Patient treatment system for detecting cardiac depolarization and / or stimulating the carotid sinus nerve, as well as related devices and methods

Abstract

An exemplary patient treatment system for detecting cardiac depolarization and stimulating the carotid sinus nerve can include a neuromodulator and an implantable signal delivery device electrically couplable to the neuromodulator. The signal delivery device includes a first region, a second region positionable over the first region, and a lead body including lead electrodes. The patient treatment system further includes a computer-readable medium having instructions that cause the patient treatment system to perform operations including (i) obtaining physiological parameters of the patient, (ii) generating neuromodulation pulses based on the obtained physiological parameters, and (iii) delivering the neuromodulation pulses to the CSN afferent fibers via one or more of the lead electrodes. The physiological parameters can include at least one of the patient's blood pressure, heart rate, bioimpedance, or activity level.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority to U.S. Patent Application No. 16 / 393,536, filed Apr. 24, 2019 (now U.S. Patent No. 10,918,865), U.S. Provisional Patent Application No. 63 / 351,748, filed Jun. 13, 2022, and U.S. Provisional Patent Application No. 63 / 496,349, filed Apr. 14, 2023, the disclosures of which are hereby incorporated by reference in their entireties.

[0002] This disclosure relates to patient treatment systems for detecting cardiac depolarization and / or stimulating the carotid sinus nerve, as well as related devices and methods.

Background Art

[0003] Millions of patients worldwide suffer from heart diseases such as hypertension (i.e., high blood pressure) and heart failure. To treat hypertension and heart failure, many different pharmaceutical and medical device - based therapies have been developed, but many of these therapies have been ineffective or at least ineffective for a majority of patients. For example, about 1 in 10 people with hypertension are treatment - resistant, and in this regard, pharmaceuticals are not useful for lowering blood pressure. Approximately 100 million people worldwide suffer from treatment - resistant hypertension, and these patients are at three times the risk of cardiovascular events such as heart attacks compared to patients whose blood pressure can be controlled with drug therapy.

[0004] Several different medical devices and procedures have attempted to treat drug-resistant hypertension. One example is a procedure in which a catheter is inserted into an artery leading to the kidney and high-frequency energy is applied to the vessel wall to denervate small nerves surrounding the artery. Another example is an implantable stimulation device for stimulating baroreceptors in the neck by applying energy to the carotid artery wall. Unfortunately, these devices and procedures have not been proven to be effective as desired. Currently, hundreds of millions of patients suffer from hypertension that cannot currently be treated, which often leads to serious cardiovascular consequences. Unfortunately, a similar situation exists for other serious health conditions such as congestive heart failure and kidney failure. Therefore, improved devices, systems, and methods for treating hypertension, heart failure, and / or other cardiovascular diseases are needed.

Summary of the Invention

[0005] The features, aspects, and advantages of the technology disclosed herein can be better understood with reference to the following figures.

Brief Description of the Drawings

[0006]

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DETAILED DESCRIPTION OF THE INVENTION

[0007] Those skilled in the art will understand that the features shown in the drawings are for illustrative purposes and that variations are possible, including different and / or additional features and configurations.

[0008] I. Overview Embodiments of the present disclosure relate to a patient treatment system for detecting cardiac depolarization events and / or providing a non-tonic therapy to the afferent fibers of a patient's carotid sinus nerve (CSN) based on one or more physiological parameters (e.g., heart rate, R-R interval, blood pressure, etc.) obtained from the patient. It is generally known that baroreceptors on the carotid sinus include stretch receptors that respond by relaying relevant signals to the brain in response to cardiac depolarization and the resulting pressure wave in the carotid sinus. In patients with hypertension, the mechanism for relaying such signals may be abnormal, and in that regard, the patient's ability to naturally regulate heart rate may be limited. Current devices that attempt to provide a patient with a therapy for treating hypertension via stimulation provide a tonic therapy (i.e., a set of frequency, amplitude, pulse width, etc.) that does not change based on the patient's activity, which is provided to an anatomical structure that has a less efficient or less desirable response to this therapy.

[0009] Embodiments of the present disclosure address at least some of the problems described above for patients having hypertension. For example, embodiments of the present disclosure utilize neuromodulation of the CSN to alter abnormal responses of a patient and reduce blood pressure. As disclosed herein, the patient treatment system of the present technology can map a patient's tissue by detecting cardiac depolarization and associated electrical and / or acoustic signals, and position a lead electrode of the patient treatment system at least substantially proximate to CSN afferent fibers. Once positioned, the patient treatment system can determine one or more physiological parameters of the patient and provide stimulation to the patient, at least in part, based on the one or more physiological parameters. Additionally, due in part to the ability to detect cardiac depolarization, the patient treatment system can, in some embodiments, provide a neuromodulation pulse having stimulation characteristics (e.g., frequency, amplitude, pulse width, delay, etc.) that mimic a natural desired baroreceptor response (e.g., the response of a patient not having hypertension). In doing so, embodiments of the present technology can automatically (e.g., without user input) adjust stimulation parameters based at least in part on the activity of the patient, and in this regard, provide a non-tonic therapy that is generally not attenuated by the activity of the patient. For these and other embodiments disclosed herein, embodiments of the present technology provide patient treatment that is an improvement over existing devices and methods.

[0010] In the figures, the same reference numerals generally identify similar and / or identical elements. Many of the details, dimensions, and other features shown in the figures merely illustrate particular embodiments of the disclosed technology. Thus, other embodiments can have other details, dimensions, and features without departing from the spirit or scope of the present disclosure. Additionally, those skilled in the art will understand that additional embodiments of the various disclosed technologies can be implemented without some of the details described below.

[0011] II. Anatomical Structure of the Carotid Sinus Nerve and Vagus Nerve Disclosed herein are methods, devices, and systems for detecting cardiac depolarization and / or stimulating nerves to treat hypertension, coronary artery disease, heart failure, kidney disease, and / or any of a number of other conditions in humans or animals. The following description focuses on the treatment of drug-resistant hypertension or hypertension, but the aspects and principles described below can be used to treat or adapted for use in the treatment of several cardiovascular or other diseases. Thus, although the following description focuses on one condition, the present disclosure and the methods, devices, and systems described herein are not limited to any one disease or disorder.

[0012] Figures 1A and 1B are anatomical diagrams of the carotid sinus and the nerves in the surrounding anatomical regions. Referring to both Figures 1A and 1B, there are two branches of the CSN that arise from the origin in the main trunk of the glossopharyngeal nerve IX (i.e., cranial nerve IX). (The vagus nerve, or cranial nerve X, is labeled "X" in Figure 1B.) One branch of the carotid sinus nerve pathway along the anterior medial side of the internal carotid artery ("Int.C" in Figure 1B) terminates at the bifurcation of the carotid sinus and nerve plexus located posterior and medial to the internal carotid artery at the bifurcation of the common carotid artery ("CC" in Figure 1B). The other branch terminates directly within the nerve plexus.

[0013] Figures 2A - 2D are anatomical diagrams showing different patterns of the vagus nerve in the region of the carotid sinus. Referring to Figures 2A - 2D together, in addition to the CSN, the intercarotid nerve plexus includes the afferent branches of the vagus nerve X that are specific to the baroreflex. Four distinct patterns are identified in Figures 2A - 2D, all of which include branches of the vagus nerve X in the intercarotid nerve plexus.

[0014] Both the CSN and the vagus nerve X include afferent nerve fibers that carry signals to the central nervous system and efferent nerve fibers that carry signals away from the central nervous system. In some embodiments, the systems, devices, and methods described herein include stimulating carotid sinus afferent nerve fibers and cardiac-specific vagal afferent nerve fibers to treat hypertension and / or other appropriate diseases. In some embodiments, one or both of these types of nerve fibers (i.e., carotid sinus afferent nerve fibers and / or cardiac-specific vagal afferent nerve fibers) can be identified before being stimulated. For the purposes of this disclosure, carotid sinus afferent nerve fibers may be collectively referred to as the "carotid sinus nerve," and cardiac-specific vagal afferent nerve fibers may be collectively referred to as the "vagus nerve." In some embodiments, for example, the electrodes of the systems described herein can be placed on or around the carotid sinus nerve and the vagus nerve, and such electrodes can be used to stimulate carotid sinus afferent nerve fibers and / or cardiac-specific vagal afferent nerve fibers.

[0015] III. Detection of cardiac depolarization, and / or stimulation of baroreceptors, and related systems, devices, and methods FIG. 3 is a partial schematic view of a patient treatment system 100 (the "system 100") implanted in a patient's CSN according to an embodiment of the present technology. The system 100 can be disposed around the CSN to target some or all of the pressure receptor afferent nerve fibers within the CSN. The system 100 can be delivered subcutaneously to the region of interest and placed over a nerve plexus including the CSN and the vagus nerve, as described above with reference to the anatomical figures of FIGS. 1A-2D. As described herein, the lead body of the signal delivery device of the system 100 can include a first region having a first lead electrode and a second region having a second electrode positionable over the first region. In such an embodiment, the lead body can be in the shape of a book in that the lead body is connected along one edge and open along the opposite edge. The open edge can open to partially enclose or surround one or more nerves and then close to hold the nerves. Accordingly, the lead electrodes can extend across the lead body along a first axis extending in a first direction, and the nerves can extend along a second direction angled and / or perpendicular to the first direction.

[0016] As described herein, system 100 can detect cardiac depolarization (e.g., via electrical or acoustic signals generated therefrom) and adjust treatment at least in part based on the signals. Signals corresponding to cardiac depolarization can be detected from various combinations of the base electrodes and / or lead electrodes of the signal delivery device, as well as via other input / output devices of system 100 (e.g., accelerometers or other acoustic devices). Additionally, signal detection can be used to map the patient's tissue, in which regard it can assist in positioning the lead body of the signal delivery device at a desired location (e.g., proximate to the patient's CSN afferent fibers). Additionally or alternatively, the patient's tissue can be mapped by imaging the tissue, e.g., using optical coherence tomography (OCT) imaging, ultrasound, and / or other suitable imaging techniques. The patient's target nerve fibers can be identified in the image and used to assist in positioning the lead body at a desired location. In these and / or other embodiments, one or more patient tissues can be mapped by applying a stimulus (e.g., electrical stimulation via a temporary or chronic stimulation device) and observing the patient's response (e.g., motor response) to the applied stimulus. System 100 can determine one or more physiological parameters of the patient and, when the lead body is in the desired position, adjust the treatment delivered to the patient at least in part based on the physiological parameters. Treatment delivery to the patient, and more particularly to the CSN afferent fibers, can be provided via one or more of the lead electrodes. In some embodiments, system 100 includes one or more sensors configured to detect muscle fascicle contractions, and the treatment can be adjusted at least in part based on one or more muscle fiber contractions detected by the one or more sensors.

[0017] Figures 4A and 4B are partial schematic diagrams of various embodiments of the system 100 shown in FIG. 3, according to embodiments of the present technology. Referring to both FIGS. 4A and 4B, the system 100 includes an implantable neuromodulator 101 (e.g., a signal generator or an implanted pulse generator (“IPG”)), and one or more signal delivery elements or devices 121 (“signal delivery device 121”) electrically connectable to the neuromodulator 101. The signal delivery device 121 can be implanted within a patient and can retain features for delivering therapy to the patient after implantation. The neuromodulator 101 can be directly connected to the signal delivery device 121, or can be connected to the signal delivery device 121 via a signal link or lead extension. As described herein (e.g., with reference to FIGS. 5A-7B), the signal delivery device 121 can include a lead body 125 having one or more lead electrodes and one or more conductors 123 extending from the lead electrodes and electrically coupling the lead electrodes to the neuromodulator 101. As used herein, the terms signal delivery device, lead, and / or lead body include any of a number of suitable substrates and / or support members that hold electrodes / devices for providing a therapy signal to a patient. For example, the lead body 125 can include one or more electrodes or electrical contacts that direct an electrical signal to a patient's tissue or fibers (e.g., to treat hypertension). In other embodiments, the signal delivery device 121 can include structures other than the lead body that also direct electrical signals and / or other types of signals to the patient.

[0018] The neuromodulator 101 can include a housing 103 made of a conductive material (e.g., titanium or other metal), and one or more base electrodes (e.g., contacts) 117A, 117B held by the housing 103 and spaced apart from each other (e.g., to generate a sufficient vector). The base electrodes 117A, 117B can serve as an anode / cathode pair and can each be electrically coupled to respective lead electrodes of a lead body 125 via a conductor 123. In some embodiments, the base electrodes 117A, 117B can be contacts that are exposed conductive portions of the housing 103. As shown in FIG. 4A, the base electrodes 117A, 117B are included in the header portion 115 of the neuromodulator 101 and are spaced apart from each other by a minimum distance (D1) that can be at least 1.0 inch, 1.5 inches, or 2 inches. As shown in FIG. 4B, the neuromodulator 101 can include an insulating or non-conductive material 104. In such embodiments, the base electrodes 117A, 117B can be spaced apart from each other along the height of the neuromodulator 101. For example, one of the base electrodes 117A can be on the header portion 115, and the other of the base electrodes 117B can be in another portion of the neuromodulator that is not covered by the insulating material 104.

[0019] Referring again to FIGS. 4A and 4B together, the neuromodulator 101 can transmit a signal (e.g., an electrical signal, a neuromodulation pulse, etc.) to a signal delivery device 121 that upregulates (e.g., excites) and / or downregulates (e.g., blocks or inhibits) the target nerve. As used herein, unless otherwise stated, the terms "modulate", "modulation", "stimulate", and "stimulation" comprehensively refer to a signal having any type of the above-described effects on the target nerve. The neuromodulator 101 can include a machine-readable (e.g., computer-readable) medium containing instructions for generating and transmitting an appropriate treatment signal. The neuromodulator 101 and / or other elements of the system 100 can include one or more processors 105, a memory unit 107, and / or an input / output device 109 ("I / O device 109"). Thus, the process of providing an adjustment signal, providing guidance information for positioning the signal delivery device 121 (e.g., with respect to the target fibers of a patient), and / or performing other related functions can be executed by a computer-readable medium located in the neuromodulator 101 and / or other system components, on this computer-readable medium, or by computer-executable instructions included in this computer-readable medium. The neuromodulator 101 and / or other system components can include dedicated hardware, firmware, and / or software for executing computer-executable instructions for performing any one or more of the methods, processes, and / or sub-processes described herein (e.g., the methods, processes, and / or sub-processes described herein). The dedicated hardware, firmware, and / or software also serves as a "means" for implementing the methods, processes, and / or sub-processes described herein. The neuromodulator 101 can also include a single housing as shown in FIGS. 4A and 4B, or a plurality of parts, elements, and / or subsystems (e.g., for directing signals according to a plurality of signal delivery parameters) held in a plurality of housings.In some embodiments, system 100 can include an external device (e.g., a controller or a physician's programmer) 111 capable of controlling and executing a treatment provided via system 100.

[0020] The neuromodulator 101 can also receive and respond to input signals received from one or more sources. The input signals can direct or affect the manner in which treatment and / or process instructions are selected, executed, updated, and / or otherwise carried out. The input signals can be received from one or more sensors (e.g., I / O device 109) that are held by the neuromodulator 101 and / or distributed outside of the neuromodulator 101 (e.g., at a location of another patient) while still communicating with the neuromodulator 101. The sensors and / or other I / O devices 109 can provide inputs that depend on or reflect the patient's state (e.g., the patient's position, the patient's posture, the patient's heart rate, the patient's blood pressure, and / or the patient's activity level), and / or inputs that are independent of the patient (e.g., time).

[0021] In some embodiments, the I / O device 109 can include an accelerometer (e.g., a multi-axis accelerometer or a tri-axis accelerometer). In such embodiments, the accelerometer can be used to detect or obtain an acoustic signal generated from and / or associated with cardiac depolarization. In addition to or alternatively to the electrical signals generated from and / or associated with cardiac depolarization detected at least via the base electrodes 117A, 117B of the neuromodulator 101 and / or the lead electrodes of the lead body 125, an acoustic signal can be utilized. In addition to or alternatively to determining an acoustic signal generated from and / or associated with cardiac depolarization, the accelerometer can be configured to detect an acoustic signal associated with an air flow, e.g., to measure the patient's respiratory rate and / or other respiration-related information (e.g., apnea, hypopnea, snoring detection, etc.). In these and / or other embodiments, the accelerometer can be used to determine the patient's posture and / or orientation with respect to the gravitational field, including whether the patient is standing, sitting, lying down (e.g., sleeping), etc. In such embodiments, the accelerometer can, for example, serve as a fall detector or a safety mechanism, and signals from the accelerometer can be used to adjust the stimulation or characteristics of the neuromodulation pulses. In some embodiments, the I / O device 109 can include a blood pressure monitor for determining the degree of arterial wall stiffness, or other devices for determining a diastolic pressure waveform or index. As described herein, the degree of arterial wall stiffness and / or the diastolic pressure waveform or index can be used as physiological parameters that can partially affect the characteristics of the neuromodulation pulses provided to the patient via the signal delivery device 121.

