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WO2025076355A1 - Système et procédé pour fournir une thérapie pour les troubles respiratoires - Google Patents

Système et procédé pour fournir une thérapie pour les troubles respiratoires Download PDF

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Publication number
WO2025076355A1
WO2025076355A1 PCT/US2024/049967 US2024049967W WO2025076355A1 WO 2025076355 A1 WO2025076355 A1 WO 2025076355A1 US 2024049967 W US2024049967 W US 2024049967W WO 2025076355 A1 WO2025076355 A1 WO 2025076355A1
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WO
WIPO (PCT)
Prior art keywords
treatment system
stimulation
patient
phrenic nerve
ipg
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/US2024/049967
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English (en)
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WO2025076355A8 (fr
Inventor
Todd P. Goblish
Randy W. Westlund
Kristofer J. James
Antonios Panteleon
Gray A. FREEMAN
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Zoll Medical Corp
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Zoll Medical Corp
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Publication date
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Publication of WO2025076355A1 publication Critical patent/WO2025076355A1/fr
Publication of WO2025076355A8 publication Critical patent/WO2025076355A8/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3601—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation of respiratory organs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Measuring devices for evaluating the respiratory organs
    • A61B5/0816—Measuring devices for examining respiratory frequency
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4806—Sleep evaluation
    • A61B5/4818—Sleep apnoea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/3611—Respiration control
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36135—Control systems using physiological parameters
    • A61N1/36139—Control systems using physiological parameters with automatic adjustment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36135—Control systems using physiological parameters
    • A61N1/3614—Control systems using physiological parameters based on impedance measurement

Definitions

  • At least one example in accordance with the present disclosure relates generally to breathing disorders.
  • Examples of the disclosure comprise a treatment system for providing disordered breathing therapy to a sleeping patient during at least one sleeping period, the system comprising: at least one first stimulation lead; at least one second stimulation lead; and an implantable pulse generator (IPG) configured to couple to the at least one first stimulation lead and the at least one second stimulation lead, the IPG comprising a processor, and a memory, the IPG configured to determine whether operational parameters comprise hypoglossal nerve electrical stimulation parameters, provide phrenic nerve electrical stimulations to a phrenic nerve of a patient via the at least one first stimulation lead during the at least one sleeping period, provide hypoglossal nerve electrical stimulations to a hypoglossal nerve of the patient via the at least one second stimulation lead during the at least one sleeping period responsive to a determination that the operational parameters comprise the hypoglossal nerve electrical stimulation parameters, and coordinate a relative timing of the hypoglossal nerve electrical stimulations to the hypoglossal nerve with the phrenic nerve electrical stimulations to the phrenic nerve of the patient.
  • the IPG is configured to provide the phrenic nerve electrical stimulations to the phrenic nerve of the patient during the at least one sleeping period via the at least one first stimulation lead in an absence of hypoglossal nerve electrical stimulation during the at least one sleeping period responsive to a determination that the operational parameters exclude the hypoglossal nerve electrical stimulation parameters.
  • the operational parameters comprise operational parameters determined prior to the at least one sleeping period and without sensed respiratory data acquired from the patient during the at least one sleeping period.
  • the IPG is configured to align a delivery start time of the hypoglossal nerve electrical stimulations with a delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the hypoglossal nerve electrical stimulations relative to the delivery stall time of the phrenic nerve electrical stimulations such that the delivery start time of the hypoglossal nerve electrical stimulations is earlier than the delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the hypoglossal nerve electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery start time of the hypoglossal nerve electrical stimulations is later than the delivery start time of the phrenic nerve electrical stimulations.
  • the phrenic nerve electrical stimulations provide a trigger for the hypoglossal nerve electrical stimulations, wherein the trigger excludes sensed respiration of the patient during the at least one sleeping period.
  • the phrenic nerve electrical stimulations and the hypoglossal nerve electrical stimulations are provided as pulse trains, each pulse train comprising a plurality of pulses, and one or more of phrenic nerve electrical stimulation parameters or the hypoglossal nerve electrical stimulation parameters comprise one or more of a pulse train parameter, a stimulation pulse frequency, a time between stimulation pulses, a current magnitude, a voltage magnitude, a relative timing for the phrenic nerve electrical stimulations and the hypoglossal nerve electrical stimulations.
  • the treatment system comprises at least one first sensor communicatively coupled to the IPG, wherein the at least one first sensor is configured to provide sensor data indicative of patient respiration.
  • the IPG is further configured to modify at least one of the phrenic nerve electrical stimulation parameters or the hypoglossal nerve electrical stimulation parameters based on the sensor data.
  • the at least one first sensor comprises a transthoracic impedance sensor.
  • the sensor data indicative of patient respiration is indicative of a respiration rate
  • the operational parameters for the IPG comprise a pre-determined phrenic nerve stimulation rate
  • the IPG is configured to: provide the phrenic nerve electrical stimulations at the pre-determined phrenic nerve stimulation rate, receive the sensor data indicative of the respiration rate from the at least one first sensor, accumulate the sensor data over a prc-dctcrmincd collection time period, and determine a degree of synchronization between the respiration rate and the pre-determined phrenic nerve stimulation rate based on the accumulated sensor data.
  • the degree of synchronization is based on a ratio of a quantity of breaths within a predetermined range of the pre-determined phrenic nerve stimulation rate to a total quantity of breaths for a particular time period. In at least one example, the degree of synchronization is based on a ratio of spectral power in a stimulation frequency band to a spectral power in an intrinsic respiratory frequency band. In at least one example, to determine the degree of synchronization, the processor is configured to calculate the degree of synchronization. In at least one example, to determine the degree of synchronization, the IPG is configured to provide the sensor data to an external computing device and receive the degree of synchronization from the external computing device.
  • the IPG is configured to compare the degree of synchronization to a degree of synchronization criterion comprising one of a target threshold or a target range, and if the degree of synchronization satisfies the degree of synchronization criterion, then maintain stimulation parameters for the disordered breathing therapy for one or more therapy cycles, else adjust the stimulation parameters and, optionally, reevaluate the degree of synchronization, wherein the stimulation parameters comprise at least one of phrenic nerve electrical stimulation parameters or hypoglossal nerve electrical stimulation parameters.
  • the IPG comprises a clock and is configured to: receive the sensor data from the at least one second sensor, receive time information from the clock, identify a commencement of the at least one sleeping period based on the sensor data and the time information, and in response to the identification of the commencement of the at least one sleeping period, provide the phrenic nerve electrical stimulations and the hypoglossal nerve electrical stimulations, or provide the phrenic nerve electrical stimulations in the absence of hypoglossal nerve electrical stimulations.
  • the IPG comprises at least two connector ports comprising: at least one first connector port configured to couple to at least one first stimulation lead, the at least one first stimulation lead comprising at least one first terminal pin configured to couple to the at least one first connector port, and at least one second connector port configured to couple to at least one second stimulation lead, the one second stimulation lead comprising at least one second terminal pin configured to couple to the at least one second connector port, and wherein the operational parameters comprise processor-executable instructions that determine which of the at least two connector ports is the at least one first connector port and which of the at least two connector ports is the at least one second connector port.
  • the IPG comprises at least one communications interface and is configured to wirelessly receive the operational parameters. In at least one example, the IPG is configured to wirelessly receive the operational parameters before implantation of the IPG. In at least one example, the IPG is configured to wirelessly receive the operational parameters after implantation of the IPG. In at least one example, the at least one communications interface comprises a telemetry interface. In at least one example, the at least one communications interface is configured to transmit and/or receive information according to a Bluetooth® communication protocol. In at least one example, the IPG is configured to provide the phrenic nerve electrical stimulations in response to a trigger comprising sensed respiration of the patient during the at least one sleeping period.
  • the IPG is configured to align a delivery start time of the hypoglossal nerve electrical stimulations with a delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the hypoglossal nerve electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery start time of the hypoglossal nerve electrical stimulations is earlier than the delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the hypoglossal nerve electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery start time of the hypoglossal nerve electrical stimulations is later than the delivery start time of the phrenic nerve electrical stimulations.
  • the phrenic nerve electrical stimulations provide a trigger for the hypoglossal nerve electrical stimulations, wherein the trigger excludes sensed respiration of the patient during the at least one sleeping period.
  • the IPG further comprises at least one communications interface configured to wirelessly receive operational parameters for the IPG.
  • the operational parameters comprise one or more of phrenic nerve electrical stimulation parameters or hypoglossal nerve electrical stimulation parameters.
  • the IPG is further configured to modify at least one of the phrenic nerve electrical stimulation parameters or the hypoglossal nerve electrical stimulation parameters based on the sensor data.
  • the degree of synchronization is based on a ratio of a quantity of breaths within a predetermined range of the pre-determined phrenic nerve stimulation rate to a total quantity of breaths for a particular time period. In at least one example, the degree of synchronization is based on a ratio of spectral power in a stimulation frequency band to a spectral power in an intrinsic respiratory frequency band. In at least one example, to determine the degree of synchronization, the processor is configured to calculate the degree of synchronization. In at least one example, to determine the degree of synchronization, the IPG is configured to provide the sensor data to an external computing device and receive the degree of synchronization from the external computing device via the at least one communications interface.
  • the IPG is configured to: compare the degree of synchronization to a degree of synchronization criterion comprising one of a target threshold or a target range, and if the degree of synchronization satisfies the degree of synchronization criterion, then maintain stimulation parameters for the disordered breathing therapy for one or more therapy cycles, else adjust the stimulation parameters and reevaluate the degree of synchronization, wherein the stimulation parameters comprise at least one of phrenic nerve electrical stimulation parameters or hypoglossal nerve electrical stimulation parameters.
  • the treatment system includes at least one first sensor communicatively coupled to the IPG, wherein the at least one first sensor is configured to provide sensor data indicative of patient respiration.
  • the IPG is further configured to modify at least one of the phrenic nerve electrical stimulation parameters or the hypoglossal nerve electrical stimulation parameters based on the sensor data.
  • the at least one first sensor comprises a transthoracic impedance sensor.
  • the sensor data indicative of patient respiration is indicative of a respiration rate
  • the operational parameters for the IPG comprise a pre-determined phrenic nerve stimulation rate
  • the IPG is configured to: provide the phrenic nerve electrical stimulations at the pre-determined phrenic nerve stimulation rate, receive the sensor data indicative of the respiration rate from the at least one first sensor, accumulate the sensor data over a pre-determined collection time period, and determine a degree of synchronization between the respiration rate and the pre-determined phrenic nerve stimulation rate based on the accumulated sensor data.
  • the treatment system includes at least one second sensor communicatively coupled to the IPG, wherein the at least one second sensor is configured to provide sensor data indicative of one or more of patient movement or patient position.
  • the at least one second sensor comprises at least one of an implantable accelerometer or an external accelerometer.
  • the IPG is configured to align a delivery start time of the hypoglossal nerve electrical stimulations with a delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the hypoglossal nerve electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery start time of the hypoglossal nerve electrical stimulations is earlier than the delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the hypoglossal nerve electrical stimulations relative to the delivery star! time of the phrenic nerve electrical stimulations such that the delivery start time of the hypoglossal nerve electrical stimulations is later than the delivery start time of the phrenic nerve electrical stimulations.
  • the degree of synchronization is based on a ratio of spectral power in a stimulation frequency band to a spectral power in an intrinsic respiratory frequency band.
  • the processor is configured to calculate the degree of synchronization.
  • the IPG is configured to provide the sensor data to an external computing device and receive the degree of synchronization from the external computing device via the at least one communications interface.
  • the IPG is configured to wirelessly receive the operational parameters before implantation of the IPG. In at least one example, the IPG is configured to wirelessly receive the operational parameters after implantation of the IPG. In at least one example, the at least one communications interface comprises a telemetry interface. In at least one example, the at least one communications interface is configured to transmit and/or receive information according to a Bluetooth® communication protocol. In at least one example, the operational parameters comprise a pre-determined phrenic nerve stimulation rate, and wherein the IPG is configured to provide the phrenic nerve electrical stimulations in response to a trigger comprising the pre-determined phrenic nerve stimulation rate, wherein the trigger excludes sensed respiration of the patient during the at least one sleeping period.
  • the IPG is configured to provide the phrenic nerve electrical stimulations in response to a trigger comprising sensed respiration of the patient during the at least one sleeping period. In at least one example, the IPG is configured to provide the phrenic nerve electrical stimulations in response to a trigger comprising a lack of a sensed respiration of the patient within a predetermined interval of an expected time for the sensed respiration of the patient during the at least one sleeping period.
  • the at least one first stimulation lead is configured to be implanted in a lumen proximate the phrenic nerve of the patient. In at least one example, the at least one first stimulation lead comprises electrodes in a nerve cuff configured to be operatively coupled to the phrenic nerve. In at least one example, the at least one second stimulation lead is configured to be implanted in a lumen proximate the hypoglossal nerve of the patient.
  • the at least one second stimulation lead comprises electrodes in a nerve cuff configured to be operatively coupled to the hypoglossal nerve.
  • the sensor data indicative of patient respiration comprises a respiration rate and at least one indicator specific to the lack of respiratory drive.
  • the at least one indicator specific to the lack of respiratory drive comprises a degree of synchronization between the respiration rate and a pre-determined phrenic nerve stimulation rate.
  • the IPG is configured to modify the phrenic nerve stimulations based on the at least one indicator specific to the lack of respiratory drive.
  • the sensor data indicative of patient respiration comprises at least one indicator specific to an airway obstruction.
  • the IPG is configured to provide the phrenic nerve electrical stimulations to the phrenic nerve of the patient during the at least one sleeping period via the at least one first stimulation lead in an absence of ansa cervicalis electrical stimulation during the at least one sleeping period responsive to a determination that the operational parameters exclude the ansa cervicalis electrical stimulation parameters.
  • the operational parameters comprise operational parameters determined prior to the at least one sleeping period and without sensed respiratory data acquired from the patient during the at least one sleeping period.
  • the operational parameters determined prior to the at least one sleeping period are based at least in part on sensed respiratory data acquired from the patient in a monitoring mode of operation of the IPG prior to the at least one sleeping period, wherein the at least one sleeping period corresponds to a therapy mode of operation of the IPG.
  • the IPG is configured to align a delivery start time of the ansa cervicalis electrical stimulations with a delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the ansa cervicalis electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery start time of the ansa cervicalis electrical stimulations is earlier than the delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the ansa ccrvicalis electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery start time of the ansa cervicalis electrical stimulations is later than the delivery start time of the phrenic nerve electrical stimulations.
  • the phrenic nerve electrical stimulations provide a trigger for the ansa cervicalis electrical stimulations, wherein the trigger excludes sensed respiration of the patient during the at least one sleeping period.
  • the phrenic nerve electrical stimulations and the ansa cervicalis electrical stimulations are provided as pulse trains, each pulse train comprising a plurality of pulses, and wherein one or more of phrenic nerve electrical stimulation parameters or the ansa cervicalis electrical stimulation parameters comprise one or more of a pulse train parameter, a stimulation rate, a time between stimulation pulses, a current magnitude, a voltage magnitude, a relative timing for the phrenic nerve electrical stimulations and the ansa cervicalis electrical stimulations.
  • the IPG is configured to: compare the degree of synchronization to a degree of synchronization criterion comprising one of a target threshold or a target range, and if the degree of synchronization satisfies the degree of synchronization criterion, then maintain stimulation parameters for the disordered breathing therapy for one or more therapy cycles, else adjust the stimulation parameters and, optionally, reevaluate the degree of synchronization, wherein the stimulation parameters comprise at least one of phrenic nerve electrical stimulation parameters or ansa cervicalis electrical stimulation parameters.
  • the system includes at least one second sensor communicatively coupled to the IPG, wherein the at least one second sensor is configured to provide sensor data indicative of one or more of patient movement or patient position.
  • the at least one second sensor comprises at least one of an implantable accelerometer or an external accelerometer.
  • the IPG comprises a clock and is configured to: receive the sensor data from the at least one second sensor, receive time information from the clock, identify a commencement of the at least one sleeping period based on the sensor data and the time information, and in response to the identification of the commencement of the at least one sleeping period, provide the phrenic nerve electrical stimulations and the ansa cervicalis electrical stimulations, or provide the phrenic nerve electrical stimulations in the absence of ansa cervicalis electrical stimulations.
  • the IPG comprises at least two connector ports comprising: at least one first connector port configured to couple to at least one first stimulation lead, the at least one first stimulation lead comprising at least one first terminal pin configured to couple to the at least one first connector port, and at least one second connector port configured to couple to at least one second stimulation lead, the one second stimulation lead comprising at least one second terminal pin configured to couple to the at least one second connector port, and wherein the operational parameters comprise processor-executable instructions that determine which of the at least two connector ports is the at least one first connector port and which of the at least two connector ports is the at least one second connector port.
  • the at least one second stimulation lead comprises electrodes in a nerve cuff configured to be operatively coupled to the ansa cervicalis.
  • the at least one second stimulation lead comprises a lead configured for stimulation of the ansa cervicalis and a lead configured for simulation of a hypoglossal nerve, and wherein the IPG is configured to determine whether the operational parameters comprise hypoglossal nerve stimulation parameters, and responsive to the determination that the operational parameters comprise the hypoglossal nerve stimulation parameters, the IPG is configured to provide the ansa cervicalis electrical stimulations via the lead configured for stimulation of the ansa cervicalis together with hypoglossal nerve electrical stimulations via the lead configured for simulation of the hypoglossal nerve.
  • Examples of the disclosure include a treatment system for providing disordered breathing therapy to a sleeping patient during at least one sleeping period, the system comprising: at least one first stimulation lead; at least one second stimulation lead; at least one first sensor configured to provide sensor data indicative of patient respiration; and an implantable pulse generator (IPG) configured to couple to the at least one first stimulation lead and the at least one second stimulation lead, the IPG comprising a processor and a memory, the IPG configured to receive the sensor data indicative of patient respiration, determine whether the sensor data indicative of patient respiration is indicative of an airway obstruction, provide phrenic nerve electrical stimulations to a phrenic nerve of a patient via the at least one first stimulation lead during the at least one sleeping period, provide ansa cervicalis electrical stimulations to an ansa cervicalis of the patient via the at least one second stimulation lead during the at least one sleeping period responsive to a determination that the sensor data indicative of patient respiration is indicative of the airway obstruction, and coordinate a relative timing of the ansa cervicalis electrical stimulations to the ansa cervical
  • the IPG is configured to provide the phrenic nerve electrical stimulations to the phrenic nerve of the patient during the at least one sleeping period via the at least one first stimulation lead in an absence of ansa cervicalis electrical stimulation during the at least one sleeping period responsive to a determination that an indication of airway obstruction is absent from the sensor data indicative of patient respiration.
  • the IPG is configured to align a delivery start time of the ansa cervicalis electrical stimulations with a delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the ansa cervicalis electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery star!
  • the phrenic nerve electrical stimulations provide a trigger for the ansa ccrvicalis electrical stimulations, wherein the trigger excludes sensed respiration of the patient during the at least one sleeping period.
  • the IPG further comprises at least one communications interface configured to wirelessly receive operational parameters for the IPG.
  • the operational parameters comprise one or more of phrenic nerve electrical stimulation parameters or ansa cervicalis electrical stimulation parameters.
  • the IPG is further configured to modify at least one of the phrenic nerve electrical stimulation parameters or the ansa cervicalis electrical stimulation parameters based on the sensor data.
  • the sensor data indicative of patient respiration is indicative of a respiration rate
  • the operational parameters for the IPG comprise a pre-determined phrenic nerve stimulation rate
  • the IPG is configured to: provide the phrenic nerve electrical stimulations at the pre-determined phrenic nerve stimulation rate, receive the sensor data indicative of the respiration rate from the at least one first sensor, accumulate the sensor data over a pre-determined collection time period, and determine a degree of synchronization between the respiration rate and the pre-determined phrenic nerve stimulation rate based on the sensor data.
  • the degree of synchronization is based on a ratio of a quantity of breaths within a predetermined range of the pre-determined phrenic nerve stimulation rate to a total quantity of breaths for a particular' time period. In at least one example, the degree of synchronization is based on a ratio of spectral power in a stimulation frequency band to a spectral power in an intrinsic respiratory frequency band. In at least one example, to determine the degree of synchronization, the processor is configured to calculate the degree of synchronization. In at least one example, to determine the degree of synchronization, the IPG is configured to provide the sensor data to an external computing device and receive the degree of synchronization from the external computing device via the at least one communications interface.
  • the IPG comprises at least two connector ports comprising: at least one first connector port configured to couple to at least one first stimulation lead, the at least one first stimulation lead comprising at least one first terminal pin configured to couple to the at least one first connector port, and at least one second connector port configured to couple to at least one second stimulation lead, the one second stimulation lead comprising at least one second terminal pin configured to couple to the at least one second connector port, and wherein the operational parameters comprise processor-executable instructions that determine which of the at least two connector ports is the at least one first connector port and which of the at least two connector ports is the at least one second connector port.
  • the IPG is configured to wirelessly receive the operational parameters before implantation of the IPG. In at least one example, the IPG is configured to wirelessly receive the operational parameters after implantation of the IPG. In at least one example, the at least one communications interface comprises a telemetry interface. In at least one example, the at least one communications interface is configured to transmit and/or receive information according to a Bluetooth® communication protocol. In at least one example, the operational parameters comprise a pre-determined phrenic nerve stimulation rate, and wherein the IPG is configured to provide the phrenic nerve electrical stimulations in response to a trigger comprising the pre-determined stimulation rate, wherein the trigger excludes sensed respiration of the patient during the at least one sleeping period.
  • the at least one second stimulation lead comprises a lead configured for stimulation of the ansa cervicalis and a lead configured for simulation of a hypoglossal nerve, and wherein, responsive to the determination that the sensor data indicative of patient respiration is indicative of the airway obstruction, the IPG is configured to provide the ansa cervicalis electrical stimulations via the lead configured for stimulation of the ansa cervicalis together with hypoglossal nerve electrical stimulations via the lead configured for simulation of the hypoglossal nerve.
  • the IPG is configured to align a delivery start time of the ansa cervicalis electrical stimulations with a delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the ansa cervicalis electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery start time of the ansa cervicalis electrical stimulations is earlier than the delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the ansa cervicalis electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery start time of the ansa cervicalis electrical stimulations is later than the delivery start time of the phrenic nerve electrical stimulations.
  • the phrenic nerve electrical stimulations provide a trigger for the ansa cervicalis electrical stimulations, wherein the trigger excludes sensed respiration of the patient during the at least one sleeping period.
  • the phrenic nerve electrical stimulations and the ansa cervicalis electrical stimulations are provided as pulse trains, each pulse train comprising a plurality of pulses, and wherein one or more of the phrenic nerve electrical stimulation parameters or ansa cervicalis electrical stimulation parameters comprise one or more of a pulse train parameter, a stimulation rate, a time between stimulation pulses, a current magnitude, a voltage magnitude, a relative timing for the phrenic nerve electrical stimulations and the ansa cervicalis electrical stimulations.
  • the sensor data indicative of patient respiration is indicative of a respiration rate
  • the operational parameters for the IPG comprise a pre-determined phrenic nerve stimulation rate
  • the IPG is configured to: provide the phrenic nerve electrical stimulations at the pre-determined phrenic nerve stimulation rate, receive the sensor data indicative of the respiration rate from the at least one first sensor, accumulate the sensor data over a prc-dctcrmincd collection time period, and determine a degree of synchronization between the respiration rate and the pre-determined phrenic nerve stimulation rate based on the accumulated sensor data.
  • the IPG is configured to: compare the degree of synchronization to a degree of synchronization criterion comprising one of a target threshold or a target range, and if the degree of synchronization satisfies the degree of synchronization criterion, then maintain stimulation parameters for the disordered breathing therapy for one or more therapy cycles, else adjust the stimulation parameters and, optionally, reevaluate the degree of synchronization, wherein the stimulation parameters comprise at least one of phrenic nerve electrical stimulation parameters or ansa cervicalis electrical stimulation parameters.
  • the system includes at least one second sensor communicatively coupled to the IPG, wherein the at least one second sensor is configured to provide sensor data indicative of one or more of patient movement or patient position.
  • the at least one second sensor comprises at least one of an implantable accelerometer or an external accelerometer.
  • the operational parameters comprise a pre-determined phrenic nerve stimulation rate
  • the IPG is configured to provide the phrenic nerve electrical stimulations in response to a trigger comprising the pre-determined stimulation rate, wherein the trigger excludes sensed respiration of the patient during the at least one sleeping period.
  • the at least one first stimulation lead is configured to be implanted in a lumen proximate the phrenic nerve of the patient.
  • the at least one first stimulation lead comprises electrodes in a nerve cuff configured to be operatively coupled to the phrenic nerve.
  • the at least one second stimulation lead is configured to be implanted in a lumen proximate the ansa cervicalis of the patient.
  • the at least one second stimulation lead comprises electrodes in a nerve cuff configured to be operatively coupled to the ansa ccrvicalis.
  • the at least one second stimulation lead comprises a lead configured for stimulation of the ansa cervicalis and a lead configured for simulation of a hypoglossal nerve, and wherein the IPG is configured to provide the ansa cervicalis electrical stimulations via the lead configured for stimulation of the ansa ccrvicalis together with hypoglossal nerve electrical stimulations via the lead configured for simulation of the hypoglossal nerve.
  • Examples of the disclosure include a treatment system for providing disordered breathing therapy to a sleeping patient during at least one sleeping period, the system comprising: at least one first stimulation lead; at least one second stimulation lead; at least one first sensor configured to provide sensor data indicative of patient respiration; and an implantable pulse generator (IPG) configured to couple to the at least one first stimulation lead and the at least one second stimulation lead, the IPG comprising a processor and a memory, the IPG configured to receive the sensor data indicative of patient respiration, determine whether the sensor data indicative of patient respiration is indicative of a lack of respiratory drive, provide phrenic nerve electrical stimulations to a phrenic nerve of a patient via the at least one first stimulation lead during the at least one sleeping period responsive to a determination that the sensor data indicative of patient respiration is indicative of the lack of central respiratory drive, provide ansa cervicalis electrical stimulations to an ansa cervicalis of the patient via the at least one second stimulation lead during the at least one sleeping period, and coordinate a relative timing of the ansa cervicalis electrical stimulations to the
  • the IPG is configured to provide the ansa cervicalis electrical stimulations to the ansa cervicalis of the patient during the at least one sleeping period via the at least one first stimulation lead in an absence of phrenic nerve electrical stimulations during the at least one sleeping period responsive to a determination that an indication of lack of respiratory drive is absent from the sensor data indicative of patient respiration.
  • the IPG is configured to align a delivery start time of the ansa cervicalis electrical stimulations with a delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the ansa cervicalis electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery start time of the ansa cervicalis electrical stimulations is earlier than the delivery start time of the phrenic nerve electrical stimulations, or stagger the delivery start time of the ansa cervicalis electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery start time of the ansa cervicalis electrical stimulations is later than the delivery start time of the phrenic nerve electrical stimulations.
  • the phrenic nerve electrical stimulations provide a trigger for the ansa cervicalis electrical stimulations, wherein the trigger excludes sensed respiration of the patient during the at least one sleeping period.
  • the IPG further comprises at least one communications interface configured to wirelessly receive operational parameters for the IPG.
  • the operational parameters comprise one or more of phrenic nerve electrical stimulation parameters or ansa cervicalis electrical stimulation parameters.
  • the IPG is further configured to modify at least one of the phrenic nerve electrical stimulation parameters or the ansa cervicalis electrical stimulation parameters based on the sensor data.
  • the sensor data indicative of patient respiration is indicative of a respiration rate
  • the operational parameters for the IPG comprise a pre-determined phrenic nerve stimulation rate
  • the IPG is configured to: provide the phrenic nerve electrical stimulations at the pre-determined phrenic nerve stimulation rate, receive the sensor data indicative of the respiration rate from the at least one first sensor, accumulate the sensor data over a pre-determined collection time period, and determine a degree of synchronization between the respiration rate and the pre-determined phrenic nerve stimulation rate based on the sensor data.
  • the degree of synchronization is based on a ratio of a quantity of breaths within a predetermined range of the pre-determined phrenic nerve stimulation rate to a total quantity of breaths for a particular time period. In at least one example, the degree of synchronization is based on a ratio of spectral power in a stimulation frequency band to a spectral power in an intrinsic respiratory frequency band. In at least one example, to determine the degree of synchronization, the processor is configured to calculate the degree of synchronization. In at least one example, to determine the degree of synchronization, the IPG is configured to provide the sensor data to an external computing device and receive the degree of synchronization from the external computing device via the at least one communications interface.
  • the IPG comprises at least two connector ports comprising: at least one first connector port configured to couple to at least one first stimulation lead, the at least one first stimulation lead comprising at least one first terminal pin configured to couple to the at least one first connector port, and at least one second connector port configured to couple to at least one second stimulation lead, the one second stimulation lead comprising at least one second terminal pin configured to couple to the at least one second connector port, and wherein the operational parameters comprise processor-executable instructions that determine which of the at least two connector ports is the at least one first connector port and which of the at least two connector ports is the at least one second connector port.
  • the phrenic nerve electrical stimulations and the ansa cervicalis electrical stimulations are provided as pulse trains, each pulse train comprising a plurality of pulses, and wherein one or more of the phrenic nerve electrical stimulation parameters or the ansa cervicalis electrical stimulation parameters comprise one or more of a pulse train parameter, a stimulation rate, a time between stimulation pulses, a current magnitude, a voltage magnitude, a relative timing for the phrenic nerve electrical stimulations and the ansa cervicalis electrical stimulations.
  • the at least one first sensor comprises a transthoracic impedance sensor.
  • the system includes at least one second sensor communicatively coupled to the IPG, wherein the at least one second sensor is configured to provide sensor data indicative of one or more of patient movement or patient position.
  • the sensor data indicative of patient respiration comprises a respiration rate and at least one indicator specific to the lack of respiratory drive.
  • the at least one indicator specific to the lack of respiratory drive comprises a degree of synchronization between the respiration rate and a pre-determined phrenic nerve stimulation rate.
  • the IPG is configured to modify the phrenic nerve stimulations based on the at least one indicator specific to the lack of respiratory drive.
  • the sensor data indicative of patient respiration comprises at least one indicator specific to an airway obstruction.
  • the IPG is configured to modify the ansa cervical is stimulations based on the at least one indicator specific to the airway obstruction.
