Delivery of cardiac pacing therapy for cardiac remodeling

Abstract

A method and apparatus for delivering remodeling pacing therapy capable of remodeling a patient's heart over a period of time, including delivering remodeling pacing during a first interval, the first interval including a first frequency and a first duration, determining whether to adjust one or both of the first frequency and the first duration during delivery of remodeling pacing during a next interval following the first interval, and delivering remodeling pacing during the next interval in response to the determination, wherein the next interval includes one of the first frequency and the first duration of the first interval, and the adjusted one or both of the first frequency and the first duration.

Description

[0001] Related applications

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 684,824, filed June 14, 2018, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0003] This disclosure relates to cardiac pacing methods and systems, and more specifically to methods and apparatus for delivering cardiac remodeling pacing in implantable medical devices. Background Technology

[0004] Heart failure (HF) is a complex disease state broadly defined by the heart's inability to adequately pump to meet its venous return and / or deliver sufficient output to meet the body's metabolic needs. HF is an increasingly prevalent life-threatening cardiovascular disease characterized by significant disability, frequent hospitalizations, and high mortality. HF is becoming increasingly common in older individuals (up to 10% of the total population) and has become the most common cause of hospitalization in people aged 65 and older. HF is a leading cause or contributing factor to hospitalization and is therefore becoming a significant contributor to healthcare spending. The specific clinical presentation of HF is determined by the underlying cause of heart failure.

[0005] The term heart failure (HF) broadly refers to a pathophysiological condition in which the heart is unable to deliver enough blood to meet metabolic demands (e.g., during physical activity, or at rest in severe cases) or to accommodate venous return. A range of further subclassifications and / or cardiac structures can then be applied based on the patient's symptoms. The New York Heart Association provides exemplary classifications of heart failure based on symptoms or objective assessment (Classes I-IV, AD). Heart failure can also be defined by ejection fraction. Typically, patients exhibiting an ejection fraction less than or equal to 0.35 are classified as having heart failure with reduced ejection fraction (HFrEF), while those with an ejection fraction greater than 0.35 are considered to have heart failure with preserved ejection fraction (HFpEF).

[0006] Symptoms of congestive heart failure indicate congestive heart failure. Exemplary symptoms of congestive heart failure include: decreased cardiac output leading to easy fatigue and organ dysfunction (such as kidney dysfunction), and symptoms associated with pulmonary congestion (leading to shortness of breath) or peripheral congestion (leading to swelling of the lower extremities and abdomen).

[0007] Based on a comparison of the incidence of ventricular arrhythmias in healthy, active men versus sedentary men and men with a history of myocardial infarction, a potential association between a sedentary lifestyle and the risk of ventricular arrhythmias was identified. One consequence of a sedentary lifestyle is that the size of the heart chambers may decrease, which is typically due to increased muscle thickness. Consequently, the highest number and grade of ventricular arrhythmias were found during exercise in healthy, sedentary men.

[0008] Nearly half of all patients with heart failure have a normal ejection fraction (EF), commonly referred to as heart failure with preserved ejection fraction (HFpEF). In patients with congestive heart failure and HFpEF, the amount of blood pumped out of the left ventricle of the heart with each stroke (ejection fraction) is greater than 50%. HFpEF is also often referred to as diastolic heart failure or diastolic dysfunction because the functional impairment is usually associated with changes that occur during diastole and ventricular filling. Approximately half of the population with heart failure has HFpEF, while the remainder exhibits heart failure with reduced ejection fraction, or heart failure with reduced ejection fraction (HFrEF).

[0009] The prevalence of heart failure with premature ventricular ejection fraction (HFpEF) continues to increase, likely due to the rising prevalence of common risk factors, including older age, hypertension, metabolic syndrome, renal insufficiency, and obesity. HFpEF is characterized by abnormal diastolic function, manifested as increased stiffness of the left ventricle, decreased left ventricular diastolic volume before the next beat, and reduced chamber volume (often due to increased muscle thickness). Patients experiencing HFpEF have an increased risk of atrial fibrillation and pulmonary hypertension. Summary of the Invention

[0010] This disclosure relates to a method and apparatus for delivering pacing therapy capable of remodeling a patient's heart over a period of time. According to one example of this disclosure, the method includes a method for delivering cardiac remodeling pacing therapy to a patient, comprising: delivering remodeling pacing during a first interval, the first interval including a first frequency and a first duration; determining whether to adjust one or both of the first frequency and the first duration during delivery of remodeling pacing in a next interval following the first interval; and, in response to the determination, delivering remodeling pacing in the next interval, wherein the next interval includes one of: a first frequency and a first duration of the first interval, and an adjusted one or both of the first frequency and the first duration.

[0011] According to another example of this disclosure, a cardiac device for delivering cardiac remodeling pacing to a patient includes: a housing; a plurality of electrodes electrically connected to the housing to deliver cardiac remodeling pacing to stimulate normalization of the patient's cardiac condition; and a processor located in the housing and configured to: deliver remodeling pacing during a first interval, the first interval including a first frequency and a first duration; determine whether to adjust one or both of the first frequency and the first duration during delivery of remodeling pacing in a next interval following the first interval; and, in response to the determination, deliver remodeling pacing in the next interval, wherein the next interval includes one of: the first frequency and the first duration of the first interval, and an adjusted one or both of the first frequency and the first duration. Attached Figure Description

[0012] Figure 1 This is a schematic diagram of an exemplary cardiac treatment delivery system that can be used to deliver pacing therapy according to the present disclosure.

[0013] Figure 2 To show in more detail Figure 1 A schematic diagram of an exemplary cardiac treatment delivery system.

[0014] Figure 3 This is an exemplary functional block diagram of an exemplary configuration of an implantable medical device according to examples of this disclosure.

[0015] Figure 4 This is an exemplary functional block diagram of the circuit system of an implantable medical device according to the present disclosure.

[0016] Figure 5 This is a flowchart of a method for delivering pacing therapy for cardiac remodeling, according to an example of this disclosure.

[0017] Figure 6 This is a graphical representation showing the effect of remodeling pacing on a patient's cardiac output.

[0018] Figure 7 This is a flowchart of a method for delivering pacing therapy for cardiac remodeling, according to an example of this disclosure.

[0019] Figure 8 This is a flowchart of a method for delivering pacing therapy for cardiac remodeling, according to an example of this disclosure.

[0020] Figure 9 This is a flowchart of a method for delivering remodeling pacing therapy according to an example of this disclosure. Detailed Implementation

[0021] It will be apparent to those skilled in the art that elements or processes from one embodiment may be used in combination with elements or processes from other embodiments, and that possible embodiments of this method, apparatus, and system using combinations of features set forth herein are not limited to the specific embodiments shown in the drawings and / or described herein. Furthermore, it will be appreciated that the embodiments described herein may include a number of elements that are not necessarily shown to scale.

[0022] Figure 1 This is a schematic diagram of an exemplary cardiac treatment delivery system that can be used to deliver pacing therapy according to the present disclosure. The treatment delivery system 10 may include an implantable medical device 16 (IMD) that can be coupled to leads 18, 20, 22 and a programmer 24. The IMD 16 may be, for example, an implantable pacemaker, cardioverter-defibrillator, and / or defibrillator that provides electrical signals to the heart 12 of a patient 14 via electrodes coupled to one or more of leads 18, 20, 22. The patient 14 may be, but is not necessarily, a person.

[0023] Leads 18, 20, and 22 extend into the heart 12 of the patient 14 to sense the electrical activity of the heart 12 and / or deliver electrical stimulation to the 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 enters the right ventricle 28. The left ventricular (LV) coronary sinus lead 20 extends through one or more veins, the vena cava, and the right atrium 26, and enters the coronary sinus 30 to reach the region adjacent to the free wall of the left ventricle 32 of the heart 12. The right atrial (RA) lead 22 extends through one or more veins and the vena cava, and enters the right atrium 26 of the heart 12. In one example, the atrial lead 22 may be positioned near the AV node / diaphragm region for His bundle pacing delivery, and at least one ventricular lead 18 may be positioned in the right ventricle or the ventricular lead 20 may be positioned in the left ventricle, as described below.

[0024] The IMD 16 can sense electrical signals associated with depolarization and repolarization of the heart 12 via electrodes coupled to at least one of leads 18, 20, 22. In some examples, the IMD 16 delivers pacing therapy (e.g., pacing pulses) to the heart 12 based on electrical signals sensed within the heart 12. The IMD 16 is operable to adjust one or more parameters associated with pacing therapy, such as, for example, pulse width, voltage amplitude, pulse train length, etc. Further, the IMD 16 is operable to deliver pacing therapy using various electrode configurations, which may be unipolar or bipolar. The IMD 16 can also deliver defibrillation therapy and / or cardioversion therapy via electrodes located on at least one of leads 18, 20, 22. Further, the IMD 16 can detect arrhythmias of the heart 12 (e.g., fibrillation of ventricles 28, 32) and deliver defibrillation therapy to the heart 12 in the form of electrical pulses. In some examples, IMD 16 can be programmed to deliver progressive treatment (e.g., pulses with increased energy levels) until the fibrillation of heart 12 stops.

[0025] In some examples, the programmer 24 may be a handheld computing device or computer workstation that can be used by a user (such as a doctor, technician, another clinician, and / or patient) to communicate with (e.g., program) the IMD 16. For example, a user may interact with the programmer 24 to retrieve information about one or more detected or indicated faults within and / or associated with pacing therapy delivered using the IMD 16. The IMD 16 and the programmer 24 may communicate wirelessly using any technology known in the art. Examples of communication technologies may include, for example, low-frequency or radio-frequency (RF) telemetry, but other technologies are also contemplated.

[0026] Figure 2 To show in more detail Figure 1 A schematic diagram of an exemplary cardiac treatment delivery system. Leads 18, 20, and 22 may be electrically coupled via connector block 34 to a treatment delivery module (e.g., for delivering pacing therapy), a sensing module (e.g., one or more electrodes for sensing or monitoring the electrical activity of the heart 12 to determine the effectiveness of pacing therapy), and / or any other module of IMD 16. In some examples, the proximal ends of leads 18, 20, and 22 may include electrical contacts that are electrically coupled to corresponding electrical contacts in connector block 34 of IMD 16. Additionally, in some examples, leads 18, 20, and 22 may be mechanically coupled to connector block 34 by means of a retaining screw, connecting pin, or other suitable mechanical coupling mechanism.

[0027] Each of leads 18, 20, and 22 comprises an elongated insulated lead body that can carry multiple conductors (e.g., concentrically coiled conductors, straight conductors, etc.) separated from each other by an insulating element (e.g., a tubular insulating sheath). In the example shown, bipolar electrodes 40 and 42 are positioned near the distal end of lead 18. Furthermore, bipolar electrodes 44 and 46 are positioned near the distal end of lead 20, and bipolar electrodes 48 and 50 are positioned near the distal end of lead 22.

