Pacing therapy selection for heart failure treatment

Abstract

A method for heart failure management includes monitoring one or more sensor-based parameters of a patient to determine pacing therapy. If the one or more parameters indicate atrial tachycardia or atrial fibrillation, a first pacing therapy is delivered. If the one or more parameters do not indicate atrial tachycardia or atrial fibrillation, it is determined whether the patient is asleep. If the patient is asleep, a second pacing therapy is delivered. If the one or more parameters do not indicate atrial tachycardi a, atrial fibrillation, or the patient is asleep, a P-wave duration of the patient is evaluated relative to a P-wave duration threshold. A third pacing therapy is delivered when it is determined that the P-wave duration of the patient exceeds the P-wave duration threshold, and a fourth pacing therapy is delivered when it is determined that the P-wave duration of the patient does not exceed the P-wave duration threshold.

Description

Background Technology

[0001] The present invention generally relates to pacing therapy for patients with heart failure. Specifically, the present invention relates to a method for selecting pacing therapy based on monitored patient parameters.

[0002] Heart failure (HF) occurs when the heart muscle is unable to pump enough blood to meet the body's needs. The volume of blood pumped by the heart is determined by the degree of cardiac contraction (i.e., muscle contraction) and the degree to which the heart relaxes and fills with blood. Ejection fraction is a measure of how much blood is pumped out of the left ventricle (LV) with each contraction. When the left ventricle pumps, not all the blood in the ventricle leaves. A normal ejection fraction is greater than about 50%. Heart failure with preserved ejection fraction (HFpEF) occurs when the left ventricle does not fill with blood as normally, but the ventricle can pump well. For example, the ventricle is rigid or has thick walls, preventing it from relaxing to fill with a normal volume of blood. Alternatively, this condition is called heart failure with preserved ejection fraction (HFrEF) when muscle contraction is abnormal (e.g., the muscles are too weak to pump properly).

[0003] Patients with heart failure pEF (HFpEF) account for nearly half of the heart failure population, and their prevalence continues to increase relative to those with heart failure rEF (HFrEF). Although the outcomes experienced by patients with heart failure pEF are just as poor as those experienced by patients with heart failure rEF, there are no evidence-based therapies to improve mortality and morbidity. The technology of this invention relates to an algorithm for selecting a pacing therapy for a heart failure patient (such as an HFpEF patient) based on monitored patient parameters, which also take into account interactions between various pacing therapies. The algorithm and pacing therapy can be implemented via implantable medical devices (IMDs), such as implantable cardioverter defibrillators (ICDs), cardiovascular implantable electronic devices (CIEDs), pacemakers, and cardiac resynchronization therapy (CRT) devices (in some cases, including defibrillation functionality (CRT-D devices)). Summary of the Invention

[0004] The embodiments described herein relate to a method for managing heart failure. The method includes monitoring one or more sensor-based parameters of a patient. Determining whether the monitored one or more sensor-based parameters indicate atrial tachycardia or atrial fibrillation, and when these parameters indicate atrial tachycardia or atrial fibrillation, delivering a first pacing therapy. In response to the one or more sensor-based parameters not indicating atrial tachycardia or atrial fibrillation, determining whether the monitored one or more sensor-based parameters indicate that the patient is asleep. In response to the one or more sensor-based parameters indicating that the patient is asleep, delivering a second therapy, and in response to the one or more sensor-based parameters not indicating atrial tachycardia, atrial fibrillation, or that the patient is asleep, determining whether the monitored one or more sensor-based parameters indicate that the patient's P-wave duration exceeds a P-wave duration threshold. In response to indicating that the patient's P-wave duration exceeds the P-wave duration threshold, delivering a third pacing therapy, and in response to indicating that the patient's P-wave duration does not exceed the P-wave duration threshold, delivering a fourth pacing therapy.

[0005] Other embodiments relate to a method for managing heart failure, the method comprising monitoring one or more sensor-based parameters of a patient. Determining whether the monitored one or more sensor-based parameters indicate atrial tachycardia or atrial fibrillation, and when these parameters indicate atrial tachycardia or atrial fibrillation, delivering a first pacing therapy. In response to the one or more sensor-based parameters not indicating atrial tachycardia or atrial fibrillation, determining whether the monitored one or more sensor-based parameters indicate that the patient is asleep. In response to the one or more sensor-based parameters indicating that the patient is asleep, delivering a second therapy.

[0006] An additional implementation relates to a method for managing heart failure, comprising monitoring one or more sensor-based parameters of a patient. Determining whether the monitored one or more sensor-based parameters indicate atrial tachycardia or atrial fibrillation, and when these parameters indicate atrial tachycardia or atrial fibrillation, delivering a first pacing therapy. In response to the one or more sensor-based parameters not indicating atrial tachycardia or atrial fibrillation, determining whether the monitored one or more sensor-based parameters indicate that the patient's P-wave duration exceeds a P-wave duration threshold. If the one or more sensor-based parameters indicate that the patient's P-wave duration exceeds the P-wave duration threshold, delivering a second pacing therapy. If the one or more sensor-based parameters indicate that the patient's P-wave duration does not exceed the P-wave duration threshold, delivering a third pacing therapy.

[0007] Other embodiments relate to a method for managing heart failure, the method comprising monitoring one or more sensor-based parameters of a patient. The method includes determining whether the monitored one or more sensor-based parameters indicate that the patient's P-wave duration exceeds a P-wave duration threshold. If the one or more sensor-based parameters indicate that the patient's P-wave duration exceeds the P-wave duration threshold, a first atrioventricular nodal stimulation (AVN) therapy is delivered. If the one or more sensor-based parameters indicate that the patient's P-wave duration does not exceed the P-wave duration threshold, a second AVN stimulation therapy is delivered.

[0008] Another embodiment relates to a heart failure management system. The system includes one or more sensors for measuring one or more sensor-based parameters, at least one storage component, and a processing circuitry operatively coupled to the one or more sensors and the at least one storage component. The processing circuitry is configured to determine whether the monitored one or more sensor-based parameters indicate atrial tachycardia or atrial fibrillation. When these parameters indicate atrial tachycardia or atrial fibrillation, the processing circuitry is configured to deliver a first pacing therapy. In response to the one or more sensor-based parameters not indicating atrial tachycardia or atrial fibrillation, the processing circuitry is configured to determine whether the monitored one or more sensor-based parameters indicate that the patient is asleep. In response to the one or more sensor-based parameters indicating that the patient is asleep, the processing circuitry is configured to deliver a second therapy, and in response to the one or more sensor-based parameters not indicating atrial tachycardia, atrial fibrillation, or that the patient is asleep, the processing circuitry is configured to determine whether the monitored one or more sensor-based parameters indicate that the patient's P-wave duration exceeds a P-wave duration threshold. In response to an indication that the patient's P-wave duration exceeds a P-wave duration threshold, the processing circuitry is configured to deliver a third pacing therapy, and in response to an indication that the patient's P-wave duration does not exceed the P-wave duration threshold, the processing circuitry is configured to deliver a fourth pacing therapy.

[0009] The above overview is not intended to describe every or every embodiment of this disclosure. The following figures and detailed description illustrate illustrative embodiments in more detail. Attached Figure Description

[0010] The following discussion refers to the following figures, where the same reference numerals may be used to identify similar / identical parts in multiple figures. However, the use of numbers to refer to parts in a given figure is not intended to limit parts labeled with the same numbers in another figure. The figures need not be drawn to scale.

[0011] Figure 1This is a diagram of a system including an IMD based on the various implementation schemes described herein.

[0012] Figure 2 yes Figure 1 A diagram of IMD.

[0013] Figure 3A Examples of implementation schemes described herein Figures 1 to 2 A block diagram of the system's IMD.

[0014] Figure 3B It is an IMD (e.g., implantable pulse generator) circuit system and in Figures 1 to 2 Another block diagram of the associated leads used in the system.

[0015] Figure 4 This is based on the demonstration of the various implementation schemes described in this document. Figure 1 A flowchart illustrating the methods for selecting pacing therapy in heart failure patients with IMD delivery.

[0016] Figure 5 This is an atrial electrocardiogram, showing an exemplary pulse train for atrioventricular node stimulation and its effect on ventricular rate during atrial fibrillation. Detailed Implementation

[0017] This disclosure generally relates to methods for selecting pacing therapies for patients with heart failure (e.g., patients with HFpEF) based on monitored patient parameters. Many different pacing therapies have been proposed for the treatment of HFpEF. These therapies include atrioventricular (AV) node stimulation for reducing ventricular rate during atrial fibrillation, nocturnal overdrive pacing, PR interval optimization via ventricular pacing, AV node stimulation for reducing inflammation, and atrial pacing and rate-response pacing. While each of these therapies provides individual benefits, they can be used in combination to take advantage of positive interactions as well as mitigate or avoid negative interactions and improve patient outcomes. Each of these therapies can be implemented using cardiac therapy systems and devices described further below.

