Neurostimulation titration utilizing T-wave alternans

• US 10,099,055 B2
• Filed: 11/11/2015
• Issued: 10/16/2018
• Est. Priority Date: 11/12/2014
• Status: Active Grant

• Current Assignee: LivaNova USA, Inc. (LivaNova Plc)
• Original Assignee: Cyberonics, Inc
• Inventors: Libbus, Imad, KenKnight, Bruce H.
• Primary Examiner(s): Holmes, Rex R
• Application Number:
  US14/938,641
• Publication Number:
  US 20160129256A1
• Time in Patent Office: 1,070 Days
• CPC Class Codes: A61B 5/349 Detecting specific parameters of the electrocardiograph cycle
• CPC Class Codes: A61N 1/0551 Spinal or peripheral nerve electrodes
• CPC Class Codes: A61N 1/36114 Cardiac control, e.g. by vagal stimulation stimulating the heart A61N1/362
• CPC Class Codes: A61N 1/36132 using patient feedback
• CPC Class Codes: A61N 1/36139 with automatic adjustment
• CPC Class Codes: A61N 1/3615 Intensity
• CPC Class Codes: A61N 1/36167 Timing, e.g. stimulation onset
• CPC Class Codes: A61N 1/3702 Physiological parameters A61N1/365 takes precedence; evoked response A61N1/371
• CPC Class Codes: A61N 1/37223 Circuits for electromagnetic coupling
• CPC Class Codes: A61N 1/37235 Aspects of the external programmer
• CPC Class Codes: G16H 20/30 relating to physical therapies or activities, e.g. physiotherapy, acupressure or exercising
• CPC Class Codes: G16H 20/40 relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
• CPC Class Codes: G16H 40/20 for the management or administration of healthcare resources or facilities, e.g. managing hospital staff or surgery rooms
• CPC Class Codes: G16H 40/63 for local operation
• CPC Class Codes: G16Z 99/00 Subject matter not provided for in other main groups of this subclass

Abstract

Systems and methods are provided for delivering neurostimulation therapies to patients. A titration process is used to gradually increase the stimulation intensity to a desired therapeutic level until a target T-wave alternans change from a baseline T-wave alternans is achieved.

Claims

1. A method of operating an implantable medical device (IMD) comprising a neurostimulator coupled to an electrode assembly, said neurostimulator adapted to deliver a stimulation signal to a patient, said method comprising:

monitoring an electrocardiogram (ECG) of the patient to determine a baseline for the patient either prior to implantation or in a post-implant period before initiation stimulation by the IMD, wherein the baseline comprises one or more of a baseline T-wave alternans (TWA), a baseline heart rate turbulence slope (TS), or a baseline heart rate turbulence onset (TO);

activating the IMD to deliver to the patient a plurality of stimulation signals at increasing stimulation intensities, causing a change from the baseline, until a target threshold is detected, wherein the target threshold comprises one or more of a target TWA threshold, a target heart rate TS threshold, or a target heart rate TO threshold; and

activating the IMD to deliver a therapeutic level of stimulation corresponding to the stimulation intensity at which the target threshold was detected.

2. The method according to claim 1, wherein:

the target threshold comprises the target TWA threshold.

3. The method according to claim 2, wherein:

the target TWA threshold comprises a TWA less than a target TWA magnitude.

4. The method according to claim 3, wherein:

the target TWA magnitude comprises approximately 47 μ

V.

5. The method according to claim 2, further comprising:

computationally determining a baseline TWA for the patient;

wherein the target TWA threshold comprises a change in TWA from the baseline TWA equal to or greater than a target TWA change.

6. The method according to claim 5, wherein:

the target TWA change comprises approximately 10 μ

V.

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

performing a baseline update process, the baseline update process comprising;

temporarily ceasing the delivery of stimulation to the patient;

monitoring the ECG of the patient to determine an updated baseline TWA for the patient;

activating the IMD to deliver to the patient a plurality of stimulation signals at increasing stimulation intensities until a target change in TWA from the updated baseline TWA is observed; and

activating the IMD to deliver a therapeutic level of stimulation corresponding to the stimulation intensity during which the target change in TWA from the updated baseline TWA was observed.