[0028] Electrodes 40, 44, and 48 may be in the form of ring electrodes, and electrodes 42, 46, and 50 may be in the form of extendable spiral-tipped electrodes retractably mounted within insulated electrode heads 52, 54, and 56, respectively. Each of electrodes 40, 42, 44, 46, 48, and 50 may be electrically coupled to a corresponding conductor (e.g., spiral and / or straight) within the lead body of its associated leads 18, 20, and 22, and thereby coupled to a corresponding electrical contact on the proximal end of leads 18, 20, and 22.

[0029] Electrodes 40, 42, 44, 46, 48, and 50 can be further used to sense electrical signals (e.g., morphological waveforms within an electrogram (EGM)) accompanying depolarization and repolarization of the heart 12. These sensed electrical signals are conducted to the IMD 16 via corresponding leads 18, 20, and 22. In some examples, the IMD 16 can also deliver pacing pulses via electrodes 40, 42, 44, 46, 48, and 50 to induce depolarization of the cardiac tissue of the patient's heart 12. In some examples, such as... Figure 2As shown, the IMD 16 includes one or more housing electrodes, such as housing electrode 58, which may be integrally formed with or otherwise coupled to the outer surface of the housing 60 (e.g., a hermetically sealed housing) of the IMD 16. Any of electrodes 40, 42, 44, 46, 48, and 50 may be combined with housing electrode 58 for unipolar sensing or pacing. In other words, any of electrodes 40, 42, 44, 46, 48, 50, and 58 may be used in combination to form a sensing vector, for example, a sensing vector that can be used to assess and / or analyze the effectiveness of pacing therapy. An example of a sensing and pacing configuration can be seen in U.S. Patent Application No. 9,002,454, filed December 23, 2011 and assigned to the assignee of this invention, the disclosure of which is incorporated herein by reference in its entirety, as modified by the preferred use of the LV tip (i.e., electrode 46) – Rv coil (i.e., electrode 62) for both the pacing and sensing vectors. The vector from the LV tip to the RV coil may be better suited for performing impedance measurements. This impedance may be negatively correlated with the LV chamber size and may decrease as the LV chamber relaxes with remodeling pacing. Those skilled in the art will generally understand that other electrodes may also be selected as the pacing and sensing vectors.

[0030] For reference Figure 3 and Figure 4 In further detail, the housing 60 may enclose a treatment delivery module and a sensing module for monitoring the patient's heart rhythm, the treatment delivery module including a stimulation generator for generating cardiac pacing pulses and defibrillation or cardioversion shocks. Leads 18, 20, and 22 may also include elongated electrodes 62, 64, and 66, respectively, which may be in the form of coils. The IMD 16 may deliver defibrillation shocks to the heart 12 via any combination of the elongated electrodes 62, 64, and 66 and the housing electrode 58. Electrodes 58, 62, 64, and 66 may also be used to deliver cardioversion pulses to the heart 12. Furthermore, electrodes 62, 64, and 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 suitable for implantable defibrillation electrodes. Since electrodes 62, 64, and 66 are not typically configured for delivering pacing therapy, any of electrodes 62, 64, and 66 can be used to sense electrical activity during pacing therapy (e.g., for analyzing the effectiveness of pacing therapy) and can be used in conjunction with any of electrodes 40, 42, 44, 46, 48, 50, and 58. In at least one embodiment, the RV elongated electrode 62 can be used to sense the electrical activity of the patient's heart during delivery of pacing therapy (e.g., in conjunction with the housing electrode 58 to form an RV elongation, coil, or defibrillator-to-housing electrode vector).

[0031] Figure 1-2The configuration of the exemplary therapeutic delivery system 10 shown is merely an example. In one example, an atrial lead 22 is positioned near the AV junction / diaphragm region for His bundle pacing delivery, and a ventricular lead 18 is positioned in the right ventricle or a ventricular lead 20 is positioned in the left ventricle, or both ventricular leads 18 and 20 may be included, as described below. Furthermore, as will be described below, the electrode 50 of lead 22 may be in the form of a helical-tipped electrode so that the lead can be securely engaged near the AV junction / diaphragm region for His bundle pacing delivery.

[0032] Figure 3 This is a functional block diagram of an exemplary configuration of an implantable medical device according to examples of this disclosure. Figure 3 As shown, the IMD 16 may include a control module 81, a treatment delivery module 84 (e.g., which may include a stimulation generator), a sensing module 86, and a power supply 90. The control module 81 may include a processor 80, a memory 82, and a telemetry module 88. The memory 82 may include computer-readable instructions that, when executed, for example, by the processor 80, cause the IMD 16 and / or the control module 81 to perform the various functions described herein attributable to the IMD 16 and / or the control module 81. Further, the memory 82 may include any volatile, non-volatile, magnetic, optical, and / or electrical medium, such as random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically erasable programmable ROM (EEPROM), flash memory, and / or any other digital medium. As will be described in detail below, the memory 82 includes computer instructions relating to capture management (including methods of capture management according to this disclosure). Furthermore, the memory 82 includes computer instructions for one or more pacing schemes (e.g., one or more pacing algorithms, etc.). For example, one or more pacing algorithms pace the heart at an elevated heart rate for a specified duration, and then pace the heart at a second heart rate level for another pre-specified duration. One or more other embodiments involve pacing a patient's heart at a first elevated frequency and a first duration. In one or more pacing protocols, the pacemaker delivers a first elevated pacing frequency (e.g., up to 30 heart beats per minute higher than the resting heart rate for up to 10 or 20 minutes). Thereafter, the pacing frequency is increased to a second elevated pacing frequency (e.g., up to 20 HBM higher than the first elevated heart rate for up to 10 or 20 minutes). Thereafter, a third pacing frequency is delivered to allow the heart to beat slower than the second elevated pacing frequency. A fourth pacing frequency, lower than the third pacing frequency, is delivered to the heart by the pacemaker. Thereafter, the heart rate is allowed to gradually return to the resting heart rate level (with or without pacing). Several other pacing protocols are disclosed herein, which pacemakers can employ to reshape the heart.

[0033] The processor 80 of the control module 81 (also referred to as processor circuitry) 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 an equivalent discrete or integrated logic circuit system. In some examples, the processor 80 may include multiple components, such as any combination of the following: one or more microprocessors, one or more controllers, one or more DSPs, one or more ASICs, and / or one or more FPGAs, and other discrete or integrated logic circuit systems. The functionality attributed to the processor 80 herein may be embodied in software, firmware, hardware, or any combination thereof.

[0034] The control module 81 controls the treatment delivery module 84 to deliver treatment (e.g., electrical stimulation therapy such as pacing) to the heart 12 according to one or more selected treatment programs that can be stored in the memory 82. More specifically, the control module 81 (e.g., processor 80) controls the treatment delivery module 84 to deliver electrical stimulation, such as pacing pulses having amplitude, pulse width, frequency, or electrode polarity specified by one or more selected treatment programs (e.g., pacing therapy program, pacing recovery program, capture management program, etc.). As shown, the treatment delivery module 84 is electrically coupled to electrodes 40, 42, 44, 46, 48, 50, 58, 62, 64, 66, for example, via conductors of the corresponding leads 18, 20, 22 or, in the case of housing electrodes 58, via electrical conductors disposed within the housing 60 of the IMD 16. The treatment delivery module 84 can be configured to generate electrical stimulation therapy, such as pacing therapy, using one or more of electrodes 40, 42, 44, 46, 48, 50, 58, 62, 64, 66 and deliver the electrical stimulation therapy to the heart 12.

[0035] For example, the treatment delivery module 84 may deliver pacing stimulation (e.g., pacing pulses) via ring electrodes 40, 44, 48 coupled to leads 18, 20, and 22, respectively, and / or helical tip electrodes 42, 46, and 50 of leads 18, 20, and 22, respectively. Further, for example, the treatment delivery module 84 may deliver a defibrillation shock to the heart 12 via at least two of electrodes 58, 62, 64, and 66. In some examples, the treatment delivery module 84 may be configured to deliver pacing, cardioversion, or defibrillation stimulation in the form of electrical pulses. In other examples, the treatment 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] The IMD 16 may further include a switching module 85, and the control module 81 (e.g., processor 80) may use the switching module 85 to select, for example via a data / address bus, which of the available electrodes are used for treatment delivery (e.g., pacing pulses for pacing therapy) or which of the available electrodes are used for sensing. The switching module 85 may include a switch array, a switch matrix, a multiplexer, or any other type of switching device suitable for selectively coupling the sensing module 86 and / or the treatment delivery module 84 to one or more selected electrodes. More specifically, the treatment delivery module 84 may include a plurality of pacing output circuits. The switching module 85 may be used, for example, to selectively couple each of the plurality of pacing output circuits to one or more of electrodes 40, 42, 44, 46, 48, 50, 58, 62, 64, 66 (e.g., a pair of electrodes for delivering treatment to a pacing vector). That is, the switching module 85 may be used to selectively couple each electrode to one of the pacing output circuits of the treatment delivery module.

[0037] The sensing module 86 is coupled (e.g., electrically coupled) to a sensing device, which, along with any additional sensing devices, may include electrodes 40, 42, 44, 46, 48, 50, 58, 62, 64, and 66 to monitor the electrical activity of the heart 12, such as electrocardiogram (ECG) / electrogram (EGM) signals. The ECG / EGM signals can be used to analyze multiple pacing events. More specifically, one or more morphological features of each pacing event within the ECG / EGM signal can be used to determine whether each pacing event has a predetermined level of effectiveness. ECG / EGM signals can be further used to monitor heart rate (HR), heart rate variability (HRV), heart rate oscillation (HRT), deceleration / acceleration ability, deceleration sequence occurrence rate, T wave alternation (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] The switching module 85 can also be used, together with the sensing module 86, to select which of the available electrodes to use, for example, to sense the electrical activity of a patient's heart (e.g., to sense one or more electrical vectors of the patient's heart using any combination of electrodes 40, 42, 44, 46, 48, 50, 58, 62, 64, 66). In some examples, the control module 81 may select the electrodes used as sensing electrodes via a switching module within the sensing module 86 (e.g., by providing a signal via a data / address bus). In some examples, the sensing module 86 may include one or more sensing channels, each of which may include an amplifier.

