Methods for planning and delivering cardiac electrical stimulation

Abstract

To provide techniques relating to cardiac electrical stimulation treatment capable of updating parameters on the basis of real heart activities and / or in response to the same.SOLUTION: A system for cardiac electrical stimulation treatment includes: an embedded pulse generator; one or more leads for applying cardiac electrical stimulation which extend from the pulse generator to a heart; and a controller programmed in at least one treatment plan for applying the cardiac electrical stimulation. The controller is configured to update the treatment plan in response to real heart activities by updating a time during which the cardiac electrical stimulation is applied, a ratio of the cardiac electrical stimulation, and one or more parameters including an amount of energy delivered in each cardiac electrical stimulation.SELECTED DRAWING: Figure 1B

Description

[Technical Field]

[0001] Related Applications This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 042,061 (Attorney Docket No. 79078), filed June 22, 2020, U.S. Provisional Patent Application No. 62 / 924,776 (Attorney Docket No. 79063), filed October 23, 2019, U.S. Provisional Patent Application No. 63 / 001,343 (Attorney Docket No. 79080), filed March 29, 2020, and U.S. Provisional Patent Application No. 62 / 924,782 (Attorney Docket No. 79062), filed October 23, 2019, the contents of which are incorporated herein by reference in their entireties.

[0002] This application is part of the following concurrently filed PCT applications, filed on the same day by the same applicant: Attorney Docket No. 85056 to PRUTCHI David et al., entitled "ENHANCEMENT OF PEAK VO2 IN HF PATIENTS USING CARDIAC CONTROL MODULATION (CCM) STIMULATION"; Attorney Docket No. 85068 to PRUTCHI David et al., entitled "CARDIAC CONTROL MODULATION FOR PATIENTS WITH ATRIAL ARRHYTHMIA"; and Attorney Docket No. 85070 to PRUTCHI David et al., entitled "CARDIAC CONTROL MODULATION IN RELATION TO RESPIRATION" [Background technology]

[0003] The present invention, in some embodiments thereof, relates to planning and delivering cardiac electrical stimulation, and more particularly, but not exclusively, to cardiac electrical stimulation therapy whose parameters can be updated based on and / or in response to actual cardiac activity. Summary of the Invention [Means for solving the problem]

[0004] According to an aspect of some embodiments, there is provided a method of cardiac electrical stimulation comprising: defining a therapy plan including parameters according to which cardiac electrical stimulation is applied to the heart; applying cardiac electrical stimulation to the heart according to the therapy plan; and, during application, adapting the therapy to actual cardiac activity; and automatically updating at least one of the parameters to compensate for changes to the therapy plan resulting from the adaptation.

[0005] In some embodiments, the parameters include one or more of the rate of cardiac electrical stimulation, the period over which the cardiac electrical stimulation should be applied, the stimulation current, the output voltage, and the duration of each stimulation.

[0006] In some embodiments, defining the treatment plan includes selecting parameters to deliver one or both of a total number of cardiac electrical stimulations, a total amount of cardiac electrical stimulation energy.

[0007] In some embodiments, automatically updating includes one or more of increasing or decreasing the rate of cardiac electrical stimulation, lengthening or shortening the time over which cardiac electrical stimulation is applied, increasing or decreasing the strength of the stimulation current, and lengthening or shortening the duration of stimulation.

[0008] In some embodiments, defining the treatment plan includes measuring or receiving input of characteristics of cardiac activity of the patient to be treated.

[0009] In some embodiments, the cardiac activity characteristics include average heart rate, average stroke volume, and incidence of irregular cardiac events.

[0010] In some embodiments, the irregular cardiac events are from the group of premature ventricular contractions (PVCs), atrial arrhythmias or ventricular arrhythmias.

[0011] In some embodiments, applying comprises delivering the electrical stimulation via an implantable device that includes one or more leads in contact with the ventricular septum of the heart.

[0012] In some embodiments, the method includes measuring actual cardiac activity using one or more sensors.

[0013] In some embodiments, defining the treatment plan includes setting one or more thresholds of heart rate during which cardiac electrical stimulation should be applied.

[0014] In some embodiments, defining the treatment plan includes selecting one or more physical conditions of the patient during which cardiac electrical stimulation is to be applied.

[0015] In some embodiments, the automatically updating is performed in response to one or more missed stimuli.

[0016] In some embodiments, the automatic updating is performed if the number of actually delivered cardiac electrical stimuli is less than the planned number of cardiac electrical stimuli.

[0017] In some embodiments, the automatic updating is performed if the total amount of cardiac electrical stimulation energy delivered is less than the planned amount of cardiac electrical stimulation energy.

[0018] In some embodiments, the cardiac electrical stimulation comprises a cardiac contractility modulation stimulation.

[0019] According to an aspect of some embodiments, there is provided a method of delivering therapeutic stimuli to a heart that includes selecting a total number of stimuli to be delivered to the heart over a selected period of time, delivering the stimuli to the heart, counting the number of stimuli actually delivered, and if the number of stimuli actually delivered is less than the planned total number of stimuli, adding a selected amount of time sufficient to deliver the additional stimuli needed.

[0020] In some embodiments, the stimulation comprises a cardiac contractility modulation stimulation.

[0021] In some embodiments, the method includes adding a selected time for delivering additional stimuli if the number of stimuli actually delivered is less than 90% of the total selected number of stimuli.

[0022] In some embodiments, adding the selected time period includes extending the originally selected time period.

[0023] In some embodiments, if the number of stimuli actually delivered is less than the selected total number of contractility modulation stimuli, the selected total number of contractility modulation stimuli is reduced for the future stimulation period.

[0024] In some embodiments, the selected time is between 4 and 8 hours per day.

[0025] According to an aspect of some embodiments, there is provided a method of planning a cardiac electrical stimulation therapy that includes selecting a total amount of energy to be delivered to a heart by cardiac electrical stimulation, and selecting one or both of times when the cardiac electrical stimulation should be applied to the heart and a stimulation current strength for each of the stimulations, wherein the times and stimulation current strength are selected to arrive at the total amount of energy.

[0026] In some embodiments, the cardiac electrical stimulation comprises a cardiac contractility modulation stimulation.

[0027] According to an aspect of some embodiments, there is provided a system for cardiac electrical stimulation therapy, including an implantable pulse generator; one or more leads extending from the pulse generator to a heart for applying cardiac electrical stimulation; a controller programmed with at least one therapy plan for applying the cardiac electrical stimulation; and the controller configured to automatically update the therapy plan in response to actual cardiac activity by updating one or more of: a time for which the cardiac electrical stimulation is applied; a rate of the cardiac electrical stimulation; and an amount of energy delivered with each cardiac electrical stimulation.

[0028] In some embodiments, the system includes one or more sensors, including an ECG sensor, configured to measure actual cardiac activity.

[0029] In some embodiments, one or more leads contact the interventricular septum of the heart.

[0030] In some embodiments, the controller is programmed with instructions for automatically updating the treatment plan, the instructions being suitable to compensate for real-time changes in the treatment plan.

[0031] In some embodiments, the instructions include a number factor according to which one or more of the following parameters are updated: stimulation current intensity; output voltage that sets the selected stimulation current intensity; duration of stimulation; duration of treatment period; stimulation ratio.

[0032] According to an aspect of some embodiments, there is provided a method of operating a cardiac electrical stimulation device, the device including a memory in which an initial treatment plan is defined, the treatment plan including parameters according to which cardiac electrical stimulation is applied to the heart, the method comprising: generating commands to charge one or more leads of the device with cardiac electrical stimulation signals via a controller of the device and in accordance with an initial treatment plan; sensing actual cardiac activity using one or more sensors; modifying the commands to adapt the therapy to actual cardiac activity sensed by the one or more sensors; and automatically updating at least one of the parameters in the device controller to compensate for changes that occur to the initial treatment plan due to the sensed actual cardiac activity.

