Respiration-based cardiac remodeling pacing therapy

Abstract

Systems, devices, and methods for performing respiration-based cardiac remodeling pacing therapies are described in the present disclosure. In some embodiments, respiration of a patient may be monitored, and cardiac remodeling pacing and pacing lower limits for supporting pacing therapy delivered to the patient may be adjusted based on the monitored respiration to achieve or restore respiratory sinus arrhythmias.

Description

[0001] This application claims the benefit of U.S. patent application serial number 18 / 101,799, filed January 26, 2023, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates to respiration-based cardiac remodeling pacing therapies, eg, for treating heart failure (HF), and more particularly to systems, devices, and methods for performing such respiration-based cardiac remodeling pacing therapies.

[0003] HF 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., the muscle contracts) and how well the heart relaxes and fills with blood. The ejection fraction is a measure of how much blood is pumped out of the left ventricle (LV) with each contraction. When the left ventricle pumps, not all of the blood in the ventricle leaves. A normal ejection fraction is greater than about 50%. Heart failure with preserved ejection fraction (HFpEF) occurs when the left ventricle does not fill with blood as normal, but the ventricle can pump well. For example, the ventricle is rigid or has thick walls, so that the ventricle does not relax to fill with a normal volume of blood. Alternatively, when the muscle contractions are abnormal (e.g., the muscle is too weak to pump properly), the condition is called heart failure with reduced ejection fraction (HFrEF).

[0004] HFpEF patients comprise nearly half of the heart failure population and continue to increase in prevalence relative to HFrEF patients. Although HFpEF patients experience outcomes that are as poor as those experienced by HFrEF patients, there are no evidence-based therapies that improve mortality and morbidity. The present technology relates to algorithms for selecting pacing therapy for a heart failure patient, such as a HFpEF patient, based on monitored patient parameters that also take into account interactions between various pacing therapies. The algorithms and pacing therapies can be implemented by implantable medical devices (IMDs), such as implantable cardioverter-defibrillators (ICDs), cardiovascular implantable electronic devices (CIEDs), pacemakers, and cardiac resynchronization therapy (CRT) devices, which in some cases include defibrillation capabilities (CRT-D devices). Summary of the Invention

[0005] The embodiments described herein relate to exemplary systems, devices, and methods for performing respiration-based cardiac remodeling pacing therapy, for example, for treating heart failure (HF), and more particularly, for treating patients with HF with preserved ejection fraction (HFpEF). Generally speaking, the exemplary systems, devices, and methods can be described as providing support pacing, cardiac remodeling pacing, and adjusting the pacing rate of each of the support pacing and cardiac remodeling pacing based on the patient's monitored or measured respiration to provide or restore respiratory sinus arrhythmia (RSA).

[0006] In addition, the present disclosure can be further described as providing exemplary systems, devices, and methods that combine features for restoring respiratory sinus arrhythmia while allowing an increase in the supported rate during cardiac remodeling pacing periods. By combining respiratory sinus arrhythmia with cardiac remodeling pacing, not only do the exemplary systems, devices, and methods independently provide both features, but cardiac remodeling pacing can also have enhanced efficacy by allowing a higher proportion of paced beats to fall within the therapeutic rate range (e.g., greater than 90 beats per minute) while potentially avoiding symptoms associated with continuous pacing at higher rates. In at least one embodiment, the exemplary systems, devices, and methods can be described as providing a rate setting feature where an effective device lower rate is defined by a supported rate, a maximum remodeling rate, and a respiratory sinus arrhythmia value or amplitude. The maximum remodeling rate can be defined as the maximum pacing rate when cardiac remodeling therapy criteria are met, and the supported rate can be defined as the minimum effective device lower rate.

[0007] An exemplary implantable medical device may include: a pacing electrode positioned near a patient's heart to deliver pacing therapy to the patient's heart; a respiration sensor for determining the patient's respiration rate; and a computing device operably coupled to the pacing electrode and the respiration sensor. The computing device may be configured to deliver pacing using at least the pacing electrode based on a lower rate limit, monitor the patient's respiration via the respiration sensor, and adjust the lower rate limit based on the patient's respiration to restore respiratory sinus arrhythmia (RSA). Additionally, the computing device may be further configured to increase the lower rate limit to provide cardiac remodeling pacing during a remodeling period.

[0008] An exemplary method using, for example, an implantable medical device may include: delivering pacing to a patient's heart based on a rate floor; monitoring the patient's respiration; adjusting the rate floor based on the patient's respiration to restore respiratory sinus arrhythmia (RSA); and increasing the rate floor to provide cardiac remodeling pacing during a remodeling period.

[0009] An exemplary implantable medical device may include: a pacing electrode positioned near a patient's heart to deliver pacing therapy to the patient's heart; a respiration sensor for determining the patient's respiration rate; and a computing device operably coupled to the pacing electrode and the respiration sensor. The computing device may be configured to switch between delivering support pacing based on a support pacing rate using at least the pacing electrode or delivering remodeling pacing based on a remodeling pacing rate using at least the pacing electrode to provide remodeling. The remodeling pacing rate may be greater than the support pacing rate. The computing device may be further configured to monitor the patient's respiration rate using the respiration sensor and adjust the remodeling pacing rate and the support pacing rate based on the patient's respiration rate to restore respiratory sinus arrhythmia (RSA).

[0010] The above summary is not intended to describe each disclosed embodiment or every embodiment of the present disclosure.The figures and detailed description that follow more particularly exemplify illustrative embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The following discussion refers to the following figures, in which the same reference numerals may be used to identify similar / identical components in multiple figures. However, the use of a number to refer to a component in a given figure is not intended to limit the component labeled with the same number in another figure. The figures are not necessarily drawn to scale.

[0012] Figure 1 is a diagram of a system including an IMD according to various embodiments described herein.

[0013] Figure 2 yes Figure 1 Figure 2 shows the IMD of the α-D-type ...

[0014] Figure 3A According to the embodiments described herein, for example Figures 1 to 2 Block diagram of the IMD system.

[0015] Figure 3B is the IMD circuit and in Figures 1 to 2 Another block diagram of the associated pins employed in the system.

[0016] Figure 4 is a flow chart illustrating one example of a method of performing breathing-based cardiac remodeling pacing therapy.

[0017] Figure 5 is a state diagram illustrating another example of a method of performing breathing-based cardiac remodeling pacing therapy.

[0018] Figure 6is a graph of pacing rate over time illustrating an example of a respiration-based cardiac remodeling pacing therapy. DETAILED DESCRIPTION

[0019] In the following detailed description of exemplary embodiments, reference is made to the accompanying drawings, which form a part hereof, and in which is shown by way of illustration specific embodiments that may be practiced. It should 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 present disclosure as presented here.

[0020] Should refer to Figures 1 to 6 Describe exemplary systems, devices and methods. It will be apparent to those skilled in the art that an element or process from one embodiment may be used in combination with an element or process of other embodiments, and the possible embodiments of such systems, devices and methods using the feature combinations set forth herein are not limited to the specific embodiments shown in the figures and / or described herein. Further, it will be appreciated that the embodiments described herein may include many elements that are not necessarily shown to scale. Still further, it will be appreciated that the timing of the processes herein and the size and shape of the various elements may be modified and still fall within the scope of the present disclosure, but certain timings, one or more shapes and / or sizes or element types may be superior to other timings, one or more shapes and / or sizes or element types.

[0021] Figure 1 is a conceptual diagram of an exemplary therapy system 10 that can be used to deliver pacing therapy (such as support pacing and cardiac remodeling pacing therapy) to a patient 14. Although patient 14 is shown as a human, patient 14 can also be various other types of animals. Therapy system 10 may include an implantable medical device 16 (IMD) that can be coupled to leads 18, 20, 22. IMD 16 can be, for example, an implantable pacemaker, cardioverter, and / or defibrillator that delivers or provides electrical signals (e.g., pacing, etc.) to and / or senses electrical signals from the heart 12 of patient 14 via electrodes coupled to one or more of leads 18, 20, 22. Although IMD 16 is configured as depicted for delivering conventional myocardial pacing therapy to one, two, or three chambers, it should be understood that the exemplary systems, devices, and methods described herein can be used with other types of pacing therapies using electrodes, leads, and leadless devices to deliver pacing therapy to other parts or regions of a patient's heart. For example, the exemplary systems, devices, and methods may utilize cardiac conduction system pacing, where pacing is delivered to one or more portions of the patient's cardiac conduction system, such as, for example, the bundle of His, the right bundle branch, the left bundle branch, etc.

[0022] Leads 18, 20, 22 extend into heart 12 of patient 14 to sense electrical activity of heart 12 and / or deliver electrical stimulation to heart 12. Figure 1 In the example shown, the right ventricular (RV) lead 18 extends through one or more veins (not shown), the superior vena cava (not shown), and the right atrium 26, and into the right ventricle 28. The right atrial (RA) lead 22 extends through one or more veins and the vena cava, and into the right atrium 26 of the heart 12. Further, the left ventricular (LV) coronary sinus lead 20 extends through one or more veins, the vena cava, the right atrium 26, and into the coronary sinus 30 to a region adjacent to the free wall of the left ventricle 32 of the heart 12.