[0039] In some examples, the sensing module 86 includes a channel comprising an amplifier having a passband relatively wider than that of an R-wave or P-wave amplifier. Signals from selected sensing electrodes chosen for coupling to this broadband amplifier can be provided to a multiplexer and subsequently converted by an analog-to-digital converter into multi-bit digital signals to be stored as EGMs in memory 82. In some examples, the storage of such EGMs in memory 82 may be under the control of direct memory access circuitry. The control module 81 (e.g., using a processor 80) may employ digital signal analysis techniques to characterize the digitized signals stored in memory 82 to analyze and / or classify one or more morphological waveforms of the EGM signal to determine the effectiveness of pacing therapy. For example, the processor 80 may be configured to determine or acquire one or more features of one or more sensed morphological waveforms within one or more electrical vectors of the patient's heart and store such features in memory 82 for use in determining the effectiveness of pacing therapy at a later time.

[0040] If the IMD 16 is configured to generate pacing pulses and deliver pacing pulses to the heart 12, the control module 81 may include a pacemaker timing and control module, which may be implemented as hardware, firmware, software, or any combination thereof. The pacemaker timing and control module may include one or more dedicated hardware circuits (such as an ASIC) separate from the processor 80 (such as a microprocessor), and / or software modules executed by components of the processor 80 (which may be a microprocessor or an ASIC). The pacemaker timing and control module may include a programmable counter that controls the base time interval associated with DDD, VVI, DVI, VDD, AAI, DDI, DDDR, VVIR, DVIR, VDDR, AAIR, DDIR, and other modes of single-chamber pacing and dual-chamber pacing. In the aforementioned pacing modes, “D” may indicate dual-chamber, “V” may indicate ventricle, “I” may indicate prohibited pacing (e.g., no pacing), “A” may indicate atrium, and “R” may indicate rate responsiveness. The first letter in pacing mode indicates the chamber being paced, the second letter indicates the chamber in which electrical signals are sensed, and the third letter indicates the chamber in which a response to the sensing is provided.

[0041] The intervals defined by the pacing timing and control module within control module 81 may include atrial and ventricular pacing escape intervals, refractory periods of sensed P and R waves that are ineffective for timing the restart of the escape interval, and / or the pulse width of the pacing pulse. As another example, the pacemaker timing and control module may define a blanking period and provide a signal from sensing module 86 to blank one or more channels (e.g., amplifiers) for a period during and after the delivery of electrical stimulation to heart 12. The duration of these intervals may be determined in response to data stored in memory 82. The pacemaker timing and control module of control module 81 may also determine the amplitude of the cardiac pacing pulse.

[0042] During pacing, the escape interval counter within the pacemaker timing / control module can be reset upon sensing of R and P waves. The treatment delivery module 84 (e.g., including a stimulation generator) may include one or more pacing output circuits, which are selectively coupled, for example via a switching module 85, to any combination of electrodes 40, 42, 44, 46, 48, 50, 58, 62, or 66 suitable for delivering bipolar or monopolar pacing pulses to one of the chambers of the heart 12. The control module 81 can reset the escape interval counter when a pacing pulse is generated by the treatment delivery module 84, and thereby control the basic timing of cardiac pacing functions, including anti-tachyarrhythmia pacing.

[0043] In some examples, the control module 81 may operate as an interrupt-driven device and may respond to an interrupt from the pacemaker timing and control module, which may correspond to the presence of sensed P and R waves and the generation of cardiac pacing pulses. Any necessary mathematical calculations may be performed by the processor 80, and any updates to values ​​or intervals controlled by the pacemaker timing and control module may occur after such an interrupt. A portion of the memory 82 may be configured as a plurality of recirculation buffers capable of storing a series of measured intervals, which may be analyzed by, for example, the processor 80 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.

[0044] The telemetry module 88 of the control module 81 may include a telemetry module for communication with, as described in this reference, etc. Figure 1 This refers to any suitable hardware, firmware, software, or any combination thereof that communicates with another device such as the described programmer 24. For example, under the control of the processor 80, the telemetry module 88 can receive downlink telemetry from the programmer 24 and send uplink telemetry to the programmer 24 by means of an antenna (which may be internal and / or external). The processor 80 can provide, for example, data to be transmitted to the programmer 24 via the uplink and control signals for the telemetry circuitry within the telemetry module 88 via an address / data bus. In some examples, the telemetry module 88 can provide the received data to the processor 80 via a multiplexer. In at least one embodiment, the telemetry module 88 can be configured to transmit a warning or alarm if pacing therapy becomes ineffective or less effective (e.g., does not have a predetermined level of effectiveness).

[0045] The various components of the IMD 16 are further coupled to a power source 90, which may include rechargeable and non-rechargeable batteries. Non-rechargeable batteries may be selected to last for several years, while rechargeable batteries may be inductively charged from an external device, for example, daily or weekly.

[0046] Figure 4 This is an exemplary functional block diagram of the circuit system of an implantable medical device according to the present disclosure. Figure 4The bipolar RA lead 22, bipolar RV lead 18, and bipolar LV CS lead 20 are depicted coupled to an implantable pulse generator (IPG) circuit 31, without LA CS pacing / sensing electrodes 28 and 30. This IPG circuit 31 has a programmable mode and parameters of the biventricular DDD / R type, as is well known in the pacing field. Furthermore, a sensor signal processing circuit 43 is indirectly coupled to a timing circuit 83 and coupled to a microcomputer circuit system 33 via a data and control bus. The IPG circuit 31 is shown in a functional block diagram generally divided into the microcomputer circuit 33 and the pacing circuit. The pacing circuit includes a digital controller / timer circuit, an output amplifier circuit 51, a sensing amplifier circuit 55, an RF telemetry transceiver 41, an activity sensor circuit 35, and several other circuits and components described below.

[0047] Crystal oscillator circuit 47 provides a basic timing clock for the pacing circuit, while battery 29 provides power. Power-on reset circuit 45 responds to the initial connection from the circuit to the battery that defines the initial operating conditions, and similarly resets the device's operating state in response to the detection of a low battery condition. Reference mode circuit 37 generates a stable voltage reference and current for the analog circuitry within the pacing circuitry, while analog-to-digital converter (ADC) and multiplexer circuit 39 digitizes the analog signals and voltages to provide real-time telemetry of cardiac signals from sensing amplifier 55 for uplink transmission via RF transmitter and receiver circuit 41. Voltage reference and bias circuit 37, ADC and multiplexer 39, power-on reset circuit 45, and crystal oscillator circuit 47 may correspond to any of the components currently used in commercially available implantable cardiac pacemakers.

[0048] IPG generates pacing pulses to the heart tissue. Typically, these pacing pulses can be timed to a target heart rate for each patient. To adjust the patient's heart rate, the pacemaker adjusts the interval between pacing pulses. For example, to increase the patient's heart rate, the interval between pulses generated by the pacemaker is decreased. Conversely, to decrease the patient's heart rate, the interval between pulses is increased. In one or more embodiments, the exercise program can be configured to include exercise intervals (i.e., a higher target heart rate than the patient's resting heart rate) interspersed with recovery intervals (i.e., a lower target heart rate than the immediately preceding exercise interval). A target heart rate zone for exercising the heart can be 50%–85% of the patient's maximum heart rate. In one or more embodiments, the target heart rate zone can be set to 75%–95% of the patient's maximum heart rate zone. In one or more other embodiments, the target heart rate zone can be set to 105% of the patient's maximum heart rate zone for a short time period (e.g., up to 20 minutes or up to 30 minutes, etc.).

[0049] An exercise protocol can be implemented using a base rate, which consists of a set of increased frequency intervals interspersed with recovery frequency intervals (also known as reduced frequency intervals). This base rate can be adjusted by modifying the pacing pulses for each interval. For example, if the resting heart rate is the base rate (the intervals are measured based on this base heart rate), the first increased frequency can be determined by adding a pre-specified number of HBMs (e.g., 20 HBM) for that particular interval to the patient's average resting heart rate (e.g., 60 HBM) to obtain 80 HBM over a first time period (e.g., 10 minutes) (i.e., 60 HBM + 20 HBM). Since the target heart rate level is now 80 HBM, the intervals between pulses generated from the pacemaker can be reduced.

[0050] A pacemaker can be configured to use the maximum heart rate level as the baseline heart rate and adjust the target frequency downwards from the maximum heart rate to a target heart rate zone (e.g., 50%–85% of the maximum heart rate zone). A patient's maximum heart rate can be determined by tracking their daily activities or by using a known formula (i.e., 220 HBPM minus the patient's age). Maximum heart rate can depend on a variety of factors, including the patient's age, physical activity, and cardiac condition.

[0051] If the IPG is programmed to a frequency-responsive mode, signals output from one or more physiological sensors are used as frequency control parameters (RCPs) to derive the physiological escape interval. For example, the escape interval is adjusted proportionally to the patient's activity level obtained in the patient activity sensor (PAS) circuitry 35 within the illustrated exemplary IPG circuitry 31. The patient activity sensor 35 is coupled to the IPG housing and may take the form of a piezoelectric crystal transducer well known in the art, and its output signal is processed and used as the RCP. Sensors 316 generate electrical signals in response to sensed bodily activity, which are processed by the activity circuitry 35 and provided to the digital controller / timer circuitry 83. The activity circuitry 35 and the associated sensor 316 may correspond to the circuit systems disclosed in U.S. Patents 5,052,388 and 4,428,378.

[0052] Conventional pacemakers are currently configured to automatically track a person's heart rate for a specific period of time (e.g., one day) and customize the pacing pulse interval in response to the patient's activity. Activity sensors monitor the person's activity throughout the day, and the processor adjusts the pacemaker's pacing rate based on the patient's activity. After the person's heart rate has been tracked for a day, rate profile optimization is automatically performed, as described in the Medtronic CLARIA MRI manual. TM / CLARIA MRI TMThe full description is found in the QUAD CRT-Ds Reference Manual M963432A001, which is incorporated herein by reference in its entirety and is available free of charge from Medtronic Corporation, 710 Medtronic Avenue, Minneapolis, 55432, Minnesota, and its website. The goal of rate distribution optimization is to ensure that the pacemaker's rate response remains appropriate for the full range of patient activity. Each day, the pacemaker collects and stores daily and long-term averages of the percentage of time the patient's sensor-indicated rate is at different pacing frequencies. The pacemaker then uses ADL response and exercise response parameters to define the percentage of time the pacing rate remains within the ADL and exercise frequency ranges, respectively. Based on daily comparisons, the pacemaker automatically adjusts the ADL setpoint, UR setpoint, or both. During exercise programs, rate distribution optimization identifies when the heart is consciously exercising without reducing pacing.

[0053] Similarly, the invention can be practiced in conjunction with alternative types of sensors such as oxygenation sensors, pressure sensors, pH sensors, and respiration sensors (all of which are known for providing rate-responsive pacing capability). Alternatively, QT time can be used as a rate indication parameter, in which case no additional sensor is required. Similarly, the invention can also be practiced in non-rate-responsive pacemakers.

