Implantable Pulse Generator Lead Positioning

Abstract

The cardiac signal processing method includes receiving measurements from at least two electrodes positioned within the heart, determining a relative positioning of the at least two electrodes with respect to one another using the measurements, and evaluating a suitability of the relative positioning of the at least two electrodes for measuring cardiac activity to determine which cardiac cycles should receive cardiac contractility modulation stimulation.

Description

[Technical field]

[0001] This application claims the benefit of priority under 119(e) to U.S. Provisional Application No. 63 / 167,192, filed March 29, 2021, and entitled “LEAD POSITIONING FOR AN IMPLANTABLE PULSE GENERATOR,” the disclosure of which is incorporated herein by reference.

[0002] The present invention, in some embodiments thereof, relates to a device for cardiac stimulation, and more particularly, but not exclusively, to the positioning of electrodes of the device for cardiac simulation. [Background technology]

[0003] Background art includes International Patent Application Publication No. WO2020 / 152619, the contents of which are incorporated by reference as if set forth in their entirety herein. Summary of the Invention [Means for solving the problem]

[0004] Below is a non-exhaustive list including some example embodiments of the present invention. The present invention also includes embodiments including less than all features of an example, and embodiments that use features from more than one example, even if not explicitly listed below.

[0005] Example 1. A method of cardiac stimulation comprising: receiving measurements from at least two electrodes positioned within the heart; designating a first electrode of the at least two electrodes and a second electrode of the at least two electrodes from the measurements; applying a cardiac contractility modulation stimulus to the heart when a ventricular event is detected at the first electrode and then, after a suitable time delay, at the second electrode.

[0006] This method and the following methods may be performed using a controller appropriately configured (eg, using circuitry and / or software) to perform these methods.

[0007] Example 2. The method of Example 1, wherein the designating includes monitoring the measurement value for a plurality of cardiac cycles and designating as the first electrode an electrode of the at least two electrodes that first senses a ventricular event in a majority of the cardiac cycles.

[0008] Example 3. The method of any one of Examples 1 or 2, wherein the measurements include cardiac electrical measurement signals from the at least two electrodes positioned on the right ventricular septum.

[0009] Example 4. The method of any one of Examples 1-3, wherein the specifying includes determining from the measurements a timing of arrival of a cardiac action potential wavefront at the at least two electrodes.

[0010] Example 5. The method of any one of Examples 1 to 3, wherein the at least two electrodes include first and second electrodes disposed on a partition and at least one additional electrode, and the measurements include measurements of the electrical potential at each of the first electrode and the second electrode relative to the additional electrode.

[0011] Example 6. The method of any one of Examples 1 to 5, wherein the delay is at least 1 ms and at most 4 ms.

[0012] In any of the above embodiments, the method may include generating an alert if the delay is not within a desired range.

[0013] In any of the above embodiments, the method may include performing impedance measurements at and / or between the two electrodes.

[0014] In any of the above embodiments, the method may include performing the applying on both of the electrodes with overlap in time.

[0015] In any of the above embodiments, the method may include performing the applying on both of the electrodes in the same cardiac cycle with at least some overlap in time.

[0016] Example 7. A monitoring method comprising: monitoring over time the time difference between arrival of a cardiac action potential wavefront at two electrodes, each placed at a different point on the heart; Based on said monitoring, assigning relative positions of the two electrodes based on the time difference to determine which cardiac cycles should receive cardiac contractility modulation stimulation; and and optionally, but not necessarily, diagnosing a cardiac condition.

[0017] Example 8. The method of example 7, wherein the two electrodes are each positioned at a different point on the cardiac septum.

[0018] Example 9. The monitoring comprises: receiving cardiac electrical measurement signals from the two electrodes; Identifying the timing at which a myocardial action potential wavefront arrives at each of the two electrodes from the measurement signal; determining a time difference between arrival of the cardiac action potential wavefront at the two electrodes for a plurality of cardiac cycles; A method according to any one of claims 7 to 8, comprising: generating a statistical representation of the time differences from the time differences determined for the plurality of cardiac cycles.

[0019] Example 10. The method of example 7, wherein said determining includes determining a sign of said time difference.

[0020] Example 11. The method of example 9, wherein the statistical representation includes a tendency for which of the two electrodes to sense the myocardial action potential wavefront first.

[0021] Example 12. The method of any one of Examples 7 to 11, wherein the designating includes designating the electrode at which the majority of wavefronts are first sensed as the electrode proximal to the atrioventricular node.

[0022] Example 13 The method of Example 9, wherein said diagnosing comprises comparing said statistical representation to a threshold value.

[0023] Example 14. A method comprising receiving heart rate measurements for the plurality of cardiac cycles, The method of any one of Examples 9 to 13, wherein the generating step includes generating a statistical representation of the time difference relative to heart rate.

[0024] Example 15. The method of Example 14, wherein if the statistical representation indicates an increase in time difference variance with increasing heart rate, then diagnosing comprises diagnosing the possibility of inducible ischemia.

[0025] Example 16. The method of example 15, wherein the increase in heart rate comprises a statistical representation of the time difference of the heart rate exceeding a threshold heart rate.

[0026] Example 17. The method of Example 14, wherein if the statistical representation indicates an increase in variability in the time differences of one or more heart rates, the diagnosing comprises diagnosing a possible cardiac arrhythmia.

[0027] Example 18. The method of any one of Examples 9 to 17, wherein the statistical representation of the time difference is the median of the time difference over a period of time.

[0028] Example 19. The method of example 18, wherein a lead misalignment is identified if the median value deviates by more than a threshold value for a period of less than 1 minute.

[0029] Example 20. A method of cardiac signal processing of electrodes pre-positioned to optionally extend into the heart, comprising: receiving measurements from at least two electrodes positioned within the heart; using the measurements to determine a relative positioning of the at least two electrodes with respect to one another; and evaluating the suitability of the relative positioning of the at least two electrodes for measuring cardiac activity to determine which cardiac cycles should receive cardiac contractility modulation stimulation.

[0030] Example 21 The method of example 20, wherein said evaluating comprises generating a signal indicating whether one or more of said electrodes should be repositioned or fixed in place.

[0031] Example 22. The method of example 20, wherein the measurements include cardiac electrical measurement signals from the at least two electrodes positioned on the right ventricular septum.

[0032] Example 23. The method of any one of Examples 20 to 22, wherein the determining includes identifying a timing of passage of a myocardial action potential wavefront from the measurement signal.

[0033] Example 24 The method of example 23, wherein the wavefront is an intraseptal myocardial action potential wavefront.

[0034] Example 25. The at least two electrodes include a first electrode and a second electrode, 25. The method of example 24, wherein the determining includes determining a delay between detection of the wavefront at the first electrode and detection of the wavefront at the second electrode.

[0035] Example 26. The method of example 25, wherein said evaluating includes evaluating said delay, and said delay is deemed to indicate proper positioning if said delay is at least 1 ms and at most 4 ms.

[0036] Example 27. The method of any one of Examples 20 to 26, wherein said evaluating comprises determining, with respect to said relative positioning, a proportion of the cardiac cycle suitable for receiving cardiac contractility modulation stimulation.

[0037] Example 28. The method of any one of Examples 20 to 27, wherein said evaluating comprises evaluating a proportion of abnormal cardiac cycles determined to be suitable for receiving cardiac contractility modulation stimulation.

[0038] Example 29. The method of Example 28, wherein the signal indicates that the electrode should be repositioned if the percentage of abnormal cardiac cycles determined to be suitable for receiving cardiac contractility modulation stimulation exceeds 5% of cardiac cycles.

[0039] Example 30. The method of any one of Examples 20 to 29, wherein said evaluating comprises evaluating a proportion of normal cardiac cycles that are determined to be unsuitable for receiving cardiac contractility modulation stimulation.

[0040] Example 31. The method of Example 30, wherein the signal indicates that the electrode should be repositioned if the proportion of normal cardiac cycles not determined to be suitable for receiving cardiac contractility modulation stimulation exceeds 20% of the cardiac cycle.

[0041] Example 32. The method of any one of Examples 27 to 31, wherein said determining the percentage of the cardiac cycle suitable for undergoing cardiac contractility modulation is based on said measurements.

[0042] Example 33. The method of any one of Examples 20 to 32, wherein the at least two electrodes include first and second electrodes disposed on a partition and at least one additional electrode, and the measurements include measurements of the potential at each of the first electrode and the second electrode relative to the additional electrode.

[0043] Example 34. The method of any one of Examples 20 to 33, wherein the measurements relate to a plurality of cardiac cycles.

[0044] Example 35. The method of any one of Examples 20 to 34, wherein the measurements include measurements taken while the heart is stimulated.

[0045] Example 36. The method according to any one of Examples 20 to 35, Based on the evaluation, repositioning one or more of the at least two electrodes; and and fixing the one or more of the at least two electrodes.

[0046] Example 37. The receiving is performed multiple times to determine multiple delays; 37. The method of example 36, wherein the evaluating comprises determining a statistical representation of the delay.

[0047] Example 38. The method of Example 37, wherein the statistical representation of the delay is the median of the plurality of delays.

[0048] Example 39. The method of any one of Examples 37-38, wherein the evaluating comprises comparing the statistical representation to a threshold value.

[0049] Example 40. The method of any one of Examples 20 to 39, wherein the determining includes determining tissue impedance between the at least two electrodes.

[0050] Example 41. The method of claim 1, wherein the determining step comprises injecting an electrical stimulation pulse. the measurements include electrical signals affected by the stimulation pulses; and The method of any one of Examples 20 to 40, wherein the determining includes determining one or more parameters from the electrical signal that are affected by the stimulation pulse.

[0051] Example 42 The method of Example 41, wherein the injecting is during a refractory period of the cardiac cycle of the heart.

[0052] Example 43. The method of any one of Examples 41-42, wherein the injecting is between the at least two electrodes.

[0053] Example 44. A device for applying cardiac contractility modulation stimuli to a heart, comprising: At least two electrodes; and a circuit, the circuit comprising: determining a relative positioning of the electrodes using measurements collected at the electrodes; and determining when to apply a cardiac contractility modulation stimulus to the electrodes based on the location.

[0054] Example 45. A first lead, The second lead, Equipped with The at least two electrodes are a first electrode and a second electrode hosted by the first lead; The device of Example 44, comprising four electrodes including a third electrode and a fourth electrode hosted by the second lead.

[0055] Example 46. The device described in Example 45, wherein the first and third electrodes are configured to be attached to the septum of the heart.

[0056] Example 47. A system for cardiac stimulation, comprising: An apparatus according to example 44, a circuit configured to evaluate the suitability of the relative positioning of the at least two electrodes for measuring cardiac activity to determine which cardiac cycles should receive cardiac contractility modulation stimulation; a user interface, coupled to the circuitry, configured to transmit the compatibility to a user.

[0057] Example 48. A method for cardiac signal processing, comprising: receiving measurements from at least two electrodes, optionally pre-placed within the heart; determining a position of the at least two electrodes within the heart using the measurements; and and evaluating the suitability of the positioning of the at least two electrodes for measurement of cardiac activity to determine which cardiac cycles should receive cardiac contractility modulation stimulation.

[0058] Example 49. The method of Example 48, wherein the determining includes identifying a timing of passage of a myocardial action potential wavefront from the measurement signal.