[0022] In some embodiments, data from an accelerometer can be used to detect whether a patient is asleep and / or the patient's actual or predicted sleep state (e.g., REM, non-REM, etc.). For example, the physical orientation of the accelerometer and / or changes (or lack thereof) in movement can indicate when a patient has been in a supine position or otherwise not moving over a long period of time, thereby indicating that the patient is asleep. In some embodiments, data from the accelerometer (e.g., one or more acoustic signals, the patient's posture, the patient's orientation, etc.) can be compared with data from one or more other sensors (e.g., a heart rate sensor) to detect whether the patient is asleep and / or the patient's actual or predicted sleep state. Using whether the patient is asleep and / or these and / or other data associated with the patient's sleep state, the neuromodulation pulses delivered to the patient can be adjusted. For example, the intensity of the neuromodulation pulses can be reduced to conserve energy during non-REM sleep. This is because, for example, the activity of the patient's sympathetic nervous system is predicted to be low or minimal during these times.

[0023] In some embodiments, the I / O device 109 can be configured to detect and / or receive input from the patient corresponding to the patient's activity or state. For example, the I / O device 109 can include a software application configured to enable the user to select one or more profiles associated with the patient's physical, mental, and / or emotional state. These can include, for example, structured exercise (e.g., aerobic exercise such as jogging, elliptical, walking, cycling, swimming, etc., strength training such as weightlifting, isometric exercise such as yoga, sit-ups, push-ups, etc.), non-active wakefulness, sleep, anxiety or stress, during and / or after meals, defecation, sexual intercourse, etc. Using these and / or other physiological parameters, the neuromodulation pulses delivered to the patient can be adjusted.

[0024] In some embodiments, the neuromodulator 101 and / or the signal delivery device 121 can obtain power from an external power source (not shown) to generate a treatment signal. In some embodiments, the external power source can transmit power to the implanted neuromodulator 101 and / or directly transmit to the signal delivery device 121 using electromagnetic induction (e.g., RF signals). For example, the external power source can include an external coil that communicates with a corresponding internal coil within the implantable neuromodulator 101, the signal delivery device 121, and / or the power relay component. The external power source may be portable for ease of use.

[0025] Figures 5A - 11 are partial schematic views of various embodiments of the lead bodies 525, 625, 725, 825, 925, 1025, 1125 of the respective signal delivery devices 521, 621, 721, 821, 921, 1021, 1121 configured according to embodiments of the present technology. Figures 5A, 6A, 7A, 8A, 9, 10, 11A, and 11 show plan views of the lead bodies 525, 625, 725, 825, 925, 1025, 1125 in an open configuration, and Figures 5B, 6B, 7B, and 8B show cross-sectional views of the lead bodies 525, 625, 725, 825 in a closed configuration. The signal delivery devices 521, 621, 721, 821, 921, 1021, 1121 shown in and described with reference to Figures 5A - 11E include any one or more of the features of the signal delivery device 121 of Figures 4A and / or 4B and can be generally similar to this signal delivery device 121. Further, the signal delivery device 121 can include any one or more of the features of the signal delivery devices 521, 621, 721, 821, 921, 1021, 1121 described herein.

[0026] As shown in FIG. 5A, the signal transmission device 521 includes a first region 530 (e.g., a first plate, a first surface, a first substrate, etc.), a second region 540 (e.g., a second plate, a second surface, a second substrate, etc.), an intermediate region 550 between the first region 530 and the second region 540, and a lead body 525 including lead electrodes. One or both of the first region 530 and the second region 540 can include one or more grip tabs, rounded edges, and / or other features to facilitate embedding. The lead electrodes can be positioned on one or more sides (e.g., the front side, the back side, etc.) of the lead body 525, and can include a first set of lead electrodes 531A - 531E (collectively referred to as the "first lead electrodes 531") on the first region 530 and a second set of lead electrodes 541A - 541E (collectively referred to as the "second lead electrodes 541") on the second region 540. The first lead electrodes 531 can be aligned on the first region 530 in a direction that is at least generally perpendicular to the intermediate region 550 (e.g., as shown in FIG. 5A) or in a direction that is at least generally parallel to the intermediate region 550 (e.g., as shown in FIG. 5C). Similarly, the second lead electrodes 541 can be aligned on the second region 540 in a direction that is at least generally perpendicular to the intermediate region 550 (e.g., as shown in FIG. 5A) or in a direction that is at least generally parallel to the intermediate region 550 (e.g., as shown in FIG. 5C). Returning to FIG. 5A, the individual ones of the first lead electrodes 531 and / or the second lead electrodes 541 can have a length and / or width of up to 5 mm, for example up to 4 mm, up to 3 mm, up to 2 mm, up to 1 mm, up to 0.5 mm, etc. In at least some embodiments, for example, one or more of the first lead electrodes 531 and / or one or more of the second lead electrodes 541 have a length of 2 mm and a width of 0.8 mm. The first and second lead electrodes 531, 541 have a rectangular shape in the embodiment shown in FIG. 5A, but in other embodiments, the individual ones of the first and / or second lead electrodes 531, 541 can have a circular, oval, square, pentagonal, hexagonal, annular, "X", zigzag, and / or other suitable shape.Each of the first lead electrode 531 and the second lead electrode 541 can be a positively charged electrode or a negatively charged electrode. In some embodiments, the first lead electrode 531 and the second lead electrode 541 can include electrodes charged alternately. For example, the primary first lead electrode 531A can be positively charged, the secondary first lead electrode 531B can be negatively charged, the tertiary first lead electrode 531C can be positively charged, and so on. In some embodiments, all of the first lead electrodes 531 are positively charged electrodes and all of the second lead electrodes 541 are negatively charged electrodes (and vice versa). The first lead electrode 531 and the second lead electrode 541 can each extend across the same distance (D2) of their respective first region 530 and second region 540. The first region 530 can be positioned over the second region 540, for example, by folding the first region 530 over the second region 540 (and vice versa) about the intermediate region 550 as a center. An individual pair of the first and / or second lead electrodes 531, 541 can be referenced relative to one or more other pairs of the first and / or second lead electrodes 531, 541 (e.g., to determine relative impedance, treatment delivery efficiency, map the patient's tissue, etc.).

[0027] The signal transmitting device 521 can further include conductors extending from the lead electrodes to the neuromodulator 101 (Figs. 4A and 4B). The conductors can include a first conductor 524A and a second conductor 523B (collectively referred to as "conductor 523"), each of which is schematically shown as a single line in Fig. 5A. Individual ones of the first conductor 523A can be electrically coupled to one of the first lead electrodes 531. For example, a primary first conductor can be electrically coupled to the primary first lead electrode 531A, a secondary first conductor can be electrically coupled to the secondary first lead electrode 531B, and so on. Similarly, individual ones of the second conductor 523B can be electrically coupled to one of the second lead electrodes 541. For example, a primary second conductor can be electrically coupled to the primary second lead electrode 541A, a secondary second conductor can be electrically coupled to the secondary second lead electrode 541B, and so on. Each of the conductors 523 is electrically coupled to (i) at least one of the first lead electrode 531 or the second lead electrode 541, and (ii) at least one of the base electrodes 117 of the neuromodulator 101 (Fig. 4A or Fig. 4B). Thus, in some embodiments, each of the lead electrodes can be individually selectable and / or addressable via a conductive path including any of the base electrodes 117.

[0028] As shown in FIG. 5B, the second region 540 is positioned over the first region 530, and in such a configuration, the individual first lead electrodes 531 are positioned over or at least partially over (e.g., at least partially aligned with and / or overlapping) the corresponding individual second lead electrodes 541. For example, when the first region 530 is positioned over the second region 540, the primary first lead electrode 531A is positioned over the primary second lead electrode 541A, the secondary first lead electrode 531B is positioned over the secondary second lead electrode 541B, and so on. In some embodiments, the individual first lead electrodes 531 and the individual second lead electrodes 541 can span the same distance (D3) of the corresponding first region 530 or second region 540 and / or can completely overlap each other. In other embodiments, one or more of the individual first lead electrodes 531 can span different distances of the corresponding first region 530 or second region 540 and / or can be offset relative to each other.

[0029] During operation, the signal delivery device 521 (more particularly, the lead body 525) can be positioned around a target area or nerve (e.g., an afferent nerve fiber) in the CSN. For example, the first region 530 and / or the first lead electrode 531 can be on a first side of the target nerve, and the second region and / or the second lead electrode 541 can be on a second, opposite side of the target nerve. The signal delivery device 521 can deliver a neuromodulation pulse to the target nerve via one or more of the lead electrodes, for example, as a monopolar stimulation or a multipolar stimulation (e.g., bipolar stimulation, tripolar stimulation, etc.). For example, the neuromodulation pulse can be delivered as a monopolar stimulation via one of the first lead electrodes 531 or one of the second lead electrodes 541, or as a bipolar stimulation via a combination of the first and second lead electrodes 531, 541 (e.g., primary first lead electrode 531A and primary second lead electrode 541A). Additionally or alternatively, the first lead electrode 531 and / or the second lead electrode 541 can be positively biased (+) or negatively biased (-) and can have a plurality of configurations. For example, adjacent electrodes can have a configuration including, among several other possibilities, +--+, +-+, -++-, -+-, +---+, -+++-, or +-, and opposing electrodes (e.g., when the second region 540 is positioned over the first region 530) can be biased complementarily. Advantageously, the configuration of the first lead electrode 531 with respect to the second lead electrode 541 can reduce the energy required to deliver a stimulus to the target nerve. In other words, by arranging the individual lead electrodes on the first region 530 and the second region 540 that face each other and on opposite sides of the target nerve, embodiments of the present technique enable the delivery of a bipolar stimulation that targets a specific nerve while also minimizing the amount of energy required to do so.

[0030] As shown in FIG. 5D, in some embodiments, the intermediate first and second lead electrodes 531, 541 can have one polarity, and the peripheral first and second lead electrodes 531, 541 can have the opposite polarity. For example, in FIG. 5D, the secondary, tertiary, and quaternary first lead electrodes 531B - D (i.e., the intermediate electrodes) are cathodes, and the primary and quinary first lead electrodes 531A, 531E (i.e., the peripheral electrodes) are anodes. In such embodiments, the secondary and quaternary lead electrodes 531B, 531D can be configured to act as guard cathodes such that the first and second electric fields EF1, EF2 generated between, for example, the tertiary first lead electrode 531C and the primary and quinary first lead electrodes 531A, 531E extend deeper into the patient's tissue. For example, the secondary first lead electrode 531B and the primary first lead electrode 531A can cooperate to generate a third electric field EF3. The first electric field EF1 between the tertiary first lead electrode 531C and the primary first lead electrode 531A can extend deeper into the patient tissue so as to avoid or bypass the third electric field EF3. Similarly, the quaternary lead electrode 531D and the quinary first lead electrode 531E can cooperate to generate a fourth electric field EF4. The second electric field EF2 between the tertiary first lead electrode 531C and the quinary first lead electrode 531E can extend deeper into the patient tissue so as to avoid or bypass the fourth electric field EF2. In some embodiments, the depth of the first and second electric fields EF1, EF2 can be improved by varying the size of the individual ones of the first lead electrodes 531. For example, the secondary and quaternary first lead electrodes 531B, 531D can be made smaller than the primary, tertiary, and / or quinary first lead electrodes 531A, C, D (e.g., can have a smaller outer perimeter and / or a smaller surface area). Each of the second lead electrodes 541 can be configured to be generally similar to or the same as the corresponding ones of the first lead electrodes 531.

[0031] As shown in FIGS. 5A to 5D, the signal transmitting device 521 includes ten lead electrodes. However, in other embodiments, as shown in FIGS. 6A to 10, the signal transmitting device can include more or fewer (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 12, 14, 15, 16, or 20) lead electrodes. Additionally or alternatively, the lead electrodes can be arranged in different configurations. As shown in FIG. 6A, the signal transmitting device 621 includes many of the same features of the signal transmitting device 521 (FIG. 5A) including a first region 530, a second region 540, an intermediate region 550, and a first lead electrode 531. The signal transmitting device 621, or more specifically the lead body 625, also includes a second lead electrode including a primary second lead electrode 641A, a secondary second lead electrode 614B, and a tertiary second lead electrode 641C (collectively referred to as the "second lead electrode 641"). The first lead electrode 531 and the second lead electrode 641 can each extend over the same distance (D2) of their respective first region 530 and second region 540. As shown in FIG. 6B, the primary second lead electrode 641A can extend over a distance (D4) equal to that of the primary and secondary first lead electrodes 531A, 531B. A first conductor 523A can be electrically coupled to the first lead electrode 531, and one or more second conductors 623B can be electrically coupled to the second lead electrode 641.

[0032] The arrangement of the lead electrodes on the lead body 625 can provide a number of advantages for delivering stimulation to a patient. For example, having a first region 530 with a first lead electrode 531 and a second region 540 with a second lead electrode 541 (FIG. 5A), but with fewer second lead electrodes 641, can reduce the energy required to deliver bipolar stimulation to the target nerve between the first and second regions 530, 540. Additionally, including a single electrode (e.g., a primary second lead electrode 641A) having a greater width or surface area that is at least equal to that of a plurality of electrodes (e.g., primary and secondary first lead electrodes 541A, 541B) can enable the signal delivery device 621 to use less energy to deliver bipolar stimulation while still covering at least the same amount of the surface area of the lead body 625. In doing so, the lead electrodes on the first region 530 and the second region 540 can still precisely target a particular nerve or area where improved treatment of the patient results. Further, including a single electrode (e.g., a primary second lead electrode 641A) having a greater width or surface area that is at least equal to that of a plurality of electrodes (e.g., primary and secondary first lead electrodes 541A, 541B) can activate more of the particular tissue that may be necessary to obtain the desired effect. In other words, smaller electrodes may not excite enough tissue to obtain the desired effect.

[0033] Next, referring to FIG. 7A, the signal transmitting device 721 includes many of the same features of the signal transmitting devices 521, 621 (FIGS. 5A and 6A) including the first region 530, the second region 540, the intermediate region 550, and the first lead electrode 531. The signal transmitting device 721, or more particularly the lead body 725, also includes a second lead electrode 741 in the second region 540. As shown in FIGS. 7A and 7B, the first lead electrode 531 and the second lead electrode 741 can each extend over the same distance (D2) of their respective first region 530 and second region 540. The first conductor 523A can be electrically coupled to the first lead electrode 531, and one or more second conductors 723B can be electrically coupled to the second lead electrode 641.

[0034] The arrangement of the lead electrodes on the lead body 725 can provide a number of advantages for delivering stimulation to a patient. For example, by having a first region 530 with a first lead electrode 531 and a second region 540 with a single second lead electrode 741 (e.g., relative to the second lead electrode 541 of FIG. 5A), the energy required to deliver bipolar stimulation to the target nerve between the first and second regions 530, 540 can be reduced. Additionally, by including a single lead electrode on the second region 540 having at least an equal width or surface area as that of a plurality of electrodes (e.g., primary and secondary first lead electrodes 541A, 541B), it is possible for the signal transmitting device to use less energy to deliver bipolar stimulation while still covering at least the same amount of the surface area of the lead body 725. In doing so, the lead electrodes on the first region 530 and the second region 540 can still precisely target a particular nerve or area that treats the patient's hypertension or provides other treatment.

[0035] Next, referring to FIG. 8A, signal transmission device 821 includes many of the same features of signal transmission device 521 (FIG. 5A) including a first region 530, a second region 540, an intermediate region 550, a first lead electrode 531, and a second lead electrode 541. Signal transmission device 821, and more particularly lead body 825, includes a first set of stitching holes 833A - 833D (collectively, "first stitching holes 833") on the first region 530 and a corresponding set of second stitching holes 843A - 843D (collectively, "second stitching holes 843") on the second region 540. In the illustrated embodiment, the first stitching holes 833 are positioned laterally between the first lead electrode 531 and the first or left end portion 827A of the lead body 825, or laterally outside the first lead electrode 531. The second stitching holes 843 are positioned laterally between the second lead electrode 541 and the second or right end portion 827B of the lead body 825, or laterally outside the second lead electrode 541. In other embodiments, one or more of the first stitching holes 833 and / or the second stitching holes 843 can be positioned at other locations on the signal transmission device, such as the top and / or bottom of the first region 530 and / or the second region 540.

[0036] Continuing to refer to the illustrated embodiment, the first stitching holes 833 are aligned with each other in the first direction, and the first lead electrodes 531 are aligned with each other in a second direction that is perpendicular or at least generally perpendicular to the first direction. In addition, the second stitching holes 843 are aligned with each other in the first direction, and the second lead electrodes 541 are aligned with each other in the second direction. In other embodiments, the first stitching holes 833 can be positioned between the first lead electrodes 531 and the intermediate region 550, toward another side of the first lead electrodes 531, between individual ones of the first lead electrodes 531, and / or at other suitable positions and / or orientations relative to the first lead electrodes 531. In these and other embodiments, the second stitching holes 843 can be positioned between the second lead electrodes 541 and the intermediate region 550, toward another side of the second lead electrodes 541, between individual ones of the second lead electrodes 541, and / or at other suitable positions and / or orientations relative to the second lead electrodes 541.

[0037] Referring further to FIG. 8B, the first region 530 can be positioned over the second region 540, for example, by folding the first region 530 over the second region 540 (and vice versa) about the intermediate region 550. In this configuration, the individual first stitching holes 833 are positioned over or at least partially over (e.g., at least partially aligned with and / or overlapping) the corresponding individual second stitching holes 843. For example, when the first region 530 is positioned over the second region 540, the primary first stitching hole 833A is positioned over the primary second stitching hole 843A, and so on. Each of the second stitching holes 843 receives the corresponding one of the first stitching holes 833 and can be configured, for example, to at least partially fix the first region 530 and the second region 540 to each other and / or to prevent or at least partially prevent the signal transmitting device 821 from transitioning from the folded state. In some embodiments, the individual first stitching holes 833 and the individual second stitching holes 843 can extend the same distance (D5) of the corresponding first region 530 or second region 540 and / or can completely overlap each other. In other embodiments, one or more of the individual first stitching holes 833 can extend different distances of the corresponding first region 530 or second region 540 and / or can be offset relative to each other.