[0054] Data transmission to and from an external programmer is accomplished using telemetry antenna 57 and an associated RF transceiver 41, which demodulates both received downlink telemetry and transmits uplink telemetry. As is known in the pacing field, uplink telemetry capability typically includes the ability to transmit stored digital information (e.g., operating modes and parameters, EGM histograms, and other events, as well as real-time EGM indicating atrial and / or ventricular electrical activity and marker channel pulses that indicate the occurrence of sensed and paced depolarization in the atria and ventricles).

[0055] The microcomputer 33 includes a microprocessor 80 and an associated system clock, and includes on-processor RAM and ROM chips 82A and 82B, respectively. 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 A-trigger (TIRG), RV-trigger, and LV-trigger signals generated by timers in the digital timer / controller circuit 83, and A-event, RV-event, and LV-event signals generated by the sense amplifier circuit 55, etc. The microcomputer circuit 33 controls specific values ​​of the timeout interval and delay performed by the digital controller / timer circuit 83 according to programmed parameter values ​​and operating modes via the data and control bus 306. Furthermore, if programmed to operate as a rate-responsive pacemaker, a timed interrupt can be provided, for example, every cycle or every two seconds, to allow the microprocessor to analyze active sensor data and update the basic AA, VA, or VV escape interval (if applicable). Additionally, the microprocessor 80 can also be used to define a variable, operable AV delay interval and the energy delivered to each ventricle.

[0056] In one embodiment, microprocessor 80 is a custom microprocessor adapted to fetch and execute instructions stored in RAM / ROM unit 82C in a conventional manner. However, it is contemplated that other implementations may be suitable for practicing the invention. For example, off-the-shelf, commercially available microprocessors or microcontrollers, or custom-designed, dedicated hardwired logic or state machine-type circuitry, may perform the functions of microprocessor 80.

[0057] The digital controller / timer circuit 83 operates under the overall control of the microcomputer 33 to control the timing function and other functions within the pacing circuit, and includes a set of timing circuits and associated logic circuits. Certain circuits of this set of timing circuits and associated logic circuits relevant to the present invention are depicted. The depicted timing circuits include a URI / LRI timer 83A, a VV delay timer 83B, an intrinsic interval timer 83C for timing the interval between past V-events or A-events or VV conduction intervals, an escape interval timer 83D for timing the escape intervals of AA, VA, and / or VV pacing, an AV delay interval timer 83E for timing the A-LVp delay (or A-RVp delay) following an A-event or A-trigger, a postventricular timer 83F for timing the postventricular time interval, and a date / time clock 83G.

[0058] The AV delay interval timer 83E is loaded with an appropriate delay interval for a ventricular chamber (i.e., an A-RVp delay or A-LVp delay determined using known methods) to count down from the start of a preceding A-pacing or A-event. The interval timer 83E triggers pacing stimulus delivery and can be based on one or more previous cardiac cycles (or from a dataset derived empirically for a given patient).

[0059] The post-event timer 83F counts down the post-ventricular time period following an RV-event, LV-event, RV-trigger, or LV-trigger, or the post-atrial time period following an A-event or A-trigger. The duration of the post-event time period can also be selected as a programmable parameter stored in the microcomputer 33. The post-ventricular time period includes PVARP, post-atrial ventricular blanking period (PAVBP), ventricular blanking period (VBP), post-ventricular atrial blanking period (PVARP), and ventricular refractory period (VRP), but other time periods can also be appropriately defined, at least in part, depending on the operating circuitry used in the pacemaker. The post-atrial time period includes the atrial refractory period (ARP) (during which A-events are ignored for the purpose of resetting any AV delays) and the atrial blanking period (ABP) (during which atrial sensing is disabled). It should be noted that the onset of the post-atrial time interval and the AV delay may begin substantially simultaneously with the start or end of each A-event or A-trigger, or, in the case of an A-trigger, at the end of A-pacing following the A-trigger. Similarly, the onset of the post-ventricular time interval and the VA escape interval may begin substantially simultaneously with the start or end of a V-event or V-trigger, or, in the case of a V-trigger, at the end of V-pacing following the V-trigger. The microprocessor 80 may also optionally calculate the AV delay, the post-ventricular time interval, and the post-atrial time interval, which vary with the sensor-based escape interval established in response to RCP(multiple) and / or with the intrinsic atrial rate.

[0060] Output amplifier circuit 51 includes an RA pacing pulse generator (and an LA pacing pulse generator, if LA pacing is provided), an RV pacing pulse generator, and an LV pacing pulse generator, or any of those currently used in commercially available cardiac pacemakers that provide atrial and ventricular pacing. To trigger the generation of an RV-pacing or LV-pacing pulse, digital controller / timer circuit 83 generates an RV-trigger signal at the timeout of an A-RVp delay (in the case of RV pre-excitation) or an LV-trigger at the timeout of an A-LVp delay (in the case of LV pre-excitation), the timeouts of which are provided by an AV delay interval timer 83E (or a VV delay timer 83B). Similarly, at the end of a VA escape interval timed by escape interval timer 83D, digital controller / timer circuit 83 generates an RA-trigger signal (or an LA-trigger signal, if provided), to trigger the output of an RA-pacing pulse.

[0061] Output amplifier circuit 51 includes switching circuitry for coupling selected pacing electrode pairs from the lead conductors and neutral canister (IND_CAN) electrode 20 to the RA pacing pulse generator (and LA pacing pulse generator, if provided), RV pacing pulse generator, and LV pacing pulse generator. Pacing / sensing electrode pair selection and control circuitry 53 selects the lead conductors and associated pacing electrode pairs to be coupled to the atrial and ventricular output amplifiers within output amplifier circuit 51 for RA, LA, RV, and LV pacing.

[0062] Sensing amplifier circuit 55 includes a sensing amplifier corresponding to any of the sensing amplifiers currently used in contemporary cardiac pacemakers for atrial and ventricular pacing and sensing. It is common in the art to use very high-impedance P-wave and R-wave sensing amplifiers to amplify the voltage difference signal generated across the sensing electrode pair by the passage of the cardiac depolarization wavefront. High-impedance sensing amplifiers use high gain to amplify low-amplitude signals and rely on passband filtering, time-domain filtering, and amplitude threshold comparison to distinguish P-waves or R-waves from background electrical noise. Digital controller / timer circuit 83 controls the sensitivity settings of atrial and ventricular sensing amplifier 55.

[0063] The sensing amplifier is typically decoupled from the sensing electrode during the blanking period before, during, and after the delivery of a pacing pulse to any electrode in the pacing system's pacing electrodes to avoid saturation of the sensing amplifier. Sensing amplifier circuit 55 includes a blanking circuit for decoupling selected pairs of lead conductors and IND_CAN electrodes 20 from the inputs of the RA sensing amplifier (and LA sensing amplifier, if provided), RV sensing amplifier, and LV sensing amplifier during ABP, PVABP, and VBP. Sensing amplifier circuit 55 also includes a switching circuit for coupling selected sensing electrode lead conductors and IND_CAN electrodes 20 to the RA sensing amplifier (and LA sensing amplifier, if provided), RV sensing amplifier, and LV sensing amplifier. Again, sensing electrode selection and control circuit 53 selects conductors and associated sensing electrode pairs to be coupled to the atrial and ventricular sensing amplifiers within output amplifier circuit 51 and sensing amplifier circuit 55 for RA, LA, RV, and LV sensing along desired unipolar and bipolar sensing vectors.

[0064] Right atrial depolarization or a P wave in the RA-sensing signal sensed by the RA sensing amplifier results in an RA-event signal being transmitted to the digital controller / timer circuit 83. Similarly, left atrial depolarization or a P wave in the LA-sensing signal sensed by the LA sensing amplifier (if provided) results in an LA-event signal being transmitted to the digital controller / timer circuit 83. Ventricular depolarization or an R wave in the RV-sensing signal sensed by the ventricular sensing amplifier results in an RV-event signal being transmitted to the digital controller / timer circuit 83. Similarly, ventricular depolarization or an R wave in the LV-sensing signal sensed by the ventricular sensing amplifier results in an LV-event signal being transmitted to the digital controller / timer circuit 83. The RV-event signal, LV-event signal, RA-event signal, and LA-sensing signal can be unintended or not, and can be inadvertently triggered by electrical noise signals or abnormally conducted depolarization waves instead of genuine R or P waves.

[0065] Figure 5This is a flowchart illustrating a method of using a pacemaker to deliver pacing therapy capable of remodeling the heart over a period of time, according to an example of this disclosure. In one or more embodiments, the pacing therapy can lead to cardiac remodeling. According to one example, an atrial lead 22 positioned near the AV junction / high septum region can be used to deliver pacing for cardiac remodeling via a tip electrode 50 and a loop electrode 48. Those skilled in the art will understand that other pacing vectors can be used to pace the heart (e.g., His bundle therapy as described in U.S. Patent Application No. 62 / 581,486, filed November 3, 2018, and U.S. Patent Application No. 62 / 573,685, filed October 17, 2018, which are incorporated herein by reference in their entirety). According to one example of this disclosure, remodeling pacing therapy can be delivered at predetermined times of day. For example, pacing therapy can be delivered when the patient is most likely to be inactive (e.g., the patient is asleep or in a supine position). Inactivity can be identified in a variety of ways (e.g., through detection monitoring, from wearable devices with sensors (e.g., such as Garmin)). TM (Historical data collected by watches, or information entered by the user). When a resting heart rate is detected, such as when the patient is asleep or in a supine position, it can be determined that the patient is inactive. Alternatively, pacing therapy can be delivered manually or automatically without sensing any data (e.g., at a certain time of day, such as nighttime). Therefore, as Figure 5 As shown, in a method for delivering pacing therapy via a pacemaker device for cardiac remodeling 101 according to an example of this disclosure, processor 80 may determine whether to initiate delivery of remodeling pacing therapy (box 100). For example, processor 80 may determine a predetermined time of day when the patient is most likely to be inactive, such as, for example, between 12:00 a.m. and 5:00 a.m., or by determining that patient activity sensed via an activity sensor is less than a predetermined threshold indicating that the patient is asleep and / or in a supine position.

[0066] When determining the delivery schedule for remodeling pacing therapy ("Yes" in box 100), processor 80 may deliver the remodeling pacing therapy at a predetermined frequency and / or duration (box 102). For example, processor 80 may deliver remodeling pacing at an elevated frequency (e.g., 100 bpm for a duration of 30 minutes), or in another example, at an elevated frequency (e.g., 100 bpm for a specific time period, such as 5 hours per day). In another example, processor 80 may deliver remodeling pacing at an initial lower frequency (e.g., 70 bpm) and gradually increase the patient's heart rate to, for example, a predetermined heart rate threshold (e.g., 100 bpm). Exemplary modes for delivering remodeling pacing at variable frequencies and / or durations are described in detail below. Additionally, exercising the heart with adjusted pacing parameters (e.g., amplitude, etc.) may continue for a period of time to increase the heart rate, and / or until a termination condition is detected.