  • the sensor data indicative of patient respiration comprises combined-effectiveness parameters indicative of the effectiveness of the disordered breathing therapy and wherein, optionally, the IPG is configured to modify at least one of the phrenic nerve stimulations and the ansa cervicalis stimulations based on the combined-effectiveness parameters.
  • the at least one second stimulation lead comprises a lead configured for stimulation of the ansa cervicalis and a lead configured for simulation of a hypoglossal nerve, and wherein the IPG is configured to provide the ansa cervicalis electrical stimulations via the lead configured for stimulation of the ansa cervicalis together with hypoglossal nerve electrical stimulations via the lead configured for simulation of the hypoglossal nerve.
  • Examples of the disclosure include a treatment system for providing disordered breathing therapy to a sleeping patient, the system comprising: at least one first stimulation lead; at least one second stimulation lead; and an implanted therapy controller configured to couple to the at least one first stimulation lead and the at least one second stimulation lead, the implanted controller configured to provide at least one phrenic nerve electrical stimulation to a phrenic nerve of a patient via the at least one first stimulation lead, receive, from at least one airwayobstruction sensor, therapy data comprising airway information indicative of a decreased airway patency of the patient, detect the decreased airway patency of the patient based on the airway information, provide at least one hypoglossal nerve electrical stimulation to a hypoglossal nerve of the patient via the at least one second stimulation lead responsive to detecting the decreased airway patency of the patient, and coordinate a relative timing of the at least one hypoglossal nerve electrical stimulation to the hypoglossal nerve with the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient
  • a delivery start time of the at least one hypoglossal nerve electrical stimulation is synchronized with a delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, a delivery start time of the at least one hypoglossal nerve electrical stimulation is earlier than a delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, a delivery start time of the at least one hypoglossal nerve electrical stimulation is later than a delivery start time of the at least one phrenic nerve electrical stimulation.
  • the at least one airway-obstruction sensor comprises at least one microphone.
  • the airway information comprises audio information.
  • detecting the decreased airway patency based on the airway information comprises determining that the audio information is indicative of the patient snoring.
  • the at least one airway-obstruction sensor comprises a transthoracic impedance sensor.
  • the airway information is indicative of a breathing rate of the patient.
  • the airway information is indicative of a lung volume of the patient.
  • the at least one airway-obstruction sensor comprises at least one accelerometer.
  • the airway information is indicative of movement of the patient. In at least one example, the movement of the patient is indicative of a position of the patient.
  • the at least one accelerometer is implanted in the patient.
  • the at least one accelerometer comprises a first accelerometer external to the patient.
  • the at least one accelerometer comprises a second accelerometer implanted in the patient.
  • the at least one airway-obstruction sensor comprises a pulse oximeter.
  • the airway information comprises a blood oxygen level of the patient.
  • the at least one airway-obstruction sensor comprises at least one heart-rate sensor.
  • the airway information is indicative of a heart rate of the patient.
  • the at least one airway-obstruction sensor comprises one or more leads to sense electrical activity of the heart of the patient.
  • the therapy data is indicative of a sleep stage of the patient.
  • the at least one airwayobstruction sensor comprises at least one pressure sensor.
  • the at least one first stimulation lead comprises one or more electrodes.
  • one or more leads of the at least one first stimulation lead arc configured to be implanted in a lumen proximate the phrenic nerve of the patient.
  • the at least one first stimulation lead comprises one or more nerve cuffs.
  • at least one nerve cuff of the one or more nerve cuffs is configured to be operatively coupled to the phrenic nerve of the patient.
  • the at least one second stimulation lead comprises one or more electrodes.
  • one or more leads of the at least one second stimulation lead are configured to be implanted in a lumen proximate the hypoglossal nerve of the patient.
  • the at least one second stimulation lead comprises one or more nerve cuffs.
  • at least one nerve cuff of the one or more nerve cuffs is configured to be operatively coupled to the hypoglossal nerve of the patient.
  • the implanted therapy controller is further configured to modify at least one of first parameters of phrenic nerve electrical stimulation via the at least one phrenic nerve electrical stimulation lead or second parameters of hypoglossal nerve electrical stimulations provided via the at least one hypoglossal nerve electrical stimulation lead based on the airway information.
  • the system includes at least one respiratory sensor configured to provide respiratory information indicative of at least one respiratory parameter, and wherein the implanted therapy controller is further configured to determine, based on the respiratory information, a therapyspecific indicator indicative of an effect of the at least one phrenic nerve electrical stimulation on respiration of the patient.
  • the at least one respiratory sensor comprises at least one transthoracic impedance sensor. In at least one example, the at least one respiratory sensor comprises at least one accelerometer. In at least one example, the therapy- specific indicator comprises an entrainment index. In at least one example, the implanted therapy controller is further configured to determine whether the therapy- specific indicator satisfies at least one therapy-effectiveness criterion by determining whether the entrainment index is within a threshold range of capture-index values.
  • the implanted therapy controller is further configured to provide, simultaneously with the at least one phrenic nerve electrical stimulation, at least one ansa cervicalis electrical stimulation to an ansa cervicalis of the patient via at least one third stimulation lead responsive to detecting the decreased airway patency.
  • the therapy data further comprises at least one of sensor data measurements or respiratory drive synchronization data
  • the implanted therapy controller is configured to: determine one or more combined-effectiveness parameters indicative of an effect on respiration of the patient of the coordinated at least one phrenic nerve electrical stimulation and at least one hypoglossal nerve electrical stimulation, and adjust one or more therapy delivery parameters based on the one or more combined-effectiveness parameters for the coordinated at least one phrenic nerve electrical stimulation and at least one hypoglossal nerve electrical stimulation.
  • the implanted therapy controller is further configured to receive sleep parameters indicative of a sleep stage of the patient.
  • the therapy data is indicative of the patient’s respiratory drive, and wherein the implanted therapy controller is configured to: evaluate an effect of the at least one phrenic nerve electrical stimulation on respiration of the patient based on the therapy data indicative of the patient’s respiratory drive, and adjust one or more parameters of the at least one phrenic nerve electrical stimulation based on the evaluation.
  • the implanted therapy controller is configured to provide the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient in response to a trigger comprising sensed respiration of the patient. In at least one example, the implanted therapy controller is configured to provide the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient in response to a trigger comprising a lack of a sensed respiration of the patient within a predetermined interval of an expected time for the sensed respiration.
  • the implanted therapy controller is configured to provide the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient in response to a trigger comprising a preprogrammed stimulation rate, wherein the trigger excludes sensed respiration of the patient.
  • the preprogrammed stimulation rate is an entrainment frequency.
  • the therapy data indicates a combination sleep apnea based on sensor data showing a decreased respiratory drive and a reduced patency of an airway of the patient.
  • the indication of the combination sleep apnea is an indication of a mixed apnea.
  • the system includes one or more implanted respiratory parameter sensors.
  • the one or more implanted respiratory parameter sensors are disposed at the implanted therapy controller.
  • the one or more implanted respiratory parameter sensors are disposed at one or more of the at least one hypoglossal nerve stimulation lead or the at least one phrenic nerve stimulation lead.
  • the one or more implanted respiratory parameter sensors are disposed at one or more of a lead body, an electrode, or a nerve cuff.
  • the system includes at least one sensor, wherein the implanted therapy controller is further configured to: receive sensor data from the at least one sensor; and determine, based on the sensor data, that the patient is asleep. In at least one example, the implanted therapy controller is further configured to: determine, responsive to determining that the patient is asleep, whether the implanted therapy controller is pre-programmed to provide obstructive sleep apnea therapy; and provide the at least one hypoglossal nerve electrical stimulation responsive to determining that the implanted therapy controller is pre-programmed to provide the obstructive sleep apnea therapy.
  • Examples of the disclosure include a treatment system for providing disordered breathing therapy to a sleeping patient, the system comprising: at least one first stimulation lead; at least one second stimulation lead; and an implanted therapy controller configured to couple to the at least one first stimulation lead and the at least one second stimulation lead, the implanted controller configured to provide at least one phrenic nerve electrical stimulation to a phrenic nerve of a patient via the at least one first stimulation lead, receive, from at least one airwayobstruction sensor, therapy data comprising airway information indicative of a decreased airway patency of the patient, detect the decreased airway patency of the patient based on the airway information, provide at least one ansa cervicalis electrical stimulation to an ansa cervicalis of the patient via the at least one second stimulation lead responsive to detecting the decreased airway patency of the patient, and coordinate a relative timing of the at least one ansa cervicalis electrical stimulation to the ansa cervicalis with the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient.
  • the at least one airway-obstruction sensor comprises at least one microphone.
  • the airway information comprises audio information.
  • detecting the decreased airway patency based on the airway information comprises determining that the audio information is indicative of the patient snoring.
  • the at least one airway-obstruction sensor comprises a transthoracic impedance sensor.
  • the airway information is indicative of a breathing rate of the patient.
  • the airway information is indicative of a lung volume of the patient.
  • the at least one airway-obstruction sensor comprises at least one accelerometer.
  • the airway information is indicative of movement of the patient. In at least one example, the movement of the patient is indicative of a position of the patient.
  • the therapy data is indicative of a sleep stage of the patient.
  • the at least one airway-obstruction sensor comprises at least one pressure sensor.
  • the at least one first stimulation lead comprises one or more electrodes.
  • one or more leads of the at least one first stimulation lead are configured to be implanted in a lumen proximate the phrenic nerve of the patient.
  • the at least one first stimulation lead comprises one or more nerve cuffs.
  • at least one nerve cuff of the one or more nerve cuffs is configured to be operatively coupled to the phrenic nerve of the patient.
  • the therapy data is indicative of the patient’s respiratory drive
  • the implanted therapy controller is configured to: evaluate an effect of the at least one phrenic nerve electrical stimulation on respiration of the patient based on the therapy data indicative of the patient’s respiratory drive, and adjust one or more parameters of the at least one phrenic nerve electrical stimulation based on the evaluation.
  • the implanted therapy controller is configured to provide a plurality of phrenic nerve electrical stimulations at an entrainment frequency, and wherein the therapy data comprises an entrainment index indicative of a degree of synchronization between the patient’s respiration rate and the entrainment frequency.
  • the implanted therapy controller is configured to: evaluate an effect of the at least one ansa cervicalis electrical stimulation on respiration of the patient based on the therapy data indicative of the patient’s airway patency, and adjust one or more parameters of the at least one ansa cervicalis electrical stimulation based on the evaluation.
  • the implanted therapy controller is configured to provide the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient in response to a trigger comprising sensed respiration of the patient. In at least one example, the implanted therapy controller is configured to provide the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient in response to a trigger comprising a lack of a sensed respiration of the patient within a predetermined interval of an expected time for the sensed respiration.
  • the implanted therapy controller is configured to provide the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient in response to a trigger comprising a preprogrammed stimulation rate, wherein the trigger excludes sensed respiration of the patient.
  • the preprogrammed stimulation rate is an entrainment frequency.
  • the therapy data indicates a combination sleep apnea based on sensor data showing a decreased respiratory drive and a reduced patency of an airway of the patient.
  • the indication of the combination sleep apnea is an indication of a mixed apnea.
  • the system includes one or more implanted respiratory parameter sensors.
  • the one or more implanted respiratory parameter sensors are disposed at the implanted therapy controller.
  • the one or more implanted respiratory parameter sensors are disposed at one or more of the at least one ansa cervicalis stimulation lead or the at least one phrenic nerve stimulation lead.
  • the one or more implanted respiratory parameter sensors are disposed at one or more of a lead body, an electrode, or a nerve cuff. In at least one example, the one or more implanted respiratory parameter sensors are disposed on an implanted lead without nerve stimulation capability. In at least one example, the one or more implanted respiratory parameter sensors are disposed proximate to the thoracic cavity. In at least one example, the one or more implanted respiratory parameter sensors are implanted unilaterally. In at least one example, the one or more implanted respiratory parameter sensors arc implanted bilaterally.
  • the system includes one or more respiratory parameter sensors disposed externally on the patient.
  • the implanted therapy controller is configured to coordinate the relative timing to provide the at least one ansa cervicalis electrical stimulation simultaneously with the at least one phrenic nerve electrical stimulation.
  • the system includes at least one sensor, wherein the implanted therapy controller is further configured to: receive sensor data from the at least one sensor; and determine, based on the sensor data, that the patient is asleep.
  • the implanted therapy controller is further configured to: determine, responsive to determining that the patient is asleep, whether the implanted therapy controller is pre-programmed to provide obstructive sleep apnea therapy; and provide the at least one ansa cervicalis electrical stimulation responsive to determining that the implanted therapy controller is pre-programmed to provide the obstructive sleep apnea therapy.
  • a treatment system for providing disordered breathing therapy to a sleeping patient comprising at least one first stimulation lead, at least one second stimulation lead, and an implanted therapy controller coupled to the at least one first stimulation lead and the at least one second stimulation lead, the implanted controller configured to provide at least one phrenic nerve electrical stimulation to a phrenic nerve of a patient via the at least one first stimulation lead, receive, from at least one airway-obstruction sensor, therapy data comprising airway information indicative of a decreased airway patency of the patient, detect the decreased airway patency of the patient based on the airway information, provide at least one hypoglossal nerve electrical stimulation to a hypoglossal nerve of the patient via the at least one second stimulation lead responsive to detecting the decreased airway patency of the patient, and coordinate a relative timing of the at least one hypoglossal nerve electrical stimulation to the hypoglossal nerve with the at least one phrenic nerve electrical stimulation to the phrenic nerve
  • a delivery start time of the at least one hypoglossal nerve electrical stimulation is synchronized with a delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, a delivery start time of the at least one hypoglossal nerve electrical stimulation is earlier than a delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one hypoglossal nerve electrical stimulation is at most 500 milliseconds earlier than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one hypoglossal nerve electrical stimulation is at most 300 milliseconds earlier than the delivery start time of the at least one phrenic nerve electrical stimulation.
  • the delivery start time of the at least one hypoglossal nerve electrical stimulation is at most 1 millisecond earlier than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one hypoglossal nerve electrical stimulation is synchronized with the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one hypoglossal nerve electrical stimulation is at least 0.1 milliseconds earlier than the delivery staid time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one hypoglossal nerve electrical stimulation is at least 0.5 milliseconds earlier than the delivery start time of the at least one phrenic nerve electrical stimulation.
  • the delivery start time of the at least one hypoglossal nerve electrical stimulation is at most 100 milliseconds later than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one hypoglossal nerve electrical stimulation is at most 50 milliseconds later than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one hypoglossal nerve electrical stimulation is at most 10 milliseconds later than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one hypoglossal nerve electrical stimulation is at most 5 milliseconds later than the delivery start time of the at least one phrenic nerve electrical stimulation.
  • the delivery start time of the at least one hypoglossal nerve electrical stimulation is at least 100 milliseconds later than the delivery start time of the at least one phrenic nerve electrical stimulation.
  • each breathing cycle of a plurality of breathing cycles of the patient includes an inspiration period and an expiration period, and wherein the implanted therapy controller is further configured, for each breathing cycle of the patient, to apply one or more phrenic nerve electrical stimulations to the phrenic nerve of the patient via the at least one first stimulation lead and to apply one or more hypoglossal nerve electrical stimulations to the hypoglossal nerve of the patient via the at least one second stimulation lead.
  • each of the one or more phrenic nerve electrical stimulations includes a first plurality of pulses, and wherein each of the one or more hypoglossal nerve electrical stimulations includes a second plurality of pulses.
  • the second plurality of pulses ramps up over a first period of time within at least one breathing cycle.
  • the second plurality of pulses remains constant over a second period of time after the first period of time within the at least one breathing cycle.
  • the second plurality of pulses ramps down over a third period of time after the second period of time within the at least one breathing cycle.
  • the first plurality of pulses ramps up over a fourth period of time within the at least one breathing cycle.
  • the first period of time ends at approximately the same time as the fourth period of time. In at least one example, the first period of time ends after the fourth period of time. In at least one example, the first period of time ends before the fourth period of time. In at least one example, the first period of time begins after the fourth period of time. In at least one example, the first period of time ends at approximately the same time as the fourth period of time. In at least one example, the first period of time ends after the fourth period of time. In at least one example, the first period of time ends before the fourth period of time. In at least one example, the first period of time begins at approximately the same time as the fourth period of time.
  • the first period of time ends at approximately the same time as the fourth period of time. In at least one example, the first period of time ends after the fourth period of time. In at least one example, the first period of time ends before the fourth period of time. In at least one example, the first plurality of pulses remains constant over a sixth period of time after the fourth period of time within the at least one breathing cycle. In at least one example, the sixth period of time at least partially overlaps with the second period of time during a seventh period of time. In at least one example, first constant pulses of the first plurality of pulses are synchronized with second constant pulses of the second plurality of pulses during the seventh period of time.
  • first constant pulses of the first plurality of pulses are independent of second constant pulses of the second plurality of pulses during the seventh period of time.
  • a number of constant pulses of the first plurality of pulses during the second period of time is synchronized with a number of constant pulses of the second plurality of pulses during the sixth period of time.
  • the second period of time begins prior to the sixth period of time.
  • the second period of time ends at approximately the same time as the sixth period of time.
  • the second period of time ends after the sixth period of time.
  • At least one of the first parameters or the second parameters includes a plurality of parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping- up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • At least one of the first parameters or the second parameters includes a number of ramping-down pulses. In at least one example, at least one of the first parameters or the second parameters includes a magnitude of at least one ramping-up pulse. In at least one example, at least one of the first parameters or the second parameters includes a magnitude of at least one ramping-down pulse. In at least one example, at least one of the first parameters or the second parameters includes a pulse width. In at least one example, at least one of the first parameters or the second parameters includes a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation. In at least one example, at least one of the first parameters or the second parameters includes a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • At least one of the first parameters or the second parameters includes at least three parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • At least one of the first parameters or the second parameters includes at least four parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • At least one of the first parameters or the second parameters includes at least five parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • At least one of the first parameters or the second parameters includes at least six parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • At least one of the first parameters or the second parameters includes at least seven parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • At least one of the first parameters or the second parameters includes at least eight parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • At least one of the first parameters or the second parameters includes at least 10 parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • At least one of the first parameters or the second parameters includes at least 11 parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • At least one of the first parameters or the second parameters includes at least 12 parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • At least one of the first parameters or the second parameters includes a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the hypoglossal nerve electrical stimulation.
  • the system includes at least one respiratory sensor configured to provide respiratory information indicative of at least one respiratory parameter, and wherein the implanted therapy controller is further configured to determine, based on the respiratory information, a therapy- specific indicator indicative of an effect of the at least one phrenic nerve electrical stimulation on respiration of the patient.
  • the at least one respiratory sensor includes at least one transthoracic impedance sensor. In at least one example, the at least one respiratory sensor includes at least one accelerometer. In at least one example, the at least one respiratory sensor includes at least one pressure sensor. In at least one example, the at least one respiratory parameter includes a breathing rate of the patient. In at least one example, the at least one respiratory parameter includes a lung volume of the patient. In at least one example, the therapyspecific indicator includes an entrainment index. In at least one example, the implanted therapy controller is further configured to determine whether the therapy-specific indicator satisfies at least one therapy-effectiveness criterion by determining whether the entrainment index is within a threshold range of capture-index values.
  • the therapy data further comprises at least one of sensor data measurements or respiratory drive synchronization data
  • the implanted therapy controller is configured to: determine one or more combined-effectiveness parameters indicative of an effect on respiration of the patient of the coordinated at least one phrenic nerve electrical stimulation and at least one hypoglossal nerve electrical stimulation, and adjust one or more therapy delivery parameters based on the one or more combined-effectiveness parameters for the coordinated at least one phrenic nerve electrical stimulation and at least one hypoglossal nerve electrical stimulation.
  • the one or more combined-effectiveness parameters comprise one or more of an indication of decreased respiratory drive and an indication of decreased airway patency.
  • the implanted therapy controller is further configured to receive sleep parameters indicative of a sleep stage of the patient.
  • the sleep parameters include at least one of a heart rate of the patient or movement of the patient.
  • the implanted therapy controller is further configured to determine, based on at least one of the heart rate of the patient or the movement of the patient, a sleep stage of the patient.
  • the sleep stage includes one of light sleep, deep sleep, rapid-eye- movement sleep, and awake.
  • the implanted therapy controller is configured to provide at least one of the at least one phrenic nerve electrical stimulation or the at least one hypoglossal nerve electrical stimulation responsive to determining that the sleep stage of the patient is one of the light sleep, the deep sleep, or the rapid-eye-movement sleep stage.
  • the therapy data is indicative of the patient’s respiratory drive
  • the implanted therapy controller is configured to: evaluate an effect of the at least one phrenic nerve electrical stimulation on respiration of the patient based on the therapy data indicative of the patient’s respiratory drive, and adjust one or more parameters of the at least one phrenic nerve electrical stimulation based on the evaluation.
  • the implanted therapy controller is configured to provide a plurality of phrenic nerve electrical stimulations at an entrainment frequency, and wherein the therapy data comprises an entrainment index indicative of a degree of synchronization between the patient’ s respiration rate and the entrainment frequency.
  • the entrainment index comprises a ratio indicative of a degree of entrainment of a patient.
  • the entrainment index is a ratio of spectral power in a stimulation frequency band to a spectral power in an intrinsic respiratory frequency band. In at least one example, the entrainment index is a ratio of a quantity of breaths within a predetermined range of a stimulation rate to a total quantity of breaths for a particular time period. In at least one example, the implanted therapy controller is configured to adjust at least one parameter of the plurality of phrenic nerve stimulations based on the entrainment index. In at least one example, the implanted therapy controller is configured to coordinate the relative timing based at least in part on the entrainment frequency.
  • the implanted therapy controller is configured to provide the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient in response to a trigger comprising a lack of a sensed respiration of the patient within a predetermined interval of an expected time for the sensed respiration.
  • the implanted therapy controller is configured to provide the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient in response to a trigger comprising a preprogrammed stimulation rate, wherein the trigger excludes sensed respiration of the patient.
  • the preprogrammed stimulation rate is an entrainment frequency.
  • the therapy data indicates a combination sleep apnea based on sensor data showing a decreased respiratory drive and a reduced patency of an airway of the patient.
  • the indication of the combination sleep apnea is an indication of a mixed apnea.
  • the indication of the mixed apnea comprises a detection of lack of respiratory drive followed by a respiratory effort against a restricted or restricting airway within a single apnea event.
  • the system includes one or more implanted respiratory parameter sensors.
  • the one or more implanted respiratory parameter sensors are disposed at the implanted therapy controller.
  • the one or more implanted respiratory parameter sensors are disposed at one or more of the at least one hypoglossal nerve stimulation lead or the at least one phrenic nerve stimulation lead.
  • the one or more implanted respiratory parameter sensors are disposed at one or more of a lead body, an electrode, or a nerve cuff.
  • the one or more implanted respiratory parameter sensors are disposed on an implanted lead without nerve stimulation capability.
  • the one or more implanted respiratory parameter sensors are disposed proximate to the thoracic cavity. In at least one example, the one or more implanted respiratory parameter sensors are implanted unilaterally. In at least one example, the one or more implanted respiratory parameter sensors are implanted bilaterally. In at least one example, the system includes one or more respiratory parameter sensors disposed externally on the patient. In at least one example, the implanted therapy controller is configured to coordinate the relative timing to provide the at least one hypoglossal nerve electrical stimulation simultaneously with the at least one phrenic nerve electrical stimulation.
  • a treatment system for providing disordered breathing therapy to a sleeping patient comprising at least one first stimulation lead; at least one second stimulation lead; and an implanted therapy controller coupled to the at least one first stimulation lead and the at least one second stimulation lead, the implanted controller configured to provide at least one phrenic nerve electrical stimulation to a phrenic nerve of a patient via the at least one first stimulation lead, receive, from at least one airway-obstruction sensor, therapy data comprising airway information indicative of a decreased airway patency of the patient, detect the decreased airway patency of the patient based on the airway information, provide at least one ansa cervical is electrical stimulation to the ansa cervicalis of the patient via the at least one second stimulation lead responsive to detecting the decreased airway patency of the patient, and coordinate a relative timing of the at least one ansa cervicalis electrical stimulation to the ansa cervicalis with the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient.
  • a delivery start time of the at least one ansa cervicalis electrical stimulation is synchronized with a delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, a delivery start time of the at least one ansa cervicalis electrical stimulation is earlier than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one ansa cervicalis electrical stimulation is at most 500 milliseconds earlier than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one ansa cervicalis electrical stimulation is at most 300 milliseconds earlier than the delivery staid time of the at least one phrenic nerve electrical stimulation.
  • the delivery start time of the at least one ansa cervicalis electrical stimulation is at most 100 milliseconds earlier than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one ansa cervicalis electrical stimulation is at most 50 milliseconds earlier than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one ansa cervicalis electrical stimulation is at most 10 milliseconds earlier than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one ansa cervicalis electrical stimulation is at most 5 milliseconds earlier than the delivery start time of the at least one phrenic nerve electrical stimulation.
  • the delivery start time of the at least one ansa cervicalis electrical stimulation is at most 1 millisecond earlier than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one ansa cervicalis electrical stimulation is synchronized with the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one ansa cervicalis electrical stimulation is at least 0.1 milliseconds earlier than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery star! time of the at least one ansa cervicalis electrical stimulation is at least 0.5 milliseconds earlier than the delivery start time of the at least one phrenic nerve electrical stimulation.
  • the delivery start time of the at least one ansa cervicalis electrical stimulation is at least 1 millisecond later than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one ansa cervicalis electrical stimulation is at least 5 milliseconds later than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one ansa cervicalis electrical stimulation is at least 10 milliseconds later than the delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, the delivery start time of the at least one ansa cervicalis electrical stimulation is at least 50 milliseconds later than the delivery start time of the at least one phrenic nerve electrical stimulation.
  • the fourth period of time at least partially overlaps with the first period of time during a fifth period of time.
  • first ramping-up pulses of the first plurality of pulses are synchronized with second ramping-up pulses of the second plurality of pulses during the fifth period of time.
  • first ramping-up pulses of the first plurality of pulses are independent of second ramping-up pulses of the second plurality of pulses during the fifth period of time.
  • a number of ramping- up pulses of the first plurality of pulses during the first period of time is synchronized with a number of ramping-up pulses of the second plurality of pulses during the fourth period of time.
  • the second period of time ends at approximately the same time as the sixth period of time. In at least one example, the second period of time ends after the sixth period of time. In at least one example, the second period of time ends before the sixth period of time. In at least one example, the second period of time begins at approximately the same time as the sixth period of time. In at least one example, the second period of time ends at approximately the same time as the sixth period of time. In at least one example, the second period of time ends after the sixth period of time. In at least one example, the second period of time ends before the sixth period of time. In at least one example, the first plurality of pulses ramps down over an eighth period of time after the sixth period of time within the at least one breathing cycle. In at least one example, the eighth period of time at least partially overlaps with the third period of time during a ninth period of time.
  • the third period of time ends at approximately the same time as the eighth period of time. In at least one example, the third period of time ends after the eighth period of time. In at least one example, the third period of time before after the eighth period of time. In at least one example, the third period of time begins after the eighth period of time. In at least one example, the third period of time ends at approximately the same time as the eighth period of time. In at least one example, the third period of time ends after the eighth period of time. In at least one example, the third period of time ends before the eighth period of time. In at least one example, the third period of time begins at approximately the same time as the eighth period of time. In at least one example, the third period of time ends at approximately the same time as the eighth period of time. In at least one example, the third period of time ends after the eighth period of time.
  • the third period of time ends before the eighth period of time.
  • the at least one airway-obstruction sensor includes at least one microphone.
  • the airway information includes audio information.
  • detecting the decreased airway patency based on the airway information includes determining that the audio information is indicative of the patient snoring.
  • determining that the audio information is indicative of the patient snoring includes determining that an amplitude of an audio waveform in the audio information is within a threshold range of amplitude values.
  • determining that the audio information is indicative of the patient snoring includes determining that an audio waveform in the audio information matches at least one stored waveform.
  • determining that the audio information is indicative of the patient snoring includes determining that a frequency of an audio waveform in the audio information is within a threshold range of frequency values.
  • the at least one accelerometer includes a first accelerometer external to the patient. In at least one example, the at least one accelerometer includes a second accelerometer implanted in the patient. In at least one example, the movement of the patient is indicative of movement of the head of the patient relative to the torso of the patient. In at least one example, the airway information is indicative of the position of the patient, and wherein detecting the decreased airway patency based on the airway information includes determining that the position of the patient is on a stored list of one or more positions.
  • the at least one airway-obstruction sensor includes a pulse oximeter.
  • the airway information includes a blood oxygen level of the patient.
  • detecting the decreased airway patency based on the airway information includes determining that the blood oxygen level of the patient is within a threshold range of blood oxygen levels.
  • detecting the decreased airway patency based on the airway information includes: determining that the blood oxygen level of the patient is within the threshold range of blood oxygen levels; and determining that the lung volume of the patient is within a threshold range of volume values.
  • the at least one airway-obstruction sensor includes at least one pressure sensor.
  • the airway information includes pressure information indicative of a pressure exerted by movement of the chest of the patient relative to the torso of the patient.
  • detecting the decreased airway patency based on the airway information includes: determining that a blood oxygen level of the patient is within a threshold range of blood oxygen levels; and determining that the pressure exerted by the movement of the chest of the patient relative to the torso of the patient is within a threshold range of pressure values.
  • the at least one first stimulation lead includes one or more electrodes.
  • one or more leads of the at least one first stimulation lead arc configured to be implanted in a lumen proximate the phrenic nerve of the patient.
  • the at least one first stimulation lead includes one or more nerve cuffs.
  • At least one nerve cuff of the one or more nerve cuffs is configured to be operatively coupled to the phrenic nerve of the patient.
  • the at least one second stimulation lead includes one or more electrodes.
  • one or more leads of the at least one second stimulation lead are configured to be implanted in a lumen proximate the ansa cervicalis of the patient.
  • the at least one second stimulation lead includes one or more nerve cuffs.
  • at least one nerve cuff of the one or more nerve cuffs is configured to be operatively coupled to the ansa cervicalis of the patient.
  • the at least one first stimulation lead includes one or more first electrodes and the at least one second stimulation lead includes one or more second electrodes.
  • one or more first leads of the at least one first stimulation lead are configured to be implanted in a lumen proximate the phrenic nerve of the patient.