[0033] In some embodiments, the parameters include one or more of the rate of cardiac electrical stimulation, the time over which the cardiac electrical stimulation should be applied, the stimulation current, the output voltage, and the duration of each stimulation.

[0034] 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.

[0035] In some embodiments, automatically updating includes one or more of increasing or decreasing the rate of cardiac electrical stimulation, lengthening or shortening the time that cardiac electrical stimulation is applied, increasing or decreasing the strength of the stimulation current, and lengthening or shortening the duration of stimulation.

[0036] In some embodiments, the treatment plan is defined and / or updated according to measured and / or received input of characteristics of the cardiac activity of the patient being treated.

[0037] In some embodiments, the cardiac activity characteristics include average heart rate, average stroke volume, and incidence of irregular cardiac events.

[0038] In some embodiments, the irregular cardiac events are from the group of premature ventricular contractions (PVCs), atrial arrhythmias or ventricular arrhythmias.

[0039] In some embodiments, the device is an implantable device in which one or more leads contact the interventricular septum of the heart.

[0040] In some embodiments, the method includes measuring actual cardiac activity using one or more sensors.

[0041] In some embodiments, the treatment plan is defined according to one or more thresholds of heart rate during which commands should be generated.

[0042] In some embodiments, the treatment plan is defined according to one or more physical conditions of the patient during which commands should be generated.

[0043] In some embodiments, the automatically updating is performed in response to one or more missed cardiac electrical stimulations.

[0044] In some embodiments, the automatic updating is performed if the number of actually delivered cardiac electrical stimuli is less than the planned number of cardiac electrical stimuli.

[0045] In some embodiments, the automatic updating is performed if the total amount of cardiac electrical stimulation energy delivered is less than the planned amount of cardiac electrical stimulation energy.

[0046] In some embodiments, the cardiac electrical stimulation comprises a cardiac contractility modulation stimulation.

[0047] According to an aspect of some embodiments, selecting a total number of stimuli to be delivered to the heart over a selected period of time; generating commands to deliver stimuli to the heart; Counting the number of stimuli generated; If the number of stimuli generated is less than the selected total number of stimuli, adding a selected amount of time sufficient to deliver the required additional stimuli is provided.

[0048] In some embodiments, the stimulation comprises a cardiac contractility modulation stimulation.

[0049] In some embodiments, the method includes adding a selected time for generating additional stimuli if the number of stimuli generated is less than 90% of the total selected number of stimuli.

[0050] In some embodiments, adding the selected time period includes extending the originally selected time period.

[0051] In some embodiments, the method includes reducing the selected total number of cardiac electrical stimuli for the future stimulation period if the number of generated stimuli is less than the selected total number of cardiac electrical stimuli.

[0052] In some embodiments, the selected time period is between 4 and 8 hours per day.

[0053] According to an aspect of some embodiments, selecting a total amount of energy delivered to the heart by cardiac electrical stimulation; A method of planning a cardiac electrical stimulation therapy is provided, comprising selecting one or both of a time period during which cardiac electrical stimuli should be applied to the heart and a stimulation current strength for each of the stimuli, wherein the time period and stimulation current strength are selected to achieve a total amount of energy.

[0054] In some embodiments, the cardiac electrical stimulation comprises a cardiac contractility modulation stimulation.

[0055] According to an aspect of some embodiments, an implantable pulse generator; one or more leads extending from the pulse generator to the heart for applying cardiac electrical stimulation; A system for cardiac electrical stimulation therapy is provided, including: a controller programmed with at least one therapy plan for applying cardiac electrical stimulation; and the controller configured to automatically update the therapy plan in response to actual cardiac activity by updating one or more parameters including the time the cardiac electrical stimulation is applied, the rate of the cardiac electrical stimulation, and the amount of energy delivered with each cardiac electrical stimulation.

[0056] In some embodiments, the system includes one or more sensors, including an ECG sensor, configured to measure actual cardiac activity.

[0057] In some embodiments, one or more leads contact the interventricular septum of the heart.

[0058] In some embodiments, the controller is programmed with instructions for automatically updating the treatment plan, the instructions being suitable to compensate for real-time changes in the treatment plan.

[0059] In some embodiments, the instructions include a number factor according to which one or more of the following parameters are updated: stimulation current intensity; output voltage that sets the selected stimulation current intensity; duration of stimulation; duration of treatment period; stimulation ratio.

[0060] In some embodiments, the controller is configured to select and / or update parameters for obtaining a total number of cardiac electrical stimulations and / or a total amount of cardiac electrical stimulation energy.

[0061] In some embodiments, the controller is configured to increase or decrease the rate of cardiac electrical stimulation; increase or decrease the time over which cardiac electrical stimulation is applied; increase or decrease the strength of the stimulation current; or increase or decrease the duration of stimulation.

[0062] In some embodiments, the controller is configured to estimate one or more of the average heart rate, the average stroke volume, and the incidence of irregular cardiac events based on data obtained by the one or more sensors.

[0063] In some embodiments, the irregular cardiac events are from the group of premature ventricular contractions (PVCs), atrial arrhythmias or ventricular arrhythmias.

[0064] In some embodiments, the controller is configured to set and / or receive as input one or more threshold values ​​for the heart rate during which cardiac electrical stimulation is applied.

[0065] In some embodiments, the controller is configured to set and / or receive as input one or more physical conditions of the patient while the cardiac electrical stimulation is being applied.

[0066] In some embodiments, the controller is configured to automatically update the therapy plan in response to one or more missed cardiac electrical stimuli.

[0067] In some embodiments, the controller is configured to automatically update the treatment plan if the number of actually delivered cardiac electrical stimuli is less than the planned number of cardiac electrical stimuli.

[0068] In some embodiments, the controller is configured to set the number of cardiac electrical stimuli delivered within a set period of time.

[0069] In some embodiments, the set period of time comprises 24 hours.

[0070] 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. Although methods and materials similar or equivalent to those described herein can be used in the practice and testing of embodiments of this invention, exemplary methods and / or materials are described below. In case of conflict, the present specification, including definitions, will control. Additionally, the materials, methods, and examples are illustrative only and are not necessarily intended to be limiting.

[0071] Implementation of the methods and / or systems of embodiments of the present invention may include performing or completing selected tasks manually, automatically, or a combination thereof. Further, in accordance with the instrumentation and devices of the method and / or system embodiments of the present invention, some selected tasks may be performed using an operating system, by hardware, by software, by firmware, and / or by a combination thereof.

[0072] For example, hardware for performing selected tasks according to embodiments of the present invention may be implemented as a chip or circuit. As software, selected tasks according to embodiments of the present invention may be implemented as a plurality of software instructions executed by a computer using a suitable operating system. In exemplary embodiments of the present 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 computer platform executing a plurality of instructions. Optionally, the data processor includes volatile memory for filtering instructions and / or data, and / or non-volatile storage, e.g., a magnetic hard disk and / or removable media for filtering instructions and / or data. Optionally, a network connection is also provided. Optionally, a display and / or a user input device, such as a keyboard or mouse, are also provided.