[0023] IMD 16 may sense electrical signals associated with depolarization and repolarization of heart 12, among other things, via electrodes coupled to at least one of leads 18, 20, 22. In some examples, IMD 16 provides pacing therapy (e.g., pacing pulses) to heart 12 based on the electrical signals sensed within heart 12. IMD 16 may be operable to adjust one or more parameters associated with pacing therapy, such as pacing rate, RR interval, AV delay, and various other timing, pulse width, amplitude, voltage, burst length, and the like. Further, IMD 16 may be operable to deliver pacing therapy using various electrode configurations, which may be unipolar, bipolar, quadripolar, or further multipolar. Thus, a multipolar lead system may provide or supply multiple electrical vectors from which to pace. The pacing vector may include at least one cathode, which may be at least one electrode located on at least one lead, and at least one anode, which may be at least one electrode located on at least one lead (e.g., the same lead or a different lead) and / or on a housing or casing of the IMD or electrode device. While improvements in cardiac function as a result of pacing therapy may be primarily dependent on the cathode, electrical parameters such as impedance, pacing threshold voltage, current draw, and lifespan may be more dependent on the pacing vector, which includes both the cathode and anode. IMD 16 may also provide defibrillation therapy and / or cardioversion therapy via electrodes located on at least one of leads 18, 20, and 22. Further, IMD 16 may detect cardiac arrhythmias in heart 12, such as fibrillation of ventricles 28 and 32, and deliver defibrillation therapy to heart 12 in the form of electrical pulses. In some examples, IMD 16 may be programmed to deliver a course of therapy, e.g., pulses of increasing energy levels, until the fibrillation of heart 12 ceases.

[0024] Figure 2 yes Figure 116. A more detailed conceptual diagram of IMD 16 and leads 18, 20, 22 of therapy system 10 is shown in FIG. Leads 18, 20, 22 may be electrically coupled to a therapy delivery module (e.g., for delivering support pacing therapy, cardiac remodeling pacing therapy, respiration-based pacing therapy, etc.), a sensing module (e.g., for sensing one or more signals from one or more electrodes), and / or any other modules of IMD 16 via connector block 34. In some examples, proximal ends of leads 18, 20, 22 may include electrical contacts that are electrically coupled to corresponding electrical contacts within connector block 34 of IMD 16. Additionally, in some examples, leads 18, 20, 22 may be mechanically coupled to connector block 34 by means of set screws, connecting pins, or another suitable mechanical coupling mechanism.

[0025] Each of leads 18, 20, 22 includes an elongated, insulated lead body that can carry multiple conductors (e.g., concentric coiled conductors, straight conductors, etc.) separated from one another by insulation (e.g., a tubular insulating sheath). In the illustrated example, bipolar electrodes 40, 42 are located near the distal end of lead 18. Additionally, bipolar electrodes 44, 45, 46, 47 are located near the distal end of lead 20, and bipolar electrodes 48, 50 are located near the distal end of lead 22.

[0026] Electrodes 40, 44, 45, 46, 47, 48 can take the form of ring electrodes, and electrodes 42, 50 can take the form of extendable spiral tip electrodes retractably mounted within insulated electrode heads 52, 54, 56, respectively. Each of electrodes 40, 42, 44, 45, 46, 47, 48, 50 can be electrically coupled to a respective one of the conductors (e.g., coiled conductors and / or straight conductors) within the lead body of its associated lead 18, 20, 22, and thereby to a respective one of the electrical contacts on the proximal end of leads 18, 20, 22.

[0027] Electrodes 40, 42, 44, 45, 46, 47, 48, 50 may further be used to sense electrical signals (e.g., morphological waveforms within an electrogram (EGM)) accompanying depolarization and repolarization of heart 12. The electrical signals are conducted to IMD 16 via corresponding leads 18, 20, 22. In some examples, IMD 16 may also deliver pacing pulses via electrodes 40, 42, 44, 45, 46, 47, 48, 50 to promote depolarization of cardiac tissue of the patient's heart 12. In some examples, as Figure 2As shown, IMD 16 includes one or more housing electrodes (such as housing electrode 58) that may be integrally formed with an outer surface of a housing 60 (e.g., a hermetic housing) of IMD 16 or otherwise coupled to housing 60. Any of electrodes 40, 42, 44, 45, 46, 47, 48, 50 may be combined with housing electrode 58 for unipolar sensing or pacing. As generally understood by those skilled in the art, other electrodes may also be selected to define or be used for pacing and sensing vectors. Further, any of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58 may be used to sense electrical activity during pacing therapy when not being used to deliver pacing therapy.

[0028] As further described in detail with reference to FIG3 , housing 60 may enclose a therapy delivery module, which may include a stimulation generator for generating cardiac pacing pulses and defibrillation or cardioversion shocks and a sensing module for monitoring electrical signals of the patient's heart (e.g., the patient's heart rhythm). Leads 18, 20, 22 may also include elongated electrodes 62, 64, 66, respectively, which may take the form of coils. IMD 16 may deliver defibrillation shocks to heart 12 via any combination of elongated electrodes 62, 64, 66 and housing electrodes 58. Electrodes 58, 62, 64, 66 may also be used to deliver cardioversion pulses to heart 12. Further, electrodes 62, 64, 66 may be made of any suitable conductive material, such as, but not limited to, platinum, platinum alloys, and / or other materials known to be useful in implantable defibrillation electrodes. Because electrodes 62, 64, 66 are generally not configured to deliver pacing therapy, any of electrodes 62, 64, 66 may be used to sense electrical activity and may be used in combination with any of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58. In at least one embodiment, RV elongated electrode 62 may be used to sense electrical activity of the patient's heart during the delivery of pacing therapy (e.g., in combination with housing electrode 58 or a defibrillation electrode-to-housing electrode vector).

[0029] The above configuration of therapy system 10 is merely one example. As described herein, the exemplary systems, devices, and methods may be configured to deliver cardiac conduction system pacing therapy to one or more portions of the cardiac conduction system. Further, the exemplary systems, devices, and methods may be configured to deliver cardiac conduction system pacing therapy in addition to or in combination with other therapies such as Figures 1 to 2The system 10 is shown as a conventional myocardial pacing. Exemplary cardiac conduction system pacing therapies that may be utilized by the exemplary systems, devices, and methods may be found in U.S. Patent No. 11,207,529, entitled “His Bundle and Bundle Branch Pacing Adjustment,” issued on December 28, 2021, U.S. Patent No. 7,177,704, entitled “Pacing Method and Apparatus,” issued on February 13, 2007, U.S. Patent Application Publication No. 2022 / 0032062A1, entitled “Cardiac Conduction System Pacing,” published on February 3, 2022, and U.S. Patent Application Publication No. 2019 / 0111264A1, entitled “Bundle Branch Pacing Devices and Methods,” published on April 18, 2019, each of which is incorporated herein by reference in its entirety. Additionally, in other examples, the therapy system 10 may include epicardial leads and / or patch electrodes in place of or in addition to Figure 1 In other embodiments, the therapy system 10 may be used in the absence of a transvenous lead (e.g., a leadless / wireless pacing system) or in the presence of a lead implanted (e.g., implanted transvenously or using a method) into the left chamber of the heart (as opposed to a conventional method). Figure 1 Implantation in / around the septal region of the heart is in addition to or as an alternative to the illustrated transvenous line placed into the right chamber of the heart.

[0030] Further, in one or more embodiments, IMD 16 need not be implanted within patient 14. For example, IMD 16 can deliver various cardiac therapies to heart 12 via percutaneous leads that extend through the skin of patient 14 to various locations within or outside of heart 12. In one or more embodiments, system 10 can utilize wireless pacing (e.g., using energy transfer to intracardiac pacing components via ultrasound, inductive coupling, RF, etc.) and sensing cardiac activation using electrodes on the housing / casing and / or on subcutaneous leads.

[0031] Other example therapy systems that provide electrical stimulation therapy to heart 12 may include any suitable number of leads coupled to IMD 16, with each of these leads extending to any location within or near heart 12. Such other therapy systems may include, for example, Figures 1 to 2Three transvenous leads are positioned as illustrated. Still other therapy systems may include a single lead extending from IMD 16 into the right atrium 26 or two leads extending into the right atrium 26 and respective ones of the left atrium. In one example, IMD 16 as a cardiac resynchronization therapy (CRT) device with a left ventricular (LV) lead may be useful for HFpEF patients in the presence of complete AV nodal block because, in such patients, an LV lead may be more beneficial than an RV lead. In some examples, it may be desirable to deliver rate-responsive pacing to the atria for HFpEF patients with chronotropic insufficiency having atrial leads (i.e., single-chamber atrial systems such as AAI) and atrial and ventricular lead systems (i.e., dual-chamber systems such as DDD and VDD).

[0032] Figure 3A is a functional block diagram of an example configuration of IMD 16. As shown, IMD 16 may include a control module 81, a therapy delivery module 84 (which may include a stimulation generator, for example), a sensing module 86, and a power source 90. Control module or device 81 may include a processor or computing device 80, a memory 82, and a telemetry module or device 88. Memory 82 may include computer-readable instructions that, when executed, for example, by processor or computing device 80, cause IMD 16 and / or control module 81 to perform the various functions attributed to IMD 16 and / or control module 81 as described herein. Further, memory 82 may include any volatile, nonvolatile, magnetic, optical, and / or electrical media, such as random access memory (RAM), read-only memory (ROM), nonvolatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, and / or any other digital media.