[0038] Next, referring to FIG. 9, signal delivery device 921 includes many of the same features of signal delivery device 821 (FIG. 8A) including a first region 530, a second region 540, an intermediate region 550, a first suture hole 833, and a second suture hole 843. Further, signal delivery device 921, or more particularly lead body 925, includes a first set of lead electrodes 931A - 931D (collectively referred to as "first lead electrodes 931") on first region 530 that may be at least generally similar or identical in structure and / or function to first lead electrode 531 (FIGS. 5A, 6A, 7A, 8A), and a second set of lead electrodes 941A - 941D (collectively referred to as "second lead electrodes 941") on second region 540 that may be at least generally similar or identical in structure and / or function to second lead electrode 541 (FIGS. 5A and 8A). Further, signal delivery device 921, or more particularly, lead body 925, includes a third lead electrode 935 on first region 530 and a fourth lead electrode 945 on second region 540. Third lead electrode 935 and first lead electrodes 931 can span the same distance (D2) on first region 530, and / or fourth lead electrode 945 and second lead electrodes 941 can span the same distance (D2) on second region 540. In the illustrated embodiment, third lead electrode 935 and fourth lead electrode 945 are positioned proximate, for example, to a third or lower end portion 927C of lead body 925 where pairs of conductors 923A - 923B are coupled. Thus, in the illustrated embodiment, first lead electrodes 931 are positioned between third lead electrode 935 and a fourth or upper end portion 927D of lead body 925, and second lead electrodes 941 are positioned between fourth lead electrode 945 and upper end portion 927D. One or more first conductors 923A can be electrically coupled to first lead electrodes 931 and / or third lead electrode 935, and / or one or more second conductors 923B can be electrically coupled to second lead electrodes 941 and / or fourth lead electrode 945.

[0039] The first region 530 can be positioned over the second region 540, for example, by folding the first region 530 over the second region 540 (and vice versa) about the intermediate region 550. In this configuration, each individual first lead electrode 931 is positioned over or at least partially over (e.g., at least partially aligned with and / or overlapping) the corresponding individual second lead electrode 941. For example, when the first region 530 is positioned over the second region 540, the primary first lead electrode 931A is positioned over the primary second lead electrode 941A, and so on. Additionally, in some embodiments, the third electrode 935 is positioned over the fourth electrode 945.

[0040] Referring next to FIG. 10, the signal transmitting device 1021 includes many of the same features of the signal transmitting device 921 (FIG. 9) including the first region 530, the second region 540, the intermediate region 550, the first lead electrodes 931, the third lead electrode 935, the stitching holes 833, and the stitching holes 843. Additionally, the signal transmitting device 921, or more particularly the lead body 925, includes a second set of lead electrodes 1041A - 1041D (collectively, "second lead electrodes 1041") on the second region 540 that can have a structure and / or function that is at least generally similar or identical to the second lead electrodes 941 (FIG.9). Further, the signal transmitting device 921, or more particularly the lead body 925, includes a fourth lead electrode 1045 on the second region 540 that can have a structure and / or function that is at least generally similar or identical to the fourth lead electrode 945 (FIG.9). The fourth lead electrode 1045 and the second lead electrodes 1041 can extend over the same distance (D2) on the second region 540. In the illustrated embodiment, the fourth lead electrode 1045 is positioned proximate the upper end portion 927D of the lead body 925 such that the second lead electrodes 1041 are positioned between the fourth lead electrode 1045 and the upper end portion 927D, e.g., on the opposite side of the configuration of the first lead electrodes 931 and the third lead electrode 935.

[0041] The first region 530 can be positioned over the second region 540, for example, by folding the first region 530 over the second region 540 (and vice versa) about the intermediate region 550. In this configuration, each individual first lead electrode 931 is positioned over or at least partially over (e.g., at least partially aligned with and / or overlapping) the corresponding individual second lead electrode 941. In some embodiments, the third lead electrode 935 can be positioned over or at least partially over one or more of the second lead electrodes 1041, and / or the fourth lead electrode 1045 can be positioned over or at least partially over one or more of the first lead electrodes 931.

[0042] The lead electrodes of the lead bodies 525, 625, 725, 825, 925, 1025 shown in FIGS. 5A, 6A, 7A, and 8A - 10 are included over both the first region 530 and the second region 540 thereof. However, in some embodiments, the lead electrodes may be included only over one of the first region 530 or the second region 540. That is, in some embodiments, the lead electrodes may not be included over one of the first region 530 or the second region 540. In such embodiments, monopolar stimulation can be delivered through one of the lead electrodes, and bipolar stimulation can be delivered through two or more of the lead electrodes (e.g., adjacent lead electrodes). Advantageously, in such embodiments, the lead electrodes can have a lower required impedance, lower energy requirements, and / or less unintended stimulation of non - target nerves and tissues.

[0043] Next, referring to FIG. 11A, signal transmission device 1121 includes a lead body 1125, one or more conductors 1123, and a connector portion 1122. The lead body 1125 will be described in more detail below with reference to FIG. 11B, and the connector portion 1122 will be described in more detail below with reference to FIG. 11C. The conductors 1123 extend between the lead body 1125 and the connector portion 1122 and can be coupled thereto (e.g., communicatively, electrically, mechanically, etc.). In the illustrated embodiment, the conductors 1123 include a first conductor branch 1123A and a second conductor branch 1123B, each of which can be coupled to a respective part or region of the lead body 1125. For example, the first conductor branch 1123A can be coupled to a first body region (and / or one or more of its features) of the lead body 1125, and the second conductor branch 1123B can be coupled to a second body region (and / or one or more of its features) of the lead body 1125.

[0044] Next, referring to FIG. 11B, the lead body 1125 includes many of the same features of the lead body 525 (FIG. 5A) including a first region 530, a second region 540, an intermediate region 550, a first lead electrode 531, and a second lead electrode 541. The lead body 1125 includes first electrical contacts 1132A / B / C / D (collectively referred to as "first electrical contacts 1132") coupled to each of the first lead electrodes 531, and second electrical contacts 1142A / B / C / D (collectively referred to as "second electrical contacts 1142") coupled to each of the second lead electrodes 541. For example, the primary first lead electrode 531A is coupled to the primary first electrical contact 1132A, the secondary first lead electrode 531B is coupled to the secondary first electrical contact 1132B, the tertiary first lead electrode 531C is coupled to the tertiary first electrical contact 1132C, and the quaternary and quinary first lead electrodes 531D, 531E share the quaternary first electrical contact 1132D. Similarly, the primary and secondary second lead electrodes 541A, 541B share the primary second electrical contact 1142A, the tertiary second lead electrode 541C is coupled to the secondary second electrical contact 1142B, the quaternary second lead electrode 541D is coupled to the tertiary second electrical contact 1142C, and the quinary second lead electrode 541E is coupled to the quaternary second electrical contact 1142D. In other embodiments, all of the first and / or second lead electrodes 531, 541 can have their own electrical contacts or can share electrical contacts. For example, as shown in FIG. 11D, in some embodiments, each of the first lead electrodes 531A-531E (collectively referred to as "first lead electrodes 531") has a corresponding first electrical contact 1132A-E (collectively referred to as "first electrical contacts 1132"), and each of the second lead electrodes 541A-541E (collectively referred to as "second lead electrodes 541") has a corresponding second electrical contact 1142A-E (collectively referred to as "second electrical contacts 1142").In these and / or other embodiments, the individual ones of the first electrical contact 1132 and / or the second electrical contact 1142 can be positioned at the sides of the corresponding ones of the first lead electrode 531 and / or the second lead electrode 541, for example, proximate to one or more side portions of the lead body 1125. For example, as shown in FIG. 11D, the first electrical contacts 1132A - C and the second electrical contacts 1142A - C are positioned proximate to the fourth or upper portion 1127D of the lead body 1125, and the first electrical contacts 1132D, 1132E and the second electrical contacts 1142D, 1142E are positioned proximate to the third or lower portion 1127C of the lead body 1125. As another example, in the embodiment shown in FIG. 11B, each of the electrical contacts 1132, 1142 is positioned proximate to the same side of the lead body 1125, for example, the same side of the first and second lead electrodes 531, 541. Additionally, in the embodiment shown in FIG. 11B, each of the electrical contacts 1132, 1142 is positioned closer to the intermediate region 550 than the corresponding first and second lead electrodes 531, 541.

[0045] Referring again to FIG. 11B, the lead body 1125 can include a first tab or elongated portion 1134 extending from a first side surface portion 1127A of the first region 530 and a second tab or elongated portion 1144 extending from a second side surface portion 1127B of the second region 540. The tabs 1134, 1144 can be tapered and can assist an operator in positioning the lead body 1125 and / or operating it in other ways. For example, the operator can grip one or both of the tabs 1134, 1144 when translating the lead body 1125 between an open configuration and a closed configuration, when implanting the lead body 1125, etc. The first side surface portion 1127A can be on the opposite side of the intermediate region 550 from the first region 530 such that the first region 530 is positioned between the first tab 1134 and the intermediate region 550. Similarly, the second side surface portion 1127B can be on the opposite side of the intermediate region 550 from the second region such that the second region 540 is positioned between the first tab 1144 and the intermediate region 550. In these and / or other embodiments, one or more tabs can be positioned on other sides of the lead body 1125, for example adjacent to the intermediate region 550. Further, in these and / or other embodiments, the lead body 1125 can include one or more alignment and / or orientation features 1124 to assist, for example, an operator in identifying which face / surface of the lead body 1125 includes the lead electrodes 531, 541. In the illustrated embodiment, the second tab 1144 includes the alignment and / or orientation features 1124. In other embodiments, the first tab 1134 and / or another portion of the lead body 1125 can include one or more of the alignment and / or orientation features 1124. In these and / or other embodiments, the individual ones of the one or more alignment and / or orientation features 1124 can be formed on the lead body 1125 by printing, etching, deposition, or other means. In the illustrated embodiment, the alignment feature 1124 includes the letter "F".The lead body 1125 can be at least partially transparent, and thus, for example, since the appearance of the character "F" is specific to the direction and has different appearances when viewed from the front and the back, the operator can use the character "F" to identify which surface of the lead body 1125 includes the lead electrodes 531, 541. In these and / or other embodiments, one or more of the alignment and / or orientation features 1124 can have a different direction-specific configuration.

[0046] Next, referring to FIG. 11C, the connector portion 1122 can include one or more lead terminals 1126 positioned at least partially around the conductor 1123. In the embodiment shown, the connector portion 1122 includes eight lead terminals 1126A - H, each electrically coupled to one of the electrical contacts 1132, 1142 (FIG. 11B). For example, the primary first electrical contact 1132A can be coupled to the first lead terminal 1126A, the secondary first electrical contact 1132B can be coupled to the second lead terminal 1126B, the tertiary first electrical contact 1132C can be coupled to the third lead terminal 1126C, the quaternary first electrical contact 1132D can be coupled to the fourth lead terminal 1126D, the primary second electrical contact 1142A can be coupled to the fifth lead terminal 1126E, the secondary second electrical contact 1142B can be coupled to the sixth lead terminal 1126F, the tertiary second electrical contact 1142C can be coupled to the seventh lead terminal 1126G, and the quaternary second electrical contact 1142D can be coupled to the eighth lead terminal 1126H. In other embodiments, one or more of the electrical contacts 1132, 1142 can be connected to one or more other and / or additional lead terminals 1126. In these and / or other embodiments, the individual ones of the lead terminals 1126 can be received by and / or electrically coupled to an implantable neuromodulator 101 (FIG. 4A) or another signal generator, for example, to enable the implantable neuromodulator 101 to deliver electrical stimulation to a patient via the individual ones of the lead electrodes 531, 541 (FIG. 11B).

[0047] Referring to FIG. 11E, as described above with reference to FIG. 11C, each of the electrical contacts 1132A - E and 1142A - E of the lead body 1125 of FIG. 11D can be connected to the corresponding lead terminals 1126A - J.

[0048] FIG. 12 is a chart 1200 showing the relationship between the frequency of neuromodulation pulses applied via a patient treatment system (e.g., system 100 (FIGS. 3, 4A, 4B)) according to an embodiment of the present technology and the patient's heart rate. In these and / or other embodiments, one or more other neuromodulation pulse parameters (e.g., amplitude, pulse width, duty cycle, etc.), and / or the overall intensity of the neuromodulation pulses (e.g., including values for one or more of the neuromodulation pulse parameters) can be adjusted depending on the heart rate. As used throughout this disclosure, "heart rate" can be an average heart rate over time (e.g., over the preceding 10 seconds, 30 seconds, 1 minute, 2 minutes, etc.), a filtered heart rate (e.g., determined at least in part based on the patient's R-R intervals), or a combination thereof. As described herein, embodiments of the present technology attempt to deliver treatment to a patient, or more particularly, to deliver stimulation to the patient's CSN that is adjusted at least in part based on the patient's activity (e.g., heart rate, R-R interval, dilation index, and / or blood pressure). To do this, the treatment can be delivered to the patient in a non-diminishing manner such that, for example, the frequency of the neuromodulation pulses delivered to the CSN increases as the patient's activity or heart rate increases. In other words, the treatment can be delivered to the patient at least in part based on the patient's heart rate such that the number of pulses delivered to the patient per cardiac cycle, or per time interval between two consecutive R waves in an electrocardiogram (ECG) (i.e., the R-R interval), is constant. In at least some embodiments, for example, a sudden change in the patient's heart rate (e.g., an increase or decrease above a predetermined threshold of at least 10 beats per minute (BPM), 20 BPM, 30 BPM, 40 BPM, 50 BPM, 60 BPM, 70 BPM, etc.) can generate a corresponding change in the rate (e.g., time factor) of the neuromodulation pulses.

[0049] As shown in FIG. 12, the frequency of the neuromodulation pulses generated and / or delivered to the patient can be adjusted depending on the patient's obtained heart rate or other parameters. For example, a first heart rate (R1) (e.g., 60 BPM) can correspond to a first frequency (F1) (e.g., 20 Hertz (Hz)) of the pulses at point 1201, and a second heart rate (R2) (e.g., 120 BPM) higher than the first heart rate (R1) can correspond to a second frequency (F2) (e.g., 40 Hz) of the pulses at point 1203, which is higher than the first frequency (F1). As also shown in FIG. 12, a third heart rate (R3) higher than the second heart rate (R2) can correspond to a third frequency (F3) of the pulses at point 1105, which is higher than the second frequency (F2) of the pulses, and a fourth heart rate (R4) lower than the first heart rate (R1) can correspond to a fourth frequency of the pulses at point 1207, which is lower than the first frequency (F1). In some embodiments, the third heart rate (R3) and the fourth heart rate (R4) serve as the respective upper and lower endpoint heart rates. In such embodiments, a heart rate above the third heart rate (R3) does not result in a pulse of an increased frequency relative to the frequency of the pulses provided at the third heart rate (R3), and a heart rate below the fourth heart rate (R4) does not result in a pulse of a decreased frequency relative to the frequency of the pulses provided at the fourth heart rate (R4).

[0050] In some embodiments, one or more of the frequencies F1 to F4 can be an average frequency, and the frequency of the signal delivered to the patient can vary from a base frequency. For example, in some embodiments, the second frequency has an average or base of 40 Hz with an average cycle length of 25 ms, but the individual cycle lengths have a randomly generated variance from the average cycle length, such as 22 ms - 26 ms - 24 ms - 25 ms - 28 ms (as opposed to 25 ms - 25 ms - 25 ms - 25 ms - 25 ms). Without being bound by theory, varying the signal frequency and / or cycle length can reduce or prevent patient habituation to neuromodulation, thereby making it more effective over time.

[0051] In some embodiments, the heart rate obtained from a patient and the corresponding frequency of the pulses delivered via a patient treatment system can serve as known points, and the devices or components of the patient treatment system can interpolate between the known points to deliver an appropriate number of pulses by adjusting the frequency. In such embodiments, the interpolation can be linear (as indicated via line 1211) or non-linear. The interpolation can be based at least in part on (i) how high or low the heart rate is for that particular patient or patient demographics (e.g., age, weight, etc.), (ii) whether the heart rate is outside of a “normal range,” and / or (iii) other inputs available to the system (e.g., the patient's resting heart rate). For example, the implantable neuromodulator 101 can store a history of the heart rate over several different time scales (e.g., one or more days, weeks, months, etc.). The stored history of the heart rate can include a histogram of the heart rate and / or associated statistics that can be used to adjust one or more of the neuromodulation pulse parameters. Further or alternatively, the interpolation can vary depending on whether the patient's heart rate is increasing or decreasing. For example, the frequency of the pulses delivered can correspond to line 1213 of the decreasing heart rate between a second heart rate (R2) and a first heart rate (R1), and can correspond to line 1215 of the increasing heart rate between the first heart rate (R1) and the second heart rate (R2). In these and / or other embodiments, the relationship between the frequency (and / or neuromodulation pulse parameters) and the heart rate (and / or other physiological parameters of the patient) can be linear, continuous, stepwise, or another suitable relationship.