[0059] Example 50. The method of example 49, wherein the determining includes determining a delay between detection of the myocardial action potential wavefront between a first electrode of the at least two electrodes and a second electrode of the at least two electrodes.

[0060] Example 51. The method of example 50, wherein said evaluating comprises evaluating said delay.

[0061] Example 52. A monitoring method comprising: monitoring over time the time difference between arrival of a cardiac action potential wavefront at two electrodes, each placed at a different point on the heart; and identifying electrode dislodgment based on the monitoring.

[0062] Example 53. A method of cardiac signal processing, optionally performed using a system comprising a circuit (optionally implantable) and at least two electrodes in the heart and configured to perform the method, injecting electrical stimulation pulses into a first electrode positioned within the heart; receiving a measurement of an electrical signal affected by the stimulation pulse from a second electrode positioned within the heart; and using the measurements to determine a relative positioning of the first electrode and the second electrode.

[0063] Example 54. A method of cardiac signal processing as described in Example 53, comprising evaluating the suitability of the relative positioning of the first electrode and the second electrode for measuring cardiac activity to determine which cardiac cycles should receive cardiac contractility modulation stimulation.

[0064] Example 55. The measurement includes a measurement pulse. 55. The method of example 54, wherein the determining comprises determining a change in amplitude between the injection pulse and the measurement pulse.

[0065] Example 56 The method of any one of Examples 53-55, wherein the injecting is during a refractory period of the cardiac cycle.

[0066] Example 57. The method of any one of Examples 53-54, wherein the injecting is during a portion of the cardiac cycle that is different from the refractory period.

[0067] Example 58. The method of example 57, wherein the determining includes determining a delay between injecting the pulse and measuring the pulse.

[0068] 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 belongs. Although methods and materials similar or equivalent to those described herein can be used to practice or test embodiments of the present invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. Additionally, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0069] Implementation of the method and / or system of the present invention may include performing or completing selected tasks manually, automatically, or a combination thereof. Further, depending on the actual instrumentation and installation of the method and / or system of the present invention, some selected tasks may be performed by hardware, software, or firmware using an operating system, or a combination thereof.

[0070] 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 number of software instructions executed by a computer using any suitable operating system. In an exemplary embodiment 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 computing platform for executing a number of instructions. Optionally, the data processor includes volatile memory for storing instructions and / or data, and / or non-volatile storage, e.g., a magnetic hard disk and / or a removable medium, for storing instructions and / or data. Optionally, a network connection is also provided. A display and / or a user input device, such as a keyboard or mouse, are also optionally provided.

[0071] As will be appreciated by those skilled in the art, some embodiments of the present invention may be embodied as a system, method, or computer program product. Accordingly, some embodiments of the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, microcode, etc.), or an embodiment combining software and hardware aspects, all of which may be generally referred to herein as a "circuit," "module," or "system." Furthermore, some embodiments of the present invention may take the form of a computer program product embodied in one or more computer readable mediums having computer readable program code embodied therein. Implementation of the method and / or system of some embodiments of the present invention may include performing and / or completing selected tasks manually, automatically, or a combination thereof. Furthermore, depending on the actual instrumentation and equipment of some embodiments of the method and / or system of the present invention, some selected tasks may be implemented by hardware, software, or firmware, and / or a combination thereof, for example using an operating system.

[0072] For example, hardware for performing selected tasks according to some embodiments of the present invention may be implemented as a chip or circuit. As software, selected tasks according to some embodiments of the present invention may be implemented as a number of software instructions executed by a computer using any suitable operating system. In an exemplary embodiment of the present invention, one or more tasks according to some exemplary embodiments of the methods and / or systems described herein are performed by a data processor, such as a computing platform for executing a number of instructions. Optionally, the data processor includes volatile memory for storing instructions and / or data, and / or non-volatile storage, e.g., a magnetic hard disk and / or a removable medium, for storing instructions and / or data. Optionally, a network connection is also provided. A display and / or a user input device, such as a keyboard or mouse, are also optionally provided.

[0073] Any combination of one or more computer readable media may be utilized in some embodiments of the present invention. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. The computer readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination thereof. More specific examples (non-exhaustive list) of computer readable storage media may include an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read only memory (ROM), an electrically erasable read only memory (EPROM or flash memory), an optical fiber, a portable compact disk read only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination thereof. In the context of this document, a computer readable storage medium may be any tangible medium that can contain or store a program for use by or in connection with an instruction execution system, apparatus, or device.

[0074] A computer-readable signal medium may include a propagated data signal in which computer-readable program code is embodied, for example, in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including, but not limited to, electromagnetic, optical, or any combination thereof. A computer-readable signal medium is not a computer-readable storage medium, but may be any computer-readable medium that can communicate, propagate, or carry a program for use by or in connection with an instruction execution system, apparatus, or device.

[0075] Program code embodied on a computer readable storage medium and / or data used thereby may be transmitted using any suitable medium, including but not limited to wireless, wired, fiber optic cable, RF, etc., or any suitable combination thereof.

[0076] Computer program code for carrying out operations for some embodiments of the present invention may be written in any combination of one or more programming languages, including object-oriented programming languages ​​such as Java, Smalltalk, C++, and the like, as well as conventional procedural programming languages ​​such as the "C" programming language or similar programming languages. The program code may run entirely on the user's computer, as a stand-alone software package, partially on the user's computer, partially on the user's computer and partially on a remote computer, or entirely on a remote computer or server. In the latter scenario, the remote computer may be connected to the user's computer via any type of network, including a local area network (LAN) or a wide area network (WAN), or may be connected to an external computer (e.g., via the Internet using an Internet Service Provider).

[0077] Some embodiments of the present invention are described below with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the present invention. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to create a machine such that the instructions, executed via the processor of the computer or other programmable data processing apparatus, create means for performing the function / act specified in the block(s) of the flowchart illustrations and / or block diagrams.

[0078] These computer program instructions, which can instruct a computer, other programmable data processing apparatus, or other device to function in a particular manner, may be stored on a computer-readable medium, such that the instructions stored on the computer-readable medium produce an article of manufacture including instructions that implement the function / act specified in the flowchart and / or block diagram block(s).

[0079] Computer program instructions may be loaded onto a computer, other programmable data processing apparatus, or other device to cause a series of operational steps to be executed on the computer, other programmable apparatus, or other device, creating a computer-implemented process, such that the instructions executing on the computer or other programmable apparatus provide a process for performing the functions / acts specified in the flowchart and / or block diagram block(s).

[0080] Some of the methods described herein are generally designed for computational use only and may not be feasible or practical to be performed entirely manually by a human expert. A human expert wishing to manually perform a similar task, such as collecting cardiac measurements, would be expected to use an entirely different method, e.g., a method that utilizes specialized knowledge and / or the pattern recognition capabilities of the human brain, which is much more efficient than performing the steps of the methods described herein manually.

[0081] Some embodiments of the present invention are herein described, by way of example only, with reference to the accompanying drawings, in which specific reference is made in detail, stressing that the particulars shown are for the purpose of illustrating and discussing embodiments of the invention by way of example, and in this regard the description taken with the aid of the drawings will make apparent to those skilled in the art how embodiments of the invention may be practiced. [Brief description of the drawings]

[0082] [Figure 1]1 is a simplified schematic diagram of a system for cardiac stimulation, according to some embodiments of the present invention. [Diagram 2] 1 is a method of assessing electrode position according to some embodiments of the present invention. [Diagram 3] 1A is a method of controlling an implantable pulse generator according to some embodiments of the present invention, and FIG. 1B is a schematic representation of the operation of a method of controlling an implantable pulse generator according to some embodiments of the present invention. [Figure 4] 1 is a method of applying cardiac contractility modulation stimulation, according to some embodiments of the present invention. [Diagram 5] A is a method of electrode selection for implementing a method of controlling an implantable pulse generator according to some embodiments of the present invention, and B is a method of monitoring according to some embodiments of the present invention. [Figure 6] 5A-D are schematic illustrations of identifying conduction patterns through the interventricular septum 636, according to some embodiments of the present invention. [Figure 7] 5A-D are simplified schematic diagrams of sensing of cardiac conduction wavefronts according to some embodiments of the present invention, and FIG. 5E is a simplified schematic diagram of a timeline of sensed ventricular events according to some embodiments of the present invention. [Figure 8] 5A-D are simplified schematic diagrams of sensing of cardiac conduction wavefronts according to some embodiments of the present invention, and FIG. 5E is a simplified schematic diagram of timing of sensed ventricular events according to some embodiments of the present invention. [Figure 9] FIG. 13 is a schematic diagram of three sensor identification of conduction patterns passing through the interventricular septum according to some embodiments of the present invention. [Figure 10] 1 is a simplified schematic diagram illustrating stimulus and measurement signals according to some embodiments of the present invention. FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0083] The present invention, in some embodiments thereof, relates to a device for cardiac stimulation, and more particularly, but not exclusively, to the positioning of electrodes of the device for cardiac simulation.

[0084] overview A broad aspect of some embodiments of the present invention relates to determining the positioning of electrodes for sensing cardiac electrical activity within the heart using measurements collected using the electrodes themselves.

[0085] In some embodiments, sensing of cardiac electrical activity by electrodes is used to determine (e.g., on a cycle-by-cycle basis) which cardiac cycles receive cardiac contractility modulation (CCM) stimulation, where in some embodiments CCM is applied septally, for example, between two electrodes positioned (e.g., fixed) on the septum. Additionally and optionally, in some embodiments, sensing of cardiac electrical activity by electrodes is used to determine when implantable cardioverter defibrillator (ICD) simulation and / or cardiac resynchronization therapy (CRT) stimulation is applied.

[0086] In some embodiments, assumed and / or determined electrical cardiac signal propagation for a normal (e.g., non-arrhythmic) cardiac cycle is used in conjunction with measurements of cardiac electrical activity collected at the electrodes to determine the location of the electrodes.

[0087] Here, in some embodiments, the measurement of cardiac electrical activity includes the relative timing of arrival of a cardiac conduction wavefront between a first measurement location and a second measurement location.

[0088] Wherein, in some embodiments, measurements at a first measurement location are collected using a first electrode pair, a first electrode of the first electrode pair being disposed at the first measurement location and a second electrode of the first electrode pair being disposed away from the first measurement location, and where in some embodiments, measurements at a second measurement location are collected using a second electrode pair, a first electrode of the second electrode pair being disposed at a second measurement location and a second electrode of the second electrode pair being disposed away from the first electrode of the second electrode pair.

[0089] In some embodiments, the first electrodes of both electrode pairs are connected (e.g., fixed to) the septum, e.g., in contact with the cardiac septum. In some embodiments, the first electrodes of both pairs are each hosted by a different cardiac lead. In some embodiments, the second electrodes are hosted by one or more leads separate from the first electrodes, e.g., the second electrodes are positioned within a heart chamber, e.g., within the right ventricle (RV).

[0090] In some embodiments, there is a single second electrode, e.g., measurements at the first electrode of the first pair and measurements at the first electrode of the second pair are both to a single second electrode, in some embodiments, each lead hosts a second electrode, where in some embodiments measurements at each first electrode are to a second electrode hosted by the same lead as the first electrode.

