD 102 including a housing containing circuitry and, in some examples, one or more sensors, such as a temperature sensor.

[0055] IMD 102 may include evaluation circuitry configured to detect or determine specific physiological information of patient 101, or to determine one or more conditions, or to provide information or alerts to a user, such as patient 101 (e.g., a patient), a clinician, or one or more other caregivers or processes. In an example, IMD 102 may be an implantable cardiac monitor (ICM) configured to collect cardiac information from a patient, optionally along with other physiological information. IMD 102 may alternatively or additionally be configured as a therapeutic device configured to treat one or more medical conditions of patient 101. Therapy may be delivered to patient 101 via a lead system and associated electrodes or using one or more other delivery mechanisms. Therapy may include delivering one or more medications to patient 101, such as using IMD 102 or one or more other ambulatory medical devices. In some examples, the therapy may include cardiac resynchronization therapy for correcting dyssynchrony and improving cardiac function in a heart failure patient. In other examples, IMD 102 may include a drug delivery system, such as a drug infusion pump, for delivering medication to the patient to manage arrhythmias or complications resulting from arrhythmias, hypertension, or one or more other physiological conditions. In other examples, IMD 102 may include one or more electrodes configured to stimulate the patient's nervous system or provide stimulation to muscles in the patient's airway, etc.

[0056] The WMD 103 may include one or more wearable or external medical sensors or devices (e.g., an automated external defibrillator (AED), a Holter monitor, a patch-based device, a smartwatch, a smart accessory, a wrist- or finger-worn medical device such as a finger-based photoplethysmography sensor, etc.).

[0057] In one example, the IMD 102 or WMD 103 may include or be coupled to an implantable or wearable sensor to sense heart sound signals and include a heart sound recognition circuit to identify one or more heart sound components, such as S1, S2, S3, or S4. The IMD 102 or WMD 103 also includes a heart sound-based event detector circuit that can detect a physiological event (e.g., an arrhythmia attack or a worsening heart failure (WHF) event) based at least on a heart sound metric of the one or more detected heart sound components. Examples of such heart sound metrics can include the amplitude or timing of a heart sound component relative to a reference point in the cardiac cycle. In some examples, at least a portion of the heart sound recognition circuit and / or the heart sound-based event detector circuit can be implemented in and executed by the external system 105.

[0058] External system 105 may include a dedicated hardware / software system, such as a programmer, a remote server-based patient management system, or alternatively, a system primarily defined by software running on a standard personal computer. External system 105 may manage patient 101 through IMD 102 or one or more other ambulatory medical devices connected to external system 105 via communication link 111. In other examples, IMD 102 may be connected to WMD 103 via communication link 111, or WMD 103 may be connected to external system 105 via communication link 111. This may include, for example, programming IMD 102 to perform one or more of acquiring physiological data, performing at least one self-diagnostic test (such as for device operational status), analyzing physiological data, or optionally delivering or adjusting therapy for patient 101. Additionally, external system 105 may send information to or receive information from IMD 102 or WMD 103 via communication link 111. Examples of information may include: real-time or stored physiological data from patient 101; diagnostic data, such as monitoring of patient hydration status, hospitalization, response to therapy delivered to patient 101, or device operating status of IMD 102 or WMD 103 (e.g., battery status, lead impedance, etc.). Communication link 111 may be an inductive telemetry link, a capacitive telemetry link, or a radio frequency (RF) telemetry link, or wireless telemetry based on, for example, "strong" Bluetooth or IEEE 802.11 Wireless Fidelity "Wi-Fi" interface standards. Other configurations and combinations of patient data source interfaces are also possible.

[0059] The external system 105 may include an external device 106 located near one or more mobile medical devices, and a remote device 108 located relatively remote from the one or more mobile medical devices, communicating with the external device 106 via a communication network 107. Examples of the external device 106 may include a medical device programmer. The remote device 108 may be configured to evaluate collected patient or patient information and provide alarm notifications, among other possible functions. In an example, the remote device 108 may include a centralized server that serves as a central hub for storing and analyzing collected data. The server may be configured as a single, multiple, or distributed computing and processing system. The remote device 108 may receive data from multiple patients. This data may be collected by one or more mobile medical devices and other data acquisition sensors or devices associated with the patient 101. The server may include a memory device to store the data in a patient database. The server may include alarm analyzer circuitry for evaluating the collected data to determine whether specific alarm conditions are met. The satisfaction of the alarm conditions may trigger the generation of an alarm notification, such as provided by one or more human-perceivable user interfaces. In some examples, the alarm condition can alternatively or additionally be evaluated by one or more mobile medical devices (such as implantable medical devices). By way of example, the alarm notification can include a web page update, a telephone or pager call, an email, SMS, a text or "instant" message, and a message to the patient and a direct notification to emergency services and clinicians simultaneously. Other alarm notifications are also possible. The server can include an alarm prioritizer circuit that is configured to prioritize the alarm notifications. For example, a similarity metric between physiological data associated with the detected physiological event and psychological data associated with historical alarms can be used to prioritize alarms for detected psychological events.

[0060] The remote device 108 may additionally include one or more locally configured clients or remote clients securely connected to the server via the communication network 107. Examples of clients may include personal desktops, laptops, mobile devices, or other computing devices. System users, such as clinicians or other qualified medical professionals, may use the clients to securely access stored patient data assembled in a database in the server and select and prioritize patients and alarms for healthcare provision. In addition to generating alarm notifications, the remote device 108, including the server and interconnected clients, may also execute a follow-up plan by sending a follow-up request to one or more ambulatory medical devices, or by sending a message or other communication as a compliance notification to the patient 101 (e.g., the patient), a clinician, or an authorized third party.

[0061] The communication network 107 can provide wired or wireless interconnection. In an example, the communication network 107 can be based on the Transmission Control Protocol / Internet Protocol (TCP / IP) network communication specification, although other types or combinations of networking implementations are also possible. Similarly, other network topologies and arrangements are also possible.

[0062] One or more of the external device 106 or remote device 108 can output the detected physiological events to a system user, such as a patient or clinician, or to a process comprising, for example, an instance of a computer program executable in a microprocessor. In an example, the process can include automatically generating a recommendation for anti-arrhythmic therapy, or a recommendation for further diagnostic testing or treatment. In an example, the external device 106 or remote device 108 can include a corresponding display unit for displaying physiological or functional signals, or an alarm, alert, emergency call, or other form of warning to signal the detection of an arrhythmia. In some examples, the external system 105 can include an external data processor configured to analyze physiological or functional signals received by one or more ambulatory medical devices and confirm or reject the detection of an arrhythmia. Computationally intensive algorithms, such as machine learning algorithms, can be implemented in the external data processor to retrospectively process data to detect arrhythmias.

[0063] Portions of one or more mobile medical devices or external systems 105 may be implemented using hardware, software, firmware, or a combination thereof. Portions of one or more mobile medical devices or external systems 105 may be implemented using dedicated circuitry that may be constructed or configured to perform one or more functions, or may be implemented using general-purpose circuitry that may be programmed or otherwise configured to perform one or more functions. Such general-purpose circuitry may include a microprocessor or portion thereof, a microcontroller or portion thereof, or programmable logic circuitry, memory circuitry, a network interface, and various components for interconnecting these components. For example, a "comparator" may include, among other things, an electronic circuit comparator that may be constructed to perform a specific function of comparing two signals, or the comparator may be implemented as part of a general-purpose circuit that may be driven by code that instructs a portion of the general-purpose circuit to perform a comparison between two signals. A "sensor" may include an electronic circuit configured to receive information and provide an electronic output representative of such received information.

[0064] The therapeutic device 110 can be configured to send information to or receive information from one or more of the ambulatory medical device or the external system 105 using the communication link 111. In an example, one or more of the ambulatory medical devices, the external device 106, or the remote device 108 can be configured to control one or more parameters of the therapeutic device 110. The external system 105 can allow programming of one or more ambulatory medical devices and can receive information about one or more signals acquired by one or more ambulatory medical devices, such as information that can be received via the communication link 111. The external system 105 can include a local external implantable medical device programmer. The external system 105 can include a remote patient management system that can monitor the patient's status or adjust one or more therapies, such as from a remote location.

[0065] Figure 2 is a schematic diagram illustrating an embodiment of a cardiac disease management system 200 and a portion of an environment in which the system 200 may operate. The cardiac disease management system 200 may perform a range of activities including remote patient monitoring, diagnosis of disease conditions, and provision of therapy to treat the disease condition and improve patient outcomes. In one example, therapy may include conduction system pacing (CSP), such as His bundle pacing (HBP), septal pacing (such as left bundle branch pacing (LBBP) or right bundle branch pacing (RBBP), or pacing at other portions of the His-Purkinje conduction system. One or more of these activities may be performed near the patient (e.g., at the patient's home or office), by a centralized server (e.g., in a hospital, clinic, or doctor's office), or by a remote workstation (e.g., a secure mobile computing device).

[0066] The cardiac management system 200 may be coupled to a patient's heart 202. The cardiac management system 200 includes an ambulatory medical device (AMD), which may be an implantable device implanted subcutaneously in the patient's chest, abdomen, or other part of the body, a subcutaneous monitor or diagnostic device, or a wearable medical device, such as a patch-based device or smart wearable device or accessory. Figure 2 In the example shown, the AMD may be an implantable medical device, such as Figure 1 IMD 102 is shown.