[0067] Once remodeling pacing delivery is initiated (box 102), processor 80 can begin monitoring the patient's symptoms caused by the delivered remodeling pacing (box 104). Furthermore, processor 80 can monitor whether a patient arousal signal has been received from the patient. Examples of a patient arousal signal could be a signal initiated by the patient indicating that the patient is experiencing discomfort due to the delivered remodeling pacing, or a signal received from activity sensor 35 indicating that the patient is no longer asleep or in a supine position (box 106). If processor 80 determines that a patient arousal signal has been received ("Yes" in box 106), processor 80 pauses the delivery of remodeling pacing therapy (box 116) and awaits the next scheduled session for remodeling pacing delivery (box 100).

[0068] Based on the monitored symptoms (box 104), and if no patient arousal signal has been received ("No" in box 106), processor 80 determines whether the delivered remodeling pacing results in a measurable effect that indicates the delivery of remodeling pacing is effective in causing some degree of normalization of the patient's cardiac condition. For example, processor 80 may monitor changes in one or more parameters, such as tissue perfusion, atrial perfusion, estimated pulmonary artery diastolic pressure (ePad), right ventricular pressure, left ventricular pressure, and pressure substitution (such as impedance), as indicators that remodeling pacing is affecting the patient's overall cardiac condition in a manner indicating the presence of some degree of cardiac normalization. In one or more other embodiments, treatment is automatically delivered and / or paused after a period of time (e.g., pausing treatment 1 / 2 hour after pacing delivery, 1 hour after pacing delivery, etc.) without detecting parameters such as tissue perfusion, atrial perfusion, estimated pulmonary artery pressure (ePad), right ventricular pressure, left ventricular pressure, and pressure substitution (such as impedance).

[0069] In one example, to determine whether a measurable normalization effect exists (box 108), processor 80 may determine whether there is a change in perfusion associated with the patient. For example, a change in tissue perfusion may be determined by measuring tissue perfusion during delivery of the remodeling pacing therapy and comparing the measured tissue perfusion to a non-pacing baseline tissue perfusion level determined before the remodeling pacing is delivered to the patient (e.g., at the time of device implantation). Although the description below uses tissue perfusion as a target parameter for adjusting treatment, other parameters mentioned above may also be used.

[0070] If the currently measured tissue perfusion level does not increase relative to the baseline tissue perfusion level, processor 80 determines that the delivered remodeling pacing has not yet resulted in a measurable effect indicative of cardiac normalization ("No" in box 108). A determination is then made regarding whether to adjust the delivery of remodeling pacing (in box 110) to increase the likelihood that subsequent deliveries of remodeling pacing will result in a measurable effect indicative of cardiac normalization.

[0071] Figure 6 This is a graphical representation illustrating the effect of remodeling pacing on a patient's cardiac output. Cardiac output (CO) is the amount of blood pumped by the heart per minute and is the product of heart rate (HR) or the number of beats per minute and stroke volume (SV), the amount of blood pumped with each beat; therefore, CO = HR x SV. Figure 6 As shown, cardiac output typically increases with increasing heart rate until it reaches its maximum increase 113. This maximum output 113 tends to vary from patient to patient and may differ for an individual patient depending on the patient's current cardiac condition. Once the maximum cardiac output 113 is reached, any further increase in the pacing heart rate will result in a decrease in the patient's cardiac output 115 and may indicate a detrimental effect on the patient's cardiac condition.

[0072] Therefore, in order to determine whether to adjust pacing therapy ( Figure 5 In the case of no detectable measurable effect indicating cardiac normalization (No in box 108), processor 80 may determine to adjust pacing therapy if the slope of the patient's cardiac output is determined to be increasing (Yes in box 110). Processor 80 may then adjust remodeling pacing by increasing the frequency and / or duration of remodeling pacing (Box 112). Typical intervention adjustment preference is to increase the maximum pacing frequency, while increasing the duration as a secondary adjustment would make the frequency effect symptomatic. However, if no increase in the slope of the patient's cardiac output is determined, processor 80 determines not to adjust pacing therapy (No in box 110).

[0073] Once processor 80 determines to adjust the treatment ("Yes" in box 110) and thus adjusts the remodeling pacing (box 112), or processor 80 determines not to adjust the treatment ("No" in box 110), it makes a determination as to whether the session time has ended (box 114). For example, processor 80 may determine whether remodeling pacing treatment is delivered at a frequency of at least 100 bpm for a certain period of time (e.g., 30 minutes), or in another example, whether remodeling pacing treatment is delivered at a frequency of at least 100 bpm for 5 hours per day.

[0074] If the session time has not yet ended ("No" in box 114), the processor 80 continues to deliver remodeling pacing therapy using the same or adjusted frequency and / or duration (box 102). On the other hand, if the session time has ended ("Yes" in box 114), the processor 80 suspends the delivery of remodeling pacing therapy (box 116) and waits for the next scheduled session for the delivery of remodeling pacing (box 100).

[0075] If the currently measured tissue perfusion level has increased relative to the baseline tissue perfusion level, processor 80 determines that the delivered remodeling pacing has resulted in a measurable effect indicating cardiac normalization ("Yes" in box 108). A determination is then made as to whether this effect exceeds a predetermined symptom avoidance threshold (box 118) that indicates remodeling pacing is too aggressive for the patient. If the effect is determined to exceed the predetermined symptom avoidance threshold ("Yes" in box 118), processor 80 determines whether to adjust and continue delivering the adjusted remodeling pacing treatment, or to pause the delivery of remodeling treatment to address the indication that remodeling pacing is too aggressive for the patient (box 120).

[0076] For example, if the number of premature ventricular contractions (PVCs) occurring during remodeling pacing delivery increases, processor 80 can determine that the effect is greater than a predetermined symptom avoidance threshold ("Yes" in box 118) and therefore determine that the remodeling treatment is too aggressive. When the increased PVCs are an indication in box 118 for determining that remodeling pacing is too aggressive, processor 80 determines not to pause the remodeling pacing delivery ("No" in box 120) and therefore adjusts the pacing treatment by reducing the pacing delivery rate by a predetermined amount ("Yes" in box 120). For example, the delivery rate could be reduced by 10 beats per minute. In another example, processor 80 can track the original baseline slope and pause treatment when the slope deviates from the baseline slope by a predetermined amount or a predetermined percentage.

[0077] In another example, if a contractility measure threshold is determined to be met, processor 80 can determine that the effect is greater than a predetermined symptom avoidance threshold ("Yes" in box 118), and therefore determine that the remodeling treatment is too aggressive. For example, determining whether a contractility measure is met may include determining whether there is a decrease in the amplitude of S1 and S2 heart sounds sensed via a phonocardiogram sensor, or whether an S3 heart sound is sensed via a cardiac sensor, during the delivered remodeling pacing. Many pacemakers are configured to detect heart sounds. An exemplary pacemaker, AMPLIA, is available from Medtronic, Inc., Minneapolis, Minnesota. TM Or CLARIA TM It is configured to detect heart sounds. When the contractility measurement threshold is the indication in box 118 for determining that remodeling therapy is too aggressive, processor 80 determines to suspend the delivery of remodeling pacing due to the indication ("Yes" in box 120), and thus suspends the delivery of remodeling pacing therapy (box 116), and waits for the next scheduled session for the delivery of remodeling pacing (box 100).

[0078] In yet another example, if a biomarker indicator exceeds a biomarker indicator threshold, processor 80 may determine that the effect is greater than a predetermined symptom avoidance threshold ("Yes" in box 118), and therefore determine that remodeling treatment is too aggressive. For example, determining whether a biomarker indicator exceeds a biomarker indicator threshold may include determining whether a biomarker indicator used to diagnose congestive heart failure (CHF), such as brain natriuretic peptide (BNP, also known as B-type natriuretic peptide), increases beyond a predetermined threshold indicating CHF. When a biomarker indicator is used as an indication that remodeling treatment is too aggressive, processor 80 determines to suspend the delivery of remodeling pacing due to the indication ("Yes" in box 120), and therefore suspends the delivery of remodeling pacing treatment (box 116), and awaits the next scheduled session for the delivery of remodeling pacing (box 100).

[0079] In another example, if the ST segment measurement result is determined to meet an ST segment threshold, the processor 80 can determine that the effect is greater than a predetermined symptom avoidance threshold ("Yes" in box 118), and thus determine that the remodeling treatment is too aggressive. For example, the ST segment measurement result during the delivered remodeling pacing can be determined based on an ECG signal sensed by the IMD 16 or based on an EGM cardiac signal sensed from an alternative location by another internal or external monitoring device. In one or more embodiments, data is stored (e.g., in a table) in a patient-specific memory, where the data associates the ST segment with acceptable pacing treatment outcomes so that pacing can continue and / or the ST segment is associated with overly aggressive pacing treatment so that treatment can be paused. The ST segment measurement result determined during the delivered pacing is compared to an ST threshold (which can be determined during non-pacing cardiac activity), and if an increase in the ST segment measurement result is determined to have occurred, the ST segment threshold is determined to be met. When a change in ST segment measurement results is an indication in box 118 that remodeling therapy is too aggressive, processor 80 determines not to pause the delivery of remodeling pacing ("No" in box 120) and thus adjusts pacing therapy by reducing the pacing delivery rate by a predetermined amount ("Yes" in box 120).

[0080] Once processor 80 adjusts the delivery of remodeling pacing (RTP) to address instances of overly aggressive RTP ("Yes" in box 118) or instances of RTP that do not result in a measurable normalization effect ("No" in box 108) (box 112), it makes a determination regarding whether the session has ended (box 114). For example, processor 80 may determine whether RTP has been delivered at a frequency of at least 100 bpm for 30 minutes. In another example, processor 80 may determine whether RTP has been delivered at a frequency of at least 100 bpm for a period of 5 hours per day for two weeks. If the session has not ended ("No" in box 114), processor 80 continues to deliver RTP (box 102), and the treatment continues. On the other hand, if the session has ended ("Yes" in box 114), processor 80 pauses the delivery of RTP (box 116) and awaits the next scheduled RTP delivery session (box 100).

[0081] In this manner, a method for delivering cardiac remodeling pacing therapy according to an example of this disclosure may include: processor 80 sensing cardiac signals 300 and monitoring cardiac symptoms via a tip electrode 50 and a loop electrode 48 of an atrial lead 22 to determine whether unwanted symptoms are induced due to the delivered remodeling pacing. For example, processor 80 may deliver cardiac remodeling pacing to stimulate normalization of a patient's cardiac condition, monitor one or more parameters in response to the delivered remodeling pacing, determine the effect on cardiac normalization in response to the monitoring, and adjust the remodeling pacing in response to the determined effect on cardiac normalization.