[0018] Figure 1 This is a conceptual diagram of an exemplary therapy system 10 that can be used to deliver pacing therapy, such as each of the therapies mentioned above, to a patient 14. Although the patient 14 is shown as a human, the patient 14 could also be a variety of other types of animals. The therapy system 10 may include an implantable medical device 16 (IMD) that can be coupled to leads 18, 20, 22. The IMD 16 may be, for example, an implantable pacemaker, cardioverter-defibrillator, and / or a defibrillator that delivers or provides electrical signals (e.g., pacing, etc.) to the heart 12 of the patient 14 via electrodes coupled to one or more of the leads 18, 20, 22 and / or senses electrical signals from the patient's heart.

[0019] 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 ventricle (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 right atrium (RA) lead 22 extends through one or more veins and the vena cava, and enters the right atrium 26 of the heart 12.

[0020] The IMD 16 can sense electrical signals, such as those associated with depolarization and repolarization of the heart 12, via electrodes coupled to at least one of the leads 18, 20, 22. In some examples, the IMD 16 delivers pacing therapy (e.g., pacing pulses) to the heart 12 based on the electrical signals sensed within the heart 12. The IMD 16 can be operable to adjust one or more parameters associated with the pacing therapy, such as pacing rate, RR interval, AV delay, and various other timing, pulse width, amplitude, voltage, burst length, etc. Furthermore, the IMD 16 can be operable to deliver pacing therapy using various electrode configurations, which can be monopolar, bipolar, quadrupole, or further multipolar. Thus, a multipolar lead system can provide or supply multiple electrical vectors for pacing from it. The pacing vector may include at least one cathode and at least one anode, the at least one cathode being at least one electrode located on at least one lead, and the at least one anode being at least one electrode located on at least one lead (e.g., the same lead or different leads) and / or on the housing or can of the IMD or electrode device. While improvements in cardiac function as a result of pacing therapy may depend primarily on the cathode, electrical parameters such as impedance, pacing threshold voltage, current consumption, and lifespan may be more dependent on the pacing vector, which includes both the cathode and anode. The IMD 16 may also deliver defibrillation therapy and / or cardioversion therapy via an electrode located on at least one of leads 18, 20, 22. Further, the IMD 16 may detect arrhythmias of heart 12, such as fibrillation of ventricles 28, 32, and deliver defibrillation therapy to heart 12 in the form of electrical pulses. In some examples, the IMD 16 may be programmed to deliver a therapy process, e.g., pulses with increasing energy levels, until the fibrillation of heart 12 ceases.

[0021] Figure 2 yes Figure 1A more detailed conceptual diagram of the IMD 16 and leads 18, 20, 22 of the therapy system 10 is provided. Leads 18, 20, 22 may be electrically coupled via connector block 34 to a therapy delivery module (e.g., for delivering pacing therapy), a sensing module (e.g., for sensing one or more signals from one or more electrodes), and / or any other module of the IMD 16. In some examples, the proximal ends of leads 18, 20, 22 may include electrical contacts electrically coupled to corresponding electrical contacts within connector block 34 of the IMD 16. Additionally, in some examples, leads 18, 20, 22 may be mechanically coupled to connector block 34 by means of a retaining screw, connecting pin, or other suitable mechanical coupling mechanism.

[0022] Each of leads 18, 20, and 22 includes an elongated insulated lead body capable of carrying multiple conductors (e.g., concentric coil conductors, straight conductors, etc.) separated from each other by insulation (e.g., a tubular insulating sheath). In the example shown, bipolar electrodes 40 and 42 are located near the distal end of lead 18. Additionally, bipolar electrodes 44, 45, 46, and 47 are located near the distal end of lead 20, and bipolar electrodes 48 and 50 are located near the distal end of lead 22.

[0023] Electrodes 40, 44, 45, 46, 47, and 48 may be in the form of ring electrodes, and electrodes 42 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, 45, 46, 47, 48, and 50 may be electrically coupled to a corresponding conductor (e.g., a coil conductor and / or a straight conductor) within the lead body of its associated leads 18, 20, and 22, and thereby coupled to a corresponding electrical contact at the proximal end of leads 18, 20, and 22.

[0024] Electrodes 40, 42, 44, 45, 46, 47, 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. The 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, 45, 46, 47, 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., an hermetically sealed housing) of the IMD 16. Any of electrodes 40, 42, 44, 45, 46, 47, 48, and 50 may be combined with housing electrode 58 for unipolar sensing or pacing. It will be understood by those skilled in the art that other electrodes may also be selected to define or be used for pacing and sensing vectors. Furthermore, any of electrodes 40, 42, 44, 45, 46, 47, 48, 50, and 58 may be used to sense electrical activity during pacing therapy when not being used for delivering pacing therapy.

[0025] For reference Figure 2 In further detail, the housing 60 may encapsulate a therapy delivery module, which may include a stimulation generator for generating cardiac pacing pulses and defibrillation or cardioversion shocks, and a sensing module for monitoring electrical signals of the patient's heart (e.g., the patient's heart rhythm). Leads 18, 20, 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 use in implantable defibrillation electrodes. Since electrodes 62, 64, and 66 are not typically configured for delivering pacing therapy, any one of electrodes 62, 64, and 66 can be used to sense electrical activity and can be used in combination with any one of electrodes 40, 42, 44, 45, 46, 47, 48, 50, and 58. In at least one embodiment, the RV elongated electrode 62 can be used to sense the electrical activity of a patient's heart during pacing therapy delivery (e.g., in combination with the housing electrode 58 or a defibrillator electrode-to-housing electrode vector).

[0026] The above configuration of the therapy system 10 is merely an example. In other examples, the therapy system may include epicardial leads and / or patch electrodes to replace or supplement it. Figure 1 The transvenous leads 18, 20, and 22 are shown in the diagram. In another embodiment, the therapy system 10 may have a lead implanted in the left chamber of the heart in the absence of a transvenous lead (e.g., a leadless / wireless pacing system) or in the presence of a lead implanted (e.g., transvenous implantation or implantation using a method of implantation) (as a counterpart to...). Figure 1In cases where the illustrated transvenous lead is placed in the right chamber of the heart (as a supplement or replacement), it is implanted in / around the cardiac septum. In one example, the left ventricular (LV) coronary sinus lead 20 extends through one or more veins, the vena cava, the right atrium 26, and into the coronary sinus 30 to reach the region adjacent to the free wall of the left ventricle 32 of the heart 12. Further, in one or more embodiments, it is not necessary to implant the IMD 16 within the patient 14. For example, the IMD 16 can deliver various cardiac therapies to the heart 12 via a percutaneous lead that extends through the skin of the patient 14 to multiple locations within or outside the heart 12. In one or more embodiments, the system 10 can utilize wireless pacing (e.g., using energy delivery via ultrasound, inductive coupling, RF, etc., to an intracardiac pacing component) and sensing cardiac activation using electrodes on the housing / shell and / or subcutaneous leads.

[0027] Other exemplary therapeutic systems that provide electrical stimulation to the heart 12 may include any suitable number of leads coupled to the IMD 16, and each of these leads may extend to any location within or near the heart 12. Such other therapeutic systems may include, for example... Figures 1 to 2 The three transvenous leads are shown for localization. Other therapeutic systems may include a single lead extending from IMD 16 into the right atrium 26, or two leads extending into the corresponding atrium in the right and left atria. In one example, IMD 16, as a cardiac resynchronization therapy (CRT) device with a left ventricular (LV) lead, may be useful for HFpEF patients in the presence of complete AV node block, as the LV lead may be more beneficial than the RV lead in such patients. In some examples, for HFpEF patients with chronotropic dysfunction who have both atrial leads (i.e., single-chamber atrial systems, such as AAI) and atrial and ventricular lead systems (i.e., dual-chamber systems, such as DDD and VDD), rate-responsive pacing delivery to the atria may be desired.

[0028] Figure 3AThis is a functional block diagram of an exemplary configuration of IMD 16. As shown, IMD 16 may include a control module 81, a therapy delivery module 84 (e.g., which may include a stimulation generator), a sensing module 86, and a power supply 90. The control module or device 81 may include a processor 80, a memory 82, and a telemetry module or device 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 various functions belonging to the IMD 16 and / or the control module 81 described herein. Further, the memory 82 may include any volatile, non-volatile, magnetic, optical, and / or electrical media, 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 media.