[0067] The cardiac management system 200 may include a lead system electrically coupled to the IMD 102. The lead system may include one or more leads or catheters that are placed intravenously, percutaneously, or minimally invasively. Each lead or catheter may include one or more electrodes. The arrangement and use of the lead system and associated electrodes may be determined by the patient's needs and capabilities of the IMD 102. The associated electrodes on the lead system may be positioned on the patient's chest or abdomen to sense physiological signals indicative of cardiac activity or physiological responses to stimulation of target tissue. The lead system may be surgically inserted into the heart 202 or positioned on the surface of the heart 202. The electrodes associated with the lead system may be positioned at a target site in the right atrium (RA), right ventricle (RV), left atrium (LA), left ventricle (LV), or other body parts. Stimulation energy may be delivered to the target site via one or more of these electrodes. Some electrodes may be used to sense cardiac activity, such as intrinsic or induced cardiac electrical activity.

[0068] In the example shown, the lead system can include a lead 206 having a proximal end 208 configured to connect to the IMD 102 and a distal end 210 including one or more electrodes configured to deliver stimulation energy (such as in the form of pacing pulses) to the His bundle 221. Figure 2Two electrodes, including a tip electrode 212A and a ring electrode 212B, are shown by way of example and not limitation. Additional electrodes may be included in lead 206 for sensing electrical activity or for delivering stimulation energy, such as an atrial lead 211. Lead 206 may be positioned so that one or more electrodes, such as electrodes 212A-212B, are positioned near or in the His bundle 221, an area distal to the blocked or slow-conducting AV node, the ventricular septum, or the right atrial region near the His bundle 221. Alternatively, one or more of electrodes 212A-212B, or other electrodes on lead 206, may be positioned at the ventricular septum 225 to provide septal pacing, which may include one or more of left bundle branch (LBB) pacing or right bundle branch (RBB) pacing. As part of the natural electrical conduction system of heart 202, the His bundle 221 transmits electrical impulses from the AV node 220 via the left and right bundle branches 222 and 223 within the ventricular septum 225 to the apex of the bundle branches. The left bundle branch 222 and the right bundle branch 223 lead to Purkinje fibers 224, which provide electrical conduction to the ventricles, resulting in ventricular contraction. In some examples, lead 206 can be positioned so that one or more electrodes associated with lead 206 (such as electrodes 212A-212B) are positioned at or near other parts of the natural cardiac conduction system, such as one of the bundle branches 222 or 223, Purkinje fibers 224, or other conductive tissue - in addition to or in place of the area at or near the His bundle 221. In some examples, the distal tip of lead 206 can be inserted into the His bundle or septal region (proximate to a portion of the LBBB or a portion of the RBBB therein) at a desired depth so that one or more of electrodes 212A-212B are closer to the cardiac conductive tissue of the His-Purkinje system, thereby improving the success rate of capturing the cardiac conductive tissue via electrical stimulation.

[0069] In some examples, one or more leads other than lead 206 can additionally or alternatively be used to provide CSP (e.g., HBP, septal pacing such as LBBP or RBBP, etc.) via one or more electrodes associated therewith. Such leads can include transvenous, subcutaneous, endocardial, epicardial, or non-invasive leads. For example, ventricular lead 207 can include an electrode configured to be positioned at the septum 225, or alternatively inserted into a septal region at a desired depth to provide septal pacing therein, such as LBBP or RBBP. Ventricular lead 207 can further include one or more electrodes, such as distal electrode 231 and proximal electrode 232, for cardiac sensing and / or ventricular pacing.

[0070] In one example, lead 206 can be a single-pass lead having multiple electrodes for stimulating multiple cardiac locations, including electrodes disposed at or near the His bundle (e.g., electrodes 212A-212B) and electrodes disposed in one or more of the RA, RV, LA, or LV of heart 202. In some examples, in addition to lead 206, the lead system can also include separate leads for placement in different cardiac chambers or locations, such as an RA lead having one or more RA electrodes to stimulate a portion of the RA or sense RA electrical activity, an RV lead having one or more RV electrodes to stimulate a portion of the RV or sense RV electrical activity, or an LV lead having one or more LV electrodes to stimulate a portion of the LV or sense LV activity. In some examples, cardiac management system 200 can include one or more leadless stimulators / sensors that are not tethered to the leads and that communicate wirelessly with IMD 102. The leadless stimulators / sensors can deliver electrical stimulation, sense physiological signals such as cardiac electrical signals in response to cardiac stimulation, and transmit the sensed data to IMD 102.

[0071] The IMD 102 may include a sealed housing 216 that houses one or more of an electrical stimulation circuit, a sensing circuit, a control circuit, a communication circuit, and a battery, among other components. In one example, the IMD 102 includes a bundle branch block (BBB) ​​detector circuit 218 that is configured to detect BBB using physiological signals sensed from the patient via one or more electrodes associated with the lead system or via physiological sensors. Examples of physiological signals may include an electrocardiogram (ECG), an intracardiac electrogram (EGM) (such as an atrial EGM, a ventricular EGM, or a His bundle EGM), a heart rate or pulse rate signal, a thoracic impedance signal, a cardiac impedance signal, an arterial pressure signal, a pulmonary artery pressure signal, a left atrial pressure signal, a RV pressure signal, a LV coronary pressure signal, a coronary blood temperature signal, a blood oxygen saturation signal, a cardiac acceleration signal, a heart sound signal, an intracardiac acceleration signal, a respiratory signal, or a physical activity or exertion level signal, a cardiac timing signal, and the like.

[0072] In one example, the IMD 102 may include or be coupled to a heart sound sensor to sense heart sound information. The heart sound information may include intrinsic heart sounds of the patient (e.g., in the absence of cardiac stimulation), or heart sounds sensed in response to cardiac stimulation (e.g., CSPs at or near locations in the cardiac conduction system, such as His bundle pacing, or septal pacing (such as left bundle branch pacing or right bundle branch pacing)). The BBB detector circuit 218 may detect the BBB based at least in part on a heart sound metric generated from the heart sound information. Detection of the BBB includes distinguishing between LBBB and RBBB. Figure 3 An example of BBB detection based on heart sounds and differentiation between LBBB and RBBB is described.

[0073] IMD 102 can include a pacing circuit 219 configured to provide cardiac pacing to restore cardiac synchronization or improve cardiac performance. In one example, cardiac pacing pulses can be delivered to a right ventricular location, such as the RV apex, via RV lead 207 and associated electrodes (such as distal electrode 231 and / or proximal electrode 232). In one example, cardiac pacing pulses can be delivered to a location at or near the patient's cardiac conduction system, such as the His bundle 221, bundle branches 222 or 223, Purkinje fibers 224, or other conductive tissue of the cardiac conduction system, via lead 206 and associated electrodes 212A or 212B. The pacing circuit 219 can be programmed to deliver unipolar His bundle pacing, where the pacing pulse can be applied between one of electrodes 212A-212B (e.g., as a cathode) and housing 216 (e.g., as an anode). Alternatively, the pacing circuit 219 can be programmed to deliver bipolar His bundle pacing, where pacing pulses can be applied between two electrodes located at or near the His bundle, such as between electrodes 212A and 212B. In some examples, electrodes for unipolar or multipolar (e.g., bipolar or quadripolar) His bundle pacing can be selected by the system user from multiple candidate electrodes from a given lead or multiple individual leads comprising the pacing system and programmed into the pacing circuit 219. In some examples, cardiac pacing pulses can be provided by a leadless device, such as a leadless cardiac pacemaker (LCP). One or more electrodes can be distributed over the body of the LCP and in contact with the His bundle region to deliver pacing pulses thereto.

[0074] The pacing circuit 219 can be coupled to the bundle branch block (BBB) ​​detector circuit 218, identify an appropriate pacing location, and determine or adjust values ​​for one or more pacing parameters based at least on the detected BBB (e.g., LBBB or RBBB). In one example, the pacing circuit 219 can select between CSP (e.g., His bundle pacing or bundle branch pacing) and RV pacing at the right ventricle (RV) apex based on whether LBBB or RBBB is detected. In one example, the pacing circuit 219 can determine an optimal or desired pacing location at or near the His-Purkinje system. The desired pacing location can include a desired pacing site and / or a desired depth of insertion of a pacing lead into the His bundle or septal region of the heart. In some examples, the pacing circuit 219 can determine a desired pacing dose or timing parameter value. The desired pacing dose or timing parameter value can be determined using heart sound information sensed in response to electrical stimulation delivered at the desired pacing location. In some examples, pacing circuitry 219 may provide ventricular backup pacing if the CSP does not capture conducting tissue at the pacing site and fails to adequately activate the ventricles and restore cardiac synchronization.

[0075] IMD 102 can communicate with external system 105 via communication link 111. Figure 1 As described, external system 105 may include a dedicated hardware / software system, such as a programmer, a remote server-based patient management system, or alternatively, a system defined primarily by software running on a standard personal computer. External system 105 may include a proximal external device near IMD 102, such as a programmer device. A clinician may manage patient 101 through IMD 102 via communication link 111, including, among other operations, initiating or adjusting pacing therapy, such as CSP. Additionally, external system 105 may receive device data from IMD 102 via communication link 111. Examples of device data may include: real-time or stored physiological signals collected from patient 101, physiological responses to therapy delivered to patient 101, or device operating status of IMD 102 (e.g., battery status and lead impedance).

[0076] The external system 105 can monitor the patient's condition and the functionality of the IMD 102. In various embodiments, the external system 105 can include a user interface for displaying received information to the user and receiving user input to control the operation of the IMD 102. In one example, the external system 105 can be configured to verify pacing capture status and perform pacing threshold testing to determine the HBP threshold. Capture verification and threshold testing can be performed periodically or triggered by specific events (such as user commands). The user can use the external system 105 to program the IMD 102, such as configuring a pacing vector (e.g., specifying anode and cathode electrodes) to deliver HBP, or configuring a sensing vector to sense physiological signals.