[0073] Several embodiments of the present invention are described herein, by way of example only, with reference to the accompanying drawings. With specific reference now to the detailed drawings, it is emphasized that the matter shown is by way of example and for purposes of illustrative discussion of embodiments of the present invention. In this regard, the description taken in conjunction with the drawings will make apparent to those skilled in the art how embodiments of the invention may be practiced. [Brief explanation of the drawings]

[0074] [Figure 1A] 1 is a flowchart of a method of cardiac electrical stimulation therapy that compensates for real-time changes in planned therapy, according to some embodiments. [Figure 1B] 1 is a flowchart of a method for planning a cardiac electrical stimulation therapy and optionally modifying the therapy according to actual cardiac activity, according to some embodiments. [Figure 2A] 1A-1C are schematic diagrams illustrating a planned cardiac electrical stimulation delivery and a modified cardiac electrical stimulation delivery that compensates for variations in the planned delivery due to actual cardiac activity, according to some embodiments. [Figure 2B] 10A-10C are schematic diagrams illustrating optional cardiac electrical stimulation therapies set according to a total amount of delivered stimulation energy, according to some embodiments. [Figure 3] 1 is a flowchart of a method for setting and / or modifying the delivery of cardiac electrical stimulation therapy according to some embodiments. [Figure 4A] FIG. 1 is a block diagram of an exemplary system for cardiac electrical stimulation therapy, according to some embodiments. [Figure 4B] FIG. 1 is a block diagram of an exemplary system for cardiac electrical stimulation therapy, according to some embodiments. [Figure 5A] 1A and 1B are schematic illustrations of exemplary implantable cardiac devices for cardiac electrical stimulation therapy, according to some embodiments. [Figure 5B] 1A and 1B are schematic illustrations of exemplary implantable cardiac devices for cardiac electrical stimulation therapy, according to some embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0075] The present invention, in some embodiments thereof, relates to planning and delivering cardiac electrical stimulation therapies, and more particularly, but not exclusively, to cardiac electrical stimulation therapies whose parameters can be updated based on and / or in response to actual cardiac activity.

[0076] A broad aspect of some embodiments relates to stimulation therapy that is planned according to characteristics of cardiac activity and optionally modified to take into account actual cardiac activity. In some embodiments, stimulation is selected and / or implemented to take into account natural variability in cardiac function, including both intra- and inter-individual variability.

[0077] An aspect of some embodiments relates to updating one or more parameters of a cardiac electrical stimulation therapy, optionally in real time, to compensate for any changes that occur in the therapy due to actual cardiac activity.

[0078] In some embodiments, the treatment plan is defined by setting parameters such as, for example, the rate of stimulation, the strength of the stimulation current, the duration of the treatment period, and / or other parameters, which in some embodiments are selected according to a general treatment goal, for example, the total number of cardiac electrical stimulations delivered to the heart and / or the total amount of cardiac electrical stimulation energy delivered to the heart.

[0079] In some embodiments, the treatment plan is defined according to characteristics of the cardiac activity of the patient being treated, for example, taking into account the patient's heart rate, stroke volume, incidence of irregular cardiac events (e.g., arrhythmias), and / or other characteristics.

[0080] In some embodiments, the treatment plan defines one or more conditions for applying cardiac electrical stimulation. For example, the plan may define that stimulation should be delivered only when the heart rate is below or above a threshold (or within a selected range). For example, the plan may define that stimulation should be delivered only when the patient is in a particular physical state, e.g., at rest.

[0081] In some embodiments, the treatment plan takes into account expected variability in cardiac activity. In some embodiments, treatment parameters, such as the total number of stimuli delivered; the total amount of stimulation energy delivered; the rate of stimulation; and the timing of stimulation, are selected taking into account that changes in parameters may have non-linear effects on the treatment itself. Thus, in some embodiments, multiple settings of parameters may be defined to achieve an equivalent therapeutic effect. For example, delivery of 8,000 stimuli randomly distributed over a day may result in a therapeutic effect equivalent to a stimulation delivered at every heartbeat for an hour at a heart rate greater than 90 bpm. In some embodiments, for example, a system and / or device such as those described herein (e.g., a system controller) is pre-programmed with a lookup table containing parameter settings that lead to an equivalent therapeutic effect and may optionally be interchangeable. In some embodiments, treatment parameters are selected and / or calculated according to one or more additional treatment parameters and / or according to a desired therapeutic effect.

[0082] In some embodiments, cardiac electrical stimulation therapy is delivered according to a plan, but variability may be created in the plan in response to actual cardiac activity. Optionally, the variability is created in real time. For example, if an irregular beat is identified, stimulation may be skipped at that beat. In some embodiments, variability in the treatment plan is created in response to actual cardiac activity measured by one or more sensors (optionally monitored over time), such as via ECG measurements.

[0083] In some embodiments, variability created in the planning is compensated for, for example, to reach a common treatment goal. In some embodiments, compensating includes updating one or more treatment parameters, such as updating the duration of a treatment period; updating the rate of cardiac electrical stimulation; updating the strength of the stimulation current; updating the number of electrodes activated (e.g., to contact different sized areas of tissue); updating the time interval and / or number of beats between successive stimulations; and / or other treatment parameters.

[0084] In some embodiments, an implantable device is provided that includes one or more leads for delivering 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 therapy parameters in response to variability in the therapy plan due to actual cardiac activity. In some embodiments, the controller is programmed with one or more therapy plans and one or more "fallback" instructions for updating the therapy parameters when therapy is being administered and optionally changed due to actual cardiac activity.

[0085] Some examples of "fallback" instructions include extending the duration of a therapy period if the number of stimuli actually delivered is less than the set number of stimuli; increasing the intensity of the stimulation current if the total amount of energy delivered is less than the set amount of energy delivered; increasing the rate of cardiac electrical stimulation if the time for the therapy period is almost up but the actual delivered stimuli are not sufficient; and updating the heart rate threshold for the application of stimulation if the actual heart rate over the therapy period (or part thereof) was not within the defined heart rate range for the delivery of stimulation.

[0086] Before describing at least one embodiment of the present invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details of construction and arrangement of components and / or methods set forth in the following description and / or illustrated in the drawings and / or examples, as the invention is capable of other embodiments or of being practiced or carried out in various ways.

[0087] Before describing at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details set forth in the following description and / or illustrated in the drawings and / or examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

[0088] Methods for planning and / or modifying cardiac electrical stimulation therapy Reference is now made to FIG. 1A, which is a flowchart of a method of cardiac electrical stimulation therapy that compensates for real-time changes in planned therapy, according to some embodiments.

[0089] In some embodiments, a decision is made to treat the patient by applying cardiac electrical stimulation to the heart (121).

[0090] In some embodiments, the stimulation signal is a cardiac contractility modulation signal. In some embodiments, the cardiac contractility modulation signal is a non-excitatory signal applied to the heart, optionally during the relative and / or absolute refractory periods of the cardiac cycle. In some embodiments, the signal is selected to increase contractility of the ventricles of the heart when the signal's electric field stimulates such ventricular tissue, e.g., the left ventricle, the right ventricle, and / or the ventricular septum. In some embodiments, modulation of contractility is provided by signal-induced phosphorylation of phospholamban. In some embodiments, modulation of contractility is caused by alterations in protein transcription and / or mRNA production, optionally in the form of reversal of a fetal genetic program.

[0091] It is noted that in some embodiments, cardiac contractility modulation signals may be excitatory to tissues other than the tissue to which they are applied. Various mechanisms by which cardiac contractility modulation signals may operate are described, for example, in “Cardiac contractility modulation: mechanisms of action in heart failure with reduced ejection fraction and beyond” by C. Tschope et al., European Journal of Heart Failure, (2018), doi:10.1002 / ejhf.1349, and may help guide the selection of signal application parameters to take advantage of and / or follow one or more of these mechanisms.

[0092] The term "cardiac electrical stimulation" is used herein as a general substitute for all such signals unless otherwise specified. In some embodiments, the term "cardiac electrical stimulation" is intended to encompass electropharmaceutical signals, e.g., therapeutic signals. In some embodiments, the stimulation is delivered to the heart and / or associated 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 synchronously to the heart chambers, e.g., synchronously with the heartbeat.