[0029] The processor 80 of the control module 81 may include any one or more of the following: a microprocessor, a controller, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), and / or an equivalent discrete or integrated logic circuit system. In some examples, the processor 80 may include multiple components, such as any combination of one or more microprocessors, one or more controllers, one or more DSPs, one or more ASICs, and / or one or more FPGAs, as well as other discrete or integrated logic circuit systems. The functionality of the processor 80 as defined herein may be embodied in software, firmware, hardware, or any combination thereof.

[0030] Control module 81 can control the therapy delivery module or device 84 to deliver therapy (e.g., electrical stimulation therapy such as pacing) to heart 12 based on one or more selected therapy programs that can be stored in memory 82 and on algorithms or methods further described below. More specifically, control module 81 (e.g., processor 80) can control various parameters of the electrical stimulation delivered by therapy delivery module 84, such as, for example, AV delay, pacing pulse with amplitude, pulse width, frequency, or electrode polarity, which can be specified by one or more selected therapy programs (e.g., AV delay adjustment program, pacing therapy program, pacing recovery program, capture management program, etc.). As shown, therapy delivery module 84 is electrically coupled to electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66, for example, via conductors of corresponding leads 18, 20, 22 or, in the case of housing electrodes 58, via electrical conductors arranged within housing 60 of IMD 16. The therapy delivery module 84 can be configured to generate an electrical stimulation therapy, such as pacing therapy, using one or more of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 and deliver the electrical stimulation therapy to the heart 12.

[0031] For example, the therapy delivery module 84 can deliver pacing stimulation (e.g., pacing pulses) via ring electrodes 40, 44, 45, 46, 47, 48 and / or helical tip electrodes 42, 50 of leads 18, 22. Further, for example, the therapy delivery module 84 can deliver a defibrillation shock to the heart 12 via at least two of electrodes 58, 62, 64, 66. In some examples, the therapy delivery module 84 can be configured to deliver pacing, cardioversion, or defibrillation stimulation in the form of electrical pulses. In other examples, the therapy delivery module 84 can 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.

[0032] The IMD 16 may further include a switching module or device 85, and the control module 81 (e.g., processor 80) may use the switching module 85 to, for example, select via a data / address bus which of the available electrodes are used for delivering therapy, such as pacing pulses for pacing therapy, or which of the available electrodes are used for sensing. The switching module 85 may include a switch array, switch matrix, multiplexer, or any other type of switching device suitable for selectively coupling the sensing module or device 86 and / or the therapy delivery module 84 to one or more selected electrodes. More specifically, the therapy delivery module 84 may include a plurality of pacing output circuits. Each of these plurality of pacing output circuits may, for example, be selectively coupled using the switching module 85 to one or more of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 (e.g., a pair of electrodes for delivering therapy to a bipolar or multipolar pacing vector). In other words, each electrode can be selectively coupled to a pacing output circuit in the pacing output circuit of the therapy delivery module using the switching module 85.

[0033] The sensing module 86 is coupled (e.g., electrically coupled) to a sensing device, which may include electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 to monitor the electrical activity of the heart 12, such as electrocardiogram (ECG) / electrogram (EGM) signals. ECG / EGM signals can be used to measure or monitor activation time (e.g., ventricular activation time), heart rate (HR), heart rate variability (HRV), heart rate oscillation (HRT), deceleration / acceleration capacity, deceleration sequence morbidity, 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 the T wave), T wave changes, QT interval, electrical vectors, etc.

[0034] The switching module 85 can also be used with the sensing module 86 to select which of the available electrodes are used or enabled to, for example, sense the electrical activity of a patient's heart (e.g., using one or more electrical vectors of a patient's heart using any combination of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66). Similarly, the switching module 85 can also be used with the sensing module 86 to select which of the available electrodes are not used (e.g., disabled) to, for example, sense the electrical activity of a patient's heart (e.g., using one or more electrical vectors of a patient's heart using any combination of electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66), etc. In some examples, the control module 81 can select the electrodes that act as sensing electrodes by providing signals, for example, via a data / address bus, through the switching module within the sensing module 86.

[0035] In some examples, the sensing module 86 includes a channel comprising an amplifier having a relatively wider passband than an R-wave or P-wave amplifier. Signals from selected sensing electrodes can be supplied to a multiplexer and subsequently converted by an analog-to-digital converter into multi-bit digital signals for storage in memory 82, for example, as an electrogram (EGM). In some examples, such storage of an EGM in memory 82 can be under the control of direct memory access circuitry.

[0036] In some examples, control module 81 can operate as an interrupt-driven device and can respond to interrupts from the pacemaker timing and control module, where the interruption may correspond to the occurrence of sensed P and R waves and the generation of cardiac pacing pulses. Any necessary mathematical calculations can be performed by processor 80, and any updates to values ​​or intervals controlled by the pacemaker timing and control module may occur after such interruptions. A portion of memory 82 can be configured as a plurality of recirculation buffers capable of holding one or more series of measurement intervals that can be analyzed by, for example, processor 80 in response to the occurrence of pacing or sensing interruptions to determine whether the patient's heart 12 is currently exhibiting atrial or ventricular tachyarrhythmias.

[0037] The telemetry module 88 of the control module 81 may include any suitable hardware, firmware, software, or any combination thereof for communicating with another device, such as a programmer. For example, under the control of the processor 80, the telemetry module 88 may receive downlink telemetry from the programmer and send uplink telemetry to the programmer via an antenna (which may be internal and / or external). The processor 80 may, for example, provide data to be transmitted uplink to the programmer and control signals for the telemetry circuitry within the telemetry module 88 via an address / data bus. In some examples, the telemetry module 88 may provide the received data to the processor 80 via a multiplexer.

[0038] The various components of the IMD 16 are further coupled to a power source 90, which may include a rechargeable or non-rechargeable battery. A non-rechargeable battery may be selected to last for several years, while a rechargeable battery may be inductively charged from an external device, for example, on a daily or weekly basis.

[0039] Figure 3B This is a functional block diagram depicting an embodiment of an IMD 16 with bipolar RA leads 22 and bipolar RV leads 18 coupled to an implantable pulse generator (IPG) circuit 31, without LA CS pacing / sensing electrodes. The implantable pulse generator circuit has programmable modes and parameters of the biventricular DDD / R type known in the pacing field. Furthermore, the sensor signal processing circuit 91 is indirectly coupled to the timing circuit 43 to the microcomputer circuit system 33 via a data and control bus. The IPG circuit 31 is shown in the functional block diagram, which is generally divided into the microcomputer circuit 33 and the pacing circuit 21. The pacing circuit 21 includes a digital controller / timer circuit 43, an output amplifier circuit 51, a sensing amplifier circuit 55, an RF telemetry transceiver 41, an activity sensor circuit 35, and many other circuits and components described below.

[0040] When battery 29 provides power, crystal oscillator circuit 89 provides a basic timing clock to pacing circuit 21. Power-on reset circuit 87 responds to the initial connection of the circuit with the battery to define initial operating conditions, and similarly resets the operating state of the device 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 pacing circuit 21. Analog-to-digital converter (ADC) and multiplexer circuit 39 digitizes the analog signals and voltages to provide, for example, 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 87, and crystal oscillator circuit 89 may correspond to any of those used in illustrative implantable cardiac pacemakers.

[0041] If the IPG is programmed to a rate-responsive mode, signals output from one or more physiological sensors are used as rate control parameters (RCPs) to derive the physiological escape interval. For example, the escape interval is adjusted proportionally to the level of patient activity generated in the patient activity sensor (PAS) circuitry 35 within the exemplary IPG circuitry 31. The patient activity sensor 27 is coupled to the IPG housing and may take the form of a piezoelectric crystal transducer. The output signal of the patient activity sensor 27 can be processed and used as the RCP. Sensor 27 generates an electrical signal in response to sensed body activity, which is processed by the activity circuitry 35 and provided to the digital controller / timer circuitry 43. Similarly, the illustrative systems, apparatus, and methods described herein can be practiced in conjunction with alternative types of sensors (such as oxygenation sensors, pressure sensors, pH sensors, temperature sensors, respiration sensors, perfusion sensors, heart sound sensors, and heart rate sensors) to provide rate-responsive pacing capabilities. For example, impedance can be measured using a loop electrode on a lead (e.g., RA or RV lead), and temperature can be measured via a sensor at the distal end of the lead. Alternatively, the QT time can be used as a rate indication parameter, in which case no additional sensor is required. Similarly, the illustrative implementation described herein can also be practiced in non-rate-responsive pacemakers.

[0042] Data transmission to and from the external programmer is achieved via telemetry antenna 57 and an associated RF transceiver 41, which demodulates both received downlink telemetry and transmits uplink telemetry. Uplink telemetry capabilities may include transmitting stored digital information, such as activity information, rate response pacemaker curves, operating modes and parameters, EGM histograms and other events, as well as real-time EGM of atrial and / or ventricular electrical activity and the ability to transmit flagged channel pulses indicating the occurrence of sensed and paced depolarization in the atria and ventricles.