  • one or more second stimulation leads of the at least one second stimulation lead are configured to be implanted in a lumen proximate the ansa cervicalis of the patient. In at least one example, one or more leads of the at least one second stimulation lead are configured to be implanted in a lumen proximate the ansa cervicalis of the patient. In at least one example, the at least one first stimulation lead includes one or more nerve cuffs and the at least one second stimulation lead includes one or more electrodes. In at least one nerve cuff of the one or more nerve cuffs is configured to be operatively coupled to the phrenic nerve of the patient. In at least one example, one or more leads of the at least one second stimulation lead are configured to be implanted in a lumen proximate the ansa cervicalis of the patient.
  • one or more leads of the at least one second stimulation lead are configured to be implanted in a lumen proximate the ansa cervicalis of the patient.
  • the at least one second stimulation lead includes one or more nerve cuffs and the at least one first stimulation lead includes one or more electrodes.
  • at least one nerve cuff of the one or more nerve cuffs is configured to be operatively coupled to the ansa cervicalis of the patient.
  • one or more leads of the at least one first stimulation lead are configured to be implanted in a lumen proximate the phrenic nerve of the patient.
  • one or more leads of the at least one first stimulation lead are configured to be implanted in a lumen proximate the phrenic nerve of the patient.
  • the at least one first stimulation lead includes one or more first nerve cuffs and the at least one second stimulation lead includes one or more second nerve cuffs.
  • one or more first nerve cuffs of the at least one first nerve cuff are configured to be operatively coupled to the phrenic nerve of the patient.
  • one or more second nerve cuffs of the at least one second nerve cuff are configured to be operatively coupled to the ansa cervicalis of the patient.
  • one or more nerve cuffs of the at least one second nerve cuff are configured to be operatively coupled to the ansa cervicalis of the patient.
  • the implanted therapy controller is further configured to modify at least one of first parameters of phrenic nerve electrical stimulation via the at least one phrenic nerve electrical stimulation lead or second parameters of ansa cervicalis electrical stimulations provided via the at least one ansa cervicalis electrical stimulation lead based on the airway information.
  • At least one of the first parameters or the second parameters includes a plurality of parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one ansa cervicalis electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the ansa cervicalis electrical stimulation.
  • At least one of the first parameters or the second parameters includes a number of pulses. In at least one example, at least one of the first parameters or the second parameters includes a current magnitude. In at least one example, at least one of the first parameters or the second parameters includes a voltage magnitude. In at least one example, at least one of the first parameters or the second parameters includes a frequency at which pulses are applied. In at least one example, at least one of the first parameters or the second parameters includes a time over which pulses are ramped up. In at least one example, at least one of the first parameters or the second parameters includes a time over which pulses are ramped down. In at least one example, at least one of the first parameters or the second parameters includes a number of ramping-up pulses.
  • At least one of the first parameters or the second parameters includes a number of ramping-down pulses. In at least one example, at least one of the first parameters or the second parameters includes a magnitude of at least one ramping-up pulse. In at least one example, at least one of the first parameters or the second parameters includes a magnitude of at least one ramping-down pulse. In at least one example, at least one of the first parameters or the second parameters includes a pulse width. In at least one example, at least one of the first parameters or the second parameters includes a time between applying the at least one phrenic nerve electrical stimulation and the at least one ansa cervicalis electrical stimulation. In at least one example, at least one of the first parameters or the second parameters includes a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the ansa cervicalis electrical stimulation.
  • At least one of the first parameters or the second parameters includes at least nine parameters from a list including a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one ansa cervicalis electrical stimulation, and a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the ansa cervicalis electrical stimulation.
  • the at least one first stimulation lead includes one or more first electrodes configured to provide at least one first anode-cathode pair configured to deliver the at least one phrenic nerve electrical stimulation
  • the at least one second stimulation lead includes one or more second electrodes configured to provide at least one second anode- cathodc pair configured to deliver the at least one hypoglossal nerve electrical stimulation.
  • one or more of the at least one first stimulation lead or the at least one second stimulation lead is a transvenous stimulation lead configured to be implanted in a lumen proximate a target nerve of the patient.
  • the implanted therapy controller comprises at least two connector ports.
  • the at least one first stimulation lead and the at least one second stimulation lead each comprise at least one terminal pin configured to couple a respective stimulation lead to at least one of the at least two connector ports.
  • the implanted therapy controller comprises at least three connector ports, and wherein at least one connector port is configured to couple to a sensor lead comprising a sensor.
  • the sensor comprises at least one of an electromyography sensor or a transthoracic impedance sensor.
  • the one or more of firmware or software is configured to provide at least one of first parameters of phrenic nerve electrical stimulation or second parameters of hypoglossal nerve electrical stimulations, and wherein the implanted therapy controller is further configured to modify at least one of the first parameters of the phrenic nerve electrical stimulation via the at least one phrenic nerve electrical stimulation lead or the second parameters of the hypoglossal nerve electrical stimulations provided via the at least one hypoglossal nerve electrical stimulation lead based on therapy sensor data.
  • the implanted therapy controller comprises at least one processor and stimulation circuitry, and wherein the at least one processor is configured to determine an entrainment index indicative of a degree of synchronization between the patient’s respiration rate and the entrainment frequency, and control the stimulation circuitry to provide a one or more of the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation based at least in part on the entrainment index.
  • a treatment system for providing disordered breathing therapy to a sleeping patient comprising at least one first stimulation lead, at least one second stimulation lead, and an implanted therapy controller configured to couple to the at least one first stimulation lead and the at least one second stimulation lead, the implanted therapy controller configured to provide at least one phrenic nerve electrical stimulation to a phrenic nerve of a patient via the at least one first stimulation lead, provide at least one hypoglossal nerve electrical stimulation to a hypoglossal nerve of the patient via the at least one second stimulation lead, and coordinate a relative timing of the at least one hypoglossal nerve electrical stimulation to the hypoglossal nerve with the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient.
  • the system includes at least one sensor configured to provide sensor data indicative of a sleep state of the patient, wherein the implanted therapy controller is configured to: determine sleep parameters of the patient based on the sensor data; determine that the patient is asleep based on the sleep parameters; and provide the at least one phrenic nerve electrical stimulation and the at least one hypoglossal nerve electrical stimulation based on the determination that the patient is asleep.
  • the at least one sensor includes at least one accelerometer.
  • the sensor data is indicative of movement of the patient.
  • the movement of the patient is indicative of a position of the patient.
  • the at least one accelerometer is implanted in the patient.
  • the at least one accelerometer is external to the patient.
  • the sensor data is indicative of the position of the patient, and wherein determining that the patient is asleep is based on the position of the patient.
  • the at least one first stimulation lead includes one or more electrodes.
  • one or more leads of the at least one first stimulation lead are configured to be implanted in a lumen proximate the phrenic nerve of the patient.
  • the at least one respiratory parameter sensor is disposed at one or more of the at least one hypoglossal nerve stimulation lead or the at least one phrenic nerve stimulation lead. In at least one example, the at least one respiratory parameter sensor is disposed at one or more of a lead body, an electrode, or a nerve cuff. In at least one example, the at least one respiratory parameter sensor is disposed on an implanted lead without nerve stimulation capability. In at least one example, the at least one respiratory parameter sensor comprises at least one of a transthoracic impedance sensor, a motion sensor, an acoustic sensor, an electromyography sensor, or a pressure sensor.
  • the implanted therapy controller is further configured to: receive, from the at least one respiratory parameter sensor, therapy sensor data, and evaluate the therapy sensor data to determine a therapy-specific indicator.
  • the therapy-specific indicator includes an entrainment index.
  • the entrainment index is indicative of a ratio of a quantity of breaths within a predetermined range of a stimulation rate to a total quantity of breaths for a particular time period.
  • the particular time period is a pre-determined collection period.
  • the implanted therapy controller is further configured to modify at least one of first parameters of phrenic nerve electrical stimulation via the at least one phrenic nerve electrical stimulation lead or second parameters of hypoglossal nerve electrical stimulations provided via the at least one hypoglossal nerve electrical stimulation lead based on the therapy sensor data.
  • the implanted therapy controller is further configured to modify at least one of the first parameters or the second parameters based on the entrainment index falling outside of a range of acceptable entrainment-index values.
  • the therapy sensor data is indicative of the patient’ s respiratory drive
  • the implanted therapy controller is configured to: evaluate an effect of the at least one phrenic nerve electrical stimulation on respiration of the patient, and adjust one or more parameters of the at least one phrenic nerve electrical stimulation based on the evaluation.
  • the implanted therapy controller is configured to provide a plurality of phrenic nerve electrical stimulations at an entrainment frequency
  • the therapy sensor data comprises an entrainment index indicative of a degree of synchronization between the patient’s respiration rate and the entrainment frequency.
  • the entrainment index comprises a ratio indicative of a degree of entrainment of the patient.
  • the entrainment index is a ratio of spectral power in a stimulation frequency band to a spectral power in an intrinsic respiratory frequency band.
  • the implanted therapy controller is configured to coordinate the relative timing based at least in part on the entrainment frequency.
  • the implanted therapy controller is configured to: evaluate an effect of the at least one hypoglossal nerve electrical stimulation on respiration of the patient, and adjust one or more parameters of the at least one hypoglossal nerve electrical stimulation based on the evaluation.
  • the implanted therapy controller is configured to provide the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient in response to a trigger comprising a preprogrammed stimulation rate, wherein the trigger excludes sensed respiration of the patient.
  • the implanted therapy controller is configured to coordinate the relative timing to provide the at least one hypoglossal nerve electrical stimulation simultaneously with the at least one phrenic nerve electrical stimulation.
  • the at least one phrenic nerve electrical stimulation includes a plurality of phrenic nerve electrical stimulations and the at least one hypoglossal nerve electrical stimulation includes a plurality of hypoglossal nerve electrical stimulations, and wherein the implanted therapy controller is further configured to increase an amplitude of at least one of the plurality of phrenic nerve electrical stimulations or the plurality of hypoglossal nerve stimulation over time.
  • At least one example of the disclosure includes a treatment system for providing disordered breathing therapy to a sleeping patient, the system comprising at least one first stimulation lead; at least one second stimulation lead; and an implanted therapy controller configured to couple to the at least one first stimulation lead and the at least one second stimulation lead, the implanted therapy controller configured to provide at least one phrenic nerve electrical stimulation to a phrenic nerve of a patient via the at least one first stimulation lead, provide at least one ansa cervicalis electrical stimulation to an ansa cervicalis of the patient via the at least one second stimulation lead, and coordinate a relative timing of the at least one ansa cervicalis electrical stimulation to the ansa cervicalis with the at least one phrenic nerve electrical stimulation to the phrenic nerve of the patient.
  • a delivery start time of the at least one ansa cervicalis electrical stimulation is synchronized with a delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, a delivery start time of the at least one ansa cervicalis electrical stimulation is earlier than a delivery start time of the at least one phrenic nerve electrical stimulation. In at least one example, a delivery start time of the at least one ansa cervicalis electrical stimulation is later than a delivery start time of the at least one phrenic nerve electrical stimulation.
  • each breathing cycle of a plurality of breathing cycles of the patient includes an inspiration period and an expiration period
  • the implanted therapy controller is further configured, for each breathing cycle of the patient, to apply one or more phrenic nerve electrical stimulations to the phrenic nerve of the patient via the at least one first stimulation lead and to apply one or more ansa cervicalis electrical stimulations to the ansa cervicalis of the patient via the at least one second stimulation lead.
  • the system includes at least one sensor configured to provide sensor data indicative of a sleep state of the patient, wherein the implanted therapy controller is configured to determine sleep parameters of the patient based on the sensor data; determine that the patient is asleep based on the sleep parameters; and provide the at least one phrenic nerve electrical stimulation and the at least one ansa cervicalis electrical stimulation based on the determination that the patient is asleep.
  • the implanted therapy controller is further configured to: determine, responsive to determining that the patient is asleep, whether the implanted therapy controller is pre-programmed to provide obstructive sleep apnea therapy; and provide the at least one ansa cervicalis electrical stimulation responsive to determining that the implanted therapy controller is pre-programmed to provide the obstructive sleep apnea therapy.
  • the at least one sensor includes at least one accelerometer.
  • the sensor data is indicative of movement of the patient.
  • the movement of the patient is indicative of a position of the patient.
  • the at least one accelerometer is implanted in the patient.
  • the at least one accelerometer is external to the patient.
  • the sensor data is indicative of the position of the patient, and wherein determining that the patient is asleep is based on the position of the patient.
  • the at least one first stimulation lead includes one or more electrodes.
  • one or more leads of the at least one first stimulation lead are configured to be implanted in a lumen proximate the phrenic nerve of the patient.
  • the at least one first stimulation lead includes one or more nerve cuffs.
  • the at least one second stimulation lead includes one or more electrodes.
  • one or more leads of the at least one second stimulation lead are configured to be implanted in a lumen proximate the ansa cervicalis of the patient.
  • the at least one second stimulation lead includes one or more nerve cuffs.
  • the system includes at least one respiratory parameter sensor.
  • the at least one respiratory parameter sensor is disposed externally on the patient.
  • the at least one respiratory parameter sensor is an implantable sensor.
  • FIG. 11 A illustrates a process of operating a disordered breathing therapy system according to an example
  • the IPG 12 may apply operational parameters that include electrical stimulation parameters for a particular nerve to the port and removably attachable lead connected to the port during implant.
  • the IPG 12 may provide stimulation to the phrenic nerve according to phrenic nerve electrical stimulation parameters via the connector port designated as a phrenic nerve stimulation port, and similarly for the hypoglossal nerve and/or the ansa cervicalis.
  • the engines 24 and 26 may include hardware (for example, one or more controllers configured to execute computer-executable instructions), software (for example, instructions stored on non-transitory computer-readable media that, when executed by hardware such as the one or more controllers, causes the treatment system 10 to deliver therapy), or a combination thereof.
  • the actions performed by engine 24 and/or 26 may be implemented by hardware, software, firmware, microcode, hardware description languages, and so forth, or any combination thereof.
  • the program code or code segments to perform the tasks may be stored in a non-transitory processor-readable medium such as a storage medium.
  • One or more processors may perform the described tasks.
  • an ordered rhythmic breathing pattern is established without a patient being dependent on the phrenic nerve stimulation for all diaphragmatic contraction.
  • the patient is thus said to be “entrained” as opposed to “paced” by the nerve stimulation. Entrainment allows the IPG 12 to modulate a patient’s breathing to occur at a physiologically beneficial rate.
  • a degree of entrainment for a patient may be indicated by an entrainment index.
  • the entrainment index may quantify or otherwise provide a metric characterizing a patient’s response to nerve stimulation. This entrainment index may indicate the extent to which the stimulation therapy has entrained the patient’s respiration and synchronized the patient’s respiration to stimulation rate.
  • the entrainment index may be an index of a degree to which the patient’s respiration rate is captured within a target range for breathing rate as determined by the entrainment therapy (for example, a capture index).
  • the processor 50 of the implantable treatment system 10 and/or the processor 102 of the external computing device 210 may calculate the entrainment index.
  • the RDS diagnostics engine 26 of the external computing device 210 may determine an entrainment index based on spectral power analysis.
  • the entrainment index represents the fraction of a total spectral plot of respiration (an intrinsic respiratory frequency band [RFB]) that falls into a frequency band proximate and/or including the stimulation rate (a stimulation frequency band [SFB]).
  • the value of the entrainment index is expected to increase proportionally with the entrainment of respiration by stimulation.
  • a higher entrainment index indicates a higher degree of entrainment by stimulation.
  • the stimulation rate thus becomes the dominant frequency of the respiration signal as entrainment increases.
  • a target entrainment index may be 0.6-0.8 (or 60%-80%).
  • the intrinsic respiratory frequency band may comprise a band of frequencies associated with the patient’s intrinsic respiration that is not triggered by stimulation from the IPG 12.
  • the stimulation frequency band may comprise a band of frequencies associated with the patient’s stimulated respiration that is triggered by stimulation from the IPG 12.
  • the entrainment index may be calculated based on a quantity of measured breaths occurring at a rate that is close to the stimulation.
  • the RDS engine 24 of the implantable treatment system 10 may determine an entrainment index based on measured breaths.
  • the implantable treatment system 10 may measure peak-to-peak timings in the respiratory signal to determine a length of each breath.
  • the system 10 may collect data for a series of breath lengths over a set amount of time (for example, one to five minutes) and classify each breath as entrained or unentrained depending on whether the breath length is within a predetermined tolerance range of the stimulation rate.
  • the system 10 may calculate a number of entrained breaths divided by a total number of breaths.
  • the system 10 may compare this ratio to a pre-determined threshold defining successful synchronization, or entrainment. For example, the threshold may be between 0.6-0.8. If the ratio meets or exceeds the threshold or falls within a target range, the system 10 may determine the patient to be entrained.
  • a histogram 40 of a number of breath periods 42 versus breath periods 44 illustrates an entrainment index calculation.
  • a range of breath periods may be predetermined as a synchronized range 46 that includes a pre-determined stimulation rate 48.
  • the pre-determined stimulation rate 48 is not responsive to the patient’s intrinsic breathing rate, and the pre-determined stimulation rate 48 enables therapy in the pre-determined stimulation rate mode 862 as shown in FIG. 8B.
  • Breaths inside of the range 46 may be designated as synchronized with the stimulation rate and breaths outside of the range 46 may be designated as unsynchronized with the stimulation rate.
  • the total number of breaths within the synchronized range 46 provides the number of target breath periods.
  • the entrainment index may be calculated as a fraction or percentage using the number of target breath periods divided by a total number of breaths.
  • the total number of breaths is 25
  • the number of breaths inside the synchronized range is 15, and the number of breaths in the unsynchronized range is 10. Therefore, the entrainment index for this example is 0.6 or 60%.
  • a target entrainment index may be between 0.6 and 0.8 (or 60%-80%). The value of the entrainment index is expected to increase proportionally with the entrainment of respiration by stimulation. Thus, a higher entrainment index indicates a higher degree of entrainment by stimulation.
  • Disordered breathing therapy may include applying electrical stimulation to one or more nerves of the patient.
  • the implantable device 12 generates an electrical current (for example, an electrical-current pulse train) and delivers the electrical current to one or more implantable leads (for example, the leads 14, 16) to electrically stimulate the one or more nerves or a group of nerves, such as a neuroplexus, in the patient’s body.
  • the treatment system 10 includes one or more controllers and/or processors configured to process information and control operation of the treatment system 10, such as by delivering and modifying the treatment.
  • the one or more controllers and/or processors of the treatment system 10 may be performing these operations.
  • the phrenic nerve stimulation leads 14 may be configured (i.e., specifically designed physically and/or electrically) to stimulate nerves related to diaphragm control for treatment of decreased respiratory drive, which may be a lack of respiratory drive.
  • the upper-airway nerve stimulation leads 16 may be configured (i.e., specifically designed physically and/or electrically) to stimulate nerves related to airway tone for treatment of airway obstruction, which, in some examples, may be due to decreased airway patency.
  • These nerves may include, for example, one or more of the hypoglossal nerve, the ansa cervicalis, a C12 group nerve, a CIO group nerve, and/or another nerve that may modulate airway patency and/or stiffness.
  • the phrenic nerve stimulation leads 14 may be proximate to and/or operatively coupled to one or more phrenic nerves of the patient such that electrical current provided by the implantable device 12 conveys a stimulation, via the phrenic nerve stimulation leads 14, to the one or more phrenic nerves.
  • the leads 14 may be physically designed to be able to enter and stabilize in a vessel or another position proximate to the phrenic nerve and electrically designed to deliver a stimulation appropriate for the phrenic nerve.
  • the upper-airway nerve stimulation leads 16 may be proximate to and/or operatively coupled to one or more hypoglossal nerves of the patient such that electrical current provided by the implantable device 12 conveys a stimulation, via the upper-airway nerve stimulation leads 16, to the one or more hypoglossal nerves.
  • the upper-airway nerve stimulation leads 16 may be proximate to and/or operatively coupled to one or more ansa cervicalis in addition to, or in lieu of, the hypoglossal nerves of the patient such that electrical current provided by the implantable device 12 conveys a stimulation, via the upper- airway nerve stimulation leads 16, to the ansa cervicalis.
  • the upper- airway nerve stimulation leads 16 may be proximate to and/or operatively couple to a C 12 group nerve, a CIO group nerve, a combination thereof, and/or another nerve or group of nerves that modulate airway tone.
  • the leads 16 may be physically designed to be able to enter and stabilize in a vessel or another position proximate to a particular upper-airway nerve and electrically designed to deliver a stimulation appropriate for the particular upper-airway nerve.
  • the leads 14 and 16 may be thin conductors, such as wires, coupled to and/or including one or more electrodes.
  • a lead including an electrode may be implanted in the patient via a physiological lumen (that is, a cavity within a tubular organ or part) to a position proximate to a target nerve.
  • the lumen may be a blood vessel, a vein, an artery, a lymphatic vessel, and so forth.
  • the lead may be structurally configured for implant within a specific lumen based on the length, diameter, stabilization mechanism, and/or electrode position, etc.
  • a lead may include one electrode or multiple electrodes.
  • the lead and electrode may be configured to stimulate a single nerve or a neuroplexus.
  • a lead including an electrode may be implanted within a blood vessel of the patient and electrical current provided to the electrode may result in electrical stimulation being applied to the target tissue trans venously.
  • this electrode may be referred to as a transvenous electrode in contrast to a nerve cuff which includes electrodes delivering a direct stimulation to the nerve without passing through a vessel wall.
  • a lead includes at least one terminal pin that connects to the IPG 12, a conductor that extends along the length of the lead (that is, the lead body) from the at least one terminal pin to one or more electrodes, and the one or more electrodes.
  • the one or more electrodes are disposed along the lead and may be at the distal end of the lead.
  • the lead may further include a central lumen (for example, a lead lumen or a bore within the physical structure of the lead and/or lead system).
  • a current pulse train generated by the IPG 12 travels along the lead via the conductor to the one or more electrodes.
  • the one or more electrodes may be in contact with the target tissue (for example, in contact with a nerve via a nerve cuff) and/or located proximately to the target tissue (for example, proximate to a nerve due to a position in a vein that is proximate to the nerve).
  • the current pulse train stimulates the target tissue via direct contact.
  • the current pulse train stimulates the target tissue trans venously.
  • one or more of the leads may include one or more nerve cuffs.
  • a lead may include at least one terminal pin that connects to the IPG 12, a conductor that extends along the length of the lead (that is, the lead body) from the at least one terminal pin to one or more nerve cuffs, and the one or more nerve cuffs.
  • a nerve cuff may be implemented around a target nerve or nerves and may be specifically configured physically and/or electronically for the specific target nerve.
  • the nerve cuff includes one or more electrodes positioned in a cuff structure. Once implanted, the nerve cuff may be disposed circumferentially around at least a portion of a target nerve.
  • the nerve cuff may be considered to be operatively coupled to the target nerve.
  • being operatively coupled may describe a relationship between a nerve cuff and a target nerve in which electrical stimulation provided by the nerve cuff stimulates the target nerve, optionally by at least a threshold amount of stimulation.
  • the threshold amount of stimulation may correspond to a level at which an electrical stimulation output by the nerve cuff actuates the muscle innervated by the nerve.
  • a nerve cuff disposed around the phrenic nerve may be operatively coupled to the phrenic nerve where an electrical stimulation provided by the nerve cuff to the phrenic nerve causes the diaphragm to contract.
  • a current or current pulse train provided for a period of time results in an electric charge.
  • the electrode(s) provides this electric charge to the nerve or other target tissue.
  • the current and the duration of the period of time determine the total electric charge applied to the target tissue.
  • a device such as the IPG 12, may be configured to provide various intensity stimulations. For example, there may be weak, medium, and strong thresholds to describe a range of functional responses.
  • the leads 14, 16 may be implanted in accordance with various configurations, such as by including only transvenous electrodes, only nerve cuffs, and/or combinations thereof. Where there are multiple leads 14 and/or multiple leads 16, the various leads may provide transvenous electrodes on some leads and nerve cuffs on other leads. With transvenous electrodes, leads 14, 16 may be disposed within various blood vessels in a patient. For example, these vessels may include one or more of the brachiocephalic vein, the superior vena cava, the internal jugular vein, the subclavian vein, the lingual vein, the ranine vein, the pericardiophrenic vein, a combination of the foregoing, and/or other blood vessels.
  • the lead 16 may be implanted in a ranine vein to provide stimulation to a hypoglossal nerve by entering the subclavian vein and the internal jugular vein to reach the ranine vein.
  • the vessels exemplified include both the right and left occurrences.
  • the aforementioned reference to the internal jugular vein may refer to either or both of the right and left internal jugular vein, and the leads 14, 16 may be disposed within either or both of the right and left internal jugular veins.
  • the leads may be routed through the internal structure of a patient so as to connect the implantable pulse generator 12 with the target nerve.
  • a surgeon may expose a nerve, preferably a nerve close to the exterior surface of a patient’s body, and route the lead with the nerve cuff to this exposed nerve.
  • FIGS. 3A-7 Examples of different configurations of the leads 14, 16 are provided below with respect to FIGS. 3A-7.
  • the examples of FIGS. 3A-7 are provided for purposes of explanation rather than limitation.
  • FIGS. 3A-7 provide various example implementations for the disordered breathing therapy system 100. Other examples and combinations of features are within the scope of the disclosure.
  • the phrenic nerve stimulation leads 14, which may include one or more leads, may include or be coupled to electrodes, nerve cuffs, a combination thereof, and so forth, to stimulate one or more phrenic nerves of a patient.
  • the upper-airway nerve stimulation leads 16, which may include one or more leads, may include or be coupled to electrodes, nerve cuffs, a combination thereof, and so forth, to stimulate one or more hypoglossal nerves of a patient.
  • the upper-airway nerve stimulation leads 16 may include one or more leads which may include or be coupled to electrodes, nerve cuff(s), a combination thereof, and so forth, to stimulate the ansa cervicalis of a patient.
  • the upperairway nerve stimulation leads 16 may include one or more leads which may include or be coupled to electrodes, nerve cuff(s), a combination thereof, and so forth, to stimulation a combination of one or more hypoglossal nerves of a patient and the ansa cervicalis of the patient.
  • Various combinations of implementations of the leads 14, 16 are within the scope of the disclosure, beyond the specific examples provided above.
  • the sensors 18 and/or 19 may include one or more sensors configured to sense physiologic parameters related to a patient, such as air flow sensors, pressure sensors, accelerometers, acoustic sensors, optical sensors (for example, pulse oximeters), effort belts, pulsatility sensors, transthoracic impedance sensors, heart-rate sensors, and so forth. As discussed in greater detail below, the sensors 18 and/or 19 may be configured to sense parameters which may be used to evaluate and/or modify therapy delivered to the patient.
  • sensors configured to sense physiologic parameters related to a patient, such as air flow sensors, pressure sensors, accelerometers, acoustic sensors, optical sensors (for example, pulse oximeters), effort belts, pulsatility sensors, transthoracic impedance sensors, heart-rate sensors, and so forth.
  • the sensors 18 and/or 19 may be configured to sense parameters which may be used to evaluate and/or modify therapy delivered to the patient.
  • FIGS. 3 A and 3B illustrate examples of disordered breathing therapy systems that include transvenous electrodes.
  • a quantity of each component in FIGS. 3A and 3B is an example only and other quantities of each, or any, component could be used.
  • the leads in FIGS. 3 A and 3B are shown as unilateral leads to deliver unilateral stimulations (for example, to deliver stimulation to a nerve having a left and right occurrence), the system may include bilateral leads to deliver bilateral stimulation (for example, to deliver stimulation to both the left and right occurrences of a nerve having left and right occurrences).
  • examples of unilateral leads to stimulate one nerve may be implemented as bilateral leads to stimulate multiple nerves in alternate examples, and vice versa.
  • FIG. 3A illustrates a perspective view of an example of a disordered breathing therapy system 300 implemented in connection with a patient 399 according to an example. The patient’s heart 398 is shown for anatomical reference.
  • the system 300 includes transvenous electrodes 306 on the lead 16 and transvenous electrodes 308 on the lead 14 implemented to deliver disordered breathing therapy to the patient 399 via stimulation of a left hypoglossal nerve 352 and the left phrenic nerve 354, respectively.
  • the lead 14 is implanted within the left pericardiophrenic vein 364 via the brachiocephalic veins 362.
  • the lead 16 is implanted within the left ranine vein 368 via the brachiocephalic veins 362 and left internal jugular (LIJ) vein 366.
  • the lead 16 may be implanted within the left ranine vein 368 via the LIJ vein 366 and a subclavian vein.
  • the at least one phrenic nerve stimulation lead 14 is configured to provide electrical stimulation to the left phrenic nerve 354 of the patient 399 responsive to the lead 14 receiving an electrical current from the IPG 12, for example a current pulse train.
  • the at least one lead 14 includes one or more transvenous electrodes 308 (coupled to the implantable device 12 via a respective lead body 310) to deliver the electrical stimulation transvenously to a phrenic nerve proximate the one or more transvenous electrodes 308.
  • the electrical current may stimulate the left phrenic nerve 354.
  • the phrenic nerve stimulation leads 14 may include more than one lead. In such an example, the phrenic nerve stimulation leads 14 may be configured to deliver electrical stimulation to more than one nerve.
  • the phrenic nerve stimulation leads 14 may be configured to deliver electrical stimulation to a left phrenic nerve 354 via a first lead 14a and to deliver electrical stimulation to a right phrenic nerve via a second lead 14b.
  • the phrenic nerve stimulation leads 14 may be configured to deliver stimulation to only the left phrenic nerve 354, to only the right phrenic nerve, or to both of the left and the right phrenic nerves.
  • the upper- airway nerve stimulation leads 16 include at least one lead implanted within the patient 399 and configured to provide electrical stimulation to a left hypoglossal nerve 352 of the patient 399 responsive to the upper- airway nerve stimulation leads 16 receiving an electrical current from the IPG 12.
  • the at least one lead 16 includes one or more transvenous electrodes 306 (coupled to the implantable device 12 via a respective lead body 312) to deliver the electrical stimulation transvenously to a left hypoglossal nerve 352 proximate the one or more transvenous electrodes 306.
  • the electrical current may stimulate the hypoglossal nerve.
  • the upper-airway nerve stimulation leads 16 may include more than one lead.
  • the upper- airway nerve stimulation leads 16 may be configured to deliver electrical stimulation to more than one nerve.
