Method for planning and delivering cardiac electrical stimulation

Abstract

A system for cardiac electrical stimulation therapy includes an implantable pulse generator, one or more leads extending from the implantable pulse generator to the heart for applying cardiac electrical stimulation, and a controller programmed with at least one therapy program for applying the cardiac electrical stimulation, the controller configured to automatically update the therapy program in response to actual cardiac activity by updating one or more parameters including a time period for applying cardiac electrical stimulation, a cardiac electrical stimulation rate, an amount of energy delivered per cardiac electrical stimulation.

Description

[0001] This application is a divisional application of the invention patent filed on October 22, 2020, with application number 202080088570.4 and invention title "Method for Planning and Transmitting Cardiac Electrical Stimulation".

[0002] Related applications

[0003] This application claims priority to U.S. Provisional Patent Application No. 63 / 042,061 (Attorney's File No. 79078), filed June 22, 2020; U.S. Provisional Patent Application No. 62 / 924,776 (Attorney's File No. 79063), filed October 23, 2019; U.S. Provisional Patent Application No. 63 / 001,343 (Attorney's File No. 79080), filed March 29, 2020; and U.S. Provisional Patent Application No. 62 / 924,782 (Attorney's File No. 79062), filed October 23, 2019, the contents of which are incorporated herein by reference in their entirety.

[0004] This application is part of a joint filing of the following PCT applications filed on the same day by the same applicant: Agent File No. 85056, David Prutchi David et al., entitled “INCREASING PEAK VO2 INPATIENTS WITH HF USING CARDIAC CONTRACTILITY MODULATION (CCM) STIMULATION”; Agent File No. 85068, David Prutchi David et al., entitled “CARDIAC CONTRACTILITY MODULATION FOR ATRIAL ARRHYTHMIA PATIENTS”; and Agent File No. 85056, David Prutchi David et al., entitled “CARDIAC CONTRACTILITY MODULATION IN ASSOCIATION WITH RESPIRATION”.

[0005] Technical Field and Background Technology

[0006] In some embodiments of the invention, the invention relates to planning and delivering cardiac electrical stimulation, and more specifically, but not exclusively, to cardiac electrical stimulation therapy in which parameters can be updated based on and / or in response to actual cardiac activity. Summary of the Invention

[0007] According to one aspect of some embodiments, a method for cardiac electrical stimulation is provided, comprising: defining a treatment plan including parameters for cardiac electrical stimulation applied to a heart; applying cardiac electrical stimulation to the heart according to the treatment plan; adapting the treatment to actual cardiac activity during application; and automatically updating at least one of the parameters to compensate for changes made relative to the treatment plan due to the adaptation.

[0008] In some embodiments, the parameters include one or more of the following: a cardiac electrical stimulation rate, a time period for which cardiac electrical stimulation will be applied, a stimulation current, an output voltage, and a stimulation duration.

[0009] In some embodiments, defining a treatment plan includes selecting the parameters to deliver one or both of the following: a total number of cardiac electrical stimulations and a total amount of cardiac electrical stimulation energy.

[0010] In some embodiments, automatic updates include one or more of the following: increasing or decreasing the cardiac electrical stimulation rate, extending or shortening the time period for applying cardiac electrical stimulation, increasing or decreasing the stimulation current intensity, and extending or shortening the stimulation duration.

[0011] In some embodiments, defining a treatment plan includes measuring or receiving input of cardiac activity characteristics of a patient being treated.

[0012] In some embodiments, the cardiac activity characteristics include: a mean heart rate, a mean stroke volume, and an incidence of irregular cardiac events.

[0013] In some embodiments, the irregular cardiac event is selected from the group consisting of premature ventricular contractions (PVCs), atrial arrhythmias, or ventricular arrhythmias.

[0014] In some embodiments, the application includes delivering an electrical stimulation via an implanted device, the implanted device comprising one or more leads that contact the ventricular septum of the heart.

[0015] In some embodiments, the method includes using the one or more sensors to measure the actual cardiac activity.

[0016] In some embodiments, defining a treatment plan includes setting one or more thresholds for a heart rate during which the cardiac electrical stimulation is applied.

[0017] In some embodiments, defining a treatment plan includes setting one or more physical states during which the cardiac electrical stimulation will be applied.

[0018] In some embodiments, automatic updates are performed in response to one or more skipped stimuli.

[0019] In some embodiments, if the actual number of cardiac electrical stimulations delivered is less than the planned number of cardiac electrical stimulations, an automatic update is performed.

[0020] In some embodiments, if the total amount of cardiac electrical stimulation energy delivered is less than the planned total amount of cardiac electrical stimulation energy, an automatic update is performed.

[0021] In some embodiments, the cardiac electrical stimulation includes cardiac contraction modulation stimulation.

[0022] According to one aspect of some embodiments, a method for delivering a therapeutic stimulus to a heart is provided, comprising: selecting a total number of stimuli to be delivered to a heart within a selected time period; delivering the stimuli to the heart; calculating the number of times the stimuli are actually delivered; and if the number of times the stimuli are actually delivered is less than the selected total number of stimuli, adding a selected time period to a degree sufficient to deliver additional stimulation as required.

[0023] In some embodiments, the stimulation includes cardiac contraction modulation stimulation.

[0024] In some embodiments, the method includes adding the selected time period to deliver additional stimuli if the number of times the actual stimulus is delivered is less than 90% of the selected total number of stimuli.

[0025] In some embodiments, adding the selected time period includes extending the initially selected time period.

[0026] In some embodiments, if the number of actual stimuli delivered is less than the selected total number of cardiac contractile modulation stimuli, the selected total number of cardiac contractile modulation stimuli is reduced for a future stimulation session.

[0027] In some embodiments, the selected time period is between 4 and 8 hours per day.

[0028] According to one aspect of some embodiments, a method for planning cardiac electrical stimulation therapy is provided, comprising: selecting a total amount of energy to be delivered to a heart via cardiac electrical stimulation; and selecting one or both of the following: a time period for the cardiac electrical stimulation to be applied to the heart, and a stimulation current intensity for each stimulation, selecting the time period and the stimulation current intensity to achieve the total amount of energy.

[0029] In some embodiments, the cardiac electrical stimulation includes cardiac contraction modulation stimulation.

[0030] According to one aspect of some embodiments, a system for cardiac electrical stimulation therapy is provided, comprising: an implantable pulse generator; one or more leads extending from the implantable pulse generator to the heart for applying cardiac electrical stimulation; and a controller programmed with at least one treatment plan for applying the cardiac electrical stimulation, the controller being configured to automatically update the treatment plan by updating one or more parameters in response to actual cardiac activity, the one or more parameters including: a duration of cardiac electrical stimulation application, a cardiac electrical stimulation rate, and an amount of energy delivered per cardiac electrical stimulation.

[0031] In some embodiments, the system includes one or more sensors, including an ECG sensor configured to measure the actual heart activity.

[0032] In some embodiments, the one or more wires contact the ventricular septum of the heart.

[0033] In some embodiments, the controller is programmed with instructions for automatically updating the treatment plan, the instructions being adapted to compensate for real-time changes in the treatment plan.

[0034] In some embodiments, the instructions include a digital factor for updating one or more of the following parameters: a stimulation current intensity, an output voltage, which sets a selected stimulation current intensity, a stimulation duration, a treatment session duration, and a stimulation rate.

[0035] According to one aspect of some embodiments, a method of operating a cardiac electrical stimulation device is provided, the cardiac electrical stimulation device including a memory defining an initial treatment plan in the memory, the initial treatment plan including parameters based on cardiac electrical stimulation applied to a heart, the method comprising: generating, via a device controller and according to the initial treatment plan, a command to energize one or more leads of the cardiac electrical stimulation device with a cardiac electrical stimulation signal;

[0036] Use one or more sensors to sense actual heart activity;

[0037] Modify the command to adapt the initial treatment plan to the actual cardiac activity sensed by the one or more sensors; and

[0038] At the device controller, at least one of the parameters is automatically updated to compensate for changes made relative to the initial treatment plan due to the sensed actual cardiac activity.

[0039] In some embodiments, the parameters include one or more of the following: a cardiac electrical stimulation rate, a time period for which cardiac electrical stimulation will be applied, a stimulation current, an output voltage, and a stimulation duration.

[0040] In some embodiments, the parameters are selected and / or updated to obtain a total number of cardiac electrical stimulations and / or a total amount of cardiac electrical stimulation energy.