[0033] The processor or computing device 80 of the control module 81 may include any one or more of the following: a microprocessor, a controller, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), and / or equivalent discrete or integrated logic circuits. Generally speaking, the processor or computing device 80 may be described as including processing circuitry. In some examples, the processor or computing device 80 may include multiple components, such as any combination of one or more microprocessors, one or more controllers, one or more DSPs, one or more ASICs, and / or one or more FPGAs, as well as other discrete or integrated logic circuits. The functionality attributed to the processor or computing device 80 herein may be embodied in software, firmware, hardware, or any combination thereof.

[0034] The control module 81 can control the therapy delivery module or device 84 to deliver therapy (e.g., electrical stimulation therapy such as cardiac remodeling pacing) to the heart 12 according to one or more selected therapy programs that may be stored in the memory 82 and based on algorithms or methods further described below. More specifically, the control module 81, including the processor 80, can be used to monitor the patient's respiration and control the pacing rate and variables related thereto (such as a rate floor) to provide support pacing therapy and cardiac remodeling pacing therapy that is adjusted to restore or provide respiratory sinus arrhythmia, as will be further described herein. Additionally, more specifically, the control module 81, including the processor 80, can control various parameters of the electrical stimulation delivered by the therapy delivery module 84, such as, for example, AV delay, pacing pulses having amplitudes, pulse widths, frequencies, or electrode polarities, which may be specified by one or more selected therapy programs (e.g., an AV delay adjustment program, a pacing therapy program, a pacing recovery program, a capture management program, etc.). As shown, therapy delivery module 84 is electrically coupled to electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66, e.g., via conductors of respective leads 18, 20, 22 or, in the case of housing electrode 58, via electrical conductors disposed within housing 60 of IMD 16. Therapy delivery module 84 may be configured to generate electrical stimulation therapy, such as pacing therapy, and deliver the electrical stimulation therapy to heart 12 using one or more of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66.

[0035] For example, therapy delivery module 84 may deliver pacing stimulation (e.g., pacing pulses) via ring electrodes 40, 44, 45, 46, 47, 48 coupled to leads 18, 20, 22 and / or helical tip electrodes 42, 50 of leads 18, 22. Further, for example, therapy delivery module 84 may deliver a defibrillation shock to heart 12 via at least two of electrodes 58, 62, 64, 66. In some examples, therapy delivery module 84 may be configured to deliver pacing, cardioversion, or defibrillation stimulation in the form of electrical pulses. In other examples, therapy delivery module 84 may be configured to deliver one or more of these types of stimulation in the form of other signals, such as sine waves, square waves, and / or other substantially continuous time signals.

[0036] IMD 16 may also include a switching module or device 85, and control module 81 (e.g., processor 80) may use switching module 85 to select, for example, via a data / address bus, which of the available electrodes are used to deliver therapy, such as pacing pulses for pacing therapy, or which of the available electrodes are used for sensing. Switching module 85 may include a switching array, a switching matrix, a multiplexer, or any other type of switching device suitable for selectively coupling sensing module or device 86 and / or therapy delivery module 84 to one or more selected electrodes. More specifically, therapy delivery module 84 may include a plurality of pacing output circuits. Each of the plurality of pacing output circuits may be selectively coupled to one or more of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 (e.g., a pair of electrodes for delivering therapy for bipolar or multipolar pacing vectors), for example, using switching module 85. In other words, each electrode may be selectively coupled to one of the pacing output circuits of the therapy delivery module using switching module 85.

[0037] The sensing module 86 is coupled (e.g., electrically coupled) to a sensing device, which may include electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 to monitor electrical activity of the heart 12, such as electrocardiogram (ECG) / electrogram (EGM) signals, etc., among other sensing devices. ECG / EGM signals can be used to measure or monitor activation time (e.g., ventricular activation time, etc.), heart rate (HR), heart rate variability (HRV), heart rate oscillations (HRT), deceleration / acceleration ability, deceleration sequence incidence, T wave alternans (TWA), P wave to P wave interval (also known as PP interval or AA interval), R wave to R wave interval (also known as RR interval or VV interval), P wave to QRS complex interval (also known as PR interval, AV interval or PQ interval), QRS complex morphology, ST segment (i.e., the segment connecting the QRS complex and T wave), T wave changes, QT interval, electrical vector, etc.

[0038] Switching module 85 can also be used with sensing module 86 to select which of the available electrodes to use or enable, for example, to sense electrical activity of the patient's heart (e.g., one or more electrical vectors of the patient's heart using any combination of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66). Similarly, switching module 85 can also be used with sensing module 86 to select which of the available electrodes not to use (e.g., disable), for example, to sense electrical activity of the patient's heart (e.g., one or more electrical vectors of the patient's heart using any combination of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66), etc. In some examples, control module 81 can provide a signal via the switching module within sensing module 86, for example, over a data / address bus, to select the electrodes to serve as sensing electrodes.

[0039] In some examples, sensing module 86 includes a channel that includes an amplifier with a relatively wider passband than an R-wave or P-wave amplifier. The signal from the selected sensing electrode can be provided to a multiplexer and thereafter converted by an analog-to-digital converter into a multi-bit digital signal for storage in memory 82, for example, as an electrogram (EGM). In some examples, the storage of such an EGM in memory 82 can be under the control of direct memory access circuitry.

[0040] As depicted, sensing module 86 includes physiological sensors 79 that generate one or more signals based on one or more patient physiological parameters, such as activity, motion, respiration, posture, etc. In one or more embodiments, processor 80 can determine that patient 14 is in a target inactivity state based on the signals generated by sensor 79 in order to trigger or initiate cardiac remodeling pacing therapy, or conversely, determine that patient 14 is not in a target inactivity state in order to trigger or maintain support pacing therapy. Additionally, in one or more embodiments, processor 80 can determine the respiration of patient 14 based on the signals generated by sensor 79. More specifically, processor 80 can use the signals and data from sensor 79 to determine the start, end, and duration of the patient's inhalation / inhalation and exhalation / exhalation.

[0041] As an example, the sensor 79 may include or comprise electrodes or other known sensors for detecting heart rate and respiratory rate, a motion sensor (e.g., a piezoelectric motion sensor), or other known sensors that can provide evidence of the patient's activity level, etc. In some embodiments, the sensor 79 may be a multi-axis accelerometer capable of detecting the patient's motion (such as overall body movement and footsteps) as well as the patient's posture (including changes in posture). Additional information regarding the use of multi-axis accelerometers to determine patient posture is found in U.S. Patent No. 5,593,431, issued on January 14, 1997, entitled "Medical service employing multiple DC accelerometers for patient activity and posture sensing and method," which is incorporated herein by reference in its entirety.

[0042] In addition, by way of example, sensor 79 may include any suitable sensor for detecting physiological parameters associated with breathing, including an oxygen level sensor (e.g., a fingertip oxygen sensor), a pulse oximeter sensor, a peripheral arterial tonometry sensor, a carbon dioxide level sensor, an impedance sensor for detecting minute ventilation (MV), a pressure sensor for monitoring blood pressure or sensing airflow (ventilation), a microphone for monitoring breath sounds, a mechanical or temperature sensor for monitoring airflow (ventilation) or chest movement, a chest force sensor (e.g., a breathing belt worn around the chest), an abdominal force sensor (e.g., a breathing belt worn around the abdomen), any other sensor capable of monitoring parameters that indicate or predict the occurrence of apnea and / or hyperpnea, and any combination of these sensors. In some embodiments, sensor 79 may be an intracardiac sensor capable of measuring impedance between an atrial electrode and a ventricular electrode, or an intrathoracic impedance sensor that measures impedance across the thoracic cavity. Additionally, sensor 79 may also provide a signal that allows processor 80 to distinguish between inhalation / inspiration and exhalation / expiration. Sensor 79 can use impedance to determine respiration, as described in U.S. patent application serial number 17 / 878,557, entitled “Lead Impedance Measurement For Physiological And Device Management,” filed on August 1, 2022, which is incorporated herein by reference in its entirety.

[0043] Additionally, physiological sensor 79 may be described as including a plurality of physiological sensors, and processor 80 may determine whether patient 14 is in a target inactivity state based on signals from the plurality of sensors, and may determine whether patient 14 is inhaling or exhaling a breath based on signals from the plurality of sensors. The plurality of sensors of physiological sensor 79 may be located within the housing of IMD 16, such as Figure 3A As proposed, either coupled to IMD 16 via leads or wireless communication.

[0044] As an example, processor 80 may determine the activity level or inactivity level of patient 14 based on changes in the signal output by sensor 79 or based on a comparison of the signal output by sensor 79 with a template or threshold stored in memory 82. Exemplary activity level sensing for providing cardiac remodeling pacing is described in U.S. Provisional Patent Application No. 63 / 304,166, filed on January 28, 2022, entitled "Activity Detection for Cardiac Remodeling Pacing," which is incorporated herein by reference in its entirety. Further, processor 80 may determine whether patient 14 is in a target high activity state or is sleeping by comparing one or more of activity counts, heart rate, heart rate variability, respiratory rate, or respiratory rate variability, for example, derived from an accelerometer or piezoelectric crystal signal, to a threshold stored in memory 82. In addition, the IMD 16 may include any of the sensors described in U.S. Patent No. 7,775,993, entitled “Detecting Sleep,” issued on August 17, 2010, and the processor 80 may use any of the techniques described in that U.S. Patent to determine whether the patient is asleep, which is incorporated herein by reference in its entirety.