[0052] As described above, the frequency of the generated pulse is based on the heart rate. However, in some embodiments, the frequency of the pulse can be based on other physiological parameters including blood pressure (e.g., systolic blood pressure, diastolic blood pressure), physical activity detected by one or more I / O devices (e.g., I / O device 109 (FIG. 4A), an accelerometer, or other sensors as disclosed herein), or the R-R interval of the QRS complex, which is a combination of three of the graphic deflections seen via an electrocardiogram (ECG or EKG). For example, the heart rate can be compared to movement data from an accelerometer to determine, for example, whether the heart rate is as expected or abnormal for a given level of patient movement (e.g., corresponding to a physical activity level) over a period of time. Additionally, or alternatively, the physiological parameters can include a pulse pressure waveform indicative of vascular wall dilation (e.g., volume conductance and / or wall stretch) and / or vascular stiffness. As described herein, the R-R interval or signals associated with the R wave can be detected via a vector of the patient treatment system. Blood pressure can be obtained via an implanted or external blood pressure measurement device directly coupled or wirelessly coupled (e.g., via Bluetooth, ANT, telemetry, etc.) to the patient treatment system, or more particularly, to the neuromodulator 101 (FIG. 4A or FIG. 4B). The obtained blood pressure measurements can be the average blood pressure measured over time (e.g., over the previous 10 seconds, 30 seconds, 1 minute, 2 minutes, etc.), filtered blood pressure, or a combination thereof.

[0053] Figures 13A - 13C are diagrams of neuromodulation pulses generated during a cardiac cycle via a patient treatment system (e.g., system 100 (Figs. 3, 4A, 4B)) according to an embodiment of the present technology. As described herein, the neuromodulation pulses generated via the neuromodulator of an embodiment of the present technology can include a burst of pulses having individual pulses with a delay that varies with respect to the immediately preceding pulse. For example, the individual pulses with respect to the immediately preceding pulse can have an increased delay, a decreased delay, or the same delay. In embodiments where the delay increases over time, the delay can be determined using a non - linear function such as Equation 1 or Equation 2 below. Delay=t*exp α+n (Equation 1) Delay=T+(t*exp α+n ) (Equation 2) Here, T = delay of the previous pulse t = time (seconds) α = programmable variable n = number of pulses

[0054] FIG. 13A shows a neuromodulation pulse 1305 generated after a cardiac cycle having an increasing delay over time. That is, the neuromodulation pulse 1305 includes a first stimulus (S1) after the start of the cardiac cycle, a second stimulus (S2) after a first time delay (T1), a third stimulus (S3) after a second time delay (T2) greater than the first time delay (T1), a fourth stimulus (S4) after a third time delay (T3) greater than the second time delay (T2), a fifth stimulus (S5) after a fourth time delay (T4) greater than the third time delay (T3), and a sixth stimulus (S6) after a fifth time delay (T5) greater than the fourth time delay (T4). In some embodiments, the first stimulus (S1) can be delayed from the start of the cardiac cycle by a time delay less than the first time delay (T1) and / or by a predetermined time. The neuromodulation pulse 1305 includes six pulses or stimuli, but in other embodiments, the neuromodulation pulse 1305 may include more or fewer (e.g., 20, 16, 12, 10, 8, or 4) pulses.

[0055] Without being bound by theory, the natural baroreceptor response can consist of a burst of pulses with increasing delay over time immediately following the detection of a cardiac depolarization event (e.g., carotid artery distension). Embodiments of the present technology can attempt to mimic the natural baroreceptor response by generating a neuromodulation pulse that increases in delay over time for a single cardiac cycle and is delivered a predetermined time after a cardiac depolarization event is detected. The frequency of the individual pulses and / or the delay between adjacent pulses can be automatically adjusted by the patient treatment system, for example, based on changes in the detected R-R interval. For example, as the heart rate increases and / or the R-R interval time decreases, the frequency of the individual pulses increases (e.g., the delay between the individual pulses decreases), and as the heart rate decreases and / or the R-R interval increases, the frequency of the individual pulses decreases (e.g., the delay between the individual pulses increases).

[0056] Figures 13B and 13C show neuromodulation pulses 1310, 1315 generated after the cardiac cycle, having different delays for individual pulses with respect to the neuromodulation pulse 1305 of Figure 13A. As shown in Figure 13B, the neuromodulation pulse 1310 has a consistent time delay (T6) for the individual stimulation pulses. As shown in Figure 13C, the neuromodulation pulse 1315 has a time delay that first increases, levels off, and then decreases. In particular, the neuromodulation pulse includes a first stimulus (S1) after the start of the cardiac cycle, a second stimulus (S2) after a first time delay (T1), a third stimulus (S3) after a second time delay (T2) greater than the first time delay (T1), a fourth stimulus (S4) after a third time delay (T3) greater than the second time delay (T2), a fifth stimulus (S5) after the third time delay (T3), a sixth stimulus (S6) after the second time delay (T2), and a seventh stimulus (S7) after the first time delay (T1). In some embodiments, the first stimulus (S1) can be delayed from the start of the cardiac cycle by a time delay less than the first time delay (T1) and / or by a predetermined time.

[0057] Referring again to Figure 13A, the time from the start of the cardiac cycle to the last stimulus or pulse can constitute a stimulation window (SW), and the time between the last stimulus or pulse and the start of the next cardiac cycle can constitute a non-stimulation window (NSW). The NSW can constitute a refractory period where no stimulation occurs, independent of the patient's heart rate or other symptoms. In some embodiments, the SW can be limited to be less than a predetermined first period, and / or the NSW can be made at least equal to a predetermined second period. By ensuring that the SW is limited to the first period and / or the NSW is at least equal to the second period, advantageously, the ability to detect subsequent R waves (e.g., via an electrical or acoustic signal) can be improved. That is, the ability to detect subsequent R waves can be enhanced only by generating and / or delivering a neuromodulation pulse during the SW between cardiac cycles.

[0058] Figures 14A - 14D are diagrams of waveforms 1405, 1410, 1415, 1420 (collectively referred to as "waveform 1400") of neuromodulation pulses generated via a patient treatment system (e.g., system 100 (Figs. 3, 4A, 4B)) according to an embodiment of the present technology. Each of the waveforms 1400 includes a stimulation portion 1430 and one or more subsequent recharge portions. The waveform of each pulse must maintain charge balance through passive and / or active means. The charge balance maintained via passive means can rely on a blocking cap that stores the emitted energy of the pulse and then passively returns it to the system of opposite polarity. The charge balance maintained via active means can utilize a biphasic waveform.

[0059] The waveforms 1400 shown in FIGS. 14A - 14D include various charge balancing techniques. As shown in FIG. 14A, waveform 1405 includes a stimulation portion 1430 and a passive - only recharge portion 1440. As shown in FIG. 14B, waveform 1410 is biphasic and includes a stimulation portion 1430 and, following it, an active recharge portion 1445 that balances at least a portion of the charge of the stimulation portion 1430. The area of the active recharge portion 1445, which is equal to the amplitude multiplied by the elapsed time, is approximately equal to that of the stimulation portion 1430, and the amplitude value of the active recharge portion 1445 is approximately equal to that of the stimulation portion 1430. Waveform 1410 also includes a passive recharge portion 1450 after the active recharge portion 1445, where the circuit tolerance can be accounted for. As shown in FIG. 14C, waveform 1415 is biphasic and includes a stimulation portion 1430 and, following it, an active recharge portion 1455 that balances not all but a portion of the charge of the stimulation portion 1430. The area of the active recharge portion 1455 is approximately equal to that of the stimulation portion 1430, and the amplitude value of the active recharge portion 1445 is less than that of the stimulation portion 1430. Waveform 1415 also includes a passive recharge portion 1460 after the active recharge portion 1455. As shown in FIG. 14D, waveform 1420 is triphasic and includes a stimulation portion 1430, a pre - recharge portion 1465 before the stimulation portion 1430, and a post - recharge portion 1470 after the stimulation portion 1430, where the combined area of the pre - and post - recharge portions 1465, 1470 is approximately equal to that of the stimulation portion 1430. The amplitude value of each of the pre - and post - recharge portions 1465, 1470 is less than that of the stimulation portion 1430 and is approximately half. Without being bound by theory, the pre - recharge portion before the stimulation pulse can "prepare" the cell to receive the stimulation pulse for depolarization, thereby advantageously reducing the stimulation energy required to depolarize the cell. Waveform 1420 also includes a passive recharge portion 1475 after the active recharge portion 1470.

[0060] FIG. 15 is a flowchart of a method 1500 for stimulating a patient's CSN according to an embodiment of the present technology. The method 1500 can include providing a treatment system including a neuromodulator and a signal delivery device coupled to the neuromodulator (process block 1502). The treatment system, the neuromodulator, and the signal delivery device can be or include respective treatment systems (e.g., treatment system 100 (FIGS. 3, 4A, 4B)), neuromodulators (e.g., neuromodulator 101 (FIGS. 4A, 4B)), and signal delivery devices disclosed herein (e.g., signal delivery devices 121, 521, 621, 721, 821, 921, 1021, 1121 (FIGS. 4A, 4B, 5A, 6A, 7A, and 8A-11E)). Thus, the signal delivery device can include a first region (e.g., first region 530 (FIGS. 5A, 6A, 7A, 8A-11B)), a second region (e.g., second region 540 (FIGS. 5A, 6A, 7A, 8A-11B)), and a lead body having lead electrodes (e.g., first lead electrodes 531, 931 (FIGS. 5A-10, 11B) (e.g., lead bodies 125, 525, 625, 725, 825, 925, 1025, 1125 (FIGS. 4A, 4B, 5A, 6A, 7A, 8A-11E)), second lead electrodes 541, 641, 741, 941, 1041 (FIGS. 5A-10, 11B), suture holes 833 (FIGS. 8A-10), suture holes 843 (FIGS. 8A-10), third lead electrodes 935 (FIGS. 9 and 10), and / or fourth lead electrodes 945, 1045 (FIGS. 9 and 10)).

[0061] Method 1500 can further include implanting a lead electrode of the signal delivery device proximate to the patient's CSN afferent fibers (process portion 1504). The lead electrode can be implanted subcutaneously in the patient's neck region and then moved to be proximate to the CSN based on mapping data obtained via the lead electrode, the base electrode, or other components of the patient treatment system. For example, depending on signals (e.g., electrical and / or acoustic signals) received via individual lead electrodes and / or other input devices (e.g., accelerometers and / or other I / O devices 109 (FIG. 4)), the position of the lead body of the signal delivery device can be adjusted until the lead electrode is properly positioned proximate to the CSN afferent fibers. Advantageously, by utilizing features of the patient treatment system to map the patient's tissue and enable proper positioning of the lead electrode, the signal delivery device can be implanted without severing nerves within the CSN area. Additionally or alternatively, for procedures where features of the patient treatment system cannot be utilized to map the patient's tissue, embodiments of the present technology can reduce the time spent in the operating room to implant and position the signal delivery device.

[0062] Method 1500 can further include determining a patient's physiological parameters (process portion 1506). Physiological parameters can include heart rate, dilation index, arrhythmia, blood pressure, bioimpedance, sleep state, one or more inputs provided by the patient, other metrics indicative of the patient's activity (e.g., pulse transit time, accelerometer data, etc.), and / or cardiac depolarization (e.g., the onset of a myocardial depolarization event or cycle), and / or any other physiological parameters and / or other patient data described herein. Cardiac depolarization can be determined or detected via a corresponding signal propagated across body tissue that can include and / or indicate an associated QRS complex, R wave, or R-R interval. Myocardial depolarization and / or the QRS complex can be electrically detected using a vector formed via the base electrodes and / or lead electrodes of the patient treatment system. For example, one of the base electrodes (e.g., base electrodes 117A, 117B (Figs. 4A, 4B)) and one of the lead electrodes (e.g., lead electrodes 531, 541, 641, 741 (Figs. 5A-7B)) can form a vector that enables determination of cardiac depolarization. As another example, two of the base electrodes can form a vector that enables determination of cardiac depolarization. In addition to or alternatively to determining physiological parameters via electrical measurements, signals associated with cardiac depolarization can be determined via heart sounds. In such embodiments, the patient treatment system or neuromodulator can include an accelerometer or other acoustic sensor capable of detecting a sound signal associated with cardiac depolarization.

[0063] Physiological parameters can include bioimpedance that can be determined or sensed via one or more sensors (e.g., electrodes) electrically coupled to one or more regions of a patient's body. In some embodiments, the sensors are positioned on and / or at least partially around a patient's chest to determine or sense chest bioimpedance. The patient's chest bioimpedance is predicted to decrease in response to an increase in blood volume and an increase in blood pressure. The increase in the patient's blood pressure can be driven by an increase in the patient's arterial blood volume. This is based at least in part on blood movement from the patient's abdominal venous circulation to the patient's arteries during, for example, an exercise period and / or other patient activity. Thus, in at least some embodiments, determining or sensing bioimpedance (e.g., chest bioimpedance) can be used to estimate or indicate a patient's blood pressure, and this can be utilized to determine or sense the effectiveness of a neuromodulation pulse applied to the patient to alter the patient's blood pressure (process portions 1508 and 1510, described in detail below).

[0064] In such embodiments where the physiological parameters include heart rate, blood pressure, bioimpedance, or other metrics indicative of a patient's activity, the physiological parameters can be determined via a neuromodulator and / or a signal delivery device based on, for example, a signal conveyed across body tissue, or obtained from a sensor (e.g., a bioimpedance sensor) that is coupled to but separate from the neuromodulator and / or the signal delivery device. In some embodiments, the physiological parameters can include other variables indicative of the response of a patient's arterial system. For example, the physiological parameters can include arterial wall stiffness, diastolic pressure, or an augmentation index.

[0065] Method 1500 can further include generating a neuromodulation pulse based on a physiological parameter (process portion 1508). Thus, instead of having tonic stimulation characteristics (e.g., frequency, pulse width, amplitude, etc.) that remain unchanged throughout patient treatment, embodiments of the present technology can use, for example, the frequency of a neuromodulation pulse that increases as the heart rate or blood pressure increases, and the frequency of a neuromodulation pulse that decreases as the heart rate or blood pressure decreases, to automatically adjust the stimulation characteristics of the neuromodulation pulse based on the patient's activity. In this regard, the frequency of the neuromodulation pulse can increase with a decrease in the R-R interval time, and the frequency of the neuromodulation pulse can decrease with an increase in the R-R interval time. Advantageously, the treatment provided to the patient is generally consistent in terms of the number of stimulation pulses per BPM, or the number of pulses per physiological parameter value, and / or is not "weakened" with an increase in the patient's physiological parameters, heart rate, blood pressure, etc.

[0066] In some embodiments, the neuromodulation pulse can include a waveform having characteristics that vary based on a physiological parameter. For example, the neuromodulation pulse can have a frequency in the range of 0 to 1000 Hertz (Hz), 20 to 800 Hz, 200 to 800 Hz, 400 to 800 Hz, or any other incremental range therebetween (e.g., 500 to 650 Hz). In some embodiments, the frequency of the neuromodulation pulse can be at least 20 Hz, 100 Hz, 200 Hz, 300 Hz, 400 Hz, 500 Hz, 600 Hz, 700 Hz, 800 Hz, or 900 Hz. As described herein, the frequency or stimulation of the neuromodulation pulse can increase with the heart rate or blood pressure, and / or can exceed 1 kHz, for example, when delivered to downregulate (e.g., block) a neural connection.

[0067] The neuromodulation pulse can have a pulse width in the range of 10 to 1000 microseconds (μs), 100 to 500 μs, 100 to 400 μs, 200 to 400 μs, or any other incremental range therebetween (e.g., 300 to 350 μs). In some embodiments, the pulse width of the neuromodulation pulse can be 400 μs, 350 μs, 300 μs, 250 μs, or 200 μs or less. As described herein (e.g., referring to FIG. 13A), the cardiac cycle length can be made equal to the sum of the SW and the NSW that occurs after the SW. The NSW can correspond to the end portion of each cardiac cycle and / or the quiescent period where no stimulation occurs. The absence of noise or sound generated from the patient treatment system at the end portion of the cardiac cycle enables the patient treatment system to listen or detect (e.g., via an electrical or acoustic signal) when a subsequent cardiac depolarization event begins, thereby determining when the first pulse of the neuromodulation pulse is delivered. In some embodiments, the pulse width or stimulation window is limited to a predetermined maximum time based on the non-stimulation window and the minimum time of the cardiac cycle.

[0068] The neuromodulation pulse can have a duty cycle of 10 to 75%, 25 to 75%, 40 to 60%, or any other incremental range therebetween (e.g., 50 to 60%). In some embodiments, the duty cycle of the neuromodulation pulse can be at least 20%, 25%, 40%, or 50%. The actual duty cycle can be based on physiological parameters and / or other elements described herein. In some embodiments, the duty cycle can correspond to time-based on and off periods (e.g., 1 minute on and then 1 minute off), and / or the desired percentage of the SW for providing stimulation. For example, a 300 millisecond (ms) SW has a duty cycle of 30% at 60 BPM, 60% at 120 BPM, and 90% at 180 BPM.