[0041] In some embodiments, automatic updates include one or more of the following: increasing or decreasing the cardiac electrical stimulation rate, extending or shortening the time period for applying cardiac electrical stimulation, increasing or decreasing the stimulation current intensity, and extending or shortening the stimulation duration.

[0042] In some embodiments, the initial treatment plan is defined and / or updated based on inputs of measured and / or received cardiac activity characteristics of a patient being treated.

[0043] In some embodiments, the cardiac activity characteristics include: a mean heart rate, a mean stroke volume, and an incidence of irregular cardiac events.

[0044] In some embodiments, the irregular cardiac event is selected from the group consisting of premature ventricular contractions (PVCs), atrial arrhythmias, or ventricular arrhythmias.

[0045] In some embodiments, the cardiac electrical stimulation device is an implantable device, and wherein one or more leads are in contact with the ventricular septum of the heart.

[0046] In some embodiments, the method further includes using the one or more sensors to measure the actual cardiac activity.

[0047] In some embodiments, the initial treatment plan is defined based on one or more thresholds of a heart rate, during which the command is generated.

[0048] In some embodiments, the initial treatment plan is defined based on one or more physical states of the patient, and the commands are generated during the one or more physical states.

[0049] In some embodiments, the automatic update is performed in response to one or more skipped cardiac electrical stimulations.

[0050] In some embodiments, the automatic update is performed if the actual number of cardiac electrical stimulations delivered is less than the planned number of cardiac electrical stimulations.

[0051] In some embodiments, the automatic update is performed if the total amount of cardiac electrical stimulation energy delivered is less than the planned total amount of cardiac electrical stimulation energy.

[0052] In some embodiments, the cardiac electrical stimulation includes cardiac contraction modulation stimulation.

[0053] According to one aspect of some embodiments, a method of operating a cardiac stimulation device is provided, comprising:

[0054] Select the total number of stimuli to be delivered to a heart within a selected time period;

[0055] Generate commands to deliver stimulation to the heart;

[0056] Calculate the number of stimuli generated;

[0057] If the number of stimuli generated is less than the selected total number of stimuli, a selected time period is added to a degree sufficient to deliver the required additional stimulation.

[0058] In some embodiments, the stimulation includes cardiac contraction modulation stimulation.

[0059] In some embodiments, the method further includes: if the number of times the generated stimulus is less than 90% of the total number of selected stimuli, then adding the selected time period to generate additional stimuli.

[0060] In some embodiments, adding the selected time period includes extending the initially selected time period.

[0061] In some embodiments, the method further includes: if the number of stimuli generated is less than the selected total number of stimuli, then reducing the selected total number of stimuli for a future stimulation session.

[0062] In some embodiments, the selected time period is between 4 and 8 hours per day.

[0063] According to one aspect of some embodiments, a method for planning cardiac electrical stimulation therapy is provided, comprising:

[0064] Select the total amount of energy to be delivered to a heart via cardiac electrical stimulation; and

[0065] Select one or both of the following: a time period for the cardiac electrical stimulation to be applied to the heart, and the stimulation current intensity for each stimulation, selecting the time period and the stimulation current intensity to achieve the total energy.

[0066] In some embodiments, the cardiac electrical stimulation includes cardiac contraction modulation stimulation.

[0067] According to one aspect of some embodiments, a system for cardiac electrical stimulation therapy is provided, comprising:

[0068] One can be implanted with a pulse generator;

[0069] One or more leads, the one or more leads extending from the implantable pulse generator to the heart, for applying electrical stimulation to the heart; and

[0070] A controller programmed with at least one treatment plan for applying the cardiac electrical stimulation, the controller being configured to automatically update the treatment plan in response to actual cardiac activity by updating one or more parameters, the one or more parameters including: a duration of cardiac electrical stimulation, a cardiac electrical stimulation rate, and an amount of energy delivered per cardiac electrical stimulation.

[0071] In some embodiments, the system further includes one or more sensors, including an ECG sensor configured to measure the actual heart activity.

[0072] In some embodiments, the one or more wires contact the ventricular septum of the heart.

[0073] In some embodiments, the controller is programmed with instructions for automatically updating the treatment plan, the instructions being adapted to compensate for real-time changes in the treatment plan.

[0074] In some embodiments, the instructions include a digital factor for updating one or more of the following parameters: a stimulation current intensity, an output voltage, which sets a selected stimulation current intensity, a stimulation duration, a treatment session duration, and a stimulation rate.

[0075] In some embodiments, the controller is configured to select and / or update the parameters to obtain a total number of cardiac electrical stimulations and / or a total amount of cardiac electrical stimulation energy.

[0076] In some embodiments, the controller is configured to: increase or decrease the cardiac electrical stimulation rate, prolong or shorten the time period of applying cardiac electrical stimulation, increase or decrease the stimulation current intensity, or prolong or shorten the duration of a stimulation.

[0077] In some embodiments, the controller is configured to derive one or more of the following: an average heart rate, an average stroke volume, and an incidence of an irregular cardiac event based on data acquired through the one or more sensors.

[0078] In some embodiments, the irregular cardiac event is selected from the group consisting of premature ventricular contractions (PVCs), atrial arrhythmias, or ventricular arrhythmias.

[0079] In some embodiments, the controller is configured to set and / or receive one or more thresholds of a heart rate during the application of the cardiac electrical stimulation as input.

[0080] In some embodiments, the controller is configured to set and / or receive one or more physical states of the patient during the application of the cardiac electrical stimulation.

[0081] In some embodiments, the controller is configured to automatically update the treatment plan in response to one or more skipped cardiac electrical stimulations.

[0082] In some embodiments, the controller is configured to automatically update the treatment plan if the actual number of cardiac electrical stimulations delivered is less than the planned number of cardiac electrical stimulations.

[0083] In some embodiments, the controller is configured to set a number of cardiac electrical stimulations to be delivered within a set time period.

[0084] In some embodiments, the time period to be set includes 24 hours.

[0085] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. While similar or equivalent methods and materials to those described and materials herein may be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification (including definitions) shall prevail. Furthermore, these materials, methods, and examples are illustrative only and are not necessarily restrictive.

[0086] Implementation of the methods and / or systems of embodiments of the present invention may involve performing or completing selected tasks manually, automatically, or in combination thereof. Furthermore, in the actual instruments and apparatus of embodiments of the methods and / or systems of the present invention, several selected tasks may be implemented by hardware, software, or firmware, or by a combination thereof using an operating system.

[0087] For example, hardware for performing selected tasks according to embodiments of the invention can be implemented as a chip or circuit. As software, the selected task according to embodiments of the invention can be implemented as a plurality of software instructions executed by a computer using any suitable operating system. In exemplary embodiments of the invention, one or more tasks according to exemplary embodiments of the methods and / or systems described herein are performed by a data processor, such as a computing platform for executing multiple instructions. Optionally, the data processor includes volatile memory for storing instructions and / or data and / or non-volatile memory for storing instructions and / or data, such as a magnetic hard disk and / or removable media. Optionally, network connectivity is also provided. A display and / or a user input device such as a keyboard or mouse are also optionally provided. Attached Figure Description

[0088] This document describes some embodiments of the invention by way of example only with reference to the accompanying drawings. Reference will now be made in detail to the drawings, with emphasis placed on the fact that the details shown are exemplary and for the purpose of illustrative discussion of embodiments of the invention. In this regard, it will become apparent to those skilled in the art from the description taken in conjunction with the drawings how embodiments of the invention can be practiced.

[0089] In the attached diagram:

[0090] Figure 1A This is a flowchart of a method for cardiac electrical stimulation therapy according to some embodiments, wherein real-time changes in the predetermined treatment are compensated.

[0091] Figure 1B This is a flowchart of a method for planning cardiac electrical stimulation therapy according to some embodiments, and optionally the treatment can be modified according to actual cardiac activity.

[0092] Figure 2A Some embodiments schematically illustrate a predetermined cardiac electrical stimulation dose and a modified cardiac electrical stimulation dose, the modified dose compensating for changes in the predetermined dose due to actual cardiac activity.

[0093] Figure 2B Some embodiments schematically illustrate cardiac electrical stimulation therapy settings selectable based on the total amount of stimulation energy to be delivered.