[0045] Further, as an example, processor 80 may determine respiration of patient 14 based on changes in the signal output by sensor 79 or based on a comparison of the signal output by sensor 79 to a template or threshold stored in memory 82. Exemplary respiration sensing for use in providing cardiac remodeling pacing may be described in U.S. Patent No. 7,896,813, issued March 1, 2011, entitled “System and Method for patanm2 Monitoring Periodic Breathing Associated with Heart Failure,” which is incorporated herein by reference in its entirety.

[0046] In some examples, the control module 81 can operate as an interrupt-driven device and can respond to interrupts from the pacemaker timing and control module, where the interrupts can correspond to the patient's respiration (e.g., inhalation and exhalation), the occurrence of sensed P and R waves, and the generation of cardiac pacing pulses. Any necessary mathematical calculations can be performed by the processor 80, and any updates to the values ​​or intervals controlled by the pacemaker timing and control module can occur after such interrupts. A portion of the memory 82 can be configured as a plurality of recirculating buffers capable of holding one or more series of measurement intervals that can be analyzed by the processor 80, for example, in response to the patient's respiration (e.g., inhalation or exhalation), in response to the patient's activity level that can signal or indicate when to provide cardiac remodeling pacing therapy or support pacing therapy, in response to the occurrence of a pacing or sensing interrupt to determine whether the patient's heart 12 is currently exhibiting an atrial or ventricular tachyarrhythmia, etc.

[0047] Telemetry module 88 of control module 81 may include any suitable hardware, firmware, software, or any combination thereof for communicating with another device, such as a programmer. For example, under the control of processor 80, telemetry module 88 may receive downlink telemetry from a programmer via an antenna (which may be internal and / or external) and transmit uplink telemetry to the programmer. Processor 80 may provide data to be uplinked to a programmer or other computing device and control signals for telemetry circuitry within telemetry module 88, for example, via an address / data bus. In some examples, telemetry module 88 may provide received data to processor 80 via a multiplexer.

[0048] The various components of IMD 16 are further coupled to a power source 90, which may include a rechargeable or non-rechargeable battery. Non-rechargeable batteries may be selected to last for several years, while rechargeable batteries may be inductively charged from an external device, for example, on a daily or weekly basis.

[0049] Figure 3B1 is a functional block diagram depicting an embodiment of an IMD 16 having a bipolar RA lead 22, a bipolar RV lead 18, without an LA CS pace / sense electrode, and coupled to an implantable pulse generator (IPG) circuit 31 with programmable modes and parameters of a biventricular DDD / R type known in the art of pacing. Furthermore, sensor signal processing circuitry 91 is indirectly coupled to a digital controller / timing circuit 43 to a microcomputer circuit 33 via a data and control bus. The IPG circuit 31 is illustrated in the functional block diagram, which is generally divided into the microcomputer circuit 33 and the pacing circuit 21. The pacing circuit 21 includes a digital controller / timing circuit 43, an output amplifier circuit 51, a sense amplifier circuit 55, an RF telemetry transceiver 41, an activity circuit or patient activity sensor (PAS) 35, and other circuits and components described below.

[0050] When powered by the battery 29, a crystal oscillator circuit 89 provides a basic timing clock to the pacing circuit 21. A power-on reset circuit 87 is responsive to the initial connection of the circuit to the battery for defining initial operating conditions and, similarly, for resetting the operating state of the device in response to detection of a low battery condition. A voltage reference and bias circuit 37 generates a stable voltage reference and current for the analog circuits within the pacing circuit 21. An analog-to-digital converter (ADC) and multiplexer circuit 39 digitizes the analog signals and voltages to provide real-time telemetry of cardiac signals, such as from the sense amplifier circuit 55, for uplink transmission via the RF telemetry transceiver 41. The voltage reference and bias circuit 37, the ADC and multiplexer circuit 39, the power-on reset circuit 87, and the crystal oscillator circuit 89 may correspond to any of those used in exemplary implantable cardiac pacemakers.

[0051] If the IPG is programmed for rate-responsive mode, the signals output by one or more physiological sensors are used as a rate control parameter (RCP) to derive the physiological escape interval. For example, the escape interval is adjusted proportionally to the patient's activity level, as generated by activity circuitry 35 in the exemplary IPG circuitry 31. Patient activity sensor 27 is coupled to the IPG housing and may take the form of a piezoelectric crystal transducer. The output signal of patient activity sensor 27 may be processed and used as the RCP. Sensor 27 generates an electrical signal in response to sensed physical activity, which is processed by activity circuitry 35 and provided to digital controller / timing circuitry 43. Additionally, patient activity sensor 27 and activity circuitry 35 may be used to determine whether or when to deliver cardiac remodeling pacing therapy. For example, patient activity sensor 27 and activity circuitry 35 may determine that the patient is inactive (e.g., at night, resting, etc.) and, therefore, may determine the length of time that cardiac remodeling pacing therapy is effective. Similarly, the exemplary systems, devices, and methods described herein can be practiced in conjunction with alternative types of sensors (such as oxygenation sensors, pressure sensors, pH sensors, temperature sensors, respiration sensors, perfusion sensors, heart sound sensors, and heart rate sensors) to provide rate-responsive pacing therapy, support pacing therapy, and cardiac remodeling pacing therapy. For example, impedance can be measured using a ring electrode on a lead (e.g., an RA or RV lead), and temperature can be measured by a sensor at the distal end of the lead. Alternatively, QT time can be used as a rate-indicating parameter, in which case no additional sensor is required. Similarly, the exemplary embodiments described herein can also be practiced in non-rate-responsive pacemakers.

[0052] Data transmission to and from the external programmer is accomplished through the telemetry antenna 57 and associated RF telemetry transceiver 41, which is used to demodulate received downlink telemetry and transmit uplink telemetry. The uplink telemetry capability may include the ability to transmit stored digital information (e.g., activity information, rate-responsive pacemaker curves, operating modes and parameters, EGM histograms and other events, as well as real-time EGMs of atrial and / or ventricular electrical activity and marker channel pulses indicating the occurrence of sensed and paced depolarizations in the atria and ventricles).

[0053] The microcomputer circuit 33 contains a microprocessor, processor, or computing device 80 and an associated system clock, as well as on-processor RAM chip 82A and ROM chip 82B. Additionally, the microcomputer circuit 33 includes a separate RAM / ROM chip 82C to provide additional memory capacity. The microprocessor 80 typically operates in a reduced power consumption mode and is interrupt-driven. The microprocessor 80 is awakened in response to defined interrupt events, which may include the A-TRIG, RV-TRIG, and LV-TRIG signals generated by the timers in the digital controller / timing circuit 43, and the A-EVENT, RV-EVENT, and LV-EVENT signals generated by the sense amplifier circuit 55. The specific values ​​of the timeout intervals and delays by the digital controller / timing circuit 43 are controlled by the microcomputer circuit 33 via the data and control bus from programmed parameter values ​​and operating modes. Furthermore, if programmed to operate as a rate-responsive pacemaker, a timed interrupt (e.g., every cycle or every two seconds) can be provided to allow the microprocessor to analyze activity sensor data and update the base pacing rate and, if applicable, AA and VA. Additionally, microprocessor 80 may be used to define variable, actionable AV delay intervals, as well as the amount of energy delivered to each ventricle and / or atrium.

[0054] In one embodiment, the microprocessor 80 is a custom microprocessor adapted to fetch and execute instructions stored in the RAM / ROM memory 82 in a conventional manner. However, it is contemplated that other embodiments may be suitable for practicing the disclosed method. For example, an off-the-shelf commercially available microprocessor or microcontroller or a custom, dedicated hard-wired logic or state machine type circuit may perform the functions of the microprocessor 80.

[0055] The digital controller / timing circuit 43 operates under the general control of the microcomputer circuit 33 to control timing and other functions within the pacing circuit 21 and includes a set of timing and associated logic circuits, some of which are depicted that are relevant to the present disclosure. The depicted timing circuits include a URI / LRI timer 83A, a VV delay timer 83B, an intrinsic interval timer 83C for timing the elapsed V-EVENT to V-EVENT interval or V-EVENT to A-EVENT interval, an escape interval timer 83D for timing the AA and / or VA pacing escape interval, an AV delay interval timer 83E for timing the A-LVp delay (or A-RVp delay) from a previous A-EVENT or A-TRIG, a post-ventricular event timer 83F for timing the post-ventricular time period, and a date / time clock 83G.

[0056] The AV delay interval timer 83E is loaded with the appropriate delay interval for one ventricular chamber (e.g., A-RVp delay or A-LVp) to time out from the previous A-PACE or A-EVENT. The interval timer 83E triggers pacing stimulus delivery and may be based on one or more previous cardiac cycles (or from a dataset empirically derived for a given patient).