[0069] (See, for example, FIGS. 13A-13C) As described herein, a neuromodulation pulse can include a burst of pulses that occur over a specific stimulation window and / or non-stimulation window of the cardiac cycle, where each individual neuromodulation pulse has a predetermined delay relative to the previous neuromodulation pulse. For example, the delay of the neuromodulation pulses can increase over time such that for a single cardiac cycle, each subsequent pulse is spaced further from the previous pulse than any previous pulse. The frequency of the individual pulses and / or the delay between adjacent pulses can be automatically adjusted by the patient treatment system, for example, based on changes to physiological parameters detected and utilized by the patient treatment system. For example, as the heart rate increases and / or the R-R interval time decreases, the frequency of the individual pulses increases (e.g., the delay between the individual pulses decreases), and as the heart rate decreases and / or the R-R interval increases, the frequency of the individual pulses decreases (e.g., the delay between the individual pulses increases). Additionally or alternatively, the neuromodulation pulses can have characteristics that generally mimic the patient's natural baroreceptor response without an abnormal response. In some embodiments, the neuromodulation pulses can have some individual pulses that exhibit an increased delay relative to the previous pulse, and other pulses that have the same or a decreased delay relative to the previous pulse.

[0070] The value of the physiological parameter utilized by the patient treatment system can be an average value (e.g., a rolling value averaged over the previous 30 seconds, 1 minute, etc.) and / or can be filtered, which can be useful for accounting for extreme (e.g., very high or very low) measurements due to, for example, atrial fibrillation or other errant cardiac signals. In this regard, in some embodiments, the need to continuously track the physiological parameter for instantaneous changes may not be important, and additionally, it is notable that not tracking the physiological parameter instantaneously can be useful for reducing the energy utilization of the patient treatment system.

[0071] (See, e.g., FIGS. 14A-14D) As described herein, the waveform of the neuromodulation pulse must maintain charge balance. Thus, the neuromodulation pulse can exhibit any of the waveforms shown and described with reference to FIGS. 14A-14D, or other waveforms that maintain charge balance. For example, the neuromodulation pulse alternates between positive and negative pulses via active means and / or passive means to ensure that charge balance is maintained.

[0072] As described above, in some embodiments, the physiological parameters can include arterial wall stiffness, diastolic pressure, diastolic index, one or more strength-duration curves, and / or aggregated or averaged strength-duration curves. Arterial wall stiffness can be an indicator of cardiovascular risk and arterial system resistance. Diastolic pressure or diastolic index (i.e., a characteristic of the diastolic pressure waveform) is also a measure of arterial wall stiffness and is derived from the ascending aortic pressure waveform. Generally, arterial wall stiffness will increase in response to cardiac depolarization, but should be kept below a predetermined threshold to keep blood pressure low. Thus, measuring arterial wall stiffness can be a useful input for adjusting the characteristics of the neuromodulation pulse. Further, measuring arterial wall stiffness can provide different data regarding the patient's cardiovascular health and the type of stimulation required there (e.g., with respect to only heart rate or blood pressure). In such embodiments, the patient treatment system can include other I / O devices, such as a blood pressure monitor for determining arterial wall stiffness, or other devices for determining the diastolic pressure waveform or index.

[0073] In this regard, one or more strength-duration curves can also be obtained and utilized as inputs to physiological parameters used by the system to determine neuromodulation. For a given stimulation target, each strength-duration curve can measure the stimulation intensity (e.g., amplitude) and the duration of the stimulation (e.g., pulse width). The individual strength-duration curves, and / or the aggregation and / or averaging of all or a subset of the strength-duration curves, can provide useful data for subsequent stimulations, including (i) a base current that generally serves as the minimum voltage required to threshold the nerve being treated, and (ii) a chronaxy that can indicate the excitability of the nerve. Additionally, or alternatively, the strength-duration curves can be used during implementation to optimize or improve the operation of the system (e.g., to determine parameters that maximize battery life, to determine when increased stimulation intensity can produce increased therapeutic effects). In at least some embodiments, there is no fixed threshold for activating the nerve; rather, it will be understood that the stimulation produces a graded effect of the stimulation (e.g., a dose-response relationship). Additionally, or alternatively, for example, to assist in avoiding producing these off-target effects, individual and / or aggregated strength-duration relationships can be established for one or more off-target effects.

[0074] In some embodiments, generating neuromodulation pulses for each process part 1508 can be based on other inputs that can make the treatment more effective for the patient. For example, in some embodiments, the patient treatment system can include an accelerometer that can be used to detect cardiac depolarization (e.g., via acoustics) as described above. Additionally, or alternatively, the accelerometer can be used to indicate the patient's position, orientation, and / or activity (e.g., similar to a heart rate responsive pacemaker). In such embodiments, the accelerometer can serve as a fall detector or safety mechanism, and signals from the accelerometer can be used to adjust the stimulation or characteristics of the neuromodulation pulses. For example, the patient treatment system can determine that a patient fall may have occurred via signals from the accelerometer and can adjust the upper and lower frequency limits of the stimulation as described with respect to FIG. 12. Additionally or alternatively, generating neuromodulation pulses for each process part 1508 can be based on subjective and / or objective feedback from the patient regarding discomfort and / or other sensations experienced during treatment. For example, if the patient feels that the neuromodulation pulse at a first intensity is uncomfortable, the neuromodulation pulse can be generated at a second intensity less than the first intensity to reduce or eliminate the patient's discomfort. In these and / or other embodiments, generating neuromodulation pulses for each process part 1508 can be based on the pulse generator, one or more of the electrodes, and / or one or more operating limitations of the patient physiology. For example, the neuromodulation pulses can be generated according to one or more signal delivery parameters below a threshold at which hydrolysis occurs.

[0075] In some embodiments, generating neuromodulation pulses for each process portion 1508 can be based, at least in part, on one or more patient states. For example, in some embodiments, the neuromodulation pulses are based, at least in part, on time. Some patients, such as those with lower nighttime blood pressure than daytime blood pressure (e.g., "dippers"), may require / receive less intense treatment at various times during the night (e.g., one or more nighttime periods) compared to during the day (e.g., one or more daytime periods). Similarly, patients with nighttime blood pressure equal to and / or exceeding their daytime blood pressure (e.g., "non-dippers") may require / receive more intense treatment at various times during the night (compared to during the day). These dipper and non-dipper patients can be identified and differentiated, at least in part, based on data from an ambulatory blood pressure monitor ("ABPM") and / or Holter electrocardiogram history of the patient's nighttime and / or daytime blood pressure and / or heart rate, heart rate and / or other data from one or more other devices, the patient's medical history (e.g., if the patient is known to have a morning myocardial infarction, "morning blood pressure surge", previous stroke episodes, arrhythmias, etc.), combinations thereof, and / or other data sources described herein. The neuromodulation pulses can be generated in response to any of these and / or other data, and / or based on one or more predicted times during the day and / or night when the patient is expected to have a varying state. For example, some patients have a "morning blood pressure surge" and, in response, may receive a relatively greater treatment during the morning.

[0076] In some embodiments, generating a neuromodulation pulse for each process portion 1508 is determined based at least in part on an arrhythmia and / or one or more arrhythmic events in a patient, such as based at least in part on depolarization of one or more cardiac chambers of the heart and / or one or more interventricular (VV) intervals and / or other detected variations in depolarization rate. In some embodiments, process portion 1508 can include reducing or discontinuing treatment, for example, for a patient having a bradycardia and / or asystole pattern and / or during a period of ventricular fibrillation (“VF”). In other embodiments, process portion 1508 can include increasing treatment, for example, during a period of atrial fibrillation (“AF”). Additionally or alternatively, process portion 1508 can include delivering a rapid increase in stimulation (e.g., a sustained or transient increase in nerve stimulation intensity, frequency, amplitude, etc.) in response to detection of ventricular tachycardia (e.g., nonsustained ventricular tachycardia, pairs or triplets of ventricular premature contractions (“PVCs”), etc.). In these and / or other embodiments, treatment can be enhanced in response to one or more triggers including ischemic ECG metrics (e.g., ST segment depression or elevation, T-wave alternans (“TWA”), etc.).

[0077] Method 1500 can further include delivering a neuromodulation pulse to the CSN fibers via one or more of the lead electrodes (process portion 1510). For example, the neuromodulation pulse can be delivered to a patient via one of the lead electrodes on the first region of the lead body of the signal delivery device (e.g., one of the first lead electrodes 531 (FIG. 5A)) and one of the lead electrodes on the second region of the lead body (e.g., one of the second lead electrodes 541, 641, 741 (FIGS. 5A-7B)). In such an embodiment, the two electrodes used to deliver the stimulation pulse can be aligned and face each other when the lead body is in the closed position and / or when the target fibers of the CSN are encircled. By delivering neuromodulation as bipolar stimulation, the energy requirements for stimulation can be reduced relative to monopolar stimulation. Additionally, as described with reference to FIGS. 6A-7B, in embodiments that include a first region having five lead electrodes and a second region having less than five electrodes (e.g., three electrodes or one electrode) but covering a similar or identical footprint, the energy requirements for stimulation can be further reduced without limiting the selectivity or ability to target specific target fibers between the first and second regions of the lead body.

[0078] In some embodiments, delivering a first neuromodulation pulse via one or more of the lead electrodes (process block 1510) further includes delivering one or more neuromodulation pulses to the CSN fibers and delivering one or more second neuromodulation pulses to additional tissue of the patient. The individual first neuromodulation pulses can have first signal delivery parameters (e.g., frequency, amplitude, pulse width, etc.), and the individual second neuromodulation pulses can have second signal delivery parameters (e.g., frequency, amplitude, pulse width, etc.) that are the same as or different from the corresponding ones of the first signal delivery parameters. The additional tissue of the patient can include one or more nerves and / or muscles including muscles innervated by the nerves described herein, and can be selected to provide the same or different physiological and / or therapeutic effects provided by delivering a neuromodulation pulse to the CSN fibers. In at least some embodiments, for example, the first neuromodulation pulse is delivered to the CSN fibers (e.g., to lower the patient's blood pressure as described above herein), and the second neuromodulation pulse is delivered to, for example, the hypoglossal nerve and / or the cervical nerve plexus to address or treat the patient's obstructive sleep apnea (OSA). Additionally, or alternatively, the second neuromodulation pulse can be delivered to one or both of the atria and / or one or both of the ventricles of the patient's heart (e.g., to prevent or at least partially prevent arrhythmias). For example, the second neuromodulation pulse can be a cardiac resynchronization pulse delivered to at least partially or fully resynchronize depolarization of various parts of the patient's heart. In some embodiments, the second neuromodulation pulse can be delivered in conjunction with complementary and / or synergistic CSN stimulation (e.g., to reduce ventricular loading while resynchronizing the patient's heart).In these and other embodiments, the second neuromodulation pulse can be delivered by the same device and / or a different neuromodulation device to address or treat other indications including, but not limited to, heart failure, OSA, central sleep apnea, and the like. For example, delivering the second neuromodulation pulse can include delivering the second neuromodulation pulse to address or treat heart failure (such as heart failure with preserved ejection fraction and / or heart failure with reduced ejection fraction), provide cardiac resynchronization therapy, provide myocardial contractility modulation therapy, or to stimulate a patient's diaphragm to address or treat central sleep apnea.

[0079] The process portions of method 1500 can be executed iteratively and can utilize feedback from the system in a closed-loop fashion. For example, process portions 1506, 1508, 1510 can be executed multiple times for a given treatment session. That is, after delivering a neuromodulation pulse to the CSN afferent fibers (process portion 1510), method 1500 can determine updated physiological parameters of the patient (process portion 1506) and generate additional neuromodulation pulses based on the updated physiological parameters (process portion 1508). The physiological parameters determined after delivering the initial neuromodulation pulse are in part a response to the initial neuromodulation pulse, and thus it is notable that they are indicators of the effect of the initial neuromodulation pulse. Accordingly, the iteration of process portions 1506, 1508, 1510 serves to provide a more effective patient treatment that can be improved with each iteration, while still providing a treatment that is not attenuated in response to the patient's activity (e.g., based on physiological parameters).

[0080] FIG. 16 is a flowchart of a method 1600 for stimulating a patient's nerve fibers (e.g., CSN) according to an embodiment of the present technology. The method 1600 can include providing a treatment system that includes a neuromodulator and a signal delivery device coupled to the neuromodulator (process block 1602). The treatment system, the neuromodulator, and the signal delivery device can be or include respective treatment systems (e.g., treatment system 100 (FIGS. 4A, 4B)), neuromodulators (e.g., neuromodulator 101 (FIGS. 4A, 4B)), and signal delivery devices described herein (e.g., signal delivery devices 121, 521, 621, 721, 821, 921, 1021, 1121 (FIGS. 4A, 4B, 5A, 6A, 7A, 8A-10, 11A-11E)). Accordingly, the signal delivery device can include a first region (e.g., first region 530 (FIGS. 5A, 6A, 7A, 8A-10, 11B)), a second region (e.g., second region 540 (FIGS. 5A, 6A, 7A, 8A-10, 11B)), and a lead body having lead electrodes (e.g., first lead electrodes 531, 931 (FIGS. 5A-10, 11B) and lead bodies 125, 525, 625, 725, 825, 925, 1025, 1125 (FIGS. 4A, 4B, 5A, 6A, 7A, 8A-111B)), second lead electrodes 541, 641, 741, 941, 1041 (FIGS. 5A-10, 11B), suture holes 833 (FIGS. 8A-10), suture holes 843 (FIGS. 8A-10), third lead electrode 935 (FIGS. 9 and 10), and / or fourth lead electrodes 945, 1045 (FIGS. 9 and 10)).

[0081] Method 1600 can further include implanting a lead electrode of a signal delivery device within a patient (process portion 1604). For example, the lead electrode can be implanted subcutaneously in the neck region of the patient. In some embodiments, implanting the lead electrode includes, for example, cutting the patient's tissue in or near the neck region at least proximate to and / or aligned with the location where the lead electrode is to be implanted. In these and / or other embodiments, implanting the lead electrode can include, for example, pre-mapping one or more tissues within the neck region to identify target tissue by providing an electrical stimulation and observing and / or detecting the patient's response to the electrical stimulation. Additionally, or alternatively, imaging techniques (e.g., ultrasound, OCT, infrared, etc.) can be used to identify the target tissue. These and / or other techniques can also be used to identify non-target tissue (e.g., patient tissue that should not receive electrical stimulation). For example, a lead electrode or another signal delivery device can be used to stimulate one or more nerves and / or other tissues near the target tissue to discover the pathways of cough and / or other off-target effects, and the lead electrode can be positioned or repositioned to avoid stimulating that area and / or causing off-target effects in other ways during stimulation. Additionally, or alternatively, ice or other cryogenic sources (e.g., a sealed container of circulating cooled alcohol) can be positioned on or near the tissue to reduce or eliminate intraoperative external stimulation, and then, when the tissue is identified as redundant or an associated pathway and is above a fibrous tissue with an off-target effect known to branch upward, the lead electrode can be positioned or repositioned to avoid or cut this tissue.

[0082] Method 1600 can further include delivering a first neuromodulation pulse to a patient's nerve fibers (e.g., afferent nerve fibers, CSN afferent fibers, efferent nerve fibers, etc.) via one or more of the lead electrodes according to a first set of stimulation parameters. The first set of stimulation parameters can include a first frequency, a first amplitude, a first pulse width, a first duty cycle, and / or a first lead electrode configuration (e.g., a first group of electrodes (e.g., two or more)). The first frequency, the first amplitude, the first pulse width, and the first duty cycle can include any of the respective frequencies, amplitudes, pulse widths, and duty cycles described herein, and the first lead electrode configuration can include any combination of the lead electrodes described herein.

[0083] Method 1600 can further include detecting parameters, such as parameters associated with a cardiac depolarization event, via vectors of the treatment system (process portion 1608). The parameters of process portion 1608 can include, for example, any of the physiological parameters described herein with reference to method 1500 or process portion 1506. As described herein, the base electrode and / or lead electrodes can form various vectors that can serve as sensing channels for detecting signals (e.g., electrical signals and / or acoustic signals). Each of the lead electrodes can be individually addressable and is electrically coupled to one or both of the base electrodes. Thus, the vectors can include any of the base electrodes and any of the lead electrodes. Additionally, the vectors can include two base electrodes that are spaced apart by a minimum distance from each other (as described with reference to FIGS. 4A and 4B) and may not include any lead electrodes at all. For embodiments in which the parameter is associated with a cardiac depolarization event, the parameter can include the onset of the cardiac depolarization event, which can define the timing of delivering an initial pulse of a neuromodulation pulse, and / or the R-R interval. In some embodiments, the patient treatment system can include other input devices (e.g., an accelerometer and / or I / O device 109 (FIG. 4A)) for providing an additional ability to detect parameters in addition to the sensing provided via the base electrodes and lead electrodes.