8. A method of operating an implantable medical device (IMD) comprising a neurostimulator coupled to an electrode assembly, said neurostimulator adapted to deliver a stimulation signal to a patient, said method comprising:

monitoring an electrocardiogram (ECG) of the patient to determine a baseline for the patient either prior to implantation or in a post-implant period before initiation stimulation by the IMD, wherein the baseline comprises one or more of a baseline T-wave alternans (TWA), a baseline heart rate turbulence slope (TS), or a baseline heart rate turbulence onset (TO);

activating the IMD to deliver to the patient a plurality of stimulation signals at increasing stimulation intensities until a target change from the baseline is observed, wherein the target change comprises one or more of a target TWA change, a target heart rate TS change, or a target heart rate TO change; and

identifying a neural fulcrum zone corresponding to the stimulation intensity during which the target change from the baseline was observed.

9. The method according to claim 8, wherein:

the baseline comprises the baseline TWA; and

the target change from the baseline comprises a target change in TWA from the baseline TWA.

10. The method according to claim 8, further comprising:

activating the IMD to chronically deliver stimulation signals in the identified neural fulcrum zone.

11. The method according to claim 10, wherein said activating the IMD to chronically deliver stimulation signals in the identified neural fulcrum zone comprises activating the IMD to treat chronic cardiac dysfunction.

12. The method according to claim 8, wherein:

said activating the IMD to deliver to the patient the plurality of stimulation signals at increasing stimulation intensities comprises activating the IMD to deliver to the patient the plurality of stimulation signals at increasing stimulation output currents until a target change from the baseline is observed.

13. The method according to claim 8, wherein:

said IMD is adapted to deliver the stimulation signal to a vagus nerve of the patient.

14. The method according to claim 8, further comprising:

performing a baseline update process, the baseline update process comprising;

temporarily ceasing the delivery of stimulation to the patient;

monitoring the ECG of the patient to determine an updated baseline for the patient;

activating the IMD to deliver to the patient a plurality of stimulation signals at increasing stimulation intensities until a target change from the updated baseline is observed; and

identifying an updated neural fulcrum zone corresponding to the stimulation intensity during which the target change from the updated baseline was observed.

15. A method of operating an implantable medical device (IMD) comprising a neurostimulator coupled to an electrode assembly, said neurostimulator adapted to deliver a stimulation signal to a patient, said method comprising:

computationally determining a baseline cardiac magnitude value for the patient either prior to implantation or in a post-implant period before initiation stimulation by the IMD, wherein the baseline cardiac magnitude value comprises one or more of a T-wave alternans (TWA) magnitude value, a heart rate turbulence slope (TS) magnitude value, or a heart rate turbulence onset (TO) magnitude value;

computationally determining a current cardiac magnitude value for the patient, wherein the current cardiac magnitude value comprises one or more of a T-wave alternans (TWA) magnitude value, a heart rate turbulence slope (TS) magnitude value, or a heart rate turbulence onset (TO) magnitude value;

activating the IMD to deliver to the patient a plurality of stimulation signals at increasing stimulation intensities, causing a change from the baseline, until the current cardiac magnitude value reaches to a target cardiac magnitude, wherein the target magnitude comprises one or more of a TWA target magnitude, a heart rate TS target magnitude, or a heart rate TO target magnitude; and

activating the IMD to deliver a therapeutic level of stimulation corresponding to the stimulation intensity during which the current cardiac magnitude value reached the target cardiac magnitude.

16. The method according to claim 15, wherein:

the computationally determining the cardiac magnitude value for the patient comprises computationally determining the TWA magnitude value;

the activating the IMD to deliver to the patient the plurality of stimulation signals at increasing stimulation intensities comprises activating the IMD to deliver to the patient the plurality of stimulation signals at increasing stimulation intensities until the determined TWA magnitude value reaches to a target TWA magnitude; and

the activating the IMD to deliver the therapeutic level of stimulation comprises activating the IMD to deliver the therapeutic level of stimulation corresponding to the stimulation intensity during which the determined TWA magnitude value reached the target TWA magnitude.