[0077] In such Figure 2 In the example shown, pacing circuit 219 is entirely within IMD 102. In some examples, a portion or all of pacing circuit 219 may be included in another device separate from IMD 102, such as an external device. Examples of such external devices may include IMD 103, a portable pacing system analyzer (PSA) device, a programmer device for programming IMD 102, and other electrical stimulator devices. The external device may be coupled to one or more leads, such as lead 206 or lead 207, to provide electrical stimulation at one or more candidate pacing locations at or near the cardiac conduction system, respectively. The external device may receive heart sound information sensed from the patient in response to the electrical stimulation at the respective candidate locations and determine a desired pacing location based at least on the heart sound information.

[0078] Figure 3An example of a phono-based cardiac monitor and pacing system 300 for monitoring cardiac conditions and providing cardiac pacing to a patient is generally shown. The system 300 can detect blockages in the patient's cardiac conduction system, such as the BBB (including the LBBB and the RBBB). Based on the detected blockages, the system 300 can initiate or adjust pacing therapy, such as RV apex pacing or CSP. In some examples, the system 300 can determine optimal or desired pacing locations and / or pacing parameter values ​​to more effectively capture cardiac conduction tissue, restore synchronization, and improve the patient's cardiac performance.

[0079] Heart sound-based cardiac monitor and pacing system 300 may include one or more of a data receiver circuit 310, a controller circuit 320, a user interface 330, and a therapy circuit 340. At least a portion of system 300 may be implemented in IMD 102, WMD 103, or an external system 105, such as one or more of external device 106 or remote device 108.

[0080] Data receiver circuit 310 can receive physiological information from a patient. In one example, data receiver circuit 310 can include a sense amplifier circuit configured to sense physiological signals from the patient via a physiological sensor, such as an implantable, wearable, or otherwise ambulatory sensor or electrode associated with the patient. The sensor can be incorporated into or associated with an ambulatory device, such as IMD 102 or WMD 103. In some examples, the physiological signals sensed from the patient can be stored in a storage device, such as an electronic medical record (EMR) system. Data receiver circuit 310 can receive the physiological signals from the storage device, such as in response to a user command or a trigger event.

[0081] By way of example and not limitation, and as Figure 3As shown, the data receiver circuit 310 can receive heart sound information 312, cardiac electrical information 314, and respiratory information 316. The heart sound information 312 that can be sensed using a heart sound sensor from the patient includes one or more of S1, S2, S3, or S4 heart sound components. In one example, the heart sound information 312 may include body motion / vibration signals indicative of heart vibrations that are associated with or indicative of heart sounds. In one example, at least one heart sound sensor may be included in a heart sound-based cardiac monitor and pacing system 300. Examples of heart sound sensors may include accelerometers, acoustic sensors, microphones, piezoelectric-based sensors, or other vibration or acoustic sensors. The accelerometer may be a single-axis, dual-axis, or three-axis accelerometer. Examples of accelerometers may include flexible piezoelectric crystal (e.g., quartz) accelerometers or capacitive accelerometers manufactured using microelectromechanical systems (MEMS) technology. A heart sound sensor can be included in IMD 102 or WMD 103, or provided on a lead, such as part of a lead system associated with IMD 102 or WMD 103. In one example, an accelerometer (or other sensor) can sense epicardial or endocardial acceleration (EA) signals from a portion of the heart, such as on the endocardial or epicardial surface of one of the left ventricle, right ventricle, left atrium, or right atrium. The EA signal can include components corresponding to various heart sound components, such as one or more of the S1, S2, S3, or S4 components.

[0082] Cardiac electrical information 314 may include, for example, a surface electrocardiogram (ECG) sensed from electrodes placed on the surface of the body, a subcutaneous ECG sensed from electrodes placed under the skin, or an intracardiac electrogram (EGM) sensed from one or more implantable electrodes. Cardiac electrical information 314 may be sensed via electrodes included in or communicatively coupled to IMD 102 or WMD 103. Cardiac electrical information 314 may also include heart rate, heart rate variability, cardiac timing parameters, etc., which may be measured or determined from cardiac electrical information 314.

[0083] Respiration information 316 can be sensed using a respiratory sensor including one of an accelerometer, a microphone, an impedance sensor, or a flow sensor. Respiration information 316 can include one or more respiratory parameters. In one example, respiration information 316 can include one or more respiratory phases within a respiratory cycle, including, for example, an inhalation phase and an exhalation phase.

[0084] Heart sound information 312, cardiac electrical information 314, and respiratory information 316 can be collected from the same patient at substantially the same time. In one example, heart sound information 312, cardiac electrical information 314, and respiratory information 316 can include heart sound signals, cardiac electrical signals, and respiratory signals, respectively, that are time-aligned with one another. This allows for accurate and reliable cross-signal measurements that can be used for BBB detection and pacing optimization, such as the Q-S1 interval between a Q wave on an ECG and an S1 heart sound on a heart sound signal within the same cardiac cycle, or a respiratory-synchronized S1 heart sound corresponding to the inspiratory phase of a respiratory signal, as described further below.

[0085] The receiver circuit 310 can receive other physiological or functional information of the patient, including, for example, body activity signals, posture signals, chest or cardiac impedance signals, arterial pressure signals, pulmonary artery pressure signals, left atrial pressure signals, RV pressure signals, LV coronary artery pressure signals, coronary blood temperature signals, blood oxygen saturation signals, heart sound signals, physiological responses to activity, apnea-hypopnea index, one or more respiratory signals (such as respiratory rate signals or tidal volume signals), brain natriuretic peptide (BNP), blood count, sodium and potassium levels, glucose levels and other biomarkers and biochemical markers.

[0086] The controller circuit 320 can detect blockages in the patient's cardiac conduction system (such as LBBB or RBBB), optimize pacing therapy, and assess the patient's cardiac or pulmonary risk based on the detected blockages. The controller circuit 320 can be implemented as part of a microprocessor circuit, which can be a dedicated processor such as a digital signal processor, an application-specific integrated circuit (ASIC), a microprocessor, or other type of processor for processing information including body activity information. Alternatively, the microprocessor circuit can be a general-purpose processor that can receive and execute a set of instructions to perform the functions, methods, or techniques described herein.

[0087] Controller circuit 320 may include a circuit set that includes one or more other circuits or subcircuits, such as a heart sound analyzer circuit 322, a bundle branch block (BBB) ​​detector 326, a pacing optimization circuit 328, and a risk assessment circuit 329. These circuits may perform the functions, methods, or techniques described herein, either individually or in combination. In an example, the hardware of the circuit set may be invariably designed to perform a specific operation (e.g., hardwired). In an example, the hardware of the circuit set may include variably connected physical components (e.g., execution units, transistors, simple circuits, etc.) that include a physically modified computer-readable medium (e.g., magnetically, electrically, removably placed invariant aggregate particles, etc.) to encode instructions for a specific operation. When the physical components are connected, the underlying electrical properties of the hardware components change, for example, from an insulator to a conductor or vice versa. The instructions enable embedded hardware (e.g., an execution unit or a loading mechanism) to create components of the circuit set in hardware via the variably connected components to perform a portion of the specific operation when in operation. Thus, when the device is operating, the computer-readable medium is communicatively coupled to the other components of the circuit set. In an example, any physical component can be used in more than one component of more than one circuit set. For example, during operation, an execution unit can be used in a first circuit of a first circuit set at one point in time and reused by a second circuit in the first circuit set, or reused by a third circuit in the second circuit set at a different time.

[0088] The heart sound analyzer circuit 322 can pre-process the heart sound information 312, such as by using a filter or filter bank to remove or attenuate one or more of low frequency signal baseline wander, high frequency noise, or other unwanted frequency components. In one example, the heart sound segment can be bandpass filtered to a frequency range of approximately 5-90 Hz or approximately 9-90 Hz. In one example, the filter can include a double-order or higher-order differentiator configured to calculate a double-order or higher-order differential of the heart sound signal. The heart sound analyzer circuit 322 can detect one or more heart sound components (e.g., S1, S2, S3, or S4) from the pre-processed heart sound signal. The heart sound components can be identified based on heart sound signal amplitude, power, timing, morphology, spectrum, statistical analysis, or signal complexity analysis (e.g., signal entropy). In some examples, the heart sound analyzer circuit 322 can further use cardiac electrical information 314 (such as the timing of the QRS complex or R wave within the cardiac cycle, heart rate, heart rate variability, etc.) to detect the heart sound components.

[0089] Heart sound analyzer circuit 322 can generate heart sound metrics based on received heart sound information 312. Heart sound information 312 can include the patient's intrinsic heart sounds (i.e., in the absence of cardiac stimulation). This heart sound information is referred to as baseline heart sound information. Cardiac electrical information 314 and respiratory information 316 can similarly include baseline cardiac electrical information and baseline respiratory information, respectively, collected when no cardiac stimulation is delivered to the heart. In some examples, heart sound information 312 can be sensed in response to cardiac stimulation (optionally along with other information received by data receiver circuit 310). This heart sound information is referred to as paced heart sound information. Paced heart sound information can be acquired during CSP at one or more His bundle locations or septal locations proximal to the left or right bundle branches, as well as other locations in the His-Purkinje system. Pacing pulses can be generated by electrical stimulator 342, which can be part of therapy circuit 340. In one example, motor 342 can be included in IMD 102 or WMD 103. In another example, motor 342 can be an external device separate from IMD 102 or WMD 103, such as within external device 106 (e.g., a programmer for programming IMD 102 or WMD 103) or a portable pacing system analyzer (PSA) device. Electrical stimulator 342 can be electrically coupled to at least one electrode that can be positioned at two or more candidate locations for delivering electrical stimulation therein. At least one electrode can be associated with a lead, such as electrodes 212A and 212B associated with lead 206, as shown. Figure 2 As shown. The lead has a proximal end coupled to the electrical stimulator 342 and a distal tip configured to be inserted into the His bundle site or septal site (e.g., the LBBP site or the RBBP site). The distal tip can be inserted into the His bundle or septal region at an adjustable depth. Pacemaker heart sound information can be acquired immediately during electrical stimulation or within a specific time period after electrical stimulation to account for delayed heart sound response after electrical stimulation is stopped.