[0084] Method 1600 can further include defining a second stimulation parameter by adjusting one or more of the first stimulation parameters based on the detected parameter (process portion 1610). Adjusting one or more of the stimulation parameters can include (i) adjusting the intensity of the stimulation (e.g., increasing or decreasing) by adjusting one or more of, for example, the frequency, amplitude, pulse width, and / or duty cycle (or another parameter) of the neuromodulation pulse used to stimulate the patient, and / or (ii) adjusting the electrode configuration for delivering the neuromodulation pulse to the patient's nerve fibers (e.g., electronic repositioning). For example, adjusting the electrode configuration based on the detected parameter can include changing the lead electrode group used to deliver the neuromodulation pulse such that different electrode groups are used to deliver the stimulation to the nerve fibers. For example, if a first lead electrode group was used to stimulate the nerve fibers based on the detected parameter (through process portion 1608) (through process portion 1606), the nerve fibers can then be stimulated using a second lead electrode group. The second lead electrode group can include at least one lead electrode different from the first lead electrode group. In some embodiments, adjusting one or more of the first stimulation parameters includes adjusting (i) the electrode configuration for delivering the neuromodulation pulse to the patient's nerve fibers and (ii) one or more of the frequency, amplitude, pulse width, and duty cycle of the neuromodulation pulse.

[0085] Method 1600 can further include delivering a second neuromodulation pulse to the patient's nerve fibers via one or more of the lead electrodes according to the second stimulation parameter. The second neuromodulation pulse can include a different frequency, amplitude, pulse width, duty cycle, and / or electrode configuration relative to each of the frequency, amplitude, pulse width, duty cycle, and electrode configuration of the first neuromodulation pulse.

[0086] Method 1600, or more particularly process portions 1608 and 1610, can be iteratively repeated and adjusted in a closed-loop fashion to determine a preferred group (e.g., pair or more) of lead electrodes proximate to the CSN afferent fibers. For example, each detected parameter associated with a cardiac depolarization event can be used to adjust the stimulation parameters such that improved stimulation is provided to the nerve fibers via the signal delivery device. For example, multiple (e.g., two or more) detections of the parameters may be required before an ideal stimulation parameter is determined. Thus, each cardiac depolarization can provide additional data obtained via the vectors of the patient treatment system that can be used to improve the treatment or stimulation provided to the nerve fibers (e.g., CSN) via the lead electrodes.

[0087] In some embodiments, the detected parameters can be used to effectively map (e.g., intraoperative mapping) the patient's tissue to the CSN afferent fibers while the lead electrodes are implanted (through process portion 1604). Advantageously, mapping the patient's tissue using the features of the patient treatment system allows the lead electrodes to be properly positioned, thereby allowing the signal delivery device to be implanted without cutting the nerves within the CSN area. Additionally or alternatively, for procedures where the patient's tissue cannot be mapped using the features of the patient treatment system, embodiments of the present technology can reduce the time spent in the operating room to implant and position the signal delivery device.

[0088] IV. Conclusion It will be apparent to those skilled in the art that various modifications may be made to the embodiments described above without departing from the principles on which the present disclosure is based. In some cases, well-known structures and functions are not shown or described in detail to avoid unnecessarily obscuring the description of the embodiments of the present technology. The steps of the method can be presented in a particular order herein, but alternative embodiments can execute the steps in a different order. Similarly, certain aspects of the present technology disclosed in the context of a particular embodiment can be combined or eliminated in other embodiments. Further, although the advantages associated with certain embodiments of the present technology have been disclosed in the context of these embodiments, other embodiments can also exhibit such embodiments, and not all embodiments necessarily exhibit such advantages or other advantages disclosed herein to the extent that they fall within the scope of the technology. Accordingly, the present disclosure and related technologies can include other embodiments not explicitly shown or described herein, and the invention is not limited except as by the appended claims.

[0089] Throughout this specification, unless the context requires otherwise, the singular forms "a", "an", and "the" include plural referents. In addition, the terms "comprising", "including", and "having" are to be construed as meaning including at least the recited features, such that any greater number of the same features and / or additional types of other features are not excluded.

[0090] References herein to "one embodiment", "an embodiment", "some embodiments", or similar language mean that a particular feature, structure, operation, or characteristic described in connection with the embodiment is included in at least one embodiment of the present technology. Thus, the appearance of such phrases or descriptions herein does not necessarily all refer to the same embodiment. Further, the various particular features, structures, operations, or characteristics can be combined in any suitable manner in one or more embodiments.

[0091] Unless otherwise indicated, it should be understood that all numbers expressing pressure, frequency, amplitude, duty cycle, and other numerical values used in this specification and the claims are modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present technology. At the very least, and not as a limitation on the application of the doctrine of equivalents to the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Further, it should be understood that all ranges disclosed herein encompass any and all subranges subsumed therein. For example, a range of "1 to 10" includes any and all subranges between the minimum value 1 and the maximum value 10 (including both values) (i.e., any and all subranges having a minimum value of 1 or more and a maximum value of 10 or less, such as 5.5 to 10).

[0092] The above disclosure is not to be construed as intending that any of the claims require more features than are expressly recited in that claim. Rather, as reflected in the following claims, aspects of the invention lie in combinations of fewer features than all of the features of any of the single above-disclosed embodiments. For this reason, the claims following this detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment. This disclosure includes all permutations of the independent claims and their dependent claims.

