Implantable neurostimulator-implemented method for managing tachyarrhythmic risk during sleep through vagus nerve stimulation

• US 10,449,363 B2
• Filed: 05/03/2017
• Issued: 10/22/2019
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: LivaNova USA, Inc. (LivaNova Plc)
• Original Assignee: LivaNova USA, Inc. (LivaNova Plc)
• Inventors: Libbus, Imad, Amurthur, Badri, Kenknight, Bruce H.
• Primary Examiner(s): Wehrheim, Lindsey G
• Application Number:
  US15/585,854
• Publication Number:
  US 20170296817A1
• Time in Patent Office: 902 Days
• CPC Class Codes: A61B 5/024 Detecting, measuring or recording pulse rate or heart rate A61B5/0205, A61B5/021 take precedence
• CPC Class Codes: A61B 5/02405 Determining heart rate variability
• CPC Class Codes: A61B 5/1116 Determining posture transitions
• CPC Class Codes: A61B 5/1118 Determining activity level
• CPC Class Codes: A61B 5/363 Detecting tachycardia or bradycardia
• CPC Class Codes: A61B 5/4809 Sleep detection, i.e. determining whether a subject is asleep or not
• CPC Class Codes: A61B 5/4836 Diagnosis combined with treatment in closed-loop systems or methods A61B5/0036 takes precedence
• CPC Class Codes: A61B 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence
• CPC Class Codes: A61N 1/36053 adapted for vagal stimulation A61N1/36114 takes precedence
• CPC Class Codes: A61N 1/36114 Cardiac control, e.g. by vagal stimulation stimulating the heart A61N1/362
• CPC Class Codes: A61N 1/36139 with automatic adjustment
• CPC Class Codes: A61N 1/3621 for treating or preventing abnormally high heart rate

Abstract

A patient suffering from congestive heart failure is at increased risk of cardiac arrhythmogenesis during sleep, particularly if experiencing central sleep apnea as a co-morbidity. Low intensity peripheral neurostimulation therapies that target imbalance of the autonomic nervous system have been shown to improve clinical outcomes. Thus, bi-directional autonomic regulation therapy is delivered to the cervical vagus nerve at an intensity that is insufficient to elicit pathological or acute physiological side effects and without the requirement of an enabling physiological feature or triggering physiological marker. The patient'"'"'s physiology is monitored to identify periods of sleep. In one embodiment, upon sensing a condition indicative of tachyarrhythmia following a period of bradycardia, as naturally occurs during sleep, an enhanced “boost” dose of bi-directional neural stimulation intended to “break” the tachyarrhythmic condition is delivered. In a further embodiment, the boost dose is delivered upon sensing a physiological pattern indicative of Cheyne-Stokes respiration.

Claims

1. A method for managing tachyarrhythmic risk accompanying central sleep apnea through vagus nerve stimulation, comprising:

providing an implantable neurostimulator comprising a pulse generator configured to deliver electrical therapeutic stimulation to a vagus nerve of a patient;

storing operating modes of the pulse generator in a recordable memory, the operating modes defining;

a maintenance dose of the electrical therapeutic stimulation; and

a boost dose of the electrical therapeutic stimulation comprising electrical pulses delivered at higher intensity than the maintenance dose;

delivering the maintenance dose to the vagus nerve via the pulse generator through an electrode electrically coupled to the pulse generator;

monitoring a physiological state of the patient via a sensor;

upon sensing a condition indicative of naturally-occurring bradycardia followed by a condition indicative of potential tachyarrhythmia, delivering the boost dose to the vagus nerve via the pulse generator through the electrode; and

progressively intensifying the electrical therapeutic stimulation as specified in the operating mode of the boost dose as the condition indicative of tachyarrhythmia continues.

2. A method according to claim 1, further comprising:

monitoring the physiological state of the patient while awake via the sensor; and

upon sensing that the patient is asleep, suspending the delivery of the maintenance dose.

3. A method according to claim 1, further comprising, upon sensing the condition indicative of naturally-occurring bradycardia followed by a condition indicative of potential tachyarrhythmia, initially resuming the delivery of the maintenance dose prior to the delivery of the boost dose.

4. A method according to claim 1, the sensor comprising a heart rate sensor, the method further comprising:

establishing a normative heart rate of the patient with the heart rate sensor as a mean heart rate sensed while awake;

periodically sensing a heart rate of the patient with the heart rate sensor; and

confirming that the patient is asleep when the heart rate of the patient gradually decreases and is sustained at an elevated heart rate below the normative heart rate by a threshold amount.

5. A method according to claim 1, the sensor comprising an accelerometer, the method further comprising:

establishing a normative activity level of the patient with the accelerometer as a mean frequency of movement sensed while awake;

periodically sensing an activity level of the patient with the accelerometer; and

confirming that the patient is asleep when the activity level of the patient gradually decreases as is sustained at an elevated activity level below the normative activity level accompanied by a decreased frequency of movement by a threshold amount.