[0093] In some embodiments, cardiac electrical stimulation is applied according to suitable parameters (e.g., current strength, timing of application, rate, anatomical location) to induce cardiac contractility modulation. In some embodiments, cardiac electrical stimulation includes stimulation of the cardiac fat pads. In some embodiments, cardiac electrical stimulation includes affecting the heart via stimulation of the vagus nerve. In some embodiments, cardiac electrical stimulation includes stimulation of the vascular innervation, e.g., stimulation of the aorta, vena cava, pulmonary artery, or pulmonary vein.

[0094] In some embodiments, the patient selected for treatment is a patient suffering from heart failure, congestive heart failure, and / or similar conditions. In some embodiments, the patient selected for treatment is a patient in which the pumping action of the heart is impaired, potentially affecting blood flow and / or oxygen delivery. In some embodiments, the patient selected for treatment is a patient in which cardiac output and / or cardiac contractility are impaired and may be improved by administering cardiac electrical stimulation therapy, e.g., by administering cardiac contractility modulation therapy. In some cases, one or more effects of cardiac electrical stimulation therapy, e.g., improved cardiac contractility and / or higher peak oxygen uptake, may improve respiration.

[0095] In some embodiments, a cardiac device configured to apply cardiac electrical stimulation is implanted in the patient (123). In some embodiments, the device includes a pulse generator optionally implanted outside the heart, e.g., in the subclavian region, and one or more leads for stimulating the heart. Optionally, the one or more leads contact the ventricular septum of the heart.

[0096] In some embodiments, therapy parameters for applying cardiac electrical stimulation are defined 125. In some embodiments, the therapy parameters are selected and the device is programmed accordingly (e.g., the device's controller).

[0097] In some embodiments, cardiac electrical therapy parameters include, for example, timing of stimulation (e.g., relative to the cardiac cycle and / or relative to previously applied stimulation), number of stimulations (optionally, the total number of stimulations applied within a defined period of time), stimulation current strength, stimulation duration, safety threshold, stimulation ratio, and / or other parameters.

[0098] In some embodiments, general treatment parameters (which may also be referred to as "treatment goals") are set, including, for example, the total amount of stimulation energy (power) to be delivered to the patient (optionally over or within a defined period of time, e.g., minutes, hours, days, weeks, months); the total number of cardiac electrical stimuli to be delivered to the patient (optionally over or within a defined period of time, e.g., minutes, hours, days, weeks, months); and the accumulated duration of stimulation pulses (optionally over or within a defined period of time, e.g., minutes, hours, days, weeks, months).

[0099] In some embodiments, the treatment parameters are selected by a clinical participant, such as an attending physician (e.g., a cardiologist). Additionally or alternatively, the treatment parameters are selected automatically, e.g., by a device controller, e.g., based on entered patient data.

[0100] In some embodiments, the patient data includes general patient information such as age, sex, medical condition, etc. In some embodiments, for example, as further described herein, the patient data includes known and / or estimated statistics of the patient's cardiac activity, including, but not limited to, heart rate (e.g., average, peak values); actual incidence and / or predicted likelihood of cardiac events, such as premature ventricular contractions (PVCs), atrial arrhythmias, and / or ventricular arrhythmias; stroke volume (e.g., mean stroke volume values); 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.

[0101] In some embodiments, cardiac electrical stimulation is applied according to selected treatment parameters (127).

[0102] In some embodiments, actual cardiac activity is detected (129), including, for example, variability in heart rate (e.g., compared to an expected average heart rate), cardiac events or episodes, changes in stroke volume, and / or the like. In some embodiments, the actual cardiac activity is sampled and / or continuously monitored. Optionally, one or more sensors are used to track the actual cardiac activity. In one example, ECG measurements are performed, optionally via intracardiac electrodes. Optionally, the intracardiac electrodes used for ECG measurements are the same electrodes that apply cardiac electrical stimulation. Optionally, intracardiac sensors, such as bioimpedance sensors and / or pressure sensors, are used to measure cardiac function parameters, such as, for example, ejection fraction, cardiac output, intracardiac pressure, and intracardiac pressure gradients over time.

[0103] Optionally, upon detection of cardiac activity, e.g., upon detection of a variation from expected cardiac activity and / or irregularity, cardiac electrical stimulation therapy is modified (131). In one example, scheduled cardiac electrical stimulation (i.e., a single stimulation) is not delivered upon detection of an irregular heartbeat (e.g., a premature ventricular contraction (PVC), an atrial arrhythmia, and / or a ventricular arrhythmia). In another example, scheduled cardiac electrical stimulation is not delivered when a defibrillation signal is delivered to the heart (optionally via the same device that delivers the cardiac electrical stimulation signal). Optionally, in such situations, cardiac electrical stimulation is not delivered for a defined period of time immediately after defibrillation to allow the heart to recover from the defibrillation.

[0104] In some embodiments, therapy is modified in response to changes in heart rate. For example, therapy is modified upon sensing a heart rate that is faster or slower than the average heart rate expected for a particular patient. For example, therapy is modified if the heart rate is 100%, 120%, 150%, 170%, or an intermediate, higher, or lower percentage of the average expected heart rate. For example, therapy is modified if the heart rate is only 70%, 50%, 30%, or an intermediate, higher, or lower percentage of the average expected heart rate.

[0105] In some embodiments, one or more treatment parameters are automatically updated to compensate for the resulting modification (133). Any of the treatment parameters mentioned above, or a combination thereof, may be modified.

[0106] In some embodiments, the therapy is updated in real time, for example, during a therapy period, e.g., a daily therapy period consisting of several hours (e.g., 1, 2, 3, 4, 5, 6 hours, or an intermediate, longer, or shorter period) during which stimulation is provided by the device. In some embodiments, the therapy is updated in response to the detection of an irregular cardiac event. Additionally or alternatively, the therapy is updated based on the action taken by the device in response to the event (e.g., a missed stimulation).

[0107] The following are examples of compensations that occur in response to modifications in therapy that may be implemented due to actual cardiac activity: In some embodiments, cardiac electrical stimulation is synchronized to be delivered with each cardiac cycle according to a planned therapy. For example, a cardiac contractility modulation signal is applied during a refractory period. Under such scheduling, a patient whose actual heart rate (i.e., heart rate during at least a portion of a treatment period) is higher than the expected average may receive an excessive number of stimuli, and a patient whose heart rate is lower than the expected average may receive fewer stimuli than planned. In some embodiments, parameters such as the duration of a treatment period or the intensity of the stimulation current may be updated to account for variability. For example, for a patient with a high heart rate, the duration of a treatment period may be shortened, thereby reducing or avoiding excessive stimulation; the intensity of the stimulation current may be reduced so that the total amount of energy delivered over the treatment period remains as planned. For example, for a patient with a low heart rate, the duration of a treatment period may be extended in an attempt to reach the planned amount of stimulation; the intensity of the stimulation current may be increased so that the total amount of energy delivered over the treatment period reaches the planned amount. In some embodiments, the intensity of the stimulation current is set by the device by controlling (and optionally adjusting) the voltage setting. In some embodiments, the current strength (or magnitude) is set by setting the output voltage under the assumption that the electrical impedance of the device components (e.g., one or more stimulation leads) remains substantially constant and does not change. In some embodiments, the magnitude of the output voltage is controlled to produce a selected stimulation current. In some embodiments, if a stimulus is skipped or canceled, for example, in response to an irregular heartbeat, compensation may include increasing the duration of the treatment period to deliver additional stimulus(s); increasing the current intensity in one or more subsequent stimuli to compensate for the amount of energy not delivered; or increasing the size (e.g., surface area) of tissue contacted and stimulated by the device electrodes. In some cases, cardiac electrical stimulation is not applied during a heartbeat if the heartbeat is deemed unsafe in the sense that cardiac electrical stimulation signals may cause arrhythmia if applied during that heartbeat. Optionally, or in addition, one or more "prohibited" heartbeats may be used to allow the heart to "recover" from the abnormal heartbeat. In some embodiments, compensation for intentionally not applied stimuli may include increasing the duration of the treatment period to deliver additional stimulus(s); increasing the current intensity in one or more subsequent stimuli to compensate for the amount of energy not delivered; increasing the size (e.g., surface area) of tissue contacted and stimulated by the device electrodes; and / or other changes in treatment parameters.