[0091] In some embodiments, cardiac contractility modulation stimulation is applied to the heart when a cardiac conduction wavefront is detected at a first electrode and then at a second electrode, hi some embodiments, stimulation is applied when there is a sufficient delay between detection at the first electrode and the second electrode.

[0092] An aspect of some embodiments of the invention relates to when two electrodes are placed in the heart, using measurements collected at the electrodes themselves to designate which electrode is considered to be the first electrode and which electrode is considered to be the second electrode. For example, in some embodiments, when placed, the first electrode that detects the cardiac conduction wavefront is designated to be the first electrode, and only those cardiac cycles in which the cardiac conduction wavefront is detected at the second electrode after the first electrode (e.g., with an appropriate time delay) will receive cardiac contractility modulation stimulation.

[0093] In some embodiments, an electrode designation is given based on a statistical analysis of which electrode senses the cardiac conduction wavefront first. For example, in some embodiments, the electrode that detects the cardiac conduction wavefront first in a majority of cardiac cycles in a given period is designated as the first electrode.

[0094] In some embodiments, characteristic(s) of electrical cardiac signal propagation of a normal cardiac cycle are determined using the electrodes, where in some embodiments multiple measurements are used to provide a statistical understanding of what constitutes normal propagation and / or the expected prevalence of a normal cardiac cycle.

[0095] In some embodiments, a single set of measurements collected at the electrodes is used to determine both the location of the electrodes and the characteristic(s) of the subject's cardiac cycle(s).

[0096] In some embodiments, the position of the electrodes and / or leads is determined by providing electrical stimulation at one electrode (and / or between another electrode pair) while the effect(s) of the stimulation are sensed at another electrode (and / or between another electrode pair). Optionally, in some embodiments, the same electrodes used to sense the cardiac conduction wavefront are used for the impedance measurement(s).

[0097] For example, in some embodiments, the distance between the electrodes is determined from tissue impedance measurement(s), which in some embodiments is measured between electrodes (e.g., between two electrodes) proximal to and / or coupled to and / or fixed to and / or embedded in the cardiac tissue.

[0098] In some embodiments, stimulation and measurement use a single electrode pair, with the simulation injected at one electrode and measured at the other. In some embodiments, tissue impedance measurements are collected using two pairs of electrodes, where electrical stimulation is delivered between a first pair of electrodes and measurement is made between a second pair of electrodes. In some embodiments, the measurement electrode pair is formed by an electrode proximal (e.g., attached, e.g., fixed) to cardiac tissue, e.g., septal tissue. In some embodiments, the measurement electrode pair is hosted by two leads, each lead hosting a measurement electrode, e.g., at the lead tip.

[0099] In some embodiments, impedance measurements are collected by injecting an electrical stimulation pulse between the electrodes of a stimulation electrode pair and measuring the decrease in amplitude of the pulse.

[0100] In some embodiments, the distance between the electrodes is determined by measuring the action potential travel time between the electrodes, for example, by stimulating cardiac tissue and then measuring the time of the resulting electrical activity associated with ventricular contractility detected at one or more other electrodes. Optionally, in some embodiments, the same electrodes used for the action potential measurement(s) are used as are used for sensing the cardiac conduction wavefront and / or impedance.

[0101] For example, in some embodiments, stimulation is provided between a pair of stimulation electrodes and action potentials are measured between a pair of measurement electrodes, where in some embodiments each electrode of the measurement pair is connected to a different region of the septum.

[0102] In some embodiments, measurements of tissue impedance and action potential travel speed are collected using the same applied stimulus (e.g., stimulation pulse), e.g., taking advantage of the potentially faster speed of tissue conduction than cell-to-cell activation travel of action potentials in cardiac tissue. For example, in some embodiments, after a stimulation pulse, a first pulse detected at a measurement electrode pair is used to determine tissue impedance and a second pulse detected is used to indicate action potential travel time. Certain aspects of some embodiments of the invention relate to positioning electrodes for sensing cardiac electrical activity in the heart using position feedback determined from electrode measurements, e.g., upon placement of a cardiac stimulator. In some embodiments, positioning of the electrodes is performed by positioning the lead(s) hosting the electrodes.

[0103] In some embodiments, an electrode lead is introduced into the heart, the position of the electrode is determined using electrode measurements, the determined position is then evaluated, and the evaluation indicates that the lead should be repositioned and / or that the position of the lead should be maintained, e.g., by fixation.

[0104] In some embodiments, positioning the electrode leads using measurement feedback minimizes the likelihood that cardiac electrical measurements collected using the leads will indicate, for example, cardiac cycle abnormalities and / or failure to detect the arrival of a cardiac conduction wavefront at one or more electrodes, generating an indication that cardiac contractility modulation stimulation should be inhibited.

[0105] For example, in an exemplary embodiment, the positions of the first and second electrodes are selected to provide sensing of the cardiac conducted wavefront at both electrodes, where one of the two electrodes senses the wavefront before the other, with a sufficient delay between sensing of the wavefront.

[0106] In some embodiments, positioning of electrodes, for example during lead placement, is an iterative process in which electrodes are placed and / or measurements are taken repeatedly until a desired location is reached, where in some embodiments the desired location is defined by the timing of cardiac wavefront sensing and / or the occurrence of an indication that cardiac contractility modulation stimulation should be inhibited.

[0107] In some embodiments, electrodes are positioned and repositioned until a maximum delay is located, hi some embodiments, electrodes are repositioned until the delay exceeds a threshold duration (and / or is within an acceptable range).

[0108] An aspect of some embodiments of the present invention relates to monitoring electrode lead positioning and / or cardiac health using measurements collected on the leads.

[0109] In some embodiments, the cardiac cycle measurements are monitored, for example for changes over time. In some embodiments, the change(s) are then evaluated to provide an indication of a change in cardiac behavior and / or a change in lead position (e.g., dislodgment). In some embodiments, the evaluation includes collecting additional measurements.

[0110] In some embodiments, the relative timing between detected cardiac wavefront arrivals at different electrode locations (e.g., the delay between cardiac wavefront arrivals) is monitored, where in some embodiments the delay is monitored by heart rate.

[0111] In some embodiments, one or more statistical representations of the delay (eg, the average) are monitored.

[0112] In some embodiments, if the delay and / or statistical representation of the delay is outside of normal ranges, lead dislodgement and / or a cardiac condition is diagnosed. In some embodiments, the normal ranges can be tailored to individual patients, for example, in subjects with pre-existing cardiac dysfunction(s), to enable tracking of changes in cardiac behavior and / or health.

[0113] In some embodiments, the median delay between detected cardiac wavefronts is monitored. In some embodiments, changes in the median delay, for example outside of a threshold and / or acceptable range, are used to diagnose changes in the subject's cardiac health. The median delay can be used to indicate changes in cardiac behavior. For example, even in subjects suffering from arrhythmia, the predicted incidence of arrhythmic cycles is less than 20%.

[0114] In some embodiments, the rapidity of change in time delay (and / or statistical representation of the time delay) is monitored, for example where in some embodiments rapid changes in time delay and / or statistical representation of the time delay (e.g., average time delay) are used to identify lead dislodgment, while in some embodiments more gradual changes are used to predict changes in cardiac behavior.

[0115] In some embodiments, the delay itself is used to identify lead dislodgment and / or optionally diagnose cardiac behavior, where the delay (and / or a statistical representation of the delay) is evaluated with heart rate (e.g., average delay for different ranges or heart rates). Alternatively or additionally, in some embodiments, how the delay varies is used to identify lead dislodgment and / or diagnose cardiac behavior.

[0116] In some embodiments, induced ischemia is associated with an increase in the variability of delay between detected cardiac wavefronts when the heart rate increases, for example above a threshold value.

[0117] In an exemplary embodiment, the possibility of inducible ischemia is diagnosed if a statistical representation of the time difference between detected cardiac conduction wavefronts (eg, median time difference) increases with heart rate (eg, above a threshold value).

[0118] An aspect of some embodiments of the invention relates to determining the distance between electrodes placed in the heart, e.g., the relative distance between the electrodes, by injection of a stimulation pulse between the electrodes. In some embodiments, the electrodes are placed (e.g., fixed) on the septum of the heart. In some embodiments, the stimulation pulse is applied at a first electrode and measured at a second electrode. In some embodiments, the pulse is applied, e.g., during a refractory period of the cardiac cycle of the heart to generate a measurement pulse (e.g., at the second electrode), and the decrease in amplitude at the second electrode is used to determine the distance between the electrodes. Alternatively or additionally, the stimulation pulse is applied at a time not during the refractory period of the cardiac cycle to stimulate a second measurement pulse of stimulated myocardial action potential in tissue between the electrodes, and in some embodiments, the measurement (e.g., delay between stimulation and detection of the measurement pulse) is used to determine the distance and / or relative positioning between the electrodes (e.g., the simulation electrode and the measurement electrode).

[0119] 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 of construction and the arrangement of components and / or methods 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.

[0120] Exemplary System FIG. 1 is a simplified schematic diagram of a system 100 for cardiac stimulation, according to some embodiments of the present invention.

[0121] In some embodiments, system 100 is a system for applying contractility modulation. Additionally or alternatively, in some embodiments, system 100 is configured to apply other type(s) of cardiac stimulation, such as pacing.

[0122] In some embodiments, the system 100 is configured to collect cardiac conduction wavefront measurements from at least two points within the heart 116, for example within the right ventricle RV of the heart 116. In an exemplary embodiment, measurements of the cardiac wavefront passing through the septum 136 are collected.

[0123] In some embodiments, measurements are collected using at least two electrodes. In an exemplary embodiment, bipolar measurements are collected using at least two electrode sets, where, for example, for each set, measurements are taken between a first electrode and a second electrode. In some embodiments, each set has a respective first electrode 103, 105 and a respective second electrode 106, 110. In an exemplary embodiment, the first lead 102 hosts the first electrode 103 and the second electrode 106 of the first electrode set, and the second lead 104 hosts the first electrode 105 and the second electrode 110 of the second electrode set. Alternatively, in some embodiments, the number of second electrodes is less than the number of first electrodes.

[0124] In some embodiments, a "bipolar electrode" is used to collect measurements where the bipolar electrode includes a first and a second electrode, e.g., as described elsewhere herein, e.g., on a single lead, e.g., one electrode (e.g., the "first electrode") is in contact with the tissue being measured and the other electrode (e.g., the "second electrode") is remote from the tissue being measured.

[0125] In the exemplary embodiment, the electrodes 103, 105 are ring electrodes.

[0126] In an exemplary embodiment, the electrode set or sets include a first electrode 106, 110 in contact with and / or in close proximity to the septum 136, and a second electrode 103, 105 of the set is located at a distance from the first electrode, for example, in the right ventricle. In some embodiments, one or both of the leads 102, 104 extend into the right ventricle through the same blood vessel (e.g., the superior vena cava). In some embodiments, the first electrodes 106, 110 of the set or sets are disposed at the distal portions of the first lead 102 and the second lead 104. In some embodiments, the second electrodes 103, 105 of the set or sets are hosted in the body portions of the leads 102, 104, respectively.

[0127] Optionally, in some embodiments, one or more of the electrodes 103, 105, 106, 110 are configured to deliver electrical energy to the heart (e.g., to measure the distance between the electrodes including one or more features as shown and / or described in connection with one or more of steps 406, 407, 408 of FIG. 4, etc.).