[0090] The heart sound analyzer circuit 322 can generate one or more heart sound metrics, including, for example, a split S1 indicator 323, a Q-S1 interval 324, or an S1 intensity 325. Heart sound metrics generated from baseline heart sound information are referred to as baseline heart sound metrics. Heart sound metrics generated based on paced heart sound information are referred to as paced heart sound metrics. The split S1 indicator 323 can indicate a change in the temporal pattern of S1, such as an elongation of S1 associated with a split S1 sound, which typically occurs when the mitral valve closes significantly before the tricuspid valve, allowing each valve to emit separate sounds or vibrations, including a mitral valve closure component M1 and a tricuspid valve closure component T1, which can be detected by the heart sound sensor. In one example, the heart sound analyzer circuit 322 can detect such a temporal elongation of S1 associated with a split S1 sound based on the morphology of the S1 sound signal. For example, a split S1 sound is detected if more than one main peak is detected from the heart sound signal in the S1 detection window. The S1 window may start at a predetermined offset from the QRS complex or R wave of the ECG and have a predetermined window size (duration). In another example, the heart sound analyzer circuit 322 may detect the elongation of S1 associated with a split S1 sound based on the width of the signal envelope of the S1 sound. The signal envelope represents the S1 sound signal power or energy over time. If the width of the S1 signal envelope within the S1 detection window (e.g., measured at 75% of the S1 energy peak) exceeds a specific signal width threshold, a split S1 sound is detected. In yet another example, the heart sound analyzer circuit 322 may use a complexity measure of the S1 sound (such as the spectral entropy of the S1 sound signal) to detect the elongation of S1 associated with a split S1 sound. Spectral entropy quantifies the complexity (or non-uniformity) of the power spectrum amplitude of the signal. A high spectral entropy indicates a more evenly distributed signal energy over a wide frequency range in the frequency domain, while a low spectral entropy indicates a less even distribution of signal energy. A split S1 sound may be detected if the spectral entropy of the S1 sound signal exceeds a spectral entropy threshold. In some examples, the cardiac sound analyzer circuit 322 can detect the presence or absence of split S1 sounds in each cardiac cycle within a specific monitoring time period or a specific number of cardiac cycles, and calculate the incidence of split S1 sounds, which represents the number of split S1 sounds detected during the monitoring period. In some examples, the cardiac sound analyzer circuit 322 can use a probabilistic model (such as a Gaussian mixture model) to detect the elongation of S1 associated with the split S1 sounds. Assuming that the data for the S1 sounds is generated by a mixture of two or more Gaussian distributions, the parameters of these Gaussian distributions can be learned using a training set of S1 sound data sets that contains samples from the available M1 and T1 components. The trained Gaussian mixture model can then be used to identify or estimate the separate M1 and T1 components from the test S1 sound data.

[0091] Although a split S1 tone is normal in many patients, it is rare in heart failure patients with LBBB. When electrical stimulation is delivered to appropriate locations at or near the cardiac conduction system in heart failure patients with LBBB, cardiac synchronization can be restored and a split S1 tone pattern can be promoted. Figures 4A-4C , these figures conceptually illustrate the pattern of a split S1 sound in a normal heart (with an intact cardiac conduction system) and in a heart with LBBB or RBBB. S1 typically includes a mitral valve closure component, M1, and a tricuspid valve closure component, T1. In a normal heart, the mitral and tricuspid valves typically close almost simultaneously, producing a single S1 sound. A slight S1 split 410 can also be seen, where the M1 sound occurs slightly earlier than the T1, as shown in FIG. Figure 4A In RBBB, the electrical impulse reaches the left ventricle before the right ventricle, causing the left ventricle to be stimulated and contract significantly earlier than the right ventricle, causing each valve to emit a separate sound. This appears as a wide split S1 sound 420 in the heart sound signal, as shown in Figure 4. Figure 4B As shown in Figure 4. In LBBB, the opposite effect on the S1 sound may occur due to the interruption or obstruction of the left bundle branch. The electrical impulse reaches the right ventricle before the left ventricle, causing the tricuspid valve to close earlier than the mitral valve, resulting in a complete overlap of the M1 and T1 sounds. This is manifested in the heart sound signal as an absence of a distinct split S1 sound 430, as shown in Figure 4. Figure 4C As discussed further below, based on the characteristics of the split S1 tone, the BBB detector 326 can detect BBB, including distinguishing between LBBB and RBBB.

[0092] Return Reference Figure 3, the Q-S1 interval 324 represents the latency period between the onset of the QRS and the S1 heart sound, also known as the pre-ejection period (PEP). The heart sound analyzer circuit 322 can determine the Q-S1 interval using the heart sound information 312 and the cardiac electrical information 314 that is collected substantially simultaneously with the heart sound information 312 and time-aligned with the heart sound information 312. Cardiac asynchrony, such as that caused by LBBB, can cause the Q-S1 interval to be prolonged. Electrical stimulation at appropriate locations at or near the cardiac conduction system can restore cardiac synchrony and enhance contractility, as reflected by a shortening of the Q-S1 interval. In addition to the Q-S1 interval, the heart sound analyzer circuit 322 can also determine other cardiac timing intervals that can be used to detect BBB, optimize pacing therapy, or assess cardiac or pulmonary risk. Examples of such cardiac timing periods may include a systolic timing period (STI) representing the time interval from the start of the QRS complex on the ECG to the S2 heart sound, a left ventricular ejection time (LVET) representing the time interval between the S1 and S2 heart sounds, or a diastolic timing period (DTI) representing the time interval between the S2 heart sound and the start of the subsequent QRS complex on the ECG, etc. These cardiac timing periods based on heart sounds may be related to the contractility or diastolic function of the heart. Heart sound metrics may also include composite metrics such as a PEP / LVET ratio, an STI / DTI ratio, an STI / cycle length (CL) ratio, or a DTI / CL ratio, etc.

[0093] S1 intensity 325 (e.g., signal amplitude or power) is associated with the vibrations generated by the heart during the closure of the atrioventricular (mitral and tricuspid) valves, when ventricular pressure exceeds atrial pressure at the beginning of systole. Cardiac asynchrony, such as due to left bundle branch block (LBBB), can cause a decrease in S1 intensity. Electrical stimulation at appropriate locations in or near the cardiac conduction system can restore cardiac synchrony and enhance contractility, as reflected by an increase in S1 intensity.

[0094] Certain respiratory activities can emphasize characteristic heart sound metrics. In some examples, the heart sound analyzer circuit 322 can determine one or more heart sound metrics, such as a split S1 indicator 323, a Q-S1 interval 324, or an S1 intensity 325, by using heart sound information corresponding to a particular respiratory phase, which can be obtained from respiratory information 316 that is collected substantially simultaneously with and time-aligned with the heart sound information 312. For example, the split S1 indicator 323 can be determined using an S1 sound corresponding to the inspiratory phase of the respiratory cycle. Inspiration delays the closure of the tricuspid valve due to increased venous return from the right ventricle of the heart, thereby enhancing the splitting of the S1 sound and improving the sensitivity of BBB detection.

[0095] The BBB detector 326 can detect the BBB based at least in part on the heart sound metric generated by the heart sound analyzer circuit 322. Detection of the BBB includes distinguishing between LBBB and RBBB. In one example, the BBB detector 326 can detect the BBB based on the split S1 indicator 323. As described above with reference to Figures 4A-4C As discussed, a split S1 sound is often prominent in RBBB but may be absent or less likely to be detected in LBBB. To distinguish LBBB from RBBB, in one example, the BBB detector 326 can detect LBBB in response to the absence of a split S1 sound or when the incidence of the split S1 sound is below a ratio threshold. The BBB detector 326 can detect RBBB in response to the presence of a split S1 sound or when the incidence of the split S1 sound is above a ratio threshold. The incidence can be determined over a specific monitoring time period or a specific number of cardiac cycles. The ratio threshold for the incidence of the split S1 sound can be determined using normal heart sounds of a subject with an intact conduction system.

[0096] In addition to or as an alternative to the split S1 indicator 323, the BBB detector 326 can use one or more other heart sound metrics to detect BBB, such as the Q-S1 interval 324 or the S1 intensity 325. In one example, the BBB detector 326 can detect LBBB when the S1 intensity 325 falls below a first threshold or falls within a first range of values, and can detect RBBB when the S1 intensity 325 falls below a second threshold different from the first threshold or falls within a second range of values ​​different from the first range of values. In another example, the BBB detector 326 can detect LBBB when the Q-S1 interval 324 exceeds a first threshold or falls within a first range of values, and can detect RBBB when the Q-S1 interval 324 exceeds a second threshold different from the first threshold or falls within a second range of values ​​different from the first range of values. In one example, the BBB detector 326 can detect BBB based on the variability of the Q-S1 interval measured over a specific monitoring period or over multiple heartbeats. Due to the more prominent and wider split S1 tone in RBBB, S1 timing (e.g., the timing of the S1 peak) can be more variable from beat to beat in RBBB. In contrast, in LBBB, the absence or low incidence of the split S1 tone can result in a narrower S1 peak and more consistent S1 timing, and thus lower beat-to-beat variability in Q-S1 timing. The BBB detector 326 can detect RBBB when the variability of the Q-S1 interval exceeds a variability threshold, and the BBB detector 326 can detect LBBB when the variability of the Q-S1 interval is below a variability threshold. In some examples, a primary BBB detection can be made using the split S1 indicator 323, and the primary BBB detection can be confirmed using a secondary BBB detection based on one or more of the Q-S1 interval 324 or the S1 intensity 325. In some examples, BBB detection (including differentiation between LBBB and RBBB) can be performed using a weighted combination or logical combination of two or more BBB detections based on split S1 indicator 323 , Q-S1 interval 324 , or S1 intensity 325 , respectively.