[0108] FIG. 1B is a flowchart of a method for planning a cardiac electrical stimulation therapy and optionally modifying the therapy according to actual cardiac activity, according to some embodiments.

[0109] In some embodiments, cardiac electrical stimulation therapy is scheduled 151 according to known and / or estimated statistics of the patient's cardiac activity.

[0110] In some embodiments, general treatment parameters (or goals) are defined, including, for example, the total number of stimuli delivered; the total amount of energy applied via the stimuli(s); the total number of stimuli delivered within a particular time window (e.g., 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 stimulation pulses delivered within a particular time window (e.g., a 1-hour window, a 12-hour window, a 24-hour window, or an intermediate, longer, or shorter time window). In one example, the total number of stimuli is set at between 5,000 and 50,000 stimuli per day, e.g., 5,500, 20,000, 40,000, or an intermediate, higher, or lower amount. In one example, the rate of stimulation is set at between 200 and 3,000 stimuli per hour, e.g., 300, 1,000, 2,500, or an intermediate, higher, or lower rate.

[0111] In some embodiments, cardiac electrical stimulation therapy is planned to achieve a general goal by taking into account the patient's known and / or expected cardiac activity according to patient demographics and / or other demographics, such as heart rate (e.g., average, peak, and / or base); stroke volume; likelihood of a cardiac event (e.g., premature ventricular contractions (PVCs), atrial arrhythmias, or ventricular arrhythmias); likelihood of needing defibrillation.

[0112] In some embodiments, the schedule defines a dose. The dose may include, for example, a time period during which stimulation is applied (e.g., within a 24-hour window). For example, the schedule defines that cardiac electrical stimulation be delivered for 1, 2, 3, 5, 6, 8 hours each day, or for an intermediate, longer, or shorter period of time. Optionally, stimulation is delivered intermittently (e.g., with periods of non-stimulation between stimulation periods, e.g., 1 hour of stimulation; 2 hours of rest; 1 hour of stimulation, etc.). In some embodiments, stimulation is applied for 5, 6, 7, or an intermediate, longer, or shorter period of time per day. Optionally, a target number and / or percentage of cardiac electrical stimulation is set during the defined period, so that, for example, stimulation will be applied at each heartbeat for at least 60%, 70%, 80%, or an intermediate, greater, or lesser percentage of the defined period of time.

[0113] In some embodiments, the plan defines that stimulation is delivered every heartbeat for a selected time period, or alternatively, the plan defines applying stimulation at spatially separated heartbeats, for example, every third heartbeat, every seventh heartbeat, every tenth heartbeat, or at intermediate or higher or lower heartbeats.

[0114] In some embodiments, therapy for a particular patient is planned so that stimulation is delivered at selected times of cardiac activity, for example, if the heart rate is greater than a particular threshold or if the heart rate is less than a particular threshold. Optionally, the threshold is the patient's average heart rate.

[0115] In some embodiments, treatment for a particular patient is planned so that stimulation is delivered during selected physiological and / or physical conditions of the patient, e.g., stimulation is delivered only during sleep, stimulation is delivered only during rest, stimulation is delivered only during physical activity, etc.

[0116] In some embodiments, a fixed dose is defined, e.g., a defined total amount of stimulation delivered per day. Optionally, the rate of stimulation over the course of the day is controlled in real time based on one or more of the following: · Patient activity (e.g., delivering more stimulation when the patient is active compared to when the patient is resting, or vice versa); the patient's ambient conditions, e.g., weather conditions (e.g., delivering more stimulation when the ambient temperature (optionally sensed by a temperature sensor in the system) is within, below, or above a selected threshold). For example, it may be desirable to reduce the rate at which cardiac electrical stimulation is applied at temperatures where it may be difficult to maintain body temperature, e.g., above 35°C, below 5°C; Patient posture, e.g., delivering more stimulation when the patient is standing and less stimulation when the patient is sitting and / or lying down, or vice versa. Optionally, patient posture is sensed using sensors, such as, for example, gyroscopes and / or other inertial motion sensors.

[0117] 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, for example, via ECG measurements performed by electrodes on the device. Optionally, the measured cardiac activity also provides an indication of the physical activity the patient is engaged in, and whether the patient is in an active or resting state.

[0118] In another example, the device is configured to detect the patient's physical and / or physiological state to deliver stimulation in a preferred manner. For example, the device is configured to detect a sleep state or a wake 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 performing a physical activity, e.g., 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, e.g., GPS, gyroscope, microphone, and / or others. Optionally, the sensors are configured in a user's personal device, e.g., a mobile phone, in communication with the stimulation device controller.

[0119] Additionally or alternatively, patient indicators and / or conditions may be input into the device (e.g., via a user interface) to configure the application of cardiac electrical stimulation accordingly, e.g., when cardiac activity is of a particular characteristic (e.g., heart rate) and / or when the patient is in a particular physical and / or physiological state.

[0120] In some embodiments, the patient may independently influence treatment (e.g., via a user interface) by, for example, setting a preferred time (during the day) at which stimulation should be delivered. In one example, the patient may ask to be treated for one hour in the morning and another hour in the evening. In some embodiments, the system (e.g., via the system's controller or user interface) is configured to suggest patient options for treatment time and / or stimulation rate and / or stimulation intensity, and the patient may select from available options based on the patient's preferences.

[0121] In some embodiments, cardiac electrical stimulation therapy is initiated and delivered according to the schedule (153).

[0122] In some embodiments, the therapy is optionally modified 155 according to a fallback plan to respond to actual cardiac activity, optionally in an attempt to reach a general therapy goal, such as, for example, the total number of stimuli delivered; the total amount of stimulation energy; delivery of a particular amount during a particular heartbeat (e.g., the heartbeat immediately following an irregular cardiac event); and / or other general therapy goal.

[0123] Some examples of situations in which therapy may be modified from the original plan to a fallback plan include a change in the actual heart rate from the expected (e.g., average) heart rate; an irregular cardiac event (e.g., arrhythmia); or delivery of a different signal to the heart, e.g., delivery of a defibrillation signal.

[0124] The following are examples of situations in which a fallback plan may be optionally followed to modify the treatment plan: The original plan defined delivery of cardiac electrical stimulation when the patient's heart rate was between 60 and 100 bpm and that the patient should be treated for a total of at least one hour per day (within a 24-hour window). However, at the 23rd hour, the patient's heart rate did not reach the defined bpm range. In such cases, the original plan may be modified to deliver stimulation at any heart rate within the remaining time of the 24-hour window.

[0125] FIG. 2A schematically illustrates the delivery of planned cardiac electrical stimulation and the delivery of modified cardiac electrical stimulation that compensates for changes in the planned delivery due to actual cardiac activity, according to some embodiments.