[0057] The post-ventricular event timer 83F times out the post-ventricular time period following an RV-EVENT or LV-EVENT or RV-TRIG or LV-TRIG, and the post-atrial time period following an A-EVENT or A-TRIG. The duration of the post-event time period may also be selected as a programmable parameter stored in the microcomputer circuit 33. The post-ventricular time period includes the post-ventricular atrial blanking period (PVARP), the post-atrial ventricular blanking period (PAVBP), the ventricular blanking period (VBP), and the ventricular refractory period (VRP), although other time periods may be appropriately defined based, at least in part, on the operating circuitry employed in the pacing engine. The post-atrial time period includes the atrial refractory period (ARP), during which the A-EVENT is ignored for the purpose of resetting any AV delay, and during which atrial sensing is disabled. It should be noted that the start of the post-atrial time period and AV delay can begin substantially simultaneously with the start or end of each A-EVENT or A-TRIG, or in the latter case, at the end of the A-PACE that may follow the A-TRIG. Similarly, the start of the post-ventricular time period and VA escape interval can begin substantially simultaneously with the start or end of the V-EVENT or V-TRIG, or in the latter case, at the end of the V-PACE that may follow the V-TRIG. The microprocessor 80 also optionally calculates the AV delay, post-ventricular time period, and post-atrial time period as a function of the sensor-based escape interval and / or the intrinsic atrial and / or ventricular rate established in response to the RCP.

[0058] The output amplifier circuit 51 contains an RA pace pulse generator (and a LA pace pulse generator, if LA pacing is provided), an RV pace pulse generator, an LV pace pulse generator, and / or any other pulse generator configured to provide atrial and ventricular pacing. To trigger the generation of an RV-PACE or LV-PACE pulse, the digital controller / timing circuit 43 may use the algorithm described below.

[0059] Output amplifier circuitry 51 includes switching circuitry for coupling selected pacing electrode pairs from among the lead conductors and IND-CAN electrodes to the RA pacing pulse generator (and LA pacing pulse generator, if provided), RV pacing pulse generator, and LV pacing pulse generator. Pace / sense electrode selection and control circuitry 53 selects lead conductors and associated pacing electrode pairs for coupling to the atrial and ventricular output amplifiers within output amplifier circuitry 51 for RA, LA, RV, and LV pacing.

[0060] Sense amplifier circuitry 55 contains sense amplifiers for atrial and ventricular pacing and sensing. High-impedance P-wave and R-wave sense amplifiers can be used to amplify the voltage difference signal generated across the sensing electrode pair due to the passage of the cardiac depolarization wavefront. The high-impedance sense amplifiers use high gain to amplify low-amplitude signals and rely on passband filters, time-domain filtering, and amplitude threshold comparisons to distinguish the P-wave or R-wave from background electrical noise. The digital controller / timing circuitry 43 controls the sensitivity settings of the atrial and ventricular sense amplifier circuitry 55.

[0061] During blanking periods before, during, and after delivery of a pacing pulse to any of the pacing electrodes of the pacing system, the sense amplifier can be decoupled from the sense electrode to avoid saturation of the sense amplifier. Sense amplifier circuitry 55 includes blanking circuitry for decoupling selected lead conductor pairs and the IND-CAN electrode from the inputs of the RA sense amplifier (and LA sense amplifier, if provided), RV sense amplifier, and LV sense amplifier during ABP, PVABP, and VBP. Sense amplifier circuitry 55 also includes switching circuitry for coupling selected sense electrode lead conductors and the IND-CAN electrode to the RA sense amplifier (and LA sense amplifier, if provided), RV sense amplifier, and LV sense amplifier. Similarly, sense electrode selection and control circuitry 53 selects conductors and associated sense electrode pairs to be coupled to the atrial and ventricular sense amplifiers within output amplifier circuitry 51 and sense amplifier circuitry 55 for achieving RA, LA, RV, and LV sensing along desired unipolar and bipolar sensing vectors.

[0062] Right atrial depolarization or a P wave in the RA-SENSE signal sensed by the RA sense amplifier results in the RA-EVENT signal, which is transmitted to the digital controller / timing circuit 43. Similarly, left atrial depolarization or a P wave in the LA-SENSE signal sensed by the LA sense amplifier (if provided) results in the LA-EVENT signal, which is transmitted to the digital controller / timing circuit 43. Ventricular depolarization or an R wave in the RV-SENSE signal sensed by the ventricular sense amplifier results in the RV-EVENT signal, which is transmitted to the digital controller / timing circuit 43. Similarly, ventricular depolarization or an R wave in the LV-SENSE signal sensed by the ventricular sense amplifier results in the LV-EVENT signal, which is transmitted to the digital controller / timing circuit 43. The RV-EVENT signal, the LV-EVENT signal, the RA-EVENT signal, and the LA-SENSE signal may be refractory or refractory and may be inadvertently triggered by electrical noise signals or abnormally conducted depolarization waves rather than by true R- or P-waves.

[0063] The techniques described in this disclosure, including those attributable to IMD 16 and / or its various component parts, may be implemented, at least in part, in hardware, software, firmware, or any combination thereof. For example, various aspects of the technology may be implemented within one or more processors embodied as a programmer (such as a physician or patient programmer), a stimulator, an image processing device, or other device, the one or more processors comprising one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuits, and any combination of such components. The terms "module," "processor," or "processing circuitry" may collectively refer to any of the aforementioned logic circuits, alone or in combination with other logic circuits, or any other equivalent circuitry.

[0064] Such hardware, software and / or firmware may be implemented within the same device or within separate devices to support the various operations and functions described in this disclosure. In addition, any described units, modules or components may be implemented together or separately in the form of discrete but interoperable logical devices. Describing different features as modules or units is intended to highlight different functional aspects and does not necessarily imply that such modules or units must be implemented by separate hardware or software components. On the contrary, the functionality associated with one or more modules or units may be performed by separate hardware or software components, or integrated in common or separate hardware or software components.

[0065] When implemented in software, the functionality attributed to the systems, devices, and techniques described in this disclosure may be embodied as instructions on a computer-readable medium, such as RAM, ROM, NVRAM, EEPROM, flash memory, magnetic data storage media, or optical data storage media. The instructions may be executed by one or more processors to support one or more aspects of the functionality described in this disclosure.

[0066] Exemplary systems, devices, and methods of the present disclosure may be described as providing a respiration-based cardiac remodeling pacing therapy in combination with support pacing. As used herein, cardiac remodeling pacing therapy may be described as pacing the patient's heart at an increased rate above the rate at which the patient's heart is currently beating to provide or cause cardiac remodeling of the patient's heart's physical structure, such as, for example, increased compliance of the left ventricular wall, thinning of the left ventricular wall, dilation of the left ventricular wall, etc. As used herein, support pacing therapy may be described as cardiac pacing in which the patient's heart rate is monitored and the patient's heart rate is prevented from falling below a defined lower rate limit. In other words, support pacing maintains the patient's heart rate above or at a lower rate limit by delivering pacing without allowing the patient's heart rate to fall below the lower rate limit.

[0067] Respiration-based cardiac remodeling pacing therapy combined with support pacing can be used to treat HF ​​patients, particularly HFpEF patients. As described herein, cardiac remodeling pacing can provide an increase in heart rate that can lead to thinning, dilation, and increased compliance of the left ventricular wall. Myocyte loss and reactive hypertrophy of myocytes can be a major component of ventricular remodeling in pacing-induced dilated cardiomyopathy. Such cardiac remodeling may be desirable for patients with HFpEF because such patients have normal-sized ventricles with increased wall thickness. In some embodiments, cardiac remodeling pacing can be defined as overdrive pacing because cardiac remodeling pacing increases heart rate (i.e., tachycardia pacing) to cause cardiac remodeling (e.g., increased compliance of the left ventricular wall, thinning of the left ventricular wall, etc.). Further details regarding cardiac remodeling pacing may be provided in U.S. Patent Application Publication No. 2019 / 0381323A1, entitled “Delivery of Cardiac Pacing Therapy for Cardiac Remodeling,” published on December 19, 2019, which is incorporated herein by reference in its entirety.

[0068] It may be optimal to deliver cardiac remodeling pacing during selected opportunities, such as when the patient is resting (e.g., when the patient is resting or resting during the day, night, etc.). Furthermore, cardiac remodeling pacing can be described as opportunistic high-rate pacing during the day, while maintaining high-rate pacing at night. For example, cardiac remodeling pacing can utilize higher-rate pacing (e.g., greater than 100 beats per minute, or at least 110 beats per minute) during periods of low activity (e.g., at night) for extended periods of time (e.g., greater than five hours or at least six hours), and additional opportunistic pacing can be provided during the day for a total of more than ten hours (e.g., approximately 12 hours) of pacing therapy.

[0069] Figure 4 An exemplary method 100 for performing a respiration-based cardiac remodeling pacing therapy is depicted in FIG. The method 100 may be performed by a processor, a microprocessor, a computing device 80, a physiological sensor 79, and a reference herein. Figure 1 3 . It should be understood that the illustrative method 100 and the processes described therein can be performed on a non-implantable device or a subcutaneous implantable device that can communicate with a pacing device to deliver support pacing and cardiac remodeling pacing. For example, the illustrative method 100 can be performed by an external device (e.g., outside the patient's body) but can communicate with an IMD to deliver pacing. Additionally, although the method 100 is depicted using boxes and arrows extending from some boxes to other boxes, it should be understood that the boxes and the functionality, method steps, and processes associated therewith do not necessarily need to be performed sequentially, and therefore, one or more of the boxes and the functionality, method steps, and processes associated therewith can be performed simultaneously and repeatedly.