[0094] Figure 3 This is a flowchart of a method for setting and / or modifying cardiac electrical stimulation therapy dosage according to some embodiments.

[0095] Figures 4A to 4B This is a block diagram of an exemplary system for cardiac electrical stimulation therapy according to some embodiments.

[0096] Figures 5A to 5BAn exemplary implantable cardiac device for cardiac electrical stimulation therapy is illustrated schematically according to some embodiments. Detailed Implementation

[0097] In some embodiments of the invention, the invention relates to planning and delivering cardiac electrical stimulation therapy, and more specifically, but not exclusively, to cardiac electrical stimulation therapy in which parameters can be updated based on and / or in response to actual cardiac activity.

[0098] A broad aspect of some embodiments relates to stimulation therapy, which is defined based on characteristics of cardiac activity and optionally modified according to actual cardiac activity. In some implementations, a natural variation in cardiac function, including intrapersonal and interpersonal variations, is taken into account when selecting and / or performing the stimulation.

[0099] One aspect of some embodiments involves optionally updating one or more parameters of the cardiac electrical stimulation in real time to compensate for any changes made during the treatment due to actual cardiac activity.

[0100] In some embodiments, a treatment plan is defined by setting parameters, such as stimulation rate, stimulation current intensity, duration of a treatment session, and / or other parameters. In some embodiments, the parameters are selected based on general treatment goals, such as the total number of cardiac electrical stimulations to be delivered to the heart, and / or the total amount of cardiac electrical stimulation energy to be delivered to the heart.

[0101] In some embodiments, the treatment plan is defined based on characteristics of the cardiac activity of the patient to be treated. For example, characteristics such as the patient's heart rate, stroke volume, incidence of an irregular cardiac event (e.g., arrhythmia), and / or other characteristics are considered.

[0102] In some embodiments, the treatment plan defines one or more conditions for applying the cardiac electrical stimulation. For example, the plan defines that stimulation should only be delivered when the heart rate is below and / or above a threshold (or within a selected range). For example, the plan defines that stimulation should only be delivered in a specific physical state of the patient, such as only during rest.

[0103] In some embodiments, the treatment plan takes into account the anticipated variability of cardiac activity. In some embodiments, when selecting treatment parameters, such as the total number of stimuli to be delivered, the total energy of the stimuli to be delivered, the stimulation rate, and the timing of the stimulation, the non-linear effect that changes in these parameters may have on the treatment itself is considered. Therefore, in some embodiments, multiple sets of parameters can be defined to obtain equivalent therapeutic effects. For example, 8000 stimuli randomly distributed throughout a day may achieve a therapeutic effect equivalent to delivering stimulation for one hour at a heart rate greater than 90 bpm per heartbeat. In some embodiments, systems and / or devices (e.g., system controllers) such as those described herein are pre-programmed with a lookup table including sets of parameters, which may optionally result in equivalent therapeutic effects and may be interchangeable. In some embodiments, a treatment parameter is selected and / or calculated based on one or more additional treatment parameters and / or based on a desired therapeutic effect.

[0104] In some embodiments, cardiac electrical stimulation therapy is delivered according to the plan, but changes may be made to the plan in response to actual cardiac activity. Optionally, changes may be made in real time. For example, if an irregular beat is identified, stimulation of that irregular beat may be skipped. In some embodiments, the treatment plan is changed in response to actual cardiac activity measured (and optionally monitored over time) by one or more sensors, such as ECG measurements.

[0105] In some embodiments, the changes in the plan are compensated for, for example, to achieve a general treatment goal. In some embodiments, compensation includes updating one or more treatment parameters, such as: updating the duration of a treatment session, updating the cardiac electrical stimulation rate, updating the stimulation current intensity, updating the number of electrodes to be activated (e.g., to contact a tissue area of ​​different sizes), updating the time interval between consecutive stimulations and / or heart rate and / or other treatment parameters.

[0106] In some embodiments, an implantable device is provided, including one or more leads for delivering the cardiac electrical stimulation and a controller configured to control the stimulation via the leads. In some embodiments, the controller is configured to automatically update one or more treatment parameters in response to changes in the treatment plan due to actual cardiac activity. In some embodiments, the controller is programmed with one or more treatment plans and one or more "backup" instructions for updating the treatment parameters during treatment and optionally modifying the "backup" instructions due to actual cardiac activity.

[0107] Some examples of "backup" instructions include: extending the duration of a treatment session if the actual number of stimuli delivered is less than a set number of stimuli; increasing the intensity of the stimulation current if the total amount of energy delivered is less than a set amount of energy to be delivered; increasing the cardiac electrical stimulation rate if a treatment session is almost over but has not actually provided enough stimulation; and updating a heart rate threshold for applying stimulation if the actual heart rate during (or part of) the treatment session is not within the defined heart rate used to deliver stimulation.

[0108] Before explaining at least one embodiment of the invention in detail, it should be understood that the invention is not necessarily limited in its application to the construction details and arrangements of the components and / or methods set forth in the following description and / or methods, or as illustrated in the drawings and / or examples. The invention can have other embodiments or can be practiced or performed in various ways.

[0109] Before explaining at least one embodiment of the invention in detail, it should be understood that the application of the invention is not necessarily limited to the details set forth in the following description or illustrated by way of example. The invention can have other embodiments or can be practiced or performed in various ways.

[0110] Planning and / or modifying the method of cardiac electrical stimulation therapy

[0111] Now refer to the attached diagram, Figure 1A This is a flowchart of a method for cardiac electrical stimulation therapy according to some embodiments, wherein real-time changes in the predetermined treatment are compensated.

[0112] In some embodiments, a decision to treat a patient is made by applying cardiac electrical stimulation to the heart (121).

[0113] In some embodiments, the stimulation signal is a cardiac contractility modulation stimulation signal. In some embodiments, the cardiac contractility modulation stimulation signal is a non-excitatory signal applied to the heart, optionally during the relative and / or absolute refractory period of the cardiac cycle. In some embodiments, the signal is selected to increase the contractility of a ventricle when the electric field of the signal stimulates ventricular tissue, such as the left ventricle, right ventricle, and / or ventricular septum. In some embodiments, contractility modulation is provided by phosphoprotein phosphorylation induced by the signal. In some embodiments, contractility modulation is caused by changes in protein transcription and / or mRNA produced by the signal, optionally in the form of fetal genetic program reversal.

[0114] It should be noted that in some embodiments, the cardiac contractility modulation signal may be excitable to tissues other than the tissue to which it is applied. Various mechanisms by which the cardiac contractility modulation signal may function have been described, for example, in “Cardiac contractility modulation: mechanisms of action in heart failure with reduced ejection fraction and beyond”, C. Tschope et al., published in the European Journal of Heart Failure (2018), doi:10.1002 / ejhf.1349, and can be used to guide the selection of parameters for the signal application in order to utilize and / or comply with one or more of these mechanisms.

[0115] Unless otherwise stated, the term "cardiac electrical stimulation" is used herein as a general placeholder for all such signals. In some embodiments, the term "cardiac electrical stimulation" is intended to encompass electrochemical, such as a therapeutic signal. In some embodiments, the stimulation is delivered to the heart and / or related organs or tissues. In some embodiments, the stimulation affects neural activity. In some embodiments, the stimulation is delivered according to a defined dose. Optionally, the stimulation is applied in sync with cardiac activity, such as in sync with the heartbeat.

[0116] In some embodiments, the cardiac electrical stimulation is applied according to parameters suitable for inducing cardiac contractile regulation (e.g., current intensity, time, rate, anatomical location of application). In some embodiments, the cardiac electrical stimulation includes stimulation of the cardiac fat pad. In some embodiments, the cardiac electrical stimulation includes affecting the heart via vagal nerve stimulation. In some embodiments, the cardiac electrical stimulation includes stimulation of the cardiac vascular innervation, such as the aorta, vena cava, pulmonary artery, and pulmonary vein.

[0117] In some embodiments, a patient selected for treatment is a patient suffering from heart failure, congestive heart failure, and / or similar symptoms. In some embodiments, a patient selected for treatment is a patient whose heart pumping action is impaired, potentially affecting blood flow and / or oxygen supply. In some embodiments, a patient selected for treatment is a patient whose cardiac output and / or cardiac contractility are impaired and can be improved by applying cardiac electrical stimulation therapy, such as by applying cardiac contractility modulation therapy. In some cases, one or more effects of said cardiac electrical stimulation therapy, such as increased cardiac contractility or higher peak oxygen uptake, can improve respiration.