[0126] In some embodiments, the stimuli 2001 are applied with an interval between successive stimuli; for example, stimuli are scheduled to be applied at intervals of 6 heartbeats (as shown), 4 heartbeats, 2 heartbeats, 10 heartbeats, or any intermediate, more, or fewer heartbeat intervals. In some cases, the scheduled stimuli are modified in real time based on actual cardiac activity. For example, an event 2005, such as an irregular heartbeat, is optionally detected by the device (e.g., via ECG measurement). Optionally, the device is configured not to stimulate during the irregular heartbeat, so that the scheduled stimulus is skipped. Due to the detected cardiac event and the skipped stimulus, the next stimulus is applied at an interval of 12 beats, as shown by the bottom bar.

[0127] In some embodiments, to compensate for the skipped stimulus, the total duration 2007 of the treatment period may be extended so that another stimulus is delivered to reach the desired total amount of stimulation within the period.

[0128] 2B is a schematic illustration of an optional cardiac electrical stimulation set according to a total amount of delivered stimulation energy, according to some embodiments. In this example, a total amount of cardiac electrical stimulation energy 2015 is set as a general goal of therapy. To reach this amount, the stimulation may be delivered as multiple stimuli at the same intensity 2017, optionally spaced apart (see 2B1) or sequentially (see 2B2). Alternatively (see 2B3), multiple stimuli (2019, 2021) may differ in intensity from one another, so that the sum of the stimulations reaches the set total amount of energy.

[0129] In some embodiments, if the stimulation causes pain or sensation to the patient, the intensity of the current is reduced. Optionally, if the stimulation does not cause pain (or if the pain is tolerable for a particular patient), the intensity of the current may be increased, potentially reducing the total number of stimulations required and / or the total duration of treatment.

[0130] Some examples of energy settings may include reaching a total of 100 joules of cardiac electrical stimulation energy per day; a total of 5 joules of cardiac electrical stimulation energy per hour; a total of 0.1 joules of cardiac electrical stimulation per minute; etc.

[0131] In some embodiments, the total amount of energy delivered is calculated (e.g., automatically calculated by the device's controller) by multiplying the number of stimulation pulses by the amplitude of the stimulation current and / or by multiplying the number of stimulation pulses by the output voltage (e.g., the voltage emitted by the pulse generator).

[0132] FIG. 3 is a flowchart of a method for setting and / or modifying the delivery of cardiac electrical stimulation therapy, according to some embodiments.

[0133] In some embodiments, cardiac electrical stimulation therapy is scheduled (301) to provide a set dose (SD) of stimulation (i.e., stimulation pulses) for a set time (TP). In some embodiments, the set time includes a day, a set number of hours (e.g., 1, 2, 5, 10, 15, 20, or intermediate, longer or shorter duration), or a set number of minutes (e.g., 5, 10, 30, 45 minutes, or intermediate, longer or shorter duration). Some examples of hourly dose settings include 25,000 stimulation pulses per day; 1000 stimulation pulses per hour; 20 stimulation pulses per minute, or intermediate, higher or lower set pulses.

[0134] In some embodiments, cardiac electrical stimulation is delivered according to a set schedule 303. Then, at the end of the set time, the number of actual stimulation pulses (NSP) delivered during the set time is calculated 305. (Optionally, the number of actual pulses delivered is counted by the device controller.)

[0135] In some cases, the actual number of stimulation pulses (NSP) may differ from the set dose (SD), e.g., may be less than the set dose 307. This may occur in some cases due to skipped stimulations, e.g., in consideration of an irregular heartbeat, an actual heartbeat not being within a defined range suitable for stimulation, and / or other circumstances that cause the delivered stimulation to differ from that planned.

[0136] If the number of actual stimulation pulses is less than the set dose, the schedule may be updated to deliver more stimulation during the next similar time (309); or alternatively, the schedule may be updated to deliver fewer stimulation during the next similar time to conform to the "real life" likelihood of delivering the planned stimulation (311).

[0137] In some embodiments, stimulation is applied if and only if the patient's heart rate is above or below a set threshold, or if and only if it is within a defined range. Optionally, the threshold is dynamically modified to take into account actual cardiac activity to reach a set dose (e.g., to reach a set number of stimuli).

[0138] In some embodiments, cardiac electrical stimulation is scheduled for delivery at each heartbeat over a specific period of time (e.g., over several hours per day); additionally, or alternatively, stimulation is scheduled for delivery at each set number of heartbeats; additionally, or alternatively, the plan defines stimulation time(s) and off-times during which stimulation is not delivered.

[0139] In some embodiments, planning is performed (and / or the treatment plan is modified) according to the actual stimulation pulses delivered and recorded by the device during one or more previous treatment periods. For example, if the number of stimulation pulses actually delivered during a previous treatment period was only 20%, 50%, 75%, or an intermediate, higher, or lower percentage of the planned number of stimuli, the time of the next treatment may be adjusted (e.g., extended) and / or the number of stimulation pulses provided during the same time period as the previous period may be reduced to approximate the number of stimulation pulses actually delivered.

[0140] In one example, if the number of stimulation pulses delivered during a 5-hour treatment period was only 50% of the planned number of stimulation pulses, the plan can be modified, for example, by extending the treatment period to 10 hours to reach the predefined number of stimulation pulses.

[0141] In one example, if the number of stimulation pulses actually delivered is less than the planned total number of stimuli by more than 10%, 20%, 25%, 30%, or an intermediate, higher, or lower percentage, the plan can be modified (e.g., by extending the duration of the treatment period).

[0142] Exemplary Devices and Systems for Cardiac Electrical Stimulation FIG. 4A is a schematic block diagram of a cardiac therapy device 200, according to some embodiments of the present invention.

[0143] Device 200 includes one or more leads 216 (optionally two leads) that may optionally be coupled to device 200 at one or more CAN connectors (not shown), as shown.

[0144] A pulse generator 204, including, for example, a power supply circuit, including, for example, one or more storage capacitors, is optionally used to generate the signal.

[0145] In some embodiments of the present invention, a ventricular detector 206 is provided and used to detect atypical ventricular activation that may be a contraindication to signal application.

[0146] In some embodiments of the present invention, an atrial detector 208 is provided and used to detect atypical atrial activation, which may be used as an input into decision making by device 200 .

[0147] The sensor input 214 may receive data from one or more sensors, such as electrical sensors or other sensors, such as flow sensors, pressure sensors, and / or acceleration sensors. The data from the sensors is optionally further processed (e.g., by the controller 202 and / or the detectors 206, 208) and optionally used as input to a decision-making process in the device 200.

[0148] A controller 202 is optionally provided, implementing one or more logic circuits for determining, for example, the timing and / or other parameters of a signal and / or whether a signal should be applied.

[0149] In some embodiments, the controller controls the application of stimulation pulses according to the treatment plan. Optionally, the controller effects changes in the plan to compensate for real-time deviations from the treatment plan (e.g., missed stimuli). In some embodiments, the controller generates commands to charge one or more leads of the device with stimulation signals. Optionally, the commands are generated according to the treatment plan. In some embodiments, when commands are generated by the controller, a current is optionally passed through one or more leads and into tissue contacted by the one or more leads.

[0150] Memory 218 is optionally provided to store, for example, logic, past effects, treatment plans, adverse events, and / or pulse parameters.

[0151] In some embodiments, the controller and / or memory are programmed with one or more treatment plans (optionally established for a particular patient) and / or with one or more fallback treatment plans.

[0152] In some embodiments, instructions for "compensating" for variations from the treatment plan are stored and processed by the device controller, including, for example, those relating to modifications in treatment duration, number of stimuli, parameters of the stimulation signal (e.g., current intensity), and / or other modifications that may be applied to compensate for real-time changes in the original plan. In some embodiments, the instructions include a factor by which one or more parameters of the treatment are modified. In some examples, the instructions may include a factor by which the stimulation current intensity should be multiplied if the actually applied stimuli do not reach a target amount of energy; a factor by which the output voltage should be modified to produce a desired current intensity; a factor by which the stimulation ratio should be multiplied if the actually applied stimuli do not reach a target total number of stimuli (optionally within a set time); a factor by which the duration of the treatment period should be extended if the target is not reached; etc.