[0082] Figure 7 This is a flowchart of a method for delivering pacing therapy for cardiac remodeling according to an example of this disclosure. According to another example, during the real-time delivery of remodeling pacing therapy, processor 80 may determine, based on short-term symptom avoidance factors, whether undesirable symptoms are induced by the delivered remodeling pacing, and adjust or suspend the delivered therapy accordingly, as described above. Additionally, processor 80 may monitor long-term efficacy improvement factors to determine whether there is a long-term improvement in cardiac condition due to the delivery of remodeling pacing therapy over an extended period. Specifically, for example, once remodeling pacing therapy has been delivered for a predetermined long period (e.g., delivered at a frequency of at least 100 bpm for 5 hours daily for, for example, two weeks), processor 80 may begin long-term monitoring of the effects of remodeling pacing to determine whether there is an improvement toward the desired level of cardiac normalization.

[0083] For example, such as Figure 7As shown in the example, during continuous real-time monitoring 101 of the remodeling pacing delivered as described above, processor 80 assesses the long-term effects of the delivered remodeling pacing to determine whether the remodeling pacing has led to successful normalization of the patient's heart. For example, once processor 80 determines that it is time to perform long-term monitoring of the remodeling pacing ("Yes" in box 200), i.e., when it is determined that the remodeling pacing has been delivered at a frequency of at least 100 bpm for a period of 5 hours per day for two weeks, processor 80 begins monitoring one or more long-term parameters associated with the long-term delivery of the remodeling pacing (box 202) and assesses the long-term effects of the delivered remodeling pacing to determine whether the remodeling pacing has led to successful normalization of the patient's heart. A determination is then made regarding whether to adjust the remodeling pacing based on the long-term parameters (box 204). If processor 80 determines that the long-term parameters indicate that the remodeling pacing should be adjusted ("Yes" in box 204), processor 80 adjusts the remodeling pacing (box 206) and waits for the next scheduled time to perform long-term monitoring of the remodeling pacing ("Yes" in box 200). On the other hand, if processor 80 determines that long-term parameters indicate that remodeling pacing should not be adjusted (No in box 204), processor 80 can determine whether to monitor additional long-term parameters (box 208) to determine whether the additional long-term parameters indicate that remodeling pacing has led to successful normalization of the patient's heart.

[0084] If the additional long-term parameter is not determined ("No" in box 208), the processor 80 waits for the next scheduled time to perform long-term monitoring of remodeling pacing ("Yes" in box 200). If the additional long-term parameter is to be determined ("Yes" in box 208), the processor 80 monitors the additional long-term parameter (box 202) to determine whether the additional long-term parameter indicates that remodeling pacing has led to successful normalization of the patient's heart. A determination is then made regarding whether to adjust the remodeling pacing based on the additional long-term parameter (box 204). If the processor 80 determines that the additional long-term parameter indicates that remodeling pacing should be adjusted ("Yes" in box 204), the processor 80 adjusts the remodeling pacing (box 206) and waits for the next scheduled time to perform long-term monitoring of remodeling pacing ("Yes" in box 200). On the other hand, if the processor 80 determines that the additional long-term parameter indicates that remodeling pacing should not be adjusted ("No" in box 204), the processor 80 may determine whether to monitor the additional long-term parameter (box 208).

[0085] In this way, in one example, processor 80 can monitor a single long-term parameter to determine whether the long-term parameter indicates that remodeling pacing should be adjusted. In another example, processor 80 can monitor multiple long-term parameters to determine whether at least one of these long-term parameters indicates that remodeling pacing should be adjusted.

[0086] According to one example, processor 80 can monitor the patient's QRS duration (box 202) to determine whether the QRS duration has increased over time due to the delivered remodeling pacing. If the QRS duration is determined to be increasing, processor 80 determines that the remodeling pacing should be adjusted ("Yes" in box 204), and therefore adjusts it by reducing the frequency and / or duration of the delivered remodeling pacing (box 206), and waits for the next scheduled time to perform long-term monitoring of the remodeling pacing ("Yes" in box 200). On the other hand, if the QRS duration is not determined to be increasing, processor 80 determines that the remodeling pacing should not be adjusted ("No" in box 204).

[0087] In another example, processor 80 may monitor one or more circadian rhythm parameters (box 202) to determine whether to adjust the time period during which remodeling pacing will be delivered. For example, assuming processor 80 delivers remodeling pacing during a predetermined time of day when the patient is most likely to be inactive (e.g., between 12:00 AM and 5:00 AM), as described above, processor 80 may divide the time period during which remodeling pacing is to be delivered into predetermined time segments (e.g., such as 20-minute time segments) and, for each of these 20-minute time segments or for a predetermined number of beats during that segment, determine whether a lack of atrium-to-ventricle conduction indicating AV block occurs within that 20-minute time segment. Processor 80 then adjusts the time period for remodeling pacing delivery (box 204) so ​​that remodeling pacing is not delivered during those 20-minute time segments where AV block is determined to be likely during the initial delivery period (i.e., between 12:00 AM and 5:00 AM).

[0088] In addition to the pacing algorithms described previously, the pacemaker can also use one or more pacing protocols to reshape the heart. In another example, processor 80 can characterize only the patient's circadian rhythm throughout the day, delivering rapid pacing during these rhythms, and determining, based on the delivered rapid pacing, when the patient's heart is likely to conduct more normally, thus indicating a lower probability of AV block. Processor 80 then adjusts the timing of reshaping pacing deliveries (box 204) by delivering reshaping pacing during those periods when AV block is less likely to occur. In this way, the processor utilizes circadian rhythm parameters to learn or determine when to deliver reshaping pacing, rather than delivering it only during fixed time periods.

[0089] In another example, processor 80 may monitor one or more long-term parameters (box 202) to identify whether there is a long-term improvement in the threshold level for cardiac normalization. For example, if the slope of a patient's cardiac output increases, processor 80 may determine that there is a long-term improvement in the threshold level. If there is a long-term improvement in the threshold level, processor 80 may adjust the frequency and / or duration of remodeling pacing. In another example, if there is a desired change in pulmonary artery pressure or a desired change in impedance (such as an impedance shift indicating ventricular diastole), processor 80 may determine that there is a long-term improvement in the threshold level. If there is a long-term improvement in the threshold level due to the delivered remodeling pacing, processor 80 may increase the frequency and / or duration of the delivered remodeling pacing (box 206).

[0090] In another example, processor 80 can be programmed to deliver remodeling pacing using a predetermined duty cycle range (e.g., a range between a minimum of 4 hours per day and a maximum of 8 hours per day). In this way, if there is a long-term improvement in the threshold level due to the delivered remodeling pacing, processor 80 can increase the duration of the delivered remodeling pacing (box 206) unless the maximum duty cycle has been reached. Once the maximum duty cycle has been reached, processor 80 can maintain the delivery of remodeling pacing at the maximum duty cycle.

[0091] Figure 8 This is a flowchart of a method for delivering pacing therapy for cardiac remodeling according to an example of this disclosure. According to another example, once processor 80 determines that it is time to perform long-term monitoring of remodeling pacing ("Yes" in box 200), processor 80 begins monitoring one or more long-term parameters associated with the long-term delivery of remodeling pacing (box 202) and assesses the long-term effects of the delivered remodeling pacing to determine whether remodeling pacing should be paused.

[0092] like Figure 8 As shown, monitoring of long-term parameters (box 202) may include: processor 80 monitoring parameters to determine whether to pause remodeling pacing delivery ("Yes" in box 210) or maintain remodeling pacing delivery at the currently set frequency and / or duration ("No" in box 210). For example, monitoring of long-term parameters (box 202) may include: monitoring the recovery of the patient's resting heart rate over an extended period of time to determine whether the patient's long-term resting heart rate has changed.

[0093] For example, processor 80 can determine a recovery rate associated with the amount of time it takes for the heart rate to return to resting heart rate after delivery of remodeling pacing, which results in an elevated heart rate during the delivery of the remodeling pacing. The determined recovery rate is compared to a baseline recovery rate, for example, determined at implantation. If the amount of time associated with the determined recovery rate does not decrease over a long period of time, such as one week, processor 80 determines that long-term parameters indicate that remodeling pacing should not be paused ("No" in box 210), and therefore continues or maintains delivery of remodeling pacing at the current frequency and / or duration. If the amount of time associated with the determined recovery rate decreases, processor 80 determines that remodeling pacing has resulted in normalization of the patient's cardiac condition to the desired level, and therefore delivery of remodeling pacing should be paused ("Yes" in box 210), and therefore pauses delivery of remodeling pacing (box 212).

[0094] In another example, if processor 80 determines, based on the determined recovery rate, that a long-term parameter indicates that remodeling pacing should not be paused ("No" in box 210), and therefore continues or sustains the delivery of remodeling pacing at the current frequency and / or duration, then processor 80 may determine whether to monitor additional long-term parameters (box 214) to determine whether the additional long-term parameters indicate that remodeling pacing should be paused.

[0095] In another example, monitoring of long-term parameters (box 202) may include monitoring the cardiac systolic time interval (STI) over an extended period to determine if the patient's long-term STI has changed. The current long-term STI is compared to a baseline STI determined, for example, at implantation. If there is no predetermined reduction in the STI, such as a 30% reduction, the processor 80 determines that the long-term parameters indicate that remodeling pacing should not be paused ("No" in box 210), and therefore continues or maintains remodeling pacing delivery at the current frequency and / or duration. If there is a predetermined reduction in the currently determined STI, the processor 80 determines that remodeling pacing has resulted in normalization of the patient's cardiac condition to the desired level, and therefore remodeling pacing delivery should be paused ("Yes" in box 210), and thus pauses remodeling pacing delivery (box 212).

[0096] In another example, if processor 80 determines, based on a decrease in the determined STI, that a long-term parameter indicates that remodeling pacing should not be paused (“No” in box 210), and therefore continues or sustains remodeling pacing delivery at the current frequency and / or duration, then processor 80 may determine whether to monitor an additional long-term parameter (box 214) to determine whether the additional long-term parameter indicates that remodeling pacing should be paused.

[0097] In another example, monitoring of long-term parameters (box 202) may include monitoring biomarker indicators (such as, for example, brain natriuretic peptide (BNP)) used to diagnose congestive heart failure (CHF) over an extended period of time to determine if there is a change in the biomarker that would indicate that the delivered remodeling pacing has resulted in the normalization of the patient's cardiac condition to the desired level. The biomarker measured over the extended period of time will be compared with baseline measurements, for example, determined at implantation. If no predetermined long-term change in the biomarker is found, processor 80 determines that the long-term parameter indicates that remodeling pacing should not be suspended ("No" in box 210) and therefore continues or maintains the delivery of remodeling pacing at the current frequency and / or duration. If a predetermined long-term change in the biomarker is found, processor 80 determines that remodeling pacing has resulted in the normalization of the patient's cardiac condition to the desired level and therefore the delivery of remodeling pacing should be suspended ("Yes" in box 210), and therefore the delivery of remodeling pacing is suspended (box 212).