[0118] In some embodiments, a cardiac device configured to apply electrical stimulation to the heart is implanted into the patient (123). In some embodiments, the device includes a pulse generator and one or more leads, the pulse generator optionally implanted outside the heart, such as in the subclavian region, and the one or more leads for stimulating the heart. Optionally, one or more leads contact the ventricular septum of the heart.

[0119] In some embodiments, treatment parameters (125) for applying cardiac electrical stimulation are defined. In some embodiments, treatment parameters are selected and the cardiac device is programmed accordingly (e.g., the device controller).

[0120] In some embodiments, the cardiac electrotherapy includes, for example, stimulation timing (e.g., relative to the cardiac cycle and / or relative to previously applied stimulation), number of stimulations (e.g., the total number of stimulations to be applied, optionally within a defined time period), stimulation current intensity, stimulation duration, safety threshold, stimulation rate, and / or other parameters.

[0121] In some embodiments, general treatment parameters (also referred to as "treatment goals") are set, including, for example, the total amount of stimulation energy (electricity) to be delivered to the patient (optionally exceeding or within a defined time period, such as one minute, one hour, one day, one week, or one month), the total number of cardiac electrical stimuli delivered to the patient (optionally exceeding or within a defined time period, such as one minute, one hour, one day, one week, or one month), and the cumulative duration of stimulation pulses (optionally exceeding or within a defined time period, such as one minute, one hour, one day, one week, or one month).

[0122] In one embodiment, treatment parameters are selected by a clinician, such as a nursing physician (e.g., a cardiologist). Alternatively or additionally, treatment parameters may be selected automatically, for example, via a device controller, based on input patient data.

[0123] In some embodiments, the patient data includes general patient information such as age, sex, and medical condition. In some embodiments, such as as further described herein, the patient data includes known and / or estimated statistics on the patient's cardiac activity, including but not limited to: heart rate (e.g., mean, peak), actual incidence and / or expected probability of cardiac events, such as premature ventricular contractions (PVCs), atrial arrhythmias and / or ventricular arrhythmias, stroke volume (e.g., mean stroke volume), ejection fraction, cardiac output, intracardiac pressure, intracardiac pressure gradient measured over time, NYHA class score, peak VO2, 6-minute walk score, and / or other statistics.

[0124] In some embodiments, cardiac electrical stimulation is applied according to the selected treatment parameters (127).

[0125] In some embodiments, actual cardiac activity is detected, including, for example, heart rate changes (e.g., relative to expected average heart rate), cardiac events or episodes, changes in stroke volume, and / or others (129). In some embodiments, actual cardiac activity is sampled and / or continuously monitored. Optionally, one or more sensors are used to track actual cardiac activity. In one example, ECG measurements are optionally performed via an intracardiac electrode. Optionally, the intracardiac electrode used for ECG measurements is the same as the electrode used to apply the cardiac electrical stimulation. Optionally, intracardiac sensors, such as bioimpedance sensors and / or pressure sensors, are used to measure cardiac performance parameters, such as ejection fraction, cardiac output, intracardiac pressure, and intracardiac pressure gradient over time.

[0126] Optionally, the cardiac electrical stimulation treatment is modified upon detection of cardiac activity, such as upon detection of anticipated changes and / or irregularities in cardiac activity (131). In one example, when an irregular heartbeat (e.g., premature ventricular contractions (PVCs), atrial arrhythmias, and / or ventricular arrhythmias) is detected, a predetermined cardiac electrical stimulation (e.g., a single stimulation) is not delivered. In another example, when a defibrillation signal is delivered to the heart, a predetermined cardiac electrical stimulation is not delivered (optionally, by the same means of delivering the cardiac stimulation signal). Optionally, in this case, cardiac electrical stimulation is not delivered for a defined period of time immediately following defibrillation to allow the heart to recover from defibrillation.

[0127] In some embodiments, treatment is modified in response to changes in heart rate. For example, treatment may be modified when the sensed heart rate is higher or lower than a specific patient's expected average heart rate. For instance, treatment may be modified when the heart rate is a percentage higher or lower than 100%, 120%, 150%, 170% or the expected average heart rate.

[0128] In some embodiments, one or more treatment parameters are automatically updated to compensate for the modifications made (133). Any of the above treatment parameters or combinations thereof may be modified.

[0129] In some embodiments, treatment is updated in real time, for example, during a stimulation session, such as during a daily stimulation session consisting of several hours (e.g., 1, 2, 3, 4, 5, 6 hours or longer or shorter) of stimulation provided by the device. In some embodiments, treatment is updated in response to the detection of an irregular cardiac event. Additionally or alternatively, treatment is updated based on an action taken by the device in response to the event (e.g., a skipped stimulus).

[0130] The following are examples of compensation made for treatment modifications that may be necessary due to actual cardiac activity:

[0131] In some embodiments, cardiac electrical stimulation is synchronized to be delivered in each cardiac cycle according to a planned treatment. For example, a cardiac contractility modulation signal is applied during the refractory period. Under such scheduling, patients with an actual heart rate (e.g., heart rate at least for a portion of the treatment) higher than the expected average may receive too many stimulations, while patients with a heart rate lower than the expected average may receive less stimulation than planned. In some embodiments, to compensate for variations, parameters such as the duration of the treatment session or the intensity of the stimulation current can be updated. For example, for patients with high heart rates: the duration of the treatment session can be shortened to reduce or avoid overstimulation; the intensity of the stimulation current can be reduced so that the total amount of energy delivered during a treatment session remains as planned. For example, for patients with low heart rates: the duration of the treatment session can be extended to achieve the planned amount of stimulation; the intensity of the stimulation current can be increased so that the total amount of energy delivered during a treatment session reaches the planned amount. In some embodiments, the intensity of the stimulation current is set by controlling (optionally, adjusting) a voltage set by the device. In some embodiments, the current intensity (or amplitude) is set by setting the output voltage, assuming that the impedance of the device components (e.g., one or more excitation leads) remains substantially constant and unchanged. In some embodiments, the amplitude of the output voltage is controlled to generate a selected stimulation current.

[0132] In some embodiments, when stimulation is skipped or canceled, such as in response to an irregular heartbeat, compensation may include: increasing the duration of the treatment session to deliver additional stimulation, increasing the current intensity in one or more subsequent stimuli to compensate for the undelivered energy, and increasing the size (e.g., surface area) of the tissue contacted and stimulated by the device electrodes. In some cases, cardiac electrical stimulation may not be applied to the heartbeat when it is considered unsafe, because applying a cardiac electrical stimulation signal during a heartbeat could lead to arrhythmia. Optionally or additionally, the heart may be allowed to “recover” from an arrhythmic beating once or multiple times from a “prohibited” beating. In some embodiments, compensation for unintentionally applied stimulation may include: increasing the duration of the treatment session to deliver additional stimulation, increasing the current intensity in one or more subsequent stimuli to compensate for the amount of undelivered energy, increasing the size (e.g., surface area) of the tissue contacted and stimulated by the device electrodes, and / or other changes to treatment parameters.

[0133] Figure 1B This is a flowchart of a method for planning cardiac electrical stimulation therapy according to some embodiments, and optionally the treatment can be modified according to actual cardiac activity.

[0134] In some embodiments, cardiac electrical stimulation therapy is planned based on known and / or estimated patient cardiac activity statistics (151).

[0135] In some embodiments, general treatment parameters (or targets) are defined, such as: the total number of stimuli to be delivered, the total amount of energy applied through the stimuli, the total number of stimuli delivered within a specific time window (e.g., within a 1-hour window, a 12-hour window, a 24-hour window, or an intermediate, longer, or shorter time window), and the total duration of the stimulation pulses delivered within a specific time window (e.g., within a 1-hour window, a 12-hour window, a 24-hour window, or an intermediate, longer, or shorter time window). In one example, the stimulation rate is set to 200-3000 stimuli per hour, such as 300, 1000, 2500, or an intermediate, higher, or lower stimulation rate per hour.

[0136] In some embodiments, to achieve the overall goal, cardiac electrical stimulation therapy is planned based on the patient’s known and / or expected cardiac activity, such as based on the patient’s statistics, such as: heart rate (e.g., average, peak and / or baseline), stroke volume, likelihood of cardiac events (e.g., premature ventricular contractions (PVCs), atrial arrhythmias or ventricular arrhythmias), likelihood of needing defibrillation and / or other statistics.