  • the upper- airway nerve stimulation leads 16 may be configured to deliver electrical stimulation to a left hypoglossal nerve 352 via a first lead 16a and to deliver electrical stimulation to a right hypoglossal nerve via a second lead 16b.
  • the upper- airway nerve stimulation leads 16 may be configured to deliver stimulation to only the left hypoglossal nerve 352, to only the right hypoglossal nerve, or to both of the left and the right hypoglossal nerves.
  • FIG. 3B illustrates a perspective view of an example of a disordered breathing therapy system 350 according to another example.
  • the disordered breathing therapy system 350 is similar to the disordered breathing therapy system 300; however, the upper-airway nerve stimulation leads 16 include one or more transvenous electrodes 309 implemented to deliver disordered breathing therapy to a patient 399 via stimulation of the ansa cervicalis 356.
  • the upper-airway nerve stimulation leads 16 may not be coupled to, nor configured to deliver electrical stimulation to, a left hypoglossal nerve 352 of the patient 399.
  • the disordered breathing therapy system 350 may provide electrical stimulation of the ansa cervicalis 356 in addition to or in lieu of providing stimulation of the left hypoglossal nerve 352.
  • the upper-airway nerve stimulation leads 16 may include one or more leads.
  • the upper-airway nerve stimulation leads 16 may include at least two leads with one or more first leads 16a configured to stimulate the left hypoglossal nerve 352 (for example, just the right hypoglossal nerve, just the left hypoglossal nerve, or the right and the left hypoglossal nerves) and/or one or more second leads 16c configured to stimulate the ansa cervicalis 356.
  • a disordered breathing therapy system that includes bilateral stimulation leads 308a and 308b implanted within a patient 399.
  • the electrodes on the lead 308a are implanted so as to transvenously stimulate the left phrenic nerve and the electrodes on the lead 308b arc implanted so as to transvenously stimulate the right phrenic nerve.
  • the stimulation leads 308a, 308b are bilateral inasmuch as they collectively stimulate both the left and right phrenic nerves.
  • the bilateral stimulation leads may include nerve cuffs.
  • FIG. 3C provides an example of stimulation leads configured to bilaterally stimulate the phrenic nerve
  • the disordered breathing therapy system may additionally or alternatively include stimulation leads configured to bilaterally stimulate upper-airway nerves.
  • One or more of the bilateral leads may include implantable sensors 19 as discussed further in regard to FIG. 5A.
  • the bilateral leads may include one or more additional leads used for sensing rather than stimulation and/or the bilateral leads may include one or more stimulation leads (14 and/or 16) in combination with one or more additional leads 20.
  • FIGS. 4A and 4B illustrate examples of disordered breathing therapy systems that include nerve cuffs.
  • a quantity of each component in FIGS. 4A and 4B is an example only and other quantities of each, or any, component could be used.
  • the leads in FIGS. 4 A and 4B are shown as unilateral leads to deliver unilateral stimulations, the system may include bilateral leads to deliver bilateral stimulation.
  • FIG. 4A illustrates a perspective view of an example of a disordered breathing therapy system 400 according to an example.
  • the disordered breathing therapy system 400 may be an example of the disordered breathing therapy system 10 in which the treatment system 10 includes nerve cuffs.
  • the system 400 includes at least one phrenic nerve cuff 402 and at least one hypoglossal nerve cuff 404 implemented to deliver disordered breathing therapy to a patient 499 via stimulation of a right phrenic nerve 358 and a left hypoglossal nerve 352, respectively.
  • the phrenic nerve stimulation leads 14 include at least one lead configured to be implanted within the patient 499 and to provide electrical stimulation to a right phrenic nerve 358.
  • the at least one lead 14 includes the at least one phrenic nerve cuff 402 (coupled to the implantable device 12 via a respective lead body 410) to deliver an electrical stimulation to a right phrenic nerve 358 around which the at least one phrenic nerve cuff 402 is disposed.
  • the electrical current provided to the lead 14 may stimulate the right phrenic nerve 358.
  • the phrenic nerve stimulation leads 14 may include more than one lead.
  • the phrenic nerve stimulation leads 14 may be configured to deliver electrical stimulation to a left phrenic nerve 354 via a first lead 14a and to deliver electrical stimulation to a right phrenic nerve 358 via a second lead 14b.
  • the phrenic nerve stimulation leads 14 may be configured to deliver stimulation to only the left phrenic nerve 354, to only the right phrenic nerve 358, or to both of the left and the right phrenic nerves.
  • the upper- airway nerve stimulation leads 16 include at least one lead implanted within the patient 499 and configured to provide electrical stimulation to a left hypoglossal nerve 352 of the patient 499.
  • the at least one lead 16 includes the at least one nerve cuff 404 (coupled to the implantable device 12 via a respective lead body 412) configured to deliver electrical stimulation to a left hypoglossal nerve 352 around which the at least nerve cuff 404 is disposed.
  • the electrical current provided to the lead 16 may stimulate the left hypoglossal nerve 352.
  • the upper-airway nerve stimulation leads 16 may include more than one lead.
  • the upper- airway nerve stimulation leads 16 may be configured to deliver electrical stimulation to a left hypoglossal nerve 352 via a first lead 16a and to deliver electrical stimulation to a right hypoglossal nerve via a second lead 16b.
  • the upper-airway nerve stimulation leads 16 may be configured to deliver stimulation to only the left hypoglossal nerve 352, to only the right hypoglossal nerve, or to both of the left and the right hypoglossal nerves.
  • FIG. 4B illustrates a perspective view of an example of a disordered breathing therapy system 450 according to another example.
  • the disordered breathing therapy system 450 is similar to the disordered breathing therapy system 400 and is configured to deliver disordered breathing therapy; however, the upper-airway nerve stimulation leads 16 include one or more nerve cuffs 452 to deliver disordered breathing therapy to a patient 499 via stimulation of the ansa cervicalis 356.
  • the upper-airway nerve stimulation leads 16 may not be coupled to, nor configured to deliver electrical stimulation to, a hypoglossal nerve of the patient 499.
  • the upper-airway nerve stimulation leads 16 may be coupled to, and configured to deliver electrical stimulation to, the ansa cervicalis 356 of the patient 499.
  • the upper-airway nerve stimulation leads 16 may include at least one lead implanted within the patient 499 and configured to provide electrical stimulation to the ansa cervicalis 356 of the patient 499.
  • the at least one lead 16 includes the at least one nerve cuff 452 (coupled to the implantable device 12 via a respective lead body 412) configured to deliver electrical stimulation to the ansa cervicalis 356 around which the at least one nerve cuff 452 is disposed.
  • the electrical current provided to the lead 16 may stimulate the ansa cervicalis 356.
  • the phrenic nerve stimulation leads 14 and the upper-airway nerve stimulation leads 16 may include more than one lead (for example, leads 14a and 14b and leads 16a and 16b).
  • the leads 14, 16 may include transvenous electrodes to deliver an electrical stimulation (examples of which are illustrated in FIGS. 3A-3C), and/or may include nerve cuffs to deliver an electrical stimulation (examples of which are illustrated in FIGS. 4A and 4B) and/or groups of leads may include a combination of electrodes and nerve cuffs in other examples.
  • FIG. 4C an example is shown of a disordered breathing therapy system 480 that includes nerve cuffs disposed on multiple airway related nerves.
  • the nerve cuff 404a is disposed on the left hypoglossal nerve 352 and the nerve cuff 404b is disposed on the ansa cervicalis 356.
  • a quantity of each component in FIGS. 4A-4C is an example only and other quantities of each, or any, component could be used.
  • the leads in FIGS. 4A and 4B are shown as unilateral leads to deliver unilateral stimulations, the system may include bilateral leads to deliver bilateral stimulation.
  • FIGS. 5A, 5B, and 5C illustrate examples of a disordered breathing therapy system 500 implemented with implanted sensors disposed on leads. Quantities of each component in FIGS. 5A, 5B, and 5C are examples only and other quantities of each, or any, component could be used.
  • the disordered breathing therapy system 500 is an example of the treatment system 10 in which the treatment system 10 includes one or more implantable sensors 19 located along a stimulation lead 14, 16 where the lead includes electrodes 504, 506.
  • the electrodes 504, 506 may be transvenous electrodes or nerve cuffs, as described herein and for which the description has not been repeated for purposes of brevity.
  • Sensors may be disposed unilaterally (that is, on one lead with an electrode implanted on or near either a right or left nerve) or disposed bilaterally (that is, on two leads with electrodes implanted on or near both of a right and a left nerve).
  • the sensor(s) 19 may be integrated into or otherwise attached to the nerve cuff and/or may be disposed along the lead body but physically separated from the nerve cuff.
  • the disordered breathing therapy system 550 is an example of the treatment system 10 in which the treatment system 10 includes one or more implantable sensors 19 disposed along the additional leads 20.
  • the treatment system 10 may include a combination of sensors disposed along one or more of the stimulation leads 14, 16 and sensors disposed along the additional lead 20.
  • the sensors 19 may he disposed unilaterally (that is, on one or more additional leads implanted on the left or right side of a patient) or disposed bilaterally (that is, on two or more additional leads with electrodes implanted on both the right and left side of the patient).
  • the sensors 19 may be disposed on at least one additional lead 20 implanted on one side of the patient (for example, right or left) and there may be further sensors disposed on one or more stimulation leads disposed on the other side of the patient.
  • the placement of the sensors may thus be tailored to an optimum or desired location for a signal of interest.
  • the implantable sensors 19 may include, for example, but not limited to, transthoracic impedance sensors 512, motion sensor(s) 514, acoustic sensor(s) 516, electromyography (EMG) sensors 517, and/or pressure sensor(s) 518.
  • the motion sensor(s) 514 may include one or more implantable accelerometers.
  • Internal EMG sensors may be disposed on a lead implanted on or proximate to a muscle of interest, such as the diaphragm or an upper-airway muscle. Such internal EMG sensors may detect muscular responses to nerve stimulation and provide signals indicative of the effects of such stimulation.
  • the at least one implantable sensor 19 may be communicatively and/or electrically coupled to the implantable device 12 via the respective phrenic nerve stimulation lead 14, the upper-airway nerve stimulation lead 16, and/or the additional lead 20 to which the additional sensor 19 is coupled.
  • the treatment system 10 may include a combination of implantable sensors 19 disposed on the leads (for example, phrenic nerve stimulation leads 14, upper-airway nerve stimulation leads 16, and/or additional leads 20) and disposed on the IPG 12 as shown in FIG. 6 and discussed below.
  • the IPG 12 may include at least two sections, including a casing 520 and a header 522.
  • the casing 520 may include a hermetically sealed casing, or can, that encloses components of the IPG 12 (for example, electronic components of the IPG 12 such as the components 50-58).
  • the casing 520 isolates the enclosed components from the body environment of a patient.
  • the header 522 includes one or more receptacles for receiving respective connector assemblies for the leads 14, 16, and/or 20. Thus the leads 14, 16, and 20 are configured to couple to the IPG 12 via the connector assemblies of the header 522.
  • Such receptacles may include, for example, the connector ports 60, 62, 64.
  • the header 522 thus provides paths between the leads 14, 16, and/or 20 and the enclosed components of the IPG 12 (for example, via the ports 60, 62, 64).
  • the header 522 and associated ports 60, 62, 64 may provide paths to electronically and/or mechanically connect electronics enclosed within the casing 520 (for example, the components 50-58) to the leads 14, 16, and/or 20. These paths arc electrically and mechanically integrated with the IPG 12 to provide a safe, long-term connection without comprising the hermetic package of the IPG 12.
  • the transthoracic impedance measurement discussed herein may be an impedance measurement along a circuit path between an electrode implanted in the thoracic region of a patient (e.g., on a lead 14 or 20) and the casing 520.
  • the at least one pressure sensor 518 may include one pressure sensor, may include multiple pressure sensors, or may be omitted completely.
  • the motion sensor 514 may similarly include one motion sensor, may include multiple motion sensors, or may be omitted completely.
  • the EMG sensor 517 may similarly include one EMG sensor, may include multiple EMG sensors, or may be omitted completely.
  • the acoustic sensor 516 may similarly include one acoustic sensor, may include multiple acoustic sensors, or may be omitted completely.
  • the implantable sensors 19 are biocompatible sensing devices with the capability of providing sensed data to the IPG 12 and/or to the external computing device 210 (for example, via telemetry).
  • the implantable sensor(s) 19 may receive power either from the IPG 12 or via telemetry.
  • the implantable sensor(s) 19 may not require power and may only transfer data determined mechanically in response to interrogation. Arrays of these devices/sensors may improve sensitivity.
  • a microelectromechanical (MEMS) process may generate the sensor(s) 19 at a small and implantable form factor.
  • An implantable pressure sensor 518 may include a membrane and a sealed cavity where pressure is measured based on deflection of the membrane. Piezoelectric or capacitor circuit components may sense and quantify the membrane deflection. For piezoresistive sensing, a piezo resistor may be patterned onto the membrane surface, and deflection of the membrane is transduced into a change in resistance, and measured, for example, via a bridge circuit. In the case of capacitive sensing, an electrode may be disposed on each of a deformable and a rigid surface of a sealed cavity. Deflection of the membrane causes changes in the capacitance measured between the electrode pair.
  • a pressure sensor 518 and an acoustic sensor 516 may be a same sensor in terms of structure and/or circuit elements, as discussed above, but with sensitivities to different induced voltage changes and therefore different frequency range outputs.
  • a pressure sensor may measure 0-100 Hz and an acoustic sensor may measure 10-500 Hz.
  • the piezoelectric or capacitive element may measure deflections due to impinging sound waves or due to the vibrations of the tissue itself.
  • the at least one motion sensor 514 may provide motion or acoustic information depending on the frequency bandwidth of the sensor.
  • the implantable sensors 19 may include multiple accelerometers.
  • One or more first accelerometers may provide patient body motion and/or orientation information which may be indicative of patient activity and/or pitch.
  • One or more second accelerometers may be disposed on or near the diaphragm and sense relative motion of the diaphragm.
  • One or more third accelerometers (and/or pressure or acoustic sensors) may be implanted into blood vessels in or near the neck to sense acoustic information indicative of obstructions.
  • the at least one motion sensor 514 is an electromechanical device that measures acceleration and the force producing the acceleration.
  • the motion sensor 514 may be a piezoelectric or capacitor device. These devices may include movable and fixed plates and measure changes in the position of the movable plate relative to the fixed plate due to an applied force. The device may produce a change in voltage in response to the applied force that measures an acceleration or deceleration in response to the applied force.
  • these implantable sensors may provide the magnitude or intensity of the sensed signal which may enable the implantable treatment system 10 to adjust therapy based on these magnitudes or intensities.
  • the intensity of sound may indicate a degree of blockage and thus inform an appropriate current level for nerve stimulation.
  • a sensor implanted in or near the thoracic cavity may provide more accurate measurements and/or data that is more responsive to physiological dynamics of the cardiac and respiratory cycles. These dynamics are attenuated by the thoracic structure of ribs and muscles so that an external sensor may measure smaller signal amplitudes, which may not exceed noise levels, than an internal sensor.
  • the at least one pressure sensor 518 may detect changes in pressure caused by physiologic processes of the patient 499, such as the beating of the patient’ s heart, the breathing of the patient, and so forth, which may be used to determine the heart rate and/or breathing rate of the patient 499.
  • a pressure sensor such as the pressure sensor 518, may sense and provide measurement of internal thoracic pressure.
  • the internal thoracic pressure varies during the respiratory and cardiac cycles. Where there is, for example, an obstructed or closed airway, as occurs during airway obstruction, an effort to breathe against this obstructed or closed airway generates a higher negative internal thoracic pressure than where there is an unobstructed or open airway.
  • Negative internal thoracic pressure generated by a contraction of the diaphragm will be of a greater magnitude with an obstruction than without an obstruction due to a reduction or lack of air inflow through the upper airway.
  • the degree of airway obstruction may change over time with the physiologic processes and/or, for example, with changes in sleeping position.
  • the IPG 12 may modify provided stimulation in response to changes in the degree of airway obstruction.
  • a disordered breathing therapy system as described herein is configured to adjust stimulation provided to both phrenic and upper-airway nerves to wholistically treat disordered breathing.
  • the at least one motion sensor 514 senses motion parameters, such as acceleration, which may be indicative of patient position and/or movement.
  • Patient position and/or movement may be indicative of a position in which the patient is sleeping or of the patient rolling during sleep.
  • Patient position and/or movement may also be indicative of a stimulation-induced arousal. Such an arousal is undesirable as one purpose of these stimulations is to improve sleep quality.
  • the IPG 12 and/or the external computing system 210 may reduce a stimulation current of either hypoglossal, ansa ccrvicalis, and/or phrenic nerve stimulation leads if data from the at least one motion sensor 514 indicates an arousal in response to a stimulation.
  • the acceleration parameters may additionally or alternatively sense acceleration parameters indicative of other the movement of internal organs and muscles, such as movement caused by the diaphragm contracting, lung motion or other respiratory system motion due to airflow (for example, the patient breathing) either produced spontaneously or in response to stimulation, the heart of the patient beating, and so forth.
  • the at least one acoustic sensor 516 may sense acoustic parameters which may be indicative of sounds related to respiration, such as the sound of the patient breathing, the sound of the patient snoring, the sound of the heart of the patient beating, and so forth.
  • an example 580 of a stimulation lead 14 configured for implantation in the thorax of the patient 499 may include sensor(s) 19.
  • the sensor(s) 19 are intrathoracic and therefore may provide a more sensitive and accurate measurement of changes and the status of respiration than sensors located at or in other parts of the patient’s body.
  • the stimulation lead 14 may include electrodes in lieu of the nerve cuff and may be situated for transvenous stimulation of the phrenic nerve.
  • the treatment system 10 may include one or more implantable sensors 19 coupled to and/or disposed on or within the IPG 12 in combination with (or independent of, in other examples) one or more implantable sensors 19 disposed on a lead (for example, leads 14, 16, and/or 20).
  • FIG. 7 illustrates a perspective view of external sensors of a disordered breathing therapy according to an example.
  • the disordered breathing therapy system 700 may be an example of the disordered breathing therapy system 10 in an implementation including one or more of a pulse oximeter 701, a pulsatility sensor 702, an effort belt 704, external motion sensor(s) 706, external transthoracic impedance sensors 708, external acoustic sensor(s) 710, and/or electromyography (EMG) sensors 712, and so forth.
  • a quantity of each component in FIG. 7 is an example only and other quantities of each, or any, component could be used.
  • the system 700 may be used in combination with the nerve stimulation implementations illustrated in FIGS. 3A-4C and may be used in combination with or in lieu of the various internal sensor implementations illustrated in FIGS. 5A-6.
  • the pulsatility sensor 702, the effort belt 704, the motion sensor(s) 706, the at least one transthoracic impedance sensor 708, the external acoustic sensor(s) 710, and/or the EMG sensors 712 may be examples of the external sensors 18 (for example, as shown in FIG. 1A).
  • One or more of the external sensors 18 may be communicatively coupled to the implantable device 12 in some examples, either directly (for example, via a wireless communication connection with the implantable device 12) or indirectly (for example, by communicating with the computing system 210 which, in turn, communicates with the implantable device 12).
  • the at least one effort belt 704 is implemented to detect breathing of a patient 799.
  • the effort belt 704 may be coupled around the chest of the patient 799.
  • the effort belt 704 may deform.
  • the effort belt 704 may include one or more pressure and/or stretch sensors to detect changes in pressure applied to the effort belt 704 and/or stretching of the effort belt 704 as a result of the patient 799 breathing. Accordingly, the effort belt 704 may sense parameters indicative of the breathing of the patient 799 which may be used to determine information such as a breathing rate of the patient 799.
  • the one or more EMG sensors 712 may be coupled to, and external to, a chest of the patient 799.
  • the EMG sensors 712 may include one or more electrodes configured to be coupled to the skin of the patient 799.
  • the EMG sensors 712 may measure electrical signals generated by muscles of the patient 799 when those muscles move (for example, expand and/or contract).
  • the EMG sensors 712 may be configured to measure electrical signals generated by the diaphragm of the patient 799 when the patient’s 799 diaphragm expands and/or contracts, and/or to measure electrical signals generated by the upper-airway muscles of the patient 799 when the patient’s upper- airway muscles expand and/or contract.
  • the EMG sensors 712 may sense parameters indicative of the breathing of the patient 799 which may be used to determine information such as a breathing rate of the patient 799.
  • the at least one pulsatility sensor 702 may be implemented to measure pulsatility parameters, such as pulse rate, heart rate, pulse amplitude fluctuations, a peripheral arterial tone, and/or SpO2, and so forth.
  • the at least one pulsatility sensor 702 may be coupled to a finger of the patient 799.
  • the at least one pulsatility sensor 702 may track pulsatility parameters of the patient 799, such as pulsatile volume changes in peripheral arterial beds as the heart of the patient 799 beats and/or as the patient 799 breathes. Accordingly, the at least one pulsatility sensor 702 may sense parameters indicative of the breathing of the patient 799 which may be used to determine information such as a breathing rate, heart rate, blood-oxygen concentration, and so forth, of the patient 799.
  • the IPG 12 may use motion data from the belt 704 to assess entrainment, presence of respiratory effort, respiratory rate, and so forth. Based on this assessment the IPG 12 may initiate, terminate, reduce, or increase stimulation to the phrenic nerve stimulation leads 14 and/or the upper-airway nerve stimulation leads 16 to fine tune the treatment provided to the patient 799. Similarly, the IPG 12 may assess data from the EMG sensors 712, the transthoracic impedance sensor(s) 708, the external motion sensor(s) 706, and/or the pulsatility sensor(s) 702 in order to initiate, terminate, reduce, or increase stimulation to the phrenic nerve stimulation leads 14 and/or the upper-airway nerve stimulation leads 16 to fine tune the treatment provided to the patient.
  • FIG. 8A illustrates a process 800 of implementing the therapy system 100 according to an example.
  • the process 800 is an example only and is not limiting.
  • the process 800 may be altered, such as by having acts added, removed, rearranged, combined, and/or performed concurrently.
  • the process 800 may be executed by the processor 50. Accordingly, where acts of the process 800 are described as being performed by the system 10 or the IPG 12, these acts may be executed by the processor 50 in some examples.
  • the disordered breathing therapy system 10 is configured to provide disordered breathing therapy by providing phrenic nerve stimulation and/or upperairway nerve stimulation.
  • the process 800 may be executed on an ongoing basis, and portions may be iterated for each target or actual breathing cycle.
  • the target or actual breathing cycle may be an entrained breathing cycle.
  • the process 800 is described as beginning when the patient goes to sleep. For example, process 800 begins after therapy activation 854 and during the therapy delivery period 860 as shown in FIG. 8B and as described below.
  • FIG. 8B examples of operational modes and time periods associated with disordered breathing therapy are shown.
  • the patient may be subject to a monitoring period 852 lasting days or weeks (for example, 1-6 weeks, 2-4 weeks, or 4-6 weeks).
  • the system 100 may operate in a monitoring mode 851 .
  • the system 100 may use sensor data to measure a sensed intrinsic respiration rate 855 of the patient.
  • the sensor data may include one or more of flow sensor data, transthoracic impedance data, blood oxygenation data, and so forth.
  • the sensed intrinsic respiration rate of the patient is a natural respiration rate that the patient exhibits without any stimulation from the implantable system 10.
  • the system 100 may store the intrinsic respiration rate of the patient.
  • the IPG 12 or treatment system 10 may be configured to receive instructions, such as operational parameters or other instructions, to cause the IPG 12 to provide or select the monitoring mode of operation 851.
  • the IPG 12 is configured to determine nerve stimulation parameters in the monitoring mode 851.
  • the nerve stimulation parameters determined during the monitoring mode 851 may be determined based on an optimization process to determine nerve stimulation parameters that are effective for the particular patient.
  • the nerve stimulation parameters may be one or more of hypoglossal, phrenic, ansa ccrvicalis (or other upper-airway nerve) stimulation parameters.
  • a physician may activate 854 therapy delivery to cause the system to provide a therapy mode 861, which enables the IPG 12 to provide therapy during regular sleep cycles of the patient at home and without real-time physician supervision.
  • the implantable system 10 may implement the process 800 shown in FIG. 8A or the process 801 shown in FIG. 8C or the process 1100 shown in FIG. 11A or the process 1101 shown in FIG. 11B in the therapy delivery mode 861.
  • the IPG 12 or treatment system 10 may be configured to receive instructions to cause the IPG 12 to provide or select a therapy mode 861.
  • the IPG 12 may be configured to deliver electrical stimulations to a respective nerve or nerves based on the nerve stimulation parameters that were determined during the monitoring mode 851.
  • the therapy mode 861 may be one of a respiration triggered stimulation rate therapy mode 864 or a pre-determined stimulation rate therapy mode 862.
  • the pre-determined stimulation rate may be one or more of a pre-determined phrenic nerve stimulation rate, or frequency, a pre-determined hypoglossal nerve stimulation rate, or frequency, or a pre-determined ansa cervicalis stimulation rate, or frequency.
  • the nerve stimulation therapy may be provided in the pre-determined stimulation rate mode 862 (or asynchronous mode 862) or the respiration triggered stimulation rate mode 864 (or synchronous mode 864).
  • the asynchronous mode 862 is a mode of therapy delivery in which the stimulation rate is prc-dctcrmincd and the IPG 12 is programmed 857 to deliver the stimulation at the pre-determined rate (e.g., based on the sensed intrinsic respiration rate 855 determined in the monitoring mode 851).
  • stimulation timing is not triggered in real-time by sensed respiration during one or more sleeping periods 869 of the patient within the therapy delivery period 860.
  • the system may provide the phrenic nerve stimulation at a pre-determined stimulation rate without a respiration-sensor-based trigger determinative of that frequency.
  • the respiration triggered stimulation rate mode 864 is a respiration triggered mode where the stimulation timing may be triggered in real-time during the one or more sleeping periods 869 of the patient within the therapy delivery period 860. These modes are described in further detail below in regard to FIGS. 9 A and 9B.
  • This nerve stimulation therapy may be provided during each sleeping period of a patient. For example, if a patient has a regular sleeping pattern of sleeping from 10 p.m. to 6 a.m. each night, then 10 p.m. to 6 a.m. may be the sleeping period of the patient. The therapy may be applied each night during this sleeping period once the system recognizes or confirms that the patient is asleep. While the patient is asleep and within a sleeping period, there may be various sleeping cycles, such as REM cycles, light non-REM cycles, deep non-REM cycles, and so forth. A patient may progress through multiple sleep cycles during a sleeping period. As discussed below, the disordered breathing therapy parameters may change dynamically during a sleeping period.
  • the disordered breathing therapy system 10 monitors and determines one or more sleep parameters.
  • Sleep parameters may include parameters which might be used to determine a patient’s sleep state.
  • the sleep state may be asleep or awake.
  • the sleep parameters may include time of day, patient motion, and patient pitch. Each of these parameters may be subject to a range or threshold criteria preprogrammed into the IPG 12 as operational parameters. In an implementation, if all three parameters satisfy respective criteria, then the IPG 12 may determine the patient to be asleep and initiate or continue therapy in an operational mode such as the therapy delivery mode 861. Conversely, if one or more of the three parameters fails to satisfy the respective criteria, then the IPG 12 may determine the patient to be awake and pause, discontinue, or delay therapy initiation. The IPG 12 may monitor each of these three parameters during the process 800, and similarly during the process 801, 1100, or 1101. The disordered breathing therapy system 10 may obtain the one or more sleep parameters from therapy data received from the clock 29, the external sensors 18 and/or the implantable sensors 19, as discussed in greater detail below.
  • the therapy system 10 determines that a patient is asleep based on one or more of an indication that the patient position, or pitch, corresponds to a lying down position, the patient activity, or motion, level being a low activity level, and a clock indication that the time of day corresponds to a pre-determined sleeping time (that is, a time during which the patient is expected to be sleeping).
  • the time during which the patient is expected to be sleeping may be a time during the night or may be a time programmed into the IPG 12 that is tailored to the patient. For example, if the patient regularly sleeps during the day, the predetermined sleeping time may include daylight hours or if the patient regularly sleeps during the night, the pre-determined sleeping time may include evening and nighttime hours.
  • the predetermined sleeping time may be a set of day and time range indications. Each indication may be of a format such as “Monday 9 PM to Tuesday 8 AM,” or “Sunday 10 AM to Sunday 6 PM,” or “Friday 12 AM to Friday 9AM,” to name a few illustrative examples not limiting of the disclosure.
  • the patient activity and patient position criteria may be subject to a time criterion, such that these parameters exceed a threshold or are outside of a range for a pre-determined amount of time.
  • the IPG 12 may determine the patient’s sleep state based on additional or alternative parameters to time of day, patient motion, and patient pitch.
  • additional or alternative parameters may include one or more of heart-rate parameters, sleep stage parameters, etc.
  • heart-rate parameters For example, while the patient is asleep and within a sleeping period, there may be various detectable sleeping cycles, or stages, such as rapid eye movement (REM) cycles, light non-REM cycles, deep non-REM cycles, and so forth.
  • REM rapid eye movement
  • a heart rate may be lower during sleep relative to the heart rate during waking hours.
  • the disordered breathing therapy system 10 determines a commencement of a sleeping period for the patient.
  • the disordered breathing therapy system 10 may determine the commencement of the sleeping period based on the one or more sleep parameters.
  • the disordered breathing therapy system 10 is configured to apply therapy when the patient is asleep. Accordingly, if the disordered breathing therapy system 10 determines based on the one or more sleep parameters that the patient is not asleep (804 NO), the process 800 returns to act 802 to repeatedly determine, monitor, and/or evaluate one or more sleep parameters. The disordered breathing therapy system 10 may continue executing acts 802 and 804 until a determination is made that the patient is asleep (804 YES), at which point the therapy system 10 commences a sleeping period and the process 800 continues to act 812.
  • the disordered breathing therapy system 10 evaluates respiratory information or data to determine which nerve stimulations to provide at the act 826.
  • the respiratory information may include sensor data, for example, data from one or more of the implantable sensors 19 and/or the external sensors 18.
  • the respiratory information may be indicative of airway obstruction and/or may be indicative of a lack of central drive.
  • the respiratory information may include respiratory drive synchronization (RDS) data indicative of a degree of synchronization between a sensed respiratory rate and a programmed stimulation rate. In an example not limiting of the disclosure, this degree of synchronization may be an entrainment index.