[0098] In another example, if processor 80 determines, based on a decrease in the determined STI, that a long-term parameter indicates that remodeling pacing should not be paused (“No” in box 210), and therefore continues or sustains remodeling pacing delivery at the current frequency and / or duration, then processor 80 may determine whether to monitor an additional long-term parameter (box 214) to determine whether the additional long-term parameter indicates that remodeling pacing should be paused.

[0099] Figure 9 This is a flowchart illustrating a method for delivering remodeling pacing therapy according to an example of this disclosure. Figure 9 As shown, to increase the likelihood that the delivery of remodeling pacing will effectively normalize the patient's cardiac condition to the desired level, processor 80 can deliver remodeling pacing over multiple intervals, wherein the intervals vary the frequency and / or duration of remodeling pacing in a manner that increases cardiac muscle endurance. For example, processor 80 can deliver remodeling pacing at a currently set frequency (box 300) for a predetermined duration, and once remodeling pacing has been delivered at the current frequency for the current duration ("Yes" in box 302), determine whether to adjust the frequency from the current frequency to the next frequency (box 304), and / or determine whether to adjust the duration from the current duration to the next duration (box 308).

[0100] In this manner, once re-pacing has been delivered at the current frequency for the current duration ("Yes" in box 302), processor 80 adjusts only the frequency (box 306) and delivers the next re-pacing interval (box 312) at the adjusted frequency for the current duration; adjusts only the duration (box 310) and delivers the next re-pacing interval (box 312) at the current frequency with the adjusted next duration; adjusts both the current frequency (box 306) and duration (box 310) and delivers the next re-pacing interval (box 312) at the adjusted frequency for the adjusted duration; or does not adjust the frequency or duration and continues to deliver the next re-pacing interval (box 312) at the current frequency for the current duration. Once the duration expires during the delivery period of the next re-pacing ("Yes" in box 302), the process is repeated to generate the next re-pacing delivery interval until the current re-pacing delivery session has ended.

[0101] In this manner, the processor 80 can deliver remodeling pacing during a first interval having a first frequency and a first duration, determine whether to adjust one or both of the first frequency and the first duration during the delivery of remodeling pacing in a next interval after the first interval, and deliver remodeling pacing in response to the determination, such that the next interval may include the delivered remodeling pacing having one of the following: both the first frequency and the first duration, the adjusted frequency and the first duration, the first frequency and the adjusted duration, and both the adjusted frequency and the adjusted duration.

[0102] Specifically, in one example, the delivery of remodeling pacing may include a warm-up interval during which remodeling pacing is delivered at a frequency slightly higher than the patient's associated resting heart rate for an initial duration, followed by an accumulation interval during which remodeling pacing is delivered at an increased frequency for a shorter duration relative to the initial duration. Once the delivery of remodeling pacing is completed during the accumulation interval, remodeling pacing may be delivered using the frequency and duration of the initial interval to generate up / down delivery of remodeling pacing, or it may be delivered at an increased frequency, at an increased duration, or at an increased frequency and duration, etc. In this way, remodeling pacing may be delivered in a pattern of repeated rising and / or falling to increase muscle endurance and thereby increase the likelihood that the delivery of remodeling pacing will effectively induce the desired level of normalization of the patient's cardiac condition.

[0103] In one example, the delivery of remodeling pacing may include: a 10-minute warm-up interval (first time interval), during which remodeling pacing is delivered at a low frequency (a first frequency used to increase the heart rate to more than 30 heart beats per minute (HBM) above the resting heart rate) just above the patient's resting rate; followed by a 3-minute first accumulation interval, during which remodeling pacing is delivered at a maximum frequency (e.g., up to 50 HBM above the first heart rate); followed by a second interval (e.g., a 2-minute interval), during which remodeling pacing is delivered at a maximum frequency (e.g., more than 50 HBM above the first heart rate); and then a second interval (e.g., a 2-minute interval) during which remodeling pacing is delivered at a maximum frequency (e.g., more than 50 HBM above the first heart rate). During the first accumulation period, re-pacing is delivered at a frequency less than the maximum rate; this is followed by a third accumulation period (e.g., a 2-minute interval), during which re-pacing is delivered at the maximum rate; then a one-minute interval, during which re-pacing is delivered at a frequency less than the maximum rate; then another one-minute interval, during which re-pacing is delivered at the maximum rate; then a one-minute interval, during which re-pacing is delivered at a frequency less than the maximum rate. This process can then be repeated. For example, this algorithm can be repeated for up to one hour per day.

[0104] In another example, remodeling pacing delivery may include delivery at the same frequency but for different durations. For example, remodeling pacing delivery may include: delivering remodeling pacing at a given frequency (first frequency) during a two-minute interval (first interval); followed by delivering remodeling pacing at the same frequency during a four-minute interval (second interval); followed by delivering remodeling pacing at the same frequency during a six-minute interval (third interval); followed by delivering remodeling pacing at the same frequency during another six-minute interval (fourth interval); followed by delivering remodeling pacing at the same frequency during a four-minute interval (fifth interval); and followed by delivering remodeling pacing at the same frequency during a two-minute interval (sixth interval). In another example, delivery may include a recovery interval (seventh interval) between each of the different intervals, during which remodeling pacing is delivered at a reduced frequency and for a reduced duration. This algorithm can be repeated up to 1 hour per day.

[0105] In another example, remodeling pacing can be delivered in a step-by-step pattern, which includes: a warm-up interval (a first interval allowing the heart rate to gradually accumulate up to 20 HBM), during which remodeling pacing is delivered at a minimum frequency (e.g., increasing the heart rate by up to 30 HBM); followed by an accumulation interval, during which remodeling pacing is delivered at a first frequency greater than the minimum frequency delivered during the warm-up interval; followed by another accumulation interval, during which remodeling pacing is delivered at a second frequency greater than the minimum frequency (e.g., increasing the heart rate by up to 30 HBM higher than the first frequency), and equal to or greater than the first frequency used during the previous accumulation interval. This algorithm can be repeated for up to 1 hour per day.

[0106] In another example, the delivery of remodeling pacing may include: an initial interval (up to 3 to 5 minutes) during which remodeling pacing is delivered at a high frequency (resulting in an increase in heart rate of up to 50 HBM); followed by a next interval during which remodeling pacing is delivered at a reduced frequency (reducing HBM by 20 HBM from the first interval); or the delivery of remodeling pacing may include: an initial interval during which remodeling pacing is delivered at a reduced frequency; followed by a next interval during which remodeling pacing is delivered at a high frequency, and may include alternation between the two.

[0107] In this way, the delivery of remodeling pacing can include a variety of combinations of different frequency and / or duration patterns delivered over long or short time periods (such as days or one or more weeks). Additionally, a recovery interval may be included, during which the delivery of remodeling pacing is suppressed for a period of time, or delivered at a reduced frequency and / or duration to allow for variable patterns of remodeling pacing delivery. This may also include a combination of one or more warm-up intervals and one or more accumulation intervals, thereby leading to the normalization of the patient's cardiac condition to the desired level.

[0108] The technologies described in this disclosure (including those attributable to IMD 16, programmer 24, processor 80, or the various constituent components) can be implemented, at least in part, in hardware, software, firmware, or any combination thereof. For example, aspects of these technologies can be implemented within one or more processors, including one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuitry systems, and any combination of such components embodied in a programmer (such as a doctor programmer or patient programmer, a stimulator, an image processing device, or other device). The terms “module,” “processor,” or “processing circuitry system” generally refer to any of the aforementioned logic circuitry systems, either independently or in conjunction with other logic circuitry systems, or any other equivalent circuitry system.

[0109] Such hardware, software, and / or firmware may be implemented within the same device or in separate devices to support the various operations and functions described in this disclosure. Furthermore, any of the described units, modules, or components may be implemented together or separately as discrete but interoperable logical devices. Describing different features as modules or units is intended to emphasize different functional aspects and does not necessarily imply that such modules or units must be implemented by separate hardware or software components. Rather, the functions associated with one or more modules or units may be performed by separate hardware or software components or may be integrated within common or separate hardware or software components.

[0110] When implemented in software, the functionality attributable to the systems, devices, and techniques described in this disclosure can be embodied as instructions on a computer-readable medium (such as RAM, ROM, NVRAM, EEPROM, flash memory, magnetic data storage medium, optical data storage medium, etc.). These instructions can be executed by one or more processors to support one or more aspects of the functionality described in this disclosure.

[0111] In one example, the exercise program described herein is performed while the patient is sleeping; however, the program can also be performed without any patient data being detected (e.g., inactivity being detected). Additionally, the exercise program is not intended for diagnostic purposes; rather, the exercise is designed to reshape the heart.

[0112] Illustrative Examples

[0113] Example 1: A cardiac device for delivering cardiac remodeling pacing to a patient, comprising:

[0114] case;

[0115] Multiple electrodes, electrically connected to a housing, are used to deliver cardiac remodeling pacing to stimulate the normalization of the patient's cardiac condition; and

[0116] A processor, which is located within a housing and configured to:

[0117] During the first interval, cardiac remodeling pacing is delivered at the first frequency for the first duration;

[0118] Determine whether to adjust one or both of the first frequency and first duration during cardiac remodeling pacing in the next interval following the first interval;

[0119] In response to determining that one or both of the first frequency and the first duration should be adjusted, one or both of the first frequency and the first duration during the remodeling pacing period are adjusted during the next interval following the first interval; and

[0120] During the next interval, cardiac remodeling pacing is delivered at the first frequency for the first duration.

[0121] Example 2: A method for delivering cardiac remodeling pacing therapy to a patient, comprising:

[0122] During the first interval, cardiac remodeling pacing is delivered at the first frequency for the first duration;

[0123] Determine whether to adjust one or both of the first frequency and first duration during cardiac remodeling pacing in the next interval following the first interval;

[0124] In response to determining that one or both of the first frequency and the first duration should be adjusted, one or both of the first frequency and the first duration during cardiac remodeling pacing are adjusted during the next interval following the first interval; and

[0125] During the next interval, cardiac remodeling pacing is delivered at the first frequency for the first duration.

[0126] Example 3: The device or method described in Example 1, wherein the processor of the device is further configured to perform or the method further includes: delivering cardiac remodeling pacing at a second frequency for a second duration, wherein the second frequency is greater than the first frequency and the second duration is less than the first duration.