[0097] The pacing optimization circuit 328 can determine optimal or desired pacing locations and / or pacing parameter values ​​based on the detection of the BBB, as provided by the BBB detector 326. In one example, based on the distinction between LBBB and RBBB, the pacing optimization circuit 328 can determine a pacing mode, such as a selection between CSP and RV pacing. In one example, when LBBB is detected, CSP can be selected to stimulate the His bundle or septal region of the heart, such as via a pacing signal connected to a lead 206 (e.g., Figure 2When RBBB is detected, RV pacing may be selected to stimulate the RV apex of the heart, such as via a lead 207 (e.g., Figure 2 Alternatively, no cardiac stimulation is delivered in the presence of an RBBB and in the absence of an LBBB to promote conduction of intrinsic impulses through the cardiac conduction system to the ventricles. In various examples, the pacing optimization circuit 328 can dynamically switch the pacing mode between CSP and RV pacing depending on whether an LBBB or RBBB is detected.

[0098] The pacing optimization circuit 328 can additionally or alternatively optimize lead or electrode placement for pacing therapy (e.g., CSP), such as during a lead implant procedure. The pacing optimization circuit 328 can determine an optimal or desired pacing location at or near the cardiac conduction system based on the distinction between LBBB and RBBB, optionally in conjunction with one or more heart sound metrics (such as a split S1 indicator 323, a Q-S1 interval 324, or an S1 intensity 325). In response to detecting LBBB, CSP (e.g., His bundle pacing or LBB pacing at the septum) can be delivered to a predetermined location in the His bundle or septal region, such as by using an electrical stimulator 342 of the therapy circuit 340. The electrical stimulator 342 can be electrically coupled to one or more electrodes that can be positioned at the His bundle or in the septal region proximal to the left bundle branch. The electrodes can be coupled to a lead (e.g., such as Figure 2, a lead 207 shown, having a distal tip configured to be inserted into the bundle of His or septal region of the heart at an adjustable insertion depth to deliver a CSP therein. A data receiver circuit 310 can receive paced heart sound information from the patient in response to the CSP. A heart sound analyzer circuit 322 can use the paced heart sound information to detect one or more paced heart sound metrics, including an elongation of S1 associated with a split S1 sound. In order to determine an optimal or desired pacing position (which can include an optimal or desired pacing site and an optimal or desired depth of insertion of the lead tip into the bundle of His or septal region), a pacing optimization circuit 328 can determine whether to adjust the pacing site or the insertion depth of the distal tip of the lead based at least on an indicator of the split S1 sound. As described above, a split S1 sound pattern is typically not present and is unlikely to be detected in LBBB. If the CSP delivered from the current pacing location does not produce a detectable split S1 tone pattern, or if the incidence of split S1 tones is below a ratio threshold (where the ratio threshold can be a baseline incidence of split S1 tones without CSP delivery), then LBBB is considered to continue to be in effect and the CSP at the current location and lead tip insertion depth is unable to correct the cardiac dyssynchrony due to LBBB. The pacing optimization circuitry 328 can generate an alert or recommendation to the user to adjust the pacing site or insertion depth, such as via the user interface 330. The recommended adjustment can include increasing the insertion depth to improve capture of the cardiac conduction system. If the CSP delivered from the current pacing location produces a detectable split S1 tone pattern, or if the incidence of split S1 tones increases above a ratio threshold, then the CSP at the current location and lead tip insertion depth is considered to correct the cardiac dyssynchrony due to LBBB. The pacing optimization circuitry 328 can recommend not adjusting the pacing site or insertion depth and indicate to the user that the current insertion depth is acceptable for subsequent pacing therapy. In some examples, heart sound metrics such as a split S1 sound can be displayed on user interface 330 in substantially real time as the pacing position is adjusted (e.g., when the distal tip of the lead is positioned at different insertion depths) to provide continuous and real-time feedback to the user.

[0099] The pacing optimization circuit 328 can additionally or alternatively optimize one or more pacing parameters of the pacing therapy based on the distinction between LBBB and RBBB and one or more heart sound metrics (such as the split S1 indicator 323, the Q-S1 interval 324, or the S1 intensity 325). By way of example and not limitation, the pacing therapy to be optimized can be cardiac resynchronization pacing therapy (CRT), in which the left and right ventricles of the heart are stimulated simultaneously or with a programmable interventricular delay. The pacing parameters can include, for example, pacing dose parameters (e.g., pulse amplitude, pulse width, pulse rate or frequency, etc.) or pacing timing parameters. Examples of pacing dose parameters can include pulse amplitude, pulse width, frequency, duration, total charge injected per unit time, cycle (e.g., on / off time), waveform shape, spatial location of the waveform shape, pulse shape, number of phases, phase sequence, interval time, charge balance, etc. Examples of pacing timing parameters can include pacing delay after an event sensed in another chamber or a paced event, atrioventricular delay (AVD), interventricular delay (VVD), etc. In response to detecting the LBBB, CRT can be delivered to the left and right ventricles of the heart according to initial CRT parameters (e.g., initial dose and timing), such as by using an electrical stimulator 342 of the therapy circuit 340. The electrical stimulator 342 can be electrically coupled to a right ventricular lead (e.g., lead 207) and a left ventricular lead (not shown) to provide CRT therein. The data receiver circuit 310 can receive paced heart sound information sensed from the patient in response to the CRT, and the heart sound analyzer circuit 322 can use the paced heart sound information to detect one or more paced heart sound metrics, including an elongation of S1 associated with a split S1 sound. To determine optimal or desired CRT parameter values, the pacing optimization circuit 328 can determine whether to adjust the CRT parameters based at least on the indicator of the split S1 sound. If CRT delivered according to the current parameter settings does not produce a detectable split S1 sound pattern, or if the incidence of split S1 sounds is below a ratio threshold (where the ratio threshold can be a baseline incidence of split S1 sounds without CRT being delivered), LBBB is considered to be still in effect and CRT under the current parameter settings is unable to correct cardiac dyssynchrony due to LBBB. The pacing optimization circuitry 328 can automatically adjust CRT pacing parameters, such as by reducing AVD or VVD to improve cardiac synchrony between ventricles. Alternatively, the pacing optimization circuitry 328 can generate an alert or recommendation to the user to adjust the CRT pacing parameters, such as via the user interface 330. If CRT delivered according to the current parameter settings produces a detectable split S1 sound pattern, or if the incidence of split S1 sounds increases above a ratio threshold, CRT is considered to correct cardiac dyssynchrony due to LBBB. No adjustment is made to the CRT parameters. A notification can be generated to indicate to the user that the current CRT parameter values ​​are acceptable for subsequent pacing therapy.In some examples, heart sound metrics such as a split S1 sound may be displayed on the user interface 330 in substantially real time to provide continuous and real-time feedback to the user as CRT parameters are adjusted so that CRT is being delivered.

[0100] The above techniques for optimizing CRT using heart sound metrics (such as a split S1 indicator) can be similarly applied to optimizing other cardiac pacing modalities. Traditionally, CRT involves pacing the left and right ventricles separately at a single pacing site, also known as single-site pacing (SSP). Alternatively, multi-site pacing (MSP) can be used, in which electrical stimulation can be delivered simultaneously or sequentially at two or more sites within a cardiac chamber (e.g., the left ventricle) during the cardiac cycle. For example, in LV MSP, multiple LV sites can be stimulated simultaneously or separated by one or more intra-LV time deviations (ILVDs). The pacing optimization circuitry 328 can select between SSP and MSP based on one or more heart sound metrics (such as the elongation of S1 associated with split S1 sounds). For example, if CRT does not produce a detectable split S1 pattern, or if the incidence of split S1 sounds falls below a ratio threshold, the pacing optimization circuitry 328 can generate an alert or recommend that the user switch from SSP to MSP or adjust one or more dose or timing parameters, such as ILVD. If the CRT delivered according to the current parameter settings produces a detectable pattern of split S1 sounds, or the incidence of split S1 sounds increases beyond a ratio threshold, no adjustment of the CRT parameter settings is made.

[0101] The risk assessment circuit 329 can generate a risk indicator indicating the risk of a cardiac or pulmonary event or disease progression based at least on the BBB indicator and optionally also on one or more heart sound metrics such as the split S1 indicator 323, the Q-S1 interval 324, or the S1 intensity 325. RBBB can be caused by pulmonary hypertension, and LBBB is a risk factor for coronary artery disease such as acute myocardial infarction (MI). Figures 5A-5B , these figures show examples of changes in S1 morphology and S1 intensity before and after a MI event. Figure 5A A segment of a baseline pre-MI S1 morphology 510 and a segment of a post-MI S1 morphology 520 within a cardiac cycle are shown, each collected from the same patient. S1 morphologies 510 and 520 are time-aligned relative to the corresponding R waves on the corresponding ECG signals. The baseline S1 morphology 510 has a clear pattern of split S1 sounds, represented by an M1 peak 511 and a T1 peak 512, which are well separated in time by troughs, as shown in box 530. In the post-MI S1 morphology 520, there are no discernible split S1 sounds, and only a single S1 peak 521. The S1 amplitude in the post-MI S1 morphology 520 is also lower than that in the baseline pre-MI S1 morphology 510. Figure 5BA time series of S1 intensity trended over time before and after an MI event 550 is shown. S1 intensity is calculated as the signal power (eg, RMS value) of the S1 tone. The intensity of the post-MI portion 570 of the S1 intensity is lower than the intensity of the pre-MI portion 560 of the S1 intensity.