  • the implantable system 10 may move from the act 804 to the act 826 based on a pre-determined stimulation selection as discussed in regard to FIGS. 11A and 11B.
  • the respiratory information may include information indicative of at least one respiratory parameter of the patient.
  • the IPG 12 may determine and/or evaluate the respiratory information based on signals and/or data from one or more of the external and/or internal sensors discussed herein.
  • Respiratory parameters include one or more parameters related to the breathing of the patient, such as one or more breathing-rate parameters, one or more lung-volume parameters, one or more blood-oxygen parameters, one or more chest-motion parameters, one or more acoustic parameters indicative of patient-breathing sounds, and so forth. Respiratory parameters may be used to determine how effectively the patient is breathing, and whether providing electrical stimulation to the patient is effectively treating the patient’s disordered breathing. Respiratory parameters may be sensed via the sensors 18 and/or 19.
  • act 812 may include evaluating respiratory data or information for evidence or indications of decreased airway patency and/or airway obstruction, and indications of a lack of respiratory drive as underlying causes of disordered breathing, which may include apneas. If the respiratory data indicates a decreased respiratory drive, which may be a lack of respiratory drive, and without indications of decreased airway patency, act 826 may only include providing electrical stimulation of one or more phrenic nerves as shown in the process 826a in FIG. 9A as an example of the act 826 in FIG. 8A.
  • act 826 may only include providing electrical stimulation of one or more upper-airway nerves as shown in the process 826b in FIG. 9B as an example of the act 826 in FIG. 8A. If the respiratory data indicates a combination of decreased airway patency and a decreased and/or a lack of respiratory drive, act 826 may include providing electrical stimulation of one or more upper-airway nerves along with one or more phrenic nerves in a combination of FIGS. 9 A and 9B. Furthermore, if the respiratory data indicated disordered breathing but is indeterminate with regard to the origin of disordered breathing, act 826 may include providing electrical stimulation of one or more upper-airway nerves along with one or more phrenic nerves.
  • act 812 may include evaluation of respiration information to determine the parameters of the disordered breathing therapy not only in terms of which leads are activated (e.g., upper-airway nerve stimulation leads 16 and/or phrenic nerve stimulation leads 14), but also when the leads are activated, the relative timing of these activations, and the stimulation intensity applied to the leads.
  • Parameters for stimulation as set and controlled by one or more of the external computing device 210 or the IPG 12 may include a relative timing between stimulations via the leads 14 and stimulations via the leads 16 and/or an adjustment of the stimulation intensity via control of various stimulation parameters discussed in regard to FIGS. 10A and 10B.
  • Nerve stimulation may be characterized by one or more electrical stimulation parameters, such as stimulation or current duration, stimulation or current intensity, stimulation or current ramp-up time, stimulation or current ramp-down time, stimulation polarity (for example, monophasic or biphasic), and other parameters discussed below.
  • the treatment system 10 may modify one or more stimulation parameters to modify the disordered breathing therapy, which may include entrainment.
  • the treatment system 10 may determine how to modify the one or more stimulation parameters in some examples.
  • the computing system 210 may determine how to modify the one or more stimulation parameters in addition to, or in lieu of, the treatment system 10 and provide this determination to the treatment system 10.
  • the IPG 12 may collect sensor data from one or more of the implantable sensors 19 or the external sensors 18.
  • the IPG 12 may store the sensor data and analyze the sensor data to determine stimulation parameters and/or modifications of stimulation parameters for disordered breathing therapy.
  • the IPG 12 may store the sensor data and periodically (for example, at or in conjunction with a patient visit to a physician’s office) download or otherwise transmit the sensor data to the external computing device 210.
  • the external computing device 210 may analyze the sensor data to determine stimulation parameters or modifications to stimulation parameters for disordered breathing therapy.
  • the external computing device 210 may then update programming of the IPG 12 to reflect these modifications. This modification may occur prior to the delivery of therapy and/or subsequent to therapy delivery 826 at the act 840.
  • the treatment system 10 may provide disordered breathing therapy.
  • the disordered breathing therapy may include stimulation of nerves related to airway patency and/or stimulation of nerves related to diaphragm contractions as shown in more detail in regard to FIGS. 9A and 9B.
  • the presence of CSA events, OSA events, and combination apnea events including mixed apnea events may vary over the course of the sleeping period. For example, for a particular patient, particular apnea events may present during certain times during the sleeping period or during particular sleep stages. As another example, particular apnea events may present only in particular body positions (for example, only in a supine position but not in a side-sleeping position). Furthermore, the presentation of combination apnea events may change the stimulation parameters used for each therapy as compared to when either lack of respiratory drive or decreased airway patency present alone.
  • the system 10 may deliver electrical stimulation for decreased airway patency together with electrical stimulation for lack of respiratory drive.
  • One or more phrenic nerve stimulation pulses and one or more upper-airway nerve stimulation pulses within a stimulation cycle may be delivered simultaneously.
  • the IPG 12 may stimulate the nerve(s) related to airway patency within a particular time interval of stimulation of the phrenic nerve.
  • the stimulation of nerve(s) related to airway patency may occur simultaneously with the phrenic nerve stimulation or at a particular time interval before or after the phrenic nerve stimulation.
  • the particular time interval may be on the order of milliseconds.
  • This stimulation pattern may recur on each breathing cycle.
  • the recurrence may be asynchronous (e.g., according to the mode 862 in FIG. 8B) and thus may not be triggered by a breathing cycle event such as, for example, inhalation and/or exhalation.
  • decreased airway patency may be characterized by a full or partial physical obstruction in the airway of the patient. Treating decreased airway patency may include removing the physical obstruction, or mitigating the effects of the physical obstruction such that the patient breathes effectively.
  • the therapy system 10 integrates the treatment of decreased airway patency with the treatment of lack of respiratory drive by delivering electrical stimulation to the hypoglossal nerve in conjunction with, for example, stimulating a phrenic nerve.
  • the therapy system 10 treats decreased airway patency by delivering electrical stimulation to the ansa cervicalis in addition to, or in lieu of, the hypoglossal nerve.
  • Electrical stimulation of these nerves may stimulate muscles in the upper airway of the patient to open up the airway and/or stiffen the airway which may improve the efficacy of the phrenic nerve stimulation therapy.
  • the electrical stimulation may cause the patient’s tongue to move forward, thereby rendering the airway unobstructed. Opening the airway may synergize with the respiratory-drive-related aspects of the disordered breathing therapy by establishing a clear, stiffened airway for the patient to breathe through once phrenic nerve stimulation therapy has established a desired breathing pattern.
  • Stimulation of the ansa cervicalis may innervate the infrahyoid muscles and contraction of one or more infrahyoid muscles may stiffen the airway.
  • a stiffened airway may be distinct from an opened or unobstructed airway. For example, if the airway is open and unobstructed but insufficiently stiffened, then that airway may close or collapse too soon at the end of an expiration and therefore reduce the efficacy of inspiration. Thus, merely opening an airway (for example, providing a nerve stimulation that results in data indicating a reduction or an elimination of an obstruction) may be insufficient to provide effective disordered breathing therapy if that opening is not maintained and coordinated with at least a portion of the diaphragm contraction and/or relaxation.
  • Electrical stimulation provided to upper-airway nerves of the patient may be characterized by one or more stimulation parameters, such as stimulation or current duration, stimulation or current intensity, stimulation or current ramp-up time, stimulation or current rampdown time, stimulation polarity, and other parameters.
  • the treatment system 10 may modify one or more stimulation parameters to modify the upper-airway nerve stimulation therapy.
  • the treatment system 10 may determine how to modify the one or more stimulation parameters in some examples.
  • the computing system 210 may determine how to modify the one or more stimulation parameters in addition to, or in lieu of, the treatment system 10.
  • the IPG 12 may collect sensor data from one or more of the implantable sensors 19 or the external sensors 18.
  • the IPG 12 may store the sensor data and analyze the sensor data to determine modifications to stimulation parameters for disordered breathing therapy.
  • the IPG 12 may store the sensor data and periodically (for example, at or in conjunction with a patient visit to a physician’s office) download or otherwise transmit the sensor data to the external computing device 210.
  • the external computing device 210 may analyze the sensor data to determine modifications to stimulation parameters for disordered breathing therapy.
  • the external computing device 210 may then update programming of the IPG 12 to reflect these modifications.
  • these modifications may change the stimulation duration of the upper-airway nerve stimulation and/or change the relative timing between the upper-airway nerve stimulation therapy and the phrenic nerve stimulation therapy.
  • the stimulation duration of the upper-airway nerve(s) may determine the efficacy of the phrenic nerve stimulation therapy because the degree to which an airway is open or stiffened may determine the ability of a particular diaphragm contraction to effectively cause air flow into the lungs.
  • the IPG 12 and/or the external computing device 210 may analyze sensor data indicative of effects of both therapies in order to determine modifications to stimulation parameters for individual leads directed at one therapy.
  • the stimulation parameters for the lead 16 configured to stimulate the upper-airway nerve(s) e.g., the hypoglossal nerve and/or ansa cervicalis
  • the stimulation parameters for the lead 16 configured to stimulate the upper-airway nerve(s) may be determined at least in part by sensor data indicating the effect on respiration of stimulation of the phrenic nerve by the lead 14.
  • a therapy-specific indicator which is determined based on this sensor data (that is, indicative of the effect on respiration of stimulation of the phrenic nerve by the lead 14), such as degree of synchronization between a sensed respiration rate and a programmed stimulation rate, may be indicative, either directly or indirectly, of the effects of stimulation provided by either or both of the lead 14 (for example, to the phrenic nerve) and the lead 16 (for example, to the hypoglossal nerve) on the respiratory system.
  • the stimulation parameters for the phrenic nerve stimulation therapy may determine the efficacy of the upper-airway nerve stimulation therapy because the extent of a particular diaphragm contraction relative to the degree of obstruction or stiffening of the airway may determine the ability of a particular upper-airway nerve stimulation to effectively cause air flow into the lungs.
  • the IPG 12 and/or the external computing device 210 may analyze sensor data indicative of effects of both therapies, as either combined indicators or therapyspecific indicators, in order to determine modifications to stimulation parameters for individual leads directed at one therapy.
  • the stimulation parameters for the lead 14 configured to stimulate the phrenic nerve may be determined at least in part by sensor data indicating the effect on respiration of stimulation of the hypoglossal nerve (and/or ansa cervicalis) by the lead 16.
  • the implantable system 10 determines if the disordered breathing therapy meets therapy effectiveness criteria or if the therapy requires an adjustment with respect to one or more combined-effectiveness criteria.
  • the implantable system 10 may evaluate the effectiveness of the disordered breathing therapy based on combined-effectiveness parameters received from at least one of the sensors 18, 19.
  • one or more combined-effectiveness parameters based on the sensor data may provide an indication of the effectiveness of the provided therapy with regard to combination apneas, in particular a mixed apnea in which both lack of respiratory drive and decreased airway patency both contribute to an apnea event.
  • the one or more combined- effectiveness parameters based on the sensor data may provide an indication of the effectiveness of the provided therapy with regard to either one or both of the lack of respiratory drive and decreased airway patency without specificity as to a mechanism.
  • the combined- effectiveness parameters may indicate an overall effectiveness of the provided therapy without an identification of the cause of disordered breathing being the lack of respiratory drive or the airway obstruction.
  • the sensors 18 and/or 19 may detect a lack of or reduction in effort to breathe (that is, lack of or reduction in respiratory drive).
  • the sensors 18 and/or 19 may also detect respiratory effort against a restricting or restricted airway (that is, an airway that is closing or has closed).
  • the sensors 18 and/or 19 may additionally determine a total time of either or both of these events.
  • combincd-cffcctivcncss parameters may include both the timing of sensing the lack of respiratory drive and the timing of respiratory effort against the rcstricting/rcstriclcd airway and identify them as an apnea event if the total time meets a target threshold range, for example 5-10 seconds, or a maximum time target, for example, 10 seconds.
  • the sensors 18 and/or 19 may detect the order of these events. For example, a sequence of lack of respiratory drive followed by respiratory effort against the restricted/restricting airway, or vice versa.
  • the implantable system 10 may use the sensor data to not only detect the occurrence of a CSA event or an OSA event, but to detect a combined apnea and specifically identify the nature of the combined apnea. With this information, the implantable system 10 may adjust and tailor the combined therapy to the particular manifestation of the combined apnea and the effect of the interaction between the lack of respiratory drive and airway obstruction on the respiratory system as a whole.
  • the combined-effectiveness criteria may include one or more ranges (for example, thresholds).
  • the implantable system 10 may evaluate the effectiveness of the combined treatment by comparing the combined-effectiveness parameters to one or more respective ranges of values.
  • the one or more combined-effectiveness criteria may change over time such that one or more combined-effectiveness parameters that meet the one or more combined-effectiveness criteria at one point in time (and is thus referred to in shorthand as effective treatment at that point in time) may not meet the one or more combined-effectiveness criteria at another point in time (and is thus referred to in shorthand as ineffective treatment at that point in time).
  • the one point in time and the another point in time may be during the same sleeping period.
  • the automatic changing of the combined-effectiveness criteria may provide for more effective determination of the efficacy of the combined therapy and/or more effective adjustment and/or tailoring of the combined therapy.
  • the combined-effectiveness parameters may include blood-oxygen parameters of the patient.
  • the sensors 18 and/or 19 may include a pulse oximeter, and the combined-effectiveness parameters may include SpO2 level information. Determining whether the combined treatment is effective may include determining whether the SpO2 level is above a threshold SpO2 level.
  • the sensors 18 and/or 19 may include at least one pulsatility sensor, and the combined-effectiveness parameters may include one or more pulsatility parameters, such as a peripheral arterial tone level, pulse rate, heart rate, pulse amplitude fluctuations, and so forth.
  • Determining whether the combined treatment is effective may include determining whether the peripheral arterial tone level is above a threshold peripheral arterial tone level.
  • Other indicators of treatment effectiveness may include blood oxygen, sleep stage, and/or heart rate. For example, increases in blood oxygen with therapy, stable average blood oxygen levels, or fluctuations in blood oxygen consistent with ordered breathing may indicate an effective therapy.
  • the achievement of various sleep stages, such as restorative sleep stages like those involving rapid eye movement, and the duration of these sleep stages may indicate less disruption of sleep due to disordered breathing and, therefore, an effective therapy.
  • a reduction in heart rate or fluctuations in heart rate consistent with ordered breathing may indicate effective therapy.
  • the implantable system 10 may determine the effectiveness of therapy based on transthoracic impedance.
  • a transthoracic impedance sensor implanted within the thoracic cavity may measure transthoracic impedance as an indicator of respiration.
  • the IPG 12 may receive the transthoracic impedance signal and store the transthoracic impedance data.
  • One or more of the IPG 12 or the external computing device 210 may analyze the transthoracic impedance data to evaluate respiratory patterns.
  • the IPG 12 may download or otherwise transmit the transthoracic impedance data to the external computing device 210 for analysis and diagnostic interpretation at the external computing device 210.
  • the respiratory patterns may indicate normal or ordered breathing and apneas, hyperpneas, or other disordered breathing.
  • the IPG 12 and/or the external computing device 210 may determine the effectiveness of therapy based on a comparison of amounts of ordered breathing with amounts of disordered breathing. For example, a threshold ratio or a target range of total duration or numbers of episodes of ordered breathing may indicate an effective therapy. Thus, an effective therapy may or may not eliminate disordered breathing. In some cases, the therapy may be deemed effective by reducing the disordered breathing below a target threshold such that the clinical impact on a patient is minimized or reduced.
  • transthoracic impedance as an indicator of respiration.
  • other sensed parameters such as motion, pressure, and acoustics may provide indicators of respiration from the IPG 12 and/or the external computing device 210 may determine an effectiveness of therapy.
  • the IPG 12 may use the transthoracic impedance and/or another sensed parameter such as motion, pressure, and acoustics to determine therapy effectiveness and may incrementally adjust stimulation current and/or other stimulation parameters to improve the therapy effectiveness.
  • the entrainment index or other therapeutic index may increase with changes in stimulation parameters that improve therapy.
  • the process 800 returns to act 806 to confinn that the patient is still asleep. Act 806 is substantially the same as act 804 as described above as an evaluation of monitored sleep parameters. Acts 826 and 830 may be repeated as therapy is delivered to the patient while the patient remains asleep. If the implantable system 10 determines that the combined treatment is not effective and an adjustment is necessary (830 YES), then the process 800 proceeds to the act 840 to adjust stimulation parameters. Modifying the treatment may include modifying the upper-airway nerve stimulation parameters, modifying the phrenic nerve stimulation parameters, modifying the relative timing and coordination of these therapies, providing only one of these therapies, or combinations thereof.
  • parameters of combined therapy may include relative timing of the stimulations from leads 14 and 16 and/or adjustments to stimulation (for example, one or more of current, voltage, ramp, duration, frequency, and so forth) based on the effect of upper-airway nerve therapy on phrenic nerve stimulation therapy indicators and/or the effect of phrenic nerve stimulation therapy on upper-airway nerve therapy indicators.
  • a nerve stimulation that results in a stiffening of the airway may reduce the amount of diaphragm contraction needed to satisfy respiration targets because the stiffer airway makes it easier for air to flow into the lungs.
  • the evaluation and adjustments at the acts 830 and 840 may focus on the wholistic behavior of the respiratory system rather than the behavior of components like upper airway and diaphragm.
  • Act 808 is substantially the same as act 804 as act 804 as described above as an evaluation of monitored sleep parameters. Acts 826, 830, and 840 may be repeated as therapy is adjusted and delivered to the patient while the patient remains asleep.
  • the system 10 substantially continuously monitors sleep parameters such that the system 10 provides therapy with possible modifications for efficacy as long as the sleep parameters satisfy the criteria indicating that the patient is asleep.
  • FIG. 8C illustrates a process 801 of implementing the therapy system 100 according to an example.
  • the process 801 is an example only and is not limiting.
  • the process 801 may be altered, such as by having acts added, removed, rearranged, combined, and/or performed concurrently.
  • the process 801 may be executed by the processor 50. Accordingly, where acts of the process 801 are described as being performed by the system 10 or the IPG 12, these acts may be executed by the processor 50 in some examples.
  • the acts of process 801 are substantially as described in regard to FIG. 8A and not repeated here for brevity.
  • the evaluation of the respiratory data may be a deterministic, or an empirical, or heuristic, evaluation of the respiratory data based on pre-determined criteria.
  • the respiratory data evaluation may include a more sophisticated evaluation using an evaluation of a respiratory model, or other physiological model, to determine an expected therapy result based on the respiratory data.
  • the act 828 includes a comparison between an actual result and the expected result from the act 824.
  • the act 831 includes this comparison result in the evaluation of the combined therapy such that the adjustments at act 840 may also reflect the comparison of the expected therapy results with actual results at the act 828 where the models used for these evaluations address the overall function of the respiratory system.
  • the process 801 determines that the combined treatment is effective and an adjustment is unnecessary (831 NO), then the process 801 returns to act 806 to confirm that the patient is still asleep. Act 806 is substantially the same as act 804 as described above as an evaluation of monitored sleep parameters. Acts 826 and 831 may be repeated as therapy is delivered to the patient while the patient remains asleep. If the implantable system 10 determines that the combined treatment is not effective and an adjustment is necessary (831 YES), then the process 801 proceeds to the act 840 to adjust stimulation parameters. Modifying the treatment may include modifying the upper-airway nerve stimulation parameters, modifying the phrenic nerve stimulation parameters, modifying the relative timing and coordination of these therapies, providing only one of these therapies, or combinations thereof.
  • the process 801 may reevaluate the models at 824 based on data reflective of the modified therapy and use a reevaluated expected therapy result for the comparison at the act 828.
  • FIG. 10A illustrates a graphical depiction 1000 of electrical stimulations provided by the implantable system 10 according to an example.
  • the graphical depiction 1000 includes a phrenic nerve stimulation graph 1002 and an upper-airway nerve stimulation graph 1004.
  • the electrical stimulations are provided a series of stimulation pulses 1080 where each stimulation pulse 1080 may be provided as a pulse train 1091.
  • each stimulation pulse 1080 may be a pulse burst where the burst refers to the series of individual pulses of the pulse train.
  • the phrenic nerve stimulation graph 1002 is indicative of electrical stimulation to provide phrenic nerve stimulation therapy, and includes a trace 1006 indicative of electrical stimulation provided by the implantable system 10 to a target tissue of the patient via the phrenic nerve stimulation leads 14.
  • the upper-airway nerve stimulation graph 1004 is indicative of upper-airway nerve stimulation therapy and includes a trace 1008 indicative of electrical stimulation provided by the implantable system 10 to a target tissue (for example, a hypoglossal nerve and/or ansa cervicalis) of the patient via the upperairway nerve stimulation leads 16.
  • a target tissue for example, a hypoglossal nerve and/or ansa cervicalis
  • the IPG 12 may align a delivery start time of the hypoglossal nerve electrical stimulations with a delivery start time of the phrenic nerve electrical stimulations or stagger the delivery start time of the hypoglossal nerve electrical stimulations relative to the delivery start time of the phrenic nerve electrical stimulations such that the delivery start time of the hypoglossal nerve electrical stimulations is earlier or later than the delivery start time of the phrenic nerve electrical stimulations. Further examples are discussed with regard to FIG. 10A.
  • the graphs 1002 and 1004 are illustrative of various temporal synchronization patterns between the electrical stimulation of the phrenic nerve! s) and the electrical stimulation of the upper-airway nerve(s). As discussed below, these stimuli may be temporally aligned or may be temporally staggered. In an implementation, regardless of the temporal synchronization pattern, the IPG 12 may determine upper-airway nerve stimulation timing relative to the phrenic nerve timing. As discussed herein, the implantable therapy system 10 may provide the electrical stimulation of the one or more phrenic nerves in an asynchronous therapy mode 862 or a synchronous therapy mode 864.
  • the system 10 provides the phrenic nerve stimulation at a pre-determined rate without a respiration-sensor-based trigger.
  • the system 10 provides the phrenic nerve stimulation according to a respiration- sensorbased trigger.
  • the IPG 12 may provide the upper-airway nerve stimulation without a respiration- sensor-based trigger such that the timing of the upperairway nerve stimulation is relative to and controlled by the phrenic nerve stimulation timing.
  • the central control of both therapies by the IPG 12 may enable this coordinated timing such that the IPG 12 may trigger the upper- airway nerve electrical stimulations based on a delivery of the phrenic nerve electrical stimulations but without a trigger based on sensed respiration of the patient during the sleeping period.
  • the phrenic nerve stimulation timing is preprogrammed (e.g., during the asynchronous therapy mode 862) then the upper-airway nerve electrical stimulation may be pre-programmed as well for a stimulation delivery timing determined from the pre-programmed phrenic nerve stimulation timing.
  • the upper-airway nerve electrical stimulation may be pre-programmed to occur at a time interval relative to the phrenic nerve stimulation but without a sensed respiration trigger for delivery such that the phrenic nerve timing controls delivery of both the upper-airway nerve stimulations and the phrenic nerve stimulations.
  • the graphs 1002, 1004 may be temporally aligned with one another.
  • the implantable system 10 may provide both phrenic and upper-airway nerve electrical stimulation therapies with the durations of these therapies overlapping one another at least partially. The lack of respiratory drive electrical stimulations may be applied simultaneously for at least some portion of time.
  • phrenic and upper-airway nerve electrical stimulation therapies may be applied simultaneously.
  • the graphs 1002, 1004 may not be temporally aligned with one another.
  • the implantable system 10 may provide phrenic and upper-airway nerve electrical stimulation therapies in a staggered fashion without any temporal overlap.
  • FIG. 10B illustrates an example of an electrical stimulation trace 1090.
  • the electrical stimulation includes a series of stimulation pulses 1080.
  • Each stimulation pulse 1080 may be provided as a pulse train 1091 where the stimulation pulse 1080 is a pulse envelope for the individual pulses (for example, the n pulses 1085a, 1085b . . . , 1085n) of the pulse train 1091.
  • the leads 14, 16 may each include electrodes to deliver electrical stimulation to a target nerve according to the electrical stimulation trace 1090.
  • the processor 50 may control the stimulation circuitry 58 to provide the electrical stimulation pulses to the leads 14, 16.
  • the stimulation pulses 1080 are delivered at a stimulation pulse period corresponding to a stimulation rate.
  • the stimulation rate may be about 0.1-0.5 Hz in correspondence with a desired stimulated breathing rate of 10-18 breaths per minute (for example, a stimulation rate of about which may be 0.1-0.3 Hz).
  • a stimulation pulse 1080 may be 1-4 seconds in total duration. In the example of FIG. 10B, the total duration of the stimulation pulse 1080 is the pulse train duration 1050. For example, the stimulation pulse may be about 2 seconds in total duration.
  • Each stimulation pulse 1080 may be provided as a pulse train having a pulse train period 1066 corresponding to a pulse train frequency. The pulse train frequency may be of 10-40 Hz.
  • An electrical stimulation profile stored in the IPG 12 may specify parameters of the electrical stimulation provided via the stimulation circuitry. These parameters may include one or more of the stimulation rate (corresponding to the stimulation pulse period 1065), the pulse train duration 1050, and the pulse train frequency (corresponding to the pulse train period 1066). Additionally, the parameters may include a time between stimulation pulses 1030.
  • the pulse train envelope forming each stimulation pulse 1080 defines the maximum pulse amplitude 1040 as the maximum amplitude of one or more individual pulses within the pulse train. Each individual pulse may be further characterized by a pulse width 1060. As illustrated in FIG.
  • the individual pulses of the pulse train may not all have the same pulse amplitude 1045 and may vary in amplitude so as to ramp up 1098 the energy of the stimulation pulse 1080 and/or ramp down 1099 the energy of the stimulation pulse 1080.
  • the ramp up may occur over a ramping-up time, for example, the time interval for the ramping up pulses 1098.
  • the ramp down may occur over a ramping-down time, for example, the time interval for the ramping down pulses 1099.
  • the stimulation pulse 1080 may not include a ramp up and/or a ramp down.
  • the IPG 12 configuration with regard to operational parameters and/or with regard to stimulation circuitry 58 may exclude a square wave capability for an electrical stimulation profile in which the pulse trains exclude both the ramping-up period and the ramping-down period.
  • the electrical stimulation delivered by the IPG 12 may be characterized by one or more electrical stimulation parameters.
  • the IPG 12 may adjust one or more of these parameters to titrate the electrical stimulation energy delivered to a target nerve.
  • the electrical stimulation parameters may include pulse train parameters.
  • the pulse train parameters may include one or more of a pulse amplitude 1045, a maximum pulse amplitude 1040, a pulse train period (or frequency) 1066, a pulse width 1060, and/or a pulse train duration 1050.
  • the pulse amplitude 1045 may include an amplitude of at least one of the ramping-up pulses, an amplitude of the constant-amplitude pulses, and/or an amplitude of at least one of the rampingdown pulses.
  • the pulse train parameters may further include one or more of a time over which an amplitude of the pulses is ramped up, a time over which the amplitude of the pulses is ramped down, a number of ramping-up pulses, and/or a number of ramping-down pulses.
  • the stimulation parameters may further include one or more of the stimulation rate corresponding to the stimulation pulse period 1065, the time between stimulation pulses 1030, a stimulation current, a stimulation voltage, and a stimulation polarity (for example, monophasic or biphasic), stimulation energy ramps, and so forth.
  • the stimulation energy ramps may include changes in energy delivered by a stimulation pulse 1080 over a series of stimulation pulses 1080.
  • One or more electrical stimulation parameters may be adjusted to change the energy delivered by stimulation pulses 1080 over time to titrate the stimulation energy delivered to the target nerve. Such titration may achieve a desirable balance between patient comfort and stimulation efficacy. For example, more intense electrical stimulation of a patient’ s phrenic nerve may yield higher activation of a patient’s diaphragm, which may increase the efficacy of nerve stimulation therapy in some examples.
  • more intense electrical stimulation may also yield a greater sensory response from a patient.
  • a patient may feel more discomfort as the stimulation intensity is increased. Experiencing discomfort may adversely impact a patient’s sleep.
  • treatment according to that particular set of stimulation parameters may be contraindicated if the particular set of stimulation parameters causes the patient to wake up and lose sleeping time, for example due to discomfort produced by the particular set of stimulation parameters. It is therefore beneficial to the efficacy of stimulation therapy to identify stimulation parameters that produce a desired muscle response (for example, diaphragm contraction and expansion) while minimizing or avoiding patient discomfort.
  • the IPG 12 may ramp up the stimulation amplitude to increase the intensity of the stimulation, or may ramp down the stimulation amplitude to decrease the intensity of the stimulation.
  • the stimulation amplitude may vary over a range from a minimum amplitude for a pulse train to a maximum amplitude for the pulse train.
  • the individual pulses within the pulse train may vary in amplitude but the maximum amplitude defines the maximum amplitude reached during a stimulation pulse train.
  • FIG. 9A illustrates further details of the act 826 of the processes 800 and 801, according to an example.
  • the process shown in FIG. 9A is an example only and not limiting and can be altered, such as by having acts added, removed, rearranged, combined, and/or performed concurrently.
  • the provision of disordered breathing therapy 826 includes a phrenic nerve stimulation subsystem 902 that enables the IPG 12 to provide nerve stimulation for phrenic nerve stimulation therapy and an upper-airway nerve stimulation subsystem 904 that enables the IPG 12 to provide nerve stimulation for upper-airway nerve stimulation therapy.
  • the subsystems 902 and 904 provide an example of act 826.
  • the act 826 may deliver only the phrenic nerve stimulation therapy or may deliver both therapies. In this manner, the therapy system 10 may treat CSA or combination apneas.
  • the implantable system 10 may implement only the phrenic nerve stimulation subsystem 902 in order to deliver and modify phrenic nerve stimulation therapy. In some implementations, the implantable system 10 may implement only the upperairway nerve stimulation subsystem 904 in order to deliver and modify upper-airway nerve stimulation therapy. In some implementations, the implantable system 10 may execute the upper-airway nerve stimulation subsystem 904 together with the phrenic nerve stimulation subsystem 902. In an example, the external computing device 210 may program the IPG 12 to deliver stimulation at parameters defining one or more of current amplitude, pulse width, pulse frequency, and frequency or duration of pulse train envelopes. The IPG 12 may deliver the current according to these parameters.
  • the implantable system 10 provides electrical stimulation to one or more phrenic nerves of the patient via the phrenic nerve stimulation lcad(s) 14.