[0137] In some embodiments, the plan defines a dosage. The dosage may include, for example, the time periods during which stimulation is applied (e.g., within a 24-hour window). For example, the plan defines cardiac electrical stimulation to be performed for 1, 2, 3, 5, 6, 8 hours, or intermediate, longer, or shorter time periods each day. Optionally, stimulation is delivered intermittently (e.g., with non-stimulation periods between stimulation periods, such as 1 hour stimulation, 2 hours rest, 1 hour stimulation, etc.). In some embodiments, stimulation is applied for 5, 6, 7 hours, or intermediate, longer, or shorter time periods each day. Optionally, a target number and / or percentage of cardiac electrical stimulation is set during the defined time periods; for example, at least 60%, 70%, 80%, or intermediate, higher, or lower percentages of stimulation will be applied with each heartbeat during the defined time periods.

[0138] In some embodiments, the plan defines how to deliver a stimulus at each heartbeat within a selected time period. Alternatively, the plan defines how to deliver a stimulus at intervals of heartbeats, such as every 3rd heartbeat, every 7th heartbeat, every 10th heartbeat, or an intermediate, larger, or smaller number of heartbeats.

[0139] In some embodiments, treatment is planned for a specific patient to deliver stimulation at selected times of cardiac activity, such as when the heart rate is above a certain threshold or when the heart rate is below a certain threshold. Optionally, the threshold is the patient's average heart rate.

[0140] In some embodiments, treatment is planned for a particular patient to deliver stimulation during selected physiological and / or physical states of the patient, such as delivering stimulation only during sleep, delivering stimulation only during rest, delivering stimulation only during physical activity, or the like.

[0141] In some embodiments, a fixed dose is defined, for example, defining the total amount of stimulation to be delivered each day. Optionally, the stimulation rate during the day is controlled in real time based on one or more of the following:

[0142] • Patient activity (e.g., delivering more stimulation when the patient is active compared to when the patient is at rest, and vice versa).

[0143] • Conditions in the patient's environment, such as weather conditions (e.g., whether more stimulation is delivered when the ambient temperature (optionally sensed by the system temperature sensor) is within or below a selected threshold. For example, at temperatures where it may be more difficult to maintain body temperature, such as above 35 degrees Celsius or below 5 degrees Celsius, it may be necessary to reduce the rate of cardiac electrical stimulation.

[0144] • The patient's posture, for example, delivers more stimulation when the patient is standing and less when the patient is sitting and / or lying down, and vice versa. Optionally, sensors such as gyroscopes and / or other inertial motion sensors are used to sense the patient's posture.

[0145] In some embodiments, the device is configured to detect conditions suitable for delivering stimulation. In some embodiments, the device is configured to detect cardiac activity, such as by ECG measurements performed by a device electrode. Optionally, the measured cardiac activity also provides an indication of the physical activity performed by the patient, and whether the patient is active or at rest.

[0146] In another example, the device is configured to detect the patient's physical and / or physiological state in order to deliver stimulation in a preferred state. For example, the device is configured to detect a sleep or wakefulness state. For example, the device is configured to determine the patient's posture. For example, the device is configured to detect whether the patient is engaged in physical activity, such as walking. In some embodiments, the determination of the patient's activity and / or state and / or posture is performed based on input from one or more sensors, such as GPS, a gyroscope, a microphone, and / or other sensors. Optionally, the sensors are configured on the user's personal device, such as a mobile phone communicating with the stimulation device controller.

[0147] Additionally or alternatively, patient instructions and / or conditions are input into the device (e.g., via a user interface) to accordingly set the application of cardiac electrical stimulation. For example, the application may be set when cardiac activity is at a specific characteristic (e.g., heart rate) and / or when the patient is in a specific physical and / or physiological state.

[0148] In some embodiments, the patient may voluntarily influence the treatment (e.g., via a user interface), for example, by setting a preferred time (e.g., during the day) when stimulation should be delivered. In some embodiments, the system (e.g., via a system controller and user interface) is configured to suggest treatment times and / or stimulation rates and / or stimulation intensities to the patient, who can choose from available options according to their preferences.

[0149] In some embodiments, cardiac electrical stimulation therapy is initiated and delivered according to the plan (153).

[0150] In some embodiments, the treatment may optionally be modified according to a backup plan to conform to actual cardiac activity (155). Optionally, the treatment may be modified to attempt to achieve general treatment goals, such as the total number of stimuli delivered, the total amount of stimulus energy, the delivery during a specific number of heartbeats (e.g., heartbeats occurring immediately after an irregular cardiac event), and / or other general treatment goals.

[0151] Some examples of how treatment can be modified from an initial plan to a backup plan include: changes in actual heart rate compared to expected (e.g., average) heart rate, irregular cardiac events (e.g., arrhythmias), and delivering different signals to the heart, such as a defibrillation signal.

[0152] Here are some examples of scenarios where treatment plans might be modified based on backup plans:

[0153] The initial plan defined cardiac electrical stimulation as being delivered when the patient's heart rate was between 60 and 100 bpm, and the patient should receive at least one hour of treatment daily (within a 24-hour window). However, during the 23-hour period, the patient's heart rate did not reach the defined bpm range. In this case, the initial plan can be modified to deliver stimulation at any heart rate during the remaining hours of the 24-hour window.

[0154] Figure 2A Some embodiments schematically illustrate a predetermined cardiac electrical stimulation dose and a modified cardiac electrical stimulation dose, the modified dose compensating for changes in the predetermined dose due to actual cardiac activity.

[0155] In some embodiments, stimulation is planned to be applied intermittently between consecutive stimuli 2001, for example, at intervals of 6 heartbeats (as shown), 4 heartbeats, 2 heartbeats, 10 heartbeats 2003, or at the middle, larger, or smaller number of heartbeats constituting the interval. In some cases, the planned stimulation is modified in real time based on actual cardiac activity. For example, optionally, an event such as an irregular heartbeat 2005 is detected by a device (e.g., via ECG measurement). Optionally, the device is configured to skip stimulation during irregular heartbeats. As shown below, due to the detection of a cardiac event and the skipped stimulation, the next stimulation is applied at an interval of 12 heartbeats.

[0156] In some embodiments, to compensate for a skipped stimulus, the total duration 2007 of the treatment session is extended, thereby allowing another stimulus to be delivered to achieve the total desired stimulus amount within the treatment session.

[0157] Figure 2B Some embodiments schematically illustrate cardiac electrical stimulation therapy settings selectable based on the total amount of stimulation energy to be delivered. In this example, the total cardiac electrical stimulation energy 2015 is set as a general target for treatment. To achieve this amount, stimulation can be delivered as multiple stimuli with the same intensity 2017, optionally delivered at intermediate intervals (see 2B1) or in sequence (see 2B2). Alternatively, (see 2B3), multiple stimuli 2019, 2021 can differ in intensity from each other, such that the sum of the stimuli reaches the set total energy.

[0158] In some embodiments, the current intensity is reduced when the stimulation causes pain or sensation to the patient. Alternatively, the current intensity can be increased if the stimulation does not cause pain (or the pain is tolerable for a particular patient), which may shorten the total number of stimulations required and / or the total duration of treatment.

[0159] Some examples of energy settings might include: a total cardiac electrical stimulation energy of 100 joules per day, a total cardiac electrical stimulation energy of 5 joules per hour, a total cardiac electrical stimulation energy of 0.1 joules per minute, and / or others.

[0160] In some embodiments, the total amount of energy to be transferred is calculated (e.g., automatically by the device controller) by multiplying the number of stimulation pulses by the stimulation current amplitude and / or by multiplying the number of stimulation pulses by the output voltage (e.g., the voltage released by the pulse generator).

[0161] Figure 3 This is a flowchart of a method for setting and / or modifying cardiac electrical stimulation therapy dosage according to some embodiments.

[0162] In some embodiments, cardiac electrical stimulation therapy is planned to provide a set dose (SD) of stimulation (i.e., stimulation pulses) during a set time period (TP) (301). In some embodiments, the set time period includes a day, a set number of hours (e.g., 1, 2, 5, 10, 15, 20, or a duration that is intermediate, longer, or shorter), and a set number of minutes (e.g., 5 minutes, 10 minutes, 30 minutes, 45 minutes, or a duration that is intermediate, longer, or shorter). Some examples of set doses for each time period include 25,000 stimulation pulses per day, 1,000 stimulation pulses per hour, 20 stimulation pulses per minute, or intermediate, higher, or lower set pulse amounts.