[0043] The microcomputer 33 includes a microprocessor 80, an associated system clock, and on-processor RAM chips 82A and ROM chips 82B. Additionally, the microcomputer circuitry 33 includes a separate RAM / ROM chip 82C to provide additional memory capacity. The microprocessor 80 typically operates in a low-power mode and is interrupt-driven. The microprocessor 80 is awakened in response to defined interrupt events, which may include A-TRIG, RV-TRIG, and LV-TRIG signals generated by timers in the digital timer / controller circuitry 43, and A-EVENT, RV-EVENT, and LV-EVENT signals generated by the sense amplifier circuitry 55. The specific values ​​of the timeout intervals and delays by the digital controller / timer circuitry 43 are controlled by the microcomputer circuitry 33 via data and control buses from programmed parameter values ​​and operating modes. Furthermore, if programmed to operate as a rate-responsive pacemaker, timed interrupts (e.g., every cycle or every two seconds) may be provided to allow the microprocessor to analyze active sensor data and update the basic pacing rate and AA, VA (if applicable). In addition, the microprocessor 80 can also be used to define variable, operable AV delay intervals, as well as the energy delivered to each ventricle and / or atrium.

[0044] In one embodiment, microprocessor 80 is a custom microprocessor adapted to fetch and execute instructions stored in RAM / ROM unit 82 in a conventional manner. However, other embodiments are considered that may be suitable for practicing the disclosed methods. For example, off-the-shelf, commercially available microprocessors or microcontrollers or custom-designed, dedicated hardwired logic or state machine type circuits may perform the functions of microprocessor 80.

[0045] The digital controller / timer circuit 43 operates under the general control of the microcomputer 33 to control timing and other functions within the pacing circuit 21, and includes a set of timing and associated logic circuits, some of which are depicted in relation to this disclosure. The depicted timing circuits include a URI / LRI timer 83A, a VV delay timer 83B, an intrinsic interval timer 83C for timing the elapsed V-EVENT to V-EVENT or V-EVENT to A-EVENT intervals, an escape interval timer 83D for timing the AA and / or VA pacing escape intervals, an AV delay interval timer 83E for timing the A-LVp delay (or A-RVp delay) from a previous A-EVENT or A-TRIG, a postventricular timer 83F for timing the postventricular time period, and a date / time clock 83G.

[0046] The AV delay interval timer 83E is loaded with an appropriate delay interval (e.g., A-RVp delay or A-LVp) for a ventricular chamber to time out from a previous A-PACE or A-EVENT. The interval timer 83E triggers pacing stimulus delivery and can be based on one or more previous cardiac cycles (or on a dataset derived empirically for a given patient).

[0047] The post-event timer 83F times out the post-ventricular time period following RV-EVENT, LV-EVENT, RV-TRIG, or LV-TRIG, and the post-atrial time period following A-EVENT or A-TRIG. 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 the post-ventricular atrial blanking period (PVARP), the post-atrial ventricular blanking period (PAVBP), the ventricular blanking period (VBP), and the ventricular refractory period (VRP), but other time periods can be appropriately limited, at least in part, according to the operating circuitry used in the pacemaker. The post-atrial time period includes the atrial refractory period (ARP) and the atrial blanking period (ABP). During the atrial refractory period, A-EVENT is ignored for the purpose of resetting any AV delays, and during the atrial blanking period, 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-TRIG, or in the latter case, at the end of an A-PACE that can follow an A-TRIG. 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-TRIG, or in the latter case, at the end of a V-PACE that can follow a V-TRIG. The microprocessor 80 also optionally calculates the AV delay, the post-ventricular time interval, and the post-atrial time interval, which vary with the sensor-based escape interval and / or intrinsic atrial and / or ventricular rates established in response to the RCP.

[0048] The output amplifier circuit 51 contains an RA pacing pulse generator (and an LA pacing pulse generator, if LA pacing is provided), an RV pacing pulse generator, an LV pacing pulse generator, and / or any other pulse generator configured to provide atrial and ventricular pacing. To trigger the generation of RV-PACE or LV-PACE pulses, the digital controller / timer circuit 43 may use the algorithm described below.

[0049] Output amplifier circuit 51 includes a switching circuit for coupling selected pacing electrode pairs from the lead conductors and IND-CAN electrodes 20 to an RA pacing pulse generator (and an LA pacing pulse generator, if provided), an RV pacing pulse generator, and an LV pacing pulse generator. Pacing / sensing electrode pair selection and control circuit 53 selects the lead conductors and associated pacing electrode pairs for coupling with atrial and ventricular output amplifiers within output amplifier circuit 51 to implement RA, LA, RV, and LV pacing.

[0050] Sensing amplifier circuit 55 contains sensing amplifiers for atrial and ventricular pacing and sensing. High-impedance P-wave and R-wave sensing amplifiers can be used to amplify the voltage difference signal generated across the sensing electrode pair due to the passage of the cardiac depolarization wavefront. The high-impedance sensing amplifier uses high gain to amplify low-amplitude signals and relies on passband filtering, time-domain filtering, and amplitude threshold comparison to distinguish the P-wave or R-wave from background electrical noise. Digital controller / timer circuit 43 controls the sensitivity settings of atrial and ventricular sensing amplifier 55.

[0051] During the blanking period before, during, and after the delivery of a pacing pulse to any of the pacing electrodes in the pacing system, the sensing amplifier can be decoupled from the sensing electrode to avoid saturation of the sensing amplifier. Sensing amplifier circuit 55 includes a blanking circuit for decoupling selected lead conductor pairs and IND-CAN electrode 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 electrode 20 to the RA sensing amplifier (and LA sensing amplifier, if provided), RV sensing amplifier, and LV sensing amplifier. Similarly, sensing electrode selection and control circuit 53 selects the 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.

[0052] Right atrial depolarization or a P wave in the RA-SENSE signal sensed by the RA sensing amplifier results in an RA-EVENT signal being transmitted to the digital controller / timer circuit 43. Similarly, left atrial depolarization or a P wave in the LA-SENSE signal sensed by the LA sensing amplifier (if provided) results in an LA-EVENT signal being transmitted to the digital controller / timer circuit 43. Ventricular depolarization or an R wave in the RV-SENSE signal sensed by the ventricular sensing amplifier results in an RV-EVENT signal being transmitted to the digital controller / timer circuit 43. Similarly, ventricular depolarization or an R wave in the LV-SENSE signal sensed by the ventricular sensing amplifier results in an LV-EVENT signal being transmitted to the digital controller / timer circuit 43. The RV-EVENT, LV-EVENT, RA-EVENT, and LA-SENSE signals may be unwanted or not unwanted, and may be unintentionally triggered by electrical noise signals or abnormally conducted depolarization waves instead of genuine R or P waves.

[0053] The technologies described in this disclosure, including those belonging to IMD 16 and / or various constituent components, can be implemented at least in part in the form of hardware, software, firmware, or any combination thereof. For example, aspects of the technology can be implemented within one or more processors embodied as programmers, stimulators, image processing devices, or other devices, such as physician or patient programmers, including one or more microprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated or discrete logic circuit systems, and any combination of such components. The terms “module,” “processor,” or “processing circuit system” can generally refer to the aforementioned logic circuit system alone, a combination of the aforementioned logic circuit system with other logic circuit systems, or any circuit system in any other equivalent circuit system.

[0054] 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 described unit, module, or component may be implemented together or individually as discrete but interoperable logical devices. Describing different features as modules or units is intended to highlight different functional aspects and does not necessarily imply that such modules or units must be implemented by separate hardware or software components. Rather, the functionality associated with one or more modules or units may be performed by separate hardware or software components, or integrated into common or separate hardware or software components.

[0055] When implemented in software, the functionality attributable to the systems, apparatus, and techniques described herein can be embodied in instructions on a computer-readable medium such as RAM, ROM, NVRAM, EEPROM, flash memory, magnetic data storage media, optical data storage media, etc. The instructions can be executed by one or more processors to support one or more aspects of the functionality described herein.

[0056] System, device, and pacing therapy selection methods can be used to provide an assessment of a patient's cardiac health and / or to evaluate and configure cardiac therapies to be delivered to the patient. For example, as further described herein, system, device, and pacing therapy selection methods can be used to determine and adjust pacing therapies for patients with HFpEF based on patient parameters monitored over time.