[0070] Method 100 may include delivering pacing 102 based on a lower rate limit. The lower rate limit may be described as a minimum pacing rate delivered at a particular time or during a particular pacing mode. The lower rate limit may be adjusted or modified depending on the pacing therapy mode in which the pacing device is configured. The initial lower rate limit may be set to a minimum lower rate limit between approximately 60 beats per minute (bpm) and approximately 100 bpm. It will be appreciated that the minimum lower rate limit may be patient specific. For example, the patient's physician may determine the minimum lower rate limit based on the patient's condition. The pacing 102 may be performed, for example, using a device described herein with reference to a preferred embodiment of the present invention. Figure 1 3 for delivery by the system and apparatus described.

[0071] The method 100 may also include monitoring the patient's breathing 104. For example, a breathing sensor (such as, for example, a breathing sensor as described herein) may be used. Figure 3AThe patient's respiration 104 may be monitored using the physiological sensors 79 described above. The delivery of pacing 102 and the monitoring of the patient's respiration 104 may occur simultaneously and independently of each other. In other words, the delivery of pacing 102 may not be dependent on the monitoring of the patient's respiration 104, and conversely, the monitoring of the patient's respiration 104 may not be dependent on the delivery of pacing 102.

[0072] Monitoring the patient's breathing 104 may include determining the patient's inhalation / inhalation and exhalation / exhalation. More specifically, based on monitoring the patient's breathing 104, one or more of a starting point (e.g., start, initiation, start time, etc.) of the patient's inhalation / inhalation, an end point (e.g., end, stop, end time, etc.) of the patient's inhalation / inhalation, a starting point (e.g., start, initiation, start time, etc.) of the patient's exhalation / exhalation, an end point (e.g., end, stop, end time, etc.) of the patient's exhalation / exhalation, an inhalation / inhalation duration (e.g., time period, length of time, etc.) of the patient's inhalation / inhalation, and an exhalation / exhalation duration (e.g., time period, length of time, etc.) of the patient's exhalation / exhalation may be determined.

[0073] The patient's breathing can be used to adjust the lower rate limit based on the patient's breathing to restore or achieve respiratory sinus arrhythmia (RSA) 106. For example, the lower rate limit can be increased during exhalation and can be decreased during inhalation, for example, to cause or induce respiratory sinus arrhythmia. Adjustment of the lower rate limit can be made or initiated at the beginning (e.g., onset or start) of inhalation or exhalation. For example, the beginning of inhalation or exhalation can trigger or initiate the lower rate limit adjustment or modification.

[0074] In at least one embodiment, the lower rate limit can be increased or decreased by a selected value, such as an RSA value or amplitude. The RSA value or amplitude can be between about 5 bpm and about 30 bpm. In one embodiment, the RSA value is 15 bpm. In some embodiments, the RSA threshold can be one or more of the following: greater than or equal to 5 bpm, greater than or equal to 7 bpm, greater than or equal to 10 bpm, greater than or equal to 13 bpm, less than or equal to 30 bpm, less than or equal to 25 bpm, less than or equal to 22 bpm, less than or equal to 20 bpm, less than or equal to 17 bpm, etc.

[0075] For example, if the current lower rate limit is 80 bpm and the RSA value is 15 bpm, the lower rate limit may be increased by 15 bpm to 95 bpm during exhalation (e.g., during the time period during which exhalation is occurring). Thus, during exhalation, the current lower rate limit is 95 bpm. After exhalation, during the next exhalation (e.g., during the time period during which inhalation is occurring), the lower rate limit of 95 bpm may be reduced by the RSA value of 15 bpm, so that the lower rate limit is 80 bpm.

[0076] In some embodiments, the RSA value or amplitude can be described in terms of a percentage of the rate limit. For example, the RSA value can be between about 5% and about 30% of the rate limit. In this way, the rate limit can be increased or decreased by its own percentage. In one embodiment, the RSA value is 20%. In some embodiments, the RSA value can be one or more of the following: greater than or equal to 5%, greater than or equal to 10%, greater than or equal to 15%, less than or equal to 30%, less than or equal to 25%, less than or equal to 20%, etc.

[0077] In some embodiments, the RSA value may be based on one or more measurable physiological parameters of the patient. For example, the RSA value may be based on one or more of the patient's heart rate, respiratory rate, and activity level. More specifically, the illustrative systems, devices, and methods may monitor or measure one or more of the patient's heart rate, respiratory rate, and activity level, and then generate or calculate the RSA value based on one or more of the patient's heart rate, respiratory rate, and activity level. In other words, RSA may be a function of one or more measurable physiological parameters of the patient (such as, for example, the patient's heart rate, respiratory rate, and activity level). For example, the RSA value may decrease as one or more of the heart rate, respiratory rate, and activity level increase.

[0078] Additionally, in one or more embodiments, different RSA values ​​may be determined and used for each of the support pacing therapy and the cardiac remodeling pacing therapy. For example, the RSA value used for the cardiac remodeling pacing therapy may be less than the RSA value used for the support pacing therapy. Thus, the exemplary systems, devices, and methods may utilize the support RSA value for adjusting the lower rate limit to restore respiratory sinus arrhythmia during support pacing, and may utilize the remodeling RSA value for adjusting the lower rate limit to restore respiratory sinus arrhythmia during cardiac remodeling pacing, where the remodeling RSA value is less than the support RSA value. For example, the support RSA value may be 15 bpm, and the remodeling RSA value may be 7 bpm. Further, for example, the support RSA value may be 20% of the lower rate limit for support pacing, and the remodeling RSA value may be 5% of the lower rate limit for cardiac remodeling pacing.

[0079] Additionally, method 100 may also include increasing the rate floor to provide cardiac remodeling pacing 108. For example, the rate floor may be increased to the cardiac remodeling pacing rate (which may be the maximum rate floor minus the RSA value or amplitude). The cardiac remodeling pacing rate may be a pacing rate that provides optimal cardiac remodeling pacing therapy during a time period during which cardiac remodeling pacing is determined to be delivered to the patient. Such a time period during which cardiac remodeling pacing is determined to be delivered to the patient may be referred to as a remodeling time period. The remodeling time period may be initiated or triggered during nighttime hours when the patient is asleep and during daytime hours when the patient is inactive or resting. Initiation of the remodeling time period may be determined based on various types of activity sensing. Exemplary activity level sensing for providing cardiac remodeling pacing is described in U.S. Provisional Patent Application No. 63 / 304,166, filed on January 28, 2022, entitled "Activity Detection for Cardiac Remodeling Pacing," which is incorporated herein by reference in its entirety. The remodeling time period may be between approximately 5 minutes and approximately 8 hours. Additionally, the remodeling time period may be patient-specific and set or configured by a physician.

[0080] The cardiac remodeling pacing rate may be between approximately 80 bpm and approximately 140 bpm. It will be appreciated that the cardiac remodeling pacing rate may be patient-specific. For example, the patient's physician may determine the cardiac remodeling pacing rate based on the patient's condition. The cardiac remodeling pacing rate may be between approximately 50% and approximately 85% of the patient's maximum heart rate. Regardless, the cardiac remodeling pacing rate will always be greater than the initial or minimum lower rate limit at which the supportive pacing therapy is being delivered. After the remodeling period expires, the lower rate limit may be reduced back to the initial or minimum lower rate limit to provide supportive pacing therapy.

[0081] Although the lower rate limit has been increased or set to the cardiac remodeling pacing rate during delivery of cardiac remodeling pacing 108, the lower rate limit may still be adjusted to restore respiratory sinus arrhythmia 106. More specifically, the lower rate limit set to the cardiac remodeling pacing rate during cardiac remodeling pacing therapy may be increased during exhalation and decreased during inhalation. The increase during exhalation and the decrease during inhalation may be an RSA value or amplitude as previously described herein.

[0082] Thus, it will be appreciated that method 100 provides support pacing and cardiac remodeling pacing while also providing adjustment of the lower rate limit to restore respiratory sinus arrhythmia during both pacing therapies. Figure 5 Another example of a method of performing respiration-based cardiac remodeling pacing therapy 200 is depicted in The method 200 is similar to the method of claim 100, but is depicted and described with respect to a state diagram.

[0083] Method 200 includes two phases: delivery of support pacing 202 and delivery of cardiac remodeling pacing 204, each of which is substantially similar to that described herein with respect to Figure 4 The method 200 may initiate or begin delivery of support pacing 202. In other words, the default state of the method 200 may be delivery of support pacing 202. The support pacing 202 may be delivered using a lower rate limit as previously described, which may be set or configured to a minimum lower rate limit or support pacing rate (e.g., 75 bpm).

[0084] When remodeling criteria are met, the method 200 can switch from delivering support pacing 202 to delivering cardiac remodeling pacing 204. The remodeling criteria can include one or more factors or elements, such as, for example, activity level, time of day, etc. For example, if it is during the day and the patient's activity is low, indicating that the patient is resting, the method 200 can switch from delivering support pacing 202 to delivering cardiac remodeling pacing 204. Further, for example, if it is nighttime and the patient's activity is low, indicating that the patient is asleep, the method 200 can switch from delivering support pacing 202 to delivering cardiac remodeling pacing 204.

[0085] As described herein, cardiac remodeling pacing 204 can include an increased lower rate limit, such as an increase to a cardiac remodeling pacing rate (e.g., 130 bpm) to provide cardiac remodeling. If the remodeling time period expires or the remodeling criteria are no longer met, method 200 can switch from delivering cardiac remodeling pacing 204 to delivering support pacing 202, where the lower rate limit can again be adjusted to the minimum lower rate limit or the support pacing rate.