[0153] In some embodiments, the controller refers to a lookup table or the like that connects a particular situation (e.g., a skipped stimulus, the number of actual stimuli delivered less than planned, etc.) with instructions to compensate for that situation (e.g., by updating one or more parameters, e.g., by updating the length of a treatment period).

[0154] A data logger 210 is optionally provided to store device and / or patient activity. Such logging and / or programming may use a communications module 21 (e.g., of a type known in the art) to transmit data from device 200, e.g., to a programmer (not shown), and / or to receive data, e.g., programming, e.g., pulse parameters, from device 200.

[0155] FIG. 4B is a schematic diagram illustrating components of an implantable cardiac device 600, according to some embodiments.

[0156] In some embodiments, the device is configured to deliver cardiac electrical stimulation, e.g., cardiac contractility modulation stimulation. Optionally, the device is further configured to function as a cardioverter-defibrillator (ICD).

[0157] In some embodiments, the device includes an ICD lead 601 and a cardiac contractility regulation lead 603 .

[0158] In some embodiments, activation of the ICD leads is by an ICD module including or connected to an ICD control 605, a defibrillation pulse generator 607 (via one or more capacitors 609), a power source (e.g., a battery 613), and power management circuitry 615, and an ICD sense 611 that senses applied pulses and verifies pulses are within a selected (e.g., programmed) amplitude and / or duration range. In some embodiments, activation of one or more cardiac contractility regulation leads 621, 623, optionally located in the right ventricle, is by a cardiac contractility regulation module including or connected to a cardiac contractility regulation control 617, a cardiac contractility regulation generator 619.

[0159] It is noted that in some embodiments, the ICD coil and one or more electrodes for pacing and / or cardiac contractility regulation are configured in the same lead.

[0160] In some embodiments, the lead is connected to isolation 625 .

[0161] In some embodiments, the device includes a housekeeping module 627, which includes or is connected to one or more sensors, for example, a temperature sensor 629, a magnetic sensor 631, and a communication means 633 such as an antenna, a receiver, etc. Other sensors may include a flow sensor, a pressure sensor, an acceleration sensor, etc.

[0162] In some embodiments, data received from one or more sensors is received as input. Optionally, the input is processed by a device control (e.g., by an ICD control, a cardiac contractility control, and / or a general controller, not shown) and optionally used as input to a decision-making process in device 600.

[0163] In some embodiments, the device control (e.g., an ICD control, a cardiac contractility regulation control, and / or a general controller, not shown) implements one or more logic circuits for determining the timing and / or other parameters of the signal and / or whether the signal should be applied.

[0164] Memory (not shown) is optionally provided to store, for example, logic, past effects, treatment regimens, adverse events, and / or pulse parameters.

[0165] A data logger (not shown) is optionally provided to store device 600 and / or patient activity. Such logging and / or programming may use communications module 633 to transmit data from device 600, e.g., to a programmer (not shown), and / or to receive data, e.g., programming, e.g., pulse parameters.

[0166] FIG. 5A is a schematic illustration of an implantable device configured to apply cardiac electrical stimulation according to some embodiments.

[0167] In some embodiments, implantable device 501 includes a pulse generator 503. In some embodiments, 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 means, and / or an operating module.

[0168] In some embodiments, one or more stimulation leads, such as 505, 507, are connected to the housing and extend outwardly therefrom. In some embodiments, the leads include one or more electrical wires surrounded by an outer insulating layer. In some embodiments, the leads are comprised of two wires with opposite polarities. The wires of the leads are coiled.

[0169] In some embodiments, the pulse generator 503 is implanted outside the heart, for example, in the subclavian region. Optionally, implantation is via a minimally invasive procedure.

[0170] In some embodiments, the housing of the pulse generator 503 is implanted subcutaneously near the left chest.

[0171] In some embodiments, leads 505 and 507 extend from pulse generator 503, with at least distal segments of the leads implanted within 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.

[0172] Additionally or alternatively, it is known that a single lead containing two spatially separated stimulating electrodes may be used.

[0173] While the figure shows both leads positioned in the right ventricle 531 relative to the interventricular septum 515, it is understood that one or more stimulation leads may be in other locations, resulting in different circles of effect and / or targeting different tissues. In some embodiments, the leads are positioned inside the heart on its right side, optionally taking advantage of two potential advantages: (a) less tissue to stimulate outside the heart; and (b) less invasive access and presence than the left side of the heart.

[0174] In some embodiments, one of the leads is implanted outside the heart and the other lead is implanted inside the heart.

[0175] In some embodiments, each of the leads terminates in a tip electrode (see 517 for lead 507, 519 for lead 505), which may be configured as a contact electrode, a screw electrode, a suture electrode, a floating electrode, and / or other types.

[0176] In some embodiments, one or both of the leads includes a ring electrode (see 521 on lead 507, 523 on lead 505) located along the lead adjacent to the tip electrode.

[0177] In some embodiments, the electrode is implanted in the right ventricle or right atrium of the heart.

[0178] In some embodiments, the tip electrode is formed by threading it through tissue, or the tip electrode is simply placed in contact with tissue.

[0179] In some embodiments, one or both of the leads includes a defibrillation coil (see 525 on lead 505). Optionally, the coil 525 is placed along the lead adjacent to the tip electrode and / or adjacent to the ring electrode.

[0180] In some embodiments, the coil is implanted in the right ventricle, right atrium, or vena cava.

[0181] In some embodiments, one or both of the leads are configured to deliver a non-excitatory signal, such as, for example, a cardiac contractility modulation signal.

[0182] In some embodiments, the cardiac contractility modulating signal is applied in contact with or within ventricular tissue.

[0183] In some embodiments, the cardiac contractility modulating 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 enhance contractility of the ventricles of the heart when the electric field of the signal stimulates such ventricular tissue, e.g., the left ventricle, the right ventricle, and / or the ventricular septum. In some embodiments of the invention, contractility modulation is provided by signal-induced phosphorylation of phospholamban. In some embodiments of the invention, contractility modulation is caused by signal-induced changes in protein transcription and / or mRNA production, optionally in the form of reversal of a fetal genetic program. In some embodiments, it is known that the cardiac contractility modulating signal may be excitatory to tissues other than the tissue to which it is applied.

[0184] While not limited to a single pulse sequence, the term cardiac contractility modulation is used to describe any family of signals that have a clinically significant effect on cardiac contractility in an acute and / or chronic manner, including a significant component applied during the absolute refractory period, and / or that cause reversal of fetal genetic programming and / or increase phosphorylation of phospholamban. In some embodiments, the signal is potentially excitatory to one portion of the heart but non-excitatory to other portions. For example, the signal can be applied at a time that is excitatory in the atria but not excitatory in the ventricles (relative to ventricular activation).

[0185] In some embodiments of the invention, the signal is potentially excitatory during the receptive phase of the cardiac cycle, while being non-excitatory due to timing: in particular, the signal is applied during the refractory period of the tissue affected thereby, optionally within the absolute refractory period.

[0186] In some embodiments, the electrodes of the device, for example, the electrodes that apply cardiac contractility modulation, are used to measure the amplitude of the R wave and / or the RR interval of the cardiac cycle.

[0187] 5B is a schematic illustration of a cardiac device including multiple leads, according to some embodiments. In some embodiments, the device 5500 is configured to deliver cardiac contractility control stimuli to the heart. In some embodiments, the device 5500 is further configured to function as an cardioverter-defibrillator (ICD).