[0057] As mentioned above, a variety of different pacing therapies have been suggested for the treatment of HFpEF. These pacing therapies include atrioventricular nodal stimulation (AVNS) to reduce ventricular rate during atrial fibrillation, atrial pacing and rate-adaptive pacing, nocturnal overdrive pacing, PR interval optimization via ventricular pacing, and AVNS to reduce inflammation. These therapies are not administered discretely or in a vacuum, as they are interconnected and can be used in various combinations. Therefore, selecting one or more of these pacing therapies involves more than just assessing discrete patient parameters to select a single pacing therapy. Instead, the approach discussed in this article considers each of these therapies and their potential interactions.

[0058] Increased heart rate can lead to thinning and dilation of the left ventricular wall. Myocyte loss and reactive hypertrophy are major components of ventricular remodeling in pacing-induced dilated cardiomyopathy. While this amplifies the problems in patients with heart failure and reduced ejection fraction (HFrEF), such remodeling is desirable in patients with HFpEF, who have normal-sized ventricles with increased wall thickness. Nocturnal overpacing, such as increasing the heart rate (i.e., tachycardia pacing) to 100 beats per minute overnight via an implanted medical device for five hours, has been tested as a therapy to thin the left ventricular wall in a controlled manner. Further details regarding overpacing are provided in U.S. Patent No. 9,737,720.

[0059] Patients with high ventricular rates during atrial fibrillation (AF) have an increased risk of receiving inappropriate implantable cardioverter defibrillator (AVD) shocks. It has been shown that the use of AVNS during AF can reduce the ventricular rate to avoid such inappropriate and unnecessary shocks. Further details regarding AVNS delivery during AF are provided in U.S. Publication No. 2017 / 0050022. However, if AVNS is delivered and the AV node is delayed, ventricular pacing should be used to improve or optimize the PR interval (the interval from atrial activation (sensing / pacing) to ventricular activation), as excessive PR prolongation can be detrimental to patients with heart failure.

[0060] With prolonged PR intervals, atrial contractions occur prematurely during diastole, resulting in atrial contractions superimposed on early left ventricular (LV) filling and occurring much earlier than the onset of LV contraction. This leads to the fusion of E and A waves. Prolonged PR intervals are associated with electrophysiological abnormalities such as atrial enlargement and myocardial fibrosis, delayed atrioventricular node conduction and / or bundle branch / Purkinje fiber conduction, altered autonomic tone, and the effects of pharmacological interventions. Prolonged PR intervals are common in both patients with reduced ejection fraction and those with normal ejection fraction in heart failure and are associated with worse survival, but this PR interval prolongation is not an independent predictor of outcome. In patients with only atrial asynchrony and HFpEF, atrial pacing appears to provide beneficial hemodynamic effects. While it is unknown whether a prolonged PR interval is a cause or effect of heart failure, restoration of the PR interval may increase LV filling. This can increase cardiac output and reduce mitral regurgitation.

[0061] AVNS can also be used to reduce inflammation. Pro-inflammatory cytokines are increased in HFpEF patients compared to HFrEF patients and can predict future heart failure development. Inflammation has been shown to be reduced by vagal nerve stimulation. For example, inflammatory reflexes indicate that efferent vagal signaling can activate acetylcholine-dependent interactions with the α7 nicotinic acetylcholine receptor subunit (a7nAChR) on monocytes and macrophages, leading to reduced cytokine production. High-frequency 6-hour stimulation of the inferior vena cava-inferior atrial ganglion plexus has shown a significant reduction in postoperative inflammation, as evidenced by decreased serum levels of IL-6, TNF-α, VEGF, and EGF. Intracardiac stimulation of the AV node (vagal nerve branch) (AVNS) can also affect intracardiac inflammation and is effective in patients with heart failure preserving ejection fraction.

[0062] To prevent arrhythmias, these AVNS therapies are administered in a sporadic manner. As shown above, AVNS have demonstrated effectiveness in reducing ventricular rate during AF and have the potential to reduce inappropriate shocks in patients in this manner. For post-coronary artery bypass graft patients, they have shown value in reducing inflammation in patients with diastolic heart failure.

[0063] Left atrial pacing can also be used to alleviate atrial conduction block. Atrial conduction block (IAB) is generally defined as a P wave duration ≥120 ms on a surface ECG. When fifty-five patients with heart failure-pEF were compared with thirty-three healthy individuals, a significant increase in intraatrial and interatrial asynchrony was observed in patients with HFpEF compared to controls. Left atrial pacing therapy has also been used to restore active left ventricular filling in patients with HFpEF who have no other known cause of heart failure besides atrial dyssynchrony syndrome.

[0064] Furthermore, chronotropic dysfunction can be limited by adapting one or more of these pacing therapies to the pacing rate. Chronic dysfunction is common in patients with high heart rate-post-excitement (HFpEF) and is characterized by a reduced heart rate response during activities of daily living or other activities requiring increased cardiac output (e.g., exercise). HFpEF patients with chronotropic dysfunction typically cannot increase their sinoatrial rate / atrial rate. For patients with chronotropic dysfunction, both maximum exercise capacity and peak heart rate reached during exercise are reduced.

[0065] Figure 4 A flowchart illustrates a method for selecting one or more of the pacing therapies described above, while considering their potential interactions with each other in the treatment of patients with heart failure, specifically those with HFpEF. The method begins with monitoring one or more patient parameters 402. These parameters can be any parameters convenient for the management of heart failure, such as one or more of the following: chest impedance, heart rate (HR), atrial-to-atrial (AA) interval for detecting AF, ventricular rate or rapid ventricular rate (RVR) during AF, daytime resting heart rate (which can be derived from the ventricular RR interval, where R is the R of the QRS complex; it can be measured in a supine position), nocturnal heart rate (NHR), heart rate variability (HRV), activity, cough, heart sounds (such as the S3 heart sound), patient weight, stroke volume (SV), cardiac output (CO), cardiac index (CI), filling pressure, systolic blood pressure (BP), and oxygen perfusion.

[0066] Typically, one or more of these parameters can be device diagnostics captured by an IMD or a patient wearable device. In some implementations, one or more diagnostics can be captured by external sensors or user input.

[0067] Electrodes can be used to measure chest impedance, such as electrodes on the IMD and intracardiac leads. For example, shell-based electrodes on the IMD housing (which can be described as a sheath) and electrodes on the RV coil leads can be used. Decreased chest impedance can be used to indicate increased cardiac preload and effusion.

[0068] Heart rate (HR), or daytime resting heart rate, can be measured using electrodes on, for example, an IMD (such as a shell-based electrode), an intracardiac lead, or an optical sensor on a patient-wearable sensor. An elevated HR can be used as an indicator of high heart failure risk. The atrial interval (AA interval) can be measured using electrodes on, for example, an IMD (such as a shell), an intracardiac lead, or an optical sensor on a patient-wearable sensor. The AA interval can be used to differentiate atrial rhythms (such as AF) from sinus rhythms. In some cases, AF can lead to worsening heart failure.

[0069] NHR can be measured using, for example, electrodes on an IMD (such as shell-based electrodes), an intracardiac lead, or an optical sensor on a patient-wearable sensor. An elevated NHR can indicate increased autonomic tone, and NHR can also be used to determine whether a patient is asleep.

[0070] HRV can be measured using electrodes on, for example, an IMD (such as a shell-based electrode), an intracardiac lead, or an optical sensor on a patient-wearable sensor. A decreased HRV can be used to indicate increased sympathetic tone and autonomic imbalance. A decreased HRV may be associated with an increased heart rate (HR).

[0071] Activity can be measured using motion sensors, such as IMDs or inertial measurement units (IMUs) in patient wearable sensors. Activity can be used to indicate a patient's overall functional status, including whether the patient is asleep. For example, activity may decrease as a patient's risk of worsening heart failure increases.

[0072] Heart sounds such as the S3 heart sound can be measured using devices such as accelerometers, piezoelectric sensors, or microphones on an IMD. The presence of the S3 heart sound can indicate elevated pulmonary atrial pressure and can also indicate an increased risk of worsening heart failure.

[0073] A weighing scale can be used, for example, to measure the patient's weight. An increase in weight can be used to indicate fluid accumulation.

[0074] SV can be measured indirectly using optical sensors and tissue oxygen sensors, such as those on an IMD or a patient-wearable sensor. A decrease in SV can be used to indicate worsening heart failure.

[0075] Oxygen perfusion can be measured using optical sensors, such as those on an IMD or wearable patient sensor. Decreased oxygen perfusion can be used to indicate worsening heart failure. Oxygen perfusion may be related to or associated with cardiac arrest (CO).

[0076] CO can be measured, for example, based on SV and HR. CO can be calculated by multiplying SV and HR. CO can be used to indicate worsening heart failure.

[0077] CI can be determined, for example, based on normalizing CO to the patient's body surface area. CI can be used to indicate worsening heart failure. In some implementations, CI can be used instead of CO, for example, when the patient's body surface area is known.