[0093] The present technology is presented, for example, for convenience, in accordance with various aspects described below as numbered sections (1, 2, 3, etc.). These are provided by way of example and are not intended to limit the present technology. It should be noted that any of the subsections may be combined in any combination and may be disposed in each independent section. 1. A patient treatment system, comprising: A neuromodulator comprising a housing and at least one base electrode held by the housing, An implantable signal delivery device electrically connectable to the neuromodulator, the signal delivery device comprising a lead body having a first region, a second region positionable over the first region, and a lead electrode electrically connectable to the base electrode of the neuromodulator, the lead electrode being configured to be proximate to and / or at least partially embedded around one or more nerves associated with the patient's baroreflex, the implantable signal delivery device; One or more processors, A tangible non-transitory computer-readable medium having instructions which, when executed by one or more processors, cause a patient treatment system to, Obtain physiological parameters of a patient, Generate a neuromodulation pulse based on the obtained physiological parameters, Deliver the neuromodulation pulse to carotid sinus nerve (CSN) afferent fibers via one or more of the lead electrodes, A patient treatment system that performs operations including. 2. Any one of the patient treatment systems in this section, wherein the one or more nerves include the patient's CSN afferent fibers. 3. Any one of the patient treatment systems in this section, wherein the lead electrode includes a first set of lead electrodes in the first region and a second set of lead electrodes in the second region. 4. Any one of the patient treatment systems in this section, wherein all of the lead electrodes are on the first region. 5. Any one of the patient treatment systems in this section, wherein the lead electrode includes at least 3, 4, 5, 6, 7, 8, 9, or 10 lead electrodes. 6. The lead electrodes include a first set of lead electrodes in a first region and a second set of lead electrodes in a second region, and the number of lead electrodes in the first set of lead electrodes is different from the number of lead electrodes in the second set of lead electrodes, for any one of the sections in this specification of a patient treatment system. 7. The lead electrodes include a first set of lead electrodes in a first region and a second set of lead electrodes in a second region, and the number of lead electrodes in the first set of lead electrodes is greater than the number of lead electrodes in the second set of lead electrodes, for any one of the sections in this specification of a patient treatment system. 8. The lead electrodes include a first set of lead electrodes in a first region and a second set of lead electrodes in a second region, the first set of lead electrodes includes at least two lead electrodes, and the second set of lead electrodes includes only a single lead electrode, for any one of the sections in this specification of a patient treatment system. 9. The lead electrodes include a first set of lead electrodes in a first region and a second set of lead electrodes in a second region, the first set of lead electrodes includes at least three lead electrodes, the second set of lead electrodes includes at least three lead electrodes, and when the first region is positioned above the second region, each of the lead electrodes in the first set of lead electrodes is aligned with the corresponding one of the lead electrodes in the second set of lead electrodes, for any one of the sections in this specification of a patient treatment system. 10. The lead electrodes include a first set of lead electrodes in a first region and a second set of lead electrodes in a second region, the first set of lead electrodes includes at least three lead electrodes extending over a first width, the second set of lead electrodes includes at least one lead electrode extending over a second width equal to the first width, and when the first region is positioned above the second region, the three lead electrodes in the first set of lead electrodes are aligned with one lead electrode in the second set of lead electrodes, for any one of the sections in this specification of a patient treatment system. 11. The lead electrodes include a first set of lead electrodes in a first region and a second set of lead electrodes in a second region, the first set of electrodes being configured to be positioned over a first side of the CSN afferent fibers, and the second set of electrodes being configured to be positioned over a second side of the CSN afferent fibers opposite the first side, for any one of the sections herein of a patient treatment system. 12. Individual lead electrodes have a different width than other individual electrodes, for any one of the sections herein of a patient treatment system. 13. The lead electrodes include a first set of lead electrodes in a first region and a second set of lead electrodes in a second region, the first set of lead electrodes and the second set of electrodes each extending across the same width, for any one of the sections herein of a patient treatment system. 14. The lead electrodes include a first set of lead electrodes in a first region, each spaced from the others in a first direction, a second set of lead electrodes in a second region, each spaced from the others in the first direction, a third electrode in the first region spaced from the first set of lead electrodes along a second direction perpendicular to the first direction, and a fourth electrode in the second region spaced from the second set of lead electrodes along the second direction, the third electrode being at least partially aligned with the fourth electrode when the first region is positioned over the second region, for any one of the sections herein of a patient treatment system. 15. The lead electrodes include a first set of lead electrodes in a first region, each spaced from one another in a first direction; a second set of lead electrodes in a second region, each spaced from one another in the first direction; a third electrode in the first region, spaced from the first set of lead electrodes along a second direction perpendicular to the first direction; and a fourth electrode in the second region, spaced from the second set of lead electrodes along the second direction. When the first region is positioned above the second region, the third electrode is at least partially aligned with the second set of lead electrodes, and the fourth electrode is at least partially aligned with the first set of lead electrodes. Any one of the patient treatment systems of the sections herein. 16. The lead electrodes include a first set of lead electrodes in a first region, each spaced from one another in a first direction; a second set of lead electrodes in a second region, each spaced from one another in the first direction; a third electrode in the first region, spaced from the first set of lead electrodes along a second direction perpendicular to the first direction; and a fourth electrode in the second region, spaced from the second set of lead electrodes along the second direction. The first set of electrodes and the third electrode are of the same width. Any one of the patient treatment systems of the sections herein. 17. The lead electrodes include a first set of lead electrodes in a first region and a second set of lead electrodes in a second region. The first set of electrodes is configured to be positioned on a first side of the CSN afferent fibers, and the second set of electrodes is configured to be positioned on a second side of the CSN afferent fibers opposite the first side. Any one of the patient treatment systems of the sections herein. 18. The lead electrodes include a first set of lead electrodes in a first region and a second set of lead electrodes in a second region. Each of the first set of lead electrodes has a first width, and at least one of the second set of lead electrodes has a second width greater than the first width. Any one of the patient treatment systems of the sections herein. 19. Each of the lead electrodes is individually addressable via a neuromodulator, for any one of the patient treatment systems of the sections herein. 20. The signal delivery device includes conductors extending from the housing to the lead body, at least one base electrode is a first base electrode, and the neuromodulator includes a second base electrode spaced from the first base electrode, each of the conductors is electrically coupled to (i) one of the first base electrode or the second base electrode, and (ii) one of the lead electrodes, for any one of the patient treatment systems of the sections herein. 21. The obtained physiological parameter indicates depolarization of the myocardium, for any one of the patient treatment systems of the sections herein. 22. The obtained physiological parameter includes a heart rate, and delivering a neuromodulation pulse includes delivering a neuromodulation pulse at a stimulation rate correlated with the determined physiological parameter such that a higher value of the determined physiological parameter corresponds to a higher value of the stimulation rate, for any one of the patient treatment systems of the sections herein. 23. Delivering a neuromodulation pulse includes delivering a neuromodulation pulse at a frequency, amplitude, and / or pulse width directly correlated with the determined physiological parameter such that a higher value of the determined physiological parameter corresponds to a higher value of the frequency, amplitude, and / or pulse width, for any one of the patient treatment systems of the sections herein. 24. Delivering a neuromodulation pulse includes delivering a neuromodulation pulse at a frequency, amplitude, and / or pulse width indirectly related to the determined physiological parameter such that a higher value of the determined physiological parameter corresponds to a lower value of the frequency, amplitude, and / or pulse width, for any one of the patient treatment systems of the sections herein. 25. A neuromodulation pulse is delivered via a set of lead electrodes, and delivering a neuromodulation pulse includes changing at least one of the lead electrodes forming the set after delivering a predetermined number of pulses, for any one of the patient treatment systems in the sections herein. 26. A neuromodulation pulse is delivered via a set of lead electrodes, and delivering a neuromodulation pulse includes changing at least one of the lead electrodes forming the set after delivering a first pulse, for any one of the patient treatment systems in the sections herein. 27. A neuromodulation pulse is delivered via a set of lead electrodes, and delivering a neuromodulation pulse includes changing at least one of the lead electrodes forming the set after delivering 2400 pulses, for any one of the patient treatment systems in the sections herein. 28. The obtained physiological parameter includes a first heart rate, and delivering a neuromodulation pulse includes delivering a first neuromodulation pulse at a first frequency, and the operation includes determining a second heart rate, and based on the second heart rate, delivering a second neuromodulation pulse at a second frequency higher than the first frequency, for any one of the patient treatment systems in the sections herein. 29. A neuromodulation pulse has a frequency that varies linearly with the obtained physiological parameter, for any one of the patient treatment systems in the sections herein. 30. A neuromodulation pulse has a frequency that varies non-linearly with the obtained physiological parameter, for any one of the patient treatment systems in the sections herein. 31. A neuromodulation pulse has a frequency that varies exponentially with the obtained physiological parameter, for any one of the patient treatment systems in the sections herein. 32. A neuromodulation pulse has a frequency between a predetermined lower frequency and a predetermined upper frequency, for any one of the patient treatment systems in the sections herein. 33. Delivering a neuromodulation pulse includes delivering the neuromodulation pulse via one or more of the lead electrodes in the first region and one or more of the lead electrodes in the second region, for any one of the patient treatment systems in the sections herein. 34. The lead electrodes include a first set of lead electrodes in the first region and a second set of lead electrodes in the second region, and the operation further includes obtaining impedance data via two or more of the lead electrodes. Delivering a neuromodulation pulse includes delivering the neuromodulation pulse via a first lead electrode of the first set of lead electrodes and a second lead electrode of the second set of lead electrodes based on the obtained impedance data, for any one of the patient treatment systems in the sections herein. 35. The operation further includes identifying CSN afferent fibers via the lead electrodes of the signal delivery device before generating a neuromodulation pulse, for any one of the patient treatment systems in the sections herein. 36. Identifying CSN afferent fibers includes obtaining data from the lead electrodes, the data including an amount of energy. Delivering a neuromodulation pulse includes delivering the neuromodulation pulse via one of the lead electrodes and a second lead electrode of the second set of lead electrodes based on the obtained data, for the patient treatment system of claim 27. 37. The lead electrodes include a first set of lead electrodes in a first region and a second set of lead electrodes in a second region. Identifying the CSN centripetal fibers includes obtaining impedance data from at least one of the first set of lead electrodes and at least one of the second set of lead electrodes. Delivering a neuromodulation pulse includes delivering a neuromodulation pulse via a first lead electrode of the first set of lead electrodes and a second lead electrode of the second set of lead electrodes based on the obtained impedance data. The patient treatment system of claim 27. 38. The lead electrodes comprise a first set of lead electrodes in a first region and a second set of lead electrodes in a second region. Delivering a neuromodulation pulse includes delivering a neuromodulation pulse via a first lead electrode of the first set of lead electrodes and a second lead electrode of the second set of lead electrodes. The operation includes obtaining a signal based on impedance data from at least one of the first lead electrode or the second lead electrode, based on the signal exceeding a predetermined threshold, delivering a first set of pulses via (i) one of the lead electrodes in the first region other than the first lead electrode and (ii) one of the lead electrodes in the second region other than the second lead electrode, and further includes any one of the patient treatment systems of the sections herein. 39. The neuromodulation pulse has a pulse width of 10 to 1000 microseconds. Any one of the patient treatment systems of the sections herein. 40. The neuromodulation pulse has a duty cycle of 50% or less. Any one of the patient treatment systems of the sections herein. 41. The neuromodulation pulse has an amplitude of 0 to 10 mA. Any one of the patient treatment systems of the sections herein. 42. A neuromodulation pulse has a frequency of 0 to 1000 Hz and is for any one of the patient treatment systems in the sections herein. 43. Individual pulses of a neuromodulation pulse have a delay with respect to a preceding pulse that increases over time and is for any one of the patient treatment systems in the sections herein. 44. A neuromodulation pulse includes a first pulse having a first delay from the immediately preceding pulse and a second pulse having a second delay from the immediately preceding pulse, and the second delay is longer than the first delay, and is for any one of the patient treatment systems in the sections herein. 45. A neuromodulation pulse includes a first pulse having a first delay from the immediately preceding pulse, a second pulse having a second delay from the immediately preceding pulse, and a third pulse having a third delay from the immediately preceding pulse, and the third delay is longer than the second delay, and the second delay is longer than the first delay, and is for any one of the patient treatment systems in the sections herein. 46. A neuromodulation pulse includes a first number of pulses having a first delay, a second number of pulses having a second delay greater than the first delay, and a third number of pulses having a third delay greater than the second delay, and is for any one of the patient treatment systems in the sections herein. 47. A neuromodulation pulse includes a first number of pulses having a first delay, a second number of pulses having a second delay greater than the first delay, and a third number of pulses having a third delay less than the second delay and the first delay, and is for any one of the patient treatment systems in the sections herein. 48. Individual pulses of a neuromodulation pulse include a delay generally corresponding to the patient's natural baroreceptor response, and is for any one of the patient treatment systems in the sections herein. 49. The obtained physiological parameter includes an instantaneous heart rate or an average heart rate, and is for any one of the patient treatment systems in the sections herein. 50. The obtained physiological parameter includes a blood pressure or an average blood pressure, and is for any one of the patient treatment systems in the sections herein. 51. The obtained physiological parameters are for any one of the patient treatment systems in this specification, including bioimpedance. 52. The obtained physiological parameters are for any one of the patient treatment systems in this specification, including thoracic bioimpedance. 53. The obtained physiological parameters are for any one of the patient treatment systems in this specification, including the activity level of the patient. 54. Further comprising a blood pressure sensor coupled to the neuromodulator and configured to generate blood pressure data, wherein generating a neuromodulation pulse is at least partially based on the blood pressure data, for any one of the patient treatment systems in this specification. 55. Further comprising a blood pressure sensor coupled to the neuromodulator and configured to generate data including at least one of blood pressure, diastolic blood pressure, or systolic blood pressure, for any one of the patient treatment systems in this specification. 56. Further comprising one or more sensors coupled to the neuromodulator and configured to generate data including at least one of stroke volume, cardiac output, end-diastolic volume of the ventricle, or end-systolic volume of the ventricle, for any one of the patient treatment systems in this specification. 57. Further comprising an oxygenation sensor coupled to the neuromodulator and configured to generate data including blood oxygenation, for any one of the patient treatment systems in this specification. 58. Further comprising a sphygmomanometer coupled to the neuromodulator and configured to generate data including arterial wall sclerosis degree, for any one of the patient treatment systems in this specification. 59. Further comprising one or more sensors communicably coupled to the neuromodulator via a wireless or wired connection, for any one of the patient treatment systems in this specification. 60. Further comprising one or more sensors implanted in the patient and communicably coupled to the neuromodulator, for any one of the patient treatment systems in this specification. Any one of the patient treatment systems in this section, further comprising one or more sensors positioned outside the patient and communicatively coupled to the neuromodulator. Any one of the patient treatment systems in this section, wherein the base electrode is a first base electrode, the neuromodulator includes a second base electrode spaced apart from the first base electrode, and the neuromodulator comprises a header including the first base electrode and the second base electrode. Any one of the patient treatment systems in this section, wherein the neuromodulator includes a tangible non-transitory computer-readable medium. Any one of the patient treatment systems in this section, further comprising a controller including a tangible non-transitory computer-readable medium, the controller communicatively wired or wirelessly to the neuromodulator. Any one of the patient treatment systems in this section, further comprising an acoustic sensor configured to detect cardiac depolarization, and generating a neuromodulation pulse is based in part on a signal from the acoustic sensor. Any one of the patient treatment systems in this section, further comprising an accelerometer configured to detect cardiac depolarization, and generating a neuromodulation pulse is based in part on a signal from the accelerometer. Any one of the patient treatment systems in this section, further comprising an accelerometer configured to output a signal including the orientation of the patient, and generating a neuromodulation pulse is based in part on a signal from the accelerometer. Any one of the patient treatment systems in this section, wherein the neuromodulation pulse is a first neuromodulation pulse, and the operation further includes delivering a second neuromodulation pulse to a different target tissue of the patient that is different from the CSN afferent fibers. 69. The neuromodulation pulse is a first neuromodulation pulse, and the operation further includes delivering a second neuromodulation pulse to the hypoglossal nerve of the patient, for any one of the patient treatment systems in the sections herein. 70. The neuromodulation pulse is a first neuromodulation pulse, and the operation further includes delivering a second neuromodulation pulse to the cervical nerve wana of the patient, for any one of the patient treatment systems in the sections herein. 71. The neuromodulation pulse is a first neuromodulation pulse, and the operation further includes delivering a second neuromodulation pulse to the vagus nerve of the patient, for any one of the patient treatment systems in the sections herein. 72. The neuromodulation pulse is a first pulse, and the operation further includes delivering a second pulse to the left atrium or right atrium of the patient, for any one of the patient treatment systems in the sections herein. 73. The neuromodulation pulse is a first pulse, and the operation further includes delivering a second pulse to the left ventricle or right ventricle of the patient, for any one of the patient treatment systems in the sections herein. 74. The neuromodulation pulse is a first pulse, and the operation further includes delivering a second pulse to the diaphragm of the patient, for any one of the patient treatment systems in the sections herein. 75. A method for configuring a treatment system to stimulate CSN afferent fibers, the method comprising: providing a treatment system including a neuromodulator and a signal delivery device electrically coupled to the neuromodulator; implanting the lead electrode of the signal delivery device proximate to the CSN afferent fibers of the patient; determining a physiological parameter of the patient; generating a neuromodulation pulse via the neuromodulator based on the determined physiological parameter; Delivering a neuromodulation pulse through two or more of the lead electrodes to the CSN afferent fibers; A method comprising. 76. A method according to any one of the sections herein, wherein the treatment system comprises any one of the treatment systems of the above sections. 77. Further comprising that the neuromodulator comprises a pulse generator and a signal delivery device, The neuromodulator comprises a housing and at least one base electrode held by the housing, The signal delivery device comprises a lead body including a first region and a second region positionable over the first region, The lead electrodes of the signal delivery device are electrically coupled to the base electrodes of the neuromodulator, The lead electrodes include a first set of lead electrodes in the first region and a second set of lead electrodes in the second region, A method according to any one of the sections herein, wherein delivering the neuromodulation pulse comprises delivering the neuromodulation pulse through one of the first set of electrodes and one of the second set of electrodes. 78. The determined physiological parameter includes a heart rate, and delivering the neuromodulation pulse comprises delivering the neuromodulation pulse at a frequency directly or indirectly correlated with the determined physiological parameter such that a higher value of the determined physiological parameter corresponds to a higher value of the frequency. A method according to any one of the sections herein. 79. The determined physiological parameter includes a first heart rate, and delivering the neuromodulation pulse comprises delivering a first neuromodulation pulse at a first frequency, and the operation is Determining a second heart rate; Based on the second heart rate, delivering a second neuromodulation pulse at a second frequency different from the first frequency; A method according to any one of the sections herein, further comprising. 80. Delivering a neuromodulation pulse includes delivering the neuromodulation pulse such that individual pulses have a frequency that varies linearly with determined physiological parameters, any one of the methods in the sections herein. 81. Delivering a neuromodulation pulse includes delivering the neuromodulation pulse such that individual pulses have a frequency that varies non-linearly with determined physiological parameters, any one of the methods in the sections herein. 82. Delivering a neuromodulation pulse includes delivering the neuromodulation pulse such that individual pulses have a frequency that varies exponentially with determined physiological parameters, any one of the methods in the sections herein. 83. Further including obtaining impedance data via two or more of the lead electrodes, delivering a neuromodulation pulse includes delivering the neuromodulation pulse via a first lead electrode of a first set of lead electrodes and a second lead electrode of a second set of lead electrodes based on the obtained impedance data, any one of the methods in the sections herein. 84. Further including identifying CSN afferent fibers via the lead electrodes of the signal delivery device before generating a neuromodulation pulse, any one of the methods in the sections herein. 85. Further including identifying CSN afferent fibers via the lead electrodes of the signal delivery device before generating a neuromodulation pulse, identifying CSN afferent fibers includes obtaining impedance data from at least one of a first set of lead electrodes and at least one of a second set of lead electrodes, delivering a neuromodulation pulse includes delivering the neuromodulation pulse via a first lead electrode of a first set of lead electrodes and a second lead electrode of a second set of lead electrodes based on the obtained impedance data, any one of the methods in the sections herein. 86. Delivering a neuromodulation pulse includes delivering the neuromodulation pulse via a first lead electrode of a first set of lead electrodes and a second lead electrode of a second set of lead electrodes, and the method comprises: obtaining a signal based on impedance data from at least one of the first lead electrode or the second lead electrode; based on the signal exceeding a predetermined threshold, delivering a first set of pulses via (i) another lead electrode in the first region other than the first lead electrode and (ii) another lead electrode in the second region other than the second lead electrode; and further comprising any one of the methods of the sections herein. 87. Individual pulses of a neuromodulation pulse have a delay relative to a preceding pulse that increases over time, any one of the methods of the sections herein. 88. Individual pulses of a neuromodulation pulse have a delay relative to a preceding pulse that decreases over time, any one of the methods of the sections herein. 89. A neuromodulation pulse includes a first pulse having a first delay from the immediately preceding pulse and a second pulse having a second delay from the immediately preceding pulse, and the second delay is longer than the first delay, any one of the methods of the sections herein. 90. A neuromodulation pulse includes a first pulse having a first delay from the immediately preceding pulse, a second pulse having a second delay from the immediately preceding pulse, and a third pulse having a third delay from the immediately preceding pulse, and the third delay is longer than the second delay, and the second delay is longer than the first delay, any one of the methods of the sections herein. 91. A neuromodulation pulse includes a first number of pulses having a first delay, a second number of pulses having a second delay greater than the first delay, and a third number of pulses having a third delay greater than the second delay, any one of the methods of the sections herein. 92. The individual pulses of the neuromodulation pulses are any one of the methods in the sections herein that include a delay generally corresponding to the patient's natural baroreceptor response. 93. The determined physiological parameter is any one of the methods in the sections herein that includes an instantaneous heart rate, a filtered heart rate, or an average heart rate. 94. The determined physiological parameter is any one of the methods in the sections herein that includes an instantaneous blood pressure or an average blood pressure. 95. The determined physiological parameter is any one of the methods in the sections herein that includes a bioimpedance. 96. The determined physiological parameter is any one of the methods in the sections herein that includes a thoracic bioimpedance. 97. Determining a physiological parameter is any one of the methods in the sections herein that includes determining the physiological parameter via at least one of the lead electrodes. 98. Before generating a neuromodulation pulse, further includes detecting a signal associated with a cardiac depolarization event via at least one of the lead electrodes, which is any one of the methods in the sections herein. 99. Before generating a neuromodulation pulse, further includes receiving a signal associated with a cardiac depolarization event, and delivering the neuromodulation pulse is at least partially based on a predetermined delay after the signal associated with the cardiac depolarization event is received, which is any one of the methods in the sections herein. 100. A method for configuring a therapy system to detect a patient's cardiac depolarization, the method comprising: providing a therapy system comprising a neuromodulator and a signal delivery device electrically coupled to the neuromodulator, wherein the neuromodulator includes a base electrode and the signal delivery device includes a lead electrode; implanting the lead electrode of the signal delivery device into the patient; Detecting parameters associated with cardiac depolarization events via vectors of a treatment system; Moving a signal delivery device based on the detected parameters such that a lead electrode is proximate to the patient's CSN afferent fibers; A method comprising the above. 101. The vector is any one of the methods in the sections herein that includes one of a lead electrode and a base electrode. 102. The base electrode is a first base electrode, the neuromodulator further comprises a second base electrode and a housing including the first base electrode and the second base electrode, and the vector is any one of the methods in the sections herein that includes the first base electrode and the second base electrode. 103. The neuromodulator comprises a housing including a conductive material, a portion of the housing is the base electrode, and the vector is any one of the methods in the sections herein that includes the base electrode and one of the lead electrodes. 104. The method further comprises: After moving the signal delivery device, generating a neuromodulation pulse via the neuromodulator; Delivering the neuromodulation pulse to the CSN afferent fibers via one or more of the lead electrodes; Any one of the methods in the sections herein further including the above. 105. The method further comprises: After moving the signal delivery device, generating a first neuromodulation pulse having a first characteristic via the neuromodulator; Delivering the first neuromodulation pulse to the CSN afferent fibers via one or more of the lead electrodes; Obtaining stimulation parameters for the first neuromodulation pulse, the stimulation parameters including at least one of amplitude, pulse width, or energy associated with the first neuromodulation pulse; Generating, based on the obtained stimulation parameters, a second neuromodulation pulse having a second characteristic different from the first characteristic via a neuromodulator; Any one of the methods in the sections herein, further comprising. 106. Embedding a lead electrode includes embedding the lead electrode in or near the patient's neck. Any one of the methods in the sections herein. 107. The treatment system comprises any one of the treatment systems in the above sections. Any one of the methods in the sections herein. 108. The neuromodulation pulse is a first neuromodulation pulse, and the method further comprises delivering a second neuromodulation pulse to a different target tissue of the patient than the CSN afferent fibers. Any one of the methods in the sections herein. 109. The neuromodulation pulse is a first neuromodulation pulse, and the method further comprises delivering a second neuromodulation pulse to the hypoglossal nerve of the patient. Any one of the methods in the sections herein. 110. The neuromodulation pulse is a first neuromodulation pulse, and the method further comprises delivering a second neuromodulation pulse to the cervical nerve wana of the patient. Any one of the methods in the sections herein. 111. The neuromodulation pulse is a first neuromodulation pulse, and the method further comprises delivering a second neuromodulation pulse to the left atrium or right atrium of the patient. Any one of the methods in the sections herein. 112. The neuromodulation pulse is a first neuromodulation pulse, and the method further comprises delivering a second neuromodulation pulse to the left ventricle or right ventricle of the patient. Any one of the methods in the sections herein. 113. The neuromodulation pulse is a first pulse, and the method further comprises delivering a second pulse to the diaphragm of the patient. Any one of the methods in the sections herein. 114. Detecting one or more cardiac depolarizations from a patient's atrium; Delivering an electrical pulse to the patient's ventricle based at least in part on the detected cardiac depolarization; Any one method among the sections herein, further comprising. 115. A patient treatment system, A neuromodulator comprising a housing and at least one base electrode held by the housing; An implantable signal delivery device electrically connectable to the neuromodulator, the signal delivery device comprising a lead body having a first region, a second region positionable over the first region, and a lead electrode electrically connectable to the base electrode of the neuromodulator, the lead electrode being configured to be proximate to and / or at least partially embedded around one or more nerves associated with the patient's baroreflex; One or more processors; A tangible non-transitory computer-readable medium having instructions that, when executed by one or more processors, cause the patient treatment system to Obtain a patient's physiological parameter, the physiological parameter including at least one of blood pressure, heart rate, bioimpedance, or patient activity level; Generate a neuromodulation pulse based on the obtained physiological parameter; Deliver the neuromodulation pulse to one or more nerves via one or more of the lead electrodes; A tangible non-transitory computer-readable medium that includes operations to be performed; A patient treatment system comprising. 116. One or more nerves include the afferent fibers of the patient's carotid sinus nerve (CSN); The lead electrode includes a first set of lead electrodes in the first region and a second set of lead electrodes in the second region; The first set of electrodes is configured to be positioned over a first side of the CSN afferent fibers, and the second set of electrodes is configured to be positioned over a second side of the CSN afferent fibers on an opposite side of the first side, of a patient treatment system of section 115 or any other section herein. 117. The lead electrode includes a first set of lead electrodes in a first region and a second set of lead electrodes in a second region, and when the first region is positioned over the second region, each of the first set of lead electrodes is aligned with a corresponding one of the second set of lead electrodes, of a patient treatment system of section 115 or any other section herein. 118. The lead electrode includes a first set of lead electrodes in a first region and a second set of lead electrodes in a second region, The number of lead electrodes in the first set of lead electrodes is different from the number of lead electrodes in the second set of lead electrodes, The first set of lead electrodes, and the second set of lead electrodes are over the same distance of the lead body, of a patient treatment system of section 115 or any other section herein. 119. The lead electrode includes a first set of lead electrodes in a first region and a second set of lead electrodes in a second region, and the individual ones of the first set of lead electrodes have a first width, and at least one of the second set of lead electrodes has a second width greater than the first width, of a patient treatment system of section 115 or any other section herein. 120. One or more nerves include the patient's CSN afferent fibers, the lead electrodes include a first set of lead electrodes in a first region and a second set of lead electrodes in a second region, and the operation further includes identifying the CSN afferent fibers by obtaining impedance data from at least one of the first set of lead electrodes or at least one of the second set of lead electrodes, and delivering a neuromodulation pulse includes delivering a neuromodulation pulse via a first lead electrode of the first set of lead electrodes and a second lead electrode of the second set of lead electrodes based on the obtained impedance data, a patient treatment system of section 115 or any other section herein. 121. Each of the lead electrodes is individually addressable via a neuromodulator, a patient treatment system of section 115 or any other section herein. 122. The signal delivery device includes a conductor extending from the housing to the lead body, at least one base electrode is a first base electrode, the neuromodulator includes a second base electrode spaced apart from the first base electrode, each of the conductors is electrically coupled to (i) one of the first base electrode or the second base electrode, and (ii) one of the lead electrodes, a patient treatment system of section 115 or any other section herein. 123. The obtained physiological parameter indicates depolarization of the myocardium, a patient treatment system of section 115 or any other section herein. 124. The obtained physiological parameter includes a heart rate, and delivering a neuromodulation pulse includes delivering a neuromodulation pulse at a stimulation rate correlated with the obtained physiological parameter such that a higher value of the obtained physiological parameter corresponds to a higher value of the stimulation rate, a patient treatment system of section 115 or any other section herein. 125. The obtained physiological parameters include a first heart rate, and delivering a neuromodulation pulse includes delivering a first neuromodulation pulse at a first frequency, and the operation comprises determining a second heart rate, and based on the second heart rate, delivering a second neuromodulation pulse at a second frequency higher than the first frequency, and further includes the patient treatment system of section 115 or any other section herein. 126. The patient treatment system of section 115 or any other section herein further comprises a blood pressure sensor operably coupled to the neuromodulator and configured to generate data including at least one of mean blood pressure, diastolic blood pressure, or systolic blood pressure, and delivering a neuromodulation pulse is at least partially based on the generated data obtained from the blood pressure sensor. 127. The patient treatment system of section 115 or any other section herein further comprises an acoustic sensor configured to detect cardiac depolarization, and generating a neuromodulation pulse is at least partially based on a signal from the acoustic sensor. 128. The patient treatment system of section 115 or any other section herein further comprises an accelerometer configured to detect cardiac depolarization, and generating a neuromodulation pulse is partially based on a signal from the accelerometer. 129. The patient treatment system of section 115 or any other section herein further comprises an accelerometer configured to output a signal indicating the orientation of the patient, and generating a neuromodulation pulse is partially based on a signal from the accelerometer. 130. The neuromodulation pulse includes a first pulse having a first delay from the immediately preceding pulse, a second pulse having a second delay from the immediately preceding pulse, and a third pulse having a third delay from the immediately preceding pulse, where the third delay is longer than the second delay, and the second delay is longer than the first delay, and the patient treatment system of section 115 or any other section herein. 131. The neuromodulation pulse has a pulse width of 10 to 1000 microseconds, a duty cycle of 50% or less, an amplitude of 0 to 10 mA, and a frequency of 0 to 1000 Hz, and has two or more of the foregoing, for a patient treatment system of section 115 or any other section herein. 132. The physiological parameter is a first physiological parameter, the neuromodulation pulse is a first neuromodulation pulse, and delivering the neuromodulation pulse includes delivering the first neuromodulation pulse to one or more nerves according to a first set of stimulation parameters, and the operation includes obtaining a second physiological parameter of the patient after delivering the first neuromodulation, generating a second neuromodulation pulse having a second set of stimulation parameters based on the second physiological parameter of the patient, and delivering the second neuromodulation pulse to one or more nerves according to the second set of stimulation parameters, wherein the first set of stimulation parameters includes a first frequency, a first amplitude, a first pulse width, and a first duty cycle, the second set of stimulation parameters includes a second frequency, a second amplitude, a second pulse width, and a second duty cycle, and at least one of the first frequency, the first amplitude, the first pulse width, or the first duty cycle is different from each of the second frequency, the second amplitude, the second pulse width, or the second duty cycle, for a patient treatment system of section 115 or any other section herein. 133. The physiological parameter is a first physiological parameter, the neuromodulation pulse is a first neuromodulation pulse, and delivering the neuromodulation pulse includes delivering the first neuromodulation pulse to one or more nerves via a first group of lead electrodes, and the operation After delivering the first neuromodulation, obtaining a second physiological parameter of the patient, Based on the second physiological parameter of the patient, generating a second neuromodulation pulse, Delivering the second neuromodulation pulse to one or more nerves via a second group of lead electrodes different from the first group of lead electrodes, Further comprising a patient treatment system of section 115 or any other section herein. 134. A method for configuring a treatment system to detect a patient's cardiac depolarization, the method comprising: Providing a treatment system comprising a neuromodulator and a signal delivery device electrically coupled to the neuromodulator, the neuromodulator including a base electrode and the signal delivery device including lead electrodes, Implanting the lead electrodes of the signal delivery device into the patient, Delivering a first neuromodulation pulse to the patient's CSN afferent fibers via one or more of the lead electrodes according to a first set of stimulation parameters, Detecting a parameter associated with a cardiac depolarization event via a vector of the treatment system, Based on the detected parameter, adjusting one or more of the first set of stimulation parameters to define a second set of stimulation parameters, Delivering a second neuromodulation pulse to the patient's CSN afferent fibers via one or more of the lead electrodes according to the second set of stimulation parameters, Including, the method. 135. The first set of stimulation parameters includes a first frequency, a first amplitude, a first pulse width, and a first duty cycle, the second set of stimulation parameters includes a second frequency, a second amplitude, a second pulse width, and a second duty cycle, and at least one of the first frequency, the first amplitude, the first pulse width, or the first duty cycle is different from each of the second frequency, the second amplitude, the second pulse width, or the second duty cycle, the method of section 134 or any other section herein. 136. Delivering a first neuromodulation pulse includes delivering the first neuromodulation pulse via a first group of lead electrodes, and delivering a second neuromodulation pulse includes delivering the second neuromodulation pulse via a second group of lead electrodes different from the first group of lead electrodes, the method of section 135 or any other section herein. 137. Adjusting one or more of the first set of stimulation parameters includes adjusting an electrode configuration to deliver a neuromodulation pulse to a patient's nerve fibers, the method of section 134 or any other section herein. 138. The vector includes one of a lead electrode and a base electrode, the method of section 134 or any other section herein. 139. The base electrode is a first base electrode, the neuromodulator further comprises (i) a second base electrode and (ii) a housing including the first base electrode and the second base electrode, and the vector includes the first base electrode and the second base electrode, the method of section 134 or any other section herein. 140. A patient treatment system, a neuromodulator comprising a housing and at least one base electrode held by the housing, an implantable signal delivery device electrically connectable to the neuromodulator, the signal delivery device A lead body comprising a first region, a second region, and an intermediate region between the first region and the second region, wherein the second region is positionable over the first region by folding the lead body along the intermediate region, the lead body, A lead electrode electrically connectable to a base electrode of a neuromodulator, the lead electrode including a first set of lead electrodes in the first region and a second set of lead electrodes in the second region, the lead electrode, Comprising, The first set of lead electrodes and the second set of lead electrodes are at the same distance over, The first set of lead electrodes and the second set of lead electrodes each include at least three electrodes, A patient treatment system, wherein the lead electrode is configured to be proximate to and / or at least partially embedded around the afferent fibers of the patient's CSN. 141. The first region is positioned over the second region, and the individual ones of the first set of lead electrodes are at least partially overlapping or aligned with the corresponding ones of the second set of lead electrodes along both the first dimension of the lead body and the second dimension of the lead body, the first dimension being perpendicular to the second dimension, the patient treatment system of clause 140 or any other clause herein. 142. The first region is positioned over the second region, and the individual ones of the first set of lead electrodes are (i) aligned with the corresponding ones of the second set of lead electrodes along the first dimension of the lead body and (ii) offset from the corresponding ones of the second set of lead electrodes along the second dimension of the lead body, the first dimension being perpendicular to the second dimension, the patient treatment system of clause 140 or any other clause herein. 143. Further comprising (i) a first suture hole laterally outward of the first set of lead electrodes in the first region and (ii) a second suture hole laterally outward of the second set of lead electrodes in the second region, the patient treatment system of clause 140 or any other clause herein. A patient treatment system of section 140 or any other section in this specification, further comprising a first tapered tab extending laterally outwardly from a side portion of the first region and a second tapered tab extending laterally outwardly from a side portion of the second region, away from the intermediate region.