  • the processor 50 may control or otherwise cause the stimulation circuitry 58 to deliver and/or modify the electrical stimulation to the one or more phrenic nerves of the patient via the phrenic nerve stimulation lead(s) 14.
  • the phrenic nerve stimulation 906 may include providing RDS therapy 908 in an asynchronous mode 862 to entrain the patient’s breathing and maintain entrainment.
  • the implantable system 10 may provide entrainment therapy, or RDS therapy 908, at the act 906.
  • the implantable system 10 may provide the RDS therapy 908 at the beginning of each sleeping period of a patient in response to a determination that the patient is asleep.
  • the disordered breathing therapy system 10 may provide electrical stimulation to a phrenic nerve of the patient via the phrenic nerve stimulation leads 14, as discussed above.
  • the entrainment therapy may include electrical stimulation of the hypoglossal nerve or the ansa cervicalis of the patient via the upper- airway nerve stimulation leads 16 in addition to stimulation via the phrenic nerve stimulation leads 14. This is because in some cases, the stimulation via the phrenic nerve stimulation leads 14 may be insufficient to entrain without stimulations to open or stiffen the upper airway.
  • the RDS engine 24 may evaluate the RDS data and adjust one or more of the current parameters as needed to improve or otherwise adjust synchronization of the patient’s breathing to the stimulation. Once synchronization conditions are met, the implantable system 10 may continue to provide the phrenic nerve stimulation therapy and/or the upper-airway nerve therapy to remedy disordered breathing that arises during a patient’s sleep cycle.
  • the system 100 may determine a sensed intrinsic respiration rate 855 for the patient.
  • the system 100 may then program 857 the IPG 12 to entrain the patient to an entrainment respiration rate based on the intrinsic respiration rate sensed in the monitoring mode 851.
  • the entrainment respiration rate may be at or within a predetermined interval from the sensed intrinsic respiration rate.
  • the predetermined interval may be 2-3 breaths per minute below the sensed intrinsic respiration rate.
  • the system 10 may pre-program 857 the IPG 12 for the stimulation rate prior to therapy activation 854.
  • the relationship between the entrainment respiration rate and a patient’s intrinsic respiration rate may be determined empirically.
  • the IPG 12 may provide stimulations of the phrenic nerve at an entrainment stimulation rate that is 2-3 breaths per minute below the sensed intrinsic respiration rate. For instance, if the sensed intrinsic respiration rate is 13 breaths per minute (bpm), then the pre-programmed stimulation rate for entrainment may be 10 stimulations per minute.
  • the IPG 12 may apply the stimulations at the entrainment frequency at a first energy and then incrementally increase the energy until the patient’s breathing becomes synchronized to the entrainment frequency.
  • the determination that the patient’s breathing is synchronized to the entrainment frequency may be based on an evaluation of an entrainment indicator, or an RDS indicator.
  • the entrainment or RDS indicator may include an entrainment index, an SpO2 level, a diaphragm motion parameter, combinations thereof, and/or another indicator of the efficiency and/or frequency of respiration.
  • the RDS engine 24 may evaluate an entrainment index and adjust the disordered breathing therapy at the act 826 until a patient reaches a target entrainment index. If the entrainment indicator does not meet the desired degree of entrainment, the IPG 12 may modify one or more of the stimulation parameters and repeat the entrainment therapy until the desired degree of entrainment is met.
  • the synchronous mode 864 may not include the RDS therapy 908 at the act 906.
  • the therapies described in regard to FIGS. 8 A, 8C, 9 A, 9B, 11 A, and/or 1 IB may each be applied in an asynchronous therapy mode 862 or a synchronous therapy mode 864.
  • the stimulation rate of the electrical stimulation applied to the phrenic nerve may be programmed to a predetermined value and/or vary within a predetermined range such that the trigger for delivery of each pulse train envelope is the programmed time interval.
  • predetermined values and/or ranges may be set by a physician based on information acquired in the monitoring mode 851.
  • this pulsetrain-delivery trigger excludes a sensed inspiration or other sensed respiratory parameter by the patient.
  • the implantable system 10 may not deliver the stimulation as a response triggered by a respiratory parameter detected by a respiration sensor such as a flow sensor, a transthoracic impedance sensor, a blood oxygen sensor, and/or other physiological sensor.
  • the implantable system 10 may provide the phrenic nerve stimulation at the entrainment frequency provided by the RDS therapy 908 at the act 906.
  • the entrainment frequency used during the RDS therapy 908 at the act 906 as delivered in the therapy mode 861 may be derived from a sensed respiration 855 of the patient in the monitoring mode 851.
  • the entrainment frequency is determined prior to the provision of therapy during each sleeping period of the patient.
  • the system 100 may utilize sensed respiratory parameters to determine the intrinsic respiration rate of the patient.
  • respiration sensed in real-time in the therapy delivery mode 861 may not provide the trigger for delivery of a phrenic nerve stimulation at the acts 906 or 908.
  • the implantable therapy controller 10 may be configured to provide electrical stimulation to the phrenic nerve of the patient in response to a preprogrammed stimulation rate trigger that excludes a sensed respiratory cycle of the patient.
  • the implantable therapy controller 10 may be configured to provide the electrical stimulation to the phrenic nerve of the patient in response to a trigger that includes one or more aspects of a sensed respiratory cycle 868 (e.g., inhalation, exhalation, etc.) of the patient.
  • a trigger for electrical stimulation in the synchronous therapy delivery mode may be respiration sensed in real-time in the therapy delivery mode 861 (i.e., the one or more aspects of the sensed respiration cycle 868).
  • the implantable system 10 may be configured to provide the electrical stimulation to the phrenic nerve of the patient in response to a lack of a sensed respiration of the patient within a predetermined interval of an expected time for the sensed respiration.
  • the expected time for the sensed respiration may be predetermined and may be the intrinsic respiration rate of the patient as determined in the monitoring mode 851.
  • the IPG 10 may synchronize or coordinate stimulation of nerves related to airway patency with particular instances of stimulation of nerves related to diaphragm contractions based on the RDS data, which includes the entrainment frequency.
  • the implantable system 10 may not require an analysis of a patient’s air flow or breathing data (for example, may not require an analysis of impedance and/or thoracic pressure data) to determine when to provide stimulations of the nerves related to airway patency.
  • the IPG 12 may control the stimulation of the upper-airway nerve(s) at the act 922 with the phrenic nerve stimulation timing as the timing trigger (e.g., according to the coordinated timing discussed in regard to FIG. 10A).
  • the system 10 may enable delivery of an airway patency targeted stimulation without a reliance on real-time respiration data.
  • the nerve stimulation may occur before an apnea occurs and thus prevent the apnea altogether, whether CSA, OSA, or combined.
  • an electrical stimulation to provide phrenic nerve stimulation therapy may begin at a first time 1010 and ends at a second time 1012.
  • the electrical stimulation includes the series of pulses (e.g., as described in regard to FIG. 10A).
  • a magnitude of the pulses for example, measured in current and/or voltage
  • the time between the first time 1010 to the third time 1014 may be referred to as a ramping-up time (e.g., the time interval 1098 in FIG. 10B), and the pulses therein may be referred to as ramping-up pulses.
  • the magnitude of the pulses remains constant until a fourth time 1016.
  • a magnitude of the pulses ramps down. Accordingly, the time between the fourth time 1016 to the second time 1012 may be referred to as a ramping-down time (e.g., the time interval 1099 in FIG. 10B), and the pulses therein may be referred to as ramping-down pulses. As discussed in greater detail below, one or more parameters of the electrical current may be modified to adjust the phrenic nerve stimulation therapy.
  • the implantable system 10 evaluates respiratory data or information which may include sensor data.
  • the implantable system 10 may determine an indicator specific to lack of respiratory drive based on the respiratory data.
  • This therapyspecific indicator may include one or more values indicative of an effect of the phrenic nerve stimulation therapy, such as an entrainment index, an SpO2 level, and so forth.
  • the therapyspecific indicator may be considered specific to lack of respiratory drive inasmuch as the therapy-specific indicator may be related or and/or indicative of lack of respiratory drive.
  • the therapy- specific indicator may also be impacted by stimulation provided to a hypoglossal nerve to address airway obstruction.
  • the therapy-specific indicator being specific to lack of respiratory drive may not mean that the therapy -specific indicator relates only to phrenic nerve stimulation therapy.
  • the therapy-specific indicator may also be impacted by electrical stimulation provided to an upper-airway nerve, such as the hypoglossal nerve and/or the ansa cervicalis, and thus electrical stimulation provided to an upper-airway nerve may be based at least in part on the therapy-specific indicator.
  • the implantable system 10 may determine that the phrenic nerve stimulation therapy is not yet sufficiently effective.
  • the implantable system 10 may determine at least one indicator specific to phrenic nerve stimulation therapy.
  • An indicator specific to phrenic nerve stimulation therapy includes at least one metric representing the effectiveness of the electrical stimulation (for example as provided at act 906).
  • the indicator specific to phrenic nerve stimulation therapy may include, for example, an SpO2 level, or another metric indicative of the effectiveness of the electrical stimulation.
  • the indicator specific to phrenic nerve stimulation therapy may be determined based on the respiratory parameters.
  • the SpO2 may be calculated based on the blood-oxygen parameters which might be acquired or evaluated at act 910.
  • the SpO2 level may be determined based on optical signals output by, and subsequently sensed by, a finger-worn pulse oximeter used by the patient.
  • act 910 may include determining multiple indicators specific to phrenic nerve stimulation therapy.
  • the indicator specific to phrenic nerve stimulation therapy may include additional or different parameters.
  • the disordered breathing therapy system 10 determining that the phrenic nerve stimulation therapy satisfies the one or more phrenic nerve stimulation therapy criteria may be referred to as the disordered breathing therapy system 10 determining that the phrenic nerve stimulation therapy is effective.
  • therapy effectiveness specific to lack of respiratory drive may be assessed using transthoracic impedance to look for the absence of apnea and/or hyperpnea periods, reduced amplitudes of the sinusoidal morphology of periodic breathing, and so forth.
  • act 912 may include determining whether the entrainment index potentially determined at act 910 is above a threshold level or within a target range (for example, around 0.6-0.8). If the indicator specific to phrenic nerve stimulation therapy includes the SpO2 level, then act 912 may include determining whether the SpO2 potentially determined at act 910 is above a threshold level (for example, around 95%). If the indicator specific to phrenic nerve stimulation therapy includes both the entrainment index and the SpO2 level, act 912 may include determining whether both the entrainment index and the SpO2 level are above respective thresholds. In still other examples, other types of indicators specific to phrenic nerve stimulation therapy may be determined and evaluated to assess whether therapy is effective.
  • the one or more phrenic nerve stimulation therapy criteria may change over time such that one or more phrenic nerve stimulation therapy parameters that meet the one or more phrenic nerve stimulation therapy criteria at one point in time (and may thus be referred to in shorthand as effective treatment at that point in time) may not meet the one or more phrenic nerve stimulation therapy criteria at another point in time (and may thus be referred to in shorthand as ineffective treatment at that point in time).
  • the disordered breathing therapy implantable system 10 determines that phrenic nerve stimulation therapy requires an adjustment (912 YES), then the subsystem 902 continues to act 914.
  • the implantable system 10 adjusts one or more stimulation parameters.
  • the stimulation parameters may include various parameters of the electrical stimulation, such as one or more of a total number of pulses (that is, between the first time 1010 and the second time 1012), a number of ramping-up pulses (that is, between the first time 1010 and the third time 1014), a number of ramping-down pulses (that is, between the fourth time 1016 and the second time 1012), a current magnitude of the electrical stimulation, a voltage magnitude of the electrical stimulation, a frequency at which the pulses are applied, a time over which the pulses are ramped up (that is, an amount of time between the first time 1010 and the third time 1014), a time over which the pulses are ramped down (that is, an amount of time between the fourth time 1016 and the second time 1012), a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of one or more of the pulses
  • the IPG 12 and/or the external computing device 210 may adjust various parameters within a range of values. For example, the IPG 12 and/or the external computing device 210 may adjust the current to values between 0-20 mA, the pulse width to values between 30-1000
  • a maximum stimulation-current threshold may be enforced with a maximum stimulation current of 4 mA, 5 mA, 6 mA, or some other value.
  • a stimulation threshold may depend on a lead impedance.
  • the lead impedance may account for one or more of the impedance of the physical leads (for example, the leads 14 or 16), the impedance of electrode/tissue interfaces, and/or the impedance of the tissues, blood, and/or bones between electrodes. In some examples, the lead impedance may be approximately 100 - 2000 .
  • a stimulation threshold and/or lead impedance may depend at least in pail on whether a target nerve is a left or right nerve (for example, a left or right phrenic nerve).
  • a stimulation threshold may be determined on a patient- by-patient basis by observing patient response to electrical stimulation.
  • a stimulation threshold may be evaluated and/or selected based various indicators.
  • indicators may include airflow, tongue movement, or other airway responses to electrical stimulation of the upper- airway nerve at one or more stimulation currents.
  • a patient’s airway response may be evaluated based on visual inspection and/or imaging (for example, fluoroscopy imaging) (for example, during an office visit or during overnight observation of the patient), evaluation of electromyography signals, and/or evaluations of other signals.
  • a stimulation threshold may be evaluated and/or selected based on various indicators.
  • indicators may include airflow, diaphragmatic movement, or other responses to electrical stimulation of a phrenic nerve at one or more stimulation currents.
  • a diaphragmatic response to phrenic nerve stimulation may be evaluated based on patient palpation and/or imaging (for example, fluoroscopy imaging) (for example, during an office visit or during overnight observation of the patient), evaluation of electromyography signals, and/or evaluations of other signals.
  • the IPG 12 may adjust these stimulation parameters without an instruction from the external computing device 210 or may require an instruction from the computing device 210 and only adjust the parameter in response to such an instruction.
  • the IPG 12 may be configured to only adjust one or a subset of these parameters during administration of therapy to a patient.
  • the IPG 12 may require an instruction from the computing device 210, for example, during a visit by the patient to a physician’s office for adjustment of the therapy.
  • the IPG 12 may only adjust current without an instruction from the computing device 210.
  • the electrical stimulation may not be sufficiently intense.
  • the implantable system 10 may therefore intensity the electrical stimulation by, for example, increasing a magnitude of the current, increasing a number of pulses of the electrical stimulation, increasing a duration of the electrical stimulation, increasing a pulse width of the pulses, increasing a speed at which the ramping-up pulses ramp up, increasing an initial and/or final magnitude of the ramping-up pulses and/or ramping-down pulses, and so forth.
  • the subsystem 902 returns to act 906.
  • the implantable system 10 provides a subsequent electrical stimulation to the phrenic nerve of the patient.
  • the electrical stimulation is now characterized by the adjusted stimulation parameters selected at act 914. Acts 906-912 may then be repeated.
  • the implantable system 10 determines whether the phrenic nerve stimulation therapy satisfies various criteria or requires an adjustment. In some examples, the implantable system 10 may wait a threshold amount of time after adjusting the one or more stimulation parameters before re-adjusting the parameters such that, for example, the patient’s body can adapt to the new electrical stimulation. If the implantable system 10 determines that the phrenic nerve stimulation therapy meets criteria and does not require any adjustment (912 NO), then the subsystem 902 continues to act 830.
  • the upper-airway nerve stimulation subsystem 904 optionally begins at act 920.
  • the therapy system 10 may automatically deliver phrenic nerve stimulation and evaluate whether or not to provide upper-airway nerve stimulation as shown in FIG. 9A. In the absence of upper-airway nerve stimulation, the therapy system 10 may only provide phrenic nerve stimulation.
  • the IPG 12 may provide upper-airway nerve stimulation therapy as part of the disordered breathing therapy based at least in part on respiration data as optionally determined at the act 812. In some examples, upper-airway nerve stimulation therapy may be delivered without a trigger in response to airway data (e.g., the pre-programmed upper-airway nerve stimulation therapy as discussed in further detail with respect to FIG. 11A).
  • the implantable system 10 may determine whether airway obstruction is likely to occur. For example, the implantable system 10 may evaluate a condition that may be associated with airway obstruction, for example, a position (also referred to as a sleeping position or body position) of the patient. Sleeping positions may include a supine position, a prone position, a left-side position, a right-side position, and, in some examples, an upright (that is, sitting or standing up) position. Accordingly, the term sleeping position may, in some examples, include a position that the patient can be in while awake.
  • a position also referred to as a sleeping position or body position
  • sleeping positions may include a supine position, a prone position, a left-side position, a right-side position, and, in some examples, an upright (that is, sitting or standing up) position. Accordingly, the term sleeping position may, in some examples, include a position that the patient can be in while awake.
  • the sleeping position of the patient may be used at act 920 to determine a likelihood that the patient is experiencing or will experience an airway obstruction. For example, a patient may be more likely to experience airway obstruction in a supine position, but less likely to experience airway obstruction in other sleeping positions. Alternatively, the patient may experience airway obstruction in all sleeping positions, but to varying degrees.
  • the system 10 may be programmed with correlation metrics for patient position and airway obstruction based on historical data collected for the patient prior to surgery 850 and/or during the monitoring period 852. Additionally or alternatively, the correlation metrics may be based on general patient populations and/or patient demographics. Thus, at the act 920, the system 10 may evaluate patient position data.
  • evaluation may include a deterministic evaluation and/or may include an evaluation of correlation metrics.
  • the position data may include accelerometer parameters received from the sensors 18 and/or 19 indicative of a position of the patient.
  • the disordered breathing therapy system 10 may determine the current sleeping position of the patient based on the accelerometer data, and at the act 920 may determine that the patient is or is not likely experiencing airway obstruction based on the position in which the patient is sleeping and the pre-programmed correlation metrics.
  • the implantable system 10 may determine if the sleeping position of the patient is one of a list of stored positions known to be associated with airway obstruction for the patient.
  • the implantable system 10 may determine that the patient is likely not experiencing an airway obstruction.
  • the implantable system 10 may determine that the patient is likely experiencing an airway obstruction.
  • the disordered breathing therapy 826 may not include stimulation of nerves via the upper-airway nerve stimulation leads 16 during a particular cycle of electrical stimulation therapy and may proceed to the act 906 without implementation of the act 922.
  • the IPG 12 may apply a set of current pulses 1006 to the phrenic nerve stimulation leads 14 without providing the set of current pulses 1008 to the upper-airway nerve stimulation leads 16.
  • implantable system 10 provides disordered breathing therapy without stimulation of the upper- airway nerve stimulation leads 16 and returns to an evaluation of disordered breathing therapy data at the act 812 prior to a subsequent stimulation cycle.
  • the act 826 includes the subsystem 904 continuing to the act 922 along with subsystem 902 implementing the act 906.
  • the implantable system 10 provides electrical stimulation to an upper- airway nerve of the patient via the upper-airway nerve stimulation leads 16.
  • the acts 922 and 928 may include stimulation of the hypoglossal nerve or another upper-airway nerve, such as the ansa cervicalis, in addition to or in lieu of the hypoglossal nerve.
  • the processor 50 may control or otherwise cause the stimulation circuitry 58 to deliver the electrical stimulation to the one or more upper-airway nerves of the patient via the upper-airway nerve stimulation lead(s) 16.
  • the IPG 12 may control the timing of the hypoglossal nerve stimulation relative to the phrenic nerve stimulation 906.
  • the implantable system 10 may provide the hypoglossal nerve stimulation 922 in response to respiratory data indicative of an airway obstruction, the implantable system 10 may determine the timing of the hypoglossal nerve stimulation pulses relative to and based on the phrenic nerve stimulation rather than relative to or based on an occurrence of a feature or event in the respiratory data.
  • the implantable system 10 may evaluate airway patency at the act 920 and provide stimulation at the act 922 during RDS therapy 908 at the act 906. Stimulations directed at airway patency delivered in coordination with stimulations for entrainment may move the patient to entrainment and/or maintain entrainment in an improved manner as compared to entrainment based on phrenic nerve stimulation along.
  • the implantable system 10 may evaluate airway patency at the act 920 and provide stimulation at the act 922 during the phrenic nerve stimulation at the act 906 after RDS therapy 908 at the act 906 is complete and the RDS data indicates that the patient is entrained.
  • the implantable system 10 may coordinate the relative timing of the upper-airway nerve stimulation and the phrenic nerve stimulation based on an entrained respiration rate of the patient. Therefore, the implantable system 10 may be configured to delay delivery of upper-airway nerve stimulations until the implantable system 10 determines that the patient’s respiration is entrained.
  • an electrical stimulation to treat airway obstruction is applied at a fifth time 1018 and ends at a sixth time 1020.
  • the graphs 1002, 1004 may be temporally aligned such that, for example, the sixth time 1020 occurs between the first time 1010 and the third time 1014 discussed above.
  • a magnitude of the pulses (for example, measured in current and/or voltage) ramps up. Accordingly, the time between the fifth time 1018 to the seventh time 1020 may be referred to as a ramping-up time, and the pulses therein may be referred to as ramping-up pulses.
  • the magnitude of the pulses remains constant until an eighth time 1022.
  • a magnitude of the pulses ramps down. Accordingly, the time between the eighth time 1022 to the sixth time 1020 may be referred to as a ramping-down time, and the pulses therein may be referred to as ramping-down pulses.
  • one or more parameters of the electrical stimulation may be modified to adjust the upper-airway nerve stimulation therapy.
  • upper-airway nerve and phrenic nerve stimulation therapy is being applied simultaneously between the first time 1010 and the second time 1012, but only upper-airway nerve stimulation therapy is being applied between the fifth time 1018 and the first time 1010, and the second time 1012 and the sixth time 1020.
  • the disclosure may be advantageous to begin applying upper-airway nerve stimulation therapy prior to beginning to apply phrenic nerve stimulation therapy. Beginning to apply the upper-airway nerve stimulation therapy may open the airway of the patient such that, when the phrenic nerve stimulation therapy prompts the patient to engage in normal breathing patterns, there is an unobstructed airway for air to be drawn into.
  • upper-airway nerve stimulation therapy may open the airway of the patient such that, when the phrenic nerve stimulation therapy prompts the patient to engage in normal breathing patterns, there is an unobstructed airway for air to be drawn into.
  • different configurations are within the scope of the disclosure.
  • the implantable system 10 evaluates respiratory information or data which may include sensor data.
  • the respiratory information may include airway information.
  • the respiratory information may be the same as, or different than, the respiratory information received at act 812 or 910.
  • the implantable system 10 may evaluate patient-position parameters as discussed above.
  • the implantable system 10 may execute an initial determination as to whether to apply upperairway nerve stimulation therapy based on patient position at act 812. Once the implantable system 10 has applied the upper-airway nerve stimulation therapy (act 922), the implantable system 10 may receive additional and/or different airway information at acts 830 and/or 924 to evaluate the effectiveness of the therapy.
  • the respiratory information may include acoustic parameters.
  • the sensors 18 and/or 19 may include a microphone configured to capture the acoustic parameters.
  • the microphone may be internal or external to the patient, and may capture acoustic parameters indicative of the breathing of the patient.
  • the acoustic parameters may capture the patient snoring, which may be an indication that the patient’s airway is obstructed.
  • the implantable system 10 may determine that the patient is not snoring.
  • Other examples of respiratory information which might be acquired at acts 812, 829 and/or 924 arc provided below.
  • the implantable system 10 determines whether the upper-airway nerve stimulation therapy satisfies one or more upper-airway nerve stimulation therapy criteria and whether this therapy needs an adjustment. As discussed below, act 926 may include evaluating airway information to determine whether the patient’s airway is obstructed after delivering therapy. The implantable system 10 may determine an indicator specific to upper-airway nerve stimulation therapy based on the airway information.
  • the implantable system 10 may determine whether the upper-airway nerve stimulation therapy satisfies the one or more upper-airway nerve stimulation therapy criteria based on the airway information evaluated at act 924. For example, the implantable system 10 may determine an indicator specific to upper-airway nerve stimulation therapy including one or more upperairway nerve stimulation therapy parameters from the respiratory information and comparing the indicator specific to upper-airway nerve stimulation therapy to the one or more upper-airway nerve stimulation therapy criteria.
  • the one or more upper-airway nerve stimulation therapy criteria may include one or more ranges, such as one or more thresholds, to which the indicator specific to upper-airway nerve stimulation therapy may be compared.
  • the disordered breathing therapy system 100 may analyze the acoustic parameters to determine whether the patient is snoring. For example, the disordered breathing therapy system 100 may determine if an attribute of the acoustic parameters (for example, a volume of the captured sound, a frequency of the sound, or a location of the sound, etc.) satisfies the one or more upper-airway nerve stimulation therapy criteria, such as by comparing the criteria with a threshold and/or a range.
  • a volume threshold may correspond to a volume above which the sound is likely produced by the patient snoring or the microphone placement may localize the sound to the throat or nose of the patient.
  • the disordered breathing therapy system 100 may analyze the frequency of one or more signals in the acoustic parameters and compare the frequency(ies) to a range and/or a threshold.
  • the at least one range may correspond to a range of frequencies associated with snoring.
  • the disordered breathing therapy system 100 may analyze the waveform of the acoustic parameters to determine if the waveform is consistent with snoring, such as by comparing the acoustic parameters to one or more stored waveforms associated with snoring. Accordingly, the system 100 may determine an indicator specific to upper-airway nerve stimulation therapy including one or more upper-airway nerve stimulation therapy parameters such as an acoustic amplitude, an acoustic frequency, and so forth.
  • the processor 50 may be configured to control the stimulation circuitry 58 to provide one or more of a phrenic nerve electrical stimulation or a hypoglossal nerve electrical stimulation based at least in pail on the entrainment index.
  • the upper-airway nerve stimulation therapy and/or an evaluation of airway collapsibility underlying such therapy may be impacted at least in part by the phrenic nerve stimulation therapy. Therefore, upper-airway nerve stimulation therapy may be based not only on the indicator specific or targeted to upper-airway nerve stimulation therapy, but also the indicator specific or targeted to phrenic nerve stimulation therapy (such as the entrainment index). Thus, an indicator specific to or targeted at provision of one nerve stimulation may directly or indirectly inform the provision of another nerve stimulation.
  • the therapy act subsystem 904 proceeds to the act 830. If the implantable system 10 determines that the indicator specific to upper-airway nerve stimulation therapy does not meet upper-airway nerve stimulation therapy criteria (for example, criteria that may indicate that the decreased airway patency treatment is meeting at least a minimum level of effectiveness), the implantable system 10 may determine that the upper-airway nerve stimulation therapy is not yet sufficiently effective and requires an adjustment upper-airway nerve (926 YES), and the subsystem 904 continues to act 928.
  • the indicator specific to upper-airway nerve stimulation therapy does not meet upper-airway nerve stimulation therapy criteria (for example, criteria that may indicate that the decreased airway patency treatment is meeting at least a minimum level of effectiveness)
  • the implantable system 10 may determine that the upper-airway nerve stimulation therapy is not yet sufficiently effective and requires an adjustment upper-airway nerve (926 YES), and the subsystem 904 continues to act 928.
  • the disordered breathing therapy system 10 adjusts one or more stimulation parameters of the electrical stimulation applied at act 922.
  • the one or more stimulation parameters that may be adjusted may be similar to those discussed at act 914, for example, with reference to FIG. 10A, one or more of a total number of pulses (that is, between the fifth time 1018 and the sixth time 1020), a number of ramping-up pulses (that is, between the fifth time 1018 and the seventh time 1022), a number of ramping-down pulses (that is, between the eighth time 1024 and the sixth time 1020), a current magnitude of the electrical stimulation, a voltage magnitude of the electrical stimulation, a frequency at which the pulses are applied, a time over which the pulses arc ramped up (that is, an amount of time between the fifth time 1018 and the seventh time 1022), a time over which the pulses are ramped down (that is, an amount of time between the eighth time 1024 and the sixth time 1020), a magnitude of at least one of the ramping-up
  • stimulation parameters may be maintained above or below certain thresholds or within certain ranges.
  • the IPG 12 may implement a stimulation threshold.
  • a stimulation threshold may be evaluated and/or selected based on tongue movement or other airway response to electrical stimulation of the upper-airway nerve at one or more stimulation currents.
  • a patient’s airway response may be evaluated based on visual inspection, imaging (for example, fluoroscopy imaging), and/or evaluations of other signals.
  • the one or more stimulation parameters may include relative timing between the electrical stimulation for phrenic nerve stimulation therapy and the electrical stimulation for upper-airway nerve stimulation therapy.
  • the delivery start time of the electrical stimulation for phrenic nerve stimulation therapy (that is, a time at which the disordered breathing therapy system 100 begins applying the electrical stimulation to the phrenic nerve, such as the first time 1010) may be synchronized with the delivery start time of the upper-airway nerve electrical stimulation (that is, a time at which the disordered breathing therapy system 100 begins applying the electrical stimulation to the hypoglossal nerve and/or the ansa cervicalis, such as the fifth time 1018). That is, the delivery start time of the electrical stimulation for phrenic nerve stimulation therapy may depend on, or be related to, the delivery start time of the electrical stimulation for upper-airway nerve stimulation therapy.
  • the disordered breathing therapy system 100 may apply one of the electrical stimulations before the other of the electrical stimulations by a set time delay.
  • the set time delay may be a specific value within a range (for example, a value between 0.1-500 ms) or may indicate a maximum value within a range (for example, less than or equal to 500 ms, 300 ms, 100 ms, 50 ms, 10 ms, 5 ms, 1ms, 0.5 ms, 0.1 ms, and so forth).
  • the electrical stimulation for phrenic nerve stimulation therapy may be applied before the upper-airway nerve electrical stimulations, or vice versa.
  • one upper-airway nerve electrical stimulation (which may include a plurality of pulses) and one electrical stimulation for lack of respiratory drive (which may include a plurality of pulses) are provided during each actual breathing cycle of the patient, that is, a period of inspiration followed by a period of expiration, or vice versa. Accordingly, an electrical stimulation may be identified as being provided first if, for example, the electrical stimulation is applied first within a given breathing cycle.
  • the implantable system 10 may entrain the patient’s breathing.
  • the natural breathing rate may deviate from a target degree of entrainment.
  • one upper-airway nerve electrical stimulation (which may include a plurality of pulses) and one electrical stimulation for phrenic nerve stimulation therapy (which may include a plurality of pulses) may be provided during each target breathing cycle, which may differ from a natural breathing cycle of a patient.
  • act 928 may include modifying additional or different stimulation parameters.