17. The method according to claim 15, wherein:

said computationally determining the cardiac magnitude value for the patient is performed by the IMD.

18. A neurostimulation system, comprising:

an implantable medical device (IMD) comprising;

an electrode assembly;

a neurostimulator coupled to the electrode assembly, wherein the neurostimulator is adapted to deliver a stimulation signal to a patient;

an electrocardiogram (ECG) sensor; and

a control system programmed to;

monitor the ECG of the patient using the ECG sensor to determine a baseline for the patient either prior to implantation or in a post-implant period before initiation stimulation by the IMD, wherein the baseline comprises one or more of a baseline T-wave alternans (TWA), a baseline heart rate turbulence slope (TS), or a baseline heart rate turbulence onset (TO);

activate the IMD to deliver to the patient a plurality of stimulation signals at increasing stimulation intensities, causing a change from the baseline, until a target threshold is detected, wherein the target threshold comprises one or more of a target TWA threshold, a target heart rate TS threshold, or a target heart rate TO threshold; and

activate the IMD to deliver a therapeutic level of stimulation corresponding to the stimulation intensity at which the target threshold was detected.

19. The system according to claim 18, wherein the target threshold comprises the target TWA threshold.

20. The system according to claim 19, wherein the control system is programmed to:

activate the IMD to deliver to the patient the plurality of stimulation signals at increasing stimulation intensities until a TWA less than a target TWA magnitude is detected.

21. The system according to claim 20, wherein:

the target TWA magnitude comprises approximately 47 μ

V.

22. The system according to claim 18, wherein the control system is programmed to:

activate the IMD to deliver to the patient the plurality of stimulation signals at increasing stimulation intensities until a change from the baseline equal to or greater than a target change is detected.

23. The system according to claim 22, wherein:

the baseline comprises the baseline TWA;

the target change comprises a target TWA change of approximately 10 μ

V.

24. The system according to claim 22, wherein the control system is programmed to:

perform a baseline update process, the baseline update process comprising;

temporarily ceasing the delivery of stimulation to the patient;

monitoring the ECG of the patient to determine an updated baseline for the patient;

activating the IMD to deliver to the patient a plurality of stimulation signals at increasing stimulation intensities until a target change from the updated baseline is observed; and

activating the IMD to deliver a therapeutic level of stimulation corresponding to the stimulation intensity during which the target change from the updated baseline was observed.

25. A neurostimulation system, comprising:

an implantable medical device (IMD) comprising;

an electrode assembly;

a neurostimulator coupled to the electrode assembly, wherein the neurostimulator is adapted to deliver a stimulation signal to a patient;

an electrocardiogram (ECG) sensor; and

a control system programmed to;

activate the IMD to deliver to the patient a plurality of stimulation signals;

monitor the ECG of the patient using the ECG sensor;

determine a baseline cardiac magnitude value for the patient either prior to implantation or in a post-implant period before initiation stimulation by the IMD, wherein the baseline cardiac magnitude value comprises one or more of a T-wave alternans (TWA) magnitude value, a heart rate turbulence slope (TS) magnitude value, or a heart rate turbulence onset (TO) magnitude value;

determine a current cardiac magnitude value based on the monitored ECG, wherein the current cardiac magnitude value comprises one or more of a TWA magnitude value, a heart rate TS magnitude value, or a heart rate TO magnitude value;

activate the IMD to deliver to the patient a plurality of stimulation signals at increasing stimulation intensities, causing a change from the baseline, until the current cardiac magnitude value reaches to a target cardiac magnitude, wherein the target magnitude comprises one or more of a TWA target magnitude, a heart rate TS target magnitude, or a heart rate TO target magnitude; and

activate the IMD to deliver a therapeutic level of stimulation corresponding to the stimulation intensity during which the current cardiac magnitude value reached the target cardiac magnitude.