[0163] In some embodiments, cardiac electrical stimulation is delivered according to a set schedule (303). Then, at the end of the set time period, the number of actual stimulation pulses (NSPs) delivered during the set time period is calculated (305). (Optionally, the number of actual pulses delivered is calculated by the device controller).

[0164] In some cases, the number of actual stimulus pulses (NSPs) may differ from the set dose (SD), for example, being less than the set dose (307). In some cases, this may be due to skipped stimuli, for example, taking into account irregular heartbeats, the actual heart rate being outside the definition of a suitable stimulus, and / or other situations that result in the delivered stimulus differing from the planned stimulus.

[0165] If the actual number of stimulation pulses is less than the set dose, the schedule can be updated to deliver more stimulation during similar upcoming time periods (309); or alternatively, the schedule can be updated to deliver fewer stimuli during similar upcoming time periods, thus conforming to the “real-life” possibility of delivering the planned stimulus (311).

[0166] In some embodiments, stimulation is applied only when the patient's heart rate is above or below a set threshold or within a defined range. Optionally, the threshold is dynamically modified based on actual cardiac activity to achieve a set dose (e.g., a set number of stimulations).

[0167] In some embodiments, cardiac electrical stimulation is planned to be delivered with each heartbeat over a specific period of time (e.g., several hours per day); additionally or alternatively, stimulation is planned for each set number of heartbeats; additionally or alternatively, the plan defines the stimulation time and the off time when no stimulation is delivered.

[0168] In some embodiments, a treatment plan (and / or modification plan) is executed based on the actual number of stimulation pulses delivered during one or more previous treatment sessions and recorded by the device. For example, if the number of stimulation pulses actually delivered during a previous treatment session is only 20%, 50%, 75%, or a middle, higher, or lower percentage of the planned number of stimulation pulses, a time period for the next treatment may be adjusted (e.g., extended) and / or the number of stimulation pulses delivered within the same time period as the previous session may be reduced to more closely approximate the actual number of stimulation pulses delivered. In one example, if the number of stimulation pulses delivered during a 5-hour treatment session is only 50% of the planned number of stimulation pulses, the plan may be modified, for example, by extending the treatment session to 10 hours to achieve a predefined number of stimulation pulses.

[0169] In one example, if the actual number of stimulation pulses delivered is less than 10%, 20%, 25%, 30%, or a middle, higher, or lower percentage of the planned total number of stimulations, the plan can be modified (e.g., by extending the duration of the treatment session).

[0170] Exemplary devices and systems for cardiac electrical stimulation

[0171] Figure 4A This is a schematic block diagram of a cardiac treatment device 200 according to some embodiments of the present invention.

[0172] As shown, the cardiac treatment device 200 includes one or more wires 216 (optionally, two wires) that are optionally coupled to the cardiac treatment device 200 at one or more CAN connectors (not shown).

[0173] A pulse generator 204 may optionally be used to generate a signal, for example, including a power supply circuit, for example, including one or more storage capacitors.

[0174] In some embodiments of the invention, a ventricular detector 206 is provided for detecting atypical ventricular excitation, which may be a contraindication to signal application.

[0175] In some embodiments of the invention, an atrial detector 208 is provided for detecting atypical atrial excitation, which can be used as an input for the cardiac treatment device 200 to make decisions.

[0176] A sensor input 214 may receive data from one or more sensors, such as electrical sensors or other sensors, such as flow, pressure, and / or acceleration sensors. The data from the sensors may optionally be further processed (e.g., via a controller 202 and / or ventricular detector 206 and / or atrial detector 208) and may optionally be used as an input to the decision-making process in the cardiac treatment device 200.

[0177] Optionally, a controller 202 is provided and executes one or more logic to determine, for example, the timing and / or other parameters of a signal and / or whether to apply a signal.

[0178] In some embodiments, the controller controls the application of stimulation pulses according to the treatment plan. Optionally, the controller influences changes to the plan, for example, to compensate for real-time deviations from the treatment plan (e.g., skipped stimulation). In some embodiments, the controller generates a command to energize one or more leads of the device with a stimulation signal. Optionally, the command is generated according to the treatment plan. In some embodiments, according to the command generated by the controller, current is conducted through one or more leads, and optionally to the tissue contacted by the one or more leads.

[0179] Optionally, a memory 218 is provided, for example, to store logic, past effects, treatment plans, adverse events, and / or pulse parameters.

[0180] In some embodiments, the controller and / or memory are programmed with one or more treatment plans (optionally set for a specific patient) and / or one or more backup treatment plans.

[0181] In some embodiments, instructions for “compensating” for changes to the planned treatment are stored and addressed via the device controller when relevant, including modifications such as treatment duration, number of stimulations, stimulation signal parameters (e.g., current intensity), and / or other modifications that can be used to compensate for real-time changes in the initial plan. In some embodiments, the instructions include digital factors that modify one or more treatment parameters. In some examples, the instructions may include: a factor that the stimulation current intensity should be multiplied if the actual applied stimulation does not reach the target energy amount; a factor that the output voltage should be adjusted to produce the desired current intensity; a factor that the stimulation rate should be multiplied if the actual applied stimulation does not reach the target total number of stimulations (optionally within a set time period); time-related modifications, such as a factor that the duration of the treatment session should be extended if the target is not reached; and so on.

[0182] In some embodiments, the controller refers to a lookup table or similar mechanism that establishes relationships between specific situations (e.g., skipped stimuli, fewer actual stimuli provided than planned, etc.) and instructions to compensate for such situations (e.g., by updating one or more parameters, such as updating the length of the treatment session).

[0183] Optionally, a recorder 210 is provided to store the activities of the cardiac treatment device 200 and / or the patient. Such recording and / or programming can be performed using a communication module 212 (e.g., of a type known in the art) to send data from the cardiac treatment device 200, for example, to a programmer (not shown), and / or to receive data, for example, programming, such as pulse parameters.

[0184] Figure 4B This is a schematic diagram illustrating components of an implantable cardiac device 600 according to some embodiments.

[0185] In some embodiments, the device is configured to deliver cardiac electrical stimulation, such as cardiac contractility modulation stimulation. Optionally, the device is also configured to function as an intracardiac cardioverter defibrillator (ICD).

[0186] In some embodiments, the device includes an ICD lead 601 and a cardiac contractility modulation lead 603.

[0187] In some embodiments, activation of the ICD leads is performed via an ICD module including or connected to: an ICD controller 605, a defibrillation pulse generator 607 (via one or more capacitors 609), a power supply (e.g., a battery 613) and power management circuitry 615, and an ICD sensor 611 that senses the applied pulse to verify the pulse for a selected (e.g., programmed) amplitude and / or duration. In some embodiments, optionally, activation of one or more cardiac contraction modulation leads 621, 623 (optionally located in the right ventricle) is performed via a cardiac contraction modulation module including or connected to: a cardiac contraction modulation controller 617 and a cardiac contraction modulation generator 619.

[0188] It should be noted that in some embodiments, the ICD coil and one or more electrodes for pacing and / or cardiac contraction regulation are configured on the same lead.

[0189] In some embodiments, the wire is connected to isolation 625.

[0190] In some embodiments, the device includes a concierge module 627 that includes or is connected to one or more sensors, such as a temperature sensor 629, a magnetic sensor 631, and a communication module 633, such as an antenna, a receiver, etc. Other sensors may include a flow sensor, a pressure sensor, an acceleration sensor, and / or other sensors.

[0191] In some embodiments, data received from the one or more sensors is used as input. Optionally, the input is processed by the device controller (e.g., by an ICD controller, a cardiac contraction regulation controller, and / or a universal controller, not shown) and may optionally be used as input to the decision-making process in the implantable cardiac device 600.

[0192] In some embodiments, a device controller (e.g., an ICD controller, a cardiac contraction regulation controller, and / or a general controller, not shown) performs one or more logic operations to determine, for example, the timing and / or other parameters of a signal and / or whether to apply a signal.

[0193] Optionally, a memory (not shown) is provided, for example, to store logic, past effects, treatment plans, adverse events, and / or pulse parameters.