[0102] Return Reference Figure 3 If the BBB detector 326 detects the presence of LBBB, the risk assessment circuit 329 can generate a coronary artery disease risk indicating the risk of myocardial infarction (MI) or ischemic stroke. If the BBB detector 326 detects the presence of RBBB, the risk assessment circuit 329 can generate a pulmonary hypertension risk. The cardiac or pulmonary risk can be a categorical value or a numerical value. In one example, the cardiac or pulmonary risk is proportional to the confidence level of the detected LBBB or RBBB, which can be determined based on the degree of S1 splitting (e.g., the incidence of split S1 sounds), the amount of Q-S1 interval prolongation, or the amount of S1 intensity reduction.

[0103] The user interface 330 may include an input unit and an output unit. In one example, at least a portion of the user interface 330 may be implemented in the external system 105. The input unit may receive user input for programming the data receiver circuit 310 and the controller circuit 320, such as parameters for sensing heart sound signals, detecting heart sound components, calculating heart sound metrics, etc. The input unit may include a keyboard, an on-screen keyboard, a mouse, a trackball, a touchpad, a touch screen, or other pointing or navigation device. The output unit may include a display that may be configured to display information (e.g., signals) received from the data receiver circuit 310, including heart sound information 312, heart sound metrics generated by the heart sound analyzer circuit 322, results of BBB detection, and distinction between LBBB and RBBB generated by the BBB detector. In one example, the controller circuit 320 may generate a control signal to the user interface 330 to display heart sound metrics, such as elongation of S1 associated with a split S1 sound, in substantially real time while cardiac pacing (e.g., CSP or CRT) is being delivered with adjusted pacing position and / or pacing parameters. The optimal or desired pacing position and / or pacing parameters determined by the pacing optimization circuit 328 can be displayed on the user interface 330 to guide lead placement and therapy programming during device and lead implantation. The cardiac or pulmonary risk generated by the risk assessment circuit 329 can be displayed on the user interface 330 or otherwise alerted to a user (e.g., a clinician) to help prevent cardiac or pulmonary events (e.g., to prevent acute MI, ischemic stroke, or pulmonary hypertension).

[0104] The output unit of the user interface 330 can also present recommended treatments to the user, including changes in treatment parameters provided by the implanted device, a prescription for the implanted device, the initiation or change of medication, or other treatment options for the patient. The output unit can include a printer for printing a hard copy of the information that can be displayed on the display unit. The signals and information can be presented in a table, chart, schematic, or any other type of text, tabular, or graphical presentation format. The presentation of the output information can include audio or other media formats. In an example, the output unit can generate an alarm, an alert, an emergency call, or other form of warning to signal the system user about a detected medical event.

[0105] The therapy circuit 340 can be configured to deliver therapy to the patient, such as in response to a detected physiological event. The therapy can be preventative or therapeutic in nature, such as modifying, restoring, or improving the patient's neurological, cardiac, or respiratory function. Examples of therapy can include electrical stimulation therapy delivered to the heart, neural tissue, other target tissue, cardioversion therapy, defibrillation therapy, or drug therapy including the delivery of a drug to the patient. The therapy circuit 340 can include an electrical stimulator 342 to provide cardiac pacing, such as CSP or CRT, as described above. In some examples, the therapy circuit 340 can modify an existing therapy, such as adjusting stimulation parameters or drug dosage. For example, electrical stimulation can be delivered to an optimal or desired pacing location based on an optimal or desired pacing dose or timing parameter value.

[0106] Figure 6 An example method 600 for detecting and managing blockages in a patient's cardiac conduction system, such as the BBB, is generally shown. The cardiac conduction system includes the His-Purkinje system, which includes the His bundle, left or right bundle branches, bundles or Purkinje fibers, and other conductive cardiac tissue. The method 600 can be implemented and executed in an ambulatory medical device, such as an implantable or wearable medical device, or in a remote patient management system. In one example, the method 600 can be implemented and executed in an IMD 102 or WMD 103, an external system 105, or a phono-based cardiac monitor and pacing system 300.

[0107] Method 600 begins at 610 to receive heart sound information sensed from a patient. The heart sound information includes one or more of S1, S2, S3, or S4 heart sound components. Heart sounds can be detected using a sensor associated with or included in an ambulatory or wearable device (such as IMD 102 or WMD 103). In some examples, endocardial acceleration signals sensed from inside the heart can be used to analyze the heart sounds. The heart sound information can include the patient's intrinsic heart sounds, also referred to as reference or baseline heart sound information, to distinguish it from paced heart sound information sensed in response to electrical stimulation delivered to the heart.

[0108] At 620, a heart sound metric can be generated from at least the received heart sound information, such as by using a heart sound analyzer circuit 322. The heart sound metric can be based on one or more of the heart sound components (e.g., S1, S2, S3, or S4), and optionally can also be based on other physiological information, such as cardiac electrical information. The heart sound metric can be related to the level of cardiac synchronization and indicate cardiac performance. By way of example and not limitation, the heart sound metric can include one or more of a split S1 indicator, S1 intensity, or a cardiac timing period (such as the pre-ejection period (PEP) or the Q-S1 interval). The split S1 indicator indicates the presence or absence of an elongation of S1 associated with a split S1 sound, which typically occurs when the mitral valve closes significantly ahead of the tricuspid valve to allow each valve to emit a separate sound or vibration that can be detected by the heart sound sensor. Cardiac asynchrony, such as due to LBBB, can result in a significant prolongation of the Q-S1 interval and / or a reduction in S1 intensity. Electrical stimulation at appropriate locations at or near the cardiac conduction system can restore cardiac synchrony and enhance contractility, as reflected by a shortening of the Q-S1 interval and / or an increase in S1 intensity.

[0109] Various techniques can be used to detect split S1 sounds. In one example, the elongation of S1 associated with a split S1 sound can be detected based on the signal morphology of the heart sound signal. For example, if more than one major S1 peak is detected within the S1 detection window, a split S1 is declared detected. In another example, the elongation of S1 associated with a split S1 sound can be detected based on the width of the signal envelope of the S1 sound. The signal envelope can represent the change in the power or energy of the S1 sound signal over time. If the width of the S1 signal envelope within the S1 detection window (e.g., measured at 75% of the S1 energy peak) exceeds a specific signal width threshold, a split S1 is detected. In yet another example, the elongation of S1 associated with a split S1 sound can be detected based on a complexity measure of the S1 sound, such as the spectral entropy of the S1 sound. If the spectral entropy of the S1 sound signal exceeds a specific spectral entropy threshold, a split S1 sound is detected. In some examples, based on the detection of the presence and absence of split S1 sounds, the incidence of split S1 sounds during a specific monitoring period or a specific number of cardiac cycles can be determined. In some examples, the S1 sound signal corresponding to the inspiration phase can be used to detect the S1 splitting sound. Due to the increase in right ventricular venous return, inspiration delays the closure of the tricuspid valve, thereby enhancing the splitting of the S1 sound and improving the detection sensitivity of the BBB.

[0110] At 630, bundle branch block (BBB) ​​can be detected based at least in part on the generated heart sound metric, such as by using the BBB detector 326. Detection of BBB includes distinguishing between LBBB and RBBB. In one example, LBBB is detected in response to the absence of a split S1 sound or an incidence of a split S1 sound below a threshold; and RBBB is detected in response to the presence of a split S1 sound or an incidence of a split S1 sound exceeding a threshold. The incidence can be determined over a specific monitoring period or a specific number of cardiac cycles.

[0111] In addition to or in lieu of the split S1 indicator 323, one or more other heart sound metrics, such as the Q-S1 interval or S1 intensity, can be used to detect the BBB and differentiate between LBBB and RBBB. In some examples, the detection of the BBB based on one or more of the Q-S1 interval 324 or S1 intensity 325 can be used to confirm a primary BBB detection based on the split S1 sound. In some examples, a composite BBB detection decision can be made using a weighted or logical combination of two or more BBB detection decisions made based on the split S1 indicator, the Q-S1 interval, or the S1 intensity, respectively.

[0112] At 640, information about the detected BBB (including the distinction between LBBB and RBBB) can be provided to a user (e.g., a clinician) or a process, such as an instance of a computer program executable in a microprocessor. The BBB detection results (including the distinction between LBBB and RBBB) along with other information (such as received heart sound information and heart sound metrics) can be displayed on a display screen of user interface 330.

[0113] Heart sound metrics and detection of the BBB (including differentiation between LBBB and RBBB) can be used for a variety of applications. At 652, an alert can be generated to notify the user of the detected BBB. Additionally or alternatively, at 654, heart sound metrics and detection of the BBB can be used to optimize cardiac pacing, as described below with reference to Figures 7A-7CFurther discussed. In some examples, a cardiac sound metric (e.g., a split S1 sound) is displayed substantially in real time while cardiac pacing is being delivered while adjusting the pacing position and / or pacing parameters during a cardiac pacing optimization process. The optimal or desired pacing position and / or pacing parameters can be displayed to the user to guide lead placement and therapy programming during device and lead implantation. Additionally or alternatively, at 656, a cardiac or pulmonary risk can be generated based at least on the detected BBB, such as by using the risk assessment circuit 329. For example, a coronary artery disease risk indicating the risk of myocardial infarction (MI) or ischemic stroke can be generated in response to detecting an LBBB, and a pulmonary hypertension risk can be generated in response to detecting an RBBB. The cardiac or pulmonary risk can take a categorical or numerical value proportional to the confidence level of the detected LBBB or RBBB, which can be determined based on the degree of S1 splitting (e.g., the incidence of split S1 sounds), the amount of prolongation of the Q-S1 interval, or the amount of reduction in S1 intensity. Cardiac or lung risks may be displayed on a user interface or otherwise alerted to the user.