[0127] Example 4: The device or method described in Example 3, wherein the processor of the device is further configured to perform or the method further includes: delivering cardiac remodeling pacing at a first frequency for a first duration after delivering cardiac remodeling pacing at a second frequency for a second duration.

[0128] Example 5: The device or method of any one of Examples 3-4, wherein the processor of the device is further configured to perform or the method further includes: delivering cardiac remodeling pacing at a third frequency for a second duration, wherein the third frequency is greater than the second frequency.

[0129] Example 6: The device or method of any one of Examples 3-5, wherein the processor of the device is further configured to perform or the method further includes: delivering cardiac remodeling pacing at a second frequency for a third duration, wherein the third duration is greater than the second duration.

[0130] Example 7: The device or method of any one of Examples 3-4, wherein the processor of the device is further configured to perform or the method further includes: delivering cardiac remodeling pacing at a third frequency for a third duration, wherein the third frequency is greater than the second frequency and the third duration is greater than the second duration.

[0131] Example 8: The device or method of any one of Examples 3-4, wherein the processor of the device is further configured to perform or the method further includes: delivering cardiac remodeling pacing at a third frequency for a third duration, wherein the third frequency is greater than the second frequency and the third duration is less than the second duration.

[0132] Example 9: The device or method described in any one of Examples 1-8, wherein the processor of the device is further configured to perform, or the method further includes:

[0133] Determine the patient's associated resting heart rate; and

[0134] The first frequency should be set based at least on the determined resting heart rate.

[0135] Example 10: The device or method of any one of Examples 1-2, wherein the processor of the device is further configured to perform or the method further includes: delivering cardiac remodeling pacing at a second frequency for a second duration, wherein the first frequency includes a patient-associated resting heart rate, the second frequency includes a patient-associated maximum heart rate, and the second duration is less than the first duration.

[0136] Example 11: The device or method of Example 10, wherein the processor of the device is further configured to perform or the method further includes: delivering cardiac remodeling pacing at a third frequency for a third duration, wherein the third frequency is less than the second frequency and the third duration is less than the second duration.

[0137] Example 12: The device or method described in Example 10, wherein the processor of the device is further configured to perform or the method further includes: delivering the heart at a fourth frequency.

[0138] The pacing is reshaped to reach a fourth duration, where the fourth frequency is equal to the second frequency and the fourth duration is equal to the third duration.

[0139] Example 13: The device or method of Example 12, wherein the processor of the device is further configured to perform or the method further includes: delivering cardiac remodeling pacing at a fifth frequency for a fifth duration, wherein the fifth frequency is equal to the fourth frequency and the fifth duration is less than the fourth duration.

[0140] Example 14: The device or method of any one of Examples 1-13, wherein the processor of the device is further configured to perform or the method further includes: delivering cardiac remodeling pacing at a reduced frequency and for a reduced duration prior to delivering cardiac remodeling pacing during the next interval.

[0141] This disclosure has been provided with reference to illustrative embodiments and is not intended to be interpreted in a limiting sense. As previously described, those skilled in the art will recognize that various other illustrative applications can be used to utilize the beneficial features of the apparatus and methods described herein. Various modifications to the illustrative embodiments and additional embodiments of this disclosure will become apparent upon reference to this specification.

Claims

1. A cardiac device for delivering cardiac remodeling pacing to a patient, comprising: case; Multiple electrodes electrically connected to the housing are used to deliver cardiac remodeling pacing to stimulate the normalization of the patient's cardiac condition. as well as A processor, located within the housing and configured to: During the first interval, cardiac remodeling pacing is delivered at the first frequency for the first duration; Based on the determination of whether the delivered cardiac remodeling pacing results in a measurable effect indicating that the delivery of remodeling pacing is effective in normalizing the patient's cardiac condition to a predetermined degree, determining whether to adjust one or both of the first frequency and the first duration during the delivery of cardiac remodeling pacing in the next interval following the first interval, including: in response to the determination that the delivered cardiac remodeling pacing has not yet resulted in the presence of the measurable effect, determining whether to adjust one or both of the first frequency and the first duration during the delivery of cardiac remodeling pacing in the next interval following the first interval; In response to determining that one or both of the first frequency and the first duration should be adjusted, one or both of the first frequency and the first duration during the delivery of remodeling pacing during the next interval following the first interval are adjusted; and During the next interval, cardiac remodeling pacing is delivered at the first frequency for the first duration.

2. The device as claimed in claim 1, wherein, The processor of the device is further configured to perform: delivering cardiac remodeling pacing at a second frequency for a second duration, wherein the second frequency is greater than the first frequency and the second duration is less than the first duration.

3. The device as described in claim 2, characterized in that, The processor of the device is further configured to perform: after delivering the cardiac remodeling pacing at the second frequency for the second duration, delivering the cardiac remodeling pacing at the first frequency for the first duration.

4. The device as described in claim 2, characterized in that, The processor of the device is further configured to perform: delivering cardiac remodeling pacing at a third frequency for the second duration, wherein the third frequency is greater than the second frequency.

5. The device as described in claim 2, characterized in that, The processor of the device is further configured to perform: delivering cardiac remodeling pacing at the second frequency for a third duration, wherein the third duration is greater than the second duration.

6. The device as described in claim 2, characterized in that, The processor of the device is further configured to perform: delivering cardiac remodeling pacing at a third frequency for a third duration, wherein the third frequency is greater than the second frequency and the third duration is greater than the second duration.

7. The device as described in claim 2, characterized in that, The processor of the device is further configured to perform: delivering cardiac remodeling pacing at a third frequency for a third duration, wherein the third frequency is greater than the second frequency and the third duration is less than the second duration.

8. The device as described in any one of claims 1-2, characterized in that, The processor of the device is further configured to perform: Determine the resting heart rate associated with the patient; and The first frequency is set based at least on the determined resting heart rate.

9. The device as described in any one of claims 1-2, characterized in that, The processor of the device is further configured to perform: delivering cardiac remodeling pacing at a second frequency for a second duration, wherein the first frequency includes the resting heart rate associated with the patient, the second frequency includes the maximum heart rate associated with the patient, and the second duration is less than the first duration.

10. The device as claimed in claim 9, characterized in that, The processor of the device is further configured to perform: delivering cardiac remodeling pacing at a third frequency for a third duration, wherein the third frequency is less than the second frequency and the third duration is less than the second duration.

11. The device as claimed in claim 10, characterized in that, The processor of the device is further configured to perform: delivering cardiac remodeling pacing at a fourth frequency for a fourth duration, wherein the fourth frequency is equal to the second frequency and the fourth duration is equal to the third duration.

12. The device as claimed in claim 11, characterized in that, The processor of the device is further configured to perform: delivering cardiac remodeling pacing at a fifth frequency for a fifth duration, wherein the fifth frequency is equal to the fourth frequency and the fifth duration is less than the fourth duration.

13. The device as described in any one of claims 1-2, characterized in that, The processor of the device is further configured to perform: delivering cardiac remodeling pacing at a reduced frequency and for a reduced duration prior to delivering cardiac remodeling pacing during the next interval.

14. A computer-readable medium comprising instructions, which, when executed by a processor of a cardiac device, cause the processor to perform a method for delivering cardiac remodeling pacing therapy to a patient, the method comprising: During the first interval, cardiac remodeling pacing is delivered at the first frequency for the first duration; Based on the determination of whether the delivered cardiac remodeling pacing results in a measurable effect indicating that the delivery of remodeling pacing is effective in normalizing the patient's cardiac condition to a predetermined degree, determining whether to adjust one or both of the first frequency and the first duration during the delivery of cardiac remodeling pacing in the next interval following the first interval, including: in response to the determination that the delivered cardiac remodeling pacing has not yet resulted in the presence of the measurable effect, determining whether to adjust one or both of the first frequency and the first duration during the delivery of cardiac remodeling pacing in the next interval following the first interval; In response to determining that one or both of the first frequency and the first duration should be adjusted, one or both of the first frequency and the first duration during cardiac remodeling pacing delivery in the next interval following the first interval are adjusted; and During the next interval, cardiac remodeling pacing is delivered at the first frequency for the first duration.

15. The computer-readable medium as claimed in claim 14, characterized in that, The method further includes: delivering cardiac remodeling pacing at a second frequency for a second duration, wherein the second frequency is greater than the first frequency and the second duration is less than the first duration.

16. The computer-readable medium as claimed in claim 15, characterized in that, The method further includes: after delivering the cardiac remodeling pacing at the second frequency for the second duration, delivering the cardiac remodeling pacing at the first frequency for the first duration.

17. The computer-readable medium as claimed in claim 15, characterized in that, The method further includes: delivering cardiac remodeling pacing at a third frequency for the second duration, wherein the third frequency is greater than the second frequency.

18. The computer-readable medium as claimed in claim 15, characterized in that, The method further includes: delivering cardiac remodeling pacing at the second frequency for a third duration, wherein the third duration is greater than the second duration.

19. The computer-readable medium as claimed in claim 15, characterized in that, The method further includes: delivering cardiac remodeling pacing at a third frequency for a third duration, wherein the third frequency is greater than the second frequency and the third duration is greater than the second duration.

20. The computer-readable medium as claimed in claim 15, characterized in that, The method further includes: delivering cardiac remodeling pacing at a third frequency for a third duration, wherein the third frequency is greater than the second frequency and the third duration is less than the second duration.

21. The computer-readable medium as claimed in any one of claims 14-15, characterized in that, The method further includes: Determine the resting heart rate associated with the patient; and The first frequency is set based at least on the determined resting heart rate.

22. The computer-readable medium as claimed in any one of claims 14-15, characterized in that, The method further includes: delivering cardiac remodeling pacing at a second frequency for a second duration, wherein the first frequency includes a resting heart rate associated with the patient, the second frequency includes a maximum heart rate associated with the patient, and the second duration is less than the first duration.

23. The computer-readable medium as claimed in claim 22, characterized in that, The method further includes: delivering cardiac remodeling pacing at a third frequency for a third duration, wherein the third frequency is less than the second frequency and the third duration is less than the second duration.

24. The computer-readable medium as claimed in claim 23, characterized in that, The method further includes: delivering cardiac remodeling pacing at a fourth frequency for a fourth duration, wherein the fourth frequency is equal to the second frequency and the fourth duration is equal to the third duration.

25. The computer-readable medium as claimed in claim 24, characterized in that, The method further includes: delivering cardiac remodeling pacing at a fifth frequency for a fifth duration, wherein the fifth frequency is equal to the fourth frequency and the fifth duration is less than the fourth duration.

26. The computer-readable medium as claimed in any one of claims 14-15, characterized in that, The method further includes delivering cardiac remodeling pacing at a reduced frequency and for a reduced duration prior to delivering cardiac remodeling pacing during the next interval.

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