[0194] Optionally, a recorder (not shown) is provided to store the activities of the implantable cardiac device 600 and / or the patient. Such recording and / or programming can be performed using a communication module 633 to send data from the implantable cardiac device 600, for example, to a programmer (not shown), and / or to receive data, for example, programming, such as pulse parameters.

[0195] Figure 5A An implantable device configured for applying cardiac electrical stimulation is illustrated schematically according to some embodiments.

[0196] In some embodiments, the implantable device 501 includes a pulse generator 503. In some embodiments, the pulse generator 503 includes a housing 509 that encloses, for example, a power supply (e.g., a battery), control circuitry (e.g., a controller) configured for timing and generating electrical pulses, sensing circuitry, communication circuitry, storage device, and / or other operating modules.

[0197] In some embodiments, one or more stimulation leads, such as 505 or 507, are connected to and extend outward from the housing. In some embodiments, the lead comprises one or more wires surrounded by an outer insulation layer. In some embodiments, the lead consists of two wires with different polarities. In some embodiments, the wires of the lead are coiled.

[0198] In some embodiments, the pulse generator 503 is implanted outside the heart, such as in the subclavian region. Optionally, implantation is performed via a minimally invasive procedure.

[0199] In some embodiments, the housing of the pulse generator 503 is implanted subcutaneously, near the left chest.

[0200] In some embodiments, leads 505 and 507 extend from the pulse generator 503, and at least one distal segment of the lead is implanted within the heart 511. In some embodiments, as shown, both leads pass through the right atrium 513 and contact the ventricular septum 515 at their distal ends. In some embodiments, each lead contacts the septum at a different location.

[0201] It should be noted that, additionally or alternatively, a single lead comprising two spaced-apart stimulation electrodes may be used.

[0202] It should also be noted that while these figures show both leads located in the right ventricle 551 adjacent to the interventricular septum 515, one or more stimulation leads may be located in other locations, thus having different effect loops and / or targeting different tissues. In some embodiments, the leads are located inside the heart, optionally on the right side, taking advantage of two potential benefits: a. less extracardiac tissue is stimulated; and b. less invasiveness and / or presence compared to the left ventricle.

[0203] In some embodiments, one of the plurality of leads is implanted outside the heart, while another of the plurality of leads is implanted inside the heart.

[0204] In some embodiments, each wire terminates with a tip electrode (see 517 of wire 507, 519 of wire 505). The tip electrode may be configured as a contact electrode, a screw-in electrode, a stitching electrode, a free-floating electrode, and / or other types.

[0205] In some embodiments, one or two of the plurality of wires include a ring electrode (see 521 of wire 507, 523 of wire 505) positioned along the wire near the tip electrode.

[0206] In some embodiments, the electrode is implanted into the right ventricle or right atrium of the heart.

[0207] In some embodiments, the tip electrode is threaded to allow it to be screwed into tissue. Alternatively, the tip electrode may only contact tissue.

[0208] In some embodiments, one or two of the plurality of wires include a defibrillation coil (see 525 of wire 505). Optionally, coil 525 is positioned along the wires, near the tip electrode and / or near the loop electrode.

[0209] In some embodiments, the coil is implanted into the right ventricle, right atrium, or vena cava.

[0210] In some embodiments, one or two wires are configured to transmit a non-excitatory signal, such as a cardiac contraction regulation signal.

[0211] In some embodiments, cardiac contraction regulation signals are applied to or within ventricular tissue.

[0212] In some embodiments, a cardiac contractility modulation signal is applied to the heart during the relative and / or absolute refractory period of the heart. In some embodiments, the signal is selected to increase ventricular contractility when the electric field of the signal stimulates ventricular tissue (e.g., the left ventricle, right ventricle, and / or ventricular septum). In some embodiments of the invention, contractility modulation is provided by phosphoprotein phosphorylation induced by the signal. In some embodiments of the invention, contractility modulation is caused by changes in protein transcription and / or mRNA production induced by the signal, optionally in the form of fetal genetic program reversal.

[0213] While not limited to a single pulse sequence, the term cardiac contractile modulation is used to describe any family of signals that includes important components applied during the absolute refractory period and have a clinically significant effect on cardiac contraction in acute and / or chronic modes and / or lead to reversal of fetal genetic programs and / or increased phosphorylation of phosphoproteins. In some embodiments, the signal may be excitatory to one part of the heart but non-excitatory to others. For example, the signal may be excitatory in the atria but applied when the ventricles are not excitatory (relative to ventricular excitation).

[0214] In some embodiments of the invention, the signal, while potentially stimulating during the receptive phase of the cardiac cycle, is non-excitatory due to its timing. In particular, the signal is applied during the refractory period of the affected tissue and optionally during the absolute refractory period.

[0215] In some embodiments, a device electrode, such as a cardiac contraction regulation application electrode, is used to measure the R-wave amplitude and / or RR interval of the cardiac cycle.

[0216] Figure 5B A cardiac device comprising a plurality of guide wires is schematically illustrated according to some embodiments. In some embodiments, the device 5500 is configured to deliver cardiac contractile modulation stimulation to the heart. In some embodiments, the device 5500 is also configured to function as a cardiac defibrillator (ICD).

[0217] In some embodiments, the device 5500 includes a plurality of leads. In the illustrated example, a first lead 5510 extends to the right atrium of the heart 5516; a second lead 5511, for example for applying cardiac contractility modulation stimulation, extends to the right ventricle, optionally contacting the interventricular septum; a third lead 5512 extends to the right ventricle, optionally contacting the interventricular septum; and a fourth lead 5514 extends to the left ventricle, for example through the coronary sinus. In some embodiments, one or more leads include a defibrillation coil. In this example, the third lead 5512 includes a superior vena cava shock coil 5530 and a right ventricular shock coil 5532.

[0218] In some embodiments, multiple wires are connected to the device housing 5520 via multiple ports (not shown). In some embodiments, the activation of one or more wires is controlled by a switching circuit, such as the switching circuit of a device controller.

[0219] The terms “including,” “contains,” “includes,” “have,” and their related terms mean “including but not limited to.”

[0220] The term "composed of" means "including and limited to".

[0221] The term "consistently made of" means that the composition, method or structure may include other components, steps and / or parts, provided that the other components, steps and / or parts do not substantially alter the essential and novel features of the claimed composition, method or structure.

[0222] As used herein, the singular forms “an,” “a,” and “the” include plural references unless the context clearly indicates otherwise. For example, the terms “a compound” or “at least one compound” can include a variety of compounds, including mixtures thereof.

[0223] Throughout this application, various embodiments of the invention may be presented in a scope format. It should be understood that the scope format is merely for convenience and brevity and should not be construed as an inflexible limitation of the scope of the invention. Therefore, the scope description should be considered as having specifically disclosed all possible sub-scopes and the individual numerical values ​​within those scopes. For example, a description of a scope such as 1 to 6 should be considered as having specifically disclosed sub-scopes, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and individual numbers within that scope, such as 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the scope.

[0224] Whenever a range of numbers is indicated herein, it is intended to include any referenced numbers (fractions or integers) within the indicated range. The phrases “range / range between the first and second indicated numbers” and “range / range from the first indicated number to the second indicated number” are used interchangeably herein and are intended to include the first and second indicated numbers as well as all decimals and integers in between.

[0225] As used herein, the term “method” means, means, techniques and procedures for accomplishing a given task, including but not limited to those known or readily developed by practitioners in the fields of chemistry, pharmacology, biology, biochemistry and medicine from known means, means, techniques and procedures.

[0226] As used herein, the term “treatment” includes eliminating, substantially inhibiting, slowing or reversing the progression of a condition, substantially improving the clinical or aesthetic symptoms of a condition, or substantially preventing the occurrence of the clinical or aesthetic symptoms of a condition.

[0227] It should be understood that, for clarity, certain features of the invention described in the context of a single embodiment may also be provided in combination in a single embodiment. Conversely, for brevity, various features of the invention described in the context of a single embodiment may also be provided individually or in any suitable sub-combination or in embodiments suitable for any other description of the invention. Certain features described in the context of various embodiments should not be considered as essential features of those embodiments unless the embodiments are invalid without these elements.

[0228] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference in their entirety, as if each individual publication, patent, or patent application were specifically and individually indicated to be incorporated herein by reference. Furthermore, any reference or designation of any reference in this application should not be construed as an admission that such reference is prior art to the invention. The use of section headings should not be construed as necessarily limiting. Additionally, any priority documents of this application are incorporated herein by reference in their entirety.