  • the subsystem 904 then proceeds to act 922, where the disordered breathing therapy system 100 applies the upper-airway nerve electrical stimulation with the adjusted one or more stimulation parameters. Acts 922-926 may be repeated until a determination is made that the airway obstruction treatment is effective without adjustment required (926 NO), and the subsystem 904 proceeds to act 830.
  • electrical stimulation may be applied to a hypoglossal nerve at act 922.
  • electrical stimulation may be applied to the ansa cervicalis at act 922 in addition to, or in lieu of, applying electrical stimulation to the hypoglossal nerve.
  • act 928 may include adjusting stimulation parameters for the electrical stimulation applied to the ansa cervicalis.
  • act 922 may include only applying electrical stimulation to the hypoglossal nerve, and act 928 may include only adjusting stimulation parameters of the electrical stimulation applied to the hypoglossal nerve.
  • acts 914 adjust phrenic nerve stimulation
  • acts 928 adjust hypoglossal stimulation
  • acts 914 and acts 928 are shown in between stimulations of the phrenic nerve at act 906 and stimulations of the hypoglossal nerve at 922
  • these adjustments may or may not occur in between each stimulation and may occur over various time frames.
  • One or more of the IPG 12 or the external computing device 210 may adjust the upper-airway nerve stimulation therapy and/or the phrenic nerve stimulation therapy over the same time frames or different time frames.
  • the IPG 12 and/or the external computing device 210 may adjust parameters based on a breath interval, such as every 5-15 breaths. Such adjustments may improve the effect of inspiration across intervals.
  • the IPG 12 may adjust parameters during a particular sleep interval. For example, the IPG 12 may adjust parameters between midnight and four in the morning as the airway obstruction and lack of respiratory drive exhibited by the patient changes during sleep (for example, due to position, motion, length of time asleep, and so forth). As a further example, the IPG 12 and/or the external computing device 210 may adjust parameters over a course of weeks or months as a patient’s condition evolves and changes due to effectiveness of therapy, changes in underlying health conditions, and so forth. These adjustments may also be combined to reflect the fact that a patient’s condition is dynamic rather than static and changes in patient condition necessitate continuing adjustment of therapy.
  • the adjustments to therapy may be parameter specific where particular parameters may be adjusted over a particular range of values, as discussed herein, but also by particular intervals. These intervals may be specific amounts (for example, 0.1 mA current adjustments) or percentages (for example, a 5% increase in current).
  • the adjustments may be limited by capabilities of the software, hardware, and/or firmware. For example, frequency increments may be limited to a selection of 10, 20, or 40 Hz).
  • the adjustments in therapy parameters may differ between the airway obstruction and lack of respiratory drive therapies.
  • the optimum pulse frequency for upper-airway nerve stimulation may be 20 Hz whereas the optimum pulse frequency for phrenic nerve stimulation may be 40 Hz.
  • Modifying the one or more stimulation parameters at acts 914 and/or 928 may include modifying a relationship between the electrical stimulation for upper-airway nerve stimulation therapy and the electrical stimulation for phrenic nerve stimulation therapy.
  • a first period of time the period of time between the fifth time 1018 and the seventh time 1022 (that is, when the upper-airway nerve electrical stimulation is ramping up) is referred to as a first period of time; the period of time between the seventh time 1022 and the eighth time 1024 (that is, when the upper-airway nerve electrical stimulation is constant) is referred to as a second period of time; the period of time between the eighth time 1024 and the sixth time 1020 (that is, when the upper-airway nerve electrical stimulation is ramping down) is referred to as a third period of time; the period of time between the first time 1010 and the third time 1014 (that is, when the electrical stimulation for phrenic nerve stimulation therapy is ramping up) is referred to as a fourth period of time; the period of time between
  • the disordered breathing therapy system 100 begins providing the upperairway nerve electrical stimulation before the electrical stimulation for phrenic nerve stimulation therapy.
  • the implantable system 10 may begin providing the upper-airway nerve electrical stimulation approximately 10 ms before providing the electrical stimulation for phrenic nerve stimulation therapy.
  • the airway obstruction treatment may precede the lack of respiratory drive treatment by 1-120 milliseconds.
  • the upper-airway nerve electrical stimulation may still be ramping up when the implantable system 10 begins providing the electrical stimulation for phrenic nerve stimulation therapy, that is, the first time 1010 may occur during the first period of time. In some examples, the first time 1010 is synchronized with the beginning of the patient breathing in.
  • the implantable system 10 may provide the electrical stimulation for phrenic nerve stimulation therapy to the patient simultaneously with the patient beginning to breathe in.
  • the upper-airway nerve electrical stimulation may precede inspiration by a time delay (for example 1 -20 ms) such that, for example, the airway of the patient is unobstructed before the patient begins to breathe in.
  • the disordered breathing therapy system 100 may modify the duration of this time delay, or offset, on a patient-by-patient basis to ensure that the airway of the patient is substantially unobstructed prior to the patient breathing in.
  • the electrical stimulations for phrenic nerve stimulation therapy and upper-airway nerve stimulation therapy may stop ramping up at approximately the same time, that is, the second time 1014 may be approximately the same time as the seventh time 1022.
  • the electrical stimulations for lack of respiratory drive and for airway obstruction may be constant for a brief amount of time before the disordered breathing therapy system 10 begins ramping down the electrical stimulation for phrenic nerve stimulation therapy.
  • the disordered breathing therapy system 100 may ramp down the electrical stimulation for phrenic nerve stimulation therapy such that the electrical stimulation for phrenic nerve stimulation therapy stops simultaneously with, or just before, the end of the patient breathing in.
  • the disordered breathing therapy system 100 may finish ramping down the electrical stimulation for phrenic nerve stimulation therapy (that is, stop providing the electrical stimulation for phrenic nerve stimulation therapy) simultaneously with, or just before, beginning to ramp down the upper-airway nerve electrical stimulation, that is, the second time 1012 may be approximately simultaneous with, or just before, the eighth time 1024.
  • the implantable system 10 may begin ramping down the upper-airway nerve electrical stimulation approximately simultaneously with the beginning of the patient breathing out, that is, the eighth time 1024 may be approximately simultaneous with the patient beginning to breathe out.
  • the first period of time may at least partially overlap with the fourth period of time such that the electrical stimulations for lack of respiratory drive and airway obstruction are ramping up simultaneously for at least a brief period of time.
  • the ramping- up pulses of the upper-airway nerve electrical stimulation may be synchronized with (for example, provided simultaneously with) respective ramping-up pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the first and fourth periods.
  • the ramping-up pulses of the upper- airway nerve electrical stimulation may be provided independently from (for example, provided simultaneously with) the ramping-up pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the first and fourth periods.
  • a number of the ramping-up pulses of the upper-airway nerve electrical stimulation may be synchronized with (for example, the same as) a number of ramping-up pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the first and fourth periods.
  • the number of ramping-up pulses of the upper-airway nerve electrical stimulation may be provided independent of the number of ramping-up pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the first and fourth periods.
  • the first period of time begins prior to the fourth period of time. In other examples, the first period of time begins after the fourth period of time. In still other examples, the first period of time begins at the same time as the fourth period of time.
  • the first period of time ends approximately at the same time as the fourth period of time. In other examples, the first period of time ends after the fourth period of time. In still other examples, the first period of time ends at the same time as the fourth period of time.
  • the first period of time ends before the fourth period of time begins. In other examples, the fourth period of time ends before the first period of time begins. In still other examples, the fourth period of time ends at the same time that the first period begins. In still other examples, the first period of time ends at the same time that the fourth period begins.
  • the second period of time may at least partially overlap with the fifth period of time such that the electrical stimulations for lack of respiratory drive and airway obstruction therapies are simultaneously constant for at least a brief period of time.
  • the constant pulses of the upper-airway nerve electrical stimulation may be synchronized with (for example, provided simultaneously with) respective constant pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the second and fifth periods.
  • the constant pulses of the upper-airway nerve electrical stimulation may be provided independently from (for example, provided simultaneously with) the constant pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the second and fifth periods.
  • a number of the constant pulses of the upper-airway nerve electrical stimulation may be synchronized with (for example, the same as) a number of constant pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the second and fifth periods.
  • the number of constant pulses of the upper-airway nerve electrical stimulation may be provided independent of the number of constant pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the second and fifth periods.
  • the second period of time begins prior to the fifth period of time. In other examples, the second period of time begins after the fifth period of time. In still other examples, the second period of time begins at the same time as the fifth period of time.
  • the second period of time ends approximately at the same time as the fifth period of time. In other examples, the second period of time ends after the fifth period of time. In still other examples, the second period of time ends at the same time as the fifth period of time.
  • the second period of time ends before the fifth period of time begins. In other examples, the fifth period of time ends before the second period of time begins. In still other examples, the fifth period of time ends at the same time that the second period begins. In still other examples, the second period of time ends at the same time that the fifth period begins.
  • the third period of time may at least partially overlap with the sixth period of time such that the electrical stimulations for lack of respiratory drive and airway obstruction therapies are ramping down simultaneously for at least a brief period of time.
  • the ramping-down pulses of the upper-airway nerve electrical stimulation may be synchronized with (for example, provided simultaneously with) respective ramping-down pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the third and sixth periods.
  • the ramping-down pulses of the upper-airway nerve electrical stimulation may be provided independently from (for example, provided simultaneously with) the ramping-down pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the third and sixth periods.
  • a number of the ramping-down pulses of the upper-airway nerve electrical stimulation may be synchronized with (for example, the same as) a number of ramping-down pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the third and sixth periods.
  • the number of ramping-down pulses of the upper-airway nerve electrical stimulation may be provided independent of the number of ramping-down pulses of the electrical stimulation for phrenic nerve stimulation therapy during the overlap of the third and sixth periods.
  • the third period of time begins prior to the sixth period of time. In other examples, the third period of time begins after the sixth period of time. In still other examples, the third period of time begins at the same time as the sixth period of time.
  • the third period of time ends approximately at the same time as the sixth period of time. In other examples, the third period of time ends after the sixth period of time. In still other examples, the third period of time ends at the same time as the sixth period of time.
  • the third period of time ends before the sixth period of time begins. In other examples, the sixth period of time ends before the third period of time begins. In still other examples, the sixth period of time ends at the same time that the third period begins. In still other examples, the third period of time ends at the same time that the sixth period begins.
  • modifying the one or more stimulation parameters at acts 914 and/or 928 may include modifying a relationship between the upper-airway nerve electrical stimulation and the electrical stimulation for phrenic nerve stimulation therapy by modifying a duration or timing of one or more of the six periods of time, and/or by modifying a relationship between the various periods of time.
  • respiratory information may include various parameters indicative of a presence or absence of an airway obstruction. These parameters may determine whether or not stimulation therapy is provided based on the determination at the act 920.
  • the at least one respiration sensor may include various different types of sensors. Various examples are provided below, which may be examples of act 920 and/or act 924.
  • airway parameters may include a position of the patient’s head and/or body.
  • the position of the patient’s head and/or body may be used at least at act 920 to determine whether an airway of the patient is likely obstructed.
  • the at least one respiration sensor includes one or more accelerometers configured to determine a position of a patient’s head and/or body.
  • a patient may be more likely to experience airway obstruction in certain head positions, that is, positions of the patient’s head relative to the patient’s torso.
  • a shape of a patient’s airway may change as the patient’s head moves. For example, a patient may be more likely to experience airway obstruction if the patient’s head is turned to the left or right as compared to if the patient is looking straight ahead.
  • the disordered breathing therapy system 10 may determine that the patient is or is not likely experiencing airway obstruction at act 920 based on a relative angle between the patient’s head and the patient’s torso. For example, the disordered breathing therapy system 10 may determine that the patient is likely experiencing airway obstruction if the relative angle is within a threshold range of degrees (for example, above a certain threshold degree value).
  • at least one of the sensors 18, 19 includes a first accelerometer coupled to the patient’s head and a second accelerometer coupled to the patient’s torso, each of which may be either internal or external to the patient, such that relative movement between the patient’s body and head can be identified.
  • the disordered breathing therapy system 10 may determine the body and/or head position of the patient based on acceleration parameters received from one or more accelerometers coupled to the patient’s body and/or head.
  • airway parameters may include acoustic parameters.
  • the at least one respiration sensor may include one or more microphones, which may be internal and/or external to the patient, configured to measure acoustic parameters, such as the sound of the patient snoring.
  • the frequencies associated with the acoustic data may differ based on whether an airway is fully open or sufficiently open to enable breathing without any apneas related to obstruction, or whether the airway is partially obstructed so as to cause apneas related to obstruction.
  • Snoring may be a symptom of obstructed breathing, and may therefore be used at act 920 to determine whether the patient is snoring and may thus be experiencing an airway obstruction, and/or may be used at act 926 to determine whether the patient is snoring and thus may be receiving at least partially ineffective upper-airway nerve stimulation therapy.
  • the disordered breathing therapy system 10 may analyze the acoustic parameters to determine whether the patient is snoring. For example, the disordered breathing therapy system 10 may determine at acts 920 and/or 924 if an attribute of the acoustic parameters (for example, a volume of the captured sound, a frequency of the sound, a location of the sound, etc.) satisfies a range or threshold criteria.
  • the threshold amplitude may correspond to a volume above which the sound is likely produced by the patient snoring.
  • the disordered breathing therapy system 10 may analyze the frequency of one or more signals in the acoustic parameters and determine whether the frequency(ies) is within at least one threshold range.
  • the at least one threshold range may correspond to a range of frequencies associated with snoring.
  • the disordered breathing therapy system 10 may analyze the waveform of the acoustic parameters to determine if the waveform is consistent with snoring at acts 920 and/or 924, such as by comparing the acoustic parameters to one or more stored waveforms associated with snoring.
  • the system 10 may determine at the act 920 that apneas related to obstruction are not occurring and withhold upper-airway nerve stimulation therapy (for example, move to the act 906 rather than proceed to the act 922 for upper-airway nerve stimulation therapy).
  • airway parameters may include blood-oxygen parameters.
  • the at least one respiration sensor may include one or more blood-oxygen sensors, such as one or more pulse oximeters configured to measure a blood-oxygen level of the patient.
  • low or erratic blood-oxygen levels may be associated with disordered breathing.
  • the disordered breathing therapy system 10 may analyze the blood-oxygen parameters at acts 920 and/or 924 to determine whether the blood-oxygen parameters are within a threshold range (for example, below a threshold value) or vary within a threshold range (for example, above a threshold value) to determine if the patient is experiencing obstructed breathing and/or if upperairway nerve stimulation therapy is achieving a desired result.
  • blood-oxygen parameters alone may not provide enough information for the disordered breathing therapy system 10 to determine if the patient is experiencing obstructed breathing and/or if the upper-airway nerve stimulation therapy is achieving a desired result.
  • the patient’s airway may be unobstructed, but the patient’s blood-oxygen levels may be low because the patient is experiencing lack of respiratory drive.
  • the patient may not be breathing regularly or properly due to the lack of respiratory drive.
  • the airway parameters may include breathing-rate and/or -depth parameters in addition to blood-oxygen parameters.
  • the breathing-rate and/or -depth parameters may indicate whether the patient is breathing normally. If the patient is breathing normally, the disordered breathing therapy system 10 may determine that the patient is not experiencing irregular breathing caused by lack of respiratory drive; accordingly, the disordered breathing therapy system 10 may determine that low or erratic blood-oxygen levels may be attributable to airway obstruction. That is, because the patient’s lungs are moving as expected yet the patient’s blood-oxygcn levels indicate that the patient’s breathing is not effective, the disordered breathing therapy system 10 may determine that an airway obstruction is likely preventing the patient from breathing normally.
  • Acts 920 and 926 may therefore include determining not only whether the patient’ s blood-oxygen levels are within ranges indicating that the blood-oxygen levels are low and/or erratic (which may indicate that the patient’s breathing may benefit from additional intervention), but may also include determining whether the patient’s chest is moving, that is, whether acceleration and/or position measurements indicative of movement and/or position of the patient’s chest are within ranges associated with normal breathing.
  • breathing-rate sensors include chest- or abdomen-motion sensors.
  • Chest- or abdomen-motion sensors may include, for example, one or more accelerometers, effort belts, pressure sensors, transthoracic impedance sensors, and so forth, to measure parameters indicative of movement and/or position of the patient’s torso.
  • Accelerometers may be coupled to the patient’s chest (for example, if the patient is a chest-breather) and/or abdomen (for example, if the patient is an abdomen-breather) to detect movement of the patient’s chest and/or abdomen.
  • an additional accelerometer may be coupled to another location of the patient’s torso to detect relative motion between the patient’s chest and/or abdomen and the rest of the patient’s torso caused by the patient breathing.
  • the disordered breathing therapy system 10 may determine that the patient is breathing regularly if the movement parameters vary within a threshold range and/or are within a threshold range of values, indicating that the patient is breathing regularly.
  • Effort belts may be coupled around the patient’s abdomen or chest to measure pressure and/or tensile changes in the effort belt caused by the patient breathing.
  • the disordered breathing therapy system 10 may determine that the patient is breathing regularly if the pressure and/or tensile parameters vary within a threshold range and/or are within a threshold range of values, indicating that the patient is breathing regularly.
  • Pressure sensors which may be internal and/or external to the patient, may measure changes in pressure applied by the expansion and contraction of the patient’s lungs.
  • the disordered breathing therapy system 10 may determine that the patient is breathing regularly if the pressure parameters vary within a threshold range and/or are within a threshold range of values, indicating that the patient is breathing regularly.
  • Transthoracic impedance sensors which may be internal and/or external to the patient, may measure changes in the patient’s lung volume caused by the expansion and contraction of the patient’s lungs.
  • the implantable system 10 may determine that the patient is breathing regularly if the lung- volume parameters vary within a threshold range and/or are within a threshold range of values, indicating that the patient is breathing regularly.
  • the disordered breathing therapy system 10 may determine that the patient is experiencing an airway obstruction and/or that upper-airway nerve stimulation therapy is not achieving a desired level of effectiveness at acts 920 and/or 926 if the blood-oxygen parameters of the patient are within a threshold range (for example, below a threshold value) indicating that the patient is not breathing effectively, and if the breathing-rate sensors indicate that the mechanical action of the patient’s breathing rhythms and depth are within a threshold range (for example, within a threshold range of variation).
  • a threshold range for example, below a threshold value
  • airway parameters include heart-rate parameters.
  • the at least one respiration sensor may include one or more heart-rate sensors, such as one or more pressure sensors, acoustic sensors, optical sensors, electrical-activity sensors, pulsatility sensors, and so forth.
  • a high or erratic heart rate may be associated with disordered breathing.
  • the disordered breathing therapy system 10 may analyze the heart-rate parameters at acts 920 and/or 926 to determine whether the heart-rate parameters are within a threshold range (for example, above a threshold value) or vary within a threshold range (for example, above a threshold value) to determine if the patient is experiencing obstructed breathing.
  • Pressure sensors which may be internal and/or external to the patient, may measure changes in pressure applied by the expansion and contraction of the patient’s heart.
  • the pressure sensors may include one or more piezoelectric sensors.
  • the implantable system 10 may determine that the patient is likely breathing regularly if the pressure parameters vary within a threshold range and/or are within a threshold range of values, indicating that the patient’s heart is beating regularly.
  • Acoustic sensors which may be internal and/or external to the patient, may measure changes in acoustic parameters indicative of the sound of the patient’s heart beating.
  • the acoustic sensors may include one or more microphones.
  • the implantable system 10 may determine that the patient is likely breathing regularly if the acoustic parameters vary within a threshold range and/or arc within a threshold range of values, indicating that the patient’s heart is beating regularly.
  • Optical sensors which may be internal and/or external to the patient, may measure changes in light parameters applied to the patient’s blood vessels indicative of changes in the blood and/or blood vessels.
  • the optical sensors may include one or more optical sources and/or sensors, which may be embedded in a wrist-worn device.
  • the disordered breathing therapy system 10 may determine that the patient is likely breathing regularly if the acoustic parameters vary within a threshold range and/or are within a threshold range of values, indicating that the patient’s heart is beating regularly.
  • Electrical-activity sensors which may be internal and/or external to the patient, may measure changes in electrical activity that causes the patient’s heart to expand and contract.
  • the electrical-activity sensors may include one or more electrodes.
  • the disordered breathing therapy system 10 may determine that the patient is likely breathing regularly if the acoustic parameters vary within a threshold range and/or are within a threshold range of values, indicating that the patient’s heart is beating regularly.
  • heart-rate parameters may be combined with other airway parameters to determine additional information.
  • heart-rate parameters may be analyzed with patient-movement parameters to determine a sleep stage of the patient, such as light sleep, deep sleep, rapid-eye-movement sleep, or awake.
  • the disordered breathing therapy system 10 may use the heart-rate parameters in combination with the patient-movement parameters to identify a sleep stage of the patient by comparing the heart-rate parameters and/or patient-movement parameters to respective threshold ranges of values associated with each sleep stage.
  • the implantable system 10 may detect or predict the presence or absence of an airway obstruction based on the sleeping position of the patient.
  • the disordered breathing therapy system 10 may detect or predict the presence or absence of an airway obstruction based on the sleep stage of the patient in addition to, or in lieu of, the sleeping position. For example, if the patient only regularly experiences airway obstructions in deep sleep, or only when the patient is in deep sleep in the supine position, the disordered breathing therapy system 10 may determine that the airway of the patient is obstructed only if the disordered breathing therapy system 10 determines that the patient is in deep sleep and/or in deep sleep and in the supine position.
  • acts 920, 924, and/or 926 may include determining a sleeping position and a sleeping stage of the patient, and determining whether the sleeping position, sleeping stage, or a combination thereof are on a stored list known to be associated with airway obstruction for the patient.
  • respiratory parameters may include lung volume, breathing rate, heart rate, SpO2 levels, patient movement, patient-chest and/or -abdomen movement, and so forth, each of which may be determined in a similar manner as discussed above.
  • the sensors 18 and/or 19 may include one or more of transthoracic impedance sensors, acoustic sensors, electricalactivity sensors, optical sensors such as pulse oximeters or near-infrared spectroscopy sensors, accelerometers, pressure sensors, pulsatility sensors, and so forth, each of which may be used to provide parameters that may be either or both respiratory parameters and airway parameters.
  • FIG. 9B illustrates further details of the act 826 of the processes 800 and 801, according to an example.
  • the process shown in FIG. 9B is an example only and not limiting and can be altered, such as by having acts added, removed, rearranged, combined, and/or performed concurrently.
  • the provision of disordered breathing therapy 826 includes a phrenic nerve stimulation subsystem 902 that enables the IPG 12 to provide nerve stimulation for phrenic nerve stimulation therapy and an upper-airway nerve stimulation subsystem 904 that enables the IPG 12 to provide nerve stimulation for upper-airway nerve stimulation therapy.
  • the subsystems 902 and 904 provide an example of act 826.
  • the therapy act 826 may deliver only the upper-airway nerve stimulation therapy or may deliver both therapies. In this manner, the therapy system 10 may treat OSA or combination apneas.
  • the phrenic nerve stimulation subsystem 902 optionally begins at act 921.
  • the therapy system 10 may automatically deliver upper- airway nerve stimulation and evaluate whether or not to provide phrenic nerve stimulation as shown in FIG. 9B. In the absence of phrenic nerve stimulation, the therapy system 10 may only provide upperairway nerve stimulation.
  • the IPG 12 may provide phrenic nerve stimulation therapy as part of the disordered breathing therapy based at least in part on respiration data as optionally determined at the act 812. In some examples, phrenic nerve stimulation therapy may be delivered without a trigger in response to airway data (e.g., the pre-programmed phrenic nerve stimulation therapy as discussed in further detail with respect to FIG. 1 IB).
  • the therapy system 10 may include an evaluation act 921 prior to act 906 to evaluate central drive reduction and automatically deliver upper-airway nerve stimulation and but evaluate whether or not to provide phrenic nerve stimulation.
  • the therapy system 10 may automatically deliver both phrenic nerve and upper-airway nerve stimulation without the evaluation steps 920 and 921, as shown in FIG. 9A and 9B respectively.
  • the act 826 may start with acts 906 and 922.
  • the IPG 12 may coordinate the relative timing of the two therapies as discussed herein and thus the acts 906 and 922 may commence according to this relative timing (e.g., act 906 may commence before the act 922, substantially simultaneously with the act 922, or after the act 922 depending on the relative timing).
  • the implantable system 10 determines whether the respiration data indicates a lack of central respiratory drive. For example, an occurrence of apneas and/or other disordered breathing events such as hypopneas and hyperpneas may indicate that the patient is responding to a lack of central respiratory drive and that the phrenic nerve stimulation therapy is needed. If the implantable system 10 determines that the patient is likely not experiencing a lack of central respiratory drive (921 NO), then the disordered breathing therapy 826 may not include stimulation of nerves via the phrenic nerve stimulation leads 14 during a particular cycle of electrical stimulation therapy and may proceed to the act 922 without implementation of the act 906.
  • the act 826 includes the subsystem 902 continuing to the act 906 along with subsystem 904 implementing the act 922.
  • the implantable system 10 may determine one or more sleep parameters indicative of whether the patient is asleep, and/or additional parameters related to the sleep of the patient. Determining whether the patient is asleep may include determining sleep- stage information from the one or more sleep parameters. Sleep- stage information may include information indicative of a sleep stage of the patient, such as awake (that is, not sleeping), light sleep, deep sleep, and REM sleep.
  • the implantable system 10 may determine the sleep-stage information based on information received from at least one of the sensors 18, 19.
  • the sleep- stage information may include heart-rate parameters and position parameters, which may be used by the implantable system 10 to determine a sleep stage of the patient. That is, the sleep stage of the patient may not be sensed directly, but may be determined based on parameters such as heart rate and position. In some examples, the sleep stage of the patient may be determined based on additional or different parameters, such as breathing- rate parameters.
  • the sensors 18 and/or 19 include at least one accelerometer and at least one heart-rate sensor.
  • the accelerometer may be coupled to the patient such that when the patient moves, the accelerometer senses the movement of the patient.
  • the heart-rate sensor may be used to determine a heartrate of the patient.
  • the implantable system 10 may determine the sleep stage of the patient (which may include determining that the patient is awake) based at least on the heart-rate parameters and/or the position parameters, because certain sleep stages may be associated with higher or lower heart rates (or variations thereof) and/or higher or lower amounts of movement. Other parameters, such as breathing-rate parameters, may alternately or additionally be used to identify and distinguish between sleep stages.
  • determining the one or more sleep parameters at act 802 may additionally include determining additional information related to the sleep of the patient, such as a position that the patient is sleeping in based on position parameters included in the sleep parameters.
  • the implantable system 10 may determine the position parameters based on parameters received from the sensors 18 and/or 19.
  • the sensors 18 and/or 19 include at least one accelerometer.
  • the accelerometer may be coupled to the patient such that when the patient moves, the accelerometer senses the movement of the patient.
  • the sensors 18 and/or 19 include multiple accelerometers, such as a first accelerometer coupled to the chest of the patient and a second accelerometer coupled to the head of the patient. Accelerometers may be external to the patient and/or implanted within the patient.
  • act 804 includes determining whether the patient is asleep and, if so, initiating treatment of the patient. In various examples, act 804 may include determining whether the patient is in a particular sleep stage generally, or for a particular amount of time. For example, certain patients may be prone to waking up if therapy is applied immediately upon transitioning from being awake to being in light sleep. In various examples, act 804 may include determining whether the patient has been asleep for at least a threshold amount of time (for example, 20 minutes) to decrease a chance of awakening the patient. In some examples, act 804 may include determining whether the patient has transitioned to a particular sleep stage, such as by waiting for the patient to transition from an initial light sleep stage to a subsequent deep sleep stage.
  • FIG. 11 A illustrates a process 1100 of implementing the disordered breathing therapy system 100 according to another example.
  • the process 1100 may provide a combination of phrenic nerve stimulation therapy and upper-airway nerve stimulation therapy.
  • the process 1100 may operate in the asynchronous mode 862 or in the synchronous mode of operation 864, as discussed above with regard to FIG. 8B.
  • the process 1100 is an example only and is not limiting.
  • the process 1100 may be altered, such as by having acts added, removed, rearranged, combined, and/or performed concurrently.
  • the process 1100 begins at act 802. Similar to the processes 800 and 801, the process 1100 begins after therapy activation 854 in the therapy delivery mode 861 as shown in FIG. 8B. At act 802, the disordered breathing therapy system 10 determines one or more sleep parameters. Act 802 is substantially similar to the act 802 discussed above with respect to FIG. 8A and is labeled accordingly. A description of act 802 is therefore not repeated. The process 1100 continues to act 804.
  • the disordered breathing therapy system 10 determines whether the patient is asleep. Act 804 is substantially similar to the act 804 discussed above with respect to FIG. 8A and is labeled accordingly. A description of act 804 is therefore not repeated. If the therapy system 10 determines that the patient is not asleep (804 NO), the process 1100 returns to act 802. Acts 802 and 804 are repeated until the therapy system 10 determines that the patient is asleep (804 YES), at which point the process 1100 continues to act 1104.
  • the IPG 12 determines whether to provide upper-airway nerve stimulation.
  • the determination may include a determination as to whether or not pre-programmed operational parameters include upper-airway nerve stimulation parameters (c.g., hypoglossal nerve stimulation parameters and/or ansa ccrvicalis stimulation).
  • a physician may evaluate the patient to determine whether the IPG 12 should provide upper-airway nerve stimulation (for example, prior to surgery 850 and/or during the monitoring period 852), and may pre-program the IPG 12 accordingly. For example, if the physician determines that the patient exhibits an airway obstruction and/or other indicators of OSA, the physician may pre-program the pulse generator 12 to provide upperairway nerve stimulation (1104 YES).
  • the trigger for providing stimulation of upper-airway nerves may be a programmed instruction to the pulse generator 12 and occur independently from any sensor measurements and/or sensor data analysis. Sensor measurements and/or sensor-data analysis may not trigger the airway nerve stimulation.
  • the acts 1108, 1120, and 1122 as described below may exclude specific airway patency analysis.
  • the physician may determine that upper-airway nerve stimulation should be provided in the monitoring period 852, the therapy delivery period 860, and/or during other encounters with the patient or other data review prior to or subsequent to the monitoring and therapy periods.
  • the pulse generator 12 may be re-programmed to provide the airway nerve stimulation.