[0128] In some embodiments, one or both of the right ventricular leads 102, 104 include anchors 106a, 110a, respectively, where in some embodiments the anchors 106, 110 are designed to hold the leads 102, 104 to the heart tissue and position the electrodes 103, 105 in the RV. The anchors 106a, 110a are configured, for example, to secure the leads 102, 104 to the septum 136 of the heart 116. In some embodiments, one or more distal ends of the leads 102, 104 and / or anchors 105, 110 include a conductive material, which in some embodiments is used as a measurement electrode 106, 110 (e.g., as described with respect to step 412 of FIG. 4).

[0129] In some embodiments, therapeutic current delivery (e.g., cardiac contractility modulation) is applied to one or more electrodes in the heart, e.g., at one or more electrodes 106, 110 (e.g., interelectrode) positioned (e.g., fixed) on the septum 136. Note that therapeutic current delivery is optionally provided during the relative and / or absolute refractory period. Optionally or additionally, the current is configured to induce cardiac remodeling, e.g., by altering and / or reversing the fetal genetic program of the heart with heart failure. Such therapeutic signals may be applied, e.g., using the "Optimizer® Smart" implantable device sold by Impulse Dynamics, Inc., Marlton, New Jersey, USA.

[0130] In some embodiments, therapeutic current delivery (e.g., cardiac contractility modulation) is applied in one or more leads within the heart, such as in one or more leads 102, 104, via one or more bipolar electrode sets, such as a set including electrodes 103 and 106, and / or a set including electrodes 105 and 110.

[0131] Alternatively or additionally, in some embodiments, the system 100 includes one or more elements 108 for therapeutic current delivery (e.g., implantable cardioverter defibrillator (ICD) simulation and / or cardiac resynchronization therapy (CRT) stimulation) to the heart 116, such as a shocking coil 108. In an exemplary embodiment, the shocking coil 108 is hosted by the second lead 104. In some embodiments, the shocking coil 108 is disposed on the second lead 104 such that when the second electrode 105 is positioned at a desired location and / or when the second lead 104 is secured to the septum 136, the shocking coil 108 is disposed at least partially within the RV. In some embodiments, the shocking coil 108 is long enough to extend into the right atrium (RA), for example as shown in FIG. 1 .

[0132] Optionally, in some embodiments, the system includes one or more additional electrodes for measuring cardiac electrical activity and / or delivering electrical stimulation, such as one or more atrial electrodes 142, 144 and / or one or more left ventricular wall electrodes 140.

[0133] In some embodiments, the system 100 includes one or more additional leads 132, 134. For example, in some embodiments, the system 100 includes a right atrial (RA) lead 132, which in some embodiments hosts one or more atrial electrodes 142, 144.

[0134] For example, in some embodiments, the system 100 includes a left ventricular (LV) lead 134, which in some embodiments hosts one or more electrodes 140. In some embodiments, the LV lead 134 extends into a blood vessel, e.g., a vein, of the LV. In some embodiments, the lead 134 includes multiple electrodes, e.g., four electrodes, disposed along the lead. In some embodiments, the lead 134 hosts at least two electrodes 140. In an exemplary embodiment, the lead 134 hosts four electrodes 140. In some embodiments, electrical stimulation is provided between one or more electrode pairs of the electrodes 140, where, for example, the stimulation is one or more of an ICD and / or a CRT.

[0135] In some embodiments, the system 100 includes an implantable pulse generator (IPG) 120. In some embodiments, the IPG 120 includes a housing 122 that is configured for implantation, e.g., sized and / or shaped for subcutaneous implantation, and / or includes a biocompatible material, e.g., a biocompatible coating.

[0136] In some embodiments, the IPG 120 includes a controller 126 configured to generate and / or transmit control signals.

[0137] Optionally, in some embodiments, the IPG includes a transmitter 128 configured to transmit, e.g., collected messages to a receiver, e.g., a receiver external to the patient's body. In some embodiments, the external receiver is connected to a user interface to generate alert(s) to a user(s) (the patient themselves and / or a medical professional(s)). In some embodiments, the transmitter 128 includes a receiver configured to receive control commands, e.g., to the controller 126, e.g., to modify the operation of the IPG.

[0138] In some embodiments, the IPG 120 includes a power source 124 configured to provide power to one or more portions of the system 100, such as to one or more of the shocking coil 108, the controller 126, the transmitter 128, and the memory 130. For example, in some embodiments, the power source 124 provides power to the shocking coil 108. In some embodiments, the controller 126 receives measurement data from one or more sensors (e.g., lead electrodes 103, 105, 106, 110, 142, 144, 140).

[0139] Exemplary Methods for Assessing Electrode Position FIG. 2 is a method for assessing electrode position according to some embodiments of the present invention.

[0140] In some embodiments, cardiac electrical activity of the heart is measured at 200, for example using one or more electrodes placed within the heart. In an exemplary embodiment, the passage of a cardiac conduction wavefront through the septum is measured using at least two electrode sets, for example electrode sets 103, 106 and electrode sets 105, 110 of FIG.

[0141] In some embodiments, at 202, the measurements collected in step 200 are used to evaluate the position of one or more electrodes placed within the heart, where in some embodiments the evaluation includes one or more of the features shown in and / or described in connection with step 412 and / or step 422 of FIG.

[0142] Exemplary Methods of Cardiac Contractility Modulation Stimulation FIG. 3A is a method of controlling an implantable pulse generator according to some embodiments of the present invention.

[0143] In some embodiments, at 300, the arrival of a cardiac electrical activity wavefront (also referred to as a "cardiac conduction wavefront" and also referred to herein as a "ventricular event") is determined from measurements collected by an electrode pair designated as being an RV electrode pair. In some embodiments, the ventricular event is the timing of the arrival of the R-wave component of an electrocardiogram (ECG). The R-wave component is relatively large in amplitude and relatively fast, which is a potential advantage for this application. However, any other component of the ongoing periodic cardiac electrical activity waveform is detected in addition to or instead of the R-wave. In some embodiments, the timing of the ventricular event is determined by identifying the peak of the R-wave. Alternatively or additionally, template correlation is used to identify the R-wave.

[0144] In some embodiments, at 302, a delay time (eg, delay 302 in FIG. 3B) is optionally introduced after a ventricular event is detected.

[0145] In some embodiments, the delay time is between about 0-100 milliseconds, or between about 0-50 milliseconds, or shorter, or longer, or a duration or range therebetween.

[0146] In some embodiments, at 304, an identification window (eg, identification window 304 of FIG. 3B) is initiated.

[0147] In some embodiments, the discrimination window closes about 1-75 milliseconds after onset, or about 1-40 milliseconds after onset, or a shorter, longer, or any range or duration therebetween.

[0148] In some embodiments, if a ventricular event is detected at the LS designated electrode set during the discrimination window (also referred to herein as a "local sense (LS) event") at 306, a delay time (e.g., delay 306 in FIG. 3B) is optionally introduced. The delay time is implemented, for example, upon detection of the LS event.

[0149] In some embodiments, cardiac contractility modulation is applied immediately after detection of the LS event at 308 (or after the delay time, in the case of a delay time in step 306). In some embodiments, if an LS event is not detected within the identification window, cardiac contractility modulation is not applied, for example, during that cardiac cycle. Additionally or alternatively, in some embodiments, if an LS event is not detected within the identification window, cardiac contractility modulation is not applied during one or more subsequent cardiac cycles.

[0150] In some embodiments, the duration of one or more of the delay time 302, the discrimination window 304, the delay time 306, and the cardiac contractility modulation stimulation duration 308 is adjustable and / or variable. For example, one or more of the durations are dependent on the heart rate. For example, in some embodiments, one or more of the durations are determined as a percentage of the heart rate. For example, the heart rate is determined from a heart rate measurement of duration and / or number of cycles. For example, a cardiac cycle or duration of 2-100 cycles, or 2-50 cycles, or 1-30 seconds, or shorter, longer, or any number in between. In some embodiments, the heart rate is continuously adjusted with the latest data. In some embodiments, the heart rate is periodically determined from the latest data, where the determined value is used until a new value is determined.

[0151] In some embodiments, cardiac contractility modulation is performed when the cardiac rhythm frequency is above a minimum threshold and / or below a maximum threshold, eg, within an acceptable range.

[0152] For example, in some embodiments, cardiac contractility modulation is provided during exercise, e.g., for a heart rate up to an upper threshold, where in some embodiments the upper threshold for the individual is a maximum exercise rate (in beats per minute, BBM), where in some embodiments the individual's maximum exercise rate M (where A is the individual's age) is determined as M=220-A.

[0153] In some embodiments, the upper threshold for an individual is 60%, or 70%, or 80%, or 85%, or 90%, or 95% of the maximum exercise rate, or a smaller, larger, or range or percentage therebetween.

[0154] In some embodiments, cardiac contractility modulation is provided for heart rates above a lower threshold, where in some embodiments the lower threshold is about 100 BPM, or about 110 BPM, or about 120 BPM, or a rate or range therebetween that is less than, greater than, or equal to therebetween.

[0155] For example, the acceptable range of cardiac contractility modulation may be between a lower threshold and an upper threshold, eg, as described above.

[0156] A windowing algorithm is described herein for illustrative purposes. It has the potential advantage that it can be calculated with minimal computational resources and / or implemented by analog timing circuitry. In some embodiments, the same cardiac electrical stimulation (e.g., cardiac contractility modulation stimulation) and / or inhibition of stimulation results is obtained in other ways. For example, in some embodiments, the apparent velocity and direction of cardiac conduction vectors (e.g., 615 in FIGS. 6A-6D) are explicitly determined, and conduction vectors that fall within certain parameter ranges for their velocity and / or direction are used to determine whether to apply cardiac contractility modulation.

[0157] FIG. 3B is a schematic representation of the operations of a method of controlling an implantable pulse generator according to some embodiments of the present invention.

[0158] Shown in FIG. 3B is a cardiac cycle trace 300 showing the P, Q, R, and T segments of the cardiac cycle.

[0159] In some embodiments, a right ventricular event (also referred to as an RV event) is detected, for example, at the transition between the Q and R portions of the cardiac cycle. Here, in some embodiments, the detection of the RV event is made from an electrical signal measured by an electrode designated as the RV electrode (e.g., the first electrode 103 in FIG. 1). A delay 302 is then introduced before the start of an identification window 304. If a locally sensed LS event is detected (e.g., from an electrical signal measured by the second electrode 105 in FIG. 1) during the identification window 304, optimally, in some embodiments, a delay 306 (referred to as the "second delay" if delay 302 is implemented, whereas delay 302 is referred to as the "first delay") is introduced upon LS event detection, after which, in some embodiments, a cardiac contractility modulation stimulus 308 is applied.

[0160] Details of an Exemplary Method of Cardiac Contractility Modulation Stimulation FIG. 4 is a method of applying cardiac contractility modulation stimulation according to some embodiments of the present invention.

[0161] In some embodiments, at 400, one or more electrodes of a cardiac device (eg, hosted by one or more leads) are placed at an initial position within the heart.

[0162] In some embodiments, one or more leads, and in exemplary embodiments, multiple leads, are delivered to a lumen(s) of the heart, where the one or more leads host one or more electrodes, where each electrode is configured to sense electrical activity of the heart and / or deliver cardiac contractility modulation.