[0078] Filling pressure can be measured using pressure sensors located, for example, in the left atrium or pulmonary artery. Elevated filling pressure can be used to indicate worsening heart failure.

[0079] For example, a wearable cuff can be used to measure blood pressure (BP). Typically, BP can be used to guide interventions. Elevated BP can indicate the availability of certain interventions for worsening heart failure. BP below a threshold can indicate that certain interventions for worsening heart failure can be ruled out.

[0080] Ventricular rate during AF or RVR can be measured using, for example, electrodes on an IMD (such as shell-based electrodes), an intracardiac lead, or an optical sensor on a patient-wearable sensor. RVR can be used to indicate worsening heart failure.

[0081] Accelerometers and / or piezoelectric sensors can be used to measure heart sounds, such as S3 and S4. These heart sounds may be present when a patient begins to have fluid buildup and when heart failure begins to worsen.

[0082] Heart sounds are typically associated with the mechanical vibrations of a patient's heart and the flow of blood through the heart valves, and therefore may be highly correlated with pressure gradients across the heart valves and blood pressure. Heart sounds may be due not only to vibrations and pressure within the heart, but also to the entire cardiac circulatory system, such as blood, the heart, and aorta. Heart sounds can be reproduced with each cardiac cycle and are separated and classified according to the activity associated with the vibrations.

[0083] The first heart sound is called "S1" and can be considered as the vibrational sound produced by the heart during the closure of the atrioventricular or AV valves (i.e., the mitral and tricuspid valves). The S1 sound can sometimes be broken down into an M1 sound component from mitral valve closure and a T1 sound component from tricuspid valve closure. The second heart sound is called "S2" and is produced by the closure of the semilunar valves (i.e., the pulmonary and aortic valves). The S2 heart sound can be considered as marking the onset of diastole. The S2 sound can also be broken down into components. The P2 sound component originates from pulmonary valve closure, and the A2 sound component originates from aortic valve closure. The third and fourth heart sounds are called "S3" and "S4," respectively, and can be conceptualized as relating to diastolic ventricular filling. S3 is due to the rapid filling of the ventricles and can occur when a large amount of blood flows from the atria into the ventricles before the ventricular walls relax. S4 is caused by the rapid filling of the ventricles with blood from the atria due to atrial contraction.

[0084] Depending on the parameters and / or the patient's condition, these parameters can be monitored continuously or at varying times and at any appropriate rate.

[0085] Monitoring parameters are used to detect atrial tachycardia (AT) and / or atrial fibrillation (AF), such as rapidly occurring AT or AF 410. If one or more parameters are determined to indicate that the patient is experiencing AT or AF, a first pacing therapy 412 is delivered. The first pacing therapy may be a first AVNS, wherein a voltage greater than the threshold voltage (V t ) pacing voltage (V p ) Delivery of stimulation. The threshold voltage is based on the magnitude necessary to prolong atrioventricular conduction time by at least 25%, and an example of a threshold voltage is about 4V or in the range of 3V to 10V. As discussed above, the first AVNS pacing therapy is delivered to reduce the ventricular rate during atrial fibrillation or tachycardia to reduce the administration of inappropriate shocks.

[0086] The first AVNS is delivered in burst form with a predetermined pulse train. The AVNS pulse train is combined... Figure 5The demonstration is presented and discussed further below. An exemplary first AVNS pulse train can be described as VsApppp+As, representing ventricular sensing followed by multi-atrial stimulation (e.g., four) 30 milliseconds later. More specifically, Apppp is a pulse train in the atrium synchronized with QRS = Vsense or Vpace, with a voltage between four and eight volts, an interval of 20 milliseconds, and a pulse width between 0.5 and 1.5 milliseconds. “+As” indicates that the atrial sensing (or multi-atrial sensing) is not triggered by the atrial pulse train but is separate. Pulses are delivered during the refractory period of the ventricle so as not to induce ventricular tachycardia or ventricular fibrillation. The first AVNS pacing therapy can also be used in combination with rate-adaptive pacing techniques. If a slower acquisition rate requires pacing, the exemplary later pulse train can involve Vsense becoming Vpace. This pulse train can be described as Vs / pApppppp-As-As-Vp, which represents ventricular sensor or pacing, followed by six atrial pacing bursts, atrial sensing, atrial sensing, and ventricular pacing when the ventricular rate is about to reach a lower rate. In the case of atrial arrhythmias, multiple pulse trains can be implemented within a single cardiac cycle.

[0087] After delivering a sequence of atrioventricular nodal stimulation pulses, parameters are evaluated to determine whether termination criterion 414 has been met. Exemplary termination criteria may include whether the first AVNS pacing therapy effectively reduced the mean ventricular rate (e.g., response time is a programmable setting, nominal value, five beats). Further termination criteria may include whether a short RR interval occurred in the detection zone during AVNS (e.g., after the response time) to ensure patient safety; a predetermined programmable interval time (e.g., up to thirty seconds); or whether actual ventricular fibrillation was detected during AVNS pacing therapy. Any one or more of these termination criteria may be used alone or in combination to determine whether to stop the first AVNS pacing therapy. If the programmed termination criteria are met, the method returns to monitoring patient parameters 402. If the termination criteria are not met, the method returns to another sequence of delivering the first AVNS pacing therapy. For additional safety, the first AVNS pacing therapy may not be delivered in events with a mean ventricular interval below a threshold (e.g., 260 milliseconds), as short VV intervals are common in oversensing situations and are uncommon with inappropriate shocks to AF delivered rapidly.

[0088] If one or more monitored patient parameters do not indicate that the patient is experiencing rapidly progressing atrial tachycardia or atrial fibrillation, it is determined whether one or more patient parameters indicate that the patient is asleep 420. If the parameters indicate that the patient is asleep, a second pacing therapy is delivered 422. In some embodiments, the second pacing therapy is nocturnal overtachycardia pacing therapy. Although this therapy is referred to as "nocturnal," it does not need to be administered during nocturnal hours. Instead, overtachycardia pacing is delivered when the patient is inactive for an extended period of time (which is typically when the patient is asleep) to avoid body self-regulation. This can be done at night or not. Overtachycardia pacing therapy is delivered at a predetermined number of beats per minute (e.g., 100 bpm) for a predetermined duration (e.g., five hours).

[0089] During overdrive pacing therapy, relative to the overdrive PR threshold interval (PR) ot Assess the patient's atrioventricular interval (PR) 424 to automatically adjust the type of therapy (e.g., atrial-based or DDD pacing) within the overdrive pacing treatment. The overdrive PR threshold interval can be in the range of approximately 240 ms to 300 ms, with an exemplary threshold of 240 ms. Select an overdrive PR threshold to limit PR such that the resulting RP interval is 300 ms or greater. If the patient's PR does not exceed the PR threshold interval, PR monitoring continues while overdrive pacing therapy is delivered 430. If the patient's PR is equal to or exceeds the PR threshold interval, additional pacing therapy is delivered concurrently with overdrive pacing to adjust or optimize the patient's PR 426. For example, the additional pacing therapy could be DDD mode pacing with a preset AV interval (e.g., 200 ms). Alternatively, the clinician can program a preset AV interval specific to the patient's condition or calculated by the implanted device to ensure that the resulting RP interval is at least 300 ms. After delivering the additional pacing therapy, determine whether termination criterion 428 is met. For example, if the patient's AV interval shortens to an acceptable and predetermined rate (e.g., below 240 milliseconds), the additional pacing therapy is terminated and the method returns to overdrive atrial pacing without ventricular pacing 422. Alternatively, if the predetermined time for overdrive pacing has been reached, the overdrive pacing therapy is terminated and the method returns to monitoring patient parameters 402. However, if the termination criteria are not met, the patient's PR will continue to be monitored while overdrive pacing therapy is delivered 430.

[0090] If one or more monitored patient parameters do not indicate that the patient is experiencing atrial tachycardia or atrial fibrillation and the patient is not asleep, one or more pacing therapies may be delivered to reduce inflammation. Because anti-inflammatory pacing may lead to neural remodeling, it is administered at a lower frequency and off-cycle (e.g., at night). To select a therapy, the patient's P-wave duration (i.e., the time taken from start to finish in both atria) is assessed relative to a P-wave duration threshold.440 Atrial block (IAB) is generally defined as a P-wave duration equal to or greater than 120 milliseconds on a surface ECG; therefore, 120 milliseconds can be an exemplary P-wave duration threshold.