  • some or all stimulation delivery parameters of the phrenic nerve stimulation may be pre-programmed based on data collected during or prior to the monitoring period 852 and as subject to change based on sensor data measured at 1108.
  • some or all of the stimulation delivery parameters of the upper-airway nerve stimulation may be preprogrammed based on data collected during or prior to the monitoring period 852. These parameters may be subject to change based on sensor data measured at 1108.
  • the decision at act 1104 is whether or not the system 10 is pre-programmed to provide upper-airway nerve stimulation of any kind. If that decision is yes (1104 YES), then the system 10 may provide that upper- airway nerve stimulation according to pre-programmed stimulation parameters. However, for the phrenic nerve stimulation, the process 1100 does not include decision step as to whether or not to provide the phrenic nerve stimulation. If the pulse generator 12 is pre-programmed to deliver airway nerve stimulation (1104 YES), the process 1100 continues to act 1110. At act 1110, the implantable system 10 provides electrical stimulation to one or more upper-airway nerves via the one or more upper-airway nerve stimulation leads 16.
  • these nerves may include one or more of the hypoglossal nerve and the ansa cervicalis of the patient.
  • a physician may preprogram a value and/or a range of values for parameters (e.g., one or more of the parameters shown in FIG. 10B) characterizing the electrical stimulation provided to the upper-airway nerve(s).
  • the physician may pre-program a value for a pulse width of the electrical stimulation as well as a range of values that the pulse width may vary within.
  • the airway nerve stimulation is pre-programmed at least inasmuch as a physician may pre -program whether airway nerve stimulation is provided, and a value and/or range of values for various parameters of the electrical stimulation(s) provided to the upper-airway nerve(s).
  • the implantable system 10 provides electrical stimulation to one or more upper-airway nerves as discussed above with respect to act 922 and may modify that therapy as discussed above with respect to act 928.
  • stimulation parameters may include one or more of a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one upper-airway nerve electrical stimulation, a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the upper-airway nerve electrical stimulation, a stimulation polarity of the electrical stimulation, and so forth
  • the process 1100 may include an airway data evaluation step substantially similar to step 902 as described in FIG. 9A.
  • the implantable system 10 may include sensors targeted specifically at airway patency data collection and/or may include data analysis targeted specifically at airway patency analysis.
  • one or more of the acts 1108, 1120, and 1122 as described below may include specific airway patency analysis.
  • sensor measurements and/or sensor data analysis may trigger the pulse generator 12 to provide stimulation of upper-airway nerves.
  • the process 1100 then proceeds from act 1110 to act 1106. Alternatively, if the therapy system 10 determines that pre-programmed upper-airway nerve stimulation is not to be provided at act 1104 (1104 NO), the process 1100 bypasses act 1110 and proceeds to act 1106.
  • act 1106 may precede act 1110.
  • the method 1100 may proceed from the act 804 to act 1106 and then to the acts 1104 and 1110. Further, the method 1100 may proceed from the act 1106 in parallel with both of act 1108 and acts 1104 and 1110.
  • acts 1106 and 1110 may occur according to one or more of the various coordinated timing patterns between phrenic nerve stimulation and upper-airway nerve stimulation as discussed in detail above with regard at least to FIG. 10A.
  • the IPG 12 may determine upper-airway nerve stimulation timing relative to the phrenic nerve timing.
  • the implantable therapy system 10 may provide the electrical stimulation of the one or more phrenic nerves in an asynchronous therapy mode 862 or a synchronous therapy mode 864.
  • the system 10 provides the phrenic nerve stimulation at a pre-determined rate without a respiration-sensor-based trigger.
  • the synchronous mode 864 the system 10 provides the phrenic nerve stimulation according to a respiration- sensorbased trigger.
  • the IPG 12 may provide the upper-airway nerve stimulation according to a pre-programmed trigger such that the timing is relative to and controlled by the phrenic nerve stimulation timing.
  • an upper-airway nerve stimulation may occur alone in the absence of a coordinated phrenic nerve stimulation.
  • a phrenic nerve stimulation may occur alone in the absence of a coordinated upper-airway nerve stimulation.
  • an instance of stimulation and/or a therapy delivery cycle may not require a stimulation of both nerves even if the pulse generator 12 is pre-preprogrammed to provide upper-airway nerve stimulation.
  • the implantable system 10 provides electrical stimulation to one or more phrenic nerves of the patient via the phrenic nerve stimulation lead(s) 14.
  • Phrenic nerve stimulation may be provided as discussed above with respect to acts 906 and 914.
  • Stimulation parameters of the phrenic nerve stimulation may include one or more of a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses arc applied, a time over which the pulses arc ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping-down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one upper-airway nerve electrical stimulation, a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of
  • Acts 1104, 1106, and 1110 include determining whether to provide upper-airway nerve stimulation, and may further include providing the upper-airway nerve stimulation and/or phrenic nerve stimulation according to various stimulation parameters described herein. Acts 1104, 1106, and 1110 may therefore be collectively referred to as a therapy act 1112.
  • the graphical depiction 1000 of FIG. 10A may also illustrate depictions of electrical stimulation provided by the implantable system 10 in executing the therapy act 1112.
  • the phrenic nerve stimulation graph 1002 may be indicative of electrical stimulation to provide phrenic nerve stimulation
  • the upper-airway nerve stimulation graph 1004 may be indicative of electrical stimulation to provide airway nerve stimulation.
  • the amplitude of the electrical stimulations provided during the therapy act 1112 may be increased over successive applications. For example, when phrenic nerve stimulation is first provided, the electrical stimulation may initially be provided at a relatively low in successive electrical stimulations is distinct from, and longer than, the ramping- up time of each individual electrical stimulation (for example, between the times 1010 and 1014 and between the times 1018 and 1022).
  • the therapy system 10 may initially only provide phrenic nerve stimulation and may not provide airway nerve stimulation.
  • the therapy system 10 may provide phrenic nerve stimulation with a gradually increasing amplitude until the full amplitude is attained minutes or hours into a patient’s sleep and/or days or weeks into a therapy program. Once the maximum amplitude is reached, the therapy system 10 may then begin providing airway nerve stimulation, either at a full amplitude or lower, but increasing, amplitude. In other examples, this order may be inverted, and airway nerve stimulation may initially be provided until the full amplitude is reached and only then is phrenic nerve stimulation provided.
  • airway nerve and phrenic nerve stimulation may be provided at the same time, but may be increased in amplitude at different times or rates.
  • upperairway nerve and phrenic nerve stimulation may be provided at the same time, and one or both of the therapies may be provided at a full intensity even from the initial application.
  • the therapy system 10 measures sensor data.
  • the sensor data may include information sensed by one or both of the sensors 18, 19.
  • the sensors 18 and/or 19 may include one or more of transthoracic impedance sensors, acoustic sensors, electrical-activity sensors, optical sensors such as pulse oximeters or near-infrared spectroscopy sensors, accelerometers, pressure sensors, pulsatility sensors, and so forth.
  • act 1108 includes only receiving transthoracic-impedance information from the implantable sensor 19, with the transthoracic-impedance information being the sensor data.
  • the sensor data includes, or may be used to determine, substantially similar data and/or information as discussed above with respect to act 910.
  • the sensor data may include therapy data such as phrenic nerve stimulation therapy data, which may include respiratory information as discussed with respect to act 910.
  • the therapy system 10 determines whether to evaluate the degree of synchronization of the patient’s breathing to the phrenic nerve stimulation 1106 provided during the therapy act 1112 (e.g., the patient’s entrainment).
  • Act 1114 may include the pulse generator 12 determining whether the IPG 12 is providing the phrenic nerve stimulation in the asynchronous mode 862 and whether enough sensor data has been acquired at act 1108 to evaluate entrainment.
  • the pulse generator 12 obtains a minimum amount of sensor data before evaluating entrainment.
  • the sensor data acquired at act 1108 includes respiratory rate information such as from transthoracic impedance as measured by implantable sensors 19.
  • transthoracic-impedance information may be used to determine breath periods, that is, a time between successive breaths.
  • the breath periods may be used to determine a quantification of the degree of synchronization which may be an entrainment index.
  • the entrainment index is a ratio of spectral power in a stimulation frequency band to a spectral power in an intrinsic respiratory frequency band.
  • the entrainment index is a ratio of a quantity of breaths within a predetermined range of a stimulation rate to a total quantity of breaths for a particular time period.
  • a patient may be considered entrained when the entrainment index satisfies at least one pre-determined threshold. For example, as discussed above with respect to FIG. IB, a patient having a pre-determined percentage of breaths with a frequency falling within a range around the stimulation rate may be considered entrained, or synchronized to the entrainment frequency of stimulation of the phrenic nerve.
  • the system 10 may collect data for a series of breath lengths over a pre-determined collection time period (for example, 30 seconds to five minutes) or a pre-determined number of breaths (for example, 3-100 breaths) in order to accurately evaluate the entrainment index.
  • the pulse generator 12 may calculate the entrainment index and compare the entrainment index with the target threshold or a target range. For example, this target threshold or range may be between 0.6-0.8. If the ratio meets or exceeds the threshold or falls within the target range, the pulse generator 12 may determine the patient to be entrained.
  • act 1114 may include determining whether a certain threshold number of breaths have been measured, and/or may include determining whether a certain threshold amount of collection time has passed during which breaths have been measured. Continuing with the latter example, if the pulse generator 12 determines that the collection time has not yet elapsed or the threshold number of breaths have not been measured (1114 NO), then the process 1100 returns to act 802.
  • Acts 802, 804, and 1104-1114 may be repeated until the pulse generator 12 determines that the requisite amount of breathing data has been collected (1114 YES).
  • the cycles of repeatedly executing these acts may be referred to as accumulating therapy cycle(s) 1116, at least because these acts are repeatedly executed to apply therapy and accumulate sensor data.
  • the pulse generator 12 determines that the requisite amount of breathing data has been collected (1114 YES)
  • the process 1100 continues to act 1118.
  • the pulse generator 12 evaluates a degree of synchronization, or entrainment, based on the sensor data acquired at act 1108.
  • evaluating entrainment may include executing a calculation to yield a quantification of the degree of synchronization which quantifies a degree to which the patient breathing is synchronized to the stimulation rate of the therapy provided at the therapy act 1112, and determining whether this degree of synchronization represents an acceptable level of synchronization based on a degree of synchronization criterion.
  • the quantification of the degree of synchronization may be the entrainment index. For example, suppose that FIG. IB represents the total number of breaths measured based on transthoracic-impedance measurements acquired at act 1108 within the collection time over which the accumulating therapy cycles 1116 are executed. As illustrated in FIG.
  • the entrainment index for this example is 0.6 or 60%.
  • the value of the entrainment index is expected to increase proportionally with the entrainment of respiration by stimulation.
  • a higher entrainment index indicates a higher degree of entrainment by stimulation.
  • the pulse generator 12 determines, based on the entrainment index, whether the therapy applied at the therapy act 1112 meets one or more degree of synchronization criteria, or entrainment criteria.
  • the entrainment criteria may include criteria that, if met, represent satisfactory entrainment.
  • act 1120 may include determining whether the entrainment index is within a threshold range, such as between 0.6 and 0.8, or above 0.6, or above 0.7, or some other value. If the therapy system 10 determines that the entrainment index meets the entrainment criteria (1120 YES), then the process 1100 returns to act 802, and the process 1100 is repeated. Otherwise, if the pulse generator 12 determines that the entrainment index does not meet the entrainment criteria (1120 NO), then the process 1100 continues to act 1122.
  • the therapy system 10 adjusts one or more parameters of the therapy. Act 1122 may be similar to act 914.
  • the therapy system 10 may adjust stimulation parameters such as one or more of a number of pulses, a current magnitude, a voltage magnitude, a frequency at which the pulses are applied, a time over which the pulses are ramped up, a time over which the pulses are ramped down, a number of ramping-up pulses, a number of ramping-down pulses, a magnitude of at least one of the ramping-up pulses, a magnitude of at least one of the ramping- down pulses, a pulse width of the pulses, a time between applying the at least one phrenic nerve electrical stimulation and the at least one upper-airway nerve electrical stimulation, a time between one or more first pulses of the phrenic nerve electrical stimulation and one or more second pulses of the upper-airway nerve electrical stimulation, and so forth.
  • the values of any of the aforementioned parameters may be varied within respective preprogrammed ranges set, for example, by a physician during the monitoring period 852.
  • the intensity of one or more stimulation parameters may be increased by a certain amount, such as 5%.
  • current magnitude as an example, if a current magnitude was previously 1 mA, the intensity of the current amplitude may be increased by 5% to yield a current magnitude of 1.05 mA.
  • Acts 1118-1122 may be referred to as entrained therapy cycle(s) 1124.
  • the accumulating therapy cycle(s) 1116 include applying therapy while accumulating sufficient sensor data to evaluate entrainment
  • the entrained therapy cycle(s) 1124 include providing the therapy to the entrained patient as long as the patient remains asleep and entrained.
  • the process 1100 may be repeatedly iterated through one or more accumulating therapy cycle(s) 1116, followed by one or more entrained therapy cycle(s) 1124 after enough sensor data has been accumulated (act 1114), followed by another set of one or more accumulating therapy cycle(s) 1116, and so forth.
  • the entrainment index may be re-evaluated. If the patient wakes up between therapy cycles and/or if the entrainment index falls below a threshold or out of a target range, then new sensor data may then be accumulated in a subsequent set of one or more accumulating therapy cycles 1116. The accumulated sensor data used to evaluate entrainment at act 1118 for a previous therapy cycle may be deleted or otherwise removed from consideration. Thus, an entrainment index may be calculated at act 1118 based on the most recent set of sensor data acquired in the most recent set of one or more accumulating therapy cycles 1116, but the sensor data used to calculate that entrainment index may not be used to calculate other entrainment indexes in the future.
  • the collection time applied at act 1114 may vary.
  • the collection time may be relative short (for example, on the order of approximately 10-30 seconds or 3-6 breaths) and thus include relatively few accumulating therapy cycles 1 116.
  • the collection time may be relatively long (for example, on the order of approximately one to five minutes or approximately 15-50 breaths) and thus include relatively many accumulating therapy cycles 1116.
  • the pulse generator 12 may determine an initial entrainment index based on relatively few breaths and refine the entrainment index based on a longer collection time. The system 10 may adjust therapy over the course of multiple therapy cycles based on changes in the entrainment index as the pulse generator 12 acquires more sensor data over the longer collection time.
  • FIG. 11B illustrates a process 1101 of implementing the disordered breathing therapy system 100 according to another example.
  • the process 1101 may provide a combination of phrenic nerve stimulation therapy and upper-airway nerve stimulation therapy.
  • the process 1101 may operate in the asynchronous mode 862 or in the synchronous mode of operation 864, as discussed above with regard to FIG. 8B.
  • the process 1101 is an example only and is not limiting.
  • the process 1100 may be altered, such as by having acts added, removed, rearranged, combined, and/or performed concurrently.
  • the process 1101 begins at act 802. Similar to the processes 800 and 801, the process 1101 begins after therapy activation 854 in the therapy delivery mode 861 as shown in FIG. 8B. At act 802, the disordered breathing therapy system 10 determines one or more sleep parameters. Act 802 is substantially similar to the act 802 discussed above with respect to FIG. 8A and is labeled accordingly. A description of act 802 is therefore not repeated. The process 1101 continues to act 804.
  • the disordered breathing therapy system 10 determines whether the patient is asleep. Act 804 is substantially similar to the act 804 discussed above with respect to FIG. 8A and is labeled accordingly. A description of act 804 is therefore not repeated. If the therapy system 10 determines that the patient is not asleep (804 NO), the process 1101 returns to act 802. Acts 802 and 804 are repeated until the therapy system 10 determines that the patient is asleep (804 YES), at which point the process 1101 continues to act 1190.
  • the therapy system 10 determines whether to provide phrenic nerve stimulation.
  • a physician may evaluate the patient to determine whether the therapy system 10 should provide phrenic nerve stimulation (for example, prior to surgery 850 and/or during the monitoring period 852), and may pre-program the pulse generator 12 accordingly. For example, if the physician determines that the patient exhibits a lack of central respiratory drive and/or other indicators of CSA, the physician may pre-program the pulse generator 12 to provide phrenic nerve stimulation (1190 YES).
  • the trigger for providing stimulation of phrenic nerves may be a programmed instruction to the pulse generator 12 and occur independently from any sensor measurements and/or sensor data analysis. Sensor measurements and/or sensor-data analysis may not trigger the phrenic nerve stimulation.
  • the acts 1108, 1120, and 1122 as described below may exclude specific central respiratory drive analysis. The physician may determine that phrenic nerve stimulation should be provided in the therapy delivery mode 861 and/or during other encounters with the patient or other data review prior to or subsequent to the monitoring and therapy periods.
  • the pulse generator 12 may be re -programmed to provide the phrenic nerve stimulation.
  • some or all stimulation delivery parameters of the phrenic nerve stimulation may be pre-programmed based on data collected during or prior to the monitoring period 852 and as subject to change based on sensor data measured at 1108.
  • some or all of the stimulation delivery parameters of the upper-airway nerve stimulation may be pre-programmed based on data collected during or prior to the monitoring period 852. These parameters may be subject to change based on sensor data measured at 1108.
  • the decision at act 1190 is whether or not the system 10 is pre-programmed to provide phrenic nerve stimulation of any kind. If that decision is yes (1190 YES), then the system 10 may provide that phrenic nerve stimulation according to pre-programmed stimulation parameters. However, for the upper-airway nerve stimulation, the process 1101 does not include a decision step as to whether or not to provide the upper-airway nerve stimulation.
  • the process 1101 continues to act 1106.
  • the implantable system 10 provides electrical stimulation to one or more phrenic nerves via the one or more phrenic nerve stimulation leads 14.
  • the therapy system 10 determines that pre-programmed phrenic nerve stimulation is not to be provided at act 1190 (1190 NO)
  • the process 1100 bypasses act 1106 and proceeds to act 1110.
  • the acts of process 1101 are substantially as described above with regard to the process 1100 and not repeated here for brevity.
  • act 1110 may precede act 1106.
  • the method 1101 may proceed from the act 804 to act 1110 and then to the acts 1190 and 1106. Further, the method 1101 may proceed with act 1110 in parallel with 1190 and 1106.
  • acts 1106 and 1110 may occur according to one or more of the various coordinated timing patterns between phrenic nerve stimulation and upper-airway nerve stimulation as discussed in detail above with regard at least to FIG. 10A.
  • the IPG 12 may determine upper- airway nerve stimulation timing relative to the phrenic nerve timing where both therapies are delivered (1190 YES).
  • the implantable therapy system 10 may provide the electrical stimulation of the one or more phrenic nerves in an asynchronous therapy mode 862 or a synchronous therapy mode 864.
  • the system 10 provides the phrenic nerve stimulation at a pre-determined rate without a respiration-sensor-based trigger.
  • the synchronous mode 864 the system 10 provides the phrenic nerve stimulation according to a respiration- sensorbased trigger.
  • the IPG 12 may provide the upper-airway nerve stimulation according to a pre-programmed trigger such that the timing of an upper-airway nerve stimulation pulse train is relative to and controlled by the phrenic nerve stimulation pulse train timing.
  • an upper-airway nerve stimulation may occur alone in the absence of a coordinated phrenic nerve stimulation.
  • a phrenic nerve stimulation may occur alone in the absence of a coordinated upper-airway nerve stimulation.
  • an instance of stimulation and/or a therapy delivery cycle may not require a stimulation of both nerves even if the pulse generator 12 is pre-preprogrammed to provide phrenic nerve stimulation.
  • particular acts or groups of acts in processes 800, 801, 1100 and 1101 may be advantageous and provided by the treatment system 100, device 12 and/or external computing device 210 independent of the other acts illustrated therein.
  • particular acts or groups of acts performed independently may include but are not limited to one or more of performing the determination of whether a patient is still asleep following stimulation or changes in stimulation; the evaluation of respiratory information following a determination of whether the patient is asleep; the evaluation of a combined therapy adjustment; evaluation of a model to determine expected therapy results; and/or entrainment evaluation.
  • controllers such as a controller implemented within the disordered breathing therapy system 100, may execute various operations discussed above. Using data stored in associated memory and/or storage, the controller also executes one or more instructions stored on one or more non-transitory computer-readable media, which the controller may include and/or be coupled to, that may result in manipulated data.
  • the controller may include one or more processors or other types of controllers.
  • the controller is or includes at least one processor.
  • the controller performs at least a portion of the operations discussed above using an application-specific integrated circuit tailored to perform particular operations.
  • examples in accordance with the present disclosure may perform the operations described herein using many specific combinations of hardware and software and the disclosure is not limited to a particular combination of hardware and software components.
  • Examples of the disclosure may include a computer-program product configured to execute methods, processes, and/or operations discussed above.
  • the computerprogram product may be, or include, one or more controllers and/or processors configured to execute instructions to perform methods, processes, and/or operations discussed above.
  • one or more of the treatment system 10, external sensors 18, and/or computing device 210 may communicate with one another via wireless standards, such as a Bluetooth® wireless communication standard.
  • the Bluetooth® connection and corresponding circuitry in the implantable system 10 can use Bluetooth® personal area network (PAN) technology, Bluetooth Low Energy® (BLE) technology, or other Bluetooth® variant technologies.
  • PAN personal area network
  • BLE Bluetooth Low Energy®
  • the components 10, 18, 210 can utilize other wireless technologies and circuitry, such as a near-field communication (NFC) compliant technology.
  • NFC is a set of communication protocols which enable two electronic devices to establish communication by bringing the devices within close distance of each other.
  • the computing device 210 provides a display 116, discussed in greater detail below with respect to FIG. 2, with a graphical user interface having features, as disclosed herein, that facilitate improved review of patient information by a clinician monitoring the treatment of the patient.
  • the computing device 210 includes a mobile computing device such as a tablet computer, a laptop computer, and so forth, though this need not be the case in all examples.
  • the computing device 210 may be a tablet computer or other type of computer, and may be coupled to an external device to communicate with, and program, the treatment system 10.
  • the computing device 210 may be coupled to an external programming device (or programming wand) via a wired connection, such as a USB connection. Accordingly, the computing device 210 may communicate with the programming device via a wired connection, and the programming device may communicate with the treatment system 10 via a wireless connection.
  • the programming device may communicate with the treatment system 10 via a magnetic inductive communication link when the programming device is within a proximity of the treatment system 10. In various examples, therefore, the computing device 210 may include or be coupled to one or more devices to enable wireless communication with the treatment system 10.
  • the computing device 210 may refer to multiple devices including, for example, a tablet computer used at least to interface with a user, as well as a programming device used to program the treatment system 10.
  • control device 12 may be programmed with functionality that is activated by the operational parameters received thereby. In other examples, the control device 12 is provided with the functionality by the operational parameters received thereby.
  • FIG. 2 shows a block diagram of a disordered breathing therapy system 200 according to an example.
  • the disordered breathing therapy system 200 is similar to the disordered breathing therapy system 100, and like components are labeled accordingly. Additionally, the disordered breathing therapy system 200 illustrates components of the computing device 210 in accordance with an example. While in some examples the external computing device 210 is a tablet type of computer or a mobile phone such as a smart phone, the device 210 can include other types of computers. In various examples, the computing device 210 includes core components 106 including at least a processing unit 102 and a system memory 104.
  • the memory 104 may include memory that is volatile (such as RAM), non-volatile (such as ROM, flash memory, and so forth) or some combination of the two.
  • the device 210 may include additional storage (removable and/or nonremovable) including, but not limited to, magnetic or optical disks or tapes, USB flash drives, memory cards, and so forth. Such additional storage is illustrated in FIG. 2 by a removable storage 108 and a non-removable storage 110.
  • Computer-storage media may include volatile and/or nonvolatile media, removable and/or non-removable media, and so forth, implemented in a method or technology for storage of information such as computer-readable instructions, data structures, program modules or other data.
  • the memory 104, the removable storage 108, and the non-removable storage 110 are examples of computer- storage media, also referred to as computer-readable media.
  • Computer- storage media includes, but is not limited to, RAM, ROM, EEPROM, flash memory or other memory technology, CDROM, digital versatile disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or another other medium that can be used to store the desired information and which can be accessed by the device 210.
  • Such computer-storage media may be part of the device 210.
  • System memory 104 may include operating system 130, one or more programming modules or applications 132, and program data 134.
  • Operating system 130 may be suitable for controlling the operation of computing device 210.
  • a number of program modules 132 and data files 134 may be stored in system memory 104, including operating system 130.
  • programming modules or applications 132 may perform processes including, for example, one or more methods described herein, using one or more of the GUI screens or windows shown and described herein.
  • the program modules or applications 132 may include routines, programs, components, data structures, and other types of structures that may perform particular tasks or that may implement particular abstract data types.
  • disclosed examples may be practiced with other computer system configurations, including multiprocessor systems, microprocessor-based or programmable consumer electronics, minicomputers, mainframe computers, and the like.
  • Disclosed embodiments may also be practiced in distributed computing environments where tasks are performed by remote processing devices that are linked through a communications network.
  • program modules may be located in both local and remote memory storage devices.
  • the processing unit 102 may be included within one or more controllers. Various controllers may execute various operations discussed herein.
  • the controller(s) Using data stored in associated memory and/or storage, the controller(s) also executes one or more instructions stored on one or more non-transitory computer-readable media, which the controller(s) may include and/or be coupled to, that may result in manipulated data.
  • the controller(s) may include one or more processors or other types of controllers.
  • the controller(s) is or includes at least one processor.
  • the controller(s) performs at least a portion of the operations discussed above using an applicationspecific integrated circuit tailored to perform particular operations. As illustrated by these examples, examples in accordance with the present disclosure may perform the operations described herein using many specific combinations of hardware and software and the disclosure is not limited to a particular combination of hardware and software components.
  • Examples of the disclosure may include a computer-program product configured to execute methods, processes, and/or operations discussed above.
  • the computer-program product may be, or include, one or more controllers and/or processors configured to execute instructions to perform methods, processes, and/or operations discussed above.
  • the device 210 may also contain a communications interface 112 that allows the device to communicate with other devices.
  • the communications interface 112 can include, for example, wired media connections such as a wired network or direct-wired connection, and wireless media connections such as acoustic, RF, infrared, telemetric wand, and other wireless media connections.
  • the communications interface 112 may include one or more wireless-communication apparatus, such as one or more antenna to enable provide wireless communicability.
  • the communications interface 112 may be configured to communicate according to one or more communication protocols, such as a Bluetooth® communication protocol, a Wi-Fi and/or internet communication protocol, and so forth.
  • the communications interface 112 is configured to provide communication between external computing device 210 and control device 12 of treatment system 10.
  • the communication interface 112 includes circuitry configured to provide a wireless communication connection as described above.
  • communication circuitry 112 can communicate through a computer and/or cellular network 34, such as the internet, to the computing dcvicc(s) 38.
  • the treatment system 10 is not communicatively coupled to the computer and/or cellular network 34 and/or the computing device(s) 38; the device 210, which may be communicatively coupled to both the treatment system 10 and the computing devices 38 via the network 34, may route communications between the treatment system 10 and devices coupled to the network 34.
  • the treatment system 10 may be communicatively coupled to the network 34 and other devices connected thereto, such as the computing devices 38.
  • the processing functions described herein are performed without the use of the computing device 210, and are instead incorporated into the treatment system 10 and/or the computing device(s) 38.
  • the treatment system 10 could include communication connections allowing communication through the network 34 to device(s) 38.
  • the treatment system 10 performs at least a portion of the processing functions described herein, and a remaining portion, if any, of the processing functions may be performed by the computing device 210 and/or one or more alternative or additional computing devices, such as the remote or cloud-based computing devices 38.
  • the processor 102 is configured to provide RDS diagnostics 230.
  • diagnostic operations which may be executed by the RDS engine 24 in some examples may be executed instead by, or in addition to, the processor 102.
  • aspects of the operations discussed above may be executed by the treatment system 10 (for example, by the RDS engine 24), the processor 102, or a combination thereof.
  • operations described as being executed by the disordered breathing therapy system 100 and/or 200 may be executed by the RDS engine 24, the processor 102, or a combination thereof.
  • the external computing device 210 has, or can be coupled to, a touch screen display device 116 which provides a touch-based GUI.
  • the device 210 may also have, or be coupled to, one or more input devices 114, such as a keyboard, mouse, pen, voice input device, and so forth, for providing other input to the computing device.
  • the device 210 may be coupled to one or more other output devices 118 such as speakers, a printer, a vibration generator, and so forth.
  • display device 116, input devices 114 and output devices 118 can all be considered to be separate from, or alternatively part of, computing device 210.
  • External computing device 210 can be provided with a portable or non-portable power source 120, such as a battery pack, a transformer, a power supply, or the like.
  • the power source 120 provides power for computations, communications and so forth by the device 210.

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Abstract

Des exemples comprennent un système de traitement pour fournir à un patient endormi une thérapie pour les troubles respiratoires, le système comprenant au moins un premier fil de stimulation, au moins un second fil de stimulation, et un dispositif de commande de thérapie implanté configuré pour s'accoupler aux fils et pour fournir au moins une stimulation électrique à un nerf phrénique d'un patient par l'intermédiaire dudit au moins un premier fil de stimulation, fournir au moins une stimulation électrique à un nerf hypoglosse du patient par l'intermédiaire dudit au moins un second fil de stimulation, et coordonner un moment relatif de la stimulation électrique au nerf hypoglosse avec la stimulation électrique au nerf phrénique du patient.
PCT/US2024/049967 2023-10-06 2024-10-04 Système et procédé pour fournir une thérapie pour les troubles respiratoires Pending WO2025076355A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150283383A1 (en) * 2014-04-04 2015-10-08 Cardiac Pacemakers, Inc. Methods and apparatus for apnea therapy stimulation
US20200147376A1 (en) * 2018-11-13 2020-05-14 Inspire Medical Systems, Inc. Multiple type sleep apnea
US20230218899A1 (en) * 2020-03-23 2023-07-13 Medtronic, Inc. Obstructive and central sleep apnea combination therapy control

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150283383A1 (en) * 2014-04-04 2015-10-08 Cardiac Pacemakers, Inc. Methods and apparatus for apnea therapy stimulation
US20200147376A1 (en) * 2018-11-13 2020-05-14 Inspire Medical Systems, Inc. Multiple type sleep apnea
US20230218899A1 (en) * 2020-03-23 2023-07-13 Medtronic, Inc. Obstructive and central sleep apnea combination therapy control

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