Claims

Claim 1 A patient treatment system comprising a neuromodulator comprising a housing and at least one base electrode held by the housing, an implantable signal delivery device electrically connectable to the neuromodulator, the signal delivery device comprising a lead body having a first region, a second region positionable over the first region, and a lead electrode electrically connectable to the base electrode of the neuromodulator, the lead electrode configured to be proximate to and / or at least partially embedded around one or more nerves associated with the baroreflex of the patient, the implantable signal delivery device one or more processors, a tangible non-transitory computer-readable medium having instructions which, when executed by the one or more processors, cause the patient treatment system to obtain physiological parameters of the patient, the physiological parameters including at least one of blood pressure, heart rate, bioimpedance, or patient activity level, generate a neuromodulation pulse based on the obtained physiological parameters, deliver the neuromodulation pulse to the one or more nerves via one or more of the lead electrodes, a tangible non-transitory computer-readable medium that causes the operations to be performed, A patient treatment system comprising the above components. Claim 2 The one or more nerves include afferent fibers of the carotid sinus nerve (CSN) of the patient, The lead electrode includes a first set of lead electrodes in the first region and a second set of lead electrodes in the second region, The first set of electrodes is configured to be positioned over a first side of the CSN afferent fibers, and the second set of electrodes is configured to be positioned over a second side of the CSN afferent fibers on the opposite side of the first side. The patient treatment system according to claim 1. Claim 3 The lead electrode includes a first set of lead electrodes in the first region and a second set of lead electrodes in the second region, and when the first region is positioned above the second region, each of the first set of lead electrodes is aligned with a corresponding one of the second set of lead electrodes. The patient treatment system according to claim 1.

4. The lead electrode includes a first set of lead electrodes in the first region and a second set of lead electrodes in the second region, The number of lead electrodes in the first set of lead electrodes is different from the number of lead electrodes in the second set of lead electrodes, The first set of lead electrodes and the second set of lead electrodes are over the same distance of the lead body. The patient treatment system according to claim 1.

5. The lead electrode includes a first set of lead electrodes in the first region and a second set of lead electrodes in the second region, and each individual one of the first set of lead electrodes has a first width, and at least one of the second set of lead electrodes has a second width greater than the first width. The patient treatment system according to claim 1.

6. The one or more nerves include the CSN afferent fibers of the patient, the lead electrode includes a first set of lead electrodes in the first region and a second set of lead electrodes in the second region, and the operation further includes identifying the CSN afferent fibers by obtaining impedance data from at least one of the first set of lead electrodes or at least one of the second set of lead electrodes, and delivering the neuromodulation pulse includes delivering the neuromodulation pulse through a first lead electrode of the first set of lead electrodes and a second lead electrode of the second set of lead electrodes based on the obtained impedance data. The patient treatment system according to claim 1.

7. Each of the lead electrodes is individually addressable via the neuromodulator. The patient treatment system according to claim 1.

8. The signal delivery device includes a conductor extending from the housing to the lead body, The at least one base electrode is a first base electrode, The neuromodulator includes a second base electrode spaced apart from the first base electrode, The patient treatment system according to claim 1, wherein each of the conductors is electrically coupled to (i) one of the first base electrode or the second base electrode, and (ii) one of the lead electrodes.

9. The patient treatment system according to claim 1, wherein the obtained physiological parameter indicates myocardial depolarization.

10. The obtained physiological parameter includes a heart rate, and delivering the neuromodulation pulse includes delivering the neuromodulation pulse at a stimulation rate correlated with the obtained physiological parameter such that a higher value of the obtained physiological parameter corresponds to a higher value of the stimulation rate. The patient treatment system according to claim 1.

11. The obtained physiological parameter includes a first heart rate, and delivering the neuromodulation pulse includes delivering a first neuromodulation pulse at a first frequency, and the operation includes determining a second heart rate; delivering a second neuromodulation pulse at a second frequency higher than the first frequency based on the second heart rate; The patient treatment system according to claim 1, further comprising:

12. The patient treatment system according to claim 1, further comprising a blood pressure sensor operably coupled to the neuromodulator and configured to generate data including at least one of mean blood pressure, diastolic blood pressure, or systolic blood pressure, and delivering the neuromodulation pulse is at least partially based on the generated data obtained from the blood pressure sensor.

13. The patient treatment system according to claim 1, further comprising an acoustic sensor configured to detect cardiac depolarization, and generating the neuromodulation pulse is at least partially based on a signal from the acoustic sensor.

14. [[ID=...]]The patient treatment system according to claim 1, further comprising an accelerometer configured to detect cardiac depolarization, and generating the neuromodulation pulse is partially based on a signal from the accelerometer.

15. The patient treatment system according to claim 1, further comprising an accelerometer configured to output a signal indicating the orientation of the patient, wherein generating the neuromodulation pulse is partially based on the signal from the accelerometer.

16. The neuromodulation pulse includes a first pulse having a first delay from the immediately preceding pulse, a second pulse having a second delay from the immediately preceding pulse, and a third pulse having a third delay from the immediately preceding pulse, wherein the third delay is longer than the second delay, and the second delay is longer than the first delay. The patient treatment system according to claim 1.

17. The neuromodulation pulse is a pulse width of from 10 to 1000 microseconds, a duty cycle of 50% or less, an amplitude of from 0 to 10 mA, and a frequency of from 0 to 1000 Hz, and has two or more of the above. The patient treatment system according to claim 1.

18. The physiological parameter is a first physiological parameter, the neuromodulation pulse is a first neuromodulation pulse, and sending the neuromodulation pulse includes sending a first neuromodulation pulse to the one or more nerves according to the first stimulation parameter. The operation is after sending the first neuromodulation, obtaining a second physiological parameter of the patient; generating a second neuromodulation pulse having a second stimulation parameter based on the second physiological parameter of the patient; sending the second neuromodulation pulse to the one or more nerves according to the second stimulation parameter; and further includes The first stimulation parameter includes a first frequency, a first amplitude, a first pulse width, and a first duty cycle. The second stimulation parameter includes a second frequency, a second amplitude, a second pulse width, and a second duty cycle. At least one of the first frequency, the first amplitude, the first pulse width, or the first duty cycle is different from each of the second frequency, the second amplitude, the second pulse width, or the second duty cycle. The patient treatment system according to claim 1.

19. The physiological parameter is a first physiological parameter, the neuromodulation pulse is a first neuromodulation pulse, and delivering the neuromodulation pulse includes delivering a first neuromodulation pulse to the one or more nerves via a first group of the lead electrodes, and the operation is after delivering the first neuromodulation, obtaining a second physiological parameter of the patient; generating a second neuromodulation pulse based on the second physiological parameter of the patient; delivering the second neuromodulation pulse to the one or more nerves via a second group of the lead electrodes different from the first group of the lead electrodes; The patient treatment system according to claim 1, further comprising.

20. A method for configuring a treatment system to detect a patient's cardiac depolarization, the method comprising: providing a treatment system comprising a neuromodulator and a signal delivery device electrically coupled to the neuromodulator, the neuromodulator including a base electrode and the signal delivery device including lead electrodes; implanting the lead electrodes of the signal delivery device into the patient; delivering a first neuromodulation pulse to the CSN afferent fibers of the patient via one or more of the lead electrodes according to a first set of stimulation parameters; detecting a parameter associated with a cardiac depolarization event via a vector of the treatment system; defining a second set of stimulation parameters by adjusting one or more of the first set of stimulation parameters based on the detected parameter; delivering a second neuromodulation pulse to the CSN afferent fibers of the patient via one or more of the lead electrodes according to the second set of stimulation parameters; A method, comprising.

21. The first stimulation parameter includes a first frequency, a first amplitude, a first pulse width, and a first duty cycle, the second stimulation parameter includes a second frequency, a second amplitude, a second pulse width, and a second duty cycle, and at least one of the first frequency, the first amplitude, the first pulse width, or the first duty cycle is different from each of the second frequency, the second amplitude, the second pulse width, or the second duty cycle. The method according to claim 20.

22. Sending the first neuromodulation pulse includes sending the first neuromodulation pulse via a first group of the lead electrodes, and sending the second neuromodulation pulse includes sending the second neuromodulation pulse via a second group of the lead electrodes different from the first group of the lead electrodes. The method according to claim 21.

23. Adjusting one or more of the first stimulation parameters includes adjusting an electrode configuration to send a neuromodulation pulse to the nerve fibers of the patient. The method according to claim 20.

24. The vector includes one of the lead electrode and the base electrode. The method according to claim 20.

25. The base electrode is a first base electrode, and the neuromodulator further includes (i) a second base electrode and (ii) a housing including the first base electrode and the second base electrode, and the vector includes the first base electrode and the second base electrode. The method according to claim 20.

26. A patient treatment system, A neuromodulator including a housing and at least one base electrode held by the housing, An implantable signal transmitting device electrically connectable to the neuromodulator, the signal transmitting device including A lead body including a first region, a second region, and an intermediate region between the first region and the second region, wherein the second region is positionable over the first region by folding the lead body along the intermediate region. The lead body, A lead electrode electrically connectable to the base electrode of the neuromodulator, the lead electrode including a first set of lead electrodes in the first region and a second set of lead electrodes in the second region, the lead electrode, comprising, The first set of the lead electrodes and the second set of the lead electrodes extend over the same distance, The first set of the lead electrodes and the second set of the lead electrodes each include at least three electrodes, The lead electrode is configured to be proximate to and / or at least partially embedded around the CSN afferent fibers of a patient, a patient treatment system.

27. The first region is positioned above the second region, and the individual ones of the first set of the lead electrodes are at least partially overlapping or aligned with the corresponding ones of the second set of the lead electrodes along both the first dimension of the lead body and the second dimension of the lead body, the first dimension being perpendicular to the second dimension, the patient treatment system according to claim 26.

28. The first region is positioned above the second region, and the individual ones of the first set of the lead electrodes are (i) aligned with the corresponding ones of the second set of the lead electrodes along the first dimension of the lead body, and (ii) offset from the corresponding ones of the second set of the lead electrodes along the second dimension of the lead body, the first dimension being perpendicular to the second dimension, the patient treatment system according to claim 26.

29. Further comprising (i) a first lateral outer suture hole of the first set of the lead electrodes in the first region and (ii) a second lateral outer suture hole of the second set of the lead electrodes in the second region, the patient treatment system according to claim 26.

30. Further comprising a first tapered tab extending laterally outward from a side portion of the first region away from the intermediate region and a second tapered tab extending laterally outward from the side portion of the second region, the patient treatment system according to claim 26.

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