[0188] In some embodiments, the device 5500 includes multiple leads. In the example shown, a first lead 5510 extends to the right atrium of the heart 5516, e.g., for applying cardiac contractility modulation stimulation; a second lead 5511 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, e.g., via the coronary sinus. In some embodiments, one or more of the leads include a defibrillation coil. In this example, the lead 5512 includes a superior vena cava shock coil 3330 and a right ventricle shock coil 5532.

[0189] In some embodiments, multiple leads are connected via multiple ports (not shown) to the device housing 5520. In some embodiments, control of activation of one or more leads is via switch circuitry, for example, switch circuitry in a controller of the device.

[0190] The terms "comprises," "comprising," "includes," "including," "having," and their cognates mean "including but not limited to."

[0191] The term "consisting of" means "including and limited to."

[0192] The term "consisting essentially of" means that a composition, method, or structure may include additional components, steps, and / or moieties, but only if the additional components, steps, and / or moieties do not materially alter the basic and novel characteristics of the claimed composition, method, or structure.

[0193] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, the terms "a compound" or "at least one compound" may include multiple compounds, including mixtures thereof.

[0194] Throughout this application, embodiments of the present invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the present invention. Accordingly, a description of a range should be construed as including all specifically disclosed possible subranges, as well as individual numerical values ​​within that range. For example, a description of a range such as "1 to 6" should be construed as including specifically disclosed subranges, such as "1 to 3," "1 to 4," "1 to 5," "2 to 4," "2 to 6," "3 to 6," etc., as well as individual numerical values ​​within that range, e.g., 1, 2, 3, 4, 5, and 6. This applies regardless of fractional ranges.

[0195] Whenever a numerical range is given herein, it is intended to include any recited number (fractional or integer) within the indicated range. The expressions "ranging / ranges between" a first recited number and a second recited number, and "ranging / ranges from" a first recited number "to" a second recited number, are used interchangeably herein and are intended to include the first and second recited numbers and all decimal and integer numbers therebetween.

[0196] As used herein, the term "method" refers to ways, means, techniques and procedures for accomplishing a given task, including, but not limited to, ways, means, techniques and procedures known to or readily developed from known ways, means, techniques and procedures by the practitioner of the chemical, pharmacological, biological, biochemical and medical arts.

[0197] As used herein, the term "treating" includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating the clinical or cosmetic symptoms of a condition, or substantially preventing the appearance of clinical or cosmetic symptoms of a condition.

[0198] It is to be appreciated that certain features of the invention that are described for clarity in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, various features of the invention that are described for brevity in the context of a single embodiment may also be provided separately or in any suitable subcombination, or as preferred, in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be construed as essential features of those embodiments, unless the embodiment is inoperable without those elements.

[0199] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference in their entirety to the same extent as if each individual publication, patent, and patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application should not be construed as an admission that such reference is available as prior art to the present invention. To the extent section headings are used, they should not be construed as necessarily limiting. Additionally, the priority document(s) of this application are incorporated herein by reference in their entirety.

Claims

1. 1. A method for planning cardiac electrical stimulation therapy, comprising: a. defining a treatment plan by setting one or more parameters; b. defining one or more expected variabilities in cardiac activity that may affect said treatment plan; c. defining one or more alternative treatment regimens according to said one or more expected variabilities; and d. providing instructions for applying an alternative treatment plan from said one or more alternative treatment plans if an expected variability is identified from said one or more expected variabilities.

2. defining said treatment plan, a. selecting a total amount of energy to be delivered to the heart by cardiac electrical stimulation; b. i. the time during which cardiac electrical stimulation is to be applied to the heart, and ii. selecting one or both of a stimulation current intensity for each of the stimuli, the duration and the stimulation current intensity being selected to achieve the total amount of energy; The method of claim 1 , comprising:

3. The method of claim 1 , wherein the cardiac electrical stimulation comprises a cardiac contractility modulation stimulation.

4. 10. The method of claim 1, wherein the parameter is one or more of a ratio of stimulations, a strength of stimulation current, a duration of a treatment period, a total number of stimuli delivered, a total amount of stimulation energy delivered, and a timing of stimulations.

5. The method of claim 1 , wherein the parameters are selected according to a general therapeutic goal.

6. The method of claim 5 , wherein the therapy goal comprises one or more of a total number of cardiac electrical stimuli delivered to the heart and a total amount of cardiac electrical stimulation energy delivered to the heart.

7. The method of claim 1 , wherein the treatment plan is defined according to characteristics of the cardiac activity of the patient to be treated.

8. The method of claim 7 , wherein the cardiac activity characteristics include one or more of the patient's heart rate, stroke volume, and incidence of irregular cardiac events.

9. The method of claim 1 , wherein the treatment plan defines one or more conditions for applying cardiac electrical stimulation.

10. 10. The method of claim 9, wherein the one or more conditions for applying are that stimulation should be delivered when the heart rate is below and / or above a threshold and / or within a selected range.

11. 10. The method of claim 9, wherein the one or more conditions for applying is that the stimulus should be delivered when the patient is in a particular physical state.

12. 10. The method of claim 1, wherein defining the one or more alternative treatment plans takes into account that changes in parameters may have non-linear effects on the treatment itself.

13. The method of claim 1 , wherein defining one or more alternative treatment plans comprises defining multiple settings of parameters to achieve equivalent therapeutic effects.

14. 10. The method of claim 1, further comprising providing a look-up table containing parameter settings that result in equivalent therapeutic effects.

15. The method of claim 14 , wherein the parameter settings are interchangeable with the one or more parameters.

16. The method of claim 1 , wherein the one or more parameters are selected and / or calculated according to one or more additional treatment parameters.

17. The method of claim 1 , wherein the one or more parameters are selected and / or calculated according to a desired therapeutic effect.

18. The method of claim 1 , further comprising providing cardiac electrical stimulation therapy according to the therapy plan.

19. 20. The method of claim 18, further comprising providing an alternative treatment plan from the one or more alternative treatment plans if an expected variability is identified from the one or more expected variabilities.

20. The method of claim 1 , wherein the one or more expected variabilities are determined in real time.

21. The method of claim 1 , further comprising monitoring changes in the treatment regimen.

22. 21. The method of claim 20, wherein the one or more expected variabilities are determined by one or more sensors.

23. 10. The method of claim 1, wherein the one or more alternative treatment plans are configured to complement each other so as to reach a common treatment goal.

24. 24. The method of claim 23, wherein the compensating comprises one or more of updating one or more therapy parameters, updating a duration of a therapy period, updating a rate of cardiac electrical stimulation, updating a strength of a stimulation current, updating a number of activated electrodes, updating a time interval and / or number of beats between successive stimulations.

25. 10. An implantable device comprising one or more leads for delivering cardiac electrical stimulation and a controller configured to control stimulation via the leads, the controller configured to perform the method of claim 1.

26. 26. The device of claim 25, wherein the controller is configured to automatically update one or more therapy parameters in response to variability in the therapy plan due to actual cardiac activity.

27. 26. The device of claim 25, wherein the controller is programmed with one or more therapy plans and one or more "fallback" instructions for updating therapy parameters when therapy is being delivered and changes due to actual cardiac activity.

28. 28. The device of claim 27, wherein the "fallback" instructions include one or more of: extending the duration of the therapy period if the number of actual delivered stimuli is less than a set number of stimuli; increasing the intensity of the stimulation current if the total amount of delivered energy is less than a set amount of delivered energy; increasing the rate of cardiac electrical stimulation if the time for the therapy period is almost up but the actual delivered stimuli are not sufficient; and updating a heart rate threshold for the application of stimulation if the actual heart rate over the therapy period is not within a defined heart rate range for the delivery of stimuli.

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