[0091] If one or more patient parameters indicate that the patient has IAB (e.g., P wave duration greater than or equal to 120 ms), a third pacing therapy 442 is delivered. The third pacing therapy may be an anti-inflammatory pacing coupled to atrial pacing (e.g., a second, different type of AVNS). However, stimulation for the second AVNS is applied at a voltage less than a threshold voltage (V0). t For example, the pacing voltage (V) is the same threshold voltage discussed above regarding the first AVNS sequence. p Delivery. The same threshold voltage can be used for both analyses in the therapy selection approach. Alternatively, separate buffers can be used between the two. For example, the voltage threshold can be programmed such that 6V is required to achieve the extension of the PR interval of the first AVNS discussed above, but 2V stimulation can be used for anti-inflammatory (second) AVNS to maintain battery life and reduce the risk of patient symptoms.

[0092] Additionally, as discussed above, the second AVNS is delivered in bursts with a predetermined pulse train. An exemplary second AVNS pulse train can be described as Vs+Apppppp, which represents ventricular sensing with multiple atrial pacing bursts (e.g., 6). However, Vs can also be Vp (ventricular pacing stimulation). As mentioned above, "+" indicates that atrial pacing is not triggered at Vs, but separately (e.g., there may be a time delay between Vs and the pulse train in the atrium). In other embodiments, the atrial pulse train can be triggered during atrial pacing. In another embodiment, the exemplary pulse train of VsApppppp+As would refer to pulses triggered during the ventricular refractory period synchronized with the QRS, i.e., pulses triggered during ventricular sensing. As shown above, the pulse train has a lower voltage (e.g., 1V-4V), but has the same frequency as the first AVNS therapy (50Hz, i.e., 20 ms pulse interval). Pulses in the atrium during the refractory period are delivered to avoid inducing atrial tachycardia or atrial fibrillation. The second AVNS pacing therapy can also be used in combination with rate-adaptive pacing techniques. An exemplary pulse sequence can be described as Apppppp-Vs (Vrate not delayed)-Appppp, which represents six atrial pacings followed by another sequence of ventricular sensing and five atrial pacing bursts.

[0093] Alternatively, if one or more patient parameters indicate that the patient does not have IAB (e.g., P wave duration less than 120 ms), a fourth pacing therapy 442 is delivered. The fourth pacing therapy can be a separate anti-inflammatory pacing therapy (e.g., a second different type of AVNS). Again, stimulation for the second AVNS is applied at a voltage less than a threshold voltage (V0). t For example, the pacing voltage (V) of the same threshold voltage discussed above regarding the first AVNS sequence or another voltage value. p Delivery. Additionally, as discussed above, the second AVNS is delivered in bursts with a predetermined pulse sequence. However, the pulse sequence used for the AVNS here differs from the pulse sequence used for patients with IAB. An exemplary second AVNS pulse sequence for fourth pacing therapy can be described as Vs+Asppppp, representing ventricular sensing, where the pulse sequence is triggered by atrial sensing, followed by multiple atrial pacing bursts (e.g., 5). Pulses are delivered to the atria during the refractory period to avoid inducing atrial tachycardia or atrial fibrillation. Second AVNS pacing therapy can also be used again in combination with rate-adaptive pacing techniques. An exemplary pulse sequence for fourth pacing therapy can be described as Aspppp-Vs (Vrate not delayed)-Appppp, representing atrial sensing and five atrial pacing bursts, followed by another sequence of ventricular sensing and five atrial pacing bursts.

[0094] During the third and / or fourth pacing therapy, relative to the PR threshold interval (PRt Assess the patient's atrioventricular interval (PR) 446 to automatically adjust the type of therapy (e.g., atrial-based or DDD pacing) within anti-inflammatory pacing treatment. The PR threshold interval can be in the range of approximately 180 ms to 350 ms, with an exemplary threshold of 200 ms, which is common among patients where the negative effects of a prolonged PR interval begin to manifest as lower pump efficiency. If the patient's PR does not exceed the PR threshold interval, PR monitoring continues while a third / fourth anti-inflammatory pacing therapy is delivered 448. If the patient's PR is equal to or exceeds the PR threshold interval, additional pacing therapy is delivered to adjust or optimize the patient's PR 450. For example, the additional pacing therapy could be DDD mode pacing with a preset AV interval (e.g., 180 ms). The additional pacing involves ventricular pacing after 180 ms, along with atrial sensing or atrial pacing. Alternatively, clinicians can program the preset AV interval for the patient's condition.

[0095] After delivery of additional pacing therapy, anti-inflammatory pacing may be continued or terminated to return to monitoring of patient parameters 402. This determination is based on an effective response to the side effects of stimulation or changes in patient condition. For example, if the desired stimulation is achieved or the patient's inherent AV conduction becomes shorter than the DDD AV interval, the third / fourth pacing therapy may be terminated. In another implementation, anti-inflammatory pacing may continue for a predetermined time or until the predetermined AV interval is achieved during anti-inflammatory pacing or additional pacing therapy. When returning to anti-inflammatory pacing, the patient's PR will continue to be monitored while the third / fourth anti-inflammatory pacing therapy is delivered 448.

[0096] AVNS pacing therapy through Figure 5 The atrial electrocardiogram further illustrates this. Figure 5 The onset of AF is shown and a typical example of the effect of AVNS on ventricular rate during AF is illustrated (e.g., Figure 4 Method 412). A rapid and irregular ventricular rate was observed in the left portion of the recording, but AVNS was activated at the black triangle 502. Figure 5 In this context, only "Ap" indicates the pulse train, referred to above as Apppp to better indicate multiple stimulation. AVNS (8V, 1.5 ms, synchronized with the QRS) is applied immediately after the QRS complex, and the ventricular rate immediately slows. Ventricular pacing is even required here, confirming the emphasis on the vagus ganglion.

[0097] While various pacing therapies have been proposed and tested for patients with heart failure pEF, no suitable coordinated pacing strategy exists for these patients. The methods described in this article provide guidance for selecting one or more pacing therapies, either individually or in combination, explaining the interoperability (or lack thereof) between various pacing therapies. These methods can be provided as programmable instructions to implantable medical devices in patients with heart failure to select an appropriate pacing therapy regimen.

[0098] Exemplary implementation plan

[0099] The techniques described herein are defined in the claims. However, a non-exhaustive list of non-limiting embodiments is provided below. Any one or more features of these embodiments may be combined with any one or more features of another embodiment, implementation, or aspect described herein.

[0100] In illustrative embodiment 1, a method for managing heart failure includes monitoring one or more sensor-based parameters of a patient. If the one or more parameters indicate atrial tachycardia or atrial fibrillation, a first pacing therapy is delivered. If the one or more parameters do not indicate atrial tachycardia or atrial fibrillation, it is determined whether the patient is asleep. If the patient is asleep, a second pacing therapy is delivered. If the one or more parameters do not indicate atrial tachycardia, atrial fibrillation, or the patient is asleep, the patient's P-wave duration is assessed relative to a P-wave duration threshold. When it is determined that the patient's P-wave duration exceeds the P-wave duration threshold, a third pacing therapy is delivered, and when it is determined that the patient's P-wave duration does not exceed the P-wave duration threshold, a fourth pacing therapy is delivered.

[0101] In illustrative embodiment 2, a method includes the method according to embodiment 1, wherein the first pacing therapy is a first atrioventricular node stimulation sequence with a voltage greater than a threshold. In illustrative embodiment 3, a method includes the method according to any one of the preceding embodiments, wherein the second pacing therapy is overdrive pacing delivering a predetermined amount of time at a predetermined frequency. In illustrative embodiment 4, a method includes the method according to any one of the preceding embodiments, wherein the third pacing therapy includes atrial pacing with a voltage less than the threshold and a second atrioventricular node stimulation sequence. In illustrative embodiment 5, a method includes the method according to any one of the preceding embodiments, wherein the fourth pacing therapy includes the second atrioventricular node stimulation sequence with a voltage less than the threshold.

[0102] In illustrative embodiment 6, a method includes the method according to any one of the preceding embodiments, wherein the P wave duration threshold is 120 milliseconds. In illustrative embodiment 7, a method includes the method according to any one of the preceding embodiments, wherein the patient suffers from heart failure with preserved ejection fraction.

[0103] In illustrative embodiment 8, a method for managing heart failure includes monitoring one or more sensor-based parameters of a patient. It is determined whether the monitored one or more sensor-based parameters indicate atrial tachycardia or atrial fibrillation, and when these parameters indicate atrial tachycardia or atrial fibrillation, a first pacing therapy is delivered. In response to the one or more sensor-based parameters not indicating atrial tachycardia or atrial fibrillation, it is determined whether the monitored one or more sensor-based parameters indicate that the patient is asleep. In response to the one or more sensor-based parameters indicating that the patient is asleep, a second therapy is delivered.

[0104] In illustrative embodiment 9, a method includes the method according to any one of the preceding embodiments, wherein the first pacing therapy is an atrioventricular node stimulation sequence with a voltage greater than a threshold. In illustrative embodiment 10, a method includes the method according to any one of the preceding embodiments, wherein the second pacing therapy is overspeed pacing that delivers a predetermined amount of time at a predetermined frequency.