6. A method according to claim 5, further comprising:

establishing a posture of the patient with the accelerometer; and

concluding that the patient is asleep when the posture of the patient is less than about 45 degrees relative to horizontal.

7. A method according to claim 5, further comprising:

establishing a posture of the patient with the accelerometer;

evaluating a severity of a heart failure condition based on the posture of the patient relative to horizontal while asleep, where the closer the posture to vertical, the more severe the heart failure condition; and

increasing the intensity of the maintenance dose relative to the heart failure condition'"'"'s severity.

8. A method according to claim 1, the sensor comprising a minute ventilation sensor, the method further comprising:

establishing a normative tidal volume and normative respiratory rate of the patient with the minute ventilation sensor sensed while awake;

periodically sensing a tidal volume and a respiratory rate of the patient with the minute ventilation sensor; and

confirming that the patient is asleep when the tidal volume and respiratory rate of the patient gradually fall and are sustained at elevated levels respectively below the normative tidal volume and the normative respiratory rate by a threshold amount.

9. A method according to claim 1, the operating modes further defining a sleep dose of the electrical therapeutic stimulation tuned to restore cardiac autonomic balance when the patient is asleep through electrical pulses delivered at a lower intensity than the maintenance dose, the method further comprising, upon suspension of the maintenance dose, delivering the sleep dose to the vagus nerve via the electrode.

10. A method according to claim 1, further comprising increasing the intensity of the electrical therapeutic stimulation to a highest level specified in the operating mode in response to the condition indicative of tachyarrhythmia failing to respond to the intensified electrical therapeutic stimulation.

11. An implantable neurostimulation system, comprising:

a pulse generator configured to deliver electrical therapeutic stimulation to a vagus nerve of a patient via an electrode coupled to the implantable neurostimulation system;

a recordable memory configured to store operating modes of the pulse generator, the operating modes defining;

a maintenance dose of the electrical therapeutic stimulation; and

a boost dose of the electrical therapeutic stimulation comprising electrical pulses delivered at higher intensity than the maintenance dose;

wherein the pulse generator is configured to;

deliver the maintenance dose to the vagus nerve via the pulse generator through the electrode;

monitor a physiological state of the patient via a sensor;

upon sensing a condition indicative of naturally-occurring bradycardia followed by a condition indicative of potential tachyarrhythmia, deliver the boost dose to the vagus nerve via the pulse generator through the electrode; and

progressively intensify the electrical therapeutic stimulation as specified in the operating mode of the boost dose as the condition indicative of tachyarrhythmia continues.

12. A system according to claim 11, wherein the pulse generator is further configured to:

monitor the physiological state of the patient while awake via the sensor; and

upon sensing that the patient is asleep, suspend the delivery of the maintenance dose.

13. A system according to claim 11, wherein the sensor is a heart rate sensor and the pulse generator is further configured to:

establish a normative heart rate of the patient with the heart rate sensor as a mean heart rate sensed while awake;

periodically sense a heart rate of the patient with the heart rate sensor; and

confirm that the patient is asleep when the heart rate of the patient gradually decreases and is sustained at an elevated heart rate below the normative heart rate by a threshold amount.

14. A system according to claim 11, wherein the sensor is an accelerometer and the pulse generator is further configured to:

establish a normative activity level of the patient with the accelerometer as a mean frequency of movement sensed while awake;

periodically sense an activity level of the patient with the accelerometer; and

confirm that the patient is asleep when the activity level of the patient gradually decreases as is sustained at an elevated activity level below the normative activity level accompanied by a decreased frequency of movement by a threshold amount.

15. A system according to claim 14, wherein the pulse generator is further configured to:

establish a posture of the patient with the accelerometer;

evaluate a severity of a heart failure condition based on the posture of the patient relative to horizontal while asleep, where the closer the posture to vertical, the more severe the heart failure condition; and

increase the intensity of the maintenance dose relative to the heart failure condition'"'"'s severity.

16. A system according to claim 11, wherein the sensor is a minute ventilation sensor and the pulse generator is further configured to:

establish a normative tidal volume and normative respiratory rate of the patient with the minute ventilation sensor sensed while awake;

periodically sense a tidal volume and a respiratory rate of the patient with the minute ventilation sensor; and

confirm that the patient is asleep when the tidal volume and respiratory rate of the patient gradually fall and are sustained at elevated levels respectively below the normative tidal volume and the normative respiratory rate by a threshold amount.

17. A system according to claim 11, wherein the operating modes of the pulse generator further comprise a sleep dose of the electrical therapeutic stimulation tuned to restore cardiac autonomic balance when the patient is asleep through electrical pulses delivered at a lower intensity than the maintenance dose, and wherein the pulse generator is further configured to, upon suspension of the maintenance dose, deliver the sleep dose to the vagus nerve via the electrode.

18. A system according to claim 11, wherein the pulse generator is further configured to increase the intensity of the electrical therapeutic stimulation to a highest level specified in the operating mode in response to the condition indicative of tachyarrhythmia failing to respond to the intensified electrical therapeutic stimulation.