[0163] In exemplary embodiments, at least the first and second electrodes are configured to detect the passage of an electrical cardiac wavefront through the septum of the heart. In some embodiments, the first and second electrodes detect the wavefront when positioned proximate the septum. For example, as described elsewhere herein, the timing of the arrival of the cardiac wavefront (e.g., through the septum), and in particular the delay between detection of the cardiac wavefront between the first and second electrodes (referred to herein as "delay"), is determined from the measurement signals of the first and second electrodes.

[0164] In some embodiments, delivery of the lead occurs through a catheter insertion procedure, optionally assisted by imaging, e.g., one or more of ultrasound, x-ray (e.g., fluoroscopy). In some embodiments, the lead(s) are advanced into the heart using a catheter insertion process, where in some embodiments pressure is applied to a distal portion of the lead to advance a proximal portion of the lead into the heart and / or tension is applied to a distal portion of the lead to withdraw the proximal portion from the heart.

[0165] In some embodiments, the location of one or more lead portions is selected (eg, prior to placing the lead(s).

[0166] For example, in some embodiments, a physician selects the positioning of the lead portions, e.g., when the physician prepares to implant a cardiac stimulation system and / or when positioning and / or repositioning a portion(s) of an implanted system (e.g., a system that includes one or more features illustrated in and / or described with respect to system 100 in FIG. 1 ).

[0167] Alternatively or additionally, in some embodiments, the selection of the positioning of the lead portion is based on patient data, such as one or more of the following: a patient diagnosis, patient imaging, patient age, patient weight, data from an implantable device measuring the patient, such as an IPG.

[0168] Alternatively or additionally, in some embodiments, the selection of lead portion positioning is automatic, e.g., automatically determined based on patient data, where in some embodiments automatic selection suggestions are presented to a user (e.g., a medical professional) that the user uses to select lead location(s).

[0169] In some embodiments, one or more leads are positioned to extend into a cardiac ventricle, e.g., the RV of the heart. In an exemplary embodiment, two leads are positioned in the RV. In some embodiments, one or more of the leads extend from the attachment to an IPG (e.g., an IPG including one or more of the features shown and / or described with respect to IPG 120 of FIG. 1). Alternatively or additionally, in some embodiments, one or more of the leads are not connected to the IPG (e.g., power source and / or controller circuitry), e.g., are connected at a later time.

[0170] In some embodiments, the location selection includes, for example, one or more dimensions relative to one or more landmarks, e.g., anatomical and / or markers. In some embodiments, the location selection includes one or more dimensions of the device outside the patient, e.g., how far the lead is inserted into the patient, e.g., from outside the patient.

[0171] In some embodiments, the leads are positioned along an inferior-inferior axis (e.g., spaced at least 0.5 cm, or 1 cm, or 2 cm apart, or less, more, or any distance therebetween), which in some embodiments corresponds to the axis along which conduction initiated in the supraventricular normally travels as it passes through the septum.

[0172] Optionally, one or more additional leads are placed, such as one or more leads extending into the atrium (e.g., lead 132 in FIG. 1) and / or into the left ventricle LV (e.g., lead 134 in FIG. 1).

[0173] In some embodiments, the leads (e.g., at least two leads) are placed in an initial position within the heart (e.g., within the right ventricle as shown by leads 102, 104 in FIG. 1). Optionally, in some embodiments, the positioning is assisted using one or more measurements, e.g., using imaging during positioning, e.g., using measurements (e.g., of the heart's electrical signal(s)) collected by the electrode(s) of the first lead, and / or measurements collected by other electrodes in the body and / or heart and / or sensing electrodes placed externally, e.g., in contact with the subject's skin surface.

[0174] In some embodiments, a first lead is placed and then the location of the first lead is determined (e.g., using one or more types of measurements as described in one or more of steps 402-409) prior to placement of the second lead, where in some embodiments the selection and / or planned positioning of the second lead is adjusted based on the determined location of the first lead. Alternatively, in some embodiments, both the first and second right ventricular leads (e.g., leads 102, 104 of FIG. 1) are placed simultaneously.

[0175] Measurements are collected using the lead electrodes at 402. In some embodiments, one or more types of measurements (e.g., one or more of the measurements described in steps 404-409) are collected for multiple cardiac cycles.

[0176] In some embodiments, at 404, the timing of arrival of cardiac conduction wavefronts at different electrodes is measured.

[0177] In some embodiments, measurements are taken of unstimulated cardiac cycles. Alternatively or additionally, in some embodiments, measurements are taken when the heart is stimulated (e.g., paced, e.g., atrial pacing), e.g., at different heart rates, e.g., where the heart is stimulated by a drug.

[0178] In some embodiments, the wave propagation in a portion or portions of the heart is measured. In some embodiments, the propagation of ventricular waves through, for example, septal tissue is measured. In some embodiments, measurements are collected for multiple cardiac cycles, for example to provide details of statistical variations in wave propagation for individual hearts. Optionally, wave propagation at different heart rates is measured.

[0179] In some embodiments, measurements of stimulated (e.g., paced, e.g., atrially paced) cardiac cycles are used to provide data on "normal" heart beats. In some embodiments, measurements of non-stimulated cardiac cycles are used to provide data on the incidence of arrhythmias, where arrhythmias are defined in some embodiments as conducted wavefronts that pass through the septum but do not originate at the atrioventricular node (AV node).

[0180] Alternatively or additionally, in some embodiments, normal cardiac propagation is determined using previously collected data of the patient and / or other subject(s), for example, optionally adjusted for the patient (e.g., by age and / or sex and / or weight and / or medical history).

[0181] In some embodiments, the relative times of arrival of cardiac electrical activity wavefronts (also referred to herein as "ventricular events") at the first and second electrodes are assessed. In some embodiments, the delay between the arrival of the conducted wavefront is measured over multiple cardiac cycles, e.g., to allow for the calculation of a statistical representation of wavefront movement at the electrode implantation site.

[0182] Optionally, the statistical representation includes a mean delay and / or a standard deviation of the delay.Optionally, the measurement of relative delay is performed at multiple heart rates.

[0183] In some embodiments, the ventricular event is the timing of the arrival of the R-wave component of an electrocardiogram (ECG). The R-wave component is of potential advantage in this application because it is relatively large in amplitude and relatively fast. However, any other component of the ongoing periodic cardiac electrical activity waveform may be detected in addition to or instead of the R-wave.

[0184] In some embodiments, the order of detection of ventricular events between the electrodes is used to determine the relative distance of the electrodes to the AV node, e.g., to designate the electrodes as RV and LS to perform the method of Figures 3A-3B. In some embodiments, it is determined which of the two electrodes is closer to the AV node (e.g., AV node 138 of Figure 1). In some embodiments, the location of the two electrodes relative to the AV node is determined using one or more features shown and / or described in Figure 5A.

[0185] In some embodiments, the designation of electrodes as RV and LS (e.g., for purposes of performing the methods of FIGS. 3A-3B) is based on the positioning (e.g., determined positioning) of the electrodes and / or electrical propagation of regular cardiac cycles. In some embodiments, the designation is made manually, e.g., as selected by a physician, and / or automatically based on preliminary measurements (e.g., external ECG sensor measurements) collected using lead electrodes and / or other measurement devices.

[0186] Alternatively or additionally, in some embodiments, tissue impedance is measured between two electrodes at 406. In some embodiments, the tissue impedance of the cardiac tissue between the electrodes is used to determine the distance between the electrodes, for example, to determine the distance between electrodes proximate to and / or in contact with and / or secured to the septum, such as electrodes 106, 110, septum 136 of FIG. 1. In some embodiments, the tissue impedance between the electrodes (e.g., at the septum) is measured by injecting a current between the electrodes and measuring the potential between the electrodes.

[0187] In an exemplary embodiment, the impedance measurement(s) are collected during the refractory period of the cardiac cycle. For example, if the cardiac cycle is monitored, the refractory period of a cycle is determined from measurements of that cycle and / or the refractory period is determined using measurements of a previous cardiac cycle. Impedance measurements are then collected during the portion of the cardiac cycle identified as being refractory.

[0188] Alternatively or additionally, in some embodiments, at 407, the distance between the first and second electrodes is measured by applying an electrical stimulus (e.g., a stimulation pulse, e.g., a current or voltage stimulus, e.g., a current or voltage stimulation pulse) to one of the first and second electrodes and measuring the decrease in amplitude (and / or arrival timing) of the pulse at the other electrode, where the measurement is used to determine the distance between the first and second electrodes.

[0189] Alternatively or additionally, in some embodiments, at 408, the distance between the first and second electrodes is measured by stimulating the cardiac tissue (e.g., at one electrode) and measuring (e.g., at the other electrode) the transit time of an action potential of the cardiac tissue evoked by the stimulation. For example, if an electrical stimulus is applied at one electrode and ventricular contractility is measured at the other electrode, a characteristic of the ventricular contractility (e.g., delay and / or amplitude) is used to determine the distance between the first and second electrodes.

[0190] In some embodiments, the same stimulation pulse is used to measure tissue impedance (e.g., as described in step 406) and to induce action potentials in cardiac tissue, e.g., as described in step 408. In some embodiments, the same stimulation pulse is used to perform one or more of the measurements described in steps 406, 407, and 408.

[0191] In some embodiments, one or more of steps 406, 407, and 408 are further described with reference to FIG.

[0192] Optionally, in some embodiments, at 409, the heart rate measurement is collected, e.g., in conjunction with one or more other measurements, e.g., one or more of the measurements collected at 404, 406, 407, 408, e.g., to provide the effect of heart rate on the measurement. In some embodiments, a different heart rate is induced during the measurement(s), e.g., by pacing, e.g., over-pacing, and / or subjecting the individual to stress (e.g., physical and / or chemical stress).

[0193] Optionally, at 410, the position of the leads and / or electrodes is measured using one or more other measurement modalities, such as imaging, for example external ECG measurement(s).

[0194] In some embodiments, at 412, the positioning of the lead is assessed using the measurement(s) collected on the lead in one or more of steps 404-410.

[0195] In some embodiments, the position of the electrodes and / or leads is evaluated based on data regarding normal cardiac activity (e.g., assumed and / or measured in step 402) and the ability to vary the values ​​of one or more parameters of the windowing algorithm of FIGS. 3A-3B.

[0196] For example, in some embodiments, an optimization process is performed in which, given cardiac activity measurements and the flexibility available within the windowing algorithm, a predicted occurrence of cardiac cycles in which cardiac contractility modulation stimulation is applied is determined for an electrode location, in some embodiments, multiple predicted occurrences are determined, e.g., for different heart rates.

[0197] In some embodiments, one or more of the delay time 302, discrimination window 304, delay time 306, and cardiac contractility modulation stimulation duration 308 of the method of FIGS. 3A-3B are adjustable.

[0198] In some embodiments, the optimization process includes varying the detection of ventricular events as an input to a windowing algorithm, where, for example, a parameter(s) for identifying the R wave of the cardiac cycle is altered, e.g., if the peak of the R wave is identified, a parameter(s) of the peak detection algorithm is altered.