[0086] As shown, both support pacing 202 and cardiac remodeling pacing 204 can be adjusted based on respiration. More specifically, the rate floor / support pacing rate utilized during support pacing 202 and the rate floor / cardiac remodeling pacing rate of cardiac remodeling pacing 204 can both be adjusted based on RSA values ​​or amplitudes according to the patient's inhalation and exhalation.

[0087] When methods 100, 200 transition from support pacing therapy to cardiac remodeling pacing therapy, or vice versa, the lower rate limit can be gradually adjusted from a current value to a new value. For example, when transitioning from support pacing therapy to cardiac remodeling pacing therapy, the lower rate limit can be gradually increased according to an increasing ramp rate until the lower rate limit equals the cardiac remodeling pacing rate. Further, for example, when transitioning from cardiac remodeling pacing therapy to support pacing therapy, the lower rate limit can be gradually decreased according to a decreasing ramp rate until the lower rate limit equals the minimum lower rate limit or the support pacing rate. The magnitude or absolute value of the increasing ramp rate and the decreasing ramp rate can be the same or different. Furthermore, the magnitude or absolute value of the increasing ramp rate can be greater than the magnitude or absolute value of the decreasing ramp rate. The ramp rate can be expressed in beats per minute (bpm) per cardiac cycle. In other words, after a number of cardiac cycles, the lower rate limit can be increased or decreased by the bpm of the ramp rate. The ramp rate may be between about 1 bpm per 8 cardiac cycles and about 5 bpm per 1 cardiac cycle. In one embodiment, the increasing ramp rate is 1 bpm per 4 cardiac cycles. In one embodiment, the decreasing ramp rate is 1 bpm per 1 cardiac cycle. In other embodiments, the ramp rate may be one or more of: greater than or equal to 1 bpm per 8 cardiac cycles, greater than or equal to 1 bpm per 6 cardiac cycles, greater than or equal to 1 bpm per 6 cardiac cycles, greater than or equal to 1 bpm per 4 cardiac cycles, greater than or equal to 1 bpm per 2 cardiac cycles, greater than or equal to 1 bpm per 1 cardiac cycle, less than or equal to 5 bpm per 1 cardiac cycle, less than or equal to 4 bpm per 1 cardiac cycle, and less than or equal to 2 bpm per 1 cardiac cycle.

[0088] Figure 6 , depicts a graph of pacing rate over time, illustrating an example of respiration-based cardiac remodeling pacing therapy. The minimum rate limit is indicated by the lower dashed-dotted horizontal line 310, the maximum rate limit is indicated by the dashed-dotted horizontal line 312, and the cardiac remodeling pacing rate is indicated by the dashed horizontal line 319. In this example, the minimum rate limit is 77 bpm, the maximum rate limit is 129 bpm, and the cardiac remodeling pacing rate is 116 (e.g., the maximum rate limit minus the RSA value or amplitude). The current pacing rate used by support pacing and cardiac remodeling pacing is indicated by the thin solid line 301. The black solid lines 302, 304 that delimit the current pacing rate 301 represent the upper and lower limits of the current pacing rate when adjusted by the RSA value or amplitude 305. In this example, the RSA value 305 is 13 bpm.

[0089] As shown, support pacing is delivered during support pacing time period 321, the current pacing rate transitions from support pacing to cardiac remodeling pacing (e.g., the ramp rate defines a slope) during ramp time period 322, and cardiac remodeling pacing is being delivered during cardiac remodeling pacing time period 323. In each of time periods 321, 322, and 323, the current pacing rate 301 is shown as being adjusted by the RSA value or amplitude 305 during exhalation and inhalation. For example, the current pacing rate 301 is shown as increasing and decreasing during each of time periods 321, 322, and 323 based on the patient's respiration. In other words, regardless of the pacing mode (even including transitions from one mode to another), the current pacing rate 301 is shown as being adjusted by the RSA value or amplitude to achieve or restore respiratory sinus arrhythmia. Additionally, it should be understood that the same concepts apply when "ramping down" from cardiac remodeling pacing to support pacing.

[0090] By implementing the exemplary systems, devices, and methods according to various embodiments, cardiac remodeling pacing or overdrive pacing may be provided for longer periods of time, resulting in fewer missed pacing opportunities and improved patient outcomes.

[0091] Although the present disclosure is not limited thereto, an understanding of various aspects of the present disclosure will be gained through a discussion of the specific examples and exemplary embodiments provided below. Various modifications of the examples and exemplary embodiments, as well as additional embodiments of the present disclosure, will become apparent herein.

[0092] Example

[0093] Example Ex1: An implantable medical device comprising: a pacing electrode positioned near a patient's heart to deliver pacing therapy to the patient's heart; a respiration sensor for determining the patient's respiration rate; and a computing device operably coupled to the pacing electrode and the respiration sensor, the computing device being configured to: deliver pacing using at least the pacing electrode based on a rate floor; monitor the patient's respiration through the respiration sensor; adjust the rate floor based on the patient's respiration to restore respiratory sinus arrhythmia (RSA); and increase the rate floor to provide cardiac remodeling pacing during a remodeling time period.

[0094] Example Ex2: A method comprising: delivering pacing to a patient's heart based on a rate floor; monitoring the patient's respiration; adjusting the rate floor based on the patient's respiration to restore respiratory sinus arrhythmia (RSA); and increasing the rate floor to provide cardiac remodeling pacing during a remodeling time period.

[0095] Example Ex3: An apparatus according to Example Ex1 or a method according to Example Ex2, wherein adjusting the rate lower limit based on the patient's breathing rate to restore RSA includes: determining exhalation based on the patient's monitored breathing; increasing the rate lower limit by the RSA value during exhalation; determining inhalation based on the patient's monitored breathing; and reducing the rate lower limit by the RSA value during inhalation.

[0096] Embodiment Ex4: The device or method of embodiment Ex3, wherein the RSA value is less than or equal to 15 beats per minute.

[0097] Embodiment Ex5: The device or method of embodiments Ex3 to Ex4, wherein the RSA value is based on one or more of the patient's heart rate, breathing rate, and activity level.

[0098] Embodiment Ex6: The apparatus or method of embodiments Ex3 to Ex5, wherein the computing device is further configured to perform or the method further comprises: reducing the RSA value for cardiac remodeling pacing.

[0099] Embodiment Ex7: The device or method of Embodiments Ex1 to Ex6, wherein increasing the rate floor to provide cardiac remodeling pacing during the remodeling period comprises increasing the rate floor to a cardiac remodeling pacing rate.

[0100] Embodiment Ex8: The device or method of embodiment Ex7, wherein the cardiac remodeling pacing rate is greater than or equal to 100 beats per minute.

[0101] Embodiment Ex9: The device or method of embodiments Ex1 to Ex8, wherein increasing the rate floor to provide cardiac remodeling pacing during the remodeling time period comprises gradually increasing the rate floor according to a ramp rate until the rate floor equals the cardiac remodeling pacing rate.

[0102] Embodiment Ex10: The device or method of embodiment Ex9, wherein the ramp rate is greater than or equal to 1 beat per minute increase for every 8 cardiac cycles.

[0103] Embodiment Ex11: The device or method of embodiments Ex1 to Ex10, wherein the lower rate limit is initially set to a minimum lower rate limit, wherein the minimum lower rate limit is greater than or equal to 60 beats per minute.

[0104] Embodiment Ex12: The device or method of Embodiments Ex1 to Ex11, wherein delivering pacing based on the lower rate limit comprises delivering cardiac conduction system pacing therapy based on the lower rate limit.

[0105] Embodiment Ex13: The apparatus or method of embodiments Ex1 to Ex12, wherein the computing device is further configured to perform or the method further comprises: initiating the cardiac remodeling pacing in response to an inactivity period when the patient is inactive or asleep.

[0106] Embodiment Ex14: An implantable medical device, comprising: a pacing electrode positioned near a patient's heart to deliver pacing therapy to the patient's heart;

[0107] a respiration sensor for determining a respiration rate of the patient; and a computing device operably coupled to the pacing electrode and the respiration sensor, the computing device configured to: switch between delivering support pacing using at least the pacing electrode based on a support pacing rate or delivering cardiac remodeling pacing using at least the pacing electrode to provide cardiac remodeling based on a cardiac remodeling pacing rate, wherein the cardiac remodeling pacing rate is greater than the support pacing rate; and monitor the patient's respiration rate using the respiration sensor; and

[0108] The cardiac remodeling pacing rate and the support pacing rate are adjusted based on the patient's respiratory rate to restore respiratory sinus arrhythmia (RSA).

[0109] Example Ex15: A method comprising: switching between delivering support pacing based on a support pacing rate or delivering cardiac remodeling pacing based on a cardiac remodeling pacing rate to provide cardiac remodeling, wherein the cardiac remodeling pacing rate is greater than the support pacing rate; monitoring the patient's respiratory rate; and adjusting the cardiac remodeling pacing rate and the support pacing rate based on the patient's respiratory rate to restore respiratory sinus arrhythmia (RSA).