Claims

1. A method of operating a cardiac electrical stimulation device, the cardiac electrical stimulation device including a memory storing data defining an initial treatment plan, the data including parameters for applying cardiac electrical stimulation to the heart within a set time period; the method comprising: The controller of the cardiac electrical stimulation device receives data on actual cardiac activity automatically sensed by one or more sensors; The controller automatically generates a command to energize one or more leads of the cardiac electrical stimulation device with a cardiac electrical stimulation signal, based on the initial treatment plan and the data sensed by the one or more sensors. as well as The controller automatically generates an updated treatment plan, in which at least one of the parameters is modified to compensate for changes made relative to the initial treatment plan due to the sensed data; The treatment plan automatically generated and updated by the controller includes: selecting and / or updating the parameters to obtain the total number of cardiac electrical stimulations and / or the total amount of cardiac electrical stimulation energy within the set time period.

2. The method of claim 1, further comprising: The command is modified to adapt the treatment to the actual cardiac activity sensed by the one or more sensors.

3. The method of claim 2, further comprising: At the device controller, at least one of the parameters is automatically updated to compensate for changes made relative to the initial treatment plan due to the sensed actual cardiac activity.

4. The method of claim 1, wherein, The parameters include one or more of the following: cardiac electrical stimulation rate; stimulation current; output voltage; duration of each stimulation.

5. The method as described in claim 1 or 2, wherein, The parameters are selected and / or updated to obtain the total number of cardiac electrical stimulations.

6. The method of claim 4, wherein, The automatically generated and updated treatment plan includes one or more of the following: increasing or decreasing the cardiac electrical stimulation rate; extending or shortening the set time period for applying cardiac electrical stimulation; increasing or decreasing the intensity of the stimulation current; and extending or shortening the duration of the stimulation.

7. The method according to any one of claims 1 to 6, wherein, The updated treatment plan is configured to modify the dose of the applied cardiac electrical stimulation in the treatment plan; as well as The modified dosage includes one of the following: If the actual number of stimulation pulses is less than the set dose, more stimulation will be set during the upcoming set time period after the set time period for delivering the actual stimulation pulses. as well as Based on the data sensed by the one or more sensors according to the treatment plan, less stimulation is set during the upcoming set time period.

8. The method of claim 6, wherein, The cardiac electrical stimulation includes cardiac contraction modulation stimulation.

9. The method according to any one of claims 1 to 6, wherein, The initial treatment plan is defined and / or updated based on input of measured and / or received cardiac activity characteristics of the patient being treated.

10. The method of claim 9, wherein, The cardiac activity characteristics include one or more of the following: average heart rate, average stroke volume, and the incidence of irregular cardiac events.

11. The method of claim 10, wherein, The irregular cardiac events are from the following groups: premature ventricular contractions (PVCs), atrial arrhythmias, and ventricular arrhythmias.

12. The method according to any one of claims 1 to 6, wherein, The cardiac electrical stimulation device is an implantable device, and wherein one or more of the leads are in contact with the ventricular septum of the heart.

13. The method according to any one of claims 1 to 6, wherein, The initial treatment plan is defined according to at least one of the following: One or more thresholds for heart rate, during which the command will be generated; and The command will be generated during one or more of the patient's physical states.

14. The method according to any one of claims 1 to 6, wherein, The automatically generated and updated treatment plan is executed in response to one or more undelivered cardiac electrical stimuli.

15. The method according to any one of claims 1 to 6, wherein, The automatically generated updated treatment plan is executed if at least one of the following conditions is met: The actual number of cardiac electrical stimulations delivered was less than the planned number; and The total amount of cardiac electrical stimulation energy delivered was lower than the planned amount of cardiac electrical stimulation energy.

16. The method according to any one of claims 1 to 6, wherein, The measured cardiac activity includes one or more measured cardiac performance parameters selected from the following groups: ejection fraction, cardiac output, intracardiac pressure, and intracardiac pressure gradient over time.

17. A method of operating a cardiac electrical stimulation device, the cardiac electrical stimulation device comprising a memory storing data defining an initial treatment plan, the data including parameters for a first selected time period, according to which cardiac electrical stimulation is applied to the heart; the method comprising: The device controller of the cardiac electrical stimulation device receives the total number of stimuli to be delivered to the heart during the first selected time period; The controller generates a command, according to the initial treatment plan, to energize one or more leads of the cardiac electrical stimulation device with a cardiac electrical stimulation signal; During the first selected time period, the controller automatically counts the number of times the stimuli are delivered; If the number of stimuli delivered during the first selected time period is less than the total number of selected stimuli, the controller automatically generates an updated treatment plan by adding a second selected time period to the extent necessary to deliver the required additional stimulation, in accordance with the initial treatment plan, so as to obtain the total number of cardiac electrical stimulations and / or the total amount of cardiac electrical stimulation energy within the second selected time period.

18. The method of claim 17, wherein, The stimulation includes cardiac contraction regulation stimulation.

19. The method of claim 17 or 18, comprising: If the number of times the stimulus is delivered is less than 90% of the total number of the selected stimuli, then the second selected time period is added to generate additional stimuli.

20. The method of claim 17, comprising: If the number of stimuli delivered during the first selected time period is less than the total number of selected cardiac electrical stimuli, then the total number of selected cardiac electrical stimuli is reduced for future stimulation sessions.

21. The method of claim 17, wherein, The first selected time period is between 4 and 8 hours a day.

22. A method for planning cardiac electrical stimulation therapy, comprising: Select the total amount of energy to be delivered to the heart through cardiac electrical stimulation; as well as Select one or both of the following: the duration of cardiac electrical stimulation to be applied to the heart, and the intensity of the stimulation current for each stimulation, wherein the duration and the intensity of the stimulation current are selected to achieve the total energy.

23. The method of claim 22, wherein, The cardiac electrical stimulation includes cardiac contraction modulation stimulation.

24. The method of claim 22, wherein, The plan includes determining the time period and / or the intensity of the stimulation current based on statistics of known or estimated cardiac activity of the patient.

25. The method of claim 22, wherein, Known or estimated statistics include one or more of the following: heart rate, stroke volume, probability of premature ventricular contractions (PVCs), probability of atrial arrhythmias, probability of ventricular arrhythmias, and probability of defibrillation.

26. The method of claim 22, wherein, Selecting the total energy amount includes selecting the total number of stimuli to be delivered within a time window, wherein the time window includes one or more of the following: a 1-hour window, a 12-hour window, and a 24-hour window.

27. The method of claim 26, wherein, The total number of stimuli includes between 5,000 and 50,000 stimuli per day.

28. The method of claim 22, wherein, The selected time period includes: selecting the stimulation duration between 1 hour and 8 hours within a 24-hour period.

29. The method of claim 22, wherein, Cardiac electrical stimulation is delivered intermittently during a selected time period, with one or more non-stimulation intervals between stimulation intervals.

30. The method of claim 22, further comprising: Electrocardiogram (ECG) measurements are used to detect heart activity.

31. The method of claim 22, further comprising: Use one or more sensors selected from the following group to detect the patient’s physiological or physical condition: GPS sensor, gyroscope, microphone, and inertial motion sensor.

32. The method of claim 31, wherein, The one or more sensors are associated with the patient's personal electronic device, which communicates with the stimulation device controller.

33. The method of claim 22, further comprising: In response to actual cardiac activity that differs from the expected cardiac activity, the delivery of cardiac electrical stimulation is modified according to the backup treatment plan.

34. The method of claim 33, wherein, Modifying the delivery of cardiac electrical stimulation includes: modifying the timing of stimulation to maintain the selected total energy.

35. The method of claim 33, wherein, The backup treatment plan is triggered in response to one or more of the following: changes in heart rate, occurrence of arrhythmia, and delivery of a defibrillation signal.

36. The method of claim 33, wherein, The initial treatment plan defines the delivery of cardiac electrical stimulation only within a predefined heart rate range, and wherein, if the treatment goal has not been achieved within a predefined time window, the backup treatment plan allows delivery outside the predefined heart rate range.

37. The method of claim 22, wherein, Selecting the stimulation current intensity for each stimulus includes selecting the stimulation current intensity such that the selected time period and the stimulation current intensity together achieve the selected total amount of energy to be delivered to the heart.

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