[0199] For example, in some embodiments, the discrimination window of the method of Figures 3A-3B is selected based on the wavefront delay measurements collected in step 404. For example, in some embodiments (e.g., for a typical Gaussian distribution of relative delays), the discrimination window duration is selected as a delay range within ±2, ±3, ±4, or another number of standard deviations of the mean delay. Optionally, the window duration (e.g., window 304 of Figures 3A-3B) and / or offset (delay 302 of Figures 3A-3B) are selected to include all measurements of relative arrival times, or at least a majority of the measurements, e.g., at least 99% of the measurements, or at least 99.9% of the measurements.

[0200] Optionally, the selected discrimination window is dynamic, e.g., heart rate dependent and / or selected according to the current heart rate, e.g., to take into account potential differences in wavefront velocity as a function of heart rate. Heart rate adjustment of the window is optionally performed based on measurements of delay at different heart rates. Optionally, heart rate adjustment of the window is performed based on a norm derived from observation of a patient population.

[0201] In some embodiments, the optimization includes one or more requirements. For example, in some embodiments, a minimum delay between ventricular events detected at the first and second electrodes is required. In some embodiments, the threshold is a fixed time, where, for example, the average and / or percentage of the delay must exceed the threshold. In some embodiments, the threshold is 1-8 ms, or 2-5 ms, or 1-4 ms, or 3-4 ms, or about 3 ms, or a duration or range shorter than, longer than, or therebetween.

[0202] In some embodiments, the delay between events detected at the first electrode and the second electrode must be within an acceptable time range, for example, 0.5-8 ms, or 0.5-5 ms, or 1-5 ms, or 2-5 ms, or 2-8 ms, or shorter, or longer, or a duration or range therebetween.

[0203] In some embodiments, at 414, one or more leads are repositioned based on the evaluation at 412, e.g., by advancing and / or retracting the lead(s).

[0204] In some embodiments, for example, if the delay is required to exceed and / or be within a threshold, the lead(s) are repositioned until the desired delay is reached.

[0205] In some embodiments, steps 402-414 are repeated multiple times. For example, a measurement(s) is collected (at one or more of steps 402-410) and then the lead is moved in a first direction. After movement, the measurement(s) are collected again, and if evaluation indicates (e.g., at step 412) that moving the lead has improved the measurement(s), the lead is again moved in the first direction. Conversely, in some embodiments, if moving the lead results in a decrease in the measurement, the lead is moved in a different direction.

[0206] In some embodiments, at 416, the positioning of the lead is maintained based on the assessment at 412, e.g., by fixating the lead to the septum, etc. In some embodiments, the lead delivery and / or positioning device is then withdrawn and / or the IPG is connected and / or implanted.

[0207] For example, in some embodiments, an IPG configured to deliver electrical stimulation to one or more electrodes of one or more leads is implanted, e.g., subcutaneously, e.g., an IPG including one or more features shown and / or described with respect to IPG 120 of FIG. 1. In some embodiments, the IPG is connected to one or more leads that are pre-positioned to extend into the heart. In some embodiments, the IPG is connected to the leads but is not implanted subcutaneously, but is connected to the outside of the patient, e.g., with leads extending through the skin surface.

[0208] In some embodiments, the determined location of the electrodes is used to determine whether a cardiac contractility modulation stimulus is applied, for example, for each cardiac cycle, at 420. For example, the determined location is used as an input to one or more features of the method described in Figures 3A and 3B. For example, one or more of the delay duration 302, discrimination window 304, delay time 306, and cardiac contractility modulation stimulus duration 308 are selected based on the electrode location.

[0209] In some embodiments, the measurements collected in step 420 are evaluated at 422, e.g., periodically, e.g., where one or more evaluation parameters are continuously updated.

[0210] In some embodiments, the duration of the time difference between the wavefronts detected at the first electrode and the second electrode is the evaluation parameter, hi some embodiments, the evaluation parameter includes one or more of the median, mean, and variance of the time difference.

[0211] In some embodiments, the timing of ventricular events is evaluated for one or more cardiac cycles, e.g., in some embodiments, the median and / or mean and / or variance of one or more timing parameters of sensed ventricular events are evaluated for an evaluation period, where in some embodiments the timing parameters include delays between sensing of ventricular events and / or sensing order of ventricular events (e.g., sign of the delays).

[0212] In some embodiments, the timing of the ventricular events is evaluated based on a heart rate associated with the measured ventricular events, for example the heart rate for each cardiac cycle and / or the heart rate over a period of time, where the heart rate period is in some embodiments the same or different from the evaluation period.

[0213] For example, in some embodiments, the measured time difference between the wavefronts detected at the first and second electrodes is stored along with the heart rate at the time of the measurement.

[0214] In some embodiments, the evaluation includes determining whether a change in the evaluation parameter(s) is associated with a change in cardiac function and / or a change in the position of the measurement electrodes and / or leads within the heart.

[0215] In some embodiments, electrode(s) migration and / or lead dislodgment are identified from the timing data. For example, in some embodiments, a warning is issued indicating possible electrode and / or lead malposition and / or dislodgment if the timing changes beyond one or more thresholds, including the order of ventricular event(s) and / or the time delay between ventricular events, optionally with respect to heart rate. In an exemplary embodiment, lead migration (e.g., dislodgment) is identified if one or more of the mean and median delays change outside of an expected range. Here, in some embodiments, lead migration is identified if the mean delay changes beyond a threshold, e.g., by more than 10%, or more than 20%, or more than 30%, or more than 40%, or by a percentage or range therebetween that is less than, greater than, or equal to or between. Alternatively or additionally, in some embodiments, lead migration is identified if the median delay changes by more than a threshold, e.g., by more than 10%, or more than 20%, or more than 30%, or more than 40%, or a smaller, larger, or a percentage or range therebetween.

[0216] Optionally, in some embodiments, the wavefront propagation of the regular cardiac cycle is updated and / or redetermined using lead electrode measurements.

[0217] In some embodiments, at 424, the lead position is updated, for example, for purposes of delivering cardiac contractility modulation stimulation.

[0218] For example, feedback from step 424, in some embodiments, is an input to step 420, where in some embodiments, one or more portions of the method for determining which cardiac cycles should receive cardiac contractility modulation of FIGS. 3A-B are adjusted based on lead position (e.g., as updated in step 424). For example, adjusting one or more of delay 302, discrimination window 304, delay 306 of FIGS. 3A-3B. For example, changing the designation of the leads as rv and ls for the method of FIGS. 3A-3B, where the designation is based on lead position, where in some embodiments the designation is changed according to, for example, one or more features shown and / or described with respect to the method of FIG. 5A. The adjustments may increase the percentage of cardiac cycles that receive cardiac contractility modulation stimulation.

[0219] In some embodiments, the position of the lead(s) and / or electrode(s) is assessed, for example using electrode measurements (and optionally additional measurements such as imaging). In some embodiments, movement of the electrode(s) and / or lead dislodgment is identified from measurements, for example from timing data of events measured by the electrodes. Optionally, a warning, for example a lead dislodgment warning, is initiated based on the determination.

[0220] In some embodiments, at 426, the patient is diagnosed based on the evaluation in step 422. For example, in some embodiments, a cardiac condition is diagnosed using the evaluation, where in some embodiments the diagnosis includes one or more of the features shown and / or described with respect to FIG. 5B. Optionally, in some embodiments, the diagnosis(es) is communicated to a user, e.g., a user interface, e.g., via transmitter 128 of FIG. 1.

[0221] Applying act 420 onwards in FIG. 4, an alert can be generated based on measurements. In one example, if the delay between two electrodes is not within a desired range, e.g., within 1-4 ms, a change is sent. In some embodiments, an alert is generated every time. Optionally or additionally, an alert is generated based on the number or frequency of events. Optionally or additionally, a report is generated periodically, e.g., once a week.

[0222] In some embodiments of the invention, alerts are transmitted to a remote monitoring site (e.g., or a cloud location), for example, using a wireless connection. Optionally or additionally, they are transmitted to a local device, such as a mobile phone (e.g., using BlueTooth or other local wireless connection), which may transmit the received data, optionally after processing. Optionally or additionally, data regarding such alerts is downloaded, optionally as reports and / or summaries, using the local device, for example, a device programmer.

[0223] In some embodiments of the invention, the measurements include delay measurements and / or impedance measurements at one or both of the electrodes and / or between the electrodes. Such impedance measurements may be useful in indicating the quality of contact between the electrodes and the cardiac tissue (e.g., dislodgment) and / or damage to the electrodes and / or leads.

[0224] With particular reference to operation 420, in some embodiments of the invention, cardiac contractility modulation stimulation is optionally applied to both electrodes simultaneously or at an overlapping time having between 10% and 99% overlap (e.g., of the same cardiac cycle, and of the same or overlapping time windows within the cardiac cycle), e.g., between 10% and 30%, between 30% and 70%, and / or between 70% and 99% overlap, etc.

[0225] Exemplary Lead Selection FIG. 5A is a method of electrode selection for implementing a method of controlling an implantable pulse generator according to some embodiments of the present invention.

[0226] In some embodiments, ventricular events passing through the first and second electrodes (e.g., electrodes 106, 110 of FIG. 1) are identified at 500. In some embodiments, the identifying is performed according to one or more features described with respect to step 404 of FIG.

[0227] In some embodiments, the time difference between the identified ventricular events is determined from the measurements. In some embodiments, an order of ventricular events sensed between the first and second electrodes is determined using the electrode measurement data. In some embodiments, the order is determined from a sign of the delay between ventricular events sensed at different electrodes, for example, in a cardiac cycle. In some embodiments, the determining is for measurements collected from a plurality of n cardiac cycles.

[0228] In some embodiments, at 502, a ventricular event order prevalence is determined, for example, for n cardiac cycles, where in some embodiments the order prevalence for a period is which electrode detects a ventricular event first for the majority of the period.

[0229] Instead of, or in addition to, measuring n cardiac cycles and determining a sequence dominance of the n cycles at 500, in some embodiments the determination of the sequence is continuous and / or the sequence dominance is continually updated, for example as measurements are collected.

[0230] At 504, the RV and LS are designated based on the determined ventricular event sequence dominance, e.g., for purposes of determining when to apply a cardiac contractility modulation stimulus, e.g., according to one or more features shown and / or described with respect to FIG.

[0231] In some embodiments, the RV and LS electrodes are assigned periodically, e.g., steps 500-504 are repeated periodically, e.g., for a set number of cardiac cycles and / or duration, e.g., repeating steps 500-504 once per hour, 1-5 times per day, once per day, once every other day, or any lesser, greater, or frequency or range of frequencies therebetween.

[0232] Additionally or alternatively, in some embodiments, steps 500-504 are repeated in response to user input requesting an evaluation and / or manually specifying an electrode order.

[0233] Additionally or alternatively, in some embodiments, steps 500 and 502 are performed continuously and step 504 is performed upon detection of a change, such as a change in the majority order dominance over a period of time (e.g., a predetermined period of time), such as a fluctuation (e.g., above a threshold) in the order dominance.

[0234] Exemplary monitoring FIG. 5B is a method of monitoring according to some embodiments of the present invention.

[0235] In some embodiments, at 501, the relative timing (e.g., time difference) between detection of conducted waveforms at different electrodes is determined from measurements collected at the electrodes, for example as described elsewhere in this document. In some embodiments, the time difference is measured for multiple cardiac cycles. Optionally, in some embodiments, the heart rate is measured.