[0105] In illustrative embodiment 11, a method includes the method according to any one of the foregoing embodiments, the method further including determining whether the patient's atrioventricular interval exceeds a threshold interval in response to the delivery of the overdrive pacing. If the patient's atrioventricular interval exceeds the threshold interval, DDD pacing is delivered at a predetermined atrioventricular interval, and if the patient's atrioventricular interval does not exceed the threshold interval, the patient's atrioventricular interval is monitored.

[0106] In illustrative embodiment 12, a method for managing heart failure includes monitoring one or more sensor-based parameters of a patient. It is determined whether the monitored one or more sensor-based parameters indicate atrial tachycardia or atrial fibrillation, and when these parameters indicate atrial tachycardia or atrial fibrillation, a first pacing therapy is delivered. In response to the one or more sensor-based parameters not indicating atrial tachycardia or atrial fibrillation, it is determined whether the monitored one or more sensor-based parameters indicate that the patient's P-wave duration exceeds a P-wave duration threshold. If the one or more sensor-based parameters indicate that the patient's P-wave duration exceeds the P-wave duration threshold, a second pacing therapy is delivered. If the one or more sensor-based parameters indicate that the patient's P-wave duration does not exceed the P-wave duration threshold, a third pacing therapy is delivered.

[0107] In illustrative embodiment 13, a method includes the method according to embodiment 12, wherein the first pacing therapy includes a first atrioventricular node stimulation sequence with a first voltage greater than a threshold. In illustrative embodiment 14, a method includes the method according to any one of embodiments 12 and 13, wherein the second pacing therapy includes atrial pacing with a second voltage less than the threshold and a second atrioventricular node stimulation sequence. In illustrative embodiment 15, a method includes the method according to any one of embodiments 12 to 14, wherein the third pacing therapy includes the second atrioventricular node stimulation sequence with a third voltage less than the threshold.

[0108] In illustrative embodiment 16, a method for managing heart failure includes monitoring one or more sensor-based parameters of a patient. The method includes determining whether the monitored one or more sensor-based parameters indicate that the patient's P-wave duration exceeds a P-wave duration threshold. If the one or more sensor-based parameters indicate that the patient's P-wave duration exceeds the P-wave duration threshold, a first atrioventricular nodal stimulation (AVN) therapy is delivered. If the one or more sensor-based parameters indicate that the patient's P-wave duration does not exceed the P-wave duration threshold, a second AVN stimulation therapy is delivered.

[0109] In illustrative embodiment 17, a method includes the method according to embodiment 16, wherein the first atrioventricular node stimulation therapy includes atrial pacing and an atrioventricular node stimulation sequence with a voltage less than a threshold. In illustrative embodiment 18, a method includes the method according to one of embodiments 16 and 17, wherein the second atrioventricular node stimulation therapy is an atrioventricular node stimulation sequence with a voltage less than the threshold.

[0110] In illustrative embodiment 19, a method includes the method according to any one of embodiments 16 to 18, the method further including determining whether the patient's atrioventricular interval exceeds a threshold interval in response to delivery of the first or second atrioventricular node stimulation therapy. In response to the patient's atrioventricular interval exceeding the threshold interval, DDD pacing is delivered at a predetermined atrioventricular interval, and in response to the patient's atrioventricular interval not exceeding the threshold interval, the patient's atrioventricular interval is monitored.

[0111] In illustrative embodiment 20, a system for managing heart failure includes one or more sensors for measuring one or more sensor-based parameters, at least one storage component, and a processing circuitry operatively coupled to the one or more sensors and the at least one storage component. The processing circuitry is configured to determine whether the monitored one or more sensor-based parameters indicate atrial tachycardia or atrial fibrillation. When these parameters indicate atrial tachycardia or atrial fibrillation, the processing circuitry is configured to deliver a first pacing therapy. In response to the one or more sensor-based parameters not indicating atrial tachycardia or atrial fibrillation, the processing circuitry is configured to determine whether the monitored one or more sensor-based parameters indicate that the patient is asleep. In response to the one or more sensor-based parameters indicating that the patient is asleep, the processing circuitry is configured to deliver a second therapy, and in response to the one or more sensor-based parameters not indicating atrial tachycardia, atrial fibrillation, or that the patient is asleep, the processing circuitry is configured to determine whether the monitored one or more sensor-based parameters indicate that the patient's P-wave duration exceeds a P-wave duration threshold. In response to an indication that the patient's P-wave duration exceeds a P-wave duration threshold, the processing circuitry is configured to deliver a third pacing therapy, and in response to an indication that the patient's P-wave duration does not exceed the P-wave duration threshold, the processing circuitry is configured to deliver a fourth pacing therapy.

[0112] It should be understood that the various aspects disclosed herein may be combined in combinations different from those specifically given in the specification and drawings. It should also be understood that, depending on the example, certain actions or events of any process or method described herein may be performed in a different order, or may be completely added, combined, or omitted (e.g., performing these techniques may not require all the described actions or events). Furthermore, although for clarity some aspects of this disclosure are described as being performed by a single module or unit, it should be understood that the techniques of this disclosure may be performed by combinations of units or modules associated with, for example, a medical device.

[0113] For all purposes, all references and publications cited herein are expressly incorporated by way of citation unless in any way directly contradict this disclosure.

[0114] Unless otherwise stated, all scientific and technical terms used herein have the meanings commonly used in the art. The definitions provided herein are intended to facilitate understanding of certain terms frequently used herein and are not intended to limit the scope of this disclosure.

[0115] Unless otherwise specified, all numerical values ​​used in the specification and claims to indicate the size, quantity, and physical properties of features are to be understood to be modified by the term “about” in all cases. Therefore, unless otherwise indicated, the numerical parameters shown in the foregoing specification and appended claims are approximate values ​​that can be varied according to the desired properties sought by a person skilled in the art using the teachings disclosed herein. The use of numerical ranges by endpoints includes all numbers within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5) and any range within that range.

[0116] The foregoing description has been presented for purposes of illustration and description. This description is not intended to be exhaustive or to limit these embodiments to the precise forms disclosed. Many modifications and variations are possible in accordance with the foregoing teachings. Any or all features of the disclosed embodiments may be applied individually or in any combination and are not intended to be limiting, but are purely illustrative. The scope of the invention is not limited to this detailed description, but is defined by the appended claims.

Claims

1. A heart failure management system, the heart failure management system comprising: One or more sensors, said one or more sensors being used to measure one or more sensor-based parameters; At least one storage component, said at least one storage component storing multiple pacing therapies; and A processing circuitry system, operatively coupled to the one or more sensors and the at least one storage unit, is configured to: Determine whether one or more sensor-based parameters being monitored indicate atrial tachycardia or atrial fibrillation; In response to one or more sensor-based parameters indicating atrial tachycardia or atrial fibrillation, a first pacing therapy from a variety of stored pacing therapies is delivered; In response to the fact that one or more sensor-based parameters do not indicate atrial tachycardia or atrial fibrillation, it is determined whether the monitored one or more sensor-based parameters indicate that the patient is asleep. In response to one or more sensor-based parameters indicating that the patient is asleep, a second pacing therapy is delivered from a stored pool of multiple pacing therapies; In response to the fact that one or more sensor-based parameters do not indicate that the patient is asleep, has atrial tachycardia, or atrial fibrillation, it is determined whether the monitored one or more sensor-based parameters indicate that the patient's P wave duration exceeds a P wave duration threshold. In response to one or more sensor-based parameters indicating that the patient's P-wave duration exceeds a P-wave duration threshold, a third pacing therapy from a stored pool of multiple pacing therapies is delivered. as well as In response to one or more sensor-based parameters not indicating that the patient's P-wave duration exceeds a P-wave duration threshold, a fourth pacing therapy from a stored pool of pacing therapies is delivered.

2. The heart failure management system according to claim 1, wherein the first pacing therapy is a first atrioventricular node stimulation sequence with a voltage greater than a threshold.

3. The heart failure management system according to any one of claims 1 to 2, wherein the second pacing therapy is overspeed pacing that delivers a predetermined amount of time at a predetermined frequency.

4. The heart failure management system according to claim 2, wherein the third pacing therapy includes atrial pacing with a voltage less than the threshold and a second atrioventricular node stimulation sequence.

5. The heart failure management system of claim 4, wherein the fourth pacing therapy comprises a second atrioventricular node stimulation sequence with a voltage less than the threshold.

6. The heart failure management system according to claim 1 or 2, wherein the P wave duration threshold is 120 milliseconds.

7. The heart failure management system according to claim 1 or 2, wherein the patient suffers from heart failure with preserved ejection fraction.

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