[0114] Figures 7A-7C In general, example methods 700A-700C are shown for optimizing cardiac pacing therapy to restore cardiac synchronization using heart sound-based BBB detection. Methods 700A-700C are each an embodiment of the cardiac pacing optimization step 654 of method 600. Optimization of cardiac pacing therapy can be based on the above-referenced Figure 6 Methods 700A-700C may each be implemented in and performed by portions of the heart sound-based cardiac monitor and pacing system 300, such as the pacing optimization circuitry 328 and the therapy circuitry 340.

[0115] Figure 7AA method 700A is shown for dynamically adjusting a pacing mode based on the distinction between LBBB and RBBB, such as by selecting between cardiac conduction system pacing (CSP) and right ventricular (RV) pacing. As described above, the elongation of S1 associated with a split S1 tone can be used to distinguish between LBBB and RBBB. Detection of a split S1 tone is performed as similarly discussed above (such as step 620 of method 600). If no split S1 is detected at 710, or if the incidence of split S1 tones during a monitoring period is below a ratio threshold, LBBB detection can be determined, and CSP can be selected at 712 for delivery to the His bundle or septal region of the heart, such as His bundle pacing or LBB septal pacing. If a split S1 tone is detected at 710, or if the incidence of split S1 tones during a monitoring period exceeds a ratio threshold, RBBB detection can be determined, and RV pacing can be selected at 714 for delivery to the RV apex of the heart. Alternatively, in the presence of the RBBB and the absence of the LBBB, no cardiac stimulation is delivered to allow natural conduction of intrinsic impulses through the cardiac conduction system.

[0116] Figure 7B A method 700B is shown for optimizing lead or electrode placement for pacing therapy (such as CSP) during lead implantation in a patient. Lead or electrode placement can be optimized based on the distinction between LBBB and RBBB and one or more heart sound metrics (such as a split S1 indicator, Q-S1 interval, or S1 intensity).

[0117] At 720, a CSP (e.g., His bundle pacing or LBB septal pacing) may be delivered to a candidate location in the His bundle or septal region. The CSP may be delivered in response to detection of an LBBB using techniques as described above with respect to step 630 of method 600. The CSP may be delivered via a lead such as a Figure 2 The lead 207 is shown as one or more electrodes associated with the lead having a distal tip that is configured to be inserted into the bundle of His or septal region of the heart at an adjustable insertion depth to deliver the CSP therein.

[0118] At 722, one or more paced heart sound metrics can be generated based on the heart sound information sensed from the patient in response to the CSP, including a heart sound metric indicating the presence or absence of a split S1 sound. Detection of a split S1 sound can be performed using the techniques discussed above with respect to step 620 of method 600. If no split S1 is detected at 724, or if the incidence of split S1 sounds is below a ratio threshold over the monitoring period (wherein the ratio threshold can be a baseline incidence of split S1 sounds without the delivery of a CSP), it is considered that LBBB continues to be in effect and that the CSP at the current location and lead tip insertion depth is unable to correct the cardiac dyssynchrony caused by the LBBB. Therefore, at 726, an adjustment to the insertion depth is required. An alert or suggestion can be provided to the user to adjust the pacing site or insertion depth, such as increasing the insertion depth to improve capture of the cardiac conduction system.

[0119] If a split S1 sound is detected at 724, or the incidence of split S1 sounds increases beyond a ratio threshold, the CSP at the current position and lead tip insertion depth is deemed to correct the cardiac dyssynchrony due to LBBB. Therefore, no adjustment to the insertion depth is required at 728. A notification may be provided to the user indicating that the current insertion depth is acceptable for subsequent pacing therapy. In some examples, a heart sound metric, such as a split S1 sound, may be displayed substantially in real time while the CSP is being delivered as the pacing position is adjusted (e.g., when the distal tip of the lead is positioned at a different insertion depth) to provide continuous and real-time feedback to the user.

[0120] Figure 7C A method 700C for optimizing cardiac resynchronization pacing therapy (CRT) is shown. This can include optimizing one or more CRT parameters, such as pacing dose parameters (e.g., pulse amplitude, pulse width, pulse rate or frequency, etc.) or pacing timing parameters (e.g., AVD, VVD). In some cases, CRT can be programmed to deliver single-site pacing (SSP) to a ventricle (e.g., left ventricle) or multi-site pacing (MSP) at two or more sites in the same ventricle (e.g., left ventricle) simultaneously or separated by one or more intra-LV time offsets (ILVDs).

[0121] At 730, CRT can be delivered to the left and right ventricles of the heart according to initial CRT parameters (e.g., initial dose and timing). CRT can be delivered in response to detection of LBBB using the techniques discussed above with respect to step 630 of method 600. CRT can be delivered via a right ventricular lead and a left ventricular lead. At 732, one or more paced heart sound metrics can be generated based on heart sound information sensed from the patient in response to CRT, including a heart sound metric indicating the presence or absence of a split S1 sound. Detection of a split S1 sound can be performed using the techniques discussed above with respect to step 620 of method 600. If no split S1 sound is detected at 734, or if the incidence of split S1 sounds during the monitoring period is below a ratio threshold (where the ratio threshold can be a baseline incidence of split S1 sounds without CRT delivery), it is considered that LBBB is still in effect and that the CSP at the current position and lead tip insertion depth is unable to correct the cardiac dyssynchrony caused by the LBBB. Therefore, at 736, one or more CRT parameters are adjusted to improve cardiac synchrony between the ventricles. In one example, the adjustment of the CRT parameters may include switching to the MSP, or modifying the ILVD associated with the MSP. The CRT parameters may be adjusted automatically. Alternatively, an alert or suggestion may be provided to the user to adjust the CRT parameters.

[0122] If a split S1 sound is detected at 734, or if the incidence of split S1 sounds increases beyond a rate threshold, then the CRT with the current parameter settings is deemed to have corrected the cardiac dyssynchrony due to the LBBB. Therefore, no adjustment of the CRT parameters is required at 738. A notification may be provided to the user indicating that the current CRT parameters are acceptable for subsequent pacing therapy. In some examples, heart sound metrics such as split S1 sounds may be displayed substantially in real time to provide continuous and real-time feedback to the user as the CRT parameters are adjusted.

[0123] Figure 8 A block diagram generally illustrates an example machine 800 on which any one or more of the techniques (e.g., methods) discussed herein may be performed. Portions of this description may be applied to the computing framework of the IMD 102, WMD 103, external system 105, or various portions of the phono-based cardiac monitor and pacing system 300.

[0124] In alternative embodiments, the machine 800 may operate as a standalone device or may be connected (e.g., networked) to other machines. In a networked deployment, the machine 800 may operate in the capacity of a server machine, a client machine, or both in a server-client network environment. In an example, the machine 800 may act as a peer machine in a peer-to-peer (P2P) (or other distributed) network environment. The machine 800 may be a personal computer (PC), a tablet PC, a set-top box (STB), a personal digital assistant (PDA), a mobile phone, a network appliance, a network router, a switch or a bridge, or any machine capable of executing instructions (sequential or otherwise) specifying actions to be taken by the machine. Furthermore, while a single machine is shown, the term "machine" shall also be construed to include any collection of machines that independently or collectively execute one (or more) sets of instructions to implement any one or more of the methodologies discussed herein, such as cloud computing, software as a service (SaaS), or other computer cluster configurations.

[0125] As described herein, examples may include or be operated by logic or multiple components or mechanisms. A circuit set is a collection of circuits implemented in a tangible entity, including hardware (e.g., simple circuits, gates, logic, etc.). Circuit set components can be flexible over time and with underlying hardware variability. A circuit set includes components that can perform specified operations individually or in combination when in operation. In an example, the hardware of a circuit set can be invariably designed to perform a specific operation (e.g., hardwired). In an example, the hardware of a circuit set can include variably connected physical components (e.g., execution units, transistors, simple circuits, etc.) that include physically modified computer-readable media (e.g., magnetic, electrical, removable placement of invariant aggregated particles, etc.) to encode instructions for a specific operation. When the physical components are connected, the underlying electrical properties of the hardware components change, for example, from an insulator to a conductor or vice versa. The instructions enable embedded hardware (e.g., an execution unit or loading mechanism) to create components of the circuit set in hardware via the variable connections to perform a portion of a specific operation when in operation. Thus, when the device is in operation, the computer-readable medium is communicatively coupled to the other components of the circuit set components. In an example, any physical component can be used in more than one component of more than one circuit set. For example, during operation, an execution unit can be used in a first circuit of a first circuit set at one point in time and reused by a second circuit in the first circuit set, or reused by a third circuit in the second circuit set at a different time.