[0236] In some embodiments, optionally, at 503, normal time difference boundary(s) and / or normal time difference value(s) are determined using the measurements collected at 501, optionally together with heart rate, where, for example, the measured time difference over time and / or with heart rate is used to provide a predictive value(s) and / or range(s) for a particular subject. In some embodiments, the normal time difference value is provided by a statistical representation of the measured normal time difference, such as one or more of the mean, median, standard deviation, variance, skewness, kurtosis, extremes, maximum, minimum, range, second moment.

[0237] Alternatively, in some embodiments, the statistical expression value(s) and / or normal boundaries are fixed and / or estimated using patient data (e.g., age, diagnosis).

[0238] In some embodiments, the normal range(s) and / or expected mean and / or statistical representation value(s) are determined using fixed or estimated values ​​and then adjusted using measured values.

[0239] In some embodiments, the normal range and / or value(s) (eg, of the statistical representation(s)) are updated periodically using the measurements.

[0240] In some embodiments, e.g., as described elsewhere in this document, measurements from cardiac cycles determined to be unsuitable for cardiac contractility modulation (and / or other therapy and / or stimulation) are excluded from the measurements used to determine normal range(s) and / or value(s) (e.g., of statistical representation value(s)).

[0241] In some embodiments, the statistical representation describes the variation of the time difference over a period of time.

[0242] In some embodiments, at 505, the measured time difference is compared to a normal value(s) and / or range(s). In some embodiments, the comparison is made for an individual cardiac cycle. Alternatively or additionally, in some embodiments, the comparison is a comparison of a statistically representative value(s) of the time difference measured over a period of time. For example, in some embodiments, the comparison is an average (e.g., median) value over a period of time, where in some embodiments the average is determined using time difference values ​​of similar heart rates.

[0243] In some embodiments, at 507, the subject is diagnosed based on the comparison performed in step 505.

[0244] In some embodiments, if the variability in time difference increases with heart rate, the likelihood of inducible ischemia and / or increased risk of arrhythmia is diagnosed.

[0245] In some embodiments, the likelihood of inducible ischemia and / or increased arrhythmia risk is diagnosed when the variability of the time difference increases at higher heart rates, where in some embodiments the likelihood of inducible ischemia is diagnosed for heart rates above 100 bpm, or above 110 bpm, or above 120 bpm, or heart rates lower, higher, or therebetween, where the statistical representation of the time difference indicates an increased variability of the time difference (e.g., above a threshold value).

[0246] As discussed with respect to FIG. 4, such measurements and / or analysis thereof may be output from the implantable device or from its controller, for example as alerts and / or reports and / or raw or processed data.

[0247] Exemplary Identification of Cardiac Conduction Patterns Referring again now to Figures 3A-3B, in some embodiments, Figures 6A-6D illustrate how an algorithm, e.g., as described and / or illustrated with respect to Figures 3A-3B, can be used to distinguish between normal sinus rhythm and arrhythmias, e.g., to provide cardiac contractility modulation only for normal cardiac cycles.

[0248] 6A-6D are schematic illustrations of differentiation of conduction patterns through the interventricular septum 636, according to some embodiments of the present invention.

[0249] 6A-8D each show leads 602, 604 and sensing (electrode) locations 611A, 612A positioned within heart 616. Also shown are different estimates of the intraseptal conduction vector 615, which varies in direction and length depending on the apparent direction and velocity of wavefront conduction between sensing locations 611A and 612A.

[0250] 6A-6D, marks 611, 612 represent the times when the conducted wavefront reaches sensing locations 611A and 612A, respectively. Time range 613, in some embodiments, represents an identification window (which in some embodiments includes one or more features of the identification window of FIGS. 3A-3B).

[0251] In some embodiments of the invention, the first division of normal and abnormal sinus rhythm may include antegrade conduction (e.g., Figures 6A, 6C) and retrograde conduction (e.g., Figures 6B, 6D) through the interventricular septum.

[0252] 6A, normal sinus rhythm and some supraventricular tachycardias (SVTs) have cardiac conduction wavefront vectors (i.e., conduction vector 615 from wavefront location 610A to wavefront location 610B) that travel in an antegrade direction to the ventricles through the normal conduction apparatus (the bundle of His and Purkinje fibers) in the interventricular septum. An antegrade SVT can include one or more of atrial tachycardia, atrial flutter, atrial fibrillation, atrioventricular nodal reentrant tachycardia (AVNRT), and antegrade Wolf-Parkinson-White atrioventricular reentrant tachycardia (antegrade WPW-AVRT).

[0253] True ventricular tachycardia, on the other hand, is conducted in a retrograde direction through the conduction system and / or causes disturbances within the conduction system itself. For example, in FIG. 6B, conduction is retrograde from wavefront location 610C to wavefront location 610D. In FIG. 6D, conduction includes a retrograde component as the wavefront moves between wavefront location 610H and wavefront location 610G. Conduction in FIG. 6C is orthodromic, but rather than originating in the supraventricular ventricles, it moves from wavefront location 610E to wavefront location 610F.

[0254] The timelines of Figures 6A-6D represent example(s) of how the method of Figures 3A-3B may be implemented in some embodiments of the invention.

[0255] In each of Figures 6A-6D, the mark 611 is either inside (Figure 6A) or outside (Figures 6B-6D) the identification window 613.

[0256] If the mark 611 is within the identification window 613, in some embodiments this is taken as an indication that a cardiac contractility modulation stimulus should be applied.

[0257] 7A-7E and 8A-8E show timing of ventricular event detection for different conduction vectors and different electrode locations relative to the conduction vectors. In some embodiments, one or more of the figures show how a windowing algorithm and / or optimization of electrode location may be used to optimize application of cardiac contractility modulation.

[0258] 7A-7D are simplified schematic diagrams of cardiac conduction wavefront sensing, according to some embodiments of the present invention.

[0259] In some embodiments, the wavefront, indicated by the arched dashed line, passes through septal tissue 750, where a normal wavefront begins at the AV node 738 and travels inferiorly through septal tissue 736, away from the AV node 738.

[0260] In some embodiments, Figures 7A-7C show different wavefront passages for a first electrode spatial configuration.

[0261] In FIG. 7A, the propagation is of a “normal” conducted wavefront 750, which emanates from the AV node 738 and travels downward through the septal tissue 736.

[0262] FIG. 7B also shows that, in some embodiments, a normally conducted wavefront, but the direction of travel of wavefront 752 is at a slight angle to vector 760 connecting electrodes 703, 704.

[0263] FIG. 7C illustrates, in some embodiments, an arrhythmia wavefront where, for example, the wavefront does not originate from the AV node 738.

[0264] FIG. 7D shows a normal wavefront in some embodiments, but with a different electrode spatial configuration than shown in FIGS. 7A-7D.

[0265] FIG. 7E is a simplified schematic diagram of a timeline of sensed ventricular events, according to some embodiments of the present invention.

[0266] In some embodiments, FIG. 7E illustrates the timing schematics of FIGS. 7A-7D.

[0267] Of note is that the timeline of sensed arrhythmia shown in FIG. 7C is the same as the timeline in FIG. 7E where one of the electrodes has moved, e.g., fallen out of position, from that shown in FIGS. 7A-7C.

[0268] 8A-8D are simplified schematic diagrams of cardiac conduction wavefront sensing, according to some embodiments of the present invention.

[0269] FIG. 8E is a simplified schematic diagram of timing of sensed ventricular events, according to some embodiments of the present invention.

[0270] In some embodiments, Figures 8A-8D show sensing of cardiac waves propagating in different directions for a second electrode spatial configuration, and Figure 8E shows a timeline of sensed ventricular events corresponding to those shown in Figures 8A-8D.

[0271] If cardiac wavefronts frequently pass in a direction that passes through the septum, such as toward the left side of septum 836 (directions herein refer to directions with respect to Figures 8A-8D), then in some embodiments the electrodes are positioned accordingly, for example as shown in Figures 8A-8D. Potentially, positioning the electrodes in a configuration that accommodates more wavefronts may increase the percentage of normal wavefronts (and cardiac cycles) to which cardiac contractility modulation stimulation is applied.

[0272] However, with reference to FIG. 8C, the angled electrode configuration as shown in FIGS. 8A-8C provides a smaller time difference between delays relative to a normal cardiac cycle than the electrode configuration of, for example, FIGS. 7A-7D.

[0273] However, referring to FIG. 8D, the angled electrode configuration potentially reduces the proportion of cardiac cycles in a direction different than the specified direction.

[0274] FIG. 9 is a schematic illustration of three sensor identification of conduction patterns passing through the interventricular septum, according to some embodiments of the present invention.

[0275] In some embodiments, when more than two electrodes are used to sense the cardiac conduction waveform, methods of positioning the electrode(s) and / or adjusting the windowing algorithm to generate optimal cardiac contractility modulation stimulation (e.g., as described elsewhere in this document) are used.

[0276] The remaining two forms of arrhythmia, retrograde Wolff-Parkinson-White atrioventricular reentrant tachycardia (retrograde WPW-AVRT) and Wolff-Parkinson-White atrial fibrillation (WPW-AF), involve SVT that may not be distinguished from true ventricular tachycardia solely by analysis of the conduction velocity and direction of the depolarization wavefront that rapidly crosses the interventricular septum.

[0277] As shown in FIG. 9, in addition to the leads 102, 104 located in the septum of the heart 916, a third lead 103 is shown located in another ventricular region. The lead 103 is shown entering the heart 916 through the same vessel (e.g., the superior vena cava) as the leads 104, 102, but is optionally routed from a different direction. Thus, a third sensing location 914A is added to the sensing (electrode) locations 911A, 912A, corresponding to the location of the electrode of the lead 103. In some embodiments, the lead 103 is an LV lead, such as a lead that runs along the coronary sinus, such as used in cardiac resynchronization therapy (RCT). In some embodiments, the lead 103 is a lead that is placed at the apex of the left atrium.

[0278] In this example, the estimate of the intraseptal conduction vector 915 appears indistinguishable from normal antegrade conduction, and in fact, the mark 911 on the timeline of FIG. 9 falls within the discrimination window 913. This may lead to the concurrent tachycardia being determined to be supraventricular in nature.

[0279] However, in some embodiments, detection of a conducted wavefront passing through sensing location 914A results in activation of a predetermined inhibition window 913B. The inhibition window 913B inhibits the defibrillation discrimination function of the discrimination window 913 such that defibrillation is not inhibited even if mark 911 is within a time period that would prevent delivery of a defibrillation shock.

[0280] In some embodiments, the inhibition window 913B is long enough to cover the time it takes for conduction to make a detouring pass between wavefront location 910J and wavefront location 910K, but not so long that it may inhibit identification of SVT (e.g., about 100-250 ms, or other suitable period). Optionally, the inhibition window 913B begins after a delay 913A (e.g., about 1-50 ms). In some embodiments, the delay 913A is set long enough so that a wavefront of atrial origin that first arrives at, for example, sensing location 914A and then arrives several milliseconds later at, for example, sensing location 912A is not confused with a wavefront beginning of ventricular origin. In some embodiments, the inhibition window 913B itself may be inhibited, for example, if detection of a conduction wavefront passing through sensing location 912A occurs just before or within a fairly short period after the wavefront passes through location 915A.