[0110] Example Ex16: The device according to Example Ex14 or the method according to Example Ex15, wherein adjusting the cardiac remodeling pacing rate and the support pacing rate based on the patient's breathing rate to restore RSA includes: determining exhalation based on the patient's monitored breathing; increasing the cardiac remodeling pacing rate and the support pacing rate by the RSA value during exhalation; determining inhalation based on the patient's monitored breathing; and reducing the cardiac remodeling pacing rate and the support pacing rate by the RSA value during inhalation.

[0111] Embodiment Ex 17: The device or method of embodiment Ex 6, wherein the RSA value is less than or equal to 15 beats per minute.

[0112] Embodiment Ex18: The device or method of embodiments Ex16 to Ex17, wherein the RSA value is based on one or more of the patient's heart rate, breathing rate, and activity level.

[0113] Embodiment Ex19: The apparatus or method of embodiments Ex16 to Ex18, wherein the computing device is further configured to perform or the method further comprises: reducing the RSA value for cardiac remodeling pacing.

[0114] Embodiment Ex20: The device or method according to embodiments Ex14 to Ex19, wherein the cardiac remodeling pacing rate is greater than or equal to 100 beats per minute.

[0115] Embodiment Ex21: A device or method according to embodiments Ex14 to Ex20, wherein switching between delivering support pacing based on a support pacing rate using at least the pacing electrode or delivering cardiac remodeling pacing based on a cardiac remodeling pacing rate using at least the pacing electrode to provide cardiac remodeling includes: when switching from the support pacing to the cardiac remodeling pacing, gradually increasing the support pacing rate according to an increasing ramp rate until the support pacing rate is equal to the cardiac remodeling pacing rate; and when switching from the cardiac remodeling pacing to the support pacing, gradually decreasing the cardiac remodeling pacing rate by a decreasing ramp rate until the cardiac remodeling pacing rate is equal to the support pacing rate.

[0116] Embodiment Ex22: The apparatus or method of embodiment Ex21, wherein the magnitude of the increasing ramp rate is greater than the magnitude of the decreasing ramp rate.

[0117] Embodiment Ex23: The device or method of embodiments Ex14 to Ex22, wherein the supported pacing rate is greater than or equal to 75 beats per minute.

[0118] Embodiment Ex24: The device or method of Embodiments Ex14 to Ex23, wherein delivering pacing based on the lower rate limit comprises delivering cardiac conduction system pacing therapy based on the lower rate limit.

[0119] Embodiment Ex25: The apparatus or method of embodiments Ex14 to Ex24, wherein the computing device is further configured to perform or the method further comprises: initiating the cardiac remodeling pacing in response to an inactivity period when the patient is inactive or asleep.

[0120] Example Ex26: A device according to Example Ex25, wherein adjusting the cardiac remodeling pacing rate and the support pacing rate based on the patient's breathing rate to restore RSA includes: determining exhalation based on the patient's monitored breathing; increasing the cardiac remodeling pacing rate and the support pacing rate by the RSA value during exhalation; determining inhalation based on the patient's monitored breathing; and reducing the cardiac remodeling pacing rate and the support pacing rate by the RSA value during inhalation.

[0121] Embodiment Ex27: The device of embodiment Ex26, wherein the RSA value for cardiac remodeling pacing is less than the RSA value for support pacing.

[0122] Example Ex28: A device according to Example Ex25, wherein switching between using at least the pacing electrode to deliver support pacing based on a support pacing rate or using at least the pacing electrode to deliver cardiac remodeling pacing based on a cardiac remodeling pacing rate to provide cardiac remodeling includes: when switching from the support pacing to the cardiac remodeling pacing, gradually increasing the support pacing rate according to an increasing ramp rate until the support pacing rate is equal to the cardiac remodeling pacing rate; and when switching from the cardiac remodeling pacing to the support pacing, gradually decreasing the cardiac remodeling pacing rate according to a decreasing ramp rate until the cardiac remodeling pacing rate is equal to the support pacing rate.

[0123] Embodiment Ex29: The apparatus of embodiment Ex28, wherein the magnitude of the increasing ramp rate is greater than the magnitude of the decreasing ramp rate.

[0124] Embodiment Ex30: An apparatus according to embodiment Ex25, wherein the computing device is further configured to determine patient activity, wherein switching between delivering support pacing based on a support pacing rate using at least the pacing electrode or delivering cardiac remodeling pacing based on a cardiac remodeling pacing rate using at least the pacing electrode to provide cardiac remodeling includes: switching from the support pacing to the cardiac remodeling pacing in response to determining that the patient is inactive or the patient is asleep.

Claims

1. An implantable medical device, comprising: a pacing electrode positioned proximate to a patient's heart to deliver pacing therapy to the patient's heart; a respiration sensor for determining the patient's respiration rate; and a computing device operably coupled to the pacing electrode and the respiration sensor, the computing device configured to: delivering pacing using at least the pacing electrode based on a lower rate limit, monitoring the patient's breathing via the breathing sensor, adjusting the lower rate limit based on the patient's respiration to restore respiratory sinus arrhythmia (RSA), and The lower rate limit is increased to provide cardiac remodeling pacing during the remodeling period.

2. The apparatus of claim 1 , wherein adjusting the lower rate limit based on the patient's respiratory rate to restore RSA comprises: determining exhalation based on monitored breathing of the patient; During outgoing calls, the lower rate limit is increased by the RSA value; determining inhalation based on monitored breathing of the patient; as well as The rate floor is reduced by the RSA value during inhalation.

3. The apparatus of claim 2, wherein the RSA value is less than or equal to 15 beats per minute and / or the RSA value is based on one or more of the patient's heart rate, respiratory rate, and activity level.

4. The apparatus of claim 2 or 3, wherein the computing device is further configured to reduce the RSA value for cardiac remodeling pacing.

5. The apparatus of any one of claims 1 to 4, wherein increasing the lower rate limit to provide cardiac remodeling pacing during a remodeling period comprises: Increase the lower rate limit to Cardiac remodeling pacing rate.

6. The apparatus of any one of claims 1 to 5, wherein increasing the lower rate limit to provide cardiac remodeling pacing during a remodeling period comprises: The lower rate limit is gradually increased according to a ramp rate until the lower rate limit equals the cardiac remodeling pacing rate.

7. The apparatus according to any one of claims 1 to 6, wherein the lower rate limit is initially set to a minimum lower rate limit, wherein the minimum lower rate limit is greater than or equal to 60 beats per minute.

8. The apparatus of any one of claims 1 to 7, wherein the pacing electrode is to be positioned proximate a portion of a cardiac conduction system of the patient's heart to deliver cardiac conduction system pacing therapy to the patient's heart, wherein delivering pacing based on the lower rate limit using at least the pacing electrode comprises: Cardiac conduction system pacing therapy is delivered using at least the pacing electrode based on the lower rate limit.

9. The apparatus of any one of claims 1 to 8, wherein the computing device is further configured to initiate the cardiac remodeling pacing in response to a period of inactivity when the patient is inactive or asleep.

10. An implantable medical device, comprising: a pacing electrode positioned proximate to a patient's heart to deliver pacing therapy to the patient's heart; a respiration sensor for determining the patient's respiration rate; and a computing device operably coupled to the pacing electrode and the respiration sensor, the computing device configured to: switching between delivering support pacing using at least the pacing electrode based on a support pacing rate or delivering cardiac remodeling pacing using at least the pacing electrode based on a cardiac remodeling pacing rate to provide cardiac remodeling, wherein the cardiac remodeling pacing rate is greater than the support pacing rate; monitoring the patient's respiratory rate using the respiratory sensor; as well as The cardiac remodeling pacing rate and the support pacing rate are adjusted based on the patient's respiratory rate to restore respiratory sinus arrhythmia (RSA).

11. The apparatus of claim 10, wherein adjusting the cardiac remodeling pacing rate and the support pacing rate based on the patient's respiratory rate to restore RSA comprises: determining exhalation based on monitored breathing of the patient; increasing the cardiac remodeling pacing rate and the support pacing rate by an RSA value during exhalation; determining inhalation based on monitored breathing of the patient; as well as The cardiac remodeling pacing rate and the support pacing rate are reduced by the RSA value during inhalation.

12. The apparatus of claim 11, wherein the RSA value for cardiac remodeling pacing is less than the RSA value for support pacing.

13. The apparatus of any one of claims 10 to 12, wherein switching between delivering support pacing using at least the pacing electrode based on a support pacing rate or delivering cardiac remodeling pacing using at least the pacing electrode based on a cardiac remodeling pacing rate to provide cardiac remodeling comprises: When switching from the support pacing to the cardiac remodeling pacing, gradually increasing the support pacing rate according to an increasing ramp rate until the support pacing rate equals the cardiac remodeling pacing rate; and When switching from the cardiac remodeling pacing to the support pacing, the cardiac remodeling pacing rate is gradually reduced according to a reduced ramp rate until the cardiac remodeling pacing rate equals the support pacing rate.

14. The apparatus of claim 13, wherein a magnitude of the increasing ramp rate is greater than a magnitude of the decreasing ramp rate.

15. The apparatus according to any one of claims 10 to 14, wherein the computing device is further configured to determine patient activity, wherein switching between delivering support pacing using at least the pacing electrode based on a support pacing rate or delivering cardiac remodeling pacing using at least the pacing electrode based on a cardiac remodeling pacing rate to provide cardiac remodeling comprises: Switching from the support pacing to the cardiac remodeling pacing is performed in response to determining that the patient is inactive or the patient is asleep.

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