[0126] The machine (e.g., a computer system) 800 may include a hardware processor 802 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), a hardware processor core, or any combination thereof), a main memory 804, and a static memory 806, some or all of which may communicate with each other via an interconnect (e.g., a bus) 808. The machine 800 may also include a display unit 810 (e.g., a raster display, a vector display, a holographic display, etc.), an alphanumeric input device 812 (e.g., a keyboard), and a user interface (UI) navigation device 814 (e.g., a mouse). In an example, the display unit 810, the input device 812, and the UI navigation device 814 may be a touch screen display. The machine 800 may additionally include a storage device (e.g., a drive unit) 816, a signal generating device 818 (e.g., a speaker), a network interface device 820, and one or more sensors 821, such as a global positioning system (GPS) sensor, a compass, an accelerometer, or other sensors. The machine 800 may include an output controller 828, such as a serial (e.g., universal serial bus (USB), parallel, or other wired or wireless (e.g., infrared (IR), near field communication (NFC), etc.) connection, to communicate with or control one or more peripheral devices (e.g., a printer, a card reader, etc.).

[0127] The storage device 816 may include a machine-readable medium 822 on which is stored one or more sets of data structures or instructions 824 (e.g., software) embodying or used by any one or more of the techniques or functionality described herein. The instructions 824 may also reside, completely or at least partially, within the main memory 804, static storage 806, or hardware processor 802 during execution of the instructions 824 by the machine 800. In an example, one or any combination of the hardware processor 802, the main memory 804, the static storage 806, or the storage device 816 may constitute a machine-readable medium.

[0128] Although the machine-readable medium 822 is illustrated as a single medium, the term “machine-readable medium” may include a single medium or multiple media (eg, a centralized or distributed database and / or associated caches and servers) configured to store one or more instructions 824 .

[0129] The term "machine-readable medium" may include any medium that can store, encode, or carry instructions executed by the machine 800 and cause the machine 800 to perform any one or more of the techniques disclosed herein, or any medium that can store, encode, or carry data structures used by or associated with these instructions. Non-limiting examples of machine-readable media may include solid-state memory and optical and magnetic media. In an example, the aggregated machine-readable medium includes a machine-readable medium having a plurality of particles with a constant (e.g., stationary) mass. Therefore, the aggregated computer-readable medium is not a transient propagating signal. Specific examples of aggregated machine-readable media may include: non-volatile memory, such as semiconductor memory devices (e.g., electrically programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EPSOM)) and flash memory devices; magnetic disks, such as internal hard disks and removable disks; magneto-optical disks; and CD-ROM and DVD-ROM disks.

[0130] The instructions 824 may also be sent or received over a communication network 826 using a transmission medium via the network interface device 820 using any of a variety of transmission protocols (e.g., Frame Relay, Internet Protocol (IP), Transmission Control Protocol (TCP), User Datagram Protocol (UDP), Hypertext Transfer Protocol (HTTP), etc.). Example communication networks may include a local area network (LAN), a wide area network (WAN), a packet data network (e.g., the Internet), a mobile telephone network (e.g., a cellular network), a plain old telephone (POTS) network, and a wireless data network (e.g., a wireless network known as a cellular network). The Institute of Electrical and Electronics Engineers (IEEE) 802.11 family of standards, known as .16 family of standards), IEEE 802.15.4 family of standards, peer-to-peer (P2P) networks, and the like. In an example, the network interface device 820 may include one or more physical jacks (e.g., Ethernet, coaxial cable, or telephone jacks) or one or more antennas to connect to the communication network 826. In an example, the network interface device 820 may include multiple antennas to enable wireless communication using at least one of single-input multiple-output (SIMO), multiple-input multiple-input (MIMO), or multiple-input single-output (MISO) technology. The term "transmission medium" shall be deemed to include any intangible medium capable of storing, encoding, or carrying instructions to be executed by the machine 800, and including digital or analog communication signals or other intangible media to facilitate the communication of such software.

[0131] Various embodiments are shown in the above-mentioned figures. One or more features from one or more of these embodiments can be combined to form other embodiments.

[0132] The method examples described herein may be at least partially machine or computer implemented. Some examples may include a computer-readable medium or machine-readable medium encoded with instructions that are operable to configure an electronic device or system to perform the methods described in the above examples. Implementations of such methods may include code, such as microcode, assembly language code, high-level language code, or the like. Such code may include computer-readable instructions for performing the various methods. The code may form part of a computer program product. Furthermore, during execution or at other times, the code may be tangibly stored on one or more volatile or non-volatile computer-readable media.

[0133] The foregoing detailed description is intended to be illustrative rather than limiting.The scope of the disclosure should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

1. A medical device system for managing a cardiac condition, comprising: a data receiver circuit configured to receive heart sound information sensed from a patient, the heart sound information including an S1 sound signal; as well as A controller circuit configured to: generating a heart sound metric using the received heart sound information; detecting bundle branch block (BBB) ​​based at least in part on the generated heart sound metric, including to distinguish between left bundle branch block (LBBB) and right bundle branch block (RBBB); as well as Information regarding the detected BBB is provided to a user or to a process executable by the medical device system.

2. The medical device system according to claim 1, wherein: the heart sound metric indicating the presence or absence of a split S1 sound, In order to detect BBB, the controller circuit is configured as follows: detecting LBBB in response to the split S1 sound being absent or the occurrence of the split S1 sound being below a threshold; and RBBB is detected in response to the presence of the split S1 sound or the occurrence rate of the split S1 sound exceeding the threshold.

3. The medical device system according to claim 2, wherein: The heart sound metric indicating the presence or absence of the split S1 sound comprises a signal width of the S1 sound signal, The controller circuit is configured to detect the presence or absence of the split S1 tone based on a comparison of a signal width of the S1 tone signal with a width threshold.

4. The medical device system according to any one of claims 2 to 3, wherein: The heart sound metric indicating the presence or absence of the split S1 sound comprises a spectral entropy of the S1 sound signal, The controller circuit is configured to detect the presence or absence of the split S1 tone based on a comparison of a spectral entropy of the S1 tone signal with a spectral entropy threshold.

5. The medical device system of any one of claims 2-4, comprising an electrical stimulator configured to provide cardiac stimulation to the patient, in, The controller circuit is configured to generate a control signal to the electrical stimulator to: delivering cardiac conduction system pacing (CSP) at the His bundle or septal region of the heart via the first one or more electrodes in response to the detected LBBB; and In response to the detected RBBB, the cardiac stimulation is withheld or RV pacing is delivered at a right ventricle (RV) apex of the heart via a second electrode or electrodes.

6. The medical device system of claim 5, comprising a lead having a distal portion configured to be inserted into the His bundle or septal region at an adjustable depth to deliver the CSP therein via the first one or more electrodes associated with the lead, in, In response to detecting the LBBB, the controller circuit is configured to: receiving paced heart sound information in response to delivery of the CSP; generating a heart sound metric indicating the presence or absence of a split S1 sound using the paced heart sound information; as well as Determining whether to adjust a depth of insertion of the distal portion of the lead into the bundle of His or the septal region comprises: not adjusting the insertion depth if the heart sound metric indicates the presence of a split S1 sound or if the incidence of the split S1 sound exceeds a ratio threshold; and adjusting the insertion depth if the heart sound metric indicates the absence of a split S1 sound or if the incidence of the split S1 sound is below the ratio threshold.

7. The medical device system according to claim 6, wherein: The controller circuit is configured to generate a control signal to a user interface to display a heart sound metric indicative of the presence or absence of the split S1 sound in real time as the distal portion of the lead is positioned at different insertion depths while the CSP is being delivered.

8. The medical device system according to any one of claims 5 to 7, wherein: The controller circuit is configured, in response to detecting the LBBB: generating a control signal to the electrical stimulator to deliver cardiac resynchronization pacing (CRT) to the left ventricle and the right ventricle of the heart according to CRT pacing parameters; receiving paced heart sound information in response to delivery of the CRT; generating a heart sound metric indicating the presence or absence of a split S1 sound using the paced heart sound information; as well as Determining whether to adjust the CRT pacing parameters includes: not adjusting the CRT pacing parameters if the heart sound metric indicates that a split S1 sound is present, or if the incidence of the split S1 sound exceeds a ratio threshold; and adjusting the CRT pacing parameters if the heart sound metric indicates that a split S1 sound is not present, or if the incidence of the split S1 sound is below a ratio threshold.

9. The medical device system according to claim 8, wherein: Adjusting the CRT pacing parameters includes adjusting pacing dose parameters or pacing timing parameters, or switching from single-site ventricular pacing to multi-site ventricular pacing.

10. The medical device system according to any one of claims 8-9, wherein: The controller circuit is configured to generate a control signal to a user interface to display the heart sound metric indicating the presence or absence of the split S1 sound in real time as CRT is being delivered according to different values ​​of the CRT pacing parameter.

11. The medical device system according to any one of claims 1 to 10, wherein: The data receiver circuit is configured to receive respiratory information sensed from the patient, the respiratory information including an inhalation phase and an exhalation phase in a respiratory cycle, Wherein, the controller circuit is configured to generate the heart sound metric using a portion of the received heart sound information corresponding to an inspiratory phase of the respiratory cycle, and to detect the BBB based on the heart sound metric during the inspiratory phase.

12. The medical device system according to any one of claims 1 to 11, wherein: The heart sound metric includes the intensity of the S1 sound signal, Wherein, the controller circuit is configured to further detect the BBB based on the S1 sound intensity.

13. The medical device system according to any one of claims 1 to 12, wherein: The data receiver circuit is configured to receive cardiac electrical activity information sensed from the patient, The controller circuit is configured to use the received heart sound information and the cardiac electrical activity information to generate a heart sound metric including a pre-ejection period measurement value, and further detect the BBB based on the pre-ejection period measurement value.

14. The medical device system of any one of claims 1-13, comprising a risk assessment circuit configured to generate a risk of heart or lung disease of the patient based at least on information of the detected BBB.

15. The medical device system of any one of claims 1-14, comprising a user interface configured to generate an alert of a detected BBB.

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