[0281] Exemplary Measurement of Electrode Position Using Electrical Stimulation FIG. 10 is a simplified schematic diagram illustrating a stimulus signal 1046 and a measurement signal 1048, according to some embodiments of the present invention.

[0282] In some embodiments, the electrical stimulation pulse 1050 is applied intracardially, for example to cardiac tissue (eg, at one of the electrodes 106, 110 of FIG. 1).

[0283] In some embodiments, the distance between the electrodes is determined using a measurement of the pulse 1050. For example, using an electrical measurement signal measured at another septum electrode, e.g., a second electrode, of two septum electrodes, e.g., when a stimulation pulse is applied to electrode 106, a measurement signal is measured at electrode 110 (see electrodes 106, 110 in FIG. 1).

[0284] In some embodiments, the measurement is of the resulting single pulse 1052, for example, if the second pulse 1054 does not occur.

[0285] For example, if a stimulation pulse is applied during the refractory period, in some embodiments, no or only minimal second pulse occurs associated with simulating cardiac contractility modulation in cardiac tissue.

[0286] In some embodiments, a second measurement pulse 1054 is observed after pulse 1052, e.g., when stimulation pulse 1050 is applied when not during the refractory period of the cardiac cycle. The delay between measurement pulses 1052, 1054 and / or the delay between pulses 1050 and 1054 in some embodiments is related to the difference in the travel rate of the electrical pulse through the tissue as opposed to the travel rate of the cardiac contractility modulation stimulated by pulse 1050. In some embodiments, the position of the electrodes (e.g., 106, 110 in FIG. 1) is additionally or alternatively determined using the measurement of second pulse 1054.

[0287] In some embodiments, the timing of one or both of the pulses 1052, 1054 is used to determine the location of the electrode. Alternatively or additionally, in some embodiments, the amplitude of one or both of the pulses 1052, 1054, optionally relative to the amplitude of the applied pulse 1050, is used to determine the location of the electrode.

[0288] In some embodiments, for example, pulse 1052 in some embodiments is measured nearly instantaneously upon injection of pulse 1050, so that the amplitude of pulse 1052 (e.g., the difference between the amplitude of pulse 1050 and the amplitude of pulse 1052) is used to determine the distance between the electrodes.

[0289] In some embodiments, the delay between pulse 1050 and / or pulse 1042 and pulse 1054 is used to determine the distance between the electrodes.

[0290] It is anticipated that many related cardiac stimulation technologies will be developed between the filing of this application and the expiration of the patent, and the scope of the term cardiac stimulation is intended to include, a priori, all such new technologies.

[0291] As used herein, the term "about" refers to ±20%.

[0292] The terms "comprises," "comprising," "includes," "including," "having" and their conjugations mean "including, but not limited to."

[0293] The term "consisting of" means "including and limited to."

[0294] 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.

[0295] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" can include a plurality of compounds, including mixtures thereof.

[0296] Throughout this application, various embodiments of the 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 invention. Thus, the description of a range should be considered to have specifically disclosed all possible subranges as well as individual numerical values ​​within that range. For example, the description of a range such as "1-6" should be considered to have specifically disclosed subranges such as "1-3", "1-4", "1-5", "2-4", "2-6", "3-6", and individual numerical values ​​within that range, e.g., 1, 2, 3, 4, 5, and 6. This is true regardless of the breadth of the range.

[0297] Whenever a numerical range is given herein, it is meant to include any recited numbers (fractional or integer) within the given range. The phrases "ranging / ranges between" a first recited number and a second recited number, and the phrases "ranging / ranges from" a first recited number "to" a second recited number are used interchangeably herein and are meant to include the first recited number and the second recited number, and all fractional and integer numbers therebetween.

[0298] As used herein, the term "method" refers to methods, means, techniques and procedures for accomplishing a given task, including, but not limited to, methods, means, techniques and procedures known by or readily developed from known methods, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.

[0299] As used herein, the term "treating" includes negating, 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.

[0300] It will be appreciated that certain features of the invention that are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination, or as appropriate in any other embodiment described in the present invention. Certain features described in the context of various embodiments should not be regarded as essential features of those embodiments, unless the embodiment cannot function without those elements.

[0301] While the present invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

[0302] It is the intention of the applicants (applicants) that all publications, patents, and patent applications referenced herein are incorporated herein by reference in their entirety as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated herein by reference. Furthermore, 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. Section headings, if used, should not necessarily be construed as limiting. Additionally, any priority document(s) of this application are hereby incorporated herein by reference in their entirety.

Claims

1. 1. A system for cardiac stimulation comprising: An implantable controller, the controller comprising: receiving measurements from at least two electrodes positioned within the heart; designating a first electrode of the at least two electrodes and a second electrode of the at least two electrodes from the measurements; applying a cardiac contractility modulation stimulus to the heart when a ventricular event is detected at the first electrode and then after a suitable time delay at the second electrode; The system is configured to perform a method including:

2. 2. The system of claim 1, wherein the designating comprises monitoring the measurement for a plurality of cardiac cycles and designating as the first electrode an electrode of the at least two electrodes that first senses a ventricular event during a majority of the cardiac cycles.

3. The system of claim 1 or 2, wherein the measurements include cardiac electrical measurement signals from the at least two electrodes positioned on the right ventricular septum.

4. The system of claim 1 , wherein the specifying comprises determining from the measurements a timing of arrival of a cardiac action potential wavefront at the at least two electrodes.

5. 4. The system of claim 1, wherein the at least two electrodes include first and second electrodes disposed on a partition and at least one additional electrode, and the measurements include measurements of electrical potential at each of the first and second electrodes relative to the additional electrode.

6. The system of any one of claims 1 to 5, wherein the delay is at least 1 ms and at most 4 ms.

7. a. generating an alert if the delay is not within a desired range; b. performing impedance measurements at and / or between the two electrodes; c. performing said applying on both of said electrodes with overlap in time; The system of any one of claims 1 to 6, configured to perform one or more of the following:

8. The system of any one of claims 1 to 7, wherein the system is configured to perform the applying on both of the electrodes in the same cardiac cycle, at least in part without overlap in time.

9. 1. A monitoring method comprising: monitoring over time the time difference between arrival of a cardiac action potential wavefront at two electrodes, each placed at a different point on the heart; Based on said monitoring, and designating a relative position of the two electrodes based on the time difference to determine which cardiac cycles should receive cardiac contractility modulation stimulation.

10. The method of claim 9 , wherein the two electrodes are each positioned at a different point on the cardiac septum.

11. said monitoring comprising: receiving cardiac electrical measurement signals from the two electrodes; determining a timing at which a wavefront of a myocardial action potential arrives at each of the two electrodes from the measurement signal; determining a time difference between arrival of the cardiac action potential wavefront at the two electrodes for a plurality of cardiac cycles; generating a statistical representation of the time differences from the determined time differences for the plurality of cardiac cycles; the statistical representation includes a tendency for which of the two electrodes to sense the cardiac action potential wavefront first; The method further includes diagnosing a cardiac condition based on the determining. The method of claim 9 or 10, wherein the diagnosing comprises comparing the statistical representation to a threshold value.

12. The method of claim 9 , wherein said determining comprises determining a sign of the time difference.

13. The method of any one of claims 9 to 12, wherein said designating comprises designating the electrode at which a majority of the wavefronts are first sensed as being proximal to the atrioventricular node.

14. receiving heart rate measurements for the plurality of cardiac cycles; generating includes generating a statistical representation of the time differences with respect to heart rate; diagnosing a possible inducible ischemia if the statistical representation indicates an increase in the variance of the time difference with an increase in heart rate; the increase in heart rate includes a statistical representation of the time difference for heart rate increases exceeding a threshold number; The method of claim 11, further comprising diagnosing a possible cardiac arrhythmia if the statistical representation indicates an increased variability in the time differences of one or more heart rates.

15. 12. The method of claim 11, wherein the statistical representation of the time difference is a median of the time difference over a period of time, and a lead loss is identified if the median deviates by more than a threshold value for a period of less than one minute.

16. 1. A method of cardiac signal processing of pre-positioned electrodes extending into the heart, comprising: receiving measurements from at least two electrodes positioned within the heart; using the measurements to determine a relative positioning of the at least two electrodes with respect to one another; and evaluating the suitability of the relative positioning of the at least two electrodes for measuring cardiac activity to determine which cardiac cycles should receive cardiac contractility modulation stimulation.

17. 17. The method of claim 16, wherein the evaluating comprises generating a signal indicating whether one or more of the electrodes should be repositioned or fixed in place.

18. 17. The method of claim 16, wherein the measurements include cardiac electrical measurement signals from the at least two electrodes positioned on the right ventricular septum.

19. said determining including identifying from the measurement signal a timing of passage of a cardiac action potential wavefront; the wavefront is an intraseptal myocardial action potential wavefront; the at least two electrodes include a first electrode and a second electrode; said determining including determining a delay between detection of the wavefront at the first electrode and detection of the wavefront at the second electrode; A method according to any one of claims 16 to 18, wherein said evaluating comprises evaluating said delay, and wherein said delay is deemed to indicate proper positioning if said delay is at least 1 ms and at most 4 ms.

20. The evaluating, a. determining a proportion of a cardiac cycle that is suitable for receiving a cardiac contractility modulation stimulus with respect to said relative positioning; b. assessing a percentage of abnormal cardiac cycles determined to be suitable for receiving cardiac contractility modulation stimulation, wherein if the percentage of abnormal cardiac cycles determined to be suitable for receiving cardiac contractility modulation stimulation exceeds 5% of cardiac cycles, the signal indicates that the electrodes should be repositioned; c. assessing a proportion of normal cardiac cycles determined to be not suitable to receive cardiac contractility modulation stimulation, wherein if the proportion of normal cardiac cycles determined to be not suitable to receive cardiac contractility modulation stimulation exceeds 20% of the cardiac cycles, the signal indicates that the electrodes should be repositioned; The method of any one of claims 16 to 19, comprising one or more of:

21. 21. The method of claim 20, wherein said determining a percentage of a cardiac cycle suitable for undergoing cardiac contractility modulation is based on said measurements.

22. 22. The method of any one of claims 16 to 21, wherein the at least two electrodes include first and second electrodes disposed on a partition and at least one additional electrode, and the measurements include measurements of the electrical potential at each of the first and second electrodes relative to the additional electrode.

23. The measurement value is a. over multiple cardiac cycles; b. Includes measurements taken while the heart is stimulated; The method according to any one of claims 16 to 22, wherein the method is one or more of:

24. Based on the evaluation, repositioning one or more of the at least two electrodes; and immobilizing the one or more of the at least two electrodes; the receiving is performed a plurality of times to determine a plurality of delays; said evaluating including determining a statistical representation of said delay; the statistical representation of the delay is a median of the plurality of delays; The method of any one of claims 16 to 23, wherein said evaluating comprises comparing said statistical representation to a threshold value.

25. The method of any one of claims 16 to 24, wherein said determining comprises determining tissue impedance between the at least two electrodes.

26. said determining including injecting an electrical stimulation pulse; the measurements include electrical signals affected by the stimulation pulses; the determining includes determining one or more parameters from the electrical signal affected by the stimulation pulse; said injecting being during a refractory period of the cardiac cycle of said heart; The method of any one of claims 16 to 25, wherein the injecting is between the at least two electrodes.

Images