Cardiac remodeling pacing therapy based on heart failure status

Abstract

This disclosure generally relates to systems, devices, and methods configured to provide cardiac remodeling pacing therapy and to assess the cardiac remodeling pacing therapy using heart failure status. The cardiac remodeling pacing therapy may be adjusted if the heart failure status indicates no change or a decline, and the cardiac remodeling pacing therapy may be maintained if the heart failure status indicates improvement.

Description

CARDIAC REMODELING PACING THERAPY BASED ON HEART FAILURE STATUS

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 675,994, filed July 26, 2024, the entire content of which is incorporated herein by reference.

[0002] This disclosure generally relates to monitoring heart failure status and adjusting cardiac remodeling pacing therapy based on the heart failure status.

[0003] Heart failure occurs when the heart muscle is unable to pump enough blood to meet the body’s needs. The volume of blood pumped by the heart is determined by how well the heart squeezes (i.e., muscle contraction) and how well the heart relaxes and fills with blood. Ejection fraction is a measure of how much blood inside the left ventricle is pumped out with each contraction. When the left ventricle pumps or contracts, not all the blood in the ventricle leaves. A normal ejection fraction is more than about 50%. Heart failure with preserved ejection fraction (HFpEF) occurs when the left ventricle does not fill with blood as well as normal, but the ventricle can pump well. Generally, patients exhibiting an ejection fraction of less than or equal to 0.35 are classified as having heart failure with reduced ejection fraction (HFrEF) while an ejection fraction of at least 0.5 is considered to be HFpEF, which ejection fractions between considered Heart Failure with Mid-Range Ejection Fraction (HFmrEF). For example, the ventricle is stiff, or has thick walls, such that the ventricle does not relax to fill with a normal volume of blood. Alternatively, when the muscle contraction is abnormal (e.g., the muscle is too weak to pump properly), the condition is referred to as heart failure with reduced ejection fraction (HFrEF). Patients with HFpEF represent nearly half of the heart failure population and continue to increase in prevalence relative to patients with HFrEF.

[0004] Heart failure patients, such as patients having HFpEF, may be provided with cardiac remodeling pacing therapy, which may result in cardiac remodeling of the patient’s heart and improved cardiac functionality. Cardiac remodeling pacing therapy may be beneficial in some cases or adverse in other cases. For example, applying high rate pacing to induce cardiac remodeling in HFpEF may overdrive a patient in a dilatory heart failure state.SUMMARY

[0005] The present disclosure is directed to monitoring heart failure status (e.g., cardiac contractility) and adjusting cardiac remodeling pacing therapy based on the heart failure status that may be useful for heart failure patients, such as patients’ with HFpEF. For example, the illustrative systems, devices, and methods may be configured to provide effective cardiac remodeling pacing therapy to heart failure patients and to avoid adversely affecting heart failure patients. It may be described that the illustrative systems, devices, and methods may be configured to trigger, adjust, and terminate cardiac remodeling pacing therapy, or pacing-induced cardiac remodeling, based on heart failure diagnostics, e.g., using a leadless implantable medical device. The adjustment of cardiac remodeling pacing therapy may ensure that the cardiac remodeling pacing therapy is beneficial. Further, the cardiac remodeling pacing therapy may be terminated, or ceased, if it is ultimately determined to not be beneficial. Still further, the cardiac remodeling pacing therapy may be changed or converted to cardiac remodeling maintenance therapy following successful cardiac remodeling pacing therapy. The cardiac remodeling maintenance therapy may be configured to maintain the successful remodeling of a patient’s heart.

[0006] In one or more embodiments, the illustrative systems, devices, and methods may be described as utilizing a closed-loop algorithm that activates and deactivates cardiac remodeling pacing therapy (such as, e.g., high-rate nocturnal pacing) based on heart failure diagnostics (e.g., provided by a leadless pacemaker). The cardiac remodeling pacing therapy can be titrated to a specific level, without driving a patient further into heart failure. In one embodiment, the illustrative process, methods, and algorithms may be provided by a leadless implantable medical device that provides atrial pacing to deliver the cardiac remodeling pacing therapy and includes an intracardiac accelerometer to detect progression of the patient into dilatory heart failure.

[0007] One illustrative system includes a computing apparatus including processing circuitry and configured to initiate delivery of cardiac remodeling pacing therapy to a patient’s heart and recurrently assess the cardiac remodeling pacing therapy. One illustrative method includes initiating delivery of cardiac remodeling pacing therapy to a patient’s heart and recurrently assessing the cardiac remodeling pacing therapy. The recurrent assessment of the cardiac remodeling pacing therapy includes monitoring at least one physiological parameter of thepatient’s heart, determining a heart failure status based on the at least one physiological parameter, and adjusting cardiac remodeling pacing therapy being delivered to the patient’s heart based on the heart failure status.

[0008] The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the techniques described in this disclosure will be apparent from the description and drawings, and from the claims.BRIEF DESCRIPTION OF DRAWINGS

[0009] FIG. 1 is a conceptual diagram of an illustrative cardiac therapy system including a leadless implantable medical device implanted in a patient’s heart and a separate medical device positioned outside of the patient’s heart.

[0010] FIG. 2 is an enlarged conceptual diagram of the leadless implantable medical device of FIG. 1 and anatomical structures of the patient’s heart.

[0011] FIG. 3 is a conceptual diagram of a map of a patient’s heart in a standard 17 segment view of the left ventricle showing various electrode implantation locations.

[0012] FIG. 4 is a perspective view of an implantable medical device having a distal fixation and electrode assembly that includes a distal housing-based electrode implemented as a ring electrode for use with, e.g., the illustrative systems and devices of FIGS. 1 and 2.

[0013] FIG. 5 is a block diagram of illustrative circuitry that may be part of, or included with, the medical devices of FIGS. 1, 2, and 4, for example, to provide the functionality and therapy described herein.

[0014] FIG. 6 is a flow diagram of an illustrative method of delivering cardiac remodeling pacing therapy and assessing the cardiac remodeling pacing therapy.

[0015] FIG. 7 is a flow diagram of another illustrative method of delivering cardiac remodeling pacing therapy and assessing the cardiac remodeling pacing therapy.

[0016] FIG. 8 is a flow diagram of another illustrative method of delivering cardiac remodeling pacing therapy and assessing the cardiac remodeling pacing therapy.DETAILED DESCRIPTION

[0017] In the following detailed description of illustrative embodiments, reference is made to the accompanying figures of the drawing which form a part thereof, and in which are shown, by way of illustration, specific embodiments which may be practiced. It is to be understood that other embodiments may be utilized, and structural changes may be made without departing from (e.g., still falling within) the scope of the disclosure presented hereby.

[0018] Illustrative systems, devices, and methods shall be described with reference to Figures 1-8. It will be apparent to one skilled in the art that elements or processes from one embodiment may be used in combination with elements or processes of the other embodiments, and that the possible embodiments of such systems, devices, and methods using combinations of features set forth herein is not limited to the specific embodiments shown in the Figures and / or described herein. Further, it will be recognized that the embodiments described herein may include many elements that are not necessarily shown to scale. Still further, it will be recognized that timing of the processes and the size and shape of various elements herein may be modified but still fall within the scope of the present disclosure, although certain timings, one or more shapes and / or sizes, or types of elements, may be advantageous over others.

[0019] The present disclosure relates to delivery of cardiac remodeling pacing therapy and assessment of the cardiac remodeling pacing therapy based on a heart failure status (e.g., cardiac contractility). The heart failure status may be generated, or determined, based one or more physiological parameters that are monitored. In one or more embodiments, the physiological parameters may be measured using electrical or mechanical activity of the patient’s heart. The cardiac remodeling pacing therapy may be delivered, and the electrical and / or mechanical activity may be monitored using medical device systems including implantable medical devices as will be described further herein with respect to FIGS. 1-5.

[0020] An illustrative cardiac therapy system 100 that may be configured to provide cardiac remodeling pacing therapy and assessment thereof is depicted in FIG. 1. The system 100 includes an implantable medical device 10 implanted in a patient’s heart and a separate medical device 50 positioned outside of the patient’s heart is depicted in FIG. 1. The implantable medical device 10 may be configured for single or dual chamber therapy and implanted in a patient’s heart 8. In some embodiments, the implantable medical device 10 may be configured for singlechamber pacing and may, for example, switch between single-chamber and multiple-chamber pacing (e.g., dual chamber pacing). As used herein, “intracardiac” refers to a device configured to be implanted entirely within a patient’s heart, for example, to provide cardiac therapy. The implantable medical device 10 is shown implanted in the right atrium (RA) of the patient’s heart 8 in a target implant region 4. The implantable medical device 10 may include one or more fixation members 20 that anchor a distal end of the device against the atrial endocardium in a target implant region 4. The target implant region 4 may he between the His bundle 5 (or bundle of His) and the coronary sinus 3 and may be adjacent the tricuspid valve 6. The implantable medical device 10 may be described as a ventricle-from-atrium (VfA) device, which may sense or provide pacing therapy to one or both ventricles (e.g., right ventricle, left ventricle, or both ventricles, depending on the circumstances) while being generally disposed in the right atrium. In particular, the implantable medical device 10 may include a tissue-piercing electrode that may be implanted in the basal region, septal region, or basal-septal region of the left ventricular myocardium of the patient’s heart from the triangle of Koch region of the right atrium through the right-atrial endocardium and central fibrous body.

[0021] The implantable medical device 10 may be described as a leadless, intracardiac implantable medical device. As used herein, “leadless” refers to a device being free of a lead extending out of the patient’s heart 8. In other words, a leadless device may have a lead that does not extend from outside of the patient’s heart to the inside of the patient’s heart. Some leadless devices may be introduced through a vein, but once implanted, the device is free of, or may not include, any transvenous lead and may be configured to provide cardiac therapy without using any transvenous lead. Further, a leadless VfA device, in particular, does not use a lead to operably connect to an electrode in the ventricle when a housing of the device is positioned in the atrium. Additionally, a leadless electrode may be coupled to the housing of the medical device without using a lead between the electrode and the housing.

[0022] The implantable medical device 10 may include a dart electrode assembly 12 defining, or having, a straight shaft extending from the distal end region of device 10. The dart electrode assembly 12 may be placed, or at least configured to be placed, through the atrial myocardium and the central fibrous body and into the ventricular myocardium 14, or along the ventricular septum, without perforating entirely through the ventricular endocardial or epicardial surfaces. The dart electrode assembly 12 may carry, or include, an electrode at the distal end region of the shaft such that the electrode may be positioned within the ventricular myocardium for sensing ventricular signals and delivering ventricular pulses (e.g., to depolarize the left ventricle to initiate a contraction of the left ventricle). In some examples, the electrode at the distal end region of the shaft is a cathode electrode provided for use in a bipolar electrode pair for pacing and sensing. While the implant region 4 as illustrated may enable one or more electrodes of the dart electrode assembly 12 to be positioned in the ventricular myocardium, it is recognized that a device having the aspects disclosed herein may be implanted at other locations for multiple chamber pacing (e.g., dual- or triple-chamber pacing), single-chamber pacing with multiple chamber sensing, single-chamber pacing and / or sensing, or other clinical therapy and applications as appropriate.

[0023] It is to be understood that although device 10 is described herein as including a single dart electrode assembly, the implantable medical device 10 may include more than one dart electrode assembly placed, or configured to be placed, through the atrial myocardium and the central fibrous body, and into the ventricular myocardium 14, or along the ventricular septum, without perforating entirely through the ventricular endocardial or epicardial surfaces. Additionally, each dart electrode assembly may carry, or include, more than a single electrode at the distal end region, or along other regions (e.g., proximal or central regions), of the shaft.

[0024] The system 100 may also include a separate medical device 50 (depicted diagrammatically in FIG. 1), which may be positioned outside the patient’s heart 8 (e.g., subcutaneously) and may be operably coupled to the patient’s heart 8 to deliver cardiac therapy thereto (such as, e.g., cardiac remodeling pacing therapy). In one example, separate medical device 50 may be a cardiac monitor or an extravascular implantable cardioverter defibrillator (ICD).

[0025] In some embodiments, the separate medical device 50 may include a variety of sensors such as electrodes, mechanical activity sensor including accelerometers, microphones, and gyroscopes, temperatures sensors, and magnetic field sensors (e.g., magnetometer). The electrodes may be configured to monitor cardiac electrical such as electrocardiograms indicative of diastolic function and / or impedance signals indicative of fluid volume (e.g., thoracic fluid volume or accumulation). The accelerometers may be configured to monitor heart movement and body movement. The gyroscopes may be configured to monitor body position (e.g., prone, supine, etc.). The temperature sensors may be configured to measure temperature of various body portions. The magnetic field sensors may be configured to monitor the magnetic field proximate various body portions.

[0026] The separate medical device 50 may further include a sensing circuit configured to receive signals or data from the variety of sensors provided thereby. For example, the sensing circuit may be configured to obtain electrical signals sensed via one or more combinations of electrodes and to process the obtained signals. The components of the sensing circuit may include analog components, digital components, or a combination thereof. The sensing circuit may, for example, include one or more sense amplifiers, filters, rectifiers, threshold detectors, analog-to-digital converters (ADCs), or the like. The sensing circuit may convert the sensed signals to digital form and provide the digital signals to the control circuit for processing and / or analysis. For example, the sensing circuit may amplify signals from sensing electrodes and may convert the amplified signals to multi-bit digital signals by an ADC, and then provide the digital signals to the control circuit. In one or more embodiments, the sensing circuit of the separate medical device 50 may also compare processed signals to a threshold to detect the existence of atrial or ventricular depolarizations (e.g., P- or R-waves). In one or more embodiments, the sensing circuit of the separate medical device 50 may be configured to measure, or monitor, one or more heart sounds using a mechanical activity sensor (e.g., one or both of an accelerometer and microphone).

[0027] The implantable medical device 10 and the separate medical device 50 may cooperate to provide cardiac remodeling pacing therapy to the patient’s heart 8 and to assess the cardiac remodeling pacing therapy using heart failure status (e.g., cardiac contractility). For example, the implantable medical device 10 may be configured to provide cardiac remodeling pacing therapyby delivering paces to one or both of the right atrium and the left ventricle and one or both of the implantable medical device 10 and the separate medical device 50 may be used to monitor at least one physiological parameter and to analyze the at least one physiological parameter to determine a heart failure status. The determined heart failure status may then be used by one or both of the implantable medical device 10 and the separate medical device 50 to adjust, continue, or terminate the cardiac remodeling pacing therapy as will be described further herein. To function in cooperation, the implantable medical device 10 may communicate with the separate medical device 50 wirelessly. As used herein, “wirelessly” refers to an operative coupling or connection without using a metal conductor between the implantable medical device 10 and the separate medical device 50. In one example, wireless communication may use a communication interface (e.g., an antenna) of the implantable medical device 10 to provide electromagnetic radiation that propagates through patient’s tissue and is detectable, for example, using a communication interface (e.g., an antenna) of the separate medical device 50. In one example, wireless communication may use a distinctive, signaling, or triggering electrical pulse provided by the implantable medical device 10 that conducts through the patient’s tissue and is detectable by the separate medical device 50.

[0028] FIG. 2 is an enlarged conceptual diagram of the implantable medical device 10 of FIG. 1 and anatomical structures of the patient’s heart 8. In particular, the implantable medical device 10 is configured to sense electrical activity and / or deliver pacing therapy. The implantable medical device 10 may include a housing 30. The housing 30 may define a hermetically sealed internal cavity in which internal components of the implantable medical device 10 reside, such as a sensing circuit, therapy delivery circuit, control circuit, memory, telemetry circuit, other optional sensors, and a power source as generally described in conjunction with FIG. 5. The housing 30 may be formed from an electrically conductive material including titanium or titanium alloy, stainless steel, MP35N (a non-magnetic nickel-cobalt-chromium-molybdenum alloy), platinum alloy, or other bio-compatible metal or metal alloy. In other examples, the housing 30 may be formed from a non-conductive material including ceramic, glass, sapphire, silicone, polyurethane, epoxy, acetyl co-polymer plastics, polyether ether ketone (PEEK), a liquid crystal polymer, or other biocompatible polymer.

[0029] In at least one embodiment, the housing 30 may be described as extending between a distal end region 32 and a proximal end region 34 in a generally cylindrical shape to facilitate catheter delivery. In other embodiments, the housing 30 may be prismatic or any other shape to perform the functionality and utility described herein. The housing 30 may include a delivery tool interface member 26, e.g., at the proximal end region 34, for engaging with a delivery tool during implantation of the implantable medical device 10.

[0030] All or a portion of the housing 30 may function as an electrode during cardiac therapy, for example, in sensing and / or pacing. In the example shown, the housing-based electrode 24 is shown to circumscribe a proximal portion (e.g., closer to the proximal end region 34 than the distal end region 32) of the housing 30. When the housing 30 is formed from an electrically conductive material, such as a titanium alloy or other examples listed above, portions of the housing 30 may be electrically insulated by a non-conductive material, such as a coating of parylene, polyurethane, silicone, epoxy, or other biocompatible polymer, leaving one or more discrete areas of conductive material exposed to define the proximal housing-based electrode 24. When the housing 30 is formed from a non-conductive material, such as a ceramic, glass or polymer material, an electrically conductive coating or layer, such as a titanium, platinum, stainless steel, or alloys thereof, may be applied to one or more discrete areas of the housing 30 to form the proximal housing-based electrode 24. In other examples, the proximal housing-based electrode 24 may be a component, such as a ring electrode, that is mounted or assembled onto the housing 30. The proximal housing-based electrode 24 may be electrically coupled to internal circuitry of the implantable medical device 10, e.g., via the electrically conductive housing 30 or an electrical conductor when the housing 30 is a non-conductive material.

[0031] In the example shown, the proximal housing-based electrode 24 is located nearer to the housing proximal end region 34 than the housing distal end region 32 and is therefore referred to as a “proximal housing-based electrode” 24. In other examples, however, the housingbased electrode 24 may be located at other positions along the housing 30, e.g., more distal relative to the position shown.

[0032] At the distal end region 32, the implantable medical device 10 may include a distal fixation and electrode assembly 36, which may include one or more fixation members 20 and one or more dart electrode assemblies 12 of equal or unequal length. In one example, a singledart electrode assembly 12 includes a shaft 40 extending distally away from the housing distal end region 32 and one or more electrode elements, such as a tip electrode 42 at or near the free, distal end region of the shaft 40. The tip electrode 42 may have a conical or hemispherical distal tip with a relatively narrow tip-diameter (e.g., less than about 1 millimeter (mm)) for penetrating into and through tissue layers without using a sharpened tip or needle-like tip having sharpened or beveled edges.

[0033] The shaft 40 of the dart electrode assembly 12 may be a normally straight member and may be rigid. In other embodiments, the shaft 40 may be described as being relatively stiff but still possessing limited flexibility in lateral directions. Further, the shaft 40 may be non-rigid to allow some lateral flexing with heart motion. However, in a relaxed state, when not subjected to any external forces, the shaft 40 may maintain a straight position as shown to hold the tip electrode 42 spaced apart from the housing distal end region 32 at least by the height 47 of the shaft 40. In other words, the dart electrode assembly 12 may be described as resilient.

[0034] The dart electrode assembly 12 may be configured to pierce through one or more tissue layers to position the tip electrode 42 within a desired tissue layer, e.g., the ventricular myocardium. As such, the height 47, or length, of the shaft 40 may correspond to the expected pacing site depth, and the shaft 40 may have a relatively high compressive strength along its longitudinal axis to resist bending in a lateral or radial direction when pressed against the implant region 4. If a second dart electrode assembly 12 is employed, its length may be unequal to the expected pacing site depth and may be configured to act as an indifferent electrode for delivering of pacing energy to the tissue. A longitudinal axial force may be applied against the tip electrode 42, e.g., by applying a longitudinal pushing force to the proximal end region 34 of the housing 30, to advance the dart electrode assembly 12 into the tissue within the target implant region. The shaft 40 may be described as longitudinally non-compressive and / or elastically deformable in lateral or radial directions when subjected to lateral or radial forces to allow temporary flexing, e.g., with tissue motion, but may return to its normally straight position when lateral forces diminish. When the shaft 40 is not exposed to any external force, or to only a force along its longitudinal central axis, the shaft 40 may retain a straight, linear position as shown.

[0035] The one or more fixation members 20 may be described as one or more “tines” having a normally curved position. The tines may be held in a distally extended position within adelivery tool. The distal tips of tines may penetrate the heart tissue to a limited depth before elastically curving back proximally into the normally curved position (shown) upon release from the delivery tool. Further, the fixation members 20 may include one or more aspects described in, for example, U.S. Patent No. 9,675,579 issued on June 13, 2017, and U.S. Patent No. 9,119,959 issued on September 1, 2015, each of which is incorporated herein by reference in its entirety.

[0036] In some examples, the distal fixation and electrode assembly 36 includes a distal housing-based electrode 22. In the case of using the implantable medical device 10 as a pacemaker for multiple chamber pacing (e.g., dual- or triple-chamber pacing) and sensing, the tip electrode 42 may be used as a cathode electrode paired with the proximal housing-based electrode 24 serving as a return anode electrode. Alternatively, the distal housing-based electrode 22 may serve as a return anode electrode paired with tip electrode 42 for sensing ventricular signals and delivering ventricular pacing pulses. In other examples, the distal housing-based electrode 22 may be a cathode electrode for sensing atrial signals and delivering pacing pulses to the atrial myocardium in the target implant region 4. When the distal housing-based electrode 22 serves as an atrial cathode electrode, the proximal housing-based electrode 24 may serve as the return anode paired with the tip electrode 42 for ventricular pacing and sensing and as the return anode paired with the distal housing-based electrode 22 for atrial pacing and sensing.

[0037] As shown in this illustration, the target implant region 4 in some pacing applications is along the atrial endocardium 18, generally inferior to the AV node 15 and the His bundle 5. The dart electrode assembly 12 may at least partially define the height 47, or length, of the shaft 40 for penetrating through the atrial endocardium 18 in the target implant region 4, through the central fibrous body 16, and into the ventricular myocardium 14 without perforating through the ventricular endocardial surface 17. When the height 47, or length, of the dart electrode assembly 12 is fully advanced into the target implant region 4, the tip electrode 42 may rest within the ventricular myocardium 14, and the distal housing-based electrode 22 may be positioned in intimate contact with or close proximity to the atrial endocardium 18. The dart electrode assembly 12 may have a total combined height 47, or length, of the tip electrode 42 and the shaft 40 from about 3 mm to about 15 mm in various examples. In one embodiment, the total combined height 47, or length, of the tip electrode 42 and the shaft 40 is 8 mm. In one or more embodiments, the total combined height 47, or length, of the tip electrode 42 and the shaft 40 isgreater than or equal to about 3 mm, greater than or equal to about 4 mm, greater than or equal to about 5 mm, greater than or equal to about 6 mm, greater than or equal to about 7 mm, or greater than or equal to about 8 mm, and / or less than or equal to about 15 mm, less than or equal to about 14 mm, less than or equal to about 13 mm, less than or equal to about 12 mm, less than or equal to about 11 mm, less than or equal to about 10 mm, or less than or equal to about 9 mm. The diameter of the shaft 40 may be less than about 2 mm, and may be about 1 mm or less, or even about 0.6 mm or less.

[0038] The implantable medical device 10 may include one or more mechanical activity sensors 11 (e.g., an acoustic or motion detector) within the housing 30. The mechanical activity sensors 11 may be operably coupled to one or more a control circuit 80, a sensing circuit 86, or therapy delivery circuit 84 as shown in FIG. 5. Further, in one or more embodiments, the mechanical activity sensors 11 may be used with methods 200, 201, and 400 as shown in FIGS. 6-8. The mechanical activity sensors 11 may be used to monitor mechanical activity, such as atrial mechanical activity (e.g., an atrial contraction) and / or ventricular mechanical activity (e.g., a ventricular contraction). In some embodiments, the mechanical activity sensors 11 may be used to detect right-atrial mechanical activity. A non-limiting example of a mechanical activity sensor 11 is an accelerometer or microphone.

[0039] In various embodiments, the mechanical activity sensor 11 may be used as a heart sound (HS) sensor and may be implemented as a microphone or a 1-, 2- or 3 -axis accelerometer. In one embodiment, the mechanical activity sensor 11 is implemented as a piezoelectric crystal mounted within an implantable medical device housing and responsive to the mechanical motion associated with heart sounds. Examples of other embodiments of mechanical activity sensors that may be adapted for implementation with the techniques of the present disclosure may be described generally in U.S. Pat. No. 4,546,777, U.S. Pat. No. 6,869,404, U.S. Pat. No. 5,554,177, and U.S. Pat. No. 7,035,684, each of which is incorporated herein by reference in its entirety.

[0040] Various types of the mechanical activity sensors 11 may be used. The mechanical activity sensor 11 may be any implantable or external sensor responsive to one or more of the heart sounds generated as described in the foregoing and thereby produces an analog electrical signal correlated in time and amplitude to the heart sounds. The analog signal may then be processed, which may include digital conversion, by a sensing circuit or other processingcircuitry to obtain heart sound parameters, such as amplitudes, durations, relative time intervals, areas under the curve, first derivatives, steepness, maximum slope, etc.

[0041] In some embodiments, the mechanical activity detected by the mechanical activity sensor 11 may be used to supplement or replace electrical activity detected by one or more of the electrodes of the implantable medical device 10 for use in delivery pacing therapy. For example, the mechanical activity sensor 11 may be used in addition to, or as an alternative to, the proximal housing-based electrode 24 for use in delivery pacing therapy. In one embodiment, the mechanical activity sensor 11 may also be used for rate response detection or to provide a rate responsive pacing therapy. Various techniques related to rate responsive therapy may be described in U.S. Patent No. 5,154,170 issued on October 13, 1992, and entitled “Optimization for Rate Responsive Cardiac Pacemaker,” and U.S. Patent No. 5,562,711 issued on October 8, 1996, and entitled “Method and Apparatus for Rate-Responsive Cardiac Pacing,” each of which is incorporated herein by reference in its entirety.

[0042] FIG. 3 is a two-dimensional (2D) ventricular map 300 of a patient’s heart (e.g., a top- down view) showing the left ventricle 320 in a standard 17 segment view and the right ventricle 322. The map 300 includes a plurality of areas 326 corresponding to different regions of a human heart. As illustrated, the areas 326 are numerically labeled 301-317 (e.g., which correspond to 17 segments of the left ventricle of a human heart). Areas 326 of the map 300 may include basal anterior area 301, basal anteroseptal area 302, basal inferoseptal area 303, basal inferior area 304, basal inferolateral area 305, basal anterolateral area 306, mid-anterior area 307, mid-anteroseptal area 308, mid-inferoseptal area 309, mid-inferior area 310, mid-inferolateral area 311, mid- anterolateral area 312, apical anterior area 313, apical septal area 314, apical inferior area 315, apical lateral area 316, and apex area 317. The inferoseptal and anteroseptal areas of the right ventricle 322 are also illustrated, as well as the right bundle branch (RBB) and left bundle branch (LBB).

[0043] In some embodiments, any of the tissue-piercing electrodes of the present disclosure may be implanted in the basal region, septal region, or basal-septal region of the left ventricular myocardium of the patient’s heart. In particular, the tissue-piercing electrode may be implanted from the triangle of Koch region of the right atrium through the right-atrial endocardium and central fibrous body.

[0044] Once implanted, the tissue-piercing electrode may be positioned in the target implant region 4 (FIGS. 1 and 2), such as the basal region, septal region, or basal-septal region of the left ventricular myocardium. With reference to map 300, the basal region includes one or more of the basal anterior area 301, basal anteroseptal area 302, basal inferoseptal area 303, basal inferior area 304, mid-anterior area 307, mid-anteroseptal area 308, mid-inferoseptal area 309, and midinferior area 310. With reference to map 300, the septal region includes one or more of the basal anteroseptal area 302, basal inferoseptal area 303, mid-anteroseptal area 308, mid-inferoseptal area 309, and apical septal area 314. In some embodiments, the tissue-piercing electrode may be positioned in the basal septal region of the left ventricular myocardium when implanted. The basal septal region may include one or more of the basal anteroseptal area 302, basal inferoseptal area 303, mid-anteroseptal area 308, and mid-inferoseptal area 309. In some embodiments, the tissue-piercing electrode may be positioned in the high inferior / posterior basal septal region of the left ventricular myocardium when implanted. The high inferior / posterior basal septal region of the left ventricular myocardium may include a portion of one or more of the basal inferoseptal area 303 and mid-inferoseptal area 309 (e.g., the basal inferoseptal area only, the mid- inferoseptal area only, or both the basal inferoseptal area and the mid-inferoseptal area). For example, the high inferior / posterior basal septal region may include region 324 illustrated generally as a dashed-line boundary. As shown, the dashed line boundary represents an approximation of where the high inferior / posterior basal septal region is located, which may take a somewhat different shape or size depending on the particular application.

[0045] FIG. 4 is a perspective view of the implantable medical device 10. As shown, the distal fixation and electrode assembly 36 includes the distal housing-based electrode 22 implemented as a ring electrode. The distal housing-based electrode 22 may be positioned in intimate contact with or operative proximity to atrial tissue when fixation member tines 20a, 20b, and 20c of the fixation members 20, engage with the atrial tissue. The tines 20a, 20b, and 20c, which may be elastically deformable, may be extended distally during delivery of device 10 to the implant site. For example, the tines 20a, 20b, and 20c may pierce the atrial endocardial surface as the implantable medical device 10 is advanced out of the delivery tool and flex back into their normally curved position (as shown) when no longer constrained within the delivery tool. As the tines 20a, 20b, and 20c curve back into their normal position, the fixation member 20 may pull the distal fixation member and electrode assembly 36 toward the atrial endocardialsurface. As the distal fixation member and electrode assembly 36 is pulled toward the atrial endocardium, the tip electrode 42 may be advanced through the atrial myocardium and the central fibrous body and into the ventricular myocardium. The distal housing-based electrode 22 may then be positioned against the atrial endocardial surface.

[0046] The distal housing-based electrode 22 may include a ring formed of an electrically conductive material, such as titanium, platinum, iridium, or alloys thereof. The distal housingbased electrode 22 may be a single, continuous ring electrode. In other examples, portions of the ring may be coated with an electrically insulating coating, e.g., parylene, polyurethane, silicone, epoxy, or another insulating coating, to reduce the electrically conductive surface area of the ring electrode. For instance, one or more sectors of the ring may be coated to separate two or more electrically conductive exposed surface areas of the distal housing-based electrode 22. Reducing the electrically conductive surface area of the distal housing-based electrode 22, e.g., by covering portions of the electrically conductive ring with an insulating coating, may increase the electrical impedance of the distal housing-based electrode 22, and thereby, reduce the current delivered during a pacing pulse that captures the myocardium, e.g., the atrial myocardial tissue. A lower current drain may conserve the power source, e.g., one or more rechargeable or non-rechargeable batteries, of the implantable medical device 10.

[0047] As described above, the distal housing-based electrode 22 may be configured as an atrial cathode electrode for delivering pacing pulses to the atrial tissue at the implant site in combination with the proximal housing-based electrode 24 as the return anode. The electrodes 22 and 24 may be used to sense atrial P- waves for use in controlling atrial pacing pulses (delivered in the absence of a sensed P-wave) and for controlling atrial-synchronized ventricular pacing pulses delivered using the tip electrode 42 as a cathode and the proximal housing-based electrode 24 as the return anode. In other examples, the distal housing-based electrode 22 may be used as a return anode in conjunction with the cathode tip electrode 42 for ventricular pacing and sensing.

[0048] FIG. 5 is a block diagram of circuitry that may be enclosed within the housing 30 to provide the functions of delivering pacing therapy including cardiac remodeling pacing therapy and assessing the cardiac remodeling pacing therapy including determining heart failure status. It is to be understood that the separate medical device 50 of FIG. 1 may include some or all the same components, which may be configured in a similar manner to assess the cardiac remodelingpacing therapy including determining heart failure status. The computing apparatus and electronic circuitry 81 enclosed within housing 30 may include software, firmware, and hardware that cooperatively measure, or monitor, at least one physiological parameter including atrial and ventricular electrical cardiac signals, mechanical signals (e.g., cardiac motion, cardiac sounds), etc. and / or deliver electrical pulses to the patient’s heart according to programmed therapy mode such as cardiac remodeling pacing therapy. The computing apparatus and electronic circuitry 81 may include a control circuit 80 (e.g., including processing circuitry), a memory 82, a therapy delivery circuit 84, a sensing circuit 86, and / or a telemetry circuit 88. The implantable medical device 10 further includes one or more sensors 90. The one or more sensors 90 may include a variety of sensors such as electrodes, the mechanical activity sensor 11 (e.g., accelerometers, microphones, and gyroscopes), temperatures sensors, and magnetic field sensors. The electrodes may be configured to monitor cardiac electrical such as electrocardiograms indicative of diastolic function and / or impedance signals indicative intracardiac fluid status and / or thoracic cavity fluid volume. The accelerometers may be configured to monitor heart movement and body movement, and the gyroscopes may be configured to monitor body position (e.g., prone, supine, etc.). The temperature sensors may be configured to measure temperature of various body portions. The magnetic field sensors may be configured to monitor the magnetic field proximate various body portions. Additionally, the one or more sensors 90 may be configured to produce one or more signals that are correlated to physiological function, state, or condition of the patient, such as a patient activity sensor, for use in determining whether a patient is in a consistent state (e.g., for the delivery of cardiac remodeling pacing therapy, for assessment of heart failure status to determine whether the cardiac remodeling pacing therapy should be adjusted, maintained, changed, or terminated).

[0049] The power source 98 may provide power to the circuitry of the implantable medical device 10 including each of the components 80, 82, 84, 86, 88, 90 as needed. The power source 98 may include one or more energy storage devices, such as one or more rechargeable or non- rechargeable batteries. The connections (not shown) between the power source 98 and each of the components 80, 82, 84, 86, 88, 90, may be understood from the general block diagram illustrated to one of ordinary skill in the art. For example, the power source 98 may be coupled to one or more charging circuits included in the therapy delivery circuit 84 for providing the power used to charge holding capacitors included in the therapy delivery circuit 84 that are dischargedat appropriate times under the control of the control circuit 80 for delivering pacing pulses, e.g., according to cardiac remodeling pacing therapy, according to a dual chamber pacing mode such as DDI(R), etc.. The power source 98 may also be coupled to components of the sensing circuit 86, such as sense amplifiers, analog-to-digital converters, switching circuitry, etc., sensors 90, the telemetry circuit 88, and the memory 82 to provide power to the various circuits.

[0050] The functional blocks shown represent functionality included in the implantable medical device 10 and may include any discrete and / or integrated electronic circuit components that implement analog, and / or digital circuits capable of producing the functions attributed to the medical device 10 herein. The various components may include processing circuitry, such as an application specific integrated circuit (ASIC), an electronic circuit, a processor (shared, dedicated, or group), and memory that execute one or more software or firmware programs, a combinational logic circuit, state machine, or other suitable components or combinations of components that provide the described functionality. The particular form of software, hardware, and / or firmware employed to implement the functionality disclosed herein will be determined primarily by the particular system architecture employed in the medical device and by the particular detection and therapy delivery methodologies employed by the medical device.

[0051] The memory 82 may include any volatile, non-volatile, magnetic, or electrical non- transitory computer-readable storage media, such as random-access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, or any other memory device. Furthermore, the memory 82 may include a non-transitory computer-readable media storing instructions that, when executed by one or more processing circuits, cause the control circuit 80 and / or other processing circuitry to perform cardiac remodeling pacing therapy, adjust or calibrate cardiac remodeling pacing therapy, perform a single, dual, or triple- chamber calibrated pacing therapy (e.g., single or multiple chamber pacing), assess cardiac remodeling pacing therapy being delivered to a patient, assess the heart failure status of a patient, or execute other cardiac therapy functions (e.g., sensing or delivering therapy), attributed to the implantable medical device 10. The non- transitory computer-readable media storing the instructions may include any of the media listed above.

[0052] The computing apparatus and electronic circuitry 81 including the control circuit 80 may communicate, e.g., via a data bus, with the therapy delivery circuit 84 and the sensing circuit 86 for sensing cardiac electrical signals and controlling delivery of cardiac electrical stimulation therapies in response to sensed cardiac events, e.g., P- waves and R- waves, or the absence thereof. The tip electrode 42, the distal housing-based electrode 22, and the proximal housing-based electrode 24 may be electrically coupled to the therapy delivery circuit 84 for delivering electrical stimulation pulses to the patient’s heart and to the sensing circuit 86 and for sensing cardiac electrical signals.

[0053] The sensing circuit 86 may include an atrial (A) sensing channel 87 and a ventricular (V) sensing channel 89. The distal housing-based electrode 22 and the proximal housing-based electrode 24 may be coupled to the atrial sensing channel 87 for sensing atrial signals, e.g., P- waves attendant to the depolarization of the atrial myocardium. In examples that include two or more selectable distal housing-based electrodes, the sensing circuit 86 may include switching circuitry for selectively coupling one or more of the available distal housing-based electrodes to cardiac event detection circuitry included in the atrial sensing channel 87. Switching circuitry may include a switch array, switch matrix, multiplexer, or any other type of switching device suitable to selectively couple components of the sensing circuit 86 to selected electrodes. The tip electrode 42 and the proximal housing-based electrode 24 may be coupled to the ventricular sensing channel 89 for sensing ventricular signals, e.g., R-waves attendant to the depolarization of the ventricular myocardium.

[0054] Each of the atrial sensing channel 87 and the ventricular sensing channel 89 may include cardiac event detection circuitry for detecting P- waves and R-waves, respectively, from the cardiac electrical signals received by the respective sensing channels. The cardiac event detection circuitry included in each of the channels 87 and 89 may be configured to amplify, filter, digitize, and rectify the cardiac electrical signal received from the selected electrodes to improve the signal quality for detecting cardiac electrical events. The cardiac event detection circuitry within channel 87 and channel 89 may include one or more sense amplifiers, filters, rectifiers, threshold detectors, comparators, analog-to-digital converters (ADCs), timers, or other analog or digital components. A cardiac event sensing threshold, e.g., a P-wave sensing threshold and an R-wave sensing threshold, may be automatically adjusted by each respective sensingchannel 87 and 89 under the control of the control circuit 80, e.g., based on timing intervals and sensing threshold values determined by the control circuit 80, stored in the memory 82, and / or controlled by hardware, firmware, and / or software of the control circuit 80 and / or the sensing circuit 86.

[0055] Upon detecting a cardiac electrical event based on a sensing threshold crossing, the sensing circuit 86 may produce a sensed event signal that is passed to the control circuit 80. For example, the atrial sensing channel 87 may produce a P-wave sensed event signal in response to a P-wave sensing threshold crossing. The ventricular sensing channel 89 may produce an R-wave sensed event signal in response to an R-wave sensing threshold crossing. The sensed event signals may be used by the control circuit 80 for setting pacing escape interval timers that control the basic time intervals used for scheduling cardiac pacing pulses. A sensed event signal may trigger or inhibit a pacing pulse depending on the particular programmed pacing mode. For example, a P-wave sensed event signal received from the atrial sensing channel 87 may cause the control circuit 80 to inhibit a scheduled atrial pacing pulse and schedule a ventricular pacing pulse at a programmed atrioventricular (AV) pacing interval. If an R-wave is sensed before the AV pacing interval expires, the ventricular pacing pulse may be inhibited. If the AV pacing interval expires before the control circuit 80 receives an R-wave sensed event signal from the ventricular sensing channel 89, the control circuit 80 may use the therapy delivery circuit 84 to deliver the scheduled ventricular pacing pulse synchronized to the sensed P-wave.

[0056] In some examples, the implantable medical device 10 may be configured to deliver a variety of pacing therapies including cardiac remodeling pacing therapy, bradycardia pacing, cardiac resynchronization therapy, post-shock pacing, and / or tachycardia-related therapy, such as ATP, among others. For example, the implantable medical device 10 may be configured to detect non-sinus tachycardia and deliver ATP. The control circuit 80 may determine cardiac event time intervals, e.g., P-P intervals between consecutive P-wave sensed event signals received from the atrial sensing channel 87, R-R intervals between consecutive R-wave sensed event signals received from the ventricular sensing channel 89, and P-R and / or R-P intervals received between P-wave sensed event signals and R-wave sensed event signals. These intervals may be compared to tachycardia detection intervals for detecting non-sinus tachycardia. Tachycardia may bedetected in a given heart chamber based on a threshold number of tachycardia detection intervals being detected.

[0057] The therapy delivery circuit 84 may include atrial pacing circuit 83 and ventricular pacing circuit 85. Each pacing circuit 83, 85 may include charging circuitry, one or more charge storage devices such as one or more low voltage holding capacitors, an output capacitor, and / or switching circuitry that controls when the holding capacitor(s) are charged and discharged across the output capacitor to deliver a pacing pulse to the pacing electrode vector coupled to respective pacing circuits 83, 85. The tip electrode 42 and the proximal housing-based electrode 24 may be coupled to the ventricular pacing circuit 85 as a bipolar cathode and anode pair for delivering ventricular pacing pulses, e.g., upon expiration of an AV or W pacing interval set by the control circuit 80 for providing atrial- synchronized ventricular pacing and a basic lower ventricular pacing rate.

[0058] The atrial pacing circuit 83 may be coupled to the distal housing-based electrode 22 and the proximal housing-based electrode 24 to deliver atrial pacing pulses. The control circuit 80 may set one or more atrial pacing intervals according to a programmed lower pacing rate or a temporary lower rate set according to a rate-responsive sensor-indicated pacing rate. Atrial pacing circuit may be controlled to deliver an atrial pacing pulse if the atrial pacing interval expires before a P-wave sensed event signal is received from the atrial sensing channel 87. The control circuit 80 starts an AV pacing interval in response to a delivered atrial pacing pulse to provide synchronized multiple chamber pacing (e.g., dual- or triple-chamber pacing).

[0059] Charging of a holding capacitor of the atrial or ventricular pacing circuit 83, 85 to a programmed pacing voltage amplitude and discharging of the capacitor for a programmed pacing pulse width may be performed by the therapy delivery circuit 84 according to control signals received from the control circuit 80. For example, a pace timing circuit included in the control circuit 80 may include programmable digital counters set by a microprocessor of the control circuit 80 for controlling the basic pacing time intervals associated with various single-chamber or multiple-chamber pacing (e.g., dual- or triple- chamber pacing) modes or anti -tachycardia pacing sequences. The microprocessor of the control circuit 80 may also set the amplitude, pulse width, polarity, or other characteristics of the cardiac pacing pulses, which may be based on programmed values stored in the memory 82.

[0060] Control parameters utilized by the control circuit 80 for sensing cardiac events and controlling pacing therapy delivery may be programmed into the memory 82 via the telemetry circuit 88, which may also be described as a communication interface. The telemetry circuit 88 includes a transceiver and antenna for communicating with the separate medical device 50 to cooperate in the delivery and assessment of cardiac remodeling pacing therapy and / or another external device, such as a programmer or home monitor, using radio frequency communication or other communication protocols. The control circuit 80 may use the telemetry circuit 88 to receive downlink telemetry from and send uplink telemetry to the separate medical device 50 and / or another external device.

[0061] An illustrative method 200 of delivering cardiac remodeling pacing therapy and assessing the cardiac remodeling pacing therapy is depicted in FIG. 6. The method 200 can be performed by the computing apparatus and electronic circuitry 81 including, among other things, the control circuit 80, the electrodes 22, 24, 42, and the one or more sensors 90 including the mechanical activity sensor 11, and any other element or portion of the implantable medical device 10 described herein with reference to FIGS. 1, 2, 4, and 5. It is to be understood that the illustrative method 200 and processes described therein may be performed or partially performed on non- implantable devices or subdermal implanted devices such as the separate medical device 50, which may communicate with the implantable medical device 10 to deliver and assess the cardiac remodeling pacing. For example, the illustrative method 200 may be performed or partially performed by an external device (e.g., outside of the patient’s body) or extracardiac medical device (e.g., implanted in the patient’s body but outside of the patient’s heart) but may communicate with the implantable medical device 10 to deliver and assess the cardiac remodeling pacing.

[0062] The method 200 includes delivering cardiac remodeling pacing therapy 202, for example, using the implantable medical device 10 as described herein with respect to FIGS. 1-5. It is to be understood that the implantable medical device 10 is just one example, and that the cardiac remodeling pacing therapy 202 may be delivered using any one or more implantable or external device able, or configured, to deliver cardiac remodeling pacing therapy. It is to be understood that, while the implantable medical device 10 or another device is delivering the cardiac remodeling pacing therapy (e.g., using pacing pulses delivered using pacing electrodes),the cardiac remodeling pacing therapy itself may be triggered or initiated by the implantable medical device 10 or the separate medical device 50. For example, the separate medical device 50 may determine when to deliver cardiac remodeling pacing therapy based on various factors (e.g., whether the patient is at rest, whether the patient is asleep, whether the patient is in a consistent state, etc.), and then instruct (e.g., signal through telemetry) the implantable medical device 10 to initiate, or trigger, the cardiac remodeling pacing therapy. Nonetheless, it is to be understood that the implantable medical device 10 itself may determine when to deliver cardiac remodeling pacing, and then in response thereto, deliver the cardiac remodeling pacing therapy.

[0063] The cardiac remodeling pacing therapy 202 may be described as overdrive pacing configured to increase the patient’s the heart rate (i.e., tachycardia pacing) to cause remodeling with rate dependent left ventricle chamber volume expansion and increased compliance. Details regarding cardiac remodeling pacing may be further provided in U.S. Patent No. 11,318,314 entitled “Delivery of Cardiac Pacing Therapy for Cardiac Remodeling” and issued on May 3, 2022, which is herein incorporated by reference in its entirety. Further, cardiac remodeling pacing therapy 202 may be described as a pacing therapy specifically configured to reverse or mitigate the adverse structural, electrical, and functional changes in the heart often associated with heart disease, worsening heart failure, chronic stress, and the like. Additionally, cardiac remodeling pacing therapy 202 may be described as being designed to increase ventricular dilation, reduce ventricular size / hypertrophy, and reestablish altered chamber geometry, which may have resulted from heart disease, worsening heart failure, chronic stress, and the like. In one or more embodiments, the cardiac remodeling pacing therapy 202 may include delivering atrial and / or ventricular pacing at a remodeling rate. The remodeling rate may be between about 80 beats per minute (bpm) and 150 bpm. In one embodiment, the remodeling rate is 110 bpm. In one or more embodiments, the remodeling rate may be greater than or equal to 80 bpm, greater than or equal to 90 bpm, greater than or equal to 100 bpm, greater than or equal to 110 bpm, greater than or equal to 120 bpm, or greater than or equal to 130 bpm, and / or less than or equal to 140 bpm, less than or equal to 125 bpm, less than or equal to 115 bpm, less than or equal to 105 bpm, or less than or equal to 95 bpm. As will be described further herein, the remodeling rate may be adjusted to improve a patient’s heart failure status if the cardiac remodeling pacing therapy is not providing beneficial, or positive, results. The adjustments to the remodeling rate, 1as will be described further herein, may include increases or decreases in the remodeling rate, among other adjustments.

[0064] The cardiac remodeling pacing therapy 202 may often only be delivered for one or more remodeling sessions during a remodeling period of time, or remodeling time period, while the patient is at rest, at sleep, and / or at a consistent state, which may be determined using, at least, the mechanical activity sensor 11 described herein. One or more illustrative processes related to initiating, or triggering, cardiac remodeling pacing therapy sessions are described in U.S. Pat. App. Pub. No. 2023 / 0241401 entitled “Activity Detection for Cardiac Remodeling Pacing” to Ippolito et al. and published on August 3, 2023, which is incorporated by reference herein in its entirety. The remodeling period of time may be between about 1 hour and 12 hours, and each remodeling session may be between about 20 minutes and 6 hours. In one embodiment, the remodeling period of time is 12 hours and may include 2 remodeling sessions, each remodeling session being 6 hours. It is to be understood that, despite being a single process box in the FIG. 6, the delivery of cardiac remodeling pacing therapy 202 may be ongoing and recurrent such as recurring every night.

[0065] The method 200 further includes recurrently assessing the cardiac remodeling pacing therapy 204. The cardiac remodeling pacing therapy may be assessed to determine whether the cardiac remodeling pacing therapy is beneficial in treating the patient’s heart failure condition. Assessing the cardiac remodeling pacing therapy 204 may be recurrent in that it is performed, or executed, multiple times over the long-term time period when cardiac remodeling pacing therapy is delivered. For example, the recurrent assessment of the cardiac remodeling pacing therapy 204 may occur daily (e.g., at night, while the patient is at rest, while the patient is in a consistent state), weekly, biweekly, or every other day.

[0066] The recurrent assessment of the cardiac remodeling pacing therapy 204 may be generally described as including monitoring at least one physiological parameter 206, determining heart failure status 210, and adjusting the cardiac remodeling pacing therapy 220. As shown, an arrow circles back from adjusting cardiac remodeling pacing therapy 220 to the monitoring at least one physiological parameter 206 to indicate that the processes 206, 210, 220 are recurrent. Additionally, although these processes are shown sequentially, it is understood thatone or more or processes 206, 210, 220 as well as delivering cardiac remodeling pacing therapy 202 may occur concurrently or overlap.

[0067] Monitoring at least one physiological parameter 206 may include measuring any one or more physiological parameters using any intracardiac device (e.g., implantable medical device 10) or extracardiac device (e.g., separate medical device 50) that may be useful in determining the patient’s heart failure status. For example, at least one physiological parameter may include various heart sounds and / or one or more metrics or parameters related thereto. More specifically, the amplitudes, relative time intervals, durations, areas under the curve, maximum slope, maximum steepness and / or first derivative of one or more of the SI, S2, S3, and S4 heart sounds may be monitored or measured, which may be useful in determining a patient’s heart failure status as will be described further herein.

[0068] The first heart sound, SI, corresponds to the start of ventricular systole. Ventricular systole begins when an action potential conducts through the atrioventricular node and quickly depolarizes the ventricular myocardium. This event is distinguished by the QRS complex on an electrocardiogram. As the ventricles contract, the pressure in the ventricles begins to rise, causing abrupt closure of the mitral and tricuspid valves between the ventricles and atria as ventricular pressure exceeds atrial pressure. This valve closure may generate SI. SI generally has a duration of about 150 milliseconds (ms) and a frequency on the order of about 20 to 250 Hertz (Hz). The amplitude of SI may provide a surrogate measurement of left ventricular contractility. Thus, an increase in SI amplitude positively may correlate with an improvement in left ventricular contractility. Other measures, like the pre-ejection period measured from the onset of QRS to SI, may also be used as a surrogate of myocardial contractility index.

[0069] The second heart sound, S2, may be generated by the closure of the aortic and pulmonary valves, near the end of ventricular systole and start of ventricular diastole. S2 may, therefore, be correlated to diastolic pressure in the aorta and the pulmonary artery. S2 generally has a duration of about 120 ms and a frequency on the order of 25 to 350 Hz. The time interval between SI and S2, i.e., S1-S2 time interval may represent the systolic time interval (STI) corresponding to the ventricular isovolumic contraction (pre- ejection) and ejection phase of the cardiac cycle. This S1-S2 time interval, or ejection time, may provide a surrogate measurementfor stroke volume. Furthermore, the ratio of the pre-ejection period (Q-Sl) to S1-S2 time may be used as an index of myocardial contractility.

[0070] The third heart sound, S3, is associated with early, passive diastolic filling of the ventricles, and the fourth heart sound, S4, may be associated with late, active filling of the ventricles due to atrial contraction. The third sound, S3, is generally difficult to hear in a normal patient using a stethoscope, and the fourth sound, S4, is generally not heard in a normal patient. Presence of the third sound, S3, and fourth heart sound, S4, during an examination using a stethoscope may indicate a pathological condition. The S3 and S4 heart sounds may be used in optimizing pace parameters as they relate to the diastolic function of the heart. Generally, the S4 heart sound would be minimized or disappear when an optimal pace parameter is identified and remodeling is proceeding favorably. The increase in amplitude of the S3 heart sound also indicates that remodeling pacing is effectively improving compliance. Other aspects of the SI, S2, S3, and S4 heart sounds and timing thereof that may be useful in cardiac pace parameter optimization as known to one having ordinary skill in the art.

[0071] Further, for example, the at least one physiological parameter may include electrocardiograms, orientation of the patient, temperature of the patient, impedance of intracardiac fluid status and / or thoracic cavity fluid volume, magnetic field of one or more portions of the patient, etc. and / or one or more metrics or parameters related thereto.

[0072] For instance, impedance indicative of one or more of intracardiac fluid status and thoracic cavity fluid volume, may be measured and used to represent as a physiological parameter to determine heart failure status. In one or more embodiments, the implantable medical device 10 and / or separate medical device 50 described herein may measure an impedance signal by injecting a current and measuring a voltage between electrodes of an electrode vector configuration (e.g., selected electrodes). For example, the implantable medical device 10 and / or separate medical device 50 may measure an impedance signal by injecting a current (e.g., a non-pacing threshold current) between a first electrode (e.g., a ventricular electrode) and a second electrode (e.g., located proximate the tricuspid valve, located subdermal with an extracardiac device, etc.) and measuring a voltage between the first and second electrodes. One will recognize that other vector pair configurations may be used for stimulation and measurement. Impedance can be measured between any set of electrodes that encompass thetissue (e.g., thoracic cavity) or cardiac chamber of interest. The impedance vectors can be configured to encompass a particular anatomical area of interest, such as the atria, ventricles, or thoracic cavity.

[0073] As used herein, the term “impedance signal” is not limited to a raw impedance signal. It should be implied that raw impedance signals may be processed, normalized, and / or filtered (e.g., to remove artifacts, noise, static, electromagnetic interference (EMI), and / or extraneous signals) to provide the impedance signal. Further, the term “impedance signal” may include various mathematical derivatives thereof including real and imaginary portions of the impedance signal, a conductance signal based on the impedance (i.e., the reciprocal or inverse of impedance), etc. In other words, the term “impedance signal” may be understood to include conductance signals, i.e., signals that are the reciprocal of the impedance signal.

[0074] In one or more embodiments, impedance (e.g., across one or more chambers of the heart, across the thoracic cavity, etc.) may be monitored for use in determining heart failure status (e.g., impedance may be indicative of fluid accumulation), and in turn, potentially adjust cardiac remodeling pacing therapy, for example, based on, or in response, impedance. One or more processes of using heart sounds and impedance to adjust cardiac therapy are described in U.S. Patent No. 9,707,399 entitled “Cardiac Resynchronization Therapy Optimization Based on Intracardiac Impedance and Heart Sounds” and issued on July 18, 2017, which is incorporated herein by reference in its entirety.

[0075] Generally, it is to be understood that the method 200 may monitor any physiological parameter that may be useful in determining a patient’s heart failure status. Additionally, it is to be understood that a single physiological parameter may be monitored in method 200 or more than one physiological parameter.

[0076] Assessment of the cardiac remodeling pacing therapy 204 further includes determining a heart failure status 210 based on the at least one physiological parameter. In other words, one or more monitored physiological parameters may be evaluated to determine the heart failure status of the patient. In one or more embodiments, the heart failure status may be representative of the patient’s cardiac contractility. In other words, the at least one physiological parameter may be used to determine a representative cardiac contractility value indicative of the patient’s heart failure status. One or more illustrative processes for determining heart failurestatus 210 may be described in U.S. Provisional Pat. No. 63 / 462,080 entitled “Heart Failure Risk Using Mechanical Activity” to Subham Ghosh (MDT A0009508US01) and filed on April 26, 2023, U.S. Patent No. 11,318,314 entitled “Delivery of Cardiac Pacing Therapy for Cardiac Remodeling” and issued on May 3, 2022, U.S. Pat. No. 11,701,517 entitled “Cardiac Resynchronization Therapy Using Accelerometer” and issued on July 18, 2023, U.S. Pat. App. Pub. No. 2022 / 0193419A1 entitled “Method and Apparatus for Monitoring Tissue Fluid Content for Use in an Implantable Cardiac Device” and published on June 23, 2022, U.S. Provisional Patent Application No. 63 / 624,023, filed January 23, 2024 (MDT A0010706), and PCT Patent Application Publication No. WO2024 / 091797 Al entitled “Implantable Medical Device to Detect Health Event” and published on May 2, 2024, each of which are incorporated by reference herein in their entireties.

[0077] In one embodiment, determining the heart failure status 210 based on at least one physiological parameter includes comparing the at least one physiological parameter to a heart failure threshold. For example, if the physiological parameter is greater than the heart failure threshold, it may indicate that the patient’s heart failure status is improving, and conversely, if the physiological parameter is less than the heart failure threshold, it may indicate that the patient’s heart failure status is declining. Further, if the physiological parameter is the same as or equal to the heart failure threshold (e.g., withing a selected percentage such as 2%), it may indicate that the patient’s heart failure status has not changed (e.g., no change).

[0078] It is to be understood that the heart failure threshold value may be different for each at physiological parameter. Likewise, whether the measured physiological parameter value is greater than, less than, or equal to heart failure threshold may indicate different heart failure statuses depending on which physiological parameter is be analyzed. Further, the heart failure threshold may be an absolute value based, for example, on a patient’s characteristics such as, e.g., age, sex, size, weight, height, heart chamber size, etc. and / or on a patient population profile.

[0079] Still further, the heart failure threshold may be a baseline value of the physiological parameter. For example, prior to or initially with the delivery of cardiac remodeling pacing therapy, the physiological parameter may be monitored or measured resulting in baseline value. The heart failure threshold may then be set or programmed to the baseline value or a selected percentage, such as 90%, of the baseline value.

[0080] In one embodiment, determining a heart failure status 210 may include generating, or calculating, an aggregate heart failure value based on at least one physiological parameter measured over an aggregation period of time or aggregation time period. The aggregation period of time may be between about 5 minutes and 8 hours. In one embodiment, the aggregation period of time is 6 hours. Then, the heart failure status may be determined, or generated, based on the aggregate heart failure value. The aggregate heart failure value may be described a statistical representative of the at least one physiological parameter that reduces noise and outlying values.

[0081] For example, in one embodiment, if the physiological parameter is SI amplitude, the SI amplitude may be measured for each cardiac cycle over 1 hour resulting a plurality of SI amplitude values, and then a statistical aggregation, such as an average, of the plurality of SI amplitude values may be calculated resulting in an average SI amplitude, which may be the aggregate heart failure value. The heart failure status may then be determined based on the aggregate heart failure value. For example, the average SI amplitude may be compared a SI threshold value. If the average SI amplitude is greater than the SI threshold value (e.g., by more than the selected percentage 2%), then the patient’s heart failure status may be determined to be “improved.” If the average SI amplitude is substantially the same as the SI threshold value (e.g., within the selected percentage such as 4%), then the patient’s heart failure status may be determined to be “no change.” If the average SI amplitude is less the SI threshold value (e.g., by less than the selected percentage 2%), then the patient’s heart failure status may be determined to be “declined.”

[0082] In one embodiment, determining a heart failure status 210 may include generating, or calculating, a heart failure trend value based on at least one physiological parameter measured over a trend period of time. The trend period of time may be between about 3 days and about 14 days. In one embodiment, the trend period of time is 7 days. Then, the heart failure status may be determined, or generated, based on the trend heart failure value. The trend value may be representative of the relative difference, or trend, in one or more physiological parameters over the trend period of time.

[0083] For example, in one embodiment, if the physiological parameter is S1-S2 duration (e.g., ejection time), the S1-S2 duration may be measured for each cardiac cycle over a selected period of time such as 2 hours while the patient is a rest each day over a trend period of time of 7days resulting a plurality of S1-S2 duration values, and then a statistical trend, such as an moving averages, regression analysis, etc., of the plurality of S1-S2 duration values may be determined, or calculated, resulting in a S1-S2 duration trend value, which may be the trend heart failure value. The heart failure status may then be determined based on the trend heart failure value. For example, if the S1-S2 duration trend value indicates an increasing S1-S2 duration, then the patient’s heart failure status may be determined to be “improved,” and conversely, if the S1-S2 duration trend value indicates a decreasing S2 duration, then the patient’s heart failure status may be determined to be “declined.” Further, if the S1-S2 duration trend value is steady or consistent (e.g., within the selected percentage such as 3%), then the patient’s heart failure status may be determined to be “no change.”

[0084] Assessment of the cardiac remodeling pacing therapy 204 further includes adjusting the cardiac remodeling pacing therapy 220 based on the heart failure status. In other words, the heart failure status of the patient may be used to modify, or titrate, the cardiac remodeling pacing therapy. For example, generally, if the patient has a declining heart failure status or has no change in heart failure status, then the cardiac remodeling pacing therapy may be adjusted. Further, if the patient has an improving heart failure status, the cardiac remodeling pacing therapy may be maintained (e.g., no adjustment). Additionally, if the cardiac remodeling pacing therapy has been adjusted for a selected number of cycles or sessions, over a selected termination period, or until the adjustments are exhausted without realizing, or seeing, an improving heart failure status, then the method may terminate, or cease, the cardiac remodeling pacing therapy as will be further described herein with respect to FIG. 7. Further, if the heart failure status has indicated an improvement over a selected number of cycles or sessions or over a selected remodeling period of time or reached a target heart failure status, then the method may shift, or change, the cardiac remodeling pacing therapy to a cardiac remodeling maintenance therapy that is configured to maintain the cardiac remodeling that took place (as opposed to continuing to remodel the heart) as will be further described herein with respect to FIG. 7.

[0085] Another illustrative method 201 of delivering cardiac remodeling pacing therapy and assessing the cardiac remodeling pacing therapy is depicted in FIG. 7. The method 201 includes delivering cardiac remodeling pacing therapy 202 and the assessing the cardiac remodeling pacing therapy 204 similar to that of method 200 but including further detail with respect to, atleast, adjusting the cardiac remodeling pacing therapy 220. For example, delivering cardiac remodeling pacing therapy 202, monitoring physiological parameters 206, and determining heart failure status 210 may be substantially the same or similar to those processes described herein with respect to FIG. 6, and as such, will not be described further below.

[0086] Determining heart failure status 210 of the method 201 results in one of the three following conditions: no change in heart failure status; a decline in heart failure status; and an improvement in heart failure status. As shown, adjusting the cardiac remodeling pacing therapy 220 in response to “no change” in heart failure status includes increasing aggressiveness of the cardiac remodeling pacing therapy 222. Increasing aggressiveness of the cardiac remodeling pacing therapy 222 is intended to titrate or tune the cardiac remodeling pacing therapy such that the cardiac remodeling pacing therapy may provide a cardiac benefit to the patient. Increasing the aggressiveness of the cardiac remodeling pacing therapy 222 may include one or more of increasing the remodeling rate, increasing the remodeling period of time, and increasing a number of sessions per day of cardiac remodeling pacing therapy. For example, the remodeling rate may be increased by a fixed value, such as, e.g., 10 bpm, or percentage, such as, e.g., 10%. For instance, if the remodeling rate was 110 bpm and it was determined that the patient’s heart failure status has no change, then the remodeling rate may be increased by 10 bpm resulting in 120 bpm for the next cardiac remodeling pacing therapy session. Further, for example, the remodeling time period may be increased by a fixed value, such as, e.g., 1 hour, or a percentage, such as, e.g., 10%. For instance, if the remodeling time period was 6 hours and it was determined that the patient’s heart failure status has no change, then the remodeling time period may be increased by 10% resulting in a 6-hour, 36-minute, remodeling time period for the next cardiac remodeling pacing therapy session.

[0087] Further, adjusting the cardiac remodeling pacing therapy 220 in response to a “decline” in heart failure status includes decreasing aggressiveness of the cardiac remodeling pacing therapy 224. Decreasing aggressiveness of the cardiac remodeling pacing therapy 224 is intended to titrate or tune the cardiac remodeling pacing therapy to avoid any potential negative effects being caused by the cardiac remodeling pacing therapy. Decreasing the aggressiveness of the cardiac remodeling pacing therapy 224 may include one or more of decreasing the remodeling rate, decreasing the remodeling period of time, and decreasing a number of sessionsper day of cardiac remodeling pacing therapy. For example, the remodeling rate may be decreased by a fixed value, such as, e.g., 15 bpm, or percentage, such as, e.g., 15%. For instance, if the remodeling rate was 110 bpm and it was determined that the patient’s heart failure status is declining, then the remodeling rate may be decreased by 15% resulting in 93.5 bpm for the next cardiac remodeling pacing therapy session. Further, for example, the remodeling time period may be decreased by a fixed value, such as, e.g., 1 hour, or a percentage, such as, e.g., 15%. For instance, if the remodeling time period was 6 hours and it was determined that the patient’s heart failure status is declining, then the remodeling time period may be decreased by 1 hour resulting in a 5-hour remodeling time period for the next cardiac remodeling pacing therapy session.

[0088] Nonetheless, the increasing or decreasing the cardiac remodeling pacing therapy may not result in effective cardiac remodeling pacing therapy or a benefit the patient’s cardiac health. Thus, the method 201 further includes determining whether to terminate, or cancel, the cardiac remodeling pacing therapy 230. For example, the cardiac remodeling pacing therapy may be terminated 230 in response to the heart failure status in decline or no change over a plurality of the recurrent assessments. For instance, the number of recurrent assessments that results in a decline or no change in the heart failure status may be compared to a termination value or count, and if the number of recurrent assessments that results in a decline or no change in the heart failure status exceeds the termination value, then the cardiac remodeling pacing therapy may be terminated. The termination value or count may be between about 2 and about 10. Additionally, in one or more embodiments, termination may only be triggered, or initiated, in response to the number of consecutive recurrent assessments that results in a decline or no change in the heart failure status exceeding the termination value. Still further, in one or more embodiments, the number of recurrent assessments that results in a decline in heart failure status and the number of recurrent assessments that results in no change in heart failure status may be counted separately and compared separately to a termination value to determine whether to terminate the cardiac remodeling pacing therapy.

[0089] Further, for example, the cardiac remodeling pacing therapy may be terminated 230 in response to exhaustion of adjustments to the cardiac remodeling pacing therapy to decrease and increase aggressiveness of the cardiac remodeling therapy. In other words, there may only be a certain number of adjustments available to one or more parameters, or settings, of the cardiacremodeling pacing therapy, and thus, when the certain number of adjustments have all been made and the heart failure status remains unchanged or declining, then it may be determined to terminate the cardiac remodeling pacing therapy 230. For instance, there may be maximum remodeling rate, such as, e.g., 140 bpm, that may not be exceeded when delivering cardiac remodeling pacing therapy, and in response to no change in heart failure status, the remodeling rate may be incrementally increased to the 140 bpm. If, upon further assessment of the cardiac remodeling pacing therapy when at 140 bpm, the patient’s heart failure status remains unchanged, then it may be determined that adjustment to the remodeling rate of the cardiac remodeling pacing therapy may be exhausted, and if no other adjustments to the cardiac remodeling pacing therapy may be made to increase the aggressiveness, then it may be determined to terminate the cardiac remodeling pacing therapy 230.

[0090] Further, for instance, there may be minimum remodeling period of time, such as, e.g., 1 hour, that the remodeling time period may not be less than, and in response to a declining heart failure status, the remodeling period of time may be decreased to the 1 -hour limit. If, upon further assessment of the cardiac remodeling pacing therapy when the remodeling period of time is 1 hour, the patient’s heart failure status remains declining, then it may be determined that adjustment to the remodeling period of time of the cardiac remodeling pacing therapy may be exhausted, and if no other adjustments to the cardiac remodeling pacing therapy are available to decrease the aggressiveness, then it may be determined to terminate the cardiac remodeling pacing therapy 230.

[0091] If it is determined to terminate, or cease, the cardiac remodeling pacing therapy 230, the method 201 may terminate (e.g., cancel, stop, cease, etc.) the cardiac remodeling pacing therapy 232. Additionally, if the cardiac remodeling pacing therapy is terminated 232, an alert or message may be provided to the patient via telemetry to an external device such as a smartphone and / or to a clinician via a network.

[0092] Still further, adjusting the cardiac remodeling pacing therapy 220 in response to an “improvement” in heart failure status includes maintaining aggressiveness of the cardiac remodeling pacing therapy 226. Maintaining aggressiveness of the cardiac remodeling pacing therapy 226 is intended to maintain the effective cardiac remodeling pacing therapy to continue the beneficial effects being provided by the cardiac remodeling pacing therapy. In oneembodiment, maintaining aggressiveness of the cardiac remodeling pacing therapy 226 includes not changing or not substantially changing any settings or parameters of the cardiac remodeling pacing therapy. In one embodiment, maintaining aggressiveness of the cardiac remodeling pacing therapy 226 includes alternating between days of less aggressive and more aggressive cardiac remodeling pacing therapy.

[0093] The maintenance of the cardiac remodeling pacing therapy may result in a patient’s heart being effectively or successfully remodeled, and thus, the cardiac remodeling pacing therapy may not be further needed. Thus, the method 201 further includes determining whether to start, or initiate, cardiac remodeling maintenance therapy 240. The cardiac remodeling maintenance therapy 242 may be similar to the cardiac remodeling pacing therapy but less aggressive to maintain the cardiac remodeling provided by the cardiac remodeling pacing therapy. For example, the cardiac remodeling maintenance therapy may be initiated 240 in response to the heart failure status achieving a target heart failure status. For example, the target heart failure status may be a target percentage for one or more physiological parameters or target absolute value for one or more physiological parameters to reach. For instance, the target heart failure status may be achieved, or met, when a presently measured SI amplitude is greater than or equal to 30% greater than a baseline SI amplitude. Thus, if the presently measured SI amplitude is greater than or equal to 30% greater than a baseline SI amplitude, then it may be determined that the heart failure status target has been met and cardiac remodeling maintenance therapy 240 may be initiated or triggered. It is to be understood that target percentages or target absolute values for the physiological parameters may vary patient-to-patient, and may be set, or programmed, by a clinician upon evaluating the patient’s heart failure status prior to beginning the cardiac remodeling pacing therapy.

[0094] Further, for example, the cardiac remodeling maintenance therapy may be initiated 240 in response to the heart failure status showing improvement over a plurality of the recurrent assessments. For instance, the number of recurrent assessments that results in an improvement in the heart failure status may be compared to a maintenance value, and if the number of recurrent assessments that results in an improvement in the heart failure status exceeds the maintenance value, then the cardiac remodeling maintenance therapy may be initiated 242. The maintenance value may be between about 2 and about 10. Additionally, in one or more embodiments, cardiacremodeling maintenance therapy 242 may only be triggered, or initiated, in response to the number of consecutive recurrent assessments that results in an improvement in the heart failure status exceeding the maintenance value.

[0095] Another illustrative method 400 of delivering cardiac remodeling pacing therapy and assessing the cardiac remodeling pacing therapy is depicted in FIG. 8. Illustrative method 400 includes implanting an implantable pacing device, or implantable medical device, and configuring the implantable pacing device to deliver traditional pacing therapy 402, such as, e.g., atrioventricular synchronous pacing, cardiac resynchronization therapy, etc. The implantable pacing device may be a leadless implantable pacing device implanted in the right atrium as described herein with respect to FIGS. 1-5.

[0096] A baseline cardiac status may be detected 404 using an accelerometer of the implantable pacing device. In one embodiment, a baseline of SI amplitude and S2 amplitude may be determined. The baseline cardiac status may be detected without the delivery of pacing therapy and when the patient is in a consistent such as, e.g., at night.

[0097] The cardiac remodeling pacing therapy may then be “turned on,” or initiated, 406. For example, the cardiac remodeling pacing therapy may include nocturnal pacing at a nominal remodeling rate such as, e.g., 110 bpm. The cardiac remodeling pacing therapy may be delivered 406 for a designated period of time such as, e.g., one or more weeks.

[0098] The method 400 further includes nightly detection of cardiac status 408 using the accelerometer of the implantable pacing device. In one embodiment, the SI amplitude and the S2 amplitude may be determined and compared to the baseline values of SI amplitude and the S2 amplitude measured during process 404. The cardiac status may be trended (e.g., for display) and stored on the implantable pacing device and / or an external device such as the separate medical device 50 described herein with respect to FIG. 1 or a smartphone.

[0099] If no change in the contractility is detected after the designated time period (e.g., one or more weeks), then the cardiac remodeling pacing therapy may be adjusted 422. For example, no change in the contractility may be detected if, or in response to, a percent change from the baseline value being less than a percentage threshold such as, e.g., 2%, or absolute amplitude value not surpassing an amplitude threshold. In response to no change in the contractility, themethod 400 may adjust the cardiac remodeling pacing therapy. For example, the nocturnal remodeling rate may be increased by 20 bpm.

[0100] If a decline in the contractility is detected after the designated time period (e.g., one or more weeks), then the cardiac remodeling pacing therapy may be adjusted 424. For example, a decline in the contractility may be detected if, or in response to, a negative percent change from the baseline value is greater or equal to than a percentage threshold such as, e.g., 2%, or an absolute amplitude value is less than an amplitude threshold. In response to a decline in the contractility, the method 400 may adjust the cardiac remodeling pacing therapy. For example, the nocturnal remodeling rate may be decreased by 20 bpm.

[0101] If an improvement in the contractility is detected after the designated time period (e.g., one or more weeks), then the cardiac remodeling pacing therapy may be maintained 426. For example, an improvement in the contractility may be detected if, or in response to, a positive percent change from the baseline value is greater or equal to than a percentage threshold such as, e.g., 2%, or an absolute amplitude value is greater than an amplitude threshold.

[0102] Additionally, in response to each of detection of no change and a decline in the contractility, a detection count may be increased. The detection count may be compared to a threshold count (which may also be referred to as a termination value) 440 to determine whether to “turn off’ the cardiac remodeling pacing therapy. More specifically, if the detection count is greater than the threshold count 440, then the method 400 may “turn off’ the cardiac remodeling pacing therapy 442, and conversely, if the detection count is less than or equal to the threshold count 440, then the method 400 may return to nightly detection of cardiac status 408 and delivery of cardiac remodeling pacing therapy.

[0103] Still further, if the method 400 “turns off’ the cardiac remodeling pacing therapy 422, the method 400 may continue to execute, or perform, nightly detection of cardiac status 444, which may be substantially similar to the nightly detection of cardiac status 408, to generate data for recordation and to provide to the patient and / or a clinician via telemetry to an external device such as a smartphone and / or to a clinic via a network.ILLUSTRATIVE EXAMPLES

[0104] Example Exl : A system comprising: a computing apparatus comprising processing circuitry and configured to: initiate delivery of cardiac remodeling pacing therapy to a patient’s heart; and recurrently assess the cardiac remodeling pacing therapy comprising: monitor at least one physiological parameter of the patient’s heart; determine a heart failure status based on the at least one physiological parameter; and adjust cardiac remodeling pacing therapy being delivered to the patient’s heart based on the heart failure status.

[0105] Example Ex2: A method comprising: initiating delivery of cardiac remodeling pacing therapy to a patient’s heart; and recurrently assessing the cardiac remodeling pacing therapy comprising: monitoring at least one physiological parameter of the patient’s heart; determining a heart failure status based on at least one physiological parameter; and adjusting cardiac remodeling pacing therapy being delivered to the patient’s heart based on the heart failure status.

[0106] Example Ex3 : The system as in Example Exl or the method as in Example Ex2, wherein the system further comprises or the method further comprises providing an implantable medical device, wherein the implantable medical device comprises an atrial electrode configured to be implanted in an atrium of the patient’s heart to deliver the cardiac remodeling pacing therapy, wherein delivering cardiac remodeling pacing therapy comprises delivering pacing therapy to the atrium using the atrial electrode.

[0107] Example Ex4: The system as in Example Exl or the method as in Example Ex2, wherein the system further comprises or the method further comprises providing an implantable medical device, wherein the implantable medical device comprises: an atrial electrode implanted in the right atrium of the patient’s heart to deliver cardiac therapy to or sense electrical activity of the right atrium of the patient’s heart; and a ventricular electrode implanted from the triangle of Koch region of the right atrium of the patient’s heart to deliver cardiac therapy to or sense electrical activity of the left ventricle inthe basal region, septal region, or basal-septal region of the left ventricular myocardium of the patient’s heart.

[0108] Example Ex5: The system or method as in any one of Examples Ex3-4, wherein the implantable medical device is leadless.

[0109] Example Ex6: The system or method as in any one of Examples Exl-5, wherein the at least one physiological parameter comprises mechanical activity measured using a mechanical activity sensor positioned proximate the patient’s heart.

[0110] Example Ex7: The system or method as in Example Ex6, wherein the mechanical activity sensor comprises one or more of an accelerometer and a microphone.

[0111] Example Ex8: The system or method as in any one of Examples Exl-7, wherein the at least one physiological parameter comprises one or more of SI amplitude, SI duration, area under the curve of SI, S2 amplitude, S2 duration, and area under the curve of S2.

[0112] Example Ex9: The system or method as in any one of Examples Exl-7, wherein the at least one physiological parameter comprises orientation of the patient measured using a gyroscope, temperature of the patient measured using a temperature sensor, impedance of one or more portions of the patient measured using one or more electrodes, and magnetic field of the patient measured using magnetometer.

[0113] Example ExlO: The system or method as in any one of Examples Exl-8, wherein the system further comprises or the method further comprises providing an extracardiac device, wherein one or both of the monitoring of the at least one physiological parameter of the patient’s heart and the determining the heart failure status based on the at least one physiological parameter are performed by the extracardiac device.

[0114] Example Exl 1 : The system or method as in any one of Examples Exl-10, wherein the recurrently assessing the cardiac remodeling pacing therapy comprises recurrently assessing the cardiac remodeling pacing therapy at least once a night.

[0115] Example Exl 2: The system or method as in any one of Examples Exl-11, wherein the computing apparatus is further configured to execute or the method further comprises monitoring a state of the patient,31wherein the recurrently assessing the cardiac remodeling pacing therapy comprises recurrently assessing the cardiac remodeling pacing therapy in response to the state of the patient indicating a consistent physiological condition.

[0116] Example Exl3: The system or method as in any one of Examples Exl-12, wherein the computing apparatus is further configured to execute or the method further comprises monitoring a state of the patient, wherein the recurrently assessing the cardiac remodeling pacing therapy comprises recurrently assessing the cardiac remodeling pacing therapy in response to the state of the patient indicating that the patient is at rest.

[0117] Example Exl4: The system or method as in any one of Examples Exl-13, wherein the determining the heart failure status based on the at least one physiological parameter comprises: generating an aggregate heart failure value based on the at least one physiological parameter measured over a period of time; and determining the heart failure status based on the aggregate heart failure value.

[0118] Example Exl 5: The system or method as in Example Exl4, wherein the period of time is less than 8 hours.

[0119] Example Exl 6: The system or method as in any one of Examples Exl-15, wherein the determining the heart failure status based on the at least one physiological parameter comprises: generating a heart failure trend value based on the at least one physiological parameter measured over a trend period of time greater than or equal to 3 days; and determining the heart failure status based on the heart failure trend value.

[0120] Example Exl7: The system or method as in any one of Examples Exl-16, wherein the determining the heart failure status based on the at least one physiological parameter comprises comparing the at least one physiological parameter to a heart failure threshold.

[0121] Example Exl 8: The system or method as in any Example Exl 7, wherein the computing apparatus is further configured to execute or the method further comprises determining a baseline value of the at least one physiological parameter, wherein the heart failure threshold is a selected percentage of the baseline value.

[0122] Example Exl9: The system or method as in any one of Examples Exl-18, wherein the heart failure status is one of no change, improvement, and decline, wherein adjusting the cardiac remodeling pacing therapy based on the heart failure status comprises: decreasing aggressiveness of the cardiac remodeling pacing therapy in response to response to the heart failure status being the decline; and increasing aggressiveness of the cardiac remodeling pacing therapy in response to response to the heart failure status being the no change.

[0123] Example Ex20: The system or method as in Example Exl9, wherein the computing apparatus is further configured to execute or the method further comprises terminating the cardiac remodeling pacing therapy in response to the heart failure status being the decline or the no change over a plurality of the recurrent assessments.

[0124] Example Ex21 : The system or method as in Example Ex 19, wherein the computing apparatus is further configured to execute or the method further comprises terminating the cardiac remodeling pacing therapy in response to exhaustion of adjustments to the cardiac remodeling pacing therapy to decrease and increase aggressiveness of the cardiac remodeling therapy.

[0125] Example Ex22: The system or method as in any one of Examples Exl9-21, wherein the computing apparatus is further configured to execute or the method further comprises maintaining aggressiveness of the cardiac remodeling pacing therapy in response to the heart failure status being the improvement.

[0126] Example Ex23: The system or method as in any one of Examples Exl9-22, wherein the computing apparatus is further configured to execute or the method further comprises changing the cardiac remodeling pacing therapy to cardiac remodeling maintenance therapy in response to the heart failure status reaching a target heart failure status indicative a successfully remodeling of the patient’s heart, wherein the cardiac remodeling maintenance therapy is configured to maintain the cardiac remodeling provided by the cardiac remodeling pacing therapy.

[0127] All references and publications cited herein are expressly incorporated herein by reference in their entirety for all purposes, except to the extent any aspect directly contradicts this disclosure.

[0128] Unless otherwise indicated, all numbers expressing feature sizes, amounts, and physical properties used in the specification and claims may be understood as being modified either by the term “exactly” or “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the foregoing specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by those skilled in the art utilizing the teachings disclosed herein or, for example, within typical ranges of experimental error.

[0129] As used herein, the term “configured to” may be used interchangeably with the terms “adapted to” or “structured to” unless the content of this disclosure clearly dictates otherwise.

[0130] The singular forms “a,” “an,” and “the” encompass embodiments having plural referents unless its context clearly dictates otherwise.

[0131] As used herein, “have,” “having,” “include,” “including,” “comprise,” “comprising” or the like are used in their open-ended sense, and generally mean “including, but not limited to.” It will be understood that “consisting essentially of,” “consisting of,” and the like are subsumed in “comprising,” and the like.

[0132] Reference to “one embodiment,” “an embodiment,” “certain embodiments,” or “some embodiments,” etc., means that a particular feature, configuration, composition, or characteristic described in connection with the embodiment is included in at least one embodiment of the disclosure. Thus, the appearances of such phrases in various places throughout are not necessarily referring to the same embodiment of the disclosure. Furthermore, the particular features, configurations, compositions, or characteristics may be combined in any suitable manner in one or more embodiments.

[0133] The words “preferred” and “preferably” refer to embodiments of the disclosure that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or morepreferred embodiments does not imply that other embodiments are not useful and is not intended to exclude other embodiments from the scope of the disclosure.

Claims

CLAIMSWhat is claimed is:

1. A system comprising: a computing apparatus comprising processing circuitry and configured to: initiate delivery of cardiac remodeling pacing therapy to a patient’s heart; and recurrently assess the cardiac remodeling pacing therapy comprising: monitor at least one physiological parameter of the patient’s heart; determine a heart failure status based on the at least one physiological parameter; and adjust cardiac remodeling pacing therapy being delivered to the patient’s heart based on the heart failure status.

2. A method comprising: initiating delivery of cardiac remodeling pacing therapy to a patient’s heart; and recurrently assessing the cardiac remodeling pacing therapy comprising: monitoring at least one physiological parameter of the patient’s heart; determining a heart failure status based on at least one physiological parameter; and adjusting cardiac remodeling pacing therapy being delivered to the patient’s heart based on the heart failure status.

3. The system as in claim 1 or the method as in claim 2, wherein the system further comprises or the method further comprises providing an implantable medical device, wherein the implantable medical device comprises an atrial electrode configured to be implanted in an atrium of the patient’s heart to deliver the cardiac remodeling pacing therapy, wherein delivering cardiac remodeling pacing therapy comprises delivering pacing therapy to the atrium using the atrial electrode.

4. The system as in claim 1 or the method as in claim 2, wherein the system further comprises or the method further comprises providing an implantable medical device, wherein the implantable medical device comprises: an atrial electrode implanted in the right atrium of the patient’s heart to deliver cardiac therapy to or sense electrical activity of the right atrium of the patient’s heart; and a ventricular electrode implanted from the triangle of Koch region of the right atrium of the patient’s heart to deliver cardiac therapy to or sense electrical activity of the left ventricle in the basal region, septal region, or basal-septal region of the left ventricular myocardium of the patient’s heart.

5. The system or method as in any one of claims 3 and 4, wherein the implantable medical device is leadless.

6. The system or method as in any one of claims 1-5, wherein the at least one physiological parameter comprises mechanical activity measured using a mechanical activity sensor positioned proximate the patient’s heart.

7. The system or method as in any one of claims 1-6, wherein the at least one physiological parameter comprises one or more of SI amplitude, SI duration, area under the curve of SI, S2 amplitude, S2 duration, and area under the curve of S2.

8. The system or method as in any one of claims 1-7, wherein the at least one physiological parameter comprises orientation of the patient measured using a gyroscope, temperature of the patient measured using a temperature sensor, impedance of one or more portions of the patient measured using one or more electrodes, and magnetic field of the patient measured using magnetometer.

9. The system or method as in any one of claims 1-8, wherein the system further comprises or the method further comprises providing an extracardiac device, wherein one or both of the monitoring of the at least one physiological parameter of the patient’s heart and the determiningthe heart failure status based on the at least one physiological parameter are performed by the extracardiac device.

10. The system or method as in any one of claims 1-9, wherein the recurrently assessing the cardiac remodeling pacing therapy comprises recurrently assessing the cardiac remodeling pacing therapy at least once a night.

11. The system or method as in any one of claims 1-10, wherein the computing apparatus is further configured to execute or the method further comprises monitoring a state of the patient, wherein the recurrently assessing the cardiac remodeling pacing therapy comprises recurrently assessing the cardiac remodeling pacing therapy in response to the state of the patient indicating a consistent physiological condition.

12. The system or method as in any one of claims 1-11, wherein the computing apparatus is further configured to execute or the method further comprises monitoring a state of the patient, wherein the recurrently assessing the cardiac remodeling pacing therapy comprises recurrently assessing the cardiac remodeling pacing therapy in response to the state of the patient indicating that the patient is at rest.

13. The system or method as in any one of claims 1-12, wherein the determining the heart failure status based on the at least one physiological parameter comprises: generating an aggregate heart failure value based on the at least one physiological parameter measured over a period of time; and determining the heart failure status based on the aggregate heart failure value.

14. The system or method as in any one of claims 1-13, wherein the determining the heart failure status based on the at least one physiological parameter comprises: generating a heart failure trend value based on the at least one physiological parameter measured over a trend period of time greater than or equal to 3 days; and determining the heart failure status based on the heart failure trend value.

15. The system or method as in any one of claims 1-14, wherein the heart failure status is one of no change, improvement, and decline, wherein adjusting the cardiac remodeling pacing therapy based on the heart failure status comprises: decreasing aggressiveness of the cardiac remodeling pacing therapy in response to response to the heart failure status being the decline; and increasing aggressiveness of the cardiac remodeling pacing therapy in response to response to the heart